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. 4 T actively detunable transmit/receive transverse electromagnetic coil and 4-channel receive-only phased array for (1)H human brain studies.

    PubMed

    Avdievich, Nikolai I; Hetherington, Hoby P

    2004-12-01

    The design and construction of a 4 T transverse electromagnetic (TEM) transmit/receive head coil and a four-channel phased array receive-only RF system are described. To enable both high-resolution imaging of the entire brain and high-resolution spectroscopic imaging, active PIN diode decoupling was used in both the TEM resonator and each surface coil in the array. This configuration allows for both transmission and reception from the volume coil as well as reception from the phased array. The surface coils were decoupled by overlapping the coils and using preamplifier decoupling. Since at high frequencies construction of a lumped element matching quarter wavelength transformer, an important component of the preamplifier decoupling, becomes difficult, a transmission line approach was used. The system was tested and compared to a TEM volume transmit/receive head coil. A four- to sixfold improvement in signal-to-noise ratio from the sensitive volume of the array was achieved.

  4. 4 T actively detunable transmit/receive transverse electromagnetic coil and 4-channel receive-only phased array for (1)H human brain studies.

    PubMed

    Avdievich, Nikolai I; Hetherington, Hoby P

    2004-12-01

    The design and construction of a 4 T transverse electromagnetic (TEM) transmit/receive head coil and a four-channel phased array receive-only RF system are described. To enable both high-resolution imaging of the entire brain and high-resolution spectroscopic imaging, active PIN diode decoupling was used in both the TEM resonator and each surface coil in the array. This configuration allows for both transmission and reception from the volume coil as well as reception from the phased array. The surface coils were decoupled by overlapping the coils and using preamplifier decoupling. Since at high frequencies construction of a lumped element matching quarter wavelength transformer, an important component of the preamplifier decoupling, becomes difficult, a transmission line approach was used. The system was tested and compared to a TEM volume transmit/receive head coil. A four- to sixfold improvement in signal-to-noise ratio from the sensitive volume of the array was achieved. PMID:15562466

  5. 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

  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. Generation of 24.0 T at 4.2 K and 23.4 T at 27 K with a high-temperature superconductor coil in a 22.54 T background field

    NASA Astrophysics Data System (ADS)

    Ohkura, K.; Sato, K.; Ueyama, M.; Fujikami, Jun; Iwasa, Y.

    1995-09-01

    The 4.2 K and 27 K current-carrying performance of a high-temperature superconducting (HTS) coil was measured in background fields up to 22.54 T generated by a hybrid magnet (Hybrid III) at the MIT Francis Bitter National Magnet Laboratory. The coil, 40 mm winding i.d., 108 mm winding o.d., and 113 mm high, consists of 17 double pancakes, each wound with silver-sheathed BSCCO-2223 tapes. Each pancake is the product of a react-and-wind method. In total, the test coil contains ˜1200 m of BSCCO-2223 conductor weighing ˜7 kg. Prior to the measurements in Hybrid III, the coil was tested in zero background field in the temperature range from 4.2 to 77 K. It was coupled to a Gifford-McMahon type cryocooler and at 15 K generated a peak field of 2.1 T; at 18 K, it generated 1.9 T, operating continuously for ˜50 h. In a 22.54 T background field of Hybrid III, the coil reached critical currents of 116.5 A ([Jc]sc, critical current density based on the BSCCO cross-sectional area only, of 261 A/mm) at 4.2 K and 67 A ([Jc]sc=150 A/mm) at 27 K, establishing record net fields at respective temperatures of 24.0 and 23.4 T for HTS magnets. These currents correspond to overall winding current densities of 47 and 27 A/mm. High-field critical current data for short samples of the tape of the same formulation at 4.2 and 27 K are also presented. Although a [J]sc of 261 A/mm at 24 T and 4.2 K for the test coil is significantly less than ˜600 A/mm for the short samples at the same operating point, if factors such as length, bending, and even differences in defining critical current are considered, the coil and short samples have nearly the same critical current performance. Electromagnetic stresses do not seem to have any negative effects on coil performance. Record fields of 24.0 and 23.4 T were achieved after the test coil had experienced, over a period of 15 months, 20 thermal cycles between room temperature and cryogenic temperatures.

  8. α/β coiled coils.

    PubMed

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

    2016-01-15

    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.

  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. Acoustic noise reduction in a 4 T MRI scanner.

    PubMed

    Mechefske, Chris K; Geris, Ryan; Gati, Joseph S; Rutt, Brian K

    2002-01-01

    High-field, high-speed magnetic resonance imaging (MRI) can generate high levels of noise. There is ongoing concern in the medical and imaging research communities regarding the detrimental effects of high acoustic levels on auditory function, patient anxiety, verbal communication between patients and health care workers and ultimately MR image quality. In order to effectively suppress the noise levels inside MRI scanners, the sound field needs to be accurately measured and characterized. This paper presents the results of measurements of the sound radiation from a gradient coil cylinder within a 4 T MRI scanner under a variety of conditions. These measurement results show: (1) that noise levels can be significantly reduced through the use of an appropriately designed passive acoustic liner; and (2) the true noise levels that are experienced by patients during echo planar imaging.

  11. Acoustic noise reduction in a 4 T MRI scanner.

    PubMed

    Mechefske, Chris K; Geris, Ryan; Gati, Joseph S; Rutt, Brian K

    2002-01-01

    High-field, high-speed magnetic resonance imaging (MRI) can generate high levels of noise. There is ongoing concern in the medical and imaging research communities regarding the detrimental effects of high acoustic levels on auditory function, patient anxiety, verbal communication between patients and health care workers and ultimately MR image quality. In order to effectively suppress the noise levels inside MRI scanners, the sound field needs to be accurately measured and characterized. This paper presents the results of measurements of the sound radiation from a gradient coil cylinder within a 4 T MRI scanner under a variety of conditions. These measurement results show: (1) that noise levels can be significantly reduced through the use of an appropriately designed passive acoustic liner; and (2) the true noise levels that are experienced by patients during echo planar imaging. PMID:11755093

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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...

  19. 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...

  20. 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...

  1. 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...

  2. 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...

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 42 CFR 405.874 - Appeals of CMS or a CMS contractor.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 2 2011-10-01 2011-10-01 false Appeals of CMS or a CMS contractor. 405.874 Section... Part B Program § 405.874 Appeals of CMS or a CMS contractor. A CMS contractor's (that is, a carrier... supplier enrollment application. If CMS or a CMS contractor denies a provider's or supplier's...

  8. 42 CFR 405.874 - Appeals of CMS or a CMS contractor.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 2 2010-10-01 2010-10-01 false Appeals of CMS or a CMS contractor. 405.874 Section... Part B Program § 405.874 Appeals of CMS or a CMS contractor. A CMS contractor's (that is, a carrier... supplier enrollment application. If CMS or a CMS contractor denies a provider's or supplier's...

  9. 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.

  10. 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.

  11. Predicting coiled coils by use of pairwise residue correlations.

    PubMed Central

    Berger, B; Wilson, D B; Wolf, E; Tonchev, T; Milla, M; Kim, P S

    1995-01-01

    A method is presented that predicts coiled-coil domains in protein sequences by using pairwise residue correlations obtained from a (two-stranded) coiled-coil database of 58,217 amino acid residues. A program called PAIRCOIL implements this method and is significantly better than existing methods at distinguishing coiled coils from alpha-helices that are not coiled coils. The database of pairwise residue correlations suggests structural features that stabilize or destabilize coiled coils. Images Fig. 1 Fig. 2 PMID:7667278

  12. 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

  13. 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.

  14. CMS Simulation Software

    NASA Astrophysics Data System (ADS)

    Banerjee, S.

    2012-12-01

    The CMS simulation, based on the Geant4 toolkit, has been operational within the new CMS software framework for more than four years. The description of the detector including the forward regions has been completed and detailed investigation of detector positioning and material budget has been carried out using collision data. Detailed modeling of detector noise has been performed and validated with the collision data. In view of the high luminosity runs of the Large Hadron Collider, simulation of pile-up events has become a key issue. Challenges have raised from the point of view of providing a realistic luminosity profile and modeling of out-of-time pileup events, as well as computing issues regarding memory footprint and IO access. These will be especially severe in the simulation of collision events for the LHC upgrades; a new pileup simulation architecture has been introduced to cope with these issues. The CMS detector has observed anomalous energy deposit in the calorimeters and there has been a substantial effort to understand these anomalous signal events present in the collision data. Emphasis has also been given to validation of the simulation code including the physics of the underlying models of Geant4. Test beam as well as collision data are used for this purpose. Measurements of mean response, resolution, energy sharing between the electromagnetic and hadron calorimeters, shower shapes for single hadrons are directly compared with predictions from Monte Carlo. A suite of performance analysis tools has been put in place and has been used to drive several optimizations to allow the code to fit the constraints posed by the CMS computing model.

  15. Sialylation regulates peripheral tolerance in CD4+ T cells.

    PubMed

    Brennan, Patrick J; Saouaf, Sandra J; Van Dyken, Steve; Marth, Jamey D; Li, Bin; Bhandoola, Avinash; Greene, Mark I

    2006-05-01

    Decreased binding by the 6C10 auto-antibody serves as a unique marker for CD4+ T cell unresponsiveness after the induction of T cell tolerance in Vbeta8.1 TCR transgenic mice. We further define the nature of the epitope recognized by the 6C10 antibody to be a subset of Thy-1 bearing incompletely sialylated N-linked glycans, and furthermore, we demonstrate that tolerant CD4+ T cells have an increased degree of cell-surface sialylation. To test the significance of the altered glycosylation state identified by the 6C10 auto-antibody in the tolerant CD4+ T cell population, surface sialic acid was cleaved enzymatically. Treatment of purified peripheral CD4+ T cells with Vibrio cholerae sialidase (VCS) leads to increased 6C10 binding, significantly enhances proliferation in the tolerant CD4+ population and corrects defects in phosphotyrosine signaling observed in the tolerant CD4+ T cell. Furthermore, in vivo administration of VCS enhances proliferation in both tolerant and naive CD4+ T cell subsets. These studies suggest that sialylation of glycoproteins on the surface of the CD4+ T cell contributes to the regulation of T cell responsiveness in the tolerant state. PMID:16291658

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. Status of RDMS CMS computing

    NASA Astrophysics Data System (ADS)

    Gavrilov, V.; Golutvin, I.; Kodolova, O.; Korenkov, V.; Levchuk, L.; Shmatov, S.; Tikhonenko, E.; Zhiltsov, V.

    2016-09-01

    The Compact Muon Solenoid (CMS) is a high-performance general-purpose detector at the Large Hadron Collider (LHC) at CERN. More than twenty institutes from Russia and Joint Institute for Nuclear Research (JINR) are involved in Russia and Dubna Member States (RDMS) CMS Collaboration. A proper computing grid-infrastructure has been constructed at the RDMS institutes for the participation in the running phase of the CMS experiment. Current status of RDMS CMS computing and plans of its development to the next LHC start are presented.

  1. The CMS Electromagnetic Calorimeter

    NASA Astrophysics Data System (ADS)

    Ryan, M.

    2008-06-01

    The CMS experiment at the CERN Large Hadron Collider has placed great emphasis on precise calorimetry. The electromagnetic calorimeter (ECAL) contains 75000 scintillating lead tungstate crystals that are read out using sophisticated electronics; this paper describes these technologies and how they were implemented in the calorimeter. The results of pre-calibration measurements for the detector modules are detailed. Installation of the ECAL into the underground cavern has commenced and the commissioning process and its status are discussed. The experiment is scheduled to start in 2008 and prospects for the first year of operation and running are given.

  2. 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.

  3. Open half-volume quadrature transverse electromagnetic coil for high-field magnetic resonance imaging.

    PubMed

    Peshkovsky, A S; Kennan, R P; Fabry, M E; Avdievich, N I

    2005-04-01

    A half-volume quadrature head transverse electromagnetic (TEM) coil has been constructed for 4 T imaging applications. This coil produces a sufficiently large homogeneous B(1) field region for the use as a volume coil. It provides superior transmission efficiency, resulting in significantly lower power deposition, as well as greater sensitivity and improved patient comfort and accessibility compared with conventional full-volume coils. Additionally, this coil suppresses the RF penetration artifact that distorts the RF magnetic field profile and alters the intensity in high-field images recorded with linear surface and volume coils. These advantages make it possible to apply this device as an efficient transmit/receive coil for high-field imaging with a restricted field of view.

  4. Coiled bodies without coilin.

    PubMed Central

    Bauer, D W; Gall, J G

    1997-01-01

    Nuclei assembled in vitro in Xenopus egg extract contain coiled bodies that have components from three different RNA processing pathways: pre-mRNA splicing, pre-rRNA processing, and histone pre-mRNA 3'-end formation. In addition, they contain SPH-1, the Xenopus homologue of p80-coilin, a protein characteristic of coiled bodies. To determine whether coilin is an essential structural component of the coiled body, we removed it from the egg extract by immunoprecipitation. We showed that nuclei with bodies morphologically identical to coiled bodies (at the light microscope level) formed in such coilin-depleted extract. As expected, these bodies did not stain with antibodies against coilin. Moreover, they failed to stain with an antibody against the Sm proteins, although Sm proteins associated with snRNAs were still present in the extract. Staining of the coilin- and Sm-depleted coiled bodies was normal with antibodies against two nucleolar proteins, fibrillarin and nucleolin. Similar results were observed when Sm proteins were depleted from egg extract: staining of the coiled bodies with antibodies against the Sm proteins and coilin was markedly reduced but bright nucleolin and fibrillarin staining remained. These immunodepletion experiments demonstrate an interdependence between coilin and Sm snRNPs and suggest that neither is essential for assembly of nucleolar components in coiled bodies. We propose that coiled bodies are structurally heterogeneous organelles in which the components of the three RNA processing pathways may occur in separate compartments. Images PMID:9017596

  5. Dysregulation of CD4(+) T Cell Subsets in Intracranial Aneurysm.

    PubMed

    Zhang, Hai-Feng; Zhao, Ming-Guang; Liang, Guo-Biao; Yu, Chun-Yong; He, Wenxiu; Li, Zhi-Qing; Gao, Xu

    2016-02-01

    Intracranial aneurysms (IAs) and potential IA rupture are one of the direct causes of permanent brain damage and mortality. Interestingly, the major risk factors of IA development, including hemodynamic stress, hypertension, smoking, and genetic predispositions, are closely associated with a proinflammatory immune status. Therefore, we examined the roles of CD4(+) T cells in IA pathogenesis. IA patients exhibited peripheral CD4(+) T-cell imbalance, with overrepresented T helper 1 (Th1) and Th17 activities and underrepresented Th2 and regulatory T (Treg) activities, including increased IFN-γ, TNF-α, and IL-17 production and decreased IL-10 production from total CD4(+) T cells. Chemokine receptors CXCR3 and CCR6 were used to identify Th1, Th2, and Th17 cell subsets, and CD4(+)CD25(hi) was used to identify Treg cells. Based on these markers, the data then showed altered cytokine production by each cell type and shifted subpopulation frequency. Moreover, this shift in frequency was directly correlated with IA severity. To examine the underlying mechanism of CD4(+) T cell skewing, we cocultured CD4(+) T cells with autologous monocytes and found that coculture with monocytes could significantly increase IFN-γ and IL-17 production through contact-independent mechanisms, demonstrating that monocytes could potentially contribute to the altered CD4(+) T cell composition in IA. Analyzing mRNA transcripts revealed significantly upregulated IL-1β and TNF-α expression by monocytes from IA patients. We found a loss of CD4(+) T cell subset balance that was likely to promote a higher state of inflammation in IA, which may exacerbate the disease through a positive feedback loop.

  6. New radiant coil technology

    SciTech Connect

    Yonezawa, M.; Amano, T.; Maruta, T.; Wall, F.

    1983-12-01

    This article demonstrates how the retrofitting of an ethylene furnace by replacing pyrolysis coils with a new design sharply improved its performance. The revamped furnace was designed and built for a 300,000 MTA (metric ton/yr) ethylene plant in the early 70s. Basic design considerations for the furnace were the use of high-severity cracking to provide high C/sub 2/H/sub 4/ and total olefin yields; by a careful selection of pyrolysis coil dimensions and materials, the coil was equipped with feedstock flexibility; and the furnace can handle four different gas fuels and two different liquid fuels. The furnace is a vertical twin-cell type with induced draft fans, and its four-pass pyrolysis coils (vertical/and single diameter) are arranged in a double staggered row. The cracked gas streams from the four-pass coils are combined at the furnace outlet by a special fitting and exit the furnace.

  7. The CMS online manual system.

    PubMed

    2008-07-01

    The U.S. Centers for Medicare & Medicaid Services (CMS) explains how health care providers can use the Web-based CMS Online Manual System to learn about the Medicare program and stay up to date with the latest program changes.

  8. 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.

  9. 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.

  10. 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

  11. 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

  12. 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

  13. 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.

  14. 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.

  15. 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.

  16. 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)

  17. 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.

  18. 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

  19. 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.

  20. Phylogenetic occurrence of coiled coil proteins: implications for tissue structure in metazoa via a coiled coil tissue matrix.

    PubMed

    Odgren, P R; Harvie, L W; Fey, E G

    1996-04-01

    We examined GenBank sequence files with a heptad repeat analysis program to assess the phylogenetic occurrence of coiled coil proteins, how heptad repeat domains are organized within them, and what structural/functional categories they comprise. Of 102,007 proteins analyzed, 5.95% (6,074) contained coiled coil domains; 1.26% (1,289) contained "extended" (> 75 amino acid) domains. While the frequency of proteins containing coiled coils was surprisingly constant among all biota, extended coiled coil proteins were fourfold more frequent in the animal kingdom and may reflect early events in the divergence of plants and animals. Structure/function categories of extended coils also revealed phylogenetic differences. In pathogens and parasites, many extended coiled coil proteins are external and bind host proteins. In animals, the majority of extended coiled coil proteins were identified as constituents of two protein categories: 1) myosins and motors; or 2) components of the nuclear matrix-intermediate filament scaffold. This scaffold, produced by sequential extraction of epithelial monolayers in situ, contains only 1-2% of the cell mass while accurately retaining morphological features of living epithelium and is greatly enriched in proteins with extensive, interrupted coiled coil forming domains. The increased occurrence of this type of protein in metazoa compared with plants or protists leads us to hypothesize a tissue-wide matrix of coiled coil interactions underlying metazoan differentiated cell and tissue structure.

  1. A periodic table of coiled-coil protein structures.

    PubMed

    Moutevelis, Efrosini; Woolfson, Derek N

    2009-01-23

    Coiled coils are protein structure domains with two or more alpha-helices packed together via interlacing of side chains known as knob-into-hole packing. We analysed and classified a large set of coiled-coil structures using a combination of automated and manual methods. This led to a systematic classification that we termed a "periodic table of coiled coils," which we have made available at http://coiledcoils.chm.bris.ac.uk/ccplus/search/periodic_table. In this table, coiled-coil assemblies are arranged in columns with increasing numbers of alpha-helices and in rows of increased complexity. The table provides a framework for understanding possibilities in and limits on coiled-coil structures and a basis for future prediction, engineering and design studies.

  2. Borehole induction coil transmitter

    SciTech Connect

    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.

  3. Enhancing Induction Coil Reliability

    NASA Astrophysics Data System (ADS)

    Kreter, K.; Goldstein, R.; Yakey, C.; Nemkov, V.

    2014-12-01

    In induction hardening, thermal fatigue is one of the main copper failure modes of induction heat treating coils. There have been papers published that describe this failure mode and others that describe some good design practices. The variables previously identified as the sources of thermal fatigue include radiation from the part surface, frequency, current, concentrator losses, water pressure and coil wall thickness. However, there is very little quantitative data on the factors that influence thermal fatigue in induction coils is available in the public domain. By using finite element analysis software this study analyzes the effect of common design variables of inductor cooling, and quantifies the relative importance of these variables. A comprehensive case study for a single shot induction coil with Fluxtrol A concentrator applied is used for the analysis.

  4. Complex Coil Assisted Single Coil Embolization for Small Intracranial Aneurysm

    PubMed Central

    Yang, Tzu-Hsien; Ou, Chang-Hsien; Chan, Si-Wa; Chen, Tai-I; Yang, Chia-Jung; Chiang, Chia-Ming; Huang, Wen-Chien

    2013-01-01

    The purpose of the technical note is to introduce the complex coil assisted coil embolization method in the treatment of intracranial small aneurysm, in order to enhance the safety of the procedure. The first microcatheter was navigated into the aneurysm sac and the ultrasoft coil was used as the embolization coil. If the embolizations coil could not stay within the aneurysm sac smoothly, such as coil herniation into parent artery during the delivery process. The second microcatheter would be navigated to the aneurysm level in the parent artery. Another complex coil was delivered within the parent artery via the second microcatheter to provide the neck bridge effect in order to enhance the stability of embolization coil. Besides, the protection coil will not disturb the parent artery flow. While the embolization coil was put into the aneurysm sac smoothly under the help of complex protective coil, the protective coil was then withdrawn gently. We use the most magnified view, dual-plane approach simultaneously to observe the stability of embolization coil. The embolization coil would be detached without any evidence of coil motion or vibration. The new method could provide the physiological protective method, without leaving any protective device such as stent within the parent artery. PMID:24024075

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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

  11. CD4 T-cell memory generation and maintenance.

    PubMed

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

    2014-01-01

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

  12. 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

  13. 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).

  14. CMS@home: Enabling Volunteer Computing Usage for CMS

    NASA Astrophysics Data System (ADS)

    Field, L.; Borras, H.; Spiga, D.; Riahi, H.

    2015-12-01

    Volunteer computing remains a largely untapped opportunistic resource for the LHC experiments. The use of virtualization in this domain was pioneered by the Test4Theory project and enabled the running of high energy particle physics simulations on home computers. This paper describes the model for CMS to run workloads using a similar volunteer computing platform. It is shown how the original approach is exploited to map onto the existing CMS workflow and identifies missing functionality along with the components and changes that are required. The final implementation of the prototype is detailed along with the identification of areas that would benefit from further development.

  15. Design of a conduction-cooled 9.4 T REBCO magnet for whole-body MRI systems

    NASA Astrophysics Data System (ADS)

    Miyazaki, Hiroshi; Iwai, Sadanori; Otani, Yasumi; Takahashi, Masahiko; Tosaka, Taizo; Tasaki, Kenji; Nomura, Shunji; Kurusu, Tsutomu; Ueda, Hiroshi; Noguchi, So; Ishiyama, Atsushi; Urayama, Shinichi; Fukuyama, Hidenao

    2016-10-01

    A project on the development of REBa2Cu3O7-δ (REBCO) magnets for ultra-high-field magnetic resonance imaging (MRI) was started in 2013. Since REBCO-coated conductors feature high mechanical strength under tensile stress and high critical current density, use of REBCO coils would allow superconducting magnets to be made smaller and lighter than conventional ones. In addition, a conduction-cooled superconducting magnet is simpler to use than one cooled by a liquid helium bath because the operation and maintenance of the cryogenic system become simpler, without the need to handle cryogenic fluid. Superconducting magnets for MRI require homogeneous, stable magnetic fields. The homogeneity of the magnetic field is highly dependent on the coil shape and position. Moreover, in REBCO magnets, the screening-current-induced magnetic field, which changes the magnetic field distribution of the magnet, is one of the critical issues. In order to evaluate the magnetic field homogeneity and the screening-current-induced magnetic field, a 1 T model magnet and some test coils were fabricated. From an evaluation of the 1 T model magnet, it was found that the main reason for magnetic field inhomogeneity was the tolerances in the z-axis positions of the coils, and therefore, it is important to control the gap between the single pancakes. In addition, we have already demonstrated the generation of an 8.27 T central magnetic field at 10 K with a small test coil. The screening-current-induced magnetic field was 0.43 T and was predictable by using an electromagnetic field simulation program. These results were reflected in the design of a conduction-cooled 9.4 T REBCO magnet for whole-body MRI systems. The magnet was composed of six main coils and two active shield coils. The total conductor length was 581 km, and the stored energy was 293 kJ. The field inhomogeneity was 24 ppm peak to peak and 3 ppm volume-root-mean-square (VRMS) for a 500 mm diameter spherical volume (DSV). The axial

  16. CMS updates discharge planning guidelines.

    PubMed

    2013-08-01

    The need for timely and comprehensive discharge planning takes on new importance as the Centers for Medicare & Medicaid Services (CMS) issues revised Discharge Planning Interpretive Guidelines for surveyors to use to assess a hospital's compliance with the Medicare Conditions of Participation. Surveyors will use the guidelines as they review medical records to determine if hospitals are following CMS criteria for evaluating patients, creating a discharge plan, and communicating with the next level of care. The guidelines provide detailed information on how patients should be evaluated to determine the need for discharge planning, how a discharge plan should be developed, and how hospitals should ensure a smooth transition as patients move from one setting to another. For the first time, CMS has included "blue boxes," which give suggestions that hospitals can use to improve discharge planning and transition and urges hospitals to voluntarily adopt them, although they will not be considered in determining compliance.

  17. CMS updates discharge planning guidelines.

    PubMed

    2013-08-01

    The need for timely and comprehensive discharge planning takes on new importance as the Centers for Medicare & Medicaid Services (CMS) issues revised Discharge Planning Interpretive Guidelines for surveyors to use to assess a hospital's compliance with the Medicare Conditions of Participation. Surveyors will use the guidelines as they review medical records to determine if hospitals are following CMS criteria for evaluating patients, creating a discharge plan, and communicating with the next level of care. The guidelines provide detailed information on how patients should be evaluated to determine the need for discharge planning, how a discharge plan should be developed, and how hospitals should ensure a smooth transition as patients move from one setting to another. For the first time, CMS has included "blue boxes," which give suggestions that hospitals can use to improve discharge planning and transition and urges hospitals to voluntarily adopt them, although they will not be considered in determining compliance. PMID:23923527

  18. 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…

  19. 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.

  20. 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.

  1. CMS - HLT Configuration Management System

    NASA Astrophysics Data System (ADS)

    Daponte, Vincenzo; Bocci, Andrea

    2015-12-01

    The CMS High Level Trigger (HLT) is a collection of software algorithms that run using an optimized version of the CMS offline reconstruction software. The HLT uses Python configuration files each containing hundreds of "modules", organized in "sequences" and "paths". Each configuration usually uses an average of 2200 different modules and more than 400 independent trigger paths. The complexity of the HLT configurations and their large number require the design of a suitable data management system. The work presented here describes the solution designed to manage the considerable number of configurations developed and to assist the editing of new configurations.

  2. CMS upgrade and future plans

    NASA Astrophysics Data System (ADS)

    Hoepfner, Kerstin

    2015-05-01

    CMS plans for operation at the LHC phase-II unprecedented in terms of luminosity thus resulting in serious consequences for detector performance. To achieve the goal to maintain the present excellent performance of the CMS detector, several upgrades are necessary. To handle the high phase-II data rates, the readout and trigger systems are redesigned using recent technology developments. The high particle rates will accelerate detector aging and require replacement of the tracker and forward calorimeters. In addition, the muon system will be extended.

  3. 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.

  4. 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.

  5. Radiofrequency heating at 9.4T: in vivo temperature measurement results in swine.

    PubMed

    Shrivastava, Devashish; Hanson, Timothy; Schlentz, Robert; Gallaghar, William; Snyder, Carl; Delabarre, Lance; Prakash, Surya; Iaizzo, Paul; Vaughan, J Thomas

    2008-01-01

    In vivo temperatures were correlated to the whole head average specific absorption rate (SAR(avg)) at 9.4T using 12 anesthetized swine (mean animal weight = 52 kg, standard deviation = 6.7 kg). Correlating the temperatures and SAR(avg) is necessary to ensure safe levels of human heating during ultra-high field MR exams. The temperatures were measured at three depths inside the brain, in the rectum, and at the head-skin of swine. A 400 MHz, continuous wave RF power was deposited to the head using a volume coil. The SAR(avg) values were varied between 2.7-5.8 W/kg. The RF power exposure durations were varied between 1.4-3.7 hr. To differentiate the temperature response caused by the RF from that of the anesthesia, the temperatures were recorded in four unheated swine. To study the effect of the spatial distribution of the RF and tissue properties, the temperature probes were placed at two brain locations (n = 4 swine for each location). Results showed that the in vivo brain temperatures correlated to the SAR(avg) in a geometry-dependent manner. Additionally, 1) the skin temperature change was not the maximum temperature change; 2) the RF heating caused an inhomogeneous brain temperature distribution; and 3) the maximum temperature occurred inside the brain.

  6. 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.

  7. 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.

  8. 42 CFR 401.108 - CMS rulings.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 2 2011-10-01 2011-10-01 false CMS rulings. 401.108 Section 401.108 Public Health... GENERAL ADMINISTRATIVE REQUIREMENTS Confidentiality and Disclosure § 401.108 CMS rulings. (a) After... regulations, but which has been adopted by CMS as having precedent, may be published in the Federal...

  9. 45 CFR 150.203 - Circumstances requiring CMS enforcement.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 45 Public Welfare 1 2011-10-01 2011-10-01 false Circumstances requiring CMS enforcement. 150.203... CARE ACCESS CMS ENFORCEMENT IN GROUP AND INDIVIDUAL INSURANCE MARKETS CMS Enforcement Processes for... requiring CMS enforcement. CMS enforces HIPAA requirements to the extent warranted (as determined by CMS)...

  10. 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

  11. Considerations in the design and optimization of coiled coil structures.

    PubMed

    Mason, Jody M; Müller, Kristian M; Arndt, Katja M

    2007-01-01

    Coiled coil motifs are, despite their apparent simplicity, highly specific, and play a significant role in the understanding of tertiary structure and its formation. The most commonly observed of the coiled coils, the parallel dimeric, is yet to be fully characterized for this structural class in general. Nonetheless, strict rules have emerged for the necessity of specific types of amino acids at specific positions. In this chapter, we discuss this system in light of existing coiled coil structures and in applying rules to coiled coils that are to be designed or optimized. Understanding and expanding on these rules is crucial in using these motifs, which play key roles in virtually every cellular process, to act as drug-delivery agents by sequestering other proteins that are not behaving natively or that have been upregulated (for example, by binding to coiled coil domains implicated in oncogenesis). The roles of the a and d "hydrophobic" core positions and the e and g "electrostatic" edge positions in directing oligomerization and pairing specificity are discussed. Also discussed is the role of these positions in concert with the b, c, and f positions in maintaining alpha-helical propensity, helix solubility, and dimer stability. PMID:17041258

  12. Considerations in the design and optimization of coiled coil structures.

    PubMed

    Mason, Jody M; Müller, Kristian M; Arndt, Katja M

    2007-01-01

    Coiled coil motifs are, despite their apparent simplicity, highly specific, and play a significant role in the understanding of tertiary structure and its formation. The most commonly observed of the coiled coils, the parallel dimeric, is yet to be fully characterized for this structural class in general. Nonetheless, strict rules have emerged for the necessity of specific types of amino acids at specific positions. In this chapter, we discuss this system in light of existing coiled coil structures and in applying rules to coiled coils that are to be designed or optimized. Understanding and expanding on these rules is crucial in using these motifs, which play key roles in virtually every cellular process, to act as drug-delivery agents by sequestering other proteins that are not behaving natively or that have been upregulated (for example, by binding to coiled coil domains implicated in oncogenesis). The roles of the a and d "hydrophobic" core positions and the e and g "electrostatic" edge positions in directing oligomerization and pairing specificity are discussed. Also discussed is the role of these positions in concert with the b, c, and f positions in maintaining alpha-helical propensity, helix solubility, and dimer stability.

  13. Transporters for Antiretroviral Drugs in Colorectal CD4+ T Cells and Circulating α4β7 Integrin CD4+ T Cells: Implications for HIV Microbicides.

    PubMed

    Mukhopadhya, Indrani; Murray, Graeme I; Duncan, Linda; Yuecel, Raif; Shattock, Robin; Kelly, Charles; Iannelli, Francesco; Pozzi, Gianni; El-Omar, Emad M; Hold, Georgina L; Hijazi, Karolin

    2016-09-01

    CD4+ T lymphocytes in the colorectal mucosa are key in HIV-1 transmission and dissemination. As such they are also the primary target for antiretroviral (ARV)-based rectal microbicides for pre-exposure prophylaxis. Drug transporters expressed in mucosal CD4+ T cells determine ARV distribution across the cell membrane and, most likely, efficacy of microbicides. We describe transporters for antiretroviral drugs in colorectal mucosal CD4+ T lymphocytes and compare gene expression with circulating α4β7+CD4+ T cells, which traffic to the intestine and have been shown to be preferentially infected by HIV-1. Purified total CD4+ T cells were obtained from colorectal tissue and blood samples by magnetic separation. CD4+ T cells expressing α4β7 integrin were isolated by fluorescence-activated cell sorting from peripheral blood mononuclear cells of healthy volunteers. Expressions of 15 efflux and uptake drug transporter genes were quantified using Taqman qPCR assays. Expression of efflux transporters MRP3, MRP5, and BCRP and uptake transporter CNT2 were significantly higher in colorectal CD4+ T cells compared to circulating CD4+ T cells (p = 0.01-0.03). Conversely, circulating α4β7+CD4+ T cells demonstrated significantly higher expression of OATPD compared to colorectal CD4+ T cells (p = 0.001). To the best of our knowledge this is the first report of drug transporter gene expression in colorectal CD4+ and peripheral α4β7+CD4+ T cells. The qualitative and quantitative differences in drug transporter gene expression profiles between α4β7+CD4+ T cells and total mucosal CD4+ T cells may have significant implications for the efficacy of rectally delivered ARV-microbicides. Most notably, we have identified efflux drug transporters that could be targeted by selective inhibitors or beneficial drug-drug interactions to enhance intracellular accumulation of antiretroviral drugs.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. CMS Pixel Data Quality Monitoring

    NASA Astrophysics Data System (ADS)

    Merkel, Petra

    2010-05-01

    We present the CMS Pixel Data Quality Monitoring (DQM) system. The concept and architecture are discussed. The monitored quantities are introduced, and the methods on how to ensure that the detector takes high-quality data with large efficiency are explained. Finally we describe the automated data certification scheme, which is used to certify and classify the data from the Pixel detector for physics analyses.

  19. CMS emphasizes quality patient care.

    PubMed

    2014-07-01

    The Inpatient Prospective Payment System proposed rule for fiscal 2015 continues the Centers for Medicare & Medicaid Services' move toward basing reimbursement on quality of care, not quantity. The rule also asks for public input on the two-midnight rule and a policy to address short-stay patients. CMS is implementing the Hospital-Acquired Condition Reduction Program, which penalizes hospitals that perform poorly. The agency proposes to add two safety measures to value-based purchasing in the future. PMID:24946382

  20. 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.

  1. Performance of jets at CMS

    NASA Astrophysics Data System (ADS)

    Schröder, Matthias; CMS Collaboration

    2015-02-01

    The calibration and reconstruction of jets critically relies on the performance of the calorimeters. Extending out to large pseudorapidities, the measurements depend on the interplay between forward calorimeters, central calorimeters, and the tracking system. The high number of additional pile-up interactions poses further complications. In CMS, these difficulties are overcome using the 'particle-flow' approach, which aims at reconstructing individually each particle in the event prior to the jet clustering. Measurements of the jet energy scale and the procedure for jet energy calibration in CMS are reviewed, which are performed with dijet, photon + jet, and Z+jet data collected in proton-proton collisions at a centre-of-mass energy of 8 TeV, corresponding to an integrated luminosity of 19.6 fb-1. The effect of pile-up interactions and the state of the art mitigation techniques used in CMS as well as the main sources of uncertainty of the jet energy calibration are also presented.

  2. Jacalin: a lectin mitogenic for human CD4 T lymphocytes.

    PubMed Central

    Pineau, N; Aucouturier, P; Brugier, J C; Preud'homme, J L

    1990-01-01

    The major protein component of seeds from jackfruit is the lectin jacalin. Jackfruit crude extracts are known to stimulate human lymphocytes, but the mitogenic properties of purified jacalin have not been studied in detail so far. Study of the proliferative response of cell populations from normal human peripheral blood to purified jacalin showed it to be mitogenic through an interaction with lymphocytes by its lectin-binding site, as shown by inhibition by IgA. Jacalin failed to stimulate B cells to proliferate and to undergo plasma cell maturation. It induced a proliferation of CD4 (and not CD8) lymphocytes, as shown by phenotypic analysis of cells recovered after culture and by studies of the response of isolated T cell subpopulations. The proliferative response to jacalin was autologous monocyte-dependent. The kinetics of jacalin-induced DNA synthesis, expression of CD25 and interleukin-2 secretion was shifted by comparison with that induced by phytohaemagglutinin. The reason for the restricted responsiveness of CD4 T cells is presently unclear; jacalin bound to all blood cells and did not significantly co-cap with CD1, CD2, CD3, CD4, CD8 and CD38, and jacalin response was neither enhanced nor inhibited by antibodies to these surface antigens. PMID:2372991

  3. 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.

  4. 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)

  5. 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.

  6. Coiled coils ensure the physiological ectodomain shedding of collagen XVII.

    PubMed

    Nishie, Wataru; Jackow, Joanna; Hofmann, Silke C; Franzke, Claus-Werner; Bruckner-Tuderman, Leena

    2012-08-24

    α-Helical coiled coils, frequent protein oligomerization motifs, are commonly observed in vital proteins. Here, using collagen XVII as an example, we provide evidence for a novel function of coiled coils in the regulation of ectodomain shedding. Transmembrane collagen XVII, an epithelial cell surface receptor, mediates dermal-epidermal adhesion in the skin, and its dysfunction is linked to human skin blistering diseases. The ectodomain of this collagen is constitutively shed from the cell surface by proteinases of a disintegrin and metalloprotease family; however, the mechanisms regulating shedding remain elusive. Here, we used site-specific mutagenesis to target the coiled-coil heptad repeats within the juxtamembranous, extracellular noncollagenous 16th A (NC16A) domain of collagen XVII. This resulted in a substantial increase of ectodomain shedding, which was not mediated by disintegrin and metalloproteases. Instead, conformational changes induced by the mutation(s) unmasked a furin recognition sequence that was used for cleavage. This study shows that apart from their functions in protein oligomerization, coiled coils can also act as regulators of ectodomain shedding depending on the biological context.

  7. Enabling opportunistic resources for CMS Computing Operations

    SciTech Connect

    Hufnagel, Dick

    2015-11-19

    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.

  8. 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.

  9. 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.

  10. 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.

  11. CD4+ T-cell deficiency in HIV patients responding to antiretroviral therapy is associated with increased expression of interferon-stimulated genes in CD4+ T cells.

    PubMed

    Fernandez, Sonia; Tanaskovic, Sara; Helbig, Karla; Rajasuriar, Reena; Kramski, Marit; Murray, John M; Beard, Michael; Purcell, Damian; Lewin, Sharon R; Price, Patricia; French, Martyn A

    2011-12-15

    Most patients with human immunodeficiency virus (HIV) who remain CD4(+) T-cell deficient on antiretroviral therapy (ART) exhibit marked immune activation. As CD4(+) T-cell activation may be mediated by microbial translocation or interferon-alpha (IFN-α), we examined these factors in HIV patients with good or poor CD4(+) T-cell recovery on long-term ART. Messenger RNA levels for 3 interferon-stimulated genes were increased in CD4(+) T cells of patients with poor CD4(+) T-cell recovery, whereas levels in patients with good recovery did not differ from those in healthy controls. Poor CD4(+) T-cell recovery was also associated with CD4(+) T-cell expression of markers of activation, senescence, and apoptosis, and with increased serum levels of the lipopolysaccharide receptor and soluble CD14, but these were not significantly correlated with expression of the interferon-stimulated genes. Therefore, CD4(+) T-cell recovery may be adversely affected by the effects of IFN-α, which may be amenable to therapeutic intervention.

  12. 17 CFR 240.11a1-4(T) - Bond transactions on national securities exchanges.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Bond transactions on national securities exchanges. 240.11a1-4(T) Section 240.11a1-4(T) Commodity and Securities Exchanges SECURITIES AND....11a1-4(T) Bond transactions on national securities exchanges. A transaction in a bond, note,...

  13. 26 CFR 1.1001-4T - Modifications of certain derivative contracts (temporary).

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... (temporary). 1.1001-4T Section 1.1001-4T Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE... Recognition of Gain Or Loss § 1.1001-4T Modifications of certain derivative contracts (temporary). (a) Certain... organization (as such term is defined in section 1a of the Commodity Exchange Act (7 U.S.C. 1a)) or a...

  14. 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.

  15. The CMS Journey to LHC Physics

    ScienceCinema

    None

    2016-07-12

    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.

  16. 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.

  17. Inverse design of an organ-oriented RF coil for open, vertical-field, MR-guided, focused ultrasound surgery.

    PubMed

    Xin, Xuegang; Han, Jijun; Feng, Yanqiu; Feng, Qianjin; Chen, Wufan

    2012-12-01

    The advantages of open, vertical-field, magnetic resonance-guided, focused ultrasound surgery (MRgFUS) are attractive. The inverse technique using the bi-boundary conditions is proposed to design a uterine-oriented intraoperative RF coil with an ultrasound aperture for the MRgFUS system. In the current proposed scheme, the desired magnetic field of the RF coil was set to completely overlap the target organ. The current density distribution on the RF coil surface, accounting for the expected magnetic field, was solved using the inverse technique. The stream function was available through the 'discretization' of the current density distribution on the RF coil surface. The coil windings were obtained from the contour plot of the stream function. As a modification of previous designs, the bi-boundary conditions are proposed in the inverse technique for the existence of the ultrasound aperture. Based on the obtained coil windings, a prototype coil was constructed. MR imaging of the phantom and the human body was performed to show the efficacy of the prototype coil. The results of temperature measurement using the prototype coil in a 0.4-T MR system were satisfactory. The performance of the prototype coil improved compared with the previously reported design.

  18. 42 CFR 423.509 - Termination of contract by CMS.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 3 2011-10-01 2011-10-01 false Termination of contract by CMS. 423.509 Section 423... Contracts with Part D plan sponsors § 423.509 Termination of contract by CMS. (a) Termination by CMS. CMS may at any time terminate a contract if CMS determines that the Part D plan sponsor meets any of...

  19. 42 CFR 422.510 - Termination of contract by CMS.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 3 2011-10-01 2011-10-01 false Termination of contract by CMS. 422.510 Section 422... Advantage Organizations § 422.510 Termination of contract by CMS. (a) Termination by CMS. CMS may at any time terminate a contract if CMS determines that the MA organization meets any of the following:...

  20. 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.

  1. 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.

  2. The CMS workload management system

    NASA Astrophysics Data System (ADS)

    Cinquilli, M.; Evans, D.; Foulkes, S.; Hufnagel, D.; Mascheroni, M.; Norman, M.; Maxa, Z.; Melo, A.; Metson, S.; Riahi, H.; Ryu, S.; Spiga, D.; Vaandering, E.; Wakefield, S.; Wilkinson, R.

    2012-12-01

    CMS has started the process of rolling out a new workload management system. This system is currently used for reprocessing and Monte Carlo production with tests under way using it for user analysis. It was decided to combine, as much as possible, the production/processing, analysis and T0 codebases so as to reduce duplicated functionality and make best use of limited developer and testing resources. This system now includes central request submission and management (Request Manager); a task queue for parcelling up and distributing work (WorkQueue) and agents which process requests by interfacing with disparate batch and storage resources (WMAgent).

  3. 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)

  4. 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

  5. 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

  6. 42 CFR 401.108 - CMS rulings.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... September 1981, a precedent final opinion or order or a statement of policy or interpretation that has not... final opinions and orders and statements of policy and interpretation that were adopted by CMS before... components, on all HHS components that adjudicate matters under the jurisdiction of CMS, and on the...

  7. CMS: Present status, limitations, and upgrade plans

    SciTech Connect

    Cheung, H.W.K.; /Fermilab

    2011-09-01

    An overview of the CMS upgrade plans will be presented. A brief status of the CMS detector will be given, covering some of the issues we have so far experienced. This will be followed by an overview of the various CMS upgrades planned, covering the main motivations for them, and the various R&D efforts for the possibilities under study. The CMS detector has been working extremely well since the start of data-taking at the LHC as is evidenced by the numerous excellent results published by CMS and presented at this workshop and recent conferences. Less well documented are the various issues that have been encountered with the detector. In the spirit of this workshop I will cover some of these issues with particular emphasis on problems that motivate some of the upgrades to the CMS detector for this decade of data-taking. Though the CMS detector has been working extremely well and expectations are great for making the most of the LHC luminosity, there have been a number of issues encountered so far. Some of these have been described and while none currently presents a problem for physics performance, some of them are expected to become more problematic, especially at the highest Phase 1 luminosities for which the majority of the integrated luminosity will be collected. These motivate upgrades for various parts of the CMS detector so that the current excellent physics performance can be maintained or even surpassed in the realm of the highest Phase 1 luminosities.

  8. 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

  9. 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.

  10. 23 CFR 500.109 - CMS.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 23 Highways 1 2011-04-01 2011-04-01 false CMS. 500.109 Section 500.109 Highways FEDERAL HIGHWAY 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...

  11. 23 CFR 500.109 - CMS.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 23 Highways 1 2013-04-01 2013-04-01 false CMS. 500.109 Section 500.109 Highways FEDERAL HIGHWAY 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...

  12. 23 CFR 500.109 - CMS.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 23 Highways 1 2014-04-01 2014-04-01 false CMS. 500.109 Section 500.109 Highways FEDERAL HIGHWAY 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...

  13. 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.

  14. 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)

  15. The evolution and structure prediction of coiled coils across all genomes.

    PubMed

    Rackham, Owen J L; Madera, Martin; Armstrong, Craig T; Vincent, Thomas L; Woolfson, Derek N; Gough, Julian

    2010-10-29

    Coiled coils are α-helical interactions found in many natural proteins. Various sequence-based coiled-coil predictors are available, but key issues remain: oligomeric state and protein-protein interface prediction and extension to all genomes. We present SpiriCoil (http://supfam.org/SUPERFAMILY/spiricoil), which is based on a novel approach to the coiled-coil prediction problem for coiled coils that fall into known superfamilies: hundreds of hidden Markov models representing coiled-coil-containing domain families. Using whole domains gives the advantage that sequences flanking the coiled coils help. SpiriCoil performs at least as well as existing methods at detecting coiled coils and significantly advances the state of the art for oligomer state prediction. SpiriCoil has been run on over 16 million sequences, including all completely sequenced genomes (more than 1200), and a resulting Web interface supplies data downloads, alignments, scores, oligomeric state classifications, three-dimensional homology models and visualisation. This has allowed, for the first time, a genomewide analysis of coiled-coil evolution. We found that coiled coils have arisen independently de novo well over a hundred times, and these are observed in 16 different oligomeric states. Coiled coils in almost all oligomeric states were present in the last universal common ancestor of life. The vast majority of occasions that individual coiled coils have arisen de novo were before the last universal common ancestor of life; we do, however, observe scattered instances throughout subsequent evolutionary history, mostly in the formation of the eukaryote superkingdom. Coiled coils do not change their oligomeric state over evolution and did not evolve from the rearrangement of existing helices in proteins; coiled coils were forged in unison with the fold of the whole protein.

  16. 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.

  17. Infrared amide I' band of the coiled coil.

    PubMed

    Reisdorf, W C; Krimm, S

    1996-02-01

    The Fourier transform infrared (FTIR) spectra of several coiled-coil proteins have been shown to possess unusual features in the amide I' region. Band maxima occur in the vicinity of 1630 cm-1, with component bands at higher frequency. This is well below the observed band at 1650 cm-1 found in standard alpha-helical polypeptides such as poly-L-alanine. Normal mode calculations on models of the coiled-coil structure have been performed to investigate this issue. We find that the observed band profile can be reproduced with very small random variation on the phi, psi of tropomyosin. We believe that the shift to lower frequency is due to additional hydrogen bonding of the solvent accessible backbone CO groups to water.

  18. 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.

  19. Technical progress in industrial COIL

    NASA Astrophysics Data System (ADS)

    Tei, K.; Sugimoto, Daichi; Ito, T.; Watanabe, G.; Vyskubyenko, O.; Takeuchi, N.; Muto, S.; Fujioka, Tomoo

    2005-03-01

    Chemical oxygen-iodine laser (COIL) has a great potential for applications such as decommissioning and dismantlement (D&D) of nuclear reactor, rock destruction and removal and extraction of a natural resource (Methane hydrate) because of the unique characteristics such as power scalability, high optical beam quality and optical fiber beam. Five-kilowatt Chemical oxygen-iodine laser (COIL) test facility has been developed. The chemical efficiency of 27% has been demonstrated with a moderate beam quality for optical fiber coupling. Our research program contains conventional/ejector-COIL scheme, Jet-SOG/Mist-SOG optimization, fiber delivery and long-term operation.

  20. 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.

  1. 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.

  2. 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.

  3. 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

  4. 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

  5. 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

  6. 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.

  7. CMS results on multijet correlations

    SciTech Connect

    Safronov, Grigory

    2015-04-10

    We present recent CMS measurements on multijet correlations using forward and low-p{sub T} jets, focusing on searches for BFKL and saturation phenomena. In pp collisions at √(s)=7 TeV, azimuthal correlations in dijets separated in rapidity by up to 9.4 units were measured. The results are compared to BFKL- and DGLAP-based predictions. In pp collisions at √(s)=8 TeV, cross sections for jets with p{sub T} > 21 GeV and |y| < 4.7, and for track-jets with p{sub T} > 1 GeV (minijets) are presented. The minijet results are sensitive to the bound imposed by the total inelastic cross section, and are compared to various models for taming the growth of the 2 → 2 cross section at low p{sub T}.

  8. 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.

  9. CMS results on multijet correlations

    NASA Astrophysics Data System (ADS)

    Safronov, Grigory

    2015-04-01

    We present recent CMS measurements on multijet correlations using forward and low-pT jets, focusing on searches for BFKL and saturation phenomena. In pp collisions at √{s }=7 TeV, azimuthal correlations in dijets separated in rapidity by up to 9.4 units were measured. The results are compared to BFKL- and DGLAP-based predictions. In pp collisions at √{s }=8 TeV, cross sections for jets with pT > 21 GeV and |y| < 4.7, and for track-jets with pT > 1 GeV (minijets) are presented. The minijet results are sensitive to the bound imposed by the total inelastic cross section, and are compared to various models for taming the growth of the 2 → 2 cross section at low pT.

  10. 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.

  11. 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.

  12. 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.

  13. Increased competition for antigen during priming negatively impacts the generation of memory CD4 T cells

    PubMed Central

    Blair, David A.; Lefrançois, Leo

    2007-01-01

    The factors involved in the differentiation of memory CD4 T cells from naïve precursors are poorly understood. We developed a system to examine the effect of increased competition for antigen by CD4 T cells on the generation of memory in response to infection with a recombinant vesicular stomatitis virus. Competition was initially regulated by increasing the precursor frequency of adoptively transferred naïve T cell antigen receptor transgenic CD4 T cells. Despite robust proliferation at high precursor frequencies, memory CD4 T cells did not develop, whereas decreasing the input number of naïve CD4 T cells promoted memory development after infection. The lack of memory development was linked to reduced blastogenesis and poor effector cell induction, but not to initial recruitment or proliferation of antigen-specific CD4 T cells. To prove that availability of antigen alone could regulate memory CD4 T cell development, we used treatment with an mAb specific for the epitope recognized by the transferred CD4 T cells. At high doses, this mAb effectively inhibited the antigen-specific CD4 T cell response. However, at a very low dose of mAb, primary CD4 T cell expansion was unaffected, although memory development was dramatically reduced. Moreover, the induction of effector function was concomitantly inhibited. Thus, competition for antigen during CD4 T cell priming is a major contributing factor to the development of the memory CD4 T cell pool. PMID:17827281

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  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. 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

  3. 42 CFR 426.517 - CMS' statement regarding new evidence.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 3 2011-10-01 2011-10-01 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... experts; and (5) Presented during any hearing. (b) CMS may submit a statement regarding whether the...

  4. 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...

  5. 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 ...

  6. 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...

  7. 26 CFR 1.883-4T - Qualified shareholder stock ownership test (temporary).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... (temporary). 1.883-4T Section 1.883-4T Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY... ownership test (temporary). (a) through (d)(4)(i)(B) For further guidance see § 1.883-4(a) through (d)(4)(i... qualified shareholders by country of residence or organization, whichever is applicable; and the...

  8. RNA-Seq Transcriptome Analysis of Direction-Selective T4/T5 Neurons in Drosophila

    PubMed Central

    Pankova, Katarina; Borst, Alexander

    2016-01-01

    Neuronal computation underlying detection of visual motion has been studied for more than a half-century. In Drosophila, direction-selective T4/T5 neurons show supralinear signal amplification in response to stimuli moving in their preferred direction, in agreement with the prediction made by the Hassenstein-Reichardt detector. Nevertheless, the molecular mechanism explaining how the Hassenstein-Reichardt model is implemented in T4/T5 cells has not been identified yet. In the present study, we utilized cell type-specific transcriptome profiling with RNA-seq to obtain a complete gene expression profile of T4/T5 neurons. We analyzed the expression of genes that affect neuronal computational properties and can underlie the molecular implementation of the core features of the Hassenstein-Reichardt model to the dendrites of T4/T5 neurons. Furthermore, we used the acquired RNA-seq data to examine the neurotransmitter system used by T4/T5 neurons. Surprisingly, we observed co-expression of the cholinergic markers and the vesicular GABA transporter in T4/T5 neurons. We verified the previously undetected expression of vesicular GABA transporter in T4/T5 cells using VGAT-LexA knock-in line. The provided gene expression dataset can serve as a useful source for studying the properties of direction-selective T4/T5 neurons on the molecular level. PMID:27684367

  9. 26 CFR 1.132-4T - Line of business limitation-1985 through 1988 (temporary).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 2 2010-04-01 2010-04-01 false Line of business limitation-1985 through 1988 (temporary). 1.132-4T Section 1.132-4T Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY... Manual (ESIC Manual) prepared by the Statistical Policy Division of the U.S. Office of Management...

  10. 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...

  11. 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.

  12. 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.

  13. 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

  14. 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

  15. CMS muon detector and trigger performance

    NASA Astrophysics Data System (ADS)

    Park, Sung Keun; CMS Collaboration

    2011-06-01

    The CMS muon system has been in full operation since its commissioning with several million events of cosmic ray data. The muon system of the CMS experiment consists of three independent detectors: Resistive Plate Chambers (RPCs) both in the barrel and the endcap, Drift Tubes (DTs) in the barrel, and Cathode Strip Chambers (CSCs) in the endcap region. In this report, the performance of each of these muon detectors and their trigger response are presented.

  16. 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.

  17. Burn-injury affects gut-associated lymphoid tissues derived CD4+ T cells☆

    PubMed Central

    Fazal, Nadeem; Shelip, Alla; Alzahrani, Alhusain J.

    2013-01-01

    After scald burn-injury, the intestinal immune system responds to maintain immune balance. In this regard CD4+T cells in Gut-Associated Lymphoid Tissues (GALT), like mesenteric lymph nodes (MLN) and Peyer's patches (PP) respond to avoid immune suppression following major injury such as burn. Therefore, we hypothesized that the gut CD4+T cells become dysfunctional and turn the immune homeostasis towards depression of CD4+ T cell-mediated adaptive immune responses. In the current study we show down regulation of mucosal CD4+ T cell proliferation, IL-2 production and cell surface marker expression of mucosal CD4+ T cells moving towards suppressive-type. Acute burn-injury lead to up-regulation of regulatory marker (CD25+), down regulation of adhesion (CD62L, CD11a) and homing receptor (CD49d) expression, and up-regulation of negative co-stimulatory (CTLA-4) molecule. Moreover, CD4+CD25+ T cells of intestinal origin showed resistance to spontaneous as well as induced apoptosis that may contribute to suppression of effector CD4+ T cells. Furthermore, gut CD4+CD25+ T cells obtained from burn-injured animals were able to down-regulate naïve CD4+ T cell proliferation following adoptive transfer of burn-injured CD4+CD25+ T cells into sham control animals, without any significant effect on cell surface activation markers. Together, these data demonstrate that the intestinal CD4+ T cells evolve a strategy to promote suppressive CD4+ T cell effector responses, as evidenced by enhanced CD4+CD25+ T cells, up-regulated CTLA-4 expression, reduced IL-2 production, tendency towards diminished apoptosis of suppressive CD4+ T cells, and thus lose their natural ability to regulate immune homeostasis following acute burn-injury and prevent immune paralysis. PMID:24600563

  18. CRAB: Distributed analysis tool for CMS

    NASA Astrophysics Data System (ADS)

    Sala, Leonardo; CMS Collaboration

    2012-12-01

    CMS has a distributed computing model, based on a hierarchy of tiered regional computing centers and adopts a data driven model for the end user analysis. This model foresees that jobs are submitted to the analysis resources where data are hosted. The increasing complexity of the whole computing infrastructure makes the simple analysis work flow more and more complicated for the end user. CMS has developed and deployed a dedicated tool named CRAB (CMS Remote Analysis Builder) in order to guarantee the physicists an efficient access to the distributed data whilst hiding the underlying complexity. This tool is used by CMS to enable the running of physics analysis jobs in a transparent manner over data distributed across sites. It factorizes out the interaction with the underlying batch farms, grid infrastructure and CMS data management tools, allowing the user to deal only with a simple and intuitive interface. We present the CRAB architecture, as well as the current status and lessons learnt in deploying this tool for use by the CMS collaboration. We also present the future development of the CRAB system.

  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. 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.

  1. 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.

  2. 26 CFR 1.103(n)-4T - Elective carryforward of unused private activity bond limit (temporary).

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... bond limit (temporary). 1.103(n)-4T Section 1.103(n)-4T Internal Revenue INTERNAL REVENUE SERVICE... Excluded from Gross Income § 1.103(n)-4T Elective carryforward of unused private activity bond limit... carryforward for any one or more projects described in A-5 of this § 1.103(n)-4T (carryforward projects)....

  3. 26 CFR 1.103(n)-4T - Elective carryforward of unused private activity bond limit (temporary).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... bond limit (temporary). 1.103(n)-4T Section 1.103(n)-4T Internal Revenue INTERNAL REVENUE SERVICE... Excluded from Gross Income § 1.103(n)-4T Elective carryforward of unused private activity bond limit... carryforward for any one or more projects described in A-5 of this § 1.103(n)-4T (carryforward projects)....

  4. Self assembly of coiled-coil peptide-porphyrin complexes.

    PubMed

    Kokona, Bashkim; Kim, Andrew M; Roden, R Claire; Daniels, Joshua P; Pepe-Mooney, Brian J; Kovaric, Brian C; de Paula, Julio C; Johnson, Karl A; Fairman, Robert

    2009-06-01

    We are interested in the controlled assembly of photoelectronic materials using peptides as scaffolds and porphyrins as the conducting material. We describe the integration of a peptide-based polymer strategy with the ability of designed basic peptides to bind anionic porphyrins in order to create regulated photoelectronically active biomaterials. We have described our peptide system in earlier work, which demonstrates the ability of a peptide to form filamentous materials made up of self-assembling coiled-coil structures. We have modified this peptide system to include lysine residues appropriately positioned to specifically bind meso-tetrakis(4-sulfonatophenyl)porphine (TPPS(4)), a porphyrin that contains four negatively charged sulfonate groups at neutral pH. We measure the binding of TPPS(4) to our peptide using UV--visible and fluorescence spectroscopies to follow the porphyrin signature. We determine the concomitant acquisition of helical secondary structure in the peptide upon TPPS(4) binding using circular dichroism spectropolarimetry. This binding fosters polymerization of the peptide, as shown by absorbance extinction effects in the peptide CD spectra. The morphologies of the peptide/porphyrin complexes, as imaged by atomic force microscopy, are consistent with the coiled-coil polymers that we had characterized earlier, except that the heights are slightly higher, consistent with porphyrin binding. Evidence for exciton coupling in the copolymers is shown by red-shifting in the UV--visible data, however, the coupling is weak based on a lack of fluorescence quenching in fluorescence experiments.

  5. 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

  6. Transmission of survival signals through Delta-like 1 on activated CD4+ T cells

    PubMed Central

    Furukawa, Takahiro; Ishifune, Chieko; Tsukumo, Shin-ichi; Hozumi, Katsuto; Maekawa, Yoichi; Matsui, Naoko; Kaji, Ryuji; Yasutomo, Koji

    2016-01-01

    Notch expressed on CD4+ T cells transduces signals that mediate their effector functions and survival. Although Notch signaling is known to be cis-inhibited by Notch ligands expressed on the same cells, the role of Notch ligands on T cells remains unclear. In this report we demonstrate that the CD4+ T cell Notch ligand Dll1 transduces signals required for their survival. Co-transfer of CD4+ T cells from Dll1−/− and control mice into recipient mice followed by immunization revealed a rapid decline of CD4+ T cells from Dll1−/− mice compared with control cells. Dll1−/− mice exhibited lower clinical scores of experimental autoimmune encephalitis than control mice. The expression of Notch target genes in CD4+ T cells from Dll1−/− mice was not affected, suggesting that Dll1 deficiency in T cells does not affect cis Notch signaling. Overexpression of the intracellular domain of Dll1 in Dll1-deficient CD4+ T cells partially rescued impaired survival. Our data demonstrate that Dll1 is an independent regulator of Notch-signaling important for the survival of activated CD4+ T cells, and provide new insight into the physiological roles of Notch ligands as well as a regulatory mechanism important for maintaining adaptive immune responses. PMID:27659682

  7. 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.

  8. IL-7 signaling imparts polyfunctionality and stemness potential to CD4(+) T cells.

    PubMed

    Ding, Zhi-Chun; Liu, Chufeng; Cao, Yang; Habtetsion, Tsadik; Kuczma, Michal; Pi, Wenhu; Kong, Heng; Cacan, Ercan; Greer, Susanna F; Cui, Yan; Blazar, Bruce R; Munn, David H; Zhou, Gang

    2016-06-01

    The functional status of CD4(+) T cells is a critical determinant of antitumor immunity. Polyfunctional CD4(+) T cells possess the ability to concomitantly produce multiple Th1-type cytokines, exhibiting a functional attribute desirable for cancer immunotherapy. However, the mechanisms by which these cells are induced are neither defined nor it is clear if these cells can be used therapeutically to treat cancer. Here, we report that CD4(+) T cells exposed to exogenous IL-7 during antigenic stimulation can acquire a polyfunctional phenotype, characterized by their ability to simultaneously express IFNγ, IL-2, TNFα and granzyme B. This IL-7-driven polyfunctional phenotype was associated with increased histone acetylation in the promoters of the effector genes, indicative of increased chromatin accessibility. Moreover, forced expression of a constitutively active (CA) form of STAT5 recapitulated IL-7 in inducing CD4(+) T-cell polyfunctionality. Conversely, the expression of a dominant negative (DN) form of STAT5 abolished the ability of IL-7 to induce polyfunctional CD4(+) T cells. These in-vitro-generated polyfunctional CD4(+) T cells can traffic to tumor and expand intratumorally in response to immunization. Importantly, adoptive transfer of polyfunctional CD4(+) T cells following lymphodepletive chemotherapy was able to eradicate large established tumors. This beneficial outcome was associated with the occurrence of antigen epitope spreading, activation of the endogenous CD8(+) T cells and persistence of donor CD4(+) T cells exhibiting memory stem cell attributes. These findings indicate that IL-7 signaling can impart polyfunctionality and stemness potential to CD4(+) T cells, revealing a previously unknown property of IL-7 that can be exploited in adoptive T-cell immunotherapy.

  9. [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

  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. A MRI rotary phased array head coil.

    PubMed

    Li, Bing Keong; Weber, Ewald; Crozier, Stuart

    2013-08-01

    A new rotary phased array (RPA) head coil that can provide homogenous brain images comparable to volumetric radiofrequency coils is proposed for magnetic resonance brain imaging applications. The design of the RPA head coil is a departure from conventional circumferential array design method, as coil elements of the RPA head coil have a "paddle-like" structure consisting of a pair of main conductors located on opposite sides, inserted equi-angularly around and over the head. A prototype 2T receive-only 4-element RPA head coil was constructed and experimentally tested against a conventional receive-only 4-element phased array head coil and a commercial receive-only quadrature birdcage head coil. Homogenous phantom images acquired by the RPA head coil show that signal intensity deep at the center of the phantom was improved as compared to the conventional phased array head coil and this improvement allow the RPA head coil to acquire homogenous brain images similar to brain images acquired with the birdcage head coil. In addition, partial parallel imaging was used in conjunction with the RPA head coil to enable rapid imaging.

  12. 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.

  13. Fit to an analytic form of the measured central CMS magnetic field

    NASA Astrophysics Data System (ADS)

    Maroussov, Vassili

    The CMS magnetic field measurements inside the hadronic calorimeter barrel (HB) had been carried out at CERN SX5 in November 2006 using the "fieldmapper" device developed at FNAL. The goal of these measurements was to provide field maps for several nominal field values with the precision of +/-5˙10 -4 T, usable for charged particle tracking. An initial analysis of the measured data indicated presence of large systematic errors, which supposedly were related to fieldmapper misalignments and errors of calibration of the Hall probes. An algorithm had been developed that allows to eliminate the systematic errors and to recover the actual field. The algorithm is based on the idea of making the measurements self-consistent (that is: the field must satisfy the Maxwell equations) by introducing fitted parameters for amplifier gain shifts and the probes position shifts. With the help of this algorithm, an analytic field representation, both for the axially symmetric and complete 3D field models, had been obtained which is within +/-4˙10 -4 T agreement with the measured field values in whole volume spanned in measurements except the most remote off center part of it, which makes only 6% of total volume. Based on this analytic axially symmetric fit, a C++ code (BFit) is developed intended to be used in the CMS offline tracking. This code is recently integrated into the CMSSW software package.

  14. Anchor Coil Technique for Arteriovenous Fistula Embolization

    PubMed Central

    Kanemaru, Kazuya; Ezura, Masayuki; Nishiyama, Yoshihisa; Yagi, Takashi; Yoshioka, Hideyuki; Fukumoto, Yuichiro; Horikoshi, Toru; Kinouch, Hiroyuki

    2014-01-01

    Summary We describe a case of arteriovenous fistula (AVF) successfully treated by coil embolization with an anchor coil inserted in the varix to facilitate dense packing at the shunting site. AVF of the left anterior choroidal artery (AChoA) draining into the ipsilateral basal vein of Rosenthal was incidentally found in a newborn female. A single detachable coil was inserted as an anchor into the varix adjacent to the shunt, and the microcatheter was pulled back to the shunting point. Three more detachable coils were delivered at the shunting point without migration under the support of the anchor coil, and the AVF was successfully obliterated with preservation of AChoA blood flow. The anchor coil technique can reduce the risk of coil migration and the number of coils required. PMID:24976089

  15. Alternating current losses in superconducting coils

    NASA Technical Reports Server (NTRS)

    Wipf, S. L.; Guderjahn, C. A.

    1972-01-01

    Report examines relationship between coil loss and frequency and heat loss in coil as a function of the magnetic field H. Information is of value to manufacturers of superconducting magnets, motors and generators.

  16. 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.)

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. Validation of software releases for CMS

    SciTech Connect

    Gutsche, Oliver; /Fermilab

    2009-03-01

    The CMS software stack currently consists of more than 2 Million lines of code developed by over 250 authors with a new version being released every week. CMS has setup a release validation process for quality assurance which enables the developers to compare to previous releases and references. This process provides the developers with reconstructed datasets of real data and MC samples. The samples span the whole range of detector effects and important physics signatures to benchmark the performance of the software. They are used to investigate interdependency effects of software packages and to find and fix bugs. The samples have to be available in a very short time after a release is published to fit into the streamlined CMS development cycle. The standard CMS processing infrastructure and dedicated resources at CERN and FNAL are used to achieve a very short turnaround of 24 hours. The here described release validation process is an integral part of CMS software development and contributes significantly to ensure stable production and analysis. It's success emphasizes the importance of a streamlined release validation process for projects with a large code basis and significant number of developers and can function as an example for future projects.

  2. 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.

  3. Tapping CD4 T cells for cancer immunotherapy: the choice of personalized genomics.

    PubMed

    Zanetti, Maurizio

    2015-03-01

    Cellular immune responses that protect against tumors typically have been attributed to CD8 T cells. However, CD4 T cells also play a central role. It was shown recently that, in a patient with metastatic cholangiocarcinoma, CD4 T cells specific for a peptide from a mutated region of ERBB2IP could arrest tumor progression. This and other recent findings highlight new opportunities for CD4 T cells in cancer immunotherapy. In this article, I discuss the role and regulation of CD4 T cells in response to tumor Ags. Emphasis is placed on the types of Ags and mechanisms that elicit tumor-protective responses. I discuss the advantages and drawbacks of cancer immunotherapy through personalized genomics. These considerations should help to guide the design of next-generation therapeutic cancer vaccines.

  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. 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.

  6. CD4 T cell activation by B cells in human Leishmania (Viannia) infection

    PubMed Central

    2014-01-01

    Background An effective adaptive immune response requires activation of specific CD4 T cells. The capacity of B cells to activate CD4 T cells in human cutaneous leishmaniasis caused by Leishmania (Viannia) has not been evaluated. Methods CD4 T cell activation by B cells of cutaneous leishmaniasis patients was evaluated by culture of PBMCs or purified B cells and CD4 T cells with Leishmania panamensis antigens. CD4 T cell and B cell activation markers were evaluated by flow cytometry and 13 cytokines were measured in supernatants with a bead-based capture assay. The effect of Leishmania antigens on BCR-mediated endocytosis of ovalbumin was evaluated in the Ramos human B cell line by targeting the antigen with anti-IgM-biotin and anti-biotin-ovalbumin-FITC. Results Culture of PBMCs from cutaneous leishmaniasis patients with Leishmania antigens resulted in upregulation of the activation markers CD25 and CD69 as well as increased frequency of CD25hiCD127- cells among CD4 T cells. Concomitantly, B cells upregulated the costimulatory molecule CD86. These changes were not observed in PBMCs from healthy subjects, indicating participation of Leishmania-specific lymphocytes expanded in vivo. Purified B cells from these patients, when interacting with purified CD4 T cells and Leishmania antigens, were capable of inducing significant increases in CD25 and CD69 expression and CD25hiCD127- frequency in CD4 T cells. These changes were associated with upregulation of CD86 in B cells. Comparison of changes in CD4 T cell activation parameters between PBMC and B cell/CD4 T cell cultures showed no statistically significant differences; further, significant secretion of IFN-γ, TNF-α, IL-6 and IL-13 was induced in both types of cultures. Additionally, culture with Leishmania antigens enhanced BCR-mediated endocytosis of ovalbumin in Ramos human B cells. Conclusions The capacity of B cells specific for Leishmania antigens in peripheral blood of cutaneous leishmaniasis patients to

  7. 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

  8. 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

  9. 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.

  10. Stephanthraniline A suppressed CD4(+) T cell-mediated immunological hepatitis through impairing PKCθ function.

    PubMed

    Chen, Feng-Yang; Zhou, Li-Fei; Li, Xiao-Yu; Zhao, Jia-Wen; Xu, Shi-Fang; Huang, Wen-Hai; Gao, Li-Juan; Hao, Shu-Juan; Ye, Yi-Ping; Sun, Hong-Xiang

    2016-10-15

    Stephanthraniline A (STA), a C21 steroid isolated from Stephanotis mucronata (Blanco) Merr., was previously shown to inhibit T cells activation and proliferation in vitro and in vivo. The purpose of this study was to further evaluate the in vivo immunosuppressive activity of STA and to elucidate its potential mechanisms. The results showed that pretreatment with STA significantly attenuated concanavalin A (Con A)-induced hepatitis and reduced CD4(+) T cells activation and aggregation in hepatic tissue in mice. STA directly suppressed the activation and proliferation of Con A-induced CD4(+) T cells, and inhibited NFAT, NFκB and MAPK signaling cascades in activated CD4(+) T cells in vitro. Moreover, it was proved that STA inhibited T cells activation and proliferation through proximal T cell-receptor (TCR) signaling- and Ca(2+) signaling-independent way. The molecular docking studies predicted that STA could tight bind to PKCθ via five hydrogen. The further findings indicated STA directly inhibited PKCθ kinase activity, and its phosphorylation in activated CD4(+) T cells in vitro. Collectively, the present study indicated that STA could protect against CD4(+) T cell-mediated immunological hepatitis in mice through PKCθ and its downstream NFAT, NFκB and MAPK signaling cascades. These results highlight the potential of STA as an effective leading compound for use in the treatment of CD4(+) T cell-mediated inflammatory and autoimmune diseases.

  11. 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

  12. 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

  13. 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.

  14. 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

  15. Myeloid dendritic cells induce HIV-1 latency in non-proliferating CD4+ T cells.

    PubMed

    Evans, Vanessa A; Kumar, Nitasha; Filali, Ali; Procopio, Francesco A; Yegorov, Oleg; Goulet, Jean-Philippe; Saleh, Suha; Haddad, Elias K; da Fonseca Pereira, Candida; Ellenberg, Paula C; Sekaly, Rafick-Pierre; Cameron, Paul U; Lewin, Sharon R

    2013-01-01

    Latently infected resting CD4(+) T cells are a major barrier to HIV cure. Understanding how latency is established, maintained and reversed is critical to identifying novel strategies to eliminate latently infected cells. We demonstrate here that co-culture of resting CD4(+) T cells and syngeneic myeloid dendritic cells (mDC) can dramatically increase the frequency of HIV DNA integration and latent HIV infection in non-proliferating memory, but not naïve, CD4(+) T cells. Latency was eliminated when cell-to-cell contact was prevented in the mDC-T cell co-cultures and reduced when clustering was minimised in the mDC-T cell co-cultures. Supernatants from infected mDC-T cell co-cultures did not facilitate the establishment of latency, consistent with cell-cell contact and not a soluble factor being critical for mediating latent infection of resting CD4(+) T cells. Gene expression in non-proliferating CD4(+) T cells, enriched for latent infection, showed significant changes in the expression of genes involved in cellular activation and interferon regulated pathways, including the down-regulation of genes controlling both NF-κB and cell cycle. We conclude that mDC play a key role in the establishment of HIV latency in resting memory CD4(+) T cells, which is predominantly mediated through signalling during DC-T cell contact.

  16. 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.

  17. Power distribution studies for CMS forward 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.

  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. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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...

  4. 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...

  5. 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...

  6. 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.

  7. Design of a superconducting volume coil for magnetic resonance microscopy of the mouse brain

    NASA Astrophysics Data System (ADS)

    Nouls, John C.; Izenson, Michael G.; Greeley, Harold P.; Johnson, G. Allan

    2008-04-01

    We present the design process of a superconducting volume coil for magnetic resonance microscopy of the mouse brain at 9.4 T. The yttrium barium copper oxide coil has been designed through an iterative process of three-dimensional finite-element simulations and validation against room temperature copper coils. Compared to previous designs, the Helmholtz pair provides substantially higher B1 homogeneity over an extended volume of interest sufficiently large to image biologically relevant specimens. A custom-built cryogenic cooling system maintains the superconducting probe at 60 ± 0.1 K. Specimen loading and probe retuning can be carried out interactively with the coil at operating temperature, enabling much higher through-put. The operation of the probe is a routine, consistent procedure. Signal-to-noise ratio in a mouse brain increased by a factor ranging from 1.1 to 2.9 as compared to a room-temperature solenoid coil optimized for mouse brain microscopy. We demonstrate images encoded at 10 × 10 × 20 μm for an entire mouse brain specimen with signal-to-noise ratio of 18 and a total acquisition time of 16.5 h, revealing neuroanatomy unseen at lower resolution. Phantom measurements show an effective spatial resolution better than 20 μm.

  8. 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.

  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. Bronchoalveolar CD4+ T cell responses to respiratory antigens are impaired in HIV-infected adults

    PubMed Central

    Sepako, Enoch; Fullerton, Duncan G; Mzinza, David; Glennie, Sarah; Wright, Adam K; Heyderman, Robert S; Gordon, Stephen B

    2011-01-01

    Rationale HIV-infected adults are at an increased risk of lower respiratory tract infections. HIV infection impairs systemic acquired immunity, but there is limited information in humans on HIV-related cell-mediated immune defects in the lung. Objective To investigate antigen-specific CD4+ T cell responses to influenza virus, Streptococcus pneumoniae and Mycobacterium tuberculosis antigens in bronchoalveolar lavage (BAL) and peripheral blood between HIV-infected individuals and HIV-uninfected Malawian adults. Methods We obtained BAL fluid and blood from HIV-infected individuals (n=21) and HIV-uninfected adults (n=24). We determined the proportion of T cell subsets including naive, memory and regulatory T cells using flow cytometry, and used intracellular cytokine staining to identify CD4+ T cells recognising influenza virus-, S pneumoniae- and M tuberculosis-antigens. Main results CD4+ T cells in BAL were predominantly of effector memory phenotype compared to blood, irrespective of HIV status (p<0.001). There was immune compartmentalisation with a higher frequency of antigen-specific CD4+ T cells against influenza virus, S pneumoniae and M tuberculosis retained in BAL compared to blood in HIV-uninfected adults (p<0.001 in each case). Influenza virus- and M tuberculosis-specific CD4+ T cell responses in BAL were impaired in HIV-infected individuals: proportions of total antigen-specific CD4+ T cells and of polyfunctional IFN-γ and TNF-α-secreting cells were lower in HIV-infected individuals than in HIV-uninfected adults (p<0.05 in each case). Conclusions BAL antigen-specific CD4+ T cell responses against important viral and bacterial respiratory pathogens are impaired in HIV-infected adults. This might contribute to the susceptibility of HIV-infected adults to lower respiratory tract infections such as pneumonia and tuberculosis. PMID:21357587

  11. TNFAIP3 promotes survival of CD4 T cells by restricting MTOR and promoting autophagy.

    PubMed

    Matsuzawa, Yu; Oshima, Shigeru; Takahara, Masahiro; Maeyashiki, Chiaki; Nemoto, Yasuhiro; Kobayashi, Masanori; Nibe, Yoichi; Nozaki, Kengo; Nagaishi, Takashi; Okamoto, Ryuichi; Tsuchiya, Kiichiro; Nakamura, Tetsuya; Ma, Averil; Watanabe, Mamoru

    2015-01-01

    Autophagy plays important roles in metabolism, differentiation, and survival in T cells. TNFAIP3/A20 is a ubiquitin-editing enzyme that is thought to be a negative regulator of autophagy in cell lines. However, the role of TNFAIP3 in autophagy remains unclear. To determine whether TNFAIP3 regulates autophagy in CD4 T cells, we first analyzed Tnfaip3-deficient naïve CD4 T cells in vitro. We demonstrated that Tnfaip3-deficient CD4 T cells exhibited reduced MAP1LC3/LC3 (microtubule-associated protein 1 light chain 3) puncta formation, increased mitochondrial content, and exaggerated reactive oxygen species (ROS) production. These results indicate that TNFAIP3 promotes autophagy after T cell receptor (TCR) stimulation in CD4 T cells. We then investigated the mechanism by which TNFAIP3 promotes autophagy signaling. We found that TNFAIP3 bound to the MTOR (mechanistic target of rapamycin) complex and that Tnfaip3-deficient cells displayed enhanced ubiquitination of the MTOR complex and MTOR activity. To confirm the effects of enhanced MTOR activity in Tnfaip3-deficient cells, we analyzed cell survival following treatment with Torin1, an MTOR inhibitor. Tnfaip3-deficient CD4 T cells exhibited fewer cell numbers than the control cells in vitro and in vivo. In addition, the impaired survival of Tnfaip3-deficient cells was ameliorated with Torin1 treatment in vitro and in vivo. The effect of Torin1 was abolished by Atg5 deficiency. Thus, enhanced MTOR activity regulates the survival of Tnfaip3-deficient CD4 T cells. Taken together, our findings illustrate that TNFAIP3 restricts MTOR signaling and promotes autophagy, providing new insight into the manner in which MTOR and autophagy regulate survival in CD4 T cells.

  12. Multiple CD4+ T cell subsets produce immunomodulatory interleukin-10 during respiratory syncytial virus infection

    PubMed Central

    Weiss, Kayla A.; Christiaansen, Allison F.; Fulton, Ross B.; Meyerholz, David K.; Varga, Steven M.

    2011-01-01

    The host immune response is believed to contribute to the severity of pulmonary disease induced by acute respiratory syncytial virus (RSV) infection. Because RSV-induced pulmonary disease is associated with immunopathology, we evaluated the role of IL-10 in modulating the RSV-specific immune response. We found that IL-10 protein levels in the lung were increased following acute RSV infection with maximum production corresponding to the peak of the virus-specific T cell response. The majority of IL-10 producing cells in the lung during acute RSV infection were CD4+ T cells. The IL-10-producing CD4+ T cells included Foxp3+Tregs, Foxp3− CD4+ T cells that co-produce IFN-γ, and Foxp3− CD4+ T cells that do not co-produce IFN-γ. RSV infection of IL-10-deficient mice resulted in more severe disease, as measured by increased weight loss and airway resistance, as compared to control mice. We also observed an increase in the magnitude of the RSV-induced CD8+ and CD4+ T cell response that correlated with increased disease severity in the absence of IL-10 or following IL-10R blockade. Interestingly, IL-10R blockade during acute RSV infection altered CD4+ T cell subset distribution, resulting in a significant increase in IL-17A-producing CD4+ T cells and a concomitant decrease in Foxp3+ regulatory T cells. These results demonstrate that IL-10 plays a critical role in modulating the adaptive immune response to RSV by limiting T-cell-mediated pulmonary inflammation and injury. PMID:21844390

  13. TNFAIP3 promotes survival of CD4 T cells by restricting MTOR and promoting autophagy

    PubMed Central

    Matsuzawa, Yu; Oshima, Shigeru; Takahara, Masahiro; Maeyashiki, Chiaki; Nemoto, Yasuhiro; Kobayashi, Masanori; Nibe, Yoichi; Nozaki, Kengo; Nagaishi, Takashi; Okamoto, Ryuichi; Tsuchiya, Kiichiro; Nakamura, Tetsuya; Ma, Averil; Watanabe, Mamoru

    2015-01-01

    Autophagy plays important roles in metabolism, differentiation, and survival in T cells. TNFAIP3/A20 is a ubiquitin-editing enzyme that is thought to be a negative regulator of autophagy in cell lines. However, the role of TNFAIP3 in autophagy remains unclear. To determine whether TNFAIP3 regulates autophagy in CD4 T cells, we first analyzed Tnfaip3-deficient naïve CD4 T cells in vitro. We demonstrated that Tnfaip3-deficient CD4 T cells exhibited reduced MAP1LC3/LC3 (microtubule-associated protein 1 light chain 3) puncta formation, increased mitochondrial content, and exaggerated reactive oxygen species (ROS) production. These results indicate that TNFAIP3 promotes autophagy after T cell receptor (TCR) stimulation in CD4 T cells. We then investigated the mechanism by which TNFAIP3 promotes autophagy signaling. We found that TNFAIP3 bound to the MTOR (mechanistic target of rapamycin) complex and that Tnfaip3-deficient cells displayed enhanced ubiquitination of the MTOR complex and MTOR activity. To confirm the effects of enhanced MTOR activity in Tnfaip3-deficient cells, we analyzed cell survival following treatment with Torin1, an MTOR inhibitor. Tnfaip3-deficient CD4 T cells exhibited fewer cell numbers than the control cells in vitro and in vivo. In addition, the impaired survival of Tnfaip3-deficient cells was ameliorated with Torin1 treatment in vitro and in vivo. The effect of Torin1 was abolished by Atg5 deficiency. Thus, enhanced MTOR activity regulates the survival of Tnfaip3-deficient CD4 T cells. Taken together, our findings illustrate that TNFAIP3 restricts MTOR signaling and promotes autophagy, providing new insight into the manner in which MTOR and autophagy regulate survival in CD4 T cells. PMID:26043155

  14. Extra Dimensions and New Vector Bosons Searches in CMS

    SciTech Connect

    Emam, W.

    2008-04-21

    This paper addresses a series of searches for signals from extra dimensions and new vector bosons in the CMS experiment. A brief review of the CMS discovery potential of these signatures in different luminosity scenarios is presented.

  15. 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.

  16. 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.

  17. Underbalanced coiled tubing sidetrack successful

    SciTech Connect

    Adam, J.; Berry, M.

    1995-12-18

    The technique of drilling through a completion string, underbalanced, with coiled tubing eliminated some of the problems encountered with overbalanced drilling in a group of offset wells. This project confirmed that performing drilling operations in live wells can be carried out safely and effectively. Dalen is a sour gas field in the eastern part of The Netherlands and produces from vertical fractures in the Zechstein carbonate reservoir. The proposal for Dalen 2 was to abandon the lower section of the original hole and subsequently sidetrack conventionally to the top of the reservoir, run and cement a 5-in. liner, complete the well with a 5-in. monobore completion, and install the christmas tree. This part of the operation would be performed with a workover hoist. Thereafter, a 3 3/4-in. hole would be drilled through the completion and into the reservoir, underbalanced with coiled tubing. The drilling proposal had to address a number of key issues: creating underbalanced conditions; handling sour gas production at surface; handling and treating drilling fluids at surface; removing drilled solids from the returned fluid system; and deploying a long coiled tubing drilling bottom hole assembly (BHA) into a live well. The paper discusses planning, legislative issues, well preparation, the drilling program, and lessons learned.

  18. 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

  19. Blood-Derived CD4 T Cells Naturally Resist Pyroptosis During Abortive HIV-1 Infection

    PubMed Central

    Muñoz-Arias, Isa; Doitsh, Gilad; Yang, Zhiyuan; Sowinski, Stefanie; Ruelas, Debbie; Greene, Warner C.

    2015-01-01

    Summary Progression to AIDS is driven by CD4 T-cell depletion, mostly involving pyroptosis elicited by abortive HIV infection of CD4 T cells in lymphoid tissues. Inefficient reverse transcription in these cells leads to cytoplasmic accumulation of viral DNAs that are detected by the DNA sensor IFI16, resulting in inflammasome assembly, caspase-1 activation, and pyroptosis. Unexpectedly, we found that peripheral blood-derived CD4 T cells naturally resist pyroptosis. This resistance is partly due to their deeper resting state, resulting in fewer HIV-1 reverse transcripts and lower IFI16 expression. However, when co-cultured with lymphoid-derived cells, blood-derived CD4 T cells become sensitized to pyroptosis, likely recapitulating interactions occurring within lymphoid tissues. Sensitization correlates with higher levels of activated NF-κB, IFI16 expression, and reverse transcription. Blood-derived lymphocytes re-purified from co-cultures lose sensitivity to pyroptosis. These differences highlight how the lymphoid tissue microenvironment encountered by trafficking CD4 T lymphocytes dynamically shapes their biological response to HIV. PMID:26468749

  20. CD4 T cells in murine acquired immunodeficiency syndrome: polyclonal progression to anergy

    PubMed Central

    1992-01-01

    We have examined the kinetics of changes that occur in the helper T cell subset during murine acquired immunodeficiency syndrome, which occurs after infection with the mix of viruses known as BM5. We find that there is expansion of the CD4 T cells by 2 wk, 50% of the CD4 T cells become large as the disease progresses, and the CD4 T cell population is increasingly comprised of cells with a memory/activated phenotype. These effects are apparent by 2 wk postinfection, and the change is nearly complete by 6-8 wk. The phenotypic shift is paralleled by the loss of the ability of the CD4 T cells to proliferate or to produce interleukin 2 (IL-2), IL-3, IL-4, and interferon gamma in response to stimulation with mitogens, superantigen, or anti-CD3. There is no obvious expansion or deletion of CD4 T cells expressing particular V beta genes, as might be expected if a conventional superantigen were driving the changes. The results suggest, however, that the total CD4 population has been driven to anergy by some potent polyclonal stimulus directly associated with viral infection. PMID:1588283

  1. 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

  2. Notch Signaling Regulates Antigen Sensitivity of Naive CD4+ T Cells by Tuning Co-stimulation

    PubMed Central

    Laky, Karen; Evans, Sharron; Perez-Diez, Ainhoa

    2015-01-01

    SUMMARY Adaptive immune responses begin when naive CD4+ T cells engage peptide+major histocompatibility complex class II and co-stimulatory molecules on antigen-presenting cells (APCs). Notch signaling can influence effector functions in differentiated CD4+ T helper and T regulatory cells. Whether and how ligand-induced Notch signaling influences the initial priming of CD4+ T cells has not been addressed. We have found that Delta Like Ligand 4 (DLL4)-induced Notch signaling potentiates phosphatidylinositol 3-OH kinase (PI3K)-dependent signaling downstream of the T cell receptor+CD28, allowing naive CD4+ T cells to respond to lower doses of antigen. In vitro, DLL4-deficient APCs were less efficient stimulators of CD4+ T cell activation, metabolism, proliferation, and cytokine secretion. With deletion of DLL4 from CD11c+ APCs in vivo, these deficits translated to an impaired ability to mount an effective CD4+-dependent anti-tumor response. These data implicate Notch signaling as an important regulator of adaptive immune responses. PMID:25607460

  3. Interleukin-27-Producing CD4(+) T Cells Regulate Protective Immunity during Malaria Parasite Infection.

    PubMed

    Kimura, Daisuke; Miyakoda, Mana; Kimura, Kazumi; Honma, Kiri; Hara, Hiromitsu; Yoshida, Hiroki; Yui, Katsuyuki

    2016-03-15

    Interleukin-27 (IL-27) is a heterodimeric regulatory cytokine of the IL-12 family, which is produced by macrophages, dendritic cells, and B cells upon stimulation through innate immune receptors. Here, we described regulatory CD4(+) T cells that produce IL-27 in response to T cell receptor stimulation during malaria infection, inhibiting IL-2 production and clonal expansion of other T cells in an IL-27-dependent manner. IL-27-producing CD4(+) T cells were Foxp3(-)CD11a(+)CD49d(+) malaria antigen-specific CD4(+) T cells and were distinct from interferon-γ (IFN-γ) producing Th1 or IL-10 producing Tr1 cells. In mice lacking IL-27 in T cells, IL-2 production was restored and clonal expansion and IFN-γ production by specific CD4(+) T cells were improved, culminating in reduced parasite burden. This study highlights a unique population of IL-27 producing regulatory CD4(+) T cells and their critical role in the regulation of the protective immune response against malaria parasites.

  4. Restoring homeostasis of CD4+ T cells in hepatitis-B-virus-related liver fibrosis

    PubMed Central

    Cheng, Li-Sha; Liu, Yun; Jiang, Wei

    2015-01-01

    Immune-mediated liver injury is widely seen during hepatitis B virus (HBV) infection. Unsuccessful immune clearance of HBV results in chronic hepatitis and increases the risk of liver cirrhosis and hepatocellular carcinoma. HBV-related liver fibrosis (HBVLF), occurring as a result of HBV-induced chronic hepatitis, is a reversible, intermediate stage of chronic hepatitis B (CHB) and liver cirrhosis. Therefore, defining the pathogenesis of HBVLF is of practical significance for achieving better clinical outcomes. Recently, the homeostasis of CD4+ T cells was considered to be pivotal in the process of HBVLF. To better uncover the underlying mechanisms, in this review, we systematically retrospect the impacts of different CD4+ T-cell subsets on CHB and HBVLF. We emphasize CD4+ T-cell homeostasis and the important balance between regulatory T (Treg) and T helper 17 (Th17) cells. We discuss some cytokines associated with Treg and Th17 cells such as interleukin (IL)-17, IL-22, IL-21, IL-23, IL-10, IL-35 and IL-33, as well as surface molecules such as programmed cell death protein 1, cytotoxic T lymphocyte-associated antigen 4, T cell immunoglobulin domain and mucin domain-containing molecule 3 and cannabinoid receptor 2 that have potential therapeutic implications for the homeostasis of CD4+ T cells in CHB and HBVLF. PMID:26478664

  5. CD4+ T cells mediate mucosal and systemic immune responses to experimental hookworm infection

    PubMed Central

    DONDJI, B.; SUN, T.; BUNGIRO, R. D.; VERMEIRE, J. J.; HARRISON, L. M.; BIFULCO, C.; CAPPELLO, M.

    2011-01-01

    SUMMARY Hookworm infection is associated with anaemia and malnutrition in many resource-limited countries. Ancylostoma hookworms have previously been shown to modulate host cellular immune responses through multiple mechanisms, including reduced mitogen-mediated lymphocyte proliferation, impaired antigen presentation/processing, and relative reductions in CD4+ T cells in the spleen and mesenteric lymph nodes. Syrian hamsters were depleted of CD4+ for up to 9 days following intraperitoneal injection (200 μg) of a murine anti-mouse CD4 monoclonal IgG (clone GK1·5). CD4+ T-cell-depleted hamsters infected with the hookworm Ancylostoma ceylanicum exhibited a threefold higher mean intestinal worm burden and more severe anaemia than animals that received isotype control IgG. In addition, depletion of CD4+ T cells was associated with impaired cellular and humoral (serum and mucosal) immune responses to hookworm antigens. These data demonstrate an effector role for CD4+ T cells in hookworm immunity and disease pathogenesis. Ultimately, these studies may yield important insights into the relationship between intestinal nematode infections and diseases that are associated with CD4+ T-cell depletion, including HIV. PMID:20500671

  6. Coinhibitory receptor PD-1H preferentially suppresses CD4+ T cell–mediated immunity

    PubMed Central

    Flies, Dallas B.; Han, Xue; Higuchi, Tomoe; Zheng, Linghua; Sun, Jingwei; Ye, Jessica Jane; Chen, Lieping

    2014-01-01

    T cell activation is regulated by the interactions of surface receptors with stimulatory and inhibitory ligands. Programmed death-1 homolog (PD-1H, also called VISTA) is a member of the CD28 family of proteins and has been shown to act as a coinhibitory ligand on APCs that suppress T cell responses. Here, we determined that PD-1H functions as a coinhibitory receptor for CD4+ T cells. CD4+ T cells in mice lacking PD-1H exhibited a dramatically increased response to antigen stimulation. Furthermore, delivery of a PD-1H–specific agonist mAb directly inhibited CD4+ T cell activation both in vitro and in vivo, validating a coinhibitory function of PD-1H. In a murine model of acute hepatitis, administration of a PD-1H agonist mAb suppressed CD4+ T cell–mediated acute inflammation. PD-1H–deficient animals were highly resistant to tumor induction in a murine brain glioma model, and depletion of CD4+ T cells, but not CD8+ T cells, promoted tumor formation. Together, our findings suggest that PD-1H has potential as a target of immune modulation in the treatment of human inflammation and malignancies. PMID:24743150

  7. 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.

  8. 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

  9. 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.

  10. 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.

  11. Computational modeling of heterogeneity and function of CD4+ T cells

    PubMed Central

    Carbo, Adria; Hontecillas, Raquel; Andrew, Tricity; Eden, Kristin; Mei, Yongguo; Hoops, Stefan; Bassaganya-Riera, Josep

    2014-01-01

    The immune system is composed of many different cell types and hundreds of intersecting molecular pathways and signals. This large biological complexity requires coordination between distinct pro-inflammatory and regulatory cell subsets to respond to infection while maintaining tissue homeostasis. CD4+ T cells play a central role in orchestrating immune responses and in maintaining a balance between pro- and anti- inflammatory responses. This tight balance between regulatory and effector reactions depends on the ability of CD4+ T cells to modulate distinct pathways within large molecular networks, since dysregulated CD4+ T cell responses may result in chronic inflammatory and autoimmune diseases. The CD4+ T cell differentiation process comprises an intricate interplay between cytokines, their receptors, adaptor molecules, signaling cascades and transcription factors that help delineate cell fate and function. Computational modeling can help to describe, simulate, analyze, and predict some of the behaviors in this complicated differentiation network. This review provides a comprehensive overview of existing computational immunology methods as well as novel strategies used to model immune responses with a particular focus on CD4+ T cell differentiation. PMID:25364738

  12. 23 CFR 500.109 - CMS.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... SYSTEMS Management Systems § 500.109 CMS. (a) For purposes of this part, congestion means the level at.... Congestion management means the application of strategies to improve system performance and reliability by... management system or process is a systematic and regionally accepted approach for managing congestion...

  13. 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.

  14. 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... SYSTEMS Management Systems § 500.109 CMS. (a) For purposes of this part, congestion means the level at which transportation system performance is unacceptable due to excessive travel times and...

  15. 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.

  16. 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.

  17. CMS muon detector and trigger performance

    NASA Astrophysics Data System (ADS)

    Piccolo, Davide; CMS Collaboration

    2011-02-01

    In the CMS experiment at the LHC proton-proton collider, a key role will be played by the muon system that is embedded inside the iron yoke used to close the magnetic flux of the CMS solenoid. The muon system of the CMS experiment performs three main tasks: triggering of muons, identifying muons, and assisting the central tracker in order to measure the momentum and charge of high-pt muons in the pseudorapidity region |η|≤2.4. The system is composed by a central barrel and two closing endcaps. Three independent technologies are used to reconstruct and trigger muons: Drift Tubes (DT) in the barrel, Cathode Strips Chambers (CSC) in the endcaps and Resistive Plate Chambers (RPC) in both barrel and endcap regions. All the detectors will contribute to the tracking and triggering of muons. Towards the end of 2008 and in 2009 the CMS experiment was commissioned with many millions of cosmic rays. These data have been fundamental to check the performance of the three sub-detectors and of the trigger response. In this paper the results in terms of the detection and trigger performance at the level of each sub-detector and at the level of the full muon system will be reported.

  18. 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.

  19. Commissioning of the CMS High Level Trigger

    SciTech Connect

    Agostino, Lorenzo; et al.

    2009-08-01

    The CMS experiment will collect data from the proton-proton collisions delivered by the Large Hadron Collider (LHC) at a centre-of-mass energy up to 14 TeV. The CMS trigger system is designed to cope with unprecedented luminosities and LHC bunch-crossing rates up to 40 MHz. The unique CMS trigger architecture only employs two trigger levels. The Level-1 trigger is implemented using custom electronics, while the High Level Trigger (HLT) is based on software algorithms running on a large cluster of commercial processors, the Event Filter Farm. We present the major functionalities of the CMS High Level Trigger system as of the starting of LHC beams operations in September 2008. The validation of the HLT system in the online environment with Monte Carlo simulated data and its commissioning during cosmic rays data taking campaigns are discussed in detail. We conclude with the description of the HLT operations with the first circulating LHC beams before the incident occurred the 19th September 2008.

  20. 42 CFR 423.2264 - Guidelines for CMS review.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 3 2011-10-01 2011-10-01 false Guidelines for CMS review. 423.2264 Section 423....2264 Guidelines for CMS review. In reviewing marketing material or enrollment forms under § 423.2262, CMS determines (unless otherwise specified in additional guidance) that the marketing materials—...

  1. 42 CFR 433.320 - Procedures for refunds to CMS.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 4 2011-10-01 2011-10-01 false Procedures for refunds to CMS. 433.320 Section 433... Overpayments to Providers § 433.320 Procedures for refunds to CMS. (a) Basic requirements. (1) The agency must refund the Federal share of overpayments that are subject to recovery to CMS through a credit on...

  2. 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... Determinations and Appeals § 405.1834 CMS reviewing official procedure. (a) Scope. A provider that is a party to... Administrator by a designated CMS reviewing official who considers whether the decision of the...

  3. 42 CFR 457.1003 - CMS review of waiver requests.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 4 2010-10-01 2010-10-01 false CMS review of waiver requests. 457.1003 Section 457.1003 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Waivers: General Provisions § 457.1003 CMS review of waiver requests. CMS will review the waiver...

  4. 42 CFR 403.248 - Administrative review of CMS determinations.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 2 2011-10-01 2011-10-01 false Administrative review of CMS determinations. 403... Certification Program: General Provisions § 403.248 Administrative review of CMS determinations. (a) This section provides for administrative review if CMS determines— (1) Not to certify a policy; or (2) That...

  5. 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...) MEDICARE PROGRAM MEDICARE ADVANTAGE PROGRAM Relationships With Providers § 422.210 Assurances to CMS. (a) Assurances to CMS. Each organization will provide assurance satisfactory to the Secretary that...

  6. 42 CFR 422.210 - Assurances to CMS.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 3 2011-10-01 2011-10-01 false Assurances to CMS. 422.210 Section 422.210 Public...) MEDICARE PROGRAM MEDICARE ADVANTAGE PROGRAM Relationships With Providers § 422.210 Assurances to CMS. (a) Assurances to CMS. Each organization will provide assurance satisfactory to the Secretary that...

  7. 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... Physicians and Entities Furnishing Designated Health Services § 411.379 When CMS accepts a request. (a) Upon receiving a request for an advisory opinion, CMS promptly makes an initial determination of whether...

  8. 42 CFR 457.1003 - CMS review of waiver requests.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 4 2011-10-01 2011-10-01 false CMS review of waiver requests. 457.1003 Section 457.1003 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Waivers: General Provisions § 457.1003 CMS review of waiver requests. CMS will review the waiver...

  9. 42 CFR 422.2264 - Guidelines for CMS review.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 3 2011-10-01 2011-10-01 false Guidelines for CMS review. 422.2264 Section 422... Guidelines for CMS review. In reviewing marketing material or election forms under § 422.2262 of this part, CMS determines that the marketing materials— (a) Provide, in a format (and, where appropriate,...

  10. 42 CFR 411.386 - CMS's advisory opinions as exclusive.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 2 2011-10-01 2011-10-01 false CMS's advisory opinions as exclusive. 411.386... Relationships Between Physicians and Entities Furnishing Designated Health Services § 411.386 CMS's advisory... described in § 411.370. CMS has not and does not issue a binding advisory opinion on the subject matter...

  11. 42 CFR 422.510 - Termination of contract by CMS.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ....510 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (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...

  12. 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.

  13. 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

  14. CCL2 Increases X4-tropic HIV-1 Entry into Resting CD4+ T Cells*

    PubMed Central

    Campbell, Grant R.; Spector, Stephen A.

    2008-01-01

    During human immunodeficiency virus type 1 (HIV-1) infection, there is a strong positive correlation between CCL2 levels and HIV viral load. To determine whether CCL2 alters HIV-1 infection of resting CD4+ T cells, we infected purified resting CD4+ T cells after incubation with CCL2. We show that CCL2 up-regulates CXCR4 on resting CD4+ T cells in a CCR2-dependent mechanism, and that this augmentation of CXCR4 expression by CCL2 increases the ability of these cells to be chemoattracted to CXCR4 using gp120 and renders them more permissive to X4-tropic HIV-1 infection. Thus, CCL2 has the capacity to render a large population of lymphocytes more susceptible to HIV-1 late in the course of infection. PMID:18784079

  15. 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

  16. 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.

  17. Impaired CD4 T Cell Memory Response to Streptococcus pneumoniae Precedes CD4 T Cell Depletion in HIV-Infected Malawian Adults

    PubMed Central

    Mzinza, David; Harawa, Visopo; Miles, David J. C.; Jambo, Kondwani C.; Gordon, Stephen B.; Williams, Neil A.; Heyderman, Robert S.

    2011-01-01

    Objective Invasive pneumococcal disease (IPD) is a leading cause of morbidity and mortality in HIV-infected African adults. CD4 T cell depletion may partially explain this high disease burden but those with relatively preserved T cell numbers are still at increased risk of IPD. This study evaluated the extent of pneumococcal-specific T cell memory dysfunction in asymptomatic HIV infection early on in the evolution of the disease. Methods Peripheral blood mononuclear cells were isolated from asymptomatic HIV-infected and HIV-uninfected Malawian adults and stained to characterize the underlying degree of CD4 T cell immune activation, senescence and regulation. Pneumococcal-specific T cell proliferation, IFN-γ, IL-17 production and CD154 expression was assessed using flow cytometry and ELISpot. Results We find that in asymptomatic HIV-infected Malawian adults, there is considerable immune disruption with an increase in activated and senescent CD4+CD38+PD-1+ and CD4+CD25highFoxp3+ Treg cells. In the context of high pneumococcal exposure and therefore immune stimulation, show a failure in pneumococcal-specific memory T cell proliferation, skewing of T cell cytokine production with preservation of interleukin-17 but decreased interferon-gamma responses, and failure of activated T cells to express the co-stimulatory molecule CD154. Conclusion Asymptomatic HIV-infected Malawian adults show early signs of pneumococcal- specific immune dysregulation with a shift in the balance of CD4 memory, T helper 17 cells and Treg. Together these data offer a mechanistic understanding of how antigen-specific T cell dysfunction occurs prior to T cell depletion and may explain the early susceptibility to IPD in those with relatively preserved CD4 T cell numbers. PMID:21980502

  18. Characterizing the dynamics of CD4+ T cell priming within a lymph node1

    PubMed Central

    Linderman, Jennifer J.; Riggs, Thomas; Pande, Manjusha; Miller, Mark; Marino, Simeone; Kirschner, Denise E.

    2011-01-01

    Generating adaptive immunity after infection or immunization requires physical interaction within a lymph node (LN) T-zone between antigen-bearing dendritic cells (DCs) and rare cognate T cells. Many fundamental questions remain regarding the dynamics of DC-CD4+ T cell interactions leading to priming. For example, it is not known how the production of primed CD4+ T cells relates to the numbers of cognate T cells, antigen-bearing DCs, or peptide-MHCII level on the DC. To address these questions, we developed an agent-based model of a LN to examine the relationships among cognate T cell frequency, DC density, parameters characterizing DC-T interactions and the output of primed T cells. We found that the output of primed CD4+ T cells is linearly related to cognate frequency, but non-linearly related to the number of antigen-bearing DCs present during infection. This addresses the applicability of two photon microscopy studies to understanding actual infection dynamics, as these types of experiments increase the cognate frequency by orders of magnitude as compared to physiologic levels. We found a trade-off between the quantity of peptide-MHCII on the surface of individual DCs and number of antigen-bearing DCs present in the LN in contributing to the production of primed CD4+ T cells. Interestingly, pMHCII half-life plays a minor, although still significant, role in determining CD4+ T cell priming, unlike the primary role that has been suggested for CD8+ T cell priming. Finally, we identify several pathogen-targeted mechanisms that, if altered in their efficiency, can significantly effect the generation of primed CD4+ T cells. PMID:20154206

  19. A quartz nanopillar hemocytometer for high-yield separation and counting of CD4+ T lymphocytes

    NASA Astrophysics Data System (ADS)

    Kim, Dong-Joo; Seol, Jin-Kyeong; Wu, Yu; Ji, Seungmuk; Kim, Gil-Sung; Hyung, Jung-Hwan; Lee, Seung-Yong; Lim, Hyuneui; Fan, Rong; Lee, Sang-Kwon

    2012-03-01

    We report the development of a novel quartz nanopillar (QNP) array cell separation system capable of selectively capturing and isolating a single cell population including primary CD4+ T lymphocytes from the whole pool of splenocytes. Integrated with a photolithographically patterned hemocytometer structure, the streptavidin (STR)-functionalized-QNP (STR-QNP) arrays allow for direct quantitation of captured cells using high content imaging. This technology exhibits an excellent separation yield (efficiency) of ~95.3 +/- 1.1% for the CD4+ T lymphocytes from the mouse splenocyte suspensions and good linear response for quantitating captured CD4+ T-lymphoblasts, which is comparable to flow cytometry and outperforms any non-nanostructured surface capture techniques, i.e. cell panning. This nanopillar hemocytometer represents a simple, yet efficient cell capture and counting technology and may find immediate applications for diagnosis and immune monitoring in the point-of-care setting.We report the development of a novel quartz nanopillar (QNP) array cell separation system capable of selectively capturing and isolating a single cell population including primary CD4+ T lymphocytes from the whole pool of splenocytes. Integrated with a photolithographically patterned hemocytometer structure, the streptavidin (STR)-functionalized-QNP (STR-QNP) arrays allow for direct quantitation of captured cells using high content imaging. This technology exhibits an excellent separation yield (efficiency) of ~95.3 +/- 1.1% for the CD4+ T lymphocytes from the mouse splenocyte suspensions and good linear response for quantitating captured CD4+ T-lymphoblasts, which is comparable to flow cytometry and outperforms any non-nanostructured surface capture techniques, i.e. cell panning. This nanopillar hemocytometer represents a simple, yet efficient cell capture and counting technology and may find immediate applications for diagnosis and immune monitoring in the point-of-care setting

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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

  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. 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

  8. Optimum coil insertion speed of various coils in brain aneurysm embolization in vitro.

    PubMed

    Konishi, Yoshifumi; Takeuchi, Masataka; Fukasaku, Kazuaki

    2016-10-01

    A coil must comprise material with shape memory to perform optimal coil embolization. To achieve this, the alloy characteristics of the coil (hardness, shape, and thickness) must be understood. In this experiment, a catheter was fixed in the bright position and the movement of the coil was observed under a constant rate of insertion; the optimal insertion rate during clinical use was investigated. The first coil insertion speed was evaluated using simulated aneurysms in an in vivo arterial model. The results showed that the insertion force relates to the deployment shape of the coil, that the feedback through the force indicator using sound is very effective, and that the recorder is useful for analysis of coil embolization. The inserted coils during aneurysm embolization were able to wind uniformly within the aneurysm due to a variety of factors (guiding or micro-catheter position and kick-back phenomenon such as delivery wire). Optimal speed is achieved with proper coil design, which allows the coil to be inserted into the aneurysm. The shape and size of the aneurysm can help determine the necessary size and design of the coil that should be used during the optimal speed range. Aneurysm wall and coil characteristics are considered, along with the friction state of the coil (hardness, shape, and thickness), leading to improvements in safety during the insertion procedure at optimum speed. PMID:27353635

  9. Optimum coil insertion speed of various coils in brain aneurysm embolization in vitro.

    PubMed

    Konishi, Yoshifumi; Takeuchi, Masataka; Fukasaku, Kazuaki

    2016-10-01

    A coil must comprise material with shape memory to perform optimal coil embolization. To achieve this, the alloy characteristics of the coil (hardness, shape, and thickness) must be understood. In this experiment, a catheter was fixed in the bright position and the movement of the coil was observed under a constant rate of insertion; the optimal insertion rate during clinical use was investigated. The first coil insertion speed was evaluated using simulated aneurysms in an in vivo arterial model. The results showed that the insertion force relates to the deployment shape of the coil, that the feedback through the force indicator using sound is very effective, and that the recorder is useful for analysis of coil embolization. The inserted coils during aneurysm embolization were able to wind uniformly within the aneurysm due to a variety of factors (guiding or micro-catheter position and kick-back phenomenon such as delivery wire). Optimal speed is achieved with proper coil design, which allows the coil to be inserted into the aneurysm. The shape and size of the aneurysm can help determine the necessary size and design of the coil that should be used during the optimal speed range. Aneurysm wall and coil characteristics are considered, along with the friction state of the coil (hardness, shape, and thickness), leading to improvements in safety during the insertion procedure at optimum speed.

  10. 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

  11. Getting the Skinny on CD4(+) T Cell Survival in Fatty Livers.

    PubMed

    Walker, Christopher M; Lemon, Stanley M

    2016-04-19

    Non-alcoholic fatty liver disease is associated with hepatocellular carcinoma. In the March 10 issue of Nature, Greten and colleagues report that this metabolic disruption affects tumor surveillance by depleting CD4+ T helper cells through lipotoxic mechanisms associated with NAFLD.

  12. 26 CFR 31.6011(a)-4T - Returns of income tax withheld (temporary).

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 15 2011-04-01 2011-04-01 false Returns of income tax withheld (temporary). 31... (CONTINUED) EMPLOYMENT TAXES AND COLLECTION OF INCOME TAX AT SOURCE EMPLOYMENT TAXES AND COLLECTION OF INCOME... Provisions of Subtitle F, Internal Revenue Code of 1954) § 31.6011(a)-4T Returns of income tax...

  13. 26 CFR 31.6011(a)-4T - Returns of income tax withheld (temporary).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 15 2010-04-01 2010-04-01 false Returns of income tax withheld (temporary). 31... (CONTINUED) EMPLOYMENT TAXES AND COLLECTION OF INCOME TAX AT SOURCE EMPLOYMENT TAXES AND COLLECTION OF INCOME... Provisions of Subtitle F, Internal Revenue Code of 1954) § 31.6011(a)-4T Returns of income tax...

  14. Bromelain treatment reduces CD25 expression on activated CD4+ T cells in vitro.

    PubMed

    Secor, Eric R; Singh, Anurag; Guernsey, Linda A; McNamara, Jeff T; Zhan, Lijun; Maulik, Nilanjana; Thrall, Roger S

    2009-03-01

    Bromelain (Br), an extract from pineapple stem with cysteine protease activity, exerts anti-inflammatory effects in a number of inflammatory models. We have previously shown that Br treatment decreased activated CD4(+) T cells and has a therapeutic role in an ovalbumin-induced murine model of allergic airway disease. The current study was designed to determine the effect of Br on CD4(+) T cell activation, specifically the expression of CD25 in vitro. CD25 is up regulated upon T cell activation, found as a soluble fraction (sCD25) and is a therapeutic target in inflammation, autoimmunity and allergy. Br treatment of anti-CD3 stimulated CD4(+) T cells reduced CD25 expression in a dose and time dependent manner. This reduction of CD25 was dependent on the proteolytic action of Br as the addition of E64 (a cysteine protease inhibitor) abrogated this response. The concentration of sCD25 was increased in supernatants of Br treated activated CD4(+) T cells as compared to control cells, suggesting that Br proteolytically cleaved cell-surface CD25. This novel mechanism of action identifies how Br may exert its therapeutic benefits in inflammatory conditions.

  15. 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...

  16. 26 CFR 1.509(a)-4T - Supporting organizations (temporary).

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 7 2014-04-01 2013-04-01 true Supporting organizations (temporary). 1.509(a)-4T... organizations (temporary). (a) through (i)(5)(ii)(A) For further guidance, see § 1.509(a)-4(a) through (i)(5)(ii... of the supporting organization's adjusted net income (as determined by applying the principles...

  17. Leishmania-infected macrophages sequester endogenously synthesized parasite antigens from presentation to CD4+ T cells.

    PubMed

    Kima, P E; Soong, L; Chicharro, C; Ruddle, N H; McMahon-Pratt, D

    1996-12-01

    CD4+ T cell lines raised against the protective leishmanial antigens GP46 and P8 were used to study the presentation of endogenously synthesized Leishmania antigens by infected cells. Using two different sources of macrophages, the I4.07 macrophage cell line (H-2k) which constitutively expresses major histocompatibility complex (MHC) class II molecules, and elicited peritoneal exudate cells, we found that cells infected with Leishmania amastigotes presented little, if any endogenously synthesized parasite antigens to CD4+ T cells. In contrast, promastigote-infected macrophages did present endogenous parasite molecules to CD4+ T cells, although only for a limited time, with maximal presentation occurring within 24 h of infection and decreasing to minimal antigen presentation at 72 h post-infection. These observations suggest that once within the macrophage, Leishmania amastigote antigens are sequestered from the MHC class II pathway of antigen presentation. This allows live parasites to persist in infected hosts by evading the activation of CD4+ T cells, a major and critical anti-leishmanial component of the host immune system. Studies with drugs that modify fusion patterns of phagosomes suggest that the mechanism of this antigen sequestration includes targeted fusion of the parasitophorous vacuole with certain endocytic compartments.

  18. 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...

  19. 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...

  20. 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

  1. 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.

  2. 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. PMID:27390762

  3. 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

  4. 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

  5. Major histocompatibility complex class I-restricted alloreactive CD4+ T cells.

    PubMed

    Boyle, Louise H; Goodall, Jane C; Gaston, J S Hill

    2004-05-01

    Although it is well established that CD4+ T cells generally recognize major histocompatibility complex (MHC) class II molecules, MHC class I-reactive CD4+ T cells have occasionally been reported. Here we describe the isolation and characterization of six MHC class I-reactive CD4+ T-cell lines, obtained by co-culture of CD4+ peripheral blood T cells with the MHC class II-negative, transporter associated with antigen processing (TAP)-negative cell line, T2, transfected with human leucocyte antigen (HLA)-B27. Responses were inhibited by the MHC class I-specific monoclonal antibody (mAb), W6/32, demonstrating the direct recognition of MHC class I molecules. In four cases, the restriction element was positively identified as HLA-A2, as responses by these clones were completely inhibited by MA2.1, an HLA-A2-specific mAb. Interestingly, three of the CD4+ T-cell lines only responded to cells expressing HLA-B27, irrespective of their restricting allele, implicating HLA-B27 as a possible source of peptides presented by the stimulatory MHC class I alleles. In addition, these CD4+ MHC class I alloreactive T-cell lines could recognize TAP-deficient cells and therefore may have particular clinical relevance to situations where the expression of TAP molecules is decreased, such as viral infection and transformation of cells. PMID:15096184

  6. 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

  7. 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...

  8. Salmonella enterica Serovar Typhi Impairs CD4 T Cell Responses by Reducing Antigen Availability

    PubMed Central

    Atif, Shaikh M.; Winter, Sebastian E.; Winter, Maria G.; McSorley, Stephen J.

    2014-01-01

    Salmonella enterica serovar Typhi is associated with a disseminated febrile illness in humans, termed typhoid fever, while Salmonella enterica serovar Typhimurium causes localized gastroenteritis in immunocompetent individuals. One of the genetic differences between both pathogens is the presence in S. Typhi of TviA, a regulatory protein that shuts down flagellin (FliC) expression when bacteria transit from the intestinal lumen into the intestinal mucosa. Here we investigated the consequences of TviA-mediated flagellum gene regulation on flagellin-specific CD4 T cell responses in a mouse model of S. Typhimurium infection. Introduction of the S. Typhi tviA gene into S. Typhimurium suppressed antigen presentation of dendritic cells to flagellin-specific CD4 T cells in vitro. Furthermore, TviA-mediated repression of flagellin expression impaired the activation and proliferation of naive flagellin-specific CD4 T cells in Peyer's patches and mesenteric lymph nodes, which was accompanied by increased bacterial dissemination to the spleen. We conclude that TviA-mediated repression of flagellin expression reduces antigen availability, thereby weakening flagellin-specific CD4 T cell responses. PMID:24643532

  9. 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...

  10. 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...

  11. HLA Class-II Associated HIV Polymorphisms Predict Escape from CD4+ T Cell Responses

    PubMed Central

    Erdmann, Nathan; Du, Victor Y.; Carlson, Jonathan; Schaefer, Malinda; Jureka, Alexander; Sterrett, Sarah; Yue, Ling; Dilernia, Dario; Lakhi, Shabir; Tang, Jianming; Sidney, John; Gilmour, Jill; Allen, Susan; Hunter, Eric; Heath, Sonya; Bansal, Anju; Goepfert, Paul A.

    2015-01-01

    Antiretroviral therapy, antibody and CD8+ T cell-mediated responses targeting human immunodeficiency virus-1 (HIV-1) exert selection pressure on the virus necessitating escape; however, the ability of CD4+ T cells to exert selective pressure remains unclear. Using a computational approach on HIV gag/pol/nef sequences and HLA-II allelic data, we identified 29 HLA-II associated HIV sequence polymorphisms or adaptations (HLA-AP) in an African cohort of chronically HIV-infected individuals. Epitopes encompassing the predicted adaptation (AE) or its non-adapted (NAE) version were evaluated for immunogenicity. Using a CD8-depleted IFN-γ ELISpot assay, we determined that the magnitude of CD4+ T cell responses to the predicted epitopes in controllers was higher compared to non-controllers (p<0.0001). However, regardless of the group, the magnitude of responses to AE was lower as compared to NAE (p<0.0001). CD4+ T cell responses in patients with acute HIV infection (AHI) demonstrated poor immunogenicity towards AE as compared to NAE encoded by their transmitted founder virus. Longitudinal data in AHI off antiretroviral therapy demonstrated sequence changes that were biologically confirmed to represent CD4+ escape mutations. These data demonstrate an innovative application of HLA-associated polymorphisms to identify biologically relevant CD4+ epitopes and suggests CD4+ T cells are active participants in driving HIV evolution. PMID:26302050

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

    PubMed

    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.

  13. 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.

  14. 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.

  15. 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

  16. Novel insights into the regulatory architecture of CD4+ T cells in rheumatoid arthritis.

    PubMed

    Aterido, Adrià; Palacio, Carlos; Marsal, Sara; Avila, 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.

  17. Increased 5-hydroxymethylcytosine in CD4(+) T cells in systemic lupus erythematosus.

    PubMed

    Zhao, Ming; Wang, Jing; Liao, Wei; Li, Duo; Li, Mengying; Wu, Haijing; Zhang, Yiqun; Gershwin, M Eric; Lu, Qianjin

    2016-05-01

    One of the major disappointments in autoimmunity has been the relative lack of informative data when genomewide associations (GWAS) have been applied to patients with systemic lupus erythematosus (SLE). Indeed, there is increasing evidence that SLE is characterized by widespread epigenetic changes. 5-Hydroxymethylcytosine (5-hmC) is a newly discovered modified form of cytosine suspected to be an important epigenetic modification in embryonic development, cell differentiation and cancer. DNA methylation dynamics have already been implicated in the pathogenesis of SLE, while little is known about hydroxymethylation in this process. Here, we show an increased 5-hmC level in genomic DNA in CD4(+) T cells of patients with SLE compared with healthy controls, accompanied by the up-regulated expression of the Ten-eleven translocation TET2 and TET3, which can enzymatically convert 5-methylcytosine (5-mC) to 5-hmC. Moreover, we present the differential patterns of DNA hydroxymethylation in genome-wide promoter regions in SLE CD4(+) T cells compared with healthy controls. We identified 2748 genes with increased 5-hmC levels in promoter regions in SLE CD4(+) T cells, which were enriched in critical pathways, including neurotrophin signaling, WNT signaling, MAPK signaling, calcium signaling and the mTOR signaling pathway. Through a combined analysis of differential DNA hydroxymethylation profile and gene expression profile in SLE CD4(+) T cells, we found 131 genes with the increased 5-hmC in promoter regions and up-regulated expression in SLE CD4(+) T cells compared with healthy controls, including selected immune-related genes, i.e. SOCS1, NR2F6 and IL15RA, which were also confirmed by ChIP-qPCR. Furthermore, we demonstrate that CTCF, as a transcription factor, can mediate DNA hydroxymethylation and contribute to overexpression of SOCS1 in CD4(+) T cells through binding to the promoter region of SOCS1. Taken together, our study reveals a critical differential 5-hmC in the

  18. 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

  19. 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

  20. 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

  1. 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

  2. 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

  3. 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.

  4. 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

  5. Reconstitution of CD4 T Cells in Bronchoalveolar Lavage Fluid after Initiation of Highly Active Antiretroviral Therapy▿

    PubMed Central

    Knox, Kenneth S.; Vinton, Carol; Hage, Chadi A.; Kohli, Lisa M.; Twigg, Homer L.; Klatt, Nichole R.; Zwickl, Beth; Waltz, Jeffrey; Goldman, Mitchell; Douek, Daniel C.; Brenchley, Jason M.

    2010-01-01

    The massive depletion of gastrointestinal-tract CD4 T cells is a hallmark of the acute phase of HIV infection. In contrast, the depletion of the lower-respiratory-tract mucosal CD4 T cells as measured in bronchoalveolar lavage (BAL) fluid is more moderate and similar to the depletion of CD4 T cells observed in peripheral blood (PB). To understand better the dynamics of disease pathogenesis and the potential for the reconstitution of CD4 T cells in the lung and PB following the administration of effective antiretroviral therapy, we studied cell-associated viral loads, CD4 T-cell frequencies, and phenotypic and functional profiles of antigen-specific CD4 T cells from BAL fluid and blood before and after the initiation of highly active antiretroviral therapy (HAART). The major findings to emerge were the following: (i) BAL CD4 T cells are not massively depleted or preferentially infected by HIV compared to levels for PB; (ii) BAL CD4 T cells reconstitute after the initiation of HAART, and their infection frequencies decrease; (iii) BAL CD4 T-cell reconstitution appears to occur via the local proliferation of resident BAL CD4 T cells rather than redistribution; and (iv) BAL CD4 T cells are more polyfunctional than CD4 T cells in blood, and their functional profile is relatively unchanged after the initiation of HAART. Taken together, these data suggest mechanisms for mucosal CD4 T-cell depletion and interventions that might aid in the reconstitution of mucosal CD4 T cells. PMID:20610726

  6. Top quark physics with ATLAS and CMS

    SciTech Connect

    Onofre, A.

    2009-12-17

    The potential of the ATLAS and CMS experiments for studying top quark physics at the LHC is reviewed. The measurements of the tt-bar production cross section and spin correlations, the top quark mass, its electric charge, the structure of the W tb vertex and the measurement of the W boson helicities, the sensitivity to anomalous couplings, top quark rare decays through Flavour Changing Neutral Currents and the single top quark production are discussed. The results shown use the fall Monte Carlo simulation of ATLAS and CMS and assume a center of mass energy of 14 TeV at the LHC. Integrated luminosities in the range between B(10 bp{sup -1}) and B(10 fb{sup -1}) are considered, depending on the physics observables under study.

  7. 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.

  8. 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.

  9. Multi-core aware applications in CMS

    NASA Astrophysics Data System (ADS)

    Jones, C. D.; Elmer, P.; Sexton-Kennedy, L.; Green, C.; Baldooci, A.

    2011-12-01

    One of the significant trends of recent years has been the move towards multicore CPU's with ever increasing numbers of cores. CMS has been preparing multicore aware applications that rely on "multi-processing", namely the sharing of memory between processes forked from a single parent process. First experience with deploying these applications for production will be presented, as well as results from detailed profiling done to understand the limits of scaling with increasing numbers of cores.

  10. 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.

  11. 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.

  12. 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

  13. Heavy-ion physics with CMS

    NASA Astrophysics Data System (ADS)

    Betts, R. R.; CMS Collaboration

    2007-08-01

    The Large Hadron Collider (LHC) at CERN will collide protons at \\sqrt{s_NN} = 14 \\ TeV and lead ions at \\sqrt{s_NN} = 5.5 \\ TeV . The research program of the Compact Muon Solenoid (CMS) experiment includes a strong heavy-ion physics agenda, especially in the measurement of hard processes. The high centre-of-mass energies available at the LHC will allow high statistics studies of high-density QCD with hard probes: heavy quarks and quarkonia with an emphasis on the J/ψ and Upsilon, high-pT jets, direct photons as well as Z0 bosons. In addition to the detailed studies of hard probes, CMS will measure charged particle multiplicity and energy flow with respect to the reaction plane on an event-by-event basis. Studies of the CMS capabilities and physics reach for different high-density QCD observables, using the full detector simulation and reconstruction, are presented.

  14. 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.

  15. Monitoring the CMS data acquisition system

    NASA Astrophysics Data System (ADS)

    Bauer, G.; Behrens, U.; Biery, K.; Branson, J.; Cano, E.; Cheung, H.; Ciganek, M.; Cittolin, S.; Coarasa, J. A.; Deldicque, C.; Dusinberre, E.; Erhan, S.; Fortes Rodrigues, F.; Gigi, D.; Glege, F.; Gomez-Reino, R.; Gutleber, J.; Hatton, D.; Laurens, J. F.; Lopez Perez, J. A.; Meijers, F.; Meschi, E.; Meyer, A.; Mommsen, R.; Moser, R.; O'Dell, V.; Oh, A.; Orsini, L. B.; Patras, V.; Paus, C.; Petrucci, A.; Pieri, M.; Racz, A.; Sakulin, H.; Sani, M.; Schieferdecker, P.; Schwick, C.; Shpakov, D.; Simon, S.; Sumorok, K.; Zanetti, M.

    2010-04-01

    The CMS data acquisition system comprises O(20000) interdependent services that need to be monitored in near real-time. The ability to monitor a large number of distributed applications accurately and effectively is of paramount importance for robust operations. Application monitoring entails the collection of a large number of simple and composed values made available by the software components and hardware devices. A key aspect is that detection of deviations from a specified behaviour is supported in a timely manner, which is a prerequisite in order to take corrective actions efficiently. Given the size and time constraints of the CMS data acquisition system, efficient application monitoring is an interesting research problem. We propose an approach that uses the emerging paradigm of Web-service based eventing systems in combination with hierarchical data collection and load balancing. Scalability and efficiency are achieved by a decentralized architecture, splitting up data collections into regions of collections. An implementation following this scheme is deployed as the monitoring infrastructure of the CMS experiment at the Large Hadron Collider. All services in this distributed data acquisition system are providing standard web service interfaces via XML, SOAP and HTTP [15,22]. Continuing on this path we adopted WS-* standards implementing a monitoring system layered on top of the W3C standards stack. We designed a load-balanced publisher/subscriber system with the ability to include high-speed protocols [10,12] for efficient data transmission [11,13,14] and serving data in multiple data formats.

  16. Pharmacological interference with protein-protein interactions mediated by coiled-coil motifs.

    PubMed

    Strauss, H M; Keller, S

    2008-01-01

    Coiled coils are bundles of intertwined alpha-helices that provide protein-protein interaction sites for the dynamic assembly and disassembly of protein complexes. The coiled-coil motif combines structural versatility and adaptability with mechanical strength and specificity. Multimeric proteins that rely on coiled-coil interactions are structurally and functionally very diverse, ranging from simple homodimeric transcription factors to elaborate heteromultimeric scaffolding clusters. Several coiled-coil-bearing proteins are of outstanding pharmacological importance, most notably SNARE proteins involved in vesicular trafficking of neurotransmitters and viral fusion proteins. Together with their crucial roles in many physiological and pathological processes, the structural simplicity and reversible nature of coiled-coil associations render them a promising target for pharmacological interference, as successfully exemplified by botulinum toxins and viral fusion inhibitors. The alpha-helical coiled coil is a ubiquitous protein domain that mediates highly specific homo- and heteromeric protein-protein interactions among a wide range of proteins. The coiled-coil motif was first proposed by Crick on the basis of X-ray diffraction data on alpha-keratin more than 50 years ago (Crick 1952, 1953) and nowadays belongs to the best-characterized protein interaction modules. By definition, a coiled coil is an oligomeric protein assembly consisting of several right-handed amphipathic alpha-helices that wind around each other into a superhelix (or a supercoil) in which the hydrophobic surfaces of the constituent helices are in continuous contact, forming a hydrophobic core. Both homomeric and heteromeric coiled coils with different stoichiometries are possible, and the helices can be aligned in either a parallel or an antiparallel topology (Harbury et al. 1993, 1994). Stoichiometry and topology are governed by the primary structure, that is, the sequence of the polypeptide chains

  17. 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.

  18. 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

  19. 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

  20. 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.

  1. 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…

  2. Functional investigation of the plant-specific long coiled-coil proteins PAMP-INDUCED COILED-COIL (PICC) and PICC-LIKE (PICL) in Arabidopsis thaliana.

    PubMed

    Venkatakrishnan, Sowmya; Mackey, David; Meier, Iris

    2013-01-01

    We have identified and characterized two Arabidopsis long coiled-coil proteins PAMP-INDUCED COILED-COIL (PICC) and PICC-LIKE (PICL). PICC (147 kDa) and PICL (87 kDa) are paralogs that consist predominantly of a long coiled-coil domain (expanded in PICC), with a predicted transmembrane domain at the immediate C-terminus. Orthologs of PICC and PICL were found exclusively in vascular plants. PICC and PICL GFP fusion proteins are anchored to the cytoplasmic surface of the endoplasmic reticulum (ER) membrane by a C-terminal transmembrane domain and a short tail domain, via a tail-anchoring mechanism. T-DNA-insertion mutants of PICC and PICL as well as the double mutant show an increased sensitivity to the plant abiotic stress hormone abscisic acid (ABA) in a post-germination growth response. PICC, but not PICL gene expression is induced by the bacterial pathogen-associated molecular pattern (PAMP) flg22. T-DNA insertion alleles of PICC, but not PICL, show increased susceptibility to the non-virulent strain P. syringae pv. tomato DC3000 hrcC, but not to the virulent strain P. syringae pv. tomato DC3000. This suggests that PICC mutants are compromised in PAMP-triggered immunity (PTI). The data presented here provide first evidence for the involvement of a plant long coiled-coil protein in a plant defense response.

  3. 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.

  4. 49 CFR 236.730 - Coil, receiver.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Coil, receiver. 236.730 Section 236.730 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION... Coil, receiver. Concentric layers of insulated wire wound around the core of a receiver of an...

  5. 49 CFR 236.730 - Coil, receiver.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 4 2011-10-01 2011-10-01 false Coil, receiver. 236.730 Section 236.730 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION... Coil, receiver. Concentric layers of insulated wire wound around the core of a receiver of an...

  6. 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.

  7. 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.

  8. Functional Investigation of the Plant-Specific Long Coiled-Coil Proteins PAMP-INDUCED COILED-COIL (PICC) and PICC-LIKE (PICL) in Arabidopsis thaliana

    PubMed Central

    Venkatakrishnan, Sowmya; Mackey, David; Meier, Iris

    2013-01-01

    We have identified and characterized two Arabidopsis long coiled-coil proteins PAMP-INDUCED COILED-COIL (PICC) and PICC-LIKE (PICL). PICC (147 kDa) and PICL (87 kDa) are paralogs that consist predominantly of a long coiled-coil domain (expanded in PICC), with a predicted transmembrane domain at the immediate C-terminus. Orthologs of PICC and PICL were found exclusively in vascular plants. PICC and PICL GFP fusion proteins are anchored to the cytoplasmic surface of the endoplasmic reticulum (ER) membrane by a C-terminal transmembrane domain and a short tail domain, via a tail-anchoring mechanism. T-DNA-insertion mutants of PICC and PICL as well as the double mutant show an increased sensitivity to the plant abiotic stress hormone abscisic acid (ABA) in a post-germination growth response. PICC, but not PICL gene expression is induced by the bacterial pathogen-associated molecular pattern (PAMP) flg22. T-DNA insertion alleles of PICC, but not PICL, show increased susceptibility to the non-virulent strain P. syringae pv. tomato DC3000 hrcC, but not to the virulent strain P. syringae pv. tomato DC3000. This suggests that PICC mutants are compromised in PAMP-triggered immunity (PTI). The data presented here provide first evidence for the involvement of a plant long coiled-coil protein in a plant defense response. PMID:23451199

  9. Functional investigation of the plant-specific long coiled-coil proteins PAMP-INDUCED COILED-COIL (PICC) and PICC-LIKE (PICL) in Arabidopsis thaliana.

    PubMed

    Venkatakrishnan, Sowmya; Mackey, David; Meier, Iris

    2013-01-01

    We have identified and characterized two Arabidopsis long coiled-coil proteins PAMP-INDUCED COILED-COIL (PICC) and PICC-LIKE (PICL). PICC (147 kDa) and PICL (87 kDa) are paralogs that consist predominantly of a long coiled-coil domain (expanded in PICC), with a predicted transmembrane domain at the immediate C-terminus. Orthologs of PICC and PICL were found exclusively in vascular plants. PICC and PICL GFP fusion proteins are anchored to the cytoplasmic surface of the endoplasmic reticulum (ER) membrane by a C-terminal transmembrane domain and a short tail domain, via a tail-anchoring mechanism. T-DNA-insertion mutants of PICC and PICL as well as the double mutant show an increased sensitivity to the plant abiotic stress hormone abscisic acid (ABA) in a post-germination growth response. PICC, but not PICL gene expression is induced by the bacterial pathogen-associated molecular pattern (PAMP) flg22. T-DNA insertion alleles of PICC, but not PICL, show increased susceptibility to the non-virulent strain P. syringae pv. tomato DC3000 hrcC, but not to the virulent strain P. syringae pv. tomato DC3000. This suggests that PICC mutants are compromised in PAMP-triggered immunity (PTI). The data presented here provide first evidence for the involvement of a plant long coiled-coil protein in a plant defense response. PMID:23451199

  10. 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.

  11. 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.

  12. Various factors affect coiled tubing limits

    SciTech Connect

    Yang, Y.S.

    1996-01-15

    Safety and reliability remain the primary concerns in coiled tubing operations. Factors affecting safety and reliability include corrosion, flexural bending, internal (or external) pressure and tension (or compression), and mechanical damage due to improper use. Such limits as coiled tubing fatigue, collapse, and buckling need to be understood to avoid disaster. With increased use of coiled tubing, operators will gain more experience. But at the same time, with further research and development of coiled tubing, the manufacturing quality will be improved and fatigue, collapse, and buckling models will become more mature, and eventually standard specifications will be available. This paper reviews the uses of coiled tubing and current research on mechanical behavior of said tubing. It also discusses several models used to help predict fatigue and failure levels.

  13. 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.

  14. 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 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. PMID:26852418

  15. Design description of the Large Coil Test Facility pulse-coil support and transport system

    SciTech Connect

    Queen, C.C.

    1981-01-01

    In order to simulate the transient fields which would be imposed on superconducting toroidal field coils in an operating tokamak reactor, the Large Coil Test Facility (LCTF) test stand includes a set of pulse coils. This set of pulse coils is designed to be moved from one test location to another within the LCTF vacuum vessel while the vessel is operating under vacuum and the test stand and test coils are at an operating temperature of 4.2K. This operating environment and the extremely high magnetic loads have necessitated some unique design features for the pulse coil support and transport system. The support structure for the pulse coil must react high overturning moments and axial loads induced on the pulse coil by the interaction of the pulse field with the field generated by the large test coils. These loads are reacted into the test stand support structure or spider frame by an arrangement of six pedestals and a support beam. In order to move the pulse coil set from one test location to another, the support beam containing the pulse coils must be driven across rollers mounted on the pedestals, then clamped securely to react the loads. Because these operations must be performed in a vacuum environment at cryogenic tmperature, special consideration was given to component design.

  16. 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.

  17. 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

  18. Inflammation-induced effector CD4+ T cell interstitial migration is alpha-v integrin dependent

    PubMed Central

    Overstreet, Michael G.; Gaylo, Alison; Angermann, Bastian; Hughson, Angela; Hyun, Young-min; Lambert, Kris; Acharya, Mridu; Billroth-Maclurg, Alison C.; Rosenberg, Alexander F.; Topham, David J.; Yagita, Hideo; Kim, Minsoo; Lacy-Hulbert, Adam; Meier-Schellersheim, Martin; Fowell, Deborah J.

    2014-01-01

    Leukocytes must traverse inflamed tissues to effectively control local infection. Although motility in dense tissues appears to be integrin-independent actin-myosin based, during inflammation changes to the extracellular matrix (ECM) may necessitate distinct motility requirements. Indeed, we found that T cell interstitial motility was critically dependent on RGD-binding integrins in the inflamed dermis. Inflammation-induced deposition of fibronectin was functionally linked to increased αv integrin expression on effector CD4+ T cells. Using intravital multi-photon imaging, we found that CD4+ T cell motility was dependent on αv expression. Selective αv blockade or knockdown arrested TH1 motility in the inflamed tissue and attenuated local effector function. These data show a context-dependent specificity of lymphocyte movement in inflamed tissues that is essential for protective immunity. PMID:23933892

  19. CD1-restricted CD4+ T cells in major histocompatibility complex class II-deficient mice

    PubMed Central

    1995-01-01

    Rather unexpectedly, major histocompatibility complex class II- deficient mice have a significant population of peripheral CD4+ T lymphocytes. We have investigated these cells at the population and clonal levels. CD4+ T lymphocytes from class II-deficient animals are thymically derived, appear early in ontogeny, exhibit the phenotype of resting memory cells, are potentially functional by several criteria, and have a diverse T cell receptor repertoire. They do not include substantially elevated numbers of NK1.1+ cells. Hybridomas derived after polyclonal stimulation of the CD4+ lymphocytes from class II- deficient animals include a subset with an unusual reactivity pattern, responding to splenocytes from many mouse strains including the strain of origin. Most members of this subset recognize the major histocompatibility complex class Ib molecule CD1; their heterogeneous reactivities and T cell receptor usage further suggest the involvement of peptides and/or highly variable posttranslational modifications. PMID:7561702

  20. Harnessing the plasticity of CD4(+) T cells to treat immune-mediated disease.

    PubMed

    DuPage, Michel; Bluestone, Jeffrey A

    2016-03-01

    CD4(+) T cells differentiate and acquire distinct functions to combat specific pathogens but can also adapt their functions in response to changing circumstances. Although this phenotypic plasticity can be potentially deleterious, driving immune pathology, it also provides important benefits that have led to its evolutionary preservation. Here, we review CD4(+) T cell plasticity by examining the molecular mechanisms that regulate it - from the extracellular cues that initiate and drive cells towards varying phenotypes, to the cytosolic signalling cascades that decipher these cues and transmit them into the cell and to the nucleus, where these signals imprint specific gene expression programmes. By understanding how this functional flexibility is achieved, we may open doors to new therapeutic approaches that harness this property of T cells. PMID:26875830

  1. 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.

  2. 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.

  3. Granzyme B mediated function of Parvovirus B19-specific CD4+ T cells

    PubMed Central

    Kumar, Arun; Perdomo, Maria F; Kantele, Anu; Hedman, Lea; Hedman, Klaus; Franssila, Rauli

    2015-01-01

    A novel conception of CD4+ T cells with cytolytic potential (CD4+ CTL) is emerging. These cells appear to have a part in controlling malignancies and chronic infections. Human parvovirus B19 can cause a persistent infection, yet no data exist on the presence of B19-specific CD4+ CTLs. Such cells could have a role in the pathogenesis of some autoimmune disorders reported to be associated with B19. We explored the cytolytic potential of human parvovirus B19-specific T cells by stimulating peripheral blood mononuclear cell (PBMC) with recombinant B19-VP2 virus-like particles. The cytolytic potential was determined by enzyme immunoassay-based quantitation of granzyme B (GrB) and perforin from the tissue culture supernatants, by intracellular cytokine staining (ICS) and by detecting direct cytotoxicity. GrB and perforin responses with the B19 antigen were readily detectable in B19-seropositive individuals. T-cell depletion, HLA blocking and ICS experiments showed GrB and perforin to be secreted by CD4+ T cells. CD4+ T cells with strong GrB responses were found to exhibit direct cytotoxicity. As anticipated, ICS of B19-specific CD4+ T cells showed expected co-expression of GrB, perforin and interferon gamma (IFN-γ). Unexpectedly, also a strong co-expression of GrB and interleukin 17 (IL-17) was detected. These cells expressed natural killer (NK) cell surface marker CD56, together with the CD4 surface marker. To our knowledge, this is the first report on virus-specific CD4+ CTLs co-expressing CD56 antigen. Our results suggest a role for CD4+ CTL in B19 immunity. Such cells could function within both immune regulation and triggering of autoimmune phenomena such as systemic lupus erythematosus (SLE) or rheumatoid arthritis. PMID:26246896

  4. 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

  5. CD4(+) T cells epigenetically modified by oxidative stress cause lupus-like autoimmunity in mice.

    PubMed

    Strickland, Faith M; Li, YePeng; Johnson, Kent; Sun, Zhichao; Richardson, Bruce C

    2015-08-01

    Lupus develops when genetically predisposed people encounter environmental agents such as UV light, silica, infections and cigarette smoke that cause oxidative stress, but how oxidative damage modifies the immune system to cause lupus flares is unknown. We previously showed that oxidizing agents decreased ERK pathway signaling in human T cells, decreased DNA methyltransferase 1 and caused demethylation and overexpression of genes similar to those from patients with active lupus. The current study tested whether oxidant-treated T cells can induce lupus in mice. We adoptively transferred CD4(+) T cells treated in vitro with oxidants hydrogen peroxide or nitric oxide or the demethylating agent 5-azacytidine into syngeneic mice and studied the development and severity of lupus in the recipients. Disease severity was assessed by measuring anti-dsDNA antibodies, proteinuria, hematuria and by histopathology of kidney tissues. The effect of the oxidants on expression of CD40L, CD70, KirL1 and DNMT1 genes and CD40L protein in the treated CD4(+) T cells was assessed by Q-RT-PCR and flow cytometry. H2O2 and ONOO(-) decreased Dnmt1 expression in CD4(+) T cells and caused the upregulation of genes known to be suppressed by DNA methylation in patients with lupus and animal models of SLE. Adoptive transfer of oxidant-treated CD4(+) T cells into syngeneic recipients resulted in the induction of anti-dsDNA antibody and glomerulonephritis. The results show that oxidative stress may contribute to lupus disease by inhibiting ERK pathway signaling in T cells leading to DNA demethylation, upregulation of immune genes and autoreactivity.

  6. 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

  7. Dendritic Cells Enhance HIV Infection of Memory CD4(+) T Cells in Human Lymphoid Tissues.

    PubMed

    Reyes-Rodriguez, Angel L; Reuter, Morgan A; McDonald, David

    2016-02-01

    Dendritic cells (DCs) play a key role in controlling infections by coordinating innate and adaptive immune responses to invading pathogens. Paradoxically, DCs can increase HIV-1 dissemination in vitro by binding and transferring infectious virions to CD4(+) T cells, a process called transinfection. Transinfection has been well characterized in cultured cell lines and circulating primary T cells, but it is unknown whether DCs enhance infection of CD4(+) T cells in vivo. In untreated HIV infection, massive CD4(+) T-cell infection and depletion occur in secondary lymphoid tissues long before decline is evident in the peripheral circulation. To study the role of DCs in HIV infection of lymphoid tissues, we utilized human tonsil tissues, cultured either as tissue blocks or as aggregate suspension cultures, in single-round infection experiments. In these experiments, addition of monocyte-derived DCs (MDDCs) to the cultures increased T-cell infection, particularly in CD4(+) T cells expressing lower levels of HLA-DR. Subset analysis demonstrated that MDDCs increased HIV-1 infection of central and effector memory T-cell populations. Depletion of endogenous myeloid DCs (myDCs) from the cultures decreased memory T-cell infection, and readdition of MDDCs restored infection to predepletion levels. Using an HIV-1 fusion assay, we found that MDDCs equally increased HIV delivery into naïve, central, and effector memory T cells in the cultures, whereas predepletion of myDCs reduced fusion into memory T cells. Together, these data suggest that resident myDCs facilitate memory T-cell infection in lymphoid tissues, implicating DC-mediated transinfection in driving HIV dissemination within these tissues in untreated HIV/AIDS.

  8. Rheumatoid arthritis-associated RBPJ polymorphism alters memory CD4+ T cells.

    PubMed

    Orent, William; Mchenry, Allison R; Rao, Deepak A; White, Charles; Klein, Hans-Ulrich; Bassil, Ribal; Srivastava, Gyan; Replogle, Joseph M; Raj, Towfique; Frangieh, Michael; Cimpean, Maria; Cuerdon, Nicole; Chibnik, Lori; Khoury, Samia J; Karlson, Elizabeth W; Brenner, Michael B; De Jager, Philip; Bradshaw, Elizabeth M; Elyaman, Wassim

    2016-01-15

    Notch signaling has recently emerged as an important regulator of immune responses in autoimmune diseases. The recombination signal-binding protein for immunoglobulin kappa J region (RBPJ) is a transcriptional repressor, but converts into a transcriptional activator upon activation of the canonical Notch pathway. Genome-wide association studies of rheumatoid arthritis (RA) identified a susceptibility locus, rs874040(CC), which implicated the RBPJ gene. Here, chromatin state mapping generated using the chromHMM algorithm reveals strong enhancer regions containing DNase I hypersensitive sites overlapping the rs874040 linkage disequilibrium block in human memory, but not in naïve CD4(+) T cells. The rs874040 overlapping this chromatin state was associated with increased RBPJ expression in stimulated memory CD4(+) T cells from healthy subjects homozygous for the risk allele (CC) compared with memory CD4(+) T cells bearing the protective allele (GG). Transcriptomic analysis of rs874040(CC) memory T cells showed a repression of canonical Notch target genes IL (interleukin)-9, IL-17 and interferon (IFN)γ in the basal state. Interestingly, activation of the Notch pathway using soluble Notch ligand, Jagged2-Fc, induced IL-9 and IL-17A while delta-like 4Fc, another Notch ligand, induced higher IFNγ expression in the rs874040(CC) memory CD4(+) T cells compared with their rs874040(GG) counterparts. In RA, RBPJ expression is elevated in memory T cells from RA patients compared with control subjects, and this was associated with induced inflammatory cytokines IL-9, IL-17A and IFNγ in response to Notch ligation in vitro. These findings demonstrate that the rs874040(CC) allele skews memory T cells toward a pro-inflammatory phenotype involving Notch signaling, thus increasing the susceptibility to develop RA. PMID:26604133

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

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 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... taxes paid or accrued. (ii) In 2008, X accrued and paid 100m of Country M taxes with respect to 400m...

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

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 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... taxes paid or accrued. (ii) In 2008, X accrued and paid 100m of Country M taxes with respect to 400m...

  11. 26 CFR 1.905-4T - Notification of foreign tax redetermination (temporary).

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 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... taxes paid or accrued. (ii) In 2008, X accrued and paid 100m of Country M taxes with respect to 400m...

  12. 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... taxes paid or accrued. (ii) In 2008, X accrued and paid 100m of Country M taxes with respect to 400m...

  13. 26 CFR 1.905-4T - Notification of foreign tax redetermination (temporary).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 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... taxes paid or accrued. (ii) In 2008, X accrued and paid 100m of Country M taxes with respect to 400m...

  14. Identification of Mycobacterium tuberculosis vaccine candidates using human CD4+ T-cells expression cloning

    PubMed Central

    Coler, Rhea N.; Dillon, Davin C.; Skeiky, Yasir A. W.; Kahn, Maria; Orme, Ian M.; Lobet, Yves; Reed, Steven G.; Alderson, Mark R.

    2009-01-01

    To identify Mycobacterium tuberculosis (Mtb) antigens as candidates for a subunit vaccine against tuberculosis (TB), we have employed a CD4+ T-cell expression screening method. Mtb-specific CD4+ T-cell lines from nine healthy PPD positive donors were stimulated with different antigenic substrates including autologous dendritic cells (DC) infected with Mtb, culture filtrate proteins (CFP), and purified protein derivative of Mtb (PPD). These lines were used to screen a genomic Mtb library expressed in Escherichia coli and processed and presented by autologous DC. This screening led to the recovery of numerous T-cell antigens, including both novel and previously described antigens. One of these novel antigens, referred to as Mtb9.8 (Rv0287), was recognized by multiple T-cell lines, stimulated with either Mtb-infected DC or CFP. Using the mouse and guinea pig models of TB, high levels of IFN-γ were produced, and solid protection from Mtb challenge was observed following immunization with Mtb9.8 formulated in either AS02A or AS01B Adjuvant Systems. These results demonstrate that T-cell screening of the Mtb genome can be used to identify CD4+ T-cell antigens that are candidates for vaccine development. PMID:19000730

  15. 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

  16. 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

  17. Metabolic programming and PDHK1 control CD4+ T cell subsets and inflammation.

    PubMed

    Gerriets, Valerie A; Kishton, Rigel J; Nichols, Amanda G; Macintyre, Andrew N; Inoue, Makoto; Ilkayeva, Olga; Winter, Peter S; Liu, Xiaojing; Priyadharshini, Bhavana; Slawinska, Marta E; Haeberli, Lea; Huck, Catherine; Turka, Laurence A; Wood, Kris C; Hale, Laura P; Smith, Paul A; Schneider, Martin A; MacIver, Nancie J; Locasale, Jason W; Newgard, Christopher B; Shinohara, Mari L; Rathmell, Jeffrey C

    2015-01-01

    Activation of CD4+ T cells results in rapid proliferation and differentiation into effector and regulatory subsets. CD4+ effector T cell (Teff) (Th1 and Th17) and Treg subsets are metabolically distinct, yet the specific metabolic differences that modify T cell populations are uncertain. Here, we evaluated CD4+ T cell populations in murine models and determined that inflammatory Teffs maintain high expression of glycolytic genes and rely on high glycolytic rates, while Tregs are oxidative and require mitochondrial electron transport to proliferate, differentiate, and survive. Metabolic profiling revealed that pyruvate dehydrogenase (PDH) is a key bifurcation point between T cell glycolytic and oxidative metabolism. PDH function is inhibited by PDH kinases (PDHKs). PDHK1 was expressed in Th17 cells, but not Th1 cells, and at low levels in Tregs, and inhibition or knockdown of PDHK1 selectively suppressed Th17 cells and increased Tregs. This alteration in the CD4+ T cell populations was mediated in part through ROS, as N-acetyl cysteine (NAC) treatment restored Th17 cell generation. Moreover, inhibition of PDHK1 modulated immunity and protected animals against experimental autoimmune encephalomyelitis, decreasing Th17 cells and increasing Tregs. Together, these data show that CD4+ subsets utilize and require distinct metabolic programs that can be targeted to control specific T cell populations in autoimmune and inflammatory diseases.

  18. Human CD4 T cell epitopes selective for Vaccinia versus Variola virus.

    PubMed

    Probst, Alicia; Besse, Aurore; Favry, Emmanuel; Imbert, Gilles; Tanchou, Valérie; Castelli, Florence Anne; Maillere, Bernard

    2013-04-01

    Due to the high degree of sequence identity between Orthopoxvirus species, the specific B and T cell responses raised against these viruses are largely cross-reactive and poorly selective. We therefore searched for CD4 T cell epitopes present in the conserved parts of the Vaccinia genome (VACV) but absent from Variola viruses (VARV), with a view to identifying immunogenic sequences selective for VACV. We identified three long peptide fragments from the B7R, B10R and E7R proteins by in silico comparisons of the poxvirus genomes, and evaluated the recognition of these fragments by VACV-specific T cell lines derived from healthy donors. For the 12 CD4 T cell epitopes identified, we assessed their binding to common HLA-DR allotypes and their capacity to induce peptide-specific CD4 T-cell lines. Four peptides from B7R and B10R displayed a broad binding specificity for HLA-DR molecules and induced multiple T cell lines from healthy donors. Besides their absence from VARV, the two B10R peptide sequences were mutated in the Cowpox virus and completely absent from the Monkeypox genome. This work contributes to the development of differential diagnosis of poxvirus infections.

  19. 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.

  20. Immune activation induces immortalization of HTLV-1 LTR-Tax transgenic CD4+ T cells.

    PubMed

    Swaims, Alison Y; Khani, Francesca; Zhang, Yingyu; Roberts, Arthur I; Devadas, Satish; Shi, Yufang; Rabson, Arnold B

    2010-10-21

    Infection with the human T-cell leukemia virus-1 (HTLV-1) results in a variety of diseases including adult T-cell leukemia/lymphoma (ATL). Although the pathogenesis of these disorders is poorly understood, it involves complex interactions with the host immune system. Activation of infected T cells may play an important role in disease pathogenesis through induction of the oncogenic HTLV-1 Tax transactivator protein. To test this hypothesis, we employed transgenic mice in which Tax is regulated by the HTLV-1 LTR. T-cell receptor stimulation of LTR-Tax CD4(+) T cells induced Tax expression, hyper-proliferation, and immortalization in culture. The transition to cellular immortalization was accompanied by markedly increased expression of the antiapoptotic gene, mcl-1, previously implicated as important in T-cell survival. Immortalized cells exhibited a CD4(+)CD25(+)CD3(-) phenotype commonly observed in ATL. Engraftment of activated LTR-Tax CD4(+) T cells into NOD/Shi-scid/IL-2Rγ null mice resulted in a leukemia-like phenotype with expansion and tissue infiltration of Tax(+), CD4(+) lymphocytes. We suggest that immune activation of infected CD4(+) T cells plays an important role in the induction of Tax expression, T-cell proliferation, and pathogenesis of ATL in HTLV-1-infected individuals. PMID:20634377

  1. Out-of-Sequence Signal 3 Paralyzes Primary CD4(+) T-Cell-Dependent Immunity.

    PubMed

    Sckisel, Gail D; Bouchlaka, Myriam N; Monjazeb, Arta M; Crittenden, Marka; Curti, Brendan D; Wilkins, Danice E C; Alderson, Kory A; Sungur, Can M; Ames, Erik; Mirsoian, Annie; Reddy, Abhinav; Alexander, Warren; Soulika, Athena; Blazar, Bruce R; Longo, Dan L; Wiltrout, Robert H; Murphy, William J

    2015-08-18

    Primary T cell activation involves the integration of three distinct signals delivered in sequence: (1) antigen recognition, (2) costimulation, and (3) cytokine-mediated differentiation and expansion. Strong immunostimulatory events such as immunotherapy or infection induce profound cytokine release causing "bystander" T cell activation, thereby increasing the potential for autoreactivity and need for control. We show that during strong stimulation, a profound suppression of primary CD4(+) T-cell-mediated immune responses ensued and was observed across preclinical models and patients undergoing high-dose interleukin-2 (IL-2) therapy. This suppression targeted naive CD4(+) but not CD8(+) T cells and was mediated through transient suppressor of cytokine signaling-3 (SOCS3) inhibition of the STAT5b transcription factor signaling pathway. These events resulted in complete paralysis of primary CD4(+) T cell activation, affecting memory generation and induction of autoimmunity as well as impaired viral clearance. These data highlight the critical regulation of naive CD4(+) T cells during inflammatory conditions.

  2. Activation of CD4+ T lymphocytes form interleukin 2-deficient mice by costimulatory B7 molecules.

    PubMed Central

    Razi-Wolf, Z; Höllander, G A; Reiser, H

    1996-01-01

    Interleukin 2 (IL-2)-deficient (IL-2-/-) mice develop hemolytic anemia and chronic inflammatory bowel disease. Importantly, the induction of disease in IL-2-deficient mice is critically dependent on CD4+ T cells. We have studied the requirements of T cells from IL-2-deficient mice for costimulation with B7 antigens. Stable B7-1 or B7-2 chinese hamster ovary (CHO) cell transfectants could synergize with anti-CD3 monoclonal antibody (mAb) to induce the proliferation of CD4+ T cells from IL-2-/- mutant mice. Further mechanistic studies established that B7-induced activation resulted in surface expression of the alpha chain of the IL-2 receptor. B7-induced proliferation occurred independently of IL-4 and was largely independent of the common gamma chain of the IL-2, IL-4, IL-7, IL-9, and IL-15 receptors. Finally, anti-B7-2 but not anti-B7-1 mAb was able to inhibit the activation of IL-2-/- T cells induced by anti-CD3 mAb in the presence of syngeneic antigen-presenting cells. The results of our experiments indicate that IL-2-/- CD4+ T cells remain responsive to B7 stimulation and raise the possibility that B7 antagonists have a role in the prevention/treatment of inflammatory bowel disease. Images Fig. 3 PMID:8610140

  3. 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

  4. 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

  5. Adenoviral transduction of naive CD4 T cells to study Treg differentiation.

    PubMed

    Warth, Sebastian C; Heissmeyer, Vigo

    2013-08-13

    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.

  6. The Influence of Costimulation and Regulatory Cd4+ T Cells on Intestinal Iga Immune Responses

    PubMed Central

    Kagrdic, Dubrav; Kjerrulf, Martin; Bromander, Annakari; Vajdy, Michael; Hörnquist, Elisabeth; Lycke, Nils

    1998-01-01

    It is thought that IgA B-cell differentiation is highly dependent on activated CD4+ T cells. In particular, cell-cell interactions in the Peyer's patches involving CD40 and/or CD80/CD86 have been implicated in germinal-center formation and IgA B-cell development. Also soluble factors, such as IL-4, IL-5, IL-6, and TGFβ may be critical for IgA B-cell differentiation in vivo. Here we report on some paradoxical findings with regard to IgA B-cell differentiation and specific mucosal immune responses that we have recently made using gene knockout mice. More specifically, we have investigated to what extent absence of CD4+ T cells, relevant cytokines, or T-cell-B-cell interactions would influence IgA B-cell differentiation in vivo. Using CD4– or IL- 4-gene knockout mice or mice made transgenic for CTLA4Ig, we found that, although specific responses were impaired, total IgA production and IgA B-cell differentiation appeared to proceed normally. However, a poor correlation was found between, on the one hand, GC formation and IgA differentiation and, on the other hand, the ability to respond to T-celldependent soluble protein antigens in these mice. Thus, despite the various deficiencies in CD4+ T-cell functions seemingly intact IgA B-cell development was observed. PMID:9716905

  7. NAFLD causes selective CD4+ T lymphocyte loss and promotes hepatocarcinogenesis

    PubMed Central

    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.

    2016-01-01

    Summary 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 a metabolic predisposition to liver cancer 1-5. However, the role of adaptive immune responses in NAFLD-promoted HCC is largely unknown. Here, we show 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 found 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-tumor surveillance. PMID:26934227

  8. CD4+ T cell–independent DNA vaccination against opportunistic infections

    PubMed Central

    Zheng, Mingquan; Ramsay, Alistair J.; Robichaux, Myles B.; Norris, Karen A.; Kliment, Corrine; Crowe, Christopher; Rapaka, Rekha R.; Steele, Chad; McAllister, Florencia; Shellito, Judd E.; Marrero, Luis; Schwarzenberger, Paul; Zhong, Qiu; Kolls, Jay K.

    2005-01-01

    Depletion or dysfunction of CD4+ T lymphocytes profoundly perturbs host defenses and impairs immunogenicity of vaccines. Here, we show that plasmid DNA vaccination with a cassette encoding antigen (OVA) and a second cassette encoding full-length CD40 ligand (CD40L), a molecule expressed on activated CD4+ T lymphocytes and critical for T cell helper function, can elicit significant titers of antigen-specific immunoglobulins in serum and Tc1 CD8+ T cell responses in CD4-deficient mice. To investigate whether this approach leads to CD4+ T cell–independent vaccine protection against a prototypic AIDS-defining infection, Pneumocystis (PC) pneumonia, we used serum from mice vaccinated with PC-pulsed, CD40L-modifed DCs to immunoprecipitate PC antigens. Kexin, a PC antigen identified by this approach, was used in a similar DNA vaccine strategy with or without CD40L. CD4-deficient mice receiving DNA vaccines encoding Kexin and CD40L showed significantly higher anti-PC IgG titers as well as opsonic killing of PC compared with those vaccinated with Kexin alone. Moreover, CD4-depleted, Kexin-vaccinated mice showed a 3-log greater protection in a PC challenge model. Adoptive transfer of CD19+ cells or IgG to SCID mice conferred protection against PC challenge, indicating a role of humoral immunity in the protection. The results of these studies show promise for CD4-independent vaccination against HIV-related or other opportunistic pathogens. PMID:16308571

  9. Out-of-Sequence Signal 3 Paralyzes Primary CD4(+) T-Cell-Dependent Immunity.

    PubMed

    Sckisel, Gail D; Bouchlaka, Myriam N; Monjazeb, Arta M; Crittenden, Marka; Curti, Brendan D; Wilkins, Danice E C; Alderson, Kory A; Sungur, Can M; Ames, Erik; Mirsoian, Annie; Reddy, Abhinav; Alexander, Warren; Soulika, Athena; Blazar, Bruce R; Longo, Dan L; Wiltrout, Robert H; Murphy, William J

    2015-08-18

    Primary T cell activation involves the integration of three distinct signals delivered in sequence: (1) antigen recognition, (2) costimulation, and (3) cytokine-mediated differentiation and expansion. Strong immunostimulatory events such as immunotherapy or infection induce profound cytokine release causing "bystander" T cell activation, thereby increasing the potential for autoreactivity and need for control. We show that during strong stimulation, a profound suppression of primary CD4(+) T-cell-mediated immune responses ensued and was observed across preclinical models and patients undergoing high-dose interleukin-2 (IL-2) therapy. This suppression targeted naive CD4(+) but not CD8(+) T cells and was mediated through transient suppressor of cytokine signaling-3 (SOCS3) inhibition of the STAT5b transcription factor signaling pathway. These events resulted in complete paralysis of primary CD4(+) T cell activation, affecting memory generation and induction of autoimmunity as well as impaired viral clearance. These data highlight the critical regulation of naive CD4(+) T cells during inflammatory conditions. PMID:26231116

  10. 1H DNP at 1.4 T of water doped with a triarylmethyl-based radical.

    PubMed

    Wind, R A; Ardenkjaer-Larsen, J H

    1999-12-01

    Recently a triarylmethyl-based (TAM) radical has been developed for research in biological and other aqueous systems, and in low magnetic fields, 10 mT or less, large (1)H dynamic nuclear polarization (DNP) enhancements have been reported. In this paper the DNP properties of this radical have been investigated in a considerably larger field of 1.4 T, corresponding to proton and electron Larmor frequencies of 60 MHz and 40 GHz, respectively. To avoid excessive microwave heating of the sample, an existing DNP NMR probe was modified with a screening coil, wound around the sample capillary and with its axis perpendicular to the electric component of the microwave field. It was found that with this probe the temperature increase in the sample after 4 s of microwave irradiation with an incident power of 10 W was only 16 degrees C. For the investigations, 10 mM of the TAM radical was dissolved in deionized, but not degassed, water and put into a 1-mm i.d. and 6-mm long capillary tube. At 26 degrees C the following results were obtained: (I) The relaxivity of the radical is 0.07 (mMs)(-1), in accordance with the value extrapolated from low-field results; (II) The leakage factor is 0.63, the saturation factor at maximum power is 0.85, and the coupling factor is -0.0187. It is shown that these results agree very well with an analysis where the electron-dipolar interactions are the dominant DNP mechanism, and where the relaxation transitions resulting from these interactions are governed by translational diffusion of the water molecules. Finally, the possibilities of combining DNP with magnetic resonance microscopy (MRM) are discussed. It is shown that at 26 degrees C the overall DNP-enhanced proton polarization should become maximal in an external field of 0.3 T and become comparable to the thermal equilibrium polarization in a field of 30 T, considerably larger than the largest high-resolution magnet available to date. It is concluded that DNP MRM in this field, which

  11. 42 CFR 416.30 - Terms of agreement with CMS.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 3 2011-10-01 2011-10-01 false Terms of agreement with CMS. 416.30 Section 416.30... of agreement with CMS. As part of the agreement under § 416.26 the ASC must agree to the following... in subpart C of this part and to report promptly to CMS any failure to do so. (b) Limitation...

  12. 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

  13. 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.

  14. Simultaneous formation of right- and left-handed anti-parallel coiled-coil interfaces by a coil2 fragment of human lamin A.

    PubMed

    Kapinos, Larisa E; Burkhard, Peter; Herrmann, Harald; Aebi, Ueli; Strelkov, Sergei V

    2011-04-22

    The elementary building block of all intermediate filaments (IFs) is a dimer featuring a central α-helical rod domain flanked by the N- and C-terminal end domains. In nuclear IF proteins (lamins), the rod domain consists of two coiled-coil segments, coil1 and coil2, that are connected by a short non-helical linker. Coil1 and the C-terminal part of coil2 contain the two highly conserved IF consensus motifs involved in the longitudinal assembly of dimers. The previously solved crystal structure of a lamin A fragment (residues 305-387) corresponding to the second half of coil2 has yielded a parallel left-handed coiled coil. Here, we present the crystal structure and solution properties of another human lamin A fragment (residues 328-398), which is largely overlapping with fragment 305-387 but harbors a short segment of the tail domain. Unexpectedly, no parallel coiled coil forms within the crystal. Instead, the α-helices are arranged such that two anti-parallel coiled-coil interfaces are formed. The most significant interface has a right-handed geometry, which is accounted for by a characteristic 15-residue repeat pattern that overlays with the canonical heptad repeat pattern. The second interface is a left-handed anti-parallel coiled coil based on the predicted heptad repeat pattern. In solution, the fragment reveals only a weak dimerization propensity. We speculate that the C-terminus of coil2 might unzip, thereby allowing for a right-handed coiled-coil interface to form between two laterally aligned dimers. Such an interface might co-exist with a heterotetrameric left-handed coiled-coil assembly, which is expected to be responsible for the longitudinal A(CN) contact.

  15. CMS memo OKs use of standing orders.

    PubMed

    2008-12-01

    The Centers for Medicare & Medicaid Services (CMS) has reversed course and clarified the use of standing orders in a manner that is much more favorable to EDs. Initiation of standing orders or protocols no longer requires prior authorization by a physician. Documentation still is required, and it must be entered into the medical record, but it can be entered following implementation of the standing order. Nurses can administer drugs if approved by protocol and if it is within their nursing scope of practice. PMID:19086739

  16. 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.

  17. CMS data quality monitoring: Systems and experiences

    NASA Astrophysics Data System (ADS)

    Tuura, L.; Meyer, A.; Segoni, I.; Della Ricca, G.

    2010-04-01

    In the last two years the CMS experiment has commissioned a full end to end data quality monitoring system in tandem with progress in the detector commissioning. We present the data quality monitoring and certification systems in place, from online data taking to delivering certified data sets for physics analyses, release validation and offline re-reconstruction activities at Tier-1s. We discuss the main results and lessons learnt so far in the commissioning and early detector operation. We outline our practical operations arrangements and the key technical implementation aspects.

  18. Jets In Heavy Ion Collisions with CMS

    NASA Astrophysics Data System (ADS)

    Salur, Sevil

    2016-08-01

    Jet physics in heavy ion collisions is a rich field which has been rapidly evolving since the first observations of medium interactions at RHIC through back-to-back hadron correlations and at LHC via reconstructed jets. In order to completely characterize the final state via jet-medium interactions and distinguish between competing energy loss mechanisms, complementary and robust jet observables are investigated. Latest developments of jet finding techniques and their applications to heavy ion environments are discussed with an emphasis given on experimental results from CMS experiment.

  19. G-2 and CMS fast optical calorimetry

    SciTech Connect

    Winn, David R.

    2001-06-01

    The following projects are discussed: (A) Operation of the muon g-2 experiment at Brookhaven National Lab (Experiment E821), especially the pulsed laser calibration system, to test the standard model of forces, and to see if new forces may exist in the vacuum. (B) The second part of this project developed fast optical forward Cerenkov jet calorimetry used in the CMS experiment collaboration (US lead organization FermiLab) at CERN on the Large Hadron Collider, designed to detect new physics at the TeV scale, such as supersymmetry and the Higgs boson.

  20. Waste Tank cooling coil leakage calculations

    SciTech Connect

    Dworjanyn, L.O.

    1991-12-20

    A high activity Waste Tank cooling coil supply line cracked on September 12, 1991 at the H-Area East pump house, draining the cooling water to the ground. This raised the possibility of draining high-activity waste to the ground by siphon action through the submerged cycling coils since some of the cooling water supply lines are located up to 40 ft. below waste tank liquid level. The following documentation summarizes conclusions and provides details of flow calculation presented earlier during the incident investigation. No plausible reason for a simultaneous rupture of the supply line and the cooling coils inside the tank was identified. Both seismic stresses and water hammer produce relatively low stresses on the cooling coils. A hypothetical simultaneous rupture of the cooling coils inside the tank and the supply line below ground could result in 100 to 200 gpm waste discharge to the ground. Waste discharge from a possible cooling coil corrosion leak would be limited to 20 gal/12-hr shift under maximum possible siphon, based on operating procedures for cooling water makeup which call for coil isolation when a cooling water loss of 40 gal/shaft is identified. This level of discharge is within the existing envelope of accident consequences for Waste Tank Form SAR.

  1. 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.

  2. Routine phasing of coiled-coil protein crystal structures with AMPLE

    PubMed Central

    Thomas, Jens M. H.; Keegan, Ronan M.; Bibby, Jaclyn; Winn, Martyn D.; Mayans, Olga; Rigden, Daniel J.

    2015-01-01

    Coiled-coil protein folds are among the most abundant in nature. These folds consist of long wound α-helices and are architecturally simple, but paradoxically their crystallographic structures are notoriously difficult to solve with molecular-replacement techniques. The program AMPLE can solve crystal structures by molecular replacement using ab initio search models in the absence of an existent homologous protein structure. AMPLE has been benchmarked on a large and diverse test set of coiled-coil crystal structures and has been found to solve 80% of all cases. Successes included structures with chain lengths of up to 253 residues and resolutions down to 2.9 Å, considerably extending the limits on size and resolution that are typically tractable by ab initio methodologies. The structures of two macromolecular complexes, one including DNA, were also successfully solved using their coiled-coil components. It is demonstrated that both the ab initio modelling and the use of ensemble search models contribute to the success of AMPLE by comparison with phasing attempts using single structures or ideal polyalanine helices. These successes suggest that molecular replacement with AMPLE should be the method of choice for the crystallo­graphic elucidation of a coiled-coil structure. Furthermore, AMPLE may be able to exploit the presence of a coiled coil in a complex to provide a convenient route for phasing. PMID:25866657

  3. Analysis of Coiled-Coil Interactions between Core Proteins of the Spindle Pole Body

    SciTech Connect

    Zizlsperger, N.; Malashkevich, V; Pillay, S; Keating, A

    2008-01-01

    The spindle pole body (SPB) is a multiprotein complex that organizes microtubules in yeast. Due to its large size and association with the nuclear membrane, little is known about its detailed structure. In particular, although many SPB components and some of the interactions between them have been identified, the molecular details of how most of these interactions occur are not known. The prevalence of predicted coiled-coil regions in SPB proteins suggests that some interactions may occur via coiled coils. Here this hypothesis is supported by biochemical characterization of isolated coiled-coil peptides derived from SPB proteins. Formation of four strongly self-associating coiled-coil complexes from Spc29, Spc42, and Spc72 was demonstrated by circular dichroism (CD) spectroscopy and a fluorescence resonance energy transfer (FRET) assay. Many weaker self- and heteroassociations were also detected by CD, FRET, and/or cross-linking. The thermal stabilities of nine candidate homooligomers were assessed; six unfolded cooperatively with melting temperatures ranging from <11 to >50 C. Solution studies established that coiled-coil peptides derived from Spc42 and Spc72 form parallel dimers, and this was confirmed for Spc42 by a high-resolution crystal structure. These data contribute to a growing body of knowledge that will ultimately provide a detailed model of the SPB structure.

  4. Crystal structure of a coiled-coil domain from human ROCK I.

    PubMed

    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

    2011-03-21

    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.

  5. 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.

  6. Crystal structure of the central coiled-coil domain from human liprin-β2.

    PubMed

    Stafford, Ryan L; Tang, Ming-Yun; Sawaya, Michael R; Phillips, Martin L; Bowie, James U

    2011-05-10

    Liprins are a conserved family of scaffolding proteins important for the proper regulation and development of neuronal synapses. Humans have four liprin-αs and two liprin-βs 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-β2 coiled-coil forms an extended dimer. Several protease-resistant subdomains within the liprin-β1 and liprin-β2 coiled-coils were also identified. A 2.0 Å crystal structure of the central, protease-resistant core of the liprin-β2 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.

  7. Cloning, overexpression, purification and crystallization of the CRN12 coiled-coil domain from Leishmania donovani

    PubMed Central

    Srivastava, Vijay Kumar; Rana, Ajay Kumar; Sahasrabuddhe, Amogh A.; Gupta, C. M; Pratap, J. V.

    2013-01-01

    Leishmania donovani coronin CRN12 is an actin-binding protein which consists of two domains: an N-terminal WD repeat domain and a C-terminal coiled-coil domain. The coiled-coil domain is 53 residues in length. Helix–helix interactions in general and coiled coils in particular are ubiquitous in the structure of proteins and play a significant role in the association among proteins, including supramolecular assemblies and transmembrane receptors that mediate cellular signalling, transport and actin dynamics. The L. donovani coronin CRN12 coiled-coil domain (5.8 kDa) was cloned, overexpressed, purified to homogeneity and the N-terminal 6×His tag was successfully removed by thrombin cleavage. Crystals of recombinant L. donovani coronin CRN12 coiled-coil domain were grown by vapour diffusion using a hanging-drop setup. Diffraction-quality crystals were obtained and data extending to 2.46 Å resolution were collected at 100 K on BM14, ESRF, Grenoble, France. The crystal belonged to the monoclinic space group C2, with unit-cell parameters a = 118.0, b = 50.6, c = 46.0 Å, β = 111.0°. Matthews coefficient (V M) calculations suggested the presence of 4–6 molecules in the asymmetric unit, corresponding to a solvent content of ∼33–55%, and are consistent with self-rotation function calculations. PMID:23695571

  8. Cloning, overexpression, purification and crystallization of the CRN12 coiled-coil domain from Leishmania donovani.

    PubMed

    Srivastava, Vijay Kumar; Rana, Ajay Kumar; Sahasrabuddhe, Amogh A; Gupta, C M; Pratap, J V

    2013-05-01

    Leishmania donovani coronin CRN12 is an actin-binding protein which consists of two domains: an N-terminal WD repeat domain and a C-terminal coiled-coil domain. The coiled-coil domain is 53 residues in length. Helix-helix interactions in general and coiled coils in particular are ubiquitous in the structure of proteins and play a significant role in the association among proteins, including supramolecular assemblies and transmembrane receptors that mediate cellular signalling, transport and actin dynamics. The L. donovani coronin CRN12 coiled-coil domain (5.8 kDa) was cloned, overexpressed, purified to homogeneity and the N-terminal 6×His tag was successfully removed by thrombin cleavage. Crystals of recombinant L. donovani coronin CRN12 coiled-coil domain were grown by vapour diffusion using a hanging-drop setup. Diffraction-quality crystals were obtained and data extending to 2.46 Å resolution were collected at 100 K on BM14, ESRF, Grenoble, France. The crystal belonged to the monoclinic space group C2, with unit-cell parameters a = 118.0, b = 50.6, c = 46.0 Å, β = 111.0°. Matthews coefficient (VM) calculations suggested the presence of 4-6 molecules in the asymmetric unit, corresponding to a solvent content of ∼33-55%, and are consistent with self-rotation function calculations. PMID:23695571

  9. COMMON COIL MAGNET PROGRAM AT BNL.

    SciTech Connect

    GUPTA, R.; ANERELLA, M.; COZZOLINO, J.; ESCALLIER, J.; GANETIS, G.; GHOSH, A.; HARRISON, M.; MORGAN, G.; MURATORE, J.; PARKER, B.; SAMPSON, W.; WANDERER, P.

    2000-09-17

    The goal of the common coil magnet R&D program at Brookhaven National Laboratory (BNL) is to develop a 12.5 T, 40 mm aperture dipole magnet using ''React and Wind Technology'' with High Temperature Superconductors (HTS) playing a major role. Due to its ''conductor friendly'' nature, the common coil design is attractive for building high field 2-in-1 dipoles with brittle materials such as HTS and Nb{sub 3}Sn. At the current rate of development, it is expected that a sufficient amount of HTS with the required performance would be available in a few years for building a short magnet. In the interim, the first generation dipoles will be built with Nb{sub 3}Sn superconductor. They will use a ''React and Wind'' technology similar to that used in HTS and will produce a 12.5 T central field in a 40 mm aperture. The Nb{sub 3}Sn coils and support structure of this magnet will become a part of the next generation hybrid magnet with inner coils made of HTS. To develop various aspects of the technology in a scientific and experimental manner, a 10-turn coil program has been started in parallel. The program allows a number of concepts to be evaluated with a rapid throughput in a cost-effective way. Three 10-turn Nb{sub 3}Sn coils have been built and one HTS coil is under construction. The initial test results of this ''React & Wind'' 10-turn coil program are presented. It is also shown that a common coil magnet design can produce a field quality that is as good as a conventional cosine theta design.

  10. Advanced COIL technologies for field applications

    NASA Astrophysics Data System (ADS)

    Tei, Kazuyoku; Sugimoto, Daichi; Ito, T.; Watanabe, G.; Vyskubenko, O.; Takeuchi, N.; Muto, S.; Kenzo, N.; Fujioka, Tomoo

    2005-01-01

    Chemical oxygen-iodine laser (COIL) has a great potential for applications such as decommissioning and dismantlement (D&D) of nuclear reactor, rock destruction and removal and extraction of a natural resource (Methane hydrate) because of the unique characteristics such as power scalability, high optical beam quality and optical fiber beam. Five-kilowatt Chemical oxygen-iodine laser (COIL) test facility has been developed. The chemical efficiency of 27% has been demonstrated with a moderate beam quality for optical fiber coupling. Our research program contains conventional/ejector-COIL scheme, Jet-SOG/Mist-SOG optimization, fiber delivery and long-term operation.

  11. 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.

  12. Coiled Fiber Pulsed Laser Simulator

    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

  13. 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.

  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. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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

  1. HIV-1 Expression Within Resting CD4+ T Cells After Multiple Doses of Vorinostat

    PubMed Central

    Archin, Nancy M.; Bateson, Rosalie; Tripathy, Manoj K.; Crooks, Amanda M.; Yang, Kuo-Hsiung; Dahl, Noelle P.; Kearney, Mary F.; Anderson, Elizabeth M.; Coffin, John M.; Strain, Matthew C.; Richman, Douglas D.; Robertson, Kevin R.; Kashuba, Angela D.; Bosch, Ronald J.; Hazuda, Daria J.; Kuruc, Joann D.; Eron, Joseph J.; Margolis, David M.

    2014-01-01

    Background. A single dose of the histone deacetylase inhibitor vorinostat (VOR) up-regulates HIV RNA expression within resting CD4+ T cells of treated, aviremic human immunodeficiency virus (HIV)–positive participants. The ability of multiple exposures to VOR to repeatedly disrupt latency has not been directly measured, to our knowledge. Methods. Five participants in whom resting CD4+ T-cell–associated HIV RNA (rc-RNA) increased after a single dose of VOR agreed to receive daily VOR Monday through Wednesday for 8 weekly cycles. VOR serum levels, peripheral blood mononuclear cell histone acetylation, plasma HIV RNA single-copy assays, rc-RNA, total cellular HIV DNA, and quantitative viral outgrowth assays from resting CD4+ T cells were assayed. Results. VOR was well tolerated, with exposures within expected parameters. However, rc-RNA measured after dose 11 (second dose of cycle 4) or dose 22 (second dose of cycle 8) increased significantly in only 3 of the 5 participants, and the magnitude of the rc-RNA increase was much reduced compared with that after a single dose. Changes in histone acetylation were blunted. Results of quantitative viral outgrowth and other assays were unchanged. Conclusions. Although HIV latency is disrupted by an initial VOR dose, the effect of subsequent doses in this protocol was much reduced. We hypothesize that the global effect of VOR results in a refractory period of ≥24 hours. The optimal schedule for VOR administration is still to be defined. PMID:24620025

  2. 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

  3. Microbiological infections in HIV positive Bahraini patients with low CD4+ T-lymphocyte count.

    PubMed

    Ehrahim, Reda Ali; Farid, Eman M A; Yousif, Aziz; Jamsheer, Afaf E

    2002-09-01

    The correlation of CD4+ T-lymphocyte count and the distribution of pathogenic or opportunistic microbial infection most commonly found in HIV positive individuals differ from one area to the other. The present study reports such findings in 67 HIV positive Bahraini patients in the period May 1997 to Nov. 1998. CD4+ T-lymphocyte count was measured using flow cytometry. Bacterial and fungal cultures were performed. Serological diagnosis was performed when indicated. Viral study was done serologically. The distribution of CD4+ T-lymphocyte count in the studied group was: 21 patients (31.3%) less than 100 cells/microl, 5 patients (7.5%) 100-200 cells/microl, 25 patients (37.3%) 201-500 cells/microl and 16 patients (23.9%) with count more than 500 cells/microl. Among patients with low CD4 count (less than 100 cells/microl) (n=21), microbial infections varied from fungal infections 66%, bacterial infections 57% and viral infections 4.8%. Bacterial infections included Salmonellosis (14.3%), Staphylococcus epidermidis (14.3%), Pseudomonas aeruginosa (9.5%), H. influenzae (9.5%), Legionellosis (4.8%) and E. coli (4.8%). Fungal infection included Candida albicans (52.4%), Pneumocystis carinii (9.5%), Cryptococcus neoformans (4.8%). Viral infection included H. simplex to (4.8%). Fungal infections were the highest common infection in thus study. The most common microbial infection was Candida albicans. P. carinii and Cryptococcus neoformans were less common than found in other studies world wide.

  4. 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

  5. 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

  6. Dose-Responsive Gene Expression in Suberoylanilide Hydroxamic Acid (SAHA) Treated Resting CD4+ T Cells

    PubMed Central

    Reardon, Brian; Beliakova-Bethell, Nadejda; Spina, Celsa A.; Singhania, Akul; Margolis, David M.; Richman, Douglas R.; Woelk, Christopher H.

    2015-01-01

    Design Persistent latently infected CD4+ T cells represent a major obstacle to HIV eradication. Histone deacetylase inhibitors (HDACis) are a proposed activation therapy. However, off-target effects on expression in host immune cells are poorly understood. We hypothesized that HDACi-modulated genes would be best identified with dose-response analysis. Methods Resting primary CD4+ T cells were treated with 0.34, 1, 3, or 10 μM of the HDACi, SAHA, for 24 hours and subjected to microarray gene expression analysis. Genes with dose-correlated expression were filtered to identify a subset with consistent up or downregulation at each SAHA dose. Histone modifications were characterized in 6 SAHA dose-responsive genes by chromatin immunoprecipitation (ChIP-RT-qPCR). Results A large number of genes were shown to be up (N=657) or downregulated (N=725) by SAHA in a dose-responsive manner (FDR p-value < 0.05, fold change ≥ |2|). Several genes (CTNNAL1, DPEP2, H1F0, IRGM, PHF15, and SELL) are potential in vivo biomarkers of SAHA activity. SAHA dose-responsive genes included transcription factors, HIV restriction factors, histone methyltransferases, and host proteins that interact with HIV. Pathway analysis suggested net downregulation of T cell activation with increasing SAHA dose. Histone acetylation was not correlated with host gene expression, but plausible alternative mechanisms for SAHA-modulated gene expression were identified. Conclusions Numerous genes in CD4+ T cells are modulated by SAHA in a dose-responsive manner, including genes that may negatively influence HIV activation from latency. Our study suggests that SAHA influences gene expression through a confluence of several mechanisms, including histone modification, and altered expression and activity of transcription factors. PMID:26258524

  7. 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

  8. 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

  9. X-ray scattering indicates that the leucine zipper is a coiled coil.

    PubMed Central

    Rasmussen, R; Benvegnu, D; O'Shea, E K; Kim, P S; Alber, T

    1991-01-01

    Dimerization of the bZIP class of eukaryotic transcriptional control proteins requires a sequence motif called the leucine zipper. We have grown two distinct crystal forms of a 33-amino acid peptide corresponding to the leucine zipper of the yeast transcriptional activator GCN4. This peptide is known to form a dimer of parallel helices in solution. X-ray scattering from both crystal forms shows reflections that are diagnostic of coiled coils. The most notable reflections occur at approximately 5.2 A resolution and correspond to the pitch of helices in coiled coils. There is no diffraction maximum near 5.4 A, the characteristic pitch of straight helices. Our results provide direct evidence that the leucine zipper of GCN4 is a coiled coil. Images PMID:1988953

  10. 26 CFR 1.1441-4T - Exemptions from withholding for certain effectively connected income and other amounts (temporary).

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 12 2013-04-01 2013-04-01 false Exemptions from withholding for certain effectively connected income and other amounts (temporary). 1.1441-4T Section 1.1441-4T Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Withholding of Tax on...

  11. 26 CFR 1.1441-4T - Exemptions from withholding for certain effectively connected income and other amounts (temporary).

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 12 2012-04-01 2012-04-01 false Exemptions from withholding for certain effectively connected income and other amounts (temporary). 1.1441-4T Section 1.1441-4T Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Withholding of Tax on...

  12. 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...

  13. 26 CFR 1.67-4T - Allocation of expenses by nongrantor trusts and estates (temporary). [Reserved

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 2 2010-04-01 2010-04-01 false Allocation of expenses by nongrantor trusts and estates (temporary). 1.67-4T Section 1.67-4T Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Definition of Gross Income,...

  14. A differential equation model of HIV infection of CD4+ T-cells with cure rate

    NASA Astrophysics Data System (ADS)

    Zhou, Xueyong; Song, Xinyu; Shi, Xiangyun

    2008-06-01

    A differential equation model of HIV infection of CD4+ T-cells with cure rate is studied. We prove that if the basic reproduction number R0<1, the HIV infection is cleared from the T-cell population and the disease dies out; if R0>1, the HIV infection persists in the host. We find that the chronic disease steady state is globally asymptotically stable if R0>1. Furthermore, we also obtain the conditions for which the system exists an orbitally asymptotically stable periodic solution. Numerical simulations are presented to illustrate the results.

  15. 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

  16. 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.

  17. 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

  18. Ferromagnetic nickel silicide nanowires for isolating primary CD4+ T lymphocytes

    NASA Astrophysics Data System (ADS)

    Kim, Dong-Joo; Seol, Jin-Kyeong; Lee, Mi-Ri; Hyung, Jung-Hwan; Kim, Gil-Sung; Ohgai, Takeshi; Lee, Sang-Kwon

    2012-04-01

    Direct CD4+ T lymphocytes were separated from whole mouse splenocytes using 1-dimensional ferromagnetic nickel silicide nanowires (NiSi NWs). NiSi NWs were prepared by silver-assisted wet chemical etching of silicon and subsequent deposition and annealing of Ni. This method exhibits a separation efficiency of ˜93.5%, which is comparable to that of the state-of-the-art superparamagnetic bead-based cell capture (˜96.8%). Furthermore, this research shows potential for separation of other lymphocytes, B, natural killer and natural killer T cells, and even rare tumor cells simply by changing the biotin-conjugated antibodies.

  19. 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.

  20. 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

  1. Cooling arrangement for a superconducting coil

    DOEpatents

    Herd, K.G.; Laskaris, E.T.

    1998-06-30

    A superconducting device is disclosed, such as a superconducting rotor for a generator or motor. A vacuum enclosure has an interior wall surrounding a cavity containing a vacuum. A superconductive coil is placed in the cavity. A generally-annularly-arranged, thermally-conductive sheet has an inward-facing surface contacting generally the entire outward-facing surface of the superconductive coil. A generally-annularly-arranged coolant tube contains a cryogenic fluid and contacts a generally-circumferential portion of the outward-facing surface of the sheet. A generally-annularly-arranged, thermally-insulative coil overwrap generally circumferentially surrounds the sheet. The coolant tube and the inward-facing surface of the coil overwrap together contact generally the entire outward-facing surface of the sheet. 3 figs.

  2. The Magnetic Field of Helmholtz Coils

    ERIC Educational Resources Information Center

    Berridge, H. J. J.

    1975-01-01

    Describes the magnetic field of Helmholtz coils qualitatively and then provides the basis for a quantitative expression. Since the mathematical calculations are very involved, a computer program for solving the mathematical expression is presented and explained. (GS)

  3. Cooling arrangement for a superconducting coil

    DOEpatents

    Herd, Kenneth Gordon; Laskaris, Evangelos Trifon

    1998-06-30

    A superconducting device, such as a superconducting rotor for a generator or motor. A vacuum enclosure has an interior wall surrounding a cavity containing a vacuum. A superconductive coil is placed in the cavity. A generally-annularly-arranged, thermally-conductive sheet has an inward-facing surface contacting generally the entire outward-facing surface of the superconductive coil. A generally-annularly-arranged coolant tube contains a cryogenic fluid and contacts a generally-circumferential portion of the outward-facing surface of the sheet. A generally-annularly-arranged, thermally-insulative coil overwrap generally circumferentially surrounds the sheet. The coolant tube and the inward-facing surface of the coil overwrap together contact generally the entire outward-facing surface of the sheet.

  4. Modular design of receiver coil arrays.

    PubMed

    De Zanche, Nicola; Massner, Jurek A; Leussler, Christoph; Pruessmann, Klaas P

    2008-07-01

    We describe a modular and hence flexible system for connecting MR surface coils to create a receiver array. Up to 16 individual coils of different size and shape depending on the application are plugged into a connector box that houses the control electronics. Preamplification, matching and detuning circuitry are housed on a circuit board directly attached to each coil loop. Electrical adjustments for tuning or decoupling for each coil configuration are not needed thanks to effective preamplifier decoupling provided through a Pi matching network. Radio-frequency safety and electrically stable cabling are ensured by multiple radio-frequency traps. Array modules for 1.5 and 3 T have been simulated, constructed, tested, and used for imaging experiments.

  5. 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.

  6. 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.

  7. Functional Analysis of the Bacteriophage T4 Rad50 Homolog (gp46) Coiled-coil Domain.

    PubMed

    Barfoot, Tasida; Herdendorf, Timothy J; Behning, Bryanna R; Stohr, Bradley A; Gao, Yang; Kreuzer, Kenneth N; Nelson, Scott W

    2015-09-25

    Rad50 and Mre11 form a complex involved in the detection and processing of DNA double strand breaks. Rad50 contains an anti-parallel coiled-coil with two absolutely conserved cysteine residues at its apex. These cysteine residues serve as a dimerization domain and bind a Zn(2+) cation in a tetrathiolate coordination complex known as the zinc-hook. Mutation of the zinc-hook in bacteriophage T4 is lethal, indicating the ability to bind Zn(2+) is critical for the functioning of the MR complex. In vitro, we found that complex formation between Rad50 and a peptide corresponding to the C-terminal domain of Mre11 enhances the ATPase activity of Rad50, supporting the hypothesis that the coiled-coil is a major conduit for communication between Mre11 and Rad50. We constructed mutations to perturb this domain in the bacteriophage T4 Rad50 homolog. Deletion of the Rad50 coiled-coil and zinc-hook eliminates Mre11 binding and ATPase activation but does not affect its basal activity. Mutation of the zinc-hook or disruption of the coiled-coil does not affect Mre11 or DNA binding, but their activation of Rad50 ATPase activity is abolished. Although these mutants excise a single nucleotide at a normal rate, they lack processivity and have reduced repetitive exonuclease rates. Restricting the mobility of the coiled-coil eliminates ATPase activation and repetitive exonuclease activity, but the ability to support single nucleotide excision is retained. These results suggest that the coiled-coiled domain adopts at least two conformations throughout the ATPase/nuclease cycle, with one conformation supporting enhanced ATPase activity and processivity and the other supporting nucleotide excision.

  8. Coiled-coils as assembly-directing domains in self-assembling structures

    NASA Astrophysics Data System (ADS)

    Sahin, Erinc

    2008-10-01

    The bioconjugation of proteins and peptides with synthetic polymers is a promising method to tailor chemical, biological and physical properties of both the polymeric and protein-based components. Here, we describe macromolecular assemblies of polyethylene glycol-coiled-coil alternating block copolymers guided by associations of coiled-coils. High molecular weight, alternating block copolymers of PEG and coiled-coil peptides were formed via facile reactions between N-hydroxysuccinimide esters and amines, leading to amide bond formation under anhydrous conditions. Confirmation of multiblock formation was assessed via a combination of NMR spectroscopy, size-exclusion chromatography, and electrophoretic analysis. Formation of the alternating block copolymers of PEG with coiled-coil peptides through the f-position on the heptads did not impair the ability of the coiled-coils to form heterodimers, as assessed via circular dichroic spectroscopy. Interestingly, the conjugation triggered homooligomer formation in one of the peptides that is monomeric in the absence of PEG. The macromolecular assembly of the homooligomer was characterized via circular dichroism, analytical ultracentrifugation, and dynamic and static light scattering. The copolymer structures were formed under physiological conditions, and exhibited controlled sizes relevant in applications such as drug delivery and controlled release. Our efforts toward synthesis of coiled-coils via recombinant expression have also lead to the discovery of an evolutionary phenomenon. We observed a strong inverse correlation between the pH of an organism's habitat and its proteomic pI, that is the isoelectric point of bulk of its proteome. This observation may be useful in informed selection of host organisms for recombinant expression of proteins with extreme isoelectric points.

  9. 42 CFR 433.320 - Procedures for refunds to CMS.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... refund the Federal share of overpayments that are subject to recovery to CMS through a credit on its... following discovery, established in accordance with § 433.316, ends. (3) A credit on the Form CMS-64 must be... reporting collections and submitting reduced expenditure claims. (1) The State is not required to refund...

  10. 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...

  11. 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.

  12. 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.

  13. 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.

  14. Heterogeneous Superconducting Low-Noise Sensing Coils

    NASA Technical Reports Server (NTRS)

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

    2008-01-01

    A heterogeneous material construction has been devised for sensing coils of superconducting quantum interference device (SQUID) magnetometers that are subject to a combination of requirements peculiar to some advanced applications, notably including low-field magnetic resonance imaging for medical diagnosis. The requirements in question are the following: The sensing coils must be large enough (in some cases having dimensions of as much as tens of centimeters) to afford adequate sensitivity; The sensing coils must be made electrically superconductive to eliminate Johnson noise (thermally induced noise proportional to electrical resistance); and Although the sensing coils must be cooled to below their superconducting- transition temperatures with sufficient cooling power to overcome moderate ambient radiative heat leakage, they must not be immersed in cryogenic liquid baths. For a given superconducting sensing coil, this combination of requirements can be satisfied by providing a sufficiently thermally conductive link between the coil and a cold source. However, the superconducting coil material is not suitable as such a link because electrically superconductive materials are typically poor thermal conductors. The heterogeneous material construction makes it possible to solve both the electrical- and thermal-conductivity problems. The basic idea is to construct the coil as a skeleton made of a highly thermally conductive material (typically, annealed copper), then coat the skeleton with an electrically superconductive alloy (typically, a lead-tin solder) [see figure]. In operation, the copper skeleton provides the required thermally conductive connection to the cold source, while the electrically superconductive coating material shields against Johnson noise that originates in the copper skeleton.

  15. Modular test facility for HTS insert coils

    SciTech Connect

    Lombardo, V; Bartalesi, A.; Barzi, E.; Lamm, M.; Turrioni, D.; Zlobin, A.V.; /Fermilab

    2009-10-01

    The final beam cooling stages of a Muon Collider may require DC solenoid magnets with magnetic fields in the range of 40-50 T. In this paper we will present a modular test facility developed for the purpose of investigating very high field levels with available 2G HTS superconducting materials. Performance of available conductors is presented, together with magnetic calculations and evaluation of Lorentz forces distribution on the HTS coils. Finally a test of a double pancake coil is presented.

  16. AC loss measurements in HTS coil assemblies with hybrid coil structures

    NASA Astrophysics Data System (ADS)

    Jiang, Zhenan; Long, Nicholas J.; Staines, Mike; Badcock, Rodney A.; Bumby, Chris W.; Buckley, Robert G.; Amemiya, Naoyuki

    2016-09-01

    Both AC loss and wire cost in coil windings are critical factors for high temperature superconductor (HTS) AC machinery applications. We present AC loss measurement results in three HTS coil assemblies at 77 K and 65 K which have a hybrid coil structure comprising one central winding (CW) and two end windings (EWs) wound with ReBCO and BSCCO wires with different self-field I c values at 77 K. All AC loss results in the coil assemblies are hysteretic and the normalized AC losses in the coil assemblies at different temperatures can be scaled with the I c value of the coil assemblies. The normalised results show that AC loss in a coil assembly with BSCCO CW can be reduced by using EWs wound with high I c ReBCO wires, whilst further AC loss reduction can be achieved by replacing the BSCCO CW with ReBCO CW. The results imply that a flexible hybrid coil structure is possible which considers both AC loss and wire cost in coil assemblies.

  17. Insertion of a coiled-coil peptide from influenza virus hemagglutinin into membranes

    SciTech Connect

    Yu, Y.G.; Shin, Y.K.; King, D.S.

    1994-10-14

    The trimeric protein hemagglutinin (HA) of the influenza viral envelope is essential for cell entry. To investigate the interaction of HA with membranes, two 40-residue, cysteine-substituted peptides comprising the loop region and the first part of the coiled-coil stem were synthesized and modified with a nitroxide spin label. Electron paramagnetic resonance analysis revealed that the peptide inserts reversibly into phospholipid vesicles under endosomal pH conditions. This result suggests that some or all of the long coiled-coil trimer of HA may insert into membranes, which could bring the viral and cell membranes closer together and facilitate fusion. 16 refs., 5 figs.

  18. Maraviroc intensification in patients with suppressed HIV viremia has limited effects on CD4+ T cell recovery and gene expression

    PubMed Central

    Beliakova-Bethell, Nadejda; Jain, Sonia; Woelk, Christopher H.; Witt, Mallory D.; Sun, Xiaoying; Lada, Steven M.; Spina, Celsa A.; Goicoechea, Miguel; Rought, Steffney E.; Haubrich, Richard; Dubé, Michael P.

    2014-01-01

    Addition of the CCR5 inhibitor Maraviroc (MVC) to ongoing antiretroviral therapy increases CD4+ T cell counts in some virologically suppressed patients with suboptimal CD4+ T cell recovery. To understand the mechanisms by which MVC elicits increases in CD4+ T cell counts, the present study was undertaken to identify host factors (i.e. genes) that are modulated and are correlated with CD4+ T cell recovery during the 24 weeks of MVC intensification in 32 subjects. Median changes of CD4+ T cell counts over 24 weeks of MVC compared to baseline were 38 cells/mm3 (p < 0.001). The median slope of CD4+ T cell recovery was 39 cells/mm3 per year before initiation of MVC and 76 cells/mm3 per year during MVC intensification, however, this increase was not statistically significant (p = 0.33). Microarray analysis (N = 31,426 genes) identified a single differentially expressed gene, tumor necrosis factor alpha (TNF), which was modestly (1.44-fold, p < 0.001) downregulated by MVC at week 24 compared to baseline. TNF differential expression was evaluated using an independent method of droplet digital PCR, but the difference was not significant (p = 0.6). Changes in gene expression did not correlate with CD4+ T cell recovery or any changes in the CD4+ T cell maturation, proliferation and activation phenotypes. In summary, our data suggest that modest improvements of CD4+ T cell counts during MVC intensification cannot be explained by changes in gene expression elicited by MVC. However, the modest changes in T cell composition, including reduction of the percentages of Tregs, proliferating CD4+ T cells and senescent CD8+ T cells, suggest immunologically favorable effects of MVC. PMID:24769244

  19. Acute Cardiac Rejection Requires Directly Cytotoxic CD4 T cells: A Parallel Pathway between Fas and Perforin1

    PubMed Central

    Grazia, Todd J.; Plenter, Robert J.; Weber, Sarah M.; Lepper, Helen M.; Victorino, Francisco; Zamora, Martin R.; Pietra, Biagio A.; Gill, Ronald G.

    2009-01-01

    Background CD4 T cells can suffice as effector cells to mediate primary acute cardiac allograft rejection. While CD4 T cells can readily kill appropriate target cells in vitro, the corresponding role of such cytolytic activity for mediating allograft rejection in vivo is unknown. Therefore, we determined whether the cytolytic effector molecules perforin and/or FasL (CD95L) were necessary for CD4 T cell-mediated rejection in vivo. Methods Wild type C3H(H-2k) or Fas (CD95)-deficient C3Hlpr (H-2k) hearts were transplanted into immune-deficient C57B6rag−/− (H-2b) mice. Recipients then were reconstituted with naïve purified CD4 T cells from either wild-type, perforin (pfp)-deficient, or FasL (gld)-deficient T cell donors. Results In vitro, alloreactive CD4 T cells were competent to lyse donor MHC class II+ target cells, largely by a Fas-dependent mechanism. In vivo, the individual disruption of either donor Fas expression (lpr) or CD4 T cell-derived perforin had no signifcant impact on acute rejection. However, FasL-deficient (gld) CD4 T cells demonstrated delayed allograft rejection. Importantly, the simultaneous removal of both donor Fas expression and CD4 T cell perforin completely abrograted acute rejection, despite the persistence of CD4 T cells within the graft. Conclusions Results demonstrate that the direct rejection of cardiac allografts by CD4 effector T cells requires the alternative contribution of graft Fas expression and T cell perforin expression. To our knowledge, this is the first demonstration that cytolytic activity by CD4 T cells can play an obligate role for primary acute allograft rejection in vivo. PMID:20061916

  20. Mycobacterium tuberculosis-Specific IL-21+IFN-γ+CD4+ T Cells Are Regulated by IL-12.

    PubMed

    Li, Li; Jiang, Yuxia; Lao, Suihua; Yang, Binyan; Yu, Sifei; Zhang, Yannan; Wu, Changyou

    2016-01-01

    In the current study of Mycobacterium tuberculosis (MTB)-specific T and B cells, we found that MTB-specific peptides from early secreted antigenic target-6 (ESAT-6) and culture filtrate protein-10 (CFP-10) induced the expression of IL-21 predominantly in CD4(+) T cells. A fraction of IL-21-expressing CD4(+) T cells simultaneously expressed Th1 cytokines but did not secrete Th2 or Th17 cytokines, suggesting that MTB-specific IL-21-expressing CD4(+) T cells were different from Th1, Th2 and Th17 subpopulations. The majority of MTB-specific IL-21-expressing CD4(+) T cells co-expressed IFN-γ and IL-21+IFN-γ(+)CD4(+) T cells exhibited obviously polyfunctionality. In addition, MTB-specific IL-21-expressing CD4(+) T cells displayed a CD45RO+CD62Ll(ow)CCR7(low)CD40L(high)ICOS(high) phenotype. Bcl-6-expression was significantly higher in IL-21-expressing CD4(+) T cells than IL-21-CD4(+) T cells. Moreover, IL-12 could up-regulate MTB-specific IL-21 expression, especially the frequency of IL-21(+)IFN-γ+CD4(+) T cells. Taken together, our results demonstrated that MTB-specific IL-21(+)IFN-γ(+)CD4(+) T cells from local sites of tuberculosis (TB) infection could be enhanced by IL-12, which have the features of both Tfh and Th1 cells and may have an important role in local immune responses against TB infection.

  1. Image reconstructions with the rotating RF coil

    NASA Astrophysics Data System (ADS)

    Trakic, A.; Wang, H.; Weber, E.; Li, B. K.; Poole, M.; Liu, F.; Crozier, S.

    2009-12-01

    Recent studies have shown that rotating a single RF transceive coil (RRFC) provides a uniform coverage of the object and brings a number of hardware advantages (i.e. requires only one RF channel, averts coil-coil coupling interactions and facilitates large-scale multi-nuclear imaging). Motion of the RF coil sensitivity profile however violates the standard Fourier Transform definition of a time-invariant signal, and the images reconstructed in this conventional manner can be degraded by ghosting artifacts. To overcome this problem, this paper presents Time Division Multiplexed — Sensitivity Encoding (TDM-SENSE), as a new image reconstruction scheme that exploits the rotation of the RF coil sensitivity profile to facilitate ghost-free image reconstructions and reductions in image acquisition time. A transceive RRFC system for head imaging at 2 Tesla was constructed and applied in a number of in vivo experiments. In this initial study, alias-free head images were obtained in half the usual scan time. It is hoped that new sequences and methods will be developed by taking advantage of coil motion.

  2. The potent oncogene NPM-ALK mediates malignant transformation of normal human CD4(+) T lymphocytes.

    PubMed

    Zhang, Qian; Wei, Fang; Wang, Hong Yi; Liu, Xiaobin; Roy, Darshan; Xiong, Qun-Bin; Jiang, Shuguang; Medvec, Andrew; Danet-Desnoyers, Gwenn; Watt, Christopher; Tomczak, Ewa; Kalos, Michael; Riley, James L; Wasik, Mariusz A

    2013-12-01

    With this study we have demonstrated that in vitro transduction of normal human CD4(+) T lymphocytes with NPM-ALK results in their malignant transformation. The transformed cells become immortalized and display morphology and immunophenotype characteristic of patient-derived anaplastic large-cell lymphomas. These unique features, which are strictly dependent on NPM-ALK activity and expression, include perpetual cell growth, proliferation, and survival; activation of the key signal transduction pathways STAT3 and mTORC1; and expression of CD30 (the hallmark of anaplastic large-cell lymphoma) and of immunosuppressive cytokine IL-10 and cell-surface protein PD-L1/CD274. Implantation of NPM-ALK-transformed CD4(+) T lymphocytes into immunodeficient mice resulted in formation of tumors indistinguishable from patients' anaplastic large-cell lymphomas. Our findings demonstrate that the key aspects of human carcinogenesis closely recapitulating the features of the native tumors can be faithfully reproduced in vitro when an appropriate oncogene is used to transform its natural target cells; this in turn points to the fundamental role in malignant cell transformation of potent oncogenes expressed in the relevant target cells. Such transformed cells should permit study of the early stages of carcinogenesis, and in particular the initial oncogene-host cell interactions. This experimental design could also be useful for studies of the effects of early therapeutic intervention and likely also the mechanisms of malignant progression.

  3. Successful immunotherapy induces previously unidentified allergen-specific CD4+ T-cell subsets

    PubMed Central

    Ryan, John F.; Hovde, Rachel; Glanville, Jacob; Lyu, Shu-Chen; Ji, Xuhuai; Gupta, Sheena; Tibshirani, Robert J.; Jay, David C.; Boyd, Scott D.; Chinthrajah, R. Sharon; Davis, Mark M.; Galli, Stephen J.; Maecker, Holden T.; Nadeau, Kari C.

    2016-01-01

    Allergen immunotherapy can desensitize even subjects with potentially lethal allergies, but the changes induced in T cells that underpin successful immunotherapy remain poorly understood. In a cohort of peanut-allergic participants, we used allergen-specific T-cell sorting and single-cell gene expression to trace the transcriptional “roadmap” of individual CD4+ T cells throughout immunotherapy. We found that successful immunotherapy induces allergen-specific CD4+ T cells to expand and shift toward an “anergic” Th2 T-cell phenotype largely absent in both pretreatment participants and healthy controls. These findings show that sustained success, even after immunotherapy is withdrawn, is associated with the induction, expansion, and maintenance of immunotherapy-specific memory and naive T-cell phenotypes as early as 3 mo into immunotherapy. These results suggest an approach for immune monitoring participants undergoing immunotherapy to predict the success of future treatment and could have implications for immunotherapy targets in other diseases like cancer, autoimmune disease, and transplantation. PMID:26811452

  4. Defining CD4 T cell memory by the epigenetic landscape of CpG DNA methylation.

    PubMed

    Komori, H Kiyomi; Hart, Traver; LaMere, Sarah A; Chew, Pamela V; Salomon, Daniel R

    2015-02-15

    Memory T cells are primed for rapid responses to Ag; however, the molecular mechanisms responsible for priming remain incompletely defined. CpG methylation in promoters is an epigenetic modification, which regulates gene transcription. Using targeted bisulfite sequencing, we examined methylation of 2100 genes (56,000 CpGs) mapped by deep sequencing of T cell activation in human naive and memory CD4 T cells. Four hundred sixty-six CpGs (132 genes) displayed differential methylation between naive and memory cells. Twenty-one genes exhibited both differential methylation and gene expression before activation, linking promoter DNA methylation states to gene regulation; 6 of 21 genes encode proteins closely studied in T cells, whereas 15 genes represent novel targets for further study. Eighty-four genes demonstrated differential methylation between memory and naive cells that correlated to differential gene expression following activation, of which 39 exhibited reduced methylation in memory cells coupled with increased gene expression upon activation compared with naive cells. These reveal a class of primed genes more rapidly expressed in memory compared with naive cells and putatively regulated by DNA methylation. These findings define a DNA methylation signature unique to memory CD4 T cells that correlates with activation-induced gene expression.

  5. Primary 4T1 tumor resection provides critical "window of opportunity" for immunotherapy.

    PubMed

    Ghochikyan, Anahit; Davtyan, Arpine; Hovakimyan, Armine; Davtyan, Hayk; Poghosyan, Anna; Bagaev, Alexander; Ataullakhanov, Ravshan I; Nelson, Edward L; Agadjanyan, Michael G

    2014-02-01

    It is believed that primary tumor resection modulates host-tumor immune interaction, but this has not been characterized in a stringent breast cancer tumor model. This report, using the 4T1 murine mammary tumor model, characterizes for the first time the dynamic longitudinal changes in immunosuppressive and effector components of the immune system after resection of an established orthotopic primary tumor with a defined natural history of developing lung metastases. More specifically, we analyzed changes of absolute numbers and frequencies of MDSC, regulatory T cells (Treg), as well as activated CD4 and CD8 positive T cells in spleens and, in some studies, lungs of 4T1 tumor-bearing mice and mice after primary tumor resection. Importantly, using mathematical analyses we established that primary resection of an orthotopic tumor had created a "window of opportunity" with decreased tumor-associated immune suppression that existed for approximately 10 days. Although tumor resection did slightly prolong survival, it did not affect the ultimate development of metastatic disease since animals with resected tumors or intact primary tumors eventually died by day 47 and 43, respectively. This window of opportunity likely occurs in humans providing a rationale and parameters for integration and testing of immunotherapeutic strategies in this critical "window of opportunity" to combat the development of metastatic disease. PMID:24096737

  6. Role of distinct CD4(+) T helper subset in pathogenesis of oral lichen planus.

    PubMed

    Wang, Hui; Zhang, Dunfang; Han, Qi; Zhao, Xin; Zeng, Xin; Xu, Yi; Sun, Zheng; Chen, Qianming

    2016-07-01

    Oral lichen planus (OLP) is one of the most common chronic inflammatory oral mucosal diseases with T-cell-mediated immune pathogenesis. In subepithelial and lamina propria of OLP local lesions, the presence of CD4(+) T helper (CD4(+) Th) cells appeared as the major lymphocytes. These CD4(+) T lymphocytes can differentiate into distinct Th cell types such as Th1, Th2, Treg, Th17, Th22, Th9, and Tfh within the context of certain cytokines environment. Growing evidence indicated that Th1/Th2 imbalance may greatly participate into the cytokine network of OLP immunopathology. In addition, Th1/Th2 imbalance can be regulated by the Treg subset and also greatly influenced by the emerging novel CD4(+) Th subset Th17. Furthermore, the presence of novel subsets Th22, Th9 and Tfh in OLP patients is yet to be clarified. All these Th subsets and their specific cytokines may play a critical role in determining the character, extent and duration of immune responses in OLP pathogenesis. Therefore, we review the roles of distinct CD4(+) Th subsets and their signature cytokines in determining disease severity and susceptibility of OLP and also reveal the novel therapeutic strategies based on T lymphocytes subsets in OLP treatment. PMID:26693958

  7. Differential Th17 CD4 T-cell depletion in pathogenic and nonpathogenic lentiviral infections

    PubMed Central

    Paiardini, Mirko; Knox, Kenneth S.; Asher, Ava I.; Cervasi, Barbara; Asher, Tedi E.; Scheinberg, Phillip; Price, David A.; Hage, Chadi A.; Kholi, Lisa M.; Khoruts, Alexander; Frank, Ian; Else, James; Schacker, Timothy; Silvestri, Guido

    2008-01-01

    Acute HIV infection is characterized by massive loss of CD4 T cells from the gastrointestinal (GI) tract. Th17 cells are critical in the defense against microbes, particularly at mucosal surfaces. Here we analyzed Th17 cells in the blood, GI tract, and broncheoalveolar lavage of HIV-infected and uninfected humans, and SIV-infected and uninfected sooty mangabeys. We found that (1) human Th17 cells are specific for extracellular bacterial and fungal antigens, but not common viral antigens; (2) Th17 cells are infected by HIV in vivo, but not preferentially so; (3) CD4 T cells in blood of HIV-infected patients are skewed away from a Th17 phenotype toward a Th1 phenotype with cellular maturation; (4) there is significant loss of Th17 cells in the GI tract of HIV-infected patients; (5) Th17 cells are not preferentially lost from the broncheoalveolar lavage of HIV-infected patients; and (6) SIV-infected sooty mangabeys maintain healthy frequencies of Th17 cells in the blood and GI tract. These observations further elucidate the immunodeficiency of HIV disease and may provide a mechanistic basis for the mucosal barrier breakdown that characterizes HIV infection. Finally, these data may help account for the nonprogressive nature of nonpathogenic SIV infection in sooty mangabeys. PMID:18664624

  8. Adjuvant-enhanced CD4 T Cell Responses are Critical to Durable Vaccine Immunity.

    PubMed

    Martins, Karen A O; Cooper, Christopher L; Stronsky, Sabrina M; Norris, Sarah L W; Kwilas, Steven A; Steffens, Jesse T; Benko, Jacqueline G; van Tongeren, Sean A; Bavari, Sina

    2016-01-01

    Protein-based vaccines offer a safer alternative to live-attenuated or inactivated vaccines but have limited immunogenicity. The identification of adjuvants that augment immunogenicity, specifically in a manner that is durable and antigen-specific, is therefore critical for advanced development. In this study, we use the filovirus virus-like particle (VLP) as a model protein-based vaccine in order to evaluate the impact of four candidate vaccine adjuvants on enhancing long term protection from Ebola virus challenge. Adjuvants tested include poly-ICLC (Hiltonol), MPLA, CpG 2395, and alhydrogel. We compared and contrasted antibody responses, neutralizing antibody responses, effector T cell responses, and T follicular helper (Tfh) cell frequencies with each adjuvant's impact on durable protection. We demonstrate that in this system, the most effective adjuvant elicits a Th1-skewed antibody response and strong CD4 T cell responses, including an increase in Tfh frequency. Using immune-deficient animals and adoptive transfer of serum and cells from vaccinated animals into naïve animals, we further demonstrate that serum and CD4 T cells play a critical role in conferring protection within effective vaccination regimens. These studies inform on the requirements of long term immune protection, which can potentially be used to guide screening of clinical-grade adjuvants for vaccine clinical development. PMID:26870818

  9. The Regulation of CD4(+) T Cell Responses during Protozoan Infections.

    PubMed

    Engwerda, Christian R; Ng, Susanna S; Bunn, Patrick T

    2014-01-01

    CD4(+) T cells are critical for defense against protozoan parasites. Intracellular protozoan parasite infections generally require the development of a Th1 cell response, characterized by the production of IFNγ and TNF that are critical for the generation of microbicidal molecules by phagocytes, as well as the expression of cytokines and cell surface molecules needed to generate cytolytic CD8(+) T cells that can recognize and kill infected host cells. Over the past 25 years, much has been learnt about the molecular and cellular components necessary for the generation of Th1 cell responses, and it has become clear that these responses need to be tightly controlled to prevent disease. However, our understanding of the immunoregulatory mechanisms activated during infection is still not complete. Furthermore, it is apparent that although these mechanisms are critical to prevent inflammation, they can also promote parasite persistence and development of disease. Here, we review how CD4(+) T cells are controlled during protozoan infections and how these regulatory mechanisms can influence parasite growth and disease outcome.

  10. Conventional and Regulatory CD4+ T Cells That Share Identical TCRs Are Derived from Common Clones.

    PubMed

    Wolf, Kyle J; Emerson, Ryan O; Pingel, Jeanette; Buller, R Mark; DiPaolo, Richard J

    2016-01-01

    Results from studies comparing the diversity and specificity of the TCR repertoires expressed by conventional (Tconv) and regulatory (Treg) CD4+ T cell have varied depending on the experimental system employed. We developed a new model in which T cells express a single fixed TCRα chain, randomly rearranged endogenous TCRβ chains, and a Foxp3-GFP reporter. We purified CD4+Foxp3- and CD4+Foxp3+ cells, then performed biased controlled multiplex PCR and high throughput sequencing of endogenous TCRβ chains. We identified >7,000 different TCRβ sequences in the periphery of 5 individual mice. On average, ~12% of TCR sequences were expressed by both conventional and regulatory populations within individual mice. The CD4+ T cells that expressed shared TCR sequences were present at higher frequencies compared to T cells expressing non-shared TCRs. Furthermore, nearly all (>90%) of the TCR sequences that were shared within mice were identical at the DNA sequence level, indicating that conventional and regulatory T cells that express shared TCRs are derived from common clones. Analysis of TCR repertoire overlap in the thymus reveals that a large proportion of Tconv and Treg sharing observed in the periphery is due to clonal expansion in the thymus. Together these data show that there are a limited number of TCR sequences shared between Tconv and Tregs. Also, Tconv and Tregs sharing identical TCRs are found at relatively high frequencies and are derived from common progenitors, of which a large portion are generated in the thymus. PMID:27100298

  11. Primary 4T1 tumor resection provides critical "window of opportunity" for immunotherapy.

    PubMed

    Ghochikyan, Anahit; Davtyan, Arpine; Hovakimyan, Armine; Davtyan, Hayk; Poghosyan, Anna; Bagaev, Alexander; Ataullakhanov, Ravshan I; Nelson, Edward L; Agadjanyan, Michael G

    2014-02-01

    It is believed that primary tumor resection modulates host-tumor immune interaction, but this has not been characterized in a stringent breast cancer tumor model. This report, using the 4T1 murine mammary tumor model, characterizes for the first time the dynamic longitudinal changes in immunosuppressive and effector components of the immune system after resection of an established orthotopic primary tumor with a defined natural history of developing lung metastases. More specifically, we analyzed changes of absolute numbers and frequencies of MDSC, regulatory T cells (Treg), as well as activated CD4 and CD8 positive T cells in spleens and, in some studies, lungs of 4T1 tumor-bearing mice and mice after primary tumor resection. Importantly, using mathematical analyses we established that primary resection of an orthotopic tumor had created a "window of opportunity" with decreased tumor-associated immune suppression that existed for approximately 10 days. Although tumor resection did slightly prolong survival, it did not affect the ultimate development of metastatic disease since animals with resected tumors or intact primary tumors eventually died by day 47 and 43, respectively. This window of opportunity likely occurs in humans providing a rationale and parameters for integration and testing of immunotherapeutic strategies in this critical "window of opportunity" to combat the development of metastatic disease.

  12. New candidates for CD4 T cell pathogenicity in experimental neuroinflammation and multiple sclerosis.

    PubMed

    Hoppmann, Nicola; Graetz, Christiane; Paterka, Magdalena; Poisa-Beiro, Laura; Larochelle, Catherine; Hasan, Maruf; Lill, Christina M; Zipp, Frauke; Siffrin, Volker

    2015-04-01

    Multiple sclerosis is a chronic autoimmune demyelinating disease of the central nervous system, which is thought to be triggered by environmental factors in genetically susceptible individuals leading to activation of autoreactive T lymphocytes. Large multi-centre genome-wide association studies have identified multiple genetic risk loci in multiple sclerosis. In this study, we investigated T cell transcriptomic changes in experimental autoimmune encephalomyelitis, an animal model for multiple sclerosis. We correlated these findings with the multiple sclerosis risk genes postulated by the most recent Immunochip analysis and found that multiple sclerosis susceptibility genes were significantly regulated in experimental autoimmune encephalomyelitis. Our data indicate that nine distinct genes associated with multiple sclerosis risk, Bach2, Il2ra, Irf8, Mertk, Odf3b, Plek, Rgs1, Slc30a7 and Thada, can be confirmed to be differentially regulated in pathogenic CD4(+) T cells. During the effector phase within the inflamed CNS, CD4(+) T cells undergo comprehensive transformation and we identified key transcription factors and signalling networks involved in this process. The transformation was linked to metabolic changes with the involvement of liver X receptor/retinoid X receptor signalling and cholesterol biosynthesis, which might control the T cell effector function in the central nervous system. Thus, our study confirms the involvement of multiple sclerosis risk genes in the pathophysiology of the animal model and sheds light on additional disease-relevant inflammatory networks.

  13. Identification of novel Mycobacterium tuberculosis CD4 T-cell antigens via high throughput proteome screening

    PubMed Central

    Nayak, Kaustuv; Jing, Lichen; Russell, Ronnie M.; Davies, D. Huw; Hermanson, Gary; Molina, Douglas M.; Liang, Xiaowu; Sherman, David R.; Kwok, William W.; Yang, Junbao; Kenneth, John; Ahamed, Syed F.; Chandele, Anmol; Kaja, Murali-Krishna; Koelle, David M.

    2015-01-01

    Elicitation of CD4 IFN-gamma T cell responses to Mycobacterium tuberculosis (MTB) is a rational vaccine strategy to prevent clinical tuberculosis. Diagnosis of MTB infection is based on T-cell immune memory to MTB antigens. The MTB proteome contains over four thousand open reading frames (ORFs). We conducted a pilot antigen identification study using 164 MTB proteins and MTB-specific T-cells expanded in vitro from 12 persons with latent MTB infection. Enrichment of MTB-reactive T-cells from PBMC used cell sorting or an alternate system compatible with limited resources. MTB proteins were used as single antigens or combinatorial matrices in proliferation and cytokine secretion readouts. Overall, our study found that 44 MTB proteins were antigenic, including 27 not previously characterized as CD4 T-cell antigens. Antigen truncation, peptide, NTM homology, and HLA class II tetramer studies confirmed malate synthase G (encoded by gene Rv1837) as a CD4 T-cell antigen. This simple, scalable system has potential utility for the identification of candidate MTB vaccine and biomarker antigens. PMID:25857935

  14. Conventional and Regulatory CD4+ T Cells That Share Identical TCRs Are Derived from Common Clones

    PubMed Central

    Emerson, Ryan O.; Pingel, Jeanette; Buller, R. Mark; DiPaolo, Richard J.

    2016-01-01

    Results from studies comparing the diversity and specificity of the TCR repertoires expressed by conventional (Tconv) and regulatory (Treg) CD4+ T cell have varied depending on the experimental system employed. We developed a new model in which T cells express a single fixed TCRα chain, randomly rearranged endogenous TCRβ chains, and a Foxp3-GFP reporter. We purified CD4+Foxp3- and CD4+Foxp3+ cells, then performed biased controlled multiplex PCR and high throughput sequencing of endogenous TCRβ chains. We identified >7,000 different TCRβ sequences in the periphery of 5 individual mice. On average, ~12% of TCR sequences were expressed by both conventional and regulatory populations within individual mice. The CD4+ T cells that expressed shared TCR sequences were present at higher frequencies compared to T cells expressing non-shared TCRs. Furthermore, nearly all (>90%) of the TCR sequences that were shared within mice were identical at the DNA sequence level, indicating that conventional and regulatory T cells that express shared TCRs are derived from common clones. Analysis of TCR repertoire overlap in the thymus reveals that a large proportion of Tconv and Treg sharing observed in the periphery is due to clonal expansion in the thymus. Together these data show that there are a limited number of TCR sequences shared between Tconv and Tregs. Also, Tconv and Tregs sharing identical TCRs are found at relatively high frequencies and are derived from common progenitors, of which a large portion are generated in the thymus. PMID:27100298

  15. Inflammatory monocytes are potent antitumor effectors controlled by regulatory CD4+ T cells

    PubMed Central

    Pommier, Arnaud; Audemard, Alexandra; Durand, Aurélie; Lengagne, Renée; Delpoux, Arnaud; Martin, Bruno; Douguet, Laetitia; Le Campion, Armelle; Kato, Masashi; Avril, Marie-Françoise; Auffray, Cédric; Lucas, Bruno; Prévost-Blondel, Armelle

    2013-01-01

    The present study evaluates the impact of immune cell populations on metastatic development in a model of spontaneous melanoma [mice expressing the human RET oncogene under the control of the metallothionein promoter (MT/ret mice)]. In this model, cancer cells disseminate early but remain dormant for several weeks. Then, MT/ret mice develop cutaneous metastases and, finally, distant metastases. A total of 35% of MT/ret mice develop a vitiligo, a skin depigmentation attributable to the lysis of normal melanocytes, associated with a delay in tumor progression. Here, we find that regulatory CD4+ T cells accumulate in the skin, the spleen, and tumor-draining lymph nodes of MT/ret mice not developing vitiligo. Regulatory T-cell depletion and IL-10 neutralization led to increased occurrence of vitiligo that correlated with a decreased incidence of melanoma metastases. In contrast, inflammatory monocytes/dendritic cells accumulate in the skin of MT/ret mice with active vitiligo. Moreover, they inhibit tumor cell proliferation in vitro through a reactive oxygen species-dependent mechanism, and both their depletion and reactive oxygen species neutralization in vivo increased tumor cell dissemination. Altogether, our data suggest that regulatory CD4+ T cells favor tumor progression, in part, by inhibiting recruitment and/or differentiation of inflammatory monocytes in the skin. PMID:23878221

  16. Successful immunotherapy induces previously unidentified allergen-specific CD4+ T-cell subsets.

    PubMed

    Ryan, John F; Hovde, Rachel; Glanville, Jacob; Lyu, Shu-Chen; Ji, Xuhuai; Gupta, Sheena; Tibshirani, Robert J; Jay, David C; Boyd, Scott D; Chinthrajah, R Sharon; Davis, Mark M; Galli, Stephen J; Maecker, Holden T; Nadeau, Kari C

    2016-03-01

    Allergen immunotherapy can desensitize even subjects with potentially lethal allergies, but the changes induced in T cells that underpin successful immunotherapy remain poorly understood. In a cohort of peanut-allergic participants, we used allergen-specific T-cell sorting and single-cell gene expression to trace the transcriptional "roadmap" of individual CD4+ T cells throughout immunotherapy. We found that successful immunotherapy induces allergen-specific CD4+ T cells to expand and shift toward an "anergic" Th2 T-cell phenotype largely absent in both pretreatment participants and healthy controls. These findings show that sustained success, even after immunotherapy is withdrawn, is associated with the induction, expansion, and maintenance of immunotherapy-specific memory and naive T-cell phenotypes as early as 3 mo into immunotherapy. These results suggest an approach for immune monitoring participants undergoing immunotherapy to predict the success of future treatment and could have implications for immunotherapy targets in other diseases like cancer, autoimmune disease, and transplantation. PMID:26811452

  17. Tetrandrine Suppresses Cancer Angiogenesis and Metastasis in 4T1 Tumor Bearing Mice

    PubMed Central

    Gao, Jian-Li; He, Tong-Chuan; He, Kai; Chen, Su-Hong; Lv, Gui-Yuan

    2013-01-01

    Metastasis remains the most deadly aspect of cancer and still evades direct treatment. Thus, there is a great need to develop new treatment regimens to suppress tumor cells that have escaped surgical removal or that may have already disseminated. We have found that tetrandrine (TET) exhibits anticolon cancer activity. Here, we investigate the inhibition effect of TET to breast cancer metastasis, angiogenesis and its molecular basis underlying TET's anticancer activity. We compare TET with chemotherapy drug doxorubicin in 4T1 tumor bearing BALB/c mice model and find that TET exhibits an anticancer metastatic and antiangiogenic activities better than those of doxorubicin. The lung metastatic sites were decreased by TET, which is confirmed by bioluminescence imaging in vivo. On the other hand, laser doppler perfusion imaging (LDI) was used for measuring the blood flow of tumor in 4T1-tumor bearing mice. As a result, the local blood perfusion of tumor was markedly decreased by TET after 3 weeks. Mechanistically, TET treatment leads to a decrease in p-ERK level and an increase in NF-κB levels in HUVECs. TET also regulated metastatic and angiogenic related proteins, including vascular endothelial growth factor, hypoxia-inducible factor-1α, integrin β5, endothelial cell specific molecule-1, and intercellular adhesion molecule-1 in vivo. PMID:23762115

  18. Friend of GATA-1 Represses GATA-3–dependent Activity in CD4+ T Cells

    PubMed Central

    Zhou, Meixia; Ouyang, Wenjun; Gong, Qian; Katz, Samuel G.; White, J. Michael; Orkin, Stuart H.; Murphy, Kenneth M.

    2001-01-01

    The development of naive CD4+ T cells into a T helper (Th) 2 subset capable of producing interleukin (IL)-4, IL-5, and IL-13 involves a signal transducer and activator of transcription (Stat)6-dependent induction of GATA-3 expression, followed by Stat6-independent GATA-3 autoactivation. The friend of GATA (FOG)-1 protein regulates GATA transcription factor activity in several stages of hematopoietic development including erythrocyte and megakaryocyte differentiation, but whether FOG-1 regulates GATA-3 in T cells is uncertain. We show that FOG-1 can repress GATA-3–dependent activation of the IL-5 promoter in T cells. Also, FOG-1 overexpression during primary activation of naive T cells inhibited Th2 development in CD4+ T cells. FOG-1 fully repressed GATA-3–dependent Th2 development and GATA-3 autoactivation, but not Stat6-dependent induction of GATA-3. FOG-1 overexpression repressed development of Th2 cells from naive T cells, but did not reverse the phenotype of fully committed Th2 cells. Thus, FOG-1 may be one factor capable of regulating the Th2 development. PMID:11714753

  19. Adjuvant-enhanced CD4 T Cell Responses are Critical to Durable Vaccine Immunity

    PubMed Central

    Martins, Karen A.O.; Cooper, Christopher L.; Stronsky, Sabrina M.; Norris, Sarah L.W.; Kwilas, Steven A.; Steffens, Jesse T.; Benko, Jacqueline G.; van Tongeren, Sean A.; Bavari, Sina

    2015-01-01

    Protein-based vaccines offer a safer alternative to live-attenuated or inactivated vaccines but have limited immunogenicity. The identification of adjuvants that augment immunogenicity, specifically in a manner that is durable and antigen-specific, is therefore critical for advanced development. In this study, we use the filovirus virus-like particle (VLP) as a model protein-based vaccine in order to evaluate the impact of four candidate vaccine adjuvants on enhancing long term protection from Ebola virus challenge. Adjuvants tested include poly-ICLC (Hiltonol), MPLA, CpG 2395, and alhydrogel. We compared and contrasted antibody responses, neutralizing antibody responses, effector T cell responses, and T follicular helper (Tfh) cell frequencies with each adjuvant's impact on durable protection. We demonstrate that in this system, the most effective adjuvant elicits a Th1-skewed antibody response and strong CD4 T cell responses, including an increase in Tfh frequency. Using immune-deficient animals and adoptive transfer of serum and cells from vaccinated animals into naïve animals, we further demonstrate that serum and CD4 T cells play a critical role in conferring protection within effective vaccination regimens. These studies inform on the requirements of long term immune protection, which can potentially be used to guide screening of clinical-grade adjuvants for vaccine clinical development. PMID:26870818

  20. Functional Heterogeneity in CD4(+) T Cell Responses Against a Bacterial Pathogen.

    PubMed

    Milam, Ashley Viehmann; Allen, Paul M

    2015-01-01

    To investigate how CD4(+) T cells function against a bacterial pathogen, we generated a Listeria monocytogenes-specific CD4(+) T cell model. In this system, two TCRtg mouse lines, LLO56 and LLO118, recognize the same immunodominant epitope (LLO190-205) of L. monocytogenes and have identical in vitro responses. However, in vivo LLO56 and LLO118 display vastly different responses during both primary and secondary infection. LLO118 dominates in the primary response and in providing CD8 T cell help. LLO56 predominates in the secondary response. We have also shown that both specific [T cell receptor (TCR)-mediated] and non-specific stimuli (bypassing the TCR) elicit distinct responses from the two transgenics, leading us to conclude that the strength of self-pMHC signaling during development tightly dictates the cell's future response in the periphery. Herein, we review our findings in this transfer system, focusing on the contribution of the immunomodulatory molecule CD5 and the importance of self-interaction in peripheral maintenance of the cell. We also discuss the manner in which individual TCR affinities to foreign and self-pMHC contribute to the outcome of an immune response; our assertion is that there exists a spectrum of possible T cell responses to recognition of cognate antigen during infection, adding immense diversity to the immune system's response to pathogens. PMID:26697015

  1. Successful immunotherapy induces previously unidentified allergen-specific CD4+ T-cell subsets.

    PubMed

    Ryan, John F; Hovde, Rachel; Glanville, Jacob; Lyu, Shu-Chen; Ji, Xuhuai; Gupta, Sheena; Tibshirani, Robert J; Jay, David C; Boyd, Scott D; Chinthrajah, R Sharon; Davis, Mark M; Galli, Stephen J; Maecker, Holden T; Nadeau, Kari C

    2016-03-01

    Allergen immunotherapy can desensitize even subjects with potentially lethal allergies, but the changes induced in T cells that underpin successful immunotherapy remain poorly understood. In a cohort of peanut-allergic participants, we used allergen-specific T-cell sorting and single-cell gene expression to trace the transcriptional "roadmap" of individual CD4+ T cells throughout immunotherapy. We found that successful immunotherapy induces allergen-specific CD4+ T cells to expand and shift toward an "anergic" Th2 T-cell phenotype largely absent in both pretreatment participants and healthy controls. These findings show that sustained success, even after immunotherapy is withdrawn, is associated with the induction, expansion, and maintenance of immunotherapy-specific memory and naive T-cell phenotypes as early as 3 mo into immunotherapy. These results suggest an approach for immune monitoring participants undergoing immunotherapy to predict the success of future treatment and could have implications for immunotherapy targets in other diseases like cancer, autoimmune disease, and transplantation.

  2. Memory CD4+ T cells do not induce graft-versus-host disease.

    PubMed

    Anderson, Britt E; McNiff, Jennifer; Yan, Jun; Doyle, Hester; Mamula, Mark; Shlomchik, Mark J; Shlomchik, Warren D

    2003-07-01

    Graft-versus-host disease (GVHD) remains a major cause of morbidity and mortality in allogeneic stem cell transplantation (alloSCT). Donor T cells that accompany stem cell grafts cause GVHD by attacking recipient tissues; therefore, all patients receive GVHD prophylaxis by depletion of T cells from the allograft or through immunosuppressant drugs. In addition to providing a graft-versus-leukemia effect, donor T cells are critical for reconstituting T cell-mediated immunity. Ideally, immunity to infectious agents would be transferred from donor to host without GVHD. Most donors have been exposed to common pathogens and have an increased precursor frequency of memory T cells against pathogenic antigens. We therefore asked whether memory CD62L-CD44+ CD4+ T cells would induce less GVHD than unfractionated or naive CD4+ T cells. Strikingly, we found that memory CD4 cells induced neither clinical nor histologic GVHD. This effect was not due to the increased number of CD4+CD25+ regulatory T cells found in the CD62L-CD44+ fraction because memory T cells depletion of these cells did not cause GVHD. Memory CD4 cells engrafted and responded to antigen both in vivo and in vitro. If these murine results are applicable to human alloSCT, selective administration of memory T cells could greatly improve post-transplant immune reconstitution.

  3. Defining CD4 T cell memory by the epigenetic landscape of CpG DNA methylation.

    PubMed

    Komori, H Kiyomi; Hart, Traver; LaMere, Sarah A; Chew, Pamela V; Salomon, Daniel R

    2015-02-15

    Memory T cells are primed for rapid responses to Ag; however, the molecular mechanisms responsible for priming remain incompletely defined. CpG methylation in promoters is an epigenetic modification, which regulates gene transcription. Using targeted bisulfite sequencing, we examined methylation of 2100 genes (56,000 CpGs) mapped by deep sequencing of T cell activation in human naive and memory CD4 T cells. Four hundred sixty-six CpGs (132 genes) displayed differential methylation between naive and memory cells. Twenty-one genes exhibited both differential methylation and gene expression before activation, linking promoter DNA methylation states to gene regulation; 6 of 21 genes encode proteins closely studied in T cells, whereas 15 genes represent novel targets for further study. Eighty-four genes demonstrated differential methylation between memory and naive cells that correlated to differential gene expression following activation, of which 39 exhibited reduced methylation in memory cells coupled with increased gene expression upon activation compared with naive cells. These reveal a class of primed genes more rapidly expressed in memory compared with naive cells and putatively regulated by DNA methylation. These findings define a DNA methylation signature unique to memory CD4 T cells that correlates with activation-induced gene expression. PMID:25576597

  4. Murine autoimmune hearing loss mediated by CD4+ T cells specific for inner ear peptides.

    PubMed

    Solares, C Arturo; Edling, Andrea E; Johnson, Justin M; Baek, Moo-Jin; Hirose, Keiko; Hughes, Gordon B; Tuohy, Vincent K

    2004-04-01

    Autoimmune sensorineural hearing loss (ASNHL) is characterized typically by bilateral, rapidly progressive hearing loss that responds therapeutically to corticosteroid treatment. Despite its name, data implicating autoimmunity in the etiopathogenesis of ASNHL have been limited, and targeted self-antigens have not been identified. In the current study we show that the inner ear-specific proteins cochlin and beta-tectorin are capable of targeting experimental autoimmune hearing loss (EAHL) in mice. Five weeks after immunization of SWXJ mice with either Coch 131-150 or beta-tectorin 71-90, auditory brainstem responses (ABR) showed significant hearing loss at all frequencies tested. Flow cytometry analysis showed that each peptide selectively activated CD4(+) T cells with a proinflammatory Th1-like phenotype. T cell mediation of EAHL was determined by showing significantly increased ABR thresholds 6 weeks after adoptive transfer of peptide-activated CD4(+) T cells into naive SWXJ recipients. Immunocytochemical analysis showed that leukocytic infiltration of inner ear tissues coincided with onset of hearing loss. Our study provides a contemporary mouse model for clarifying our understanding of ASNHL and facilitating the development of novel effective treatments for this clinical entity. Moreover, our data provide experimental confirmation that ASNHL may be a T cell-mediated organ-specific autoimmune disorder of the inner ear.

  5. Radio-Frequency Heating at 9.4 T (400.2 MHz) – In Vivo Thermoregulatory Temperature Response in Swine

    PubMed Central

    Shrivastava, Devashish; Hanson, Timothy; Kulesa, Jeramy; DelaBarre, Lance; Iaizzo, Paul; Vaughan, J. Thomas

    2009-01-01

    In vivo thermoregulatory temperature response to RF heating at 9.4 T was studied by measuring temperatures in nine anesthetized swine. Temperatures were measured in the scalp, brain, and rectum. The RF energy was deposited using a four loop head coil tuned to 400.2 MHz. Sham RF was delivered to three swine to understand thermal effects of anesthesia (animal weight = 54.16 kg, SD = 3.08 kg). Continuous wave RF energy was delivered to the other six animals for 2.5–3.4 hours (animal weight = 74.01 ± 26.0 kg, heating duration = 3.05 ± 0.29 hours). The whole head specific absorption rate (SAR) varied between 2.71 W/kg and 3.20 W/kg (SAR = 2.93 ± 0.18 W/kg). Anesthesia caused the brain and rectal temperatures to drop linearly. Altered thermoregulatory response was detected by comparing the difference in the temperature slopes before and after the RF delivery from zero. RF heating statistically significantly altered the rate of cooling down of the animal. The temperature slope changes correlated well with the RF energy per unit head weight and heating duration, and the maximum rectal temperature change during heating in heated animals. The temperature slope changes did not correlate well to the whole head average SARs. PMID:19572392

  6. Myd88 Initiates Early Innate Immune Responses and Promotes CD4 T Cells during Coronavirus Encephalomyelitis

    PubMed Central

    Butchi, Niranjan; Kapil, Parul; Puntambekar, Shweta; Stohlman, Stephen A.; Hinton, David R.

    2015-01-01

    ABSTRACT Myd88 signaling is critical to the control of numerous central nervous system (CNS) infections by promoting both innate and adaptive immune responses. Nevertheless, the extent to which Myd88 regulates type I interferon (IFN) versus proinflammatory factors and T cell function, as well as the anatomical site of action, varies extensively with the pathogen. CNS infection by neurotropic coronavirus with replication confined to the brain and spinal cord induces protective IFN-α/β via Myd88-independent activation of melanoma differentiation-associated gene 5 (MDA5). However, a contribution of Myd88-dependent signals to CNS pathogenesis has not been assessed. Infected Myd88−/− mice failed to control virus, exhibited enhanced clinical disease coincident with increased demyelination, and succumbed to infection within 3 weeks. The induction of IFN-α/β, as well as of proinflammatory cytokines and chemokines, was impaired early during infection. However, defects in both IFN-α/β and select proinflammatory factors were rapidly overcome prior to T cell recruitment. Myd88 deficiency also specifically blunted myeloid and CD4 T cell recruitment into the CNS without affecting CD8 T cells. Moreover, CD4 T cells but not CD8 T cells were impaired in IFN-γ production. Ineffective virus control indeed correlated most prominently with reduced antiviral IFN-γ in the CNS of Myd88−/− mice. The results demonstrate a crucial role for Myd88 both in early induction of innate immune responses during coronavirus-induced encephalomyelitis and in specifically promoting protective CD4 T cell activation. In the absence of these responses, functional CD8 T cells are insufficient to control viral spread within the CNS, resulting in severe demyelination. IMPORTANCE During central nervous system (CNS) infections, signaling through the adaptor protein Myd88 promotes both innate and adaptive immune responses. The extent to which Myd88 regulates antiviral type I IFN, proinflammatory

  7. Radiation-hard electrical coil and method for its fabrication

    DOEpatents

    Grieggs, R.J.; Blake, R.D.; Gac, F.D.

    1982-06-29

    A radiation-hard insulated electrical coil and method for making the same are disclosed. In accordance with the method, a conductor, preferably copper, is wrapped with an aluminum strip and then tightly wound into a coil. The aluminum-wrapped coil is then annealed to relax the conductor in the coiled configuration. The annealed coil is then immersed in an alkaline solution to dissolve the aluminum strip, leaving the bare conductor in a coiled configuration with all of the windings closely packed yet uniformly spaced from one another. The coil is then insulated with a refractory insulating material. In the preferred embodiment, the coil is insulated by coating it with a vitreous enamel and subsequently potting the enamelled coil in a castable ceramic concrete. The resulting coil is substantially insensitive to radiation and may be operated continuously in high radiation environments for long periods of time.

  8. Transient CD4+ T Cell Depletion Results in Delayed Development of Functional Vaccine-Elicited Antibody Responses

    PubMed Central

    Provine, Nicholas M.; Badamchi-Zadeh, Alexander; Bricault, Christine A.; Penaloza-MacMaster, Pablo; Larocca, Rafael A.; Borducchi, Erica N.; Seaman, Michael S.

    2016-01-01

    ABSTRACT We have recently demonstrated that CD4+ T cell help is required at the time of adenovirus (Ad) vector immunization for the development of functional CD8+ T cell responses, but the temporal requirement for CD4+ T cell help for the induction of antibody responses remains unclear. Here we demonstrate that induction of antibody responses in C57BL/6 mice can occur at a time displaced from the time of Ad vector immunization by depletion of CD4+ T cells. Transient depletion of CD4+ T cells at the time of immunization delays the development of antigen-specific antibody responses but does not permanently impair their development or induce tolerance against the transgene. Upon CD4+ T cell recovery, transgene-specific serum IgG antibody titers develop and reach a concentration equivalent to that in undepleted control animals. These delayed antibody responses exhibit no functional defects with regard to isotype, functional avidity, expansion after boosting immunization, or the capacity to neutralize a simian immunodeficiency virus (SIV) Env-expressing pseudovirus. The development of this delayed transgene-specific antibody response is temporally linked to the expansion of de novo antigen-specific CD4+ T cell responses, which develop after transient depletion of CD4+ T cells. These data demonstrate that functional vaccine-elicited antibody responses can be induced even if CD4+ T cell help is provided at a time markedly separated from the time of vaccination. IMPORTANCE CD4+ T cells have a critical role in providing positive help signals to B cells, which promote robust antibody responses. The paradigm is that helper signals must be provided immediately upon antigen exposure, and their absence results in tolerance against the antigen. Here we demonstrate that, in contrast to the current model that the absence of CD4+ T cell help at priming results in long-term antibody nonresponsiveness, antibody responses can be induced by adenovirus vector immunization or alum

  9. Deployment of the CMS Tracker AMC as backend for the CMS pixel detector

    NASA Astrophysics Data System (ADS)

    Auzinger, G.

    2016-01-01

    The silicon pixel detector of the CMS experiment at CERN will be replaced with an upgraded version at the beginning of 2017 with the new detector featuring an additional barrel- and end-cap layer resulting in an increased number of fully digital read-out links running at 400 Mbps. New versions of the PSI46 Read-Out Chip and Token Bit Manager have been developed to operate at higher rates and reduce data loss. Front-End Controller and Front-End Driver boards, based on the μTCA compatible CMS Tracker AMC, a variant of the FC7 card, are being developed using different mezzanines to host the optical links for the digital read-out and control system. An overview of the system architecture is presented, with details on the implementation, and first results obtained from test systems.

  10. Transient Heat Transfer in TCAP Coils

    SciTech Connect

    Steimke, J.L.

    1999-03-09

    The Thermal Cycling Absorption Process (TCAP) is used to separate isotopes of hydrogen. TCAP involves passing a stream of mixed hydrogen isotopes through palladium deposited on kieselguhr (Pd/k) while cycling the temperature of the Pd/k. Kieselguhr is a silica mineral also called diatomite. To aid in the design of a full scale facility, the Thermal Fluids Laboratory was used by the Chemical and Hydrogen Technology Section to compare the heat transfer properties of three different configurations of stainless steel coils containing kieselguhr and helium. Testing of coils containing Pd/k and hydrogen isotopes would have been more prototypical but would have been too expensive. Three stainless steel coils filled with kieselguhr were tested; one made from 2.0 inch diameter tubing, one made from 2.0 inch diameter tubing with foam copper embedded in the kieselguhr and one made from 1.25 inch diameter tubing. It was known prior to testing that increasing the tubing diameter from 1.25 inch to 2.0 inch would slow the rate of temperature change. The primary purpose of the testing was to measure to what extent the presence of copper foam in a 2.0" tubing coil would compensate for the effect of larger diameter. Each coil was connected to a pressure gage and the coil was evacuated and backfilled with helium gas. Helium was used instead of a mixture of hydrogen isotopes for reasons of safety. Each coil was quickly immersed in a stirred bath of ethylene glycol at a temperature of approximately 100 degrees Celsius. The coil pressure increased, reflecting the increase in average temperature of its contents. The pressure transient was recored as a function of time after immersion. Because of the actual process will use Pd/k instead of kieselguhr, additional tests were run to determine the differences in thermal properties between the two materials. The method was to position a thermocouple at the center of a hollow sphere and pack the sphere with Pd/k. The sphere was sealed, quickly

  11. Transient Heat Transfer in TCAP Coils

    SciTech Connect

    Steimke, J.L.

    1999-03-09

    The Thermal Cycling Absorption Process (TCAP) is used to separate isotopes of hydrogen. TCAP involves passing a stream of mixed hydrogen isotopes through palladium deposited on kieselguhr (Pd/k) while cycling the temperature of the Pd/k. Kieselguhr is a silica mineral also called diatomite. To aid in the design of a full scale facility, the Thermal Fluids Laboratory was used by the Chemical and Hydrogen Technology Section to compare the heat transfer properties of three different configurations of stainless steel coils containing kieselguhr and helium. Testing of coils containing Pd/k and hydrogen isotopes would have been more prototypical but would have been too expensive. Three stainless steel coils filled with kieselguhr were tested; one made from 2.0 inch diameter tubing, one made from 2.0 inch diameter tubing with foam copper embedded in the kieselguhr and one made from 1.25 inch diameter tubing. It was known prior to testing that increasing the tubing diameter from 1.25 inch to 2.0 inch would slow the rate of temperature change. The primary purpose of the testing was to measure to what extent the presence of copper foam in a 2.0 tubing coil would compensate for the effect of larger diameter. Each coil was connected to a pressure gage and the coil was evacuated and backfilled with helium gas. Helium was used instead of a mixture of hydrogen isotopes for reasons of safety. Each coil was quickly immersed in a stirred bath of ethylene glycol at a temperature of approximately 100 degrees Celsius. The coil pressure increased, reflecting the increase in average temperature of its contents. The pressure transient was recored as a function of time after immersion. Because of the actual process will use Pd/k instead of kieselguhr, additional tests were run to determine the differences in thermal properties between the two materials. The method was to position a thermocouple at the center of a hollow sphere and pack the sphere with Pd/k. The sphere was sealed, quickly

  12. The predicted coiled-coil domain of myosin 10 forms a novel elongated domain that lengthens the head.

    PubMed

    Knight, Peter J; Thirumurugan, Kavitha; Xu, Yuhui; Wang, Fei; Kalverda, Arnout P; Stafford, Walter F; Sellers, James R; Peckham, Michelle

    2005-10-14

    Myosin 10 contains a region of predicted coiled coil 120 residues long. However, the highly charged nature and pattern of charges in the proximal 36 residues appear incompatible with coiled-coil formation. Circular dichroism, NMR, and analytical ultracentrifugation show that a synthesized peptide containing this region forms a stable single alpha-helix (SAH) domain in solution and does not dimerize to form a coiled coil even at millimolar concentrations. Additionally, electron microscopy of a recombinant myosin 10 containing the motor, the three calmodulin binding domains, and the full-length predicted coiled coil showed that it was mostly monomeric at physiological protein concentration. In dimers the molecules were joined only at their extreme distal ends, and no coiled-coil tail was visible. Furthermore, the neck lengths of both monomers and dimers were much longer than expected from the number of calmodulin binding domains. In contrast, micrographs of myosin 5 heavy meromyosin obtained under the same conditions clearly showed a coiled-coil tail, and the necks were the predicted length. Thus the predicted coiled coil of myosin 10 forms a novel elongated structure in which the proximal region is a SAH domain and the distal region is a SAH domain (or has an unknown extended structure) that dimerizes only at its end. Sequence comparisons show that similar structures may exist in the predicted coiled-coil domains of myosins 6 and 7a and MyoM and could function to increase the size of the working stroke. PMID:16030012

  13. CMS data quality monitoring web service

    NASA Astrophysics Data System (ADS)

    Tuura, L.; Eulisse, G.; Meyer, A.

    2010-04-01

    A central component of the data quality monitoring system of the CMS experiment at the Large Hadron Collider is a web site for browsing data quality histograms. The production servers in data taking provide access to several hundred thousand histograms per run, both live in online as well as for up to several terabytes of archived histograms for the online data taking, Tier-0 prompt reconstruction, prompt calibration and analysis activities, for re-reconstruction at Tier-1s and for release validation. At the present usage level the servers currently handle in total around a million authenticated HTTP requests per day. We describe the main features and components of the system, our implementation for web-based interactive rendering, and the server design. We give an overview of the deployment and maintenance procedures. We discuss the main technical challenges and our solutions to them, with emphasis on functionality, long-term robustness and performance.

  14. The CMS electromagnetic calorimeter at the LHC

    NASA Astrophysics Data System (ADS)

    Ryan, M.

    2009-01-01

    The CMS experiment at the CERN Large Hadron Collider has placed great emphasis on precise calorimetry for electrons and photons. The electromagnetic calorimeter (ECAL) contains about 75 000 scintillating lead tungstate crystals that are read out using sophisticated electronics. This paper will describe the ECAL and the experimental factors that influenced the choice of the technologies used in the detector design. The barrel ECAL has been installed into the experiment and installation of the endcaps will commence in early 2008. The pre-calibration and commissioning of these detectors will be described and the current status of the ECAL reviewed. The prospects for the initial operation period in 2008, when beams are first collided in the LHC, will be discussed.

  15. Radiation simulations of the CMS detector

    NASA Astrophysics Data System (ADS)

    Stoddard, Graham J.

    This thesis presents results of recent radiation simulations for the Compact Muon Solenoid detector at the Large Hadron Collider at CERN performed using the Monte Carlo simulation package FLUKA. High statistics simulations with a fine granularity in the detector were carried out using the Condor batch system at the Fermilab LHC Physics Center. In addition, an existing web tool for accessing and displaying simulation data was upgraded. The FLUKA data and previously generated MARS Monte Carlo data can be plotted using 1-D or 2-D plotting functionalities along R and Z, the transverse distance from the beamline and the distance along the beamline, respectively. Comparisons between the data sets have been carried out; the effect of particle transport thresholds in both packages was explored, comparisons with zero magnetic field in the CMS solenoid and full field are made, a model of non-ionizing energy losses is examined, and sensitive areas of interest within the simulation are identified.

  16. Estimating job runtime for CMS analysis jobs

    NASA Astrophysics Data System (ADS)

    Sfiligoi, I.

    2014-06-01

    The basic premise of pilot systems is to create an overlay scheduling system on top of leased resources. And by definition, leases have a limited lifetime, so any job that is scheduled on such resources must finish before the lease is over, or it will be killed and all the computation is wasted. In order to effectively schedule jobs to resources, the pilot system thus requires the expected runtime of the users' jobs. Past studies have shown that relying on user provided estimates is not a valid strategy, so the system should try to make an estimate by itself. This paper provides a study of the historical data obtained from the Compact Muon Solenoid (CMS) experiment's Analysis Operations submission system. Clear patterns are observed, suggesting that making prediction of an expected job lifetime range is achievable with high confidence level in this environment.

  17. Optimizing CMS build infrastructure via Apache Mesos

    NASA Astrophysics Data System (ADS)

    Abdurachmanov, David; Degano, Alessandro; Elmer, Peter; Eulisse, Giulio; Mendez, David; Muzaffar, Shahzad

    2015-12-01

    The Offline Software of the CMS Experiment at the Large Hadron Collider (LHC) at CERN consists of 6M lines of in-house code, developed over a decade by nearly 1000 physicists, as well as a comparable amount of general use open-source code. A critical ingredient to the success of the construction and early operation of the WLCG was the convergence, around the year 2000, on the use of a homogeneous environment of commodity x86-64 processors and Linux. Apache Mesos is a cluster manager that provides efficient resource isolation and sharing across distributed applications, or frameworks. It can run Hadoop, Jenkins, Spark, Aurora, and other applications on a dynamically shared pool of nodes. We present how we migrated our continuous integration system to schedule jobs on a relatively small Apache Mesos enabled cluster and how this resulted in better resource usage, higher peak performance and lower latency thanks to the dynamic scheduling capabilities of Mesos.

  18. PD-1/PD-Ls pathways between CD4(+) T cells and pleural mesothelial cells in human tuberculous pleurisy.

    PubMed

    Yin, Wen; Tong, Zhao-Hui; Cui, Ai; Zhang, Jian-Chu; Ye, Zhi-Jian; Yuan, Ming-Li; Zhou, Qiong; Shi, Huan-Zhong

    2014-03-01

    Programmed death 1 (PD-1), PD-ligand 1 (PD-L1), and PD-L2 have been demonstrated to be involved in tuberculosis immunity, however, the expression and regulation of PD-1/PD-Ls pathways in pleural mesothelial cells (PMCs) and CD4(+) T cells in tuberculous pleural effusion (TPE) have not been investigated. Expression of PD-1 on CD4(+) T cells and expressions of PD-L1 and PD-L2 on PMCs in TPE were determined. The impacts of PD-1/PD-Ls pathways on proliferation, apoptosis, adhesion, and migration of CD4(+) T cells were explored. Concentrations of soluble PD-l, but not of soluble PD-Ls, were much higher in TPE than in serum. Expressions of PD-1 on CD4(+) T cells in TPE were significantly higher than those in blood. Expressions of PD-Ls were much higher on PMCs from TPE when compared with those from transudative effusion. Interferon-γ not only upregulated the expression of PD-1 on CD4(+) T cells, but also upregulated the expressions of PD-Ls on PMCs. Blockage PD-1/PD-Ls pathways abolished the inhibitory effects on proliferation and adhesion activity of CD4(+) T cells induced by PMCs. PD-1/PD-Ls pathways on PMCs inhibited proliferation and adhesion activity of CD4(+) T cells, suggesting that Mycobacterium tuberculosis might exploit PD-1/PD-Ls pathways to evade host cell immune response in human.

  19. Self-tolerance eliminates CD4+ T, but not CD8+ T or B, cells corrupting cancer immunotherapy

    PubMed Central

    Snook, Adam E.; Magee, Michael S.; Schulz, Stephanie; Waldman, Scott A.

    2014-01-01

    Self-tolerance, presumably through elimination of all lineages of self antigen-specific lymphocytes (CD4+ T, CD8+ T and B cells), creates a formidable barrier to cancer immunotherapy. In contrast to this prevailing paradigm, we demonstrate that for some antigens self-tolerance reflects selective elimination of antigen-specific CD4+ T, but preservation of CD8+ T and B, cell populations. Antigen-specific CD4+ T cell tolerance is the primary mechanism restricting immunotherapeutic responses to the endogenous self antigen guanylyl cyclase c (GUCY2C) in colorectal cancer. Although CD4+ T cell tolerance blocks antitumor immunity, it offers a unique solution to the inefficacy of cancer vaccines through recruitment of self antigen-independent CD4+ T cell help. Incorporating foreign antigen-specific MHC class II epitopes into self antigen-targeted vaccines against GUCY2C, as well as vaccines targeting endogenous self antigens in melanoma and breast cancer, reconstituted CD4+ T cell help, revealing the latent functional capacity of self antigen-specific CD8+ T and B cell pools, producing durable antitumor immunity without autoimmunity. Identification of self antigens characterized by selective CD4+ T cell tolerance and abrogation of such tolerance through self antigen-independent T cell help is essential for future immunotherapeutic strategies. PMID:24771148

  20. Analysis of HIV-1- and CMV-specific memory CD4 T-cell responses during primary and chronic infection.

    PubMed

    Harari, Alexandre; Rizzardi, G Paolo; Ellefsen, Kim; Ciuffreda, Donatella; Champagne, Patrick; Bart, Pierre-Alexandre; Kaufmann, Daniel; Telenti, Amalio; Sahli, Roland; Tambussi, Giuseppe; Kaiser, Laurent; Lazzarin, Adriano; Perrin, Luc; Pantaleo, Giuseppe

    2002-08-15

    CD4 T-cell-specific memory antiviral responses to human immunodeficiency virus type 1 (HIV-1) and cytomegalovirus (CMV) were investigated in 16 patients with documented primary HIV-1 infection (4 of the 16 subjects also had primary CMV infection) and compared with those observed in patients with chronic HIV-1 and CMV coinfection. Virus-specific memory CD4 T cells were characterized on the basis of the expression of the chemokine receptor CCR7. HIV-1- and CMV-specific interferon-gamma-secreting CD4 T cells were detected in patients with primary and chronic HIV-1 and CMV coinfection and were mostly contained in the cell population lacking expression of CCR7. The magnitude of the primary CMV-specific CD4 T-cell response was significantly greater than that of chronic CMV infection, whereas there were no differences between primary and chronic HIV-1-specific CD4 T-cell responses. A substantial proportion of CD4(+)CCR7(-) T cells were infected with HIV-1. These results advance the characterization of antiviral memory CD4 T-cell response and the delineation of the potential mechanisms that likely prevent the generation of a robust CD4 T-cell immune response during primary infection.