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Sample records for 4t proton magnetic

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

    NASA Astrophysics Data System (ADS)

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

    2014-02-01

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

  2. 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

  3. Suppressive effects of a proton beam on tumor growth and lung metastasis through the inhibition of metastatic gene expression in 4T1 orthotopic breast cancer model.

    PubMed

    Kwon, Yun-Suk; Lee, Kyu-Shik; Chun, So-Young; Jang, Tae Jung; Nam, Kyung-Soo

    2016-07-01

    A proton beam is a next generation tool to treat intractable cancer. Although the therapeutic effects of a proton beam are well known, the effect on tumor metastasis is not fully described. Here, we investigated the effects of a proton beam on metastasis in highly invasive 4T1 murine breast cancer cells and their orthotopic breast cancer model. Cells were irradiated with 2, 4, 8 or 16 Gy proton beam, and changes in cell proliferation, survival, and migration were observed by MTT, colony forming and wound healing assays. 4T1 breast cancer cell-implanted BALB/c mice were established and the animals were randomly divided into 4 groups when tumor size reached 200 mm3. Breast tumors were selectively irradiated with 10, 20 or 30 Gy proton beam. Breast tumor sizes were measured twice a week, and breast tumor and lung tissues were pathologically observed. Metastasis-regulating gene expression was assessed with quantitative RT-PCR. A proton beam dose-dependently decreased cell proliferation, survival and migration in 4T1 murine breast cancer cells. Also, growth of breast tumors in the 4T1 orthotopic breast cancer model was significantly suppressed by proton beam irradiation without significant change of body weight. Furthermore, fewer tumor nodules metastasized from breast tumor into lung in mice irradiated with 30 Gy proton beam, but not with 10 and 20 Gy, than in control. We observed correspondingly lower expression levels of urokinase plasminogen activator (uPA), uPA receptor, cyclooxygenase (COX)-2, and vascular endothelial growth factor (VEGF), which are important factors in cancer metastasis, in breast tumor irradiated with 30 Gy proton beam. Proton beam irradiation did not affect expressions of matrix metalloproteinase (MMP)-9 and MMP-2. Taken together, the data suggest that, although proton beam therapy is an effective tool for breast cancer treatment, a suitable dose is necessary to prevent metastasis-linked relapse and poor prognosis. PMID:27176787

  4. Chemical Principles Revisited. Proton Magnetic Resonance Spectroscopy.

    ERIC Educational Resources Information Center

    McQuarrie, Donald A.

    1988-01-01

    Discusses how to interpret nuclear magnetic resonance (NMR) spectra and how to use them to determine molecular structures. This discussion is limited to spectra that are a result of observation of only the protons in a molecule. This type is called proton magnetic resonance (PMR) spectra. (CW)

  5. Magnets for high intensity proton synchrotrons

    SciTech Connect

    Jean-Francois Ostiguy, Vladimir Kashikhine and Alexander Makarov

    2002-09-19

    Recently, there has been considerable interest at Fermilab for the Proton Driver, a future high intensity proton machine. Various scenarios are under consideration, including a superconducting linac. Each scenario present some special challenges. We describe here the magnets proposed in a recent study, the Proton Driver Study II, which assumes a conventional warm synchrotron, roughly of the size of the existing FNAL booster, but capable of delivering 380 kW at 8 GeV.

  6. Proton magnetic resonance spectroscopy in multiple sclerosis

    SciTech Connect

    Wolinsky, J.S.; Narayana, P.A.; Fenstermacher, M.J. )

    1990-11-01

    Regional in vivo proton magnetic resonance spectroscopy provides quantitative data on selected chemical constituents of brain. We imaged 16 volunteers with clinically definite multiple sclerosis on a 1.5 tesla magnetic resonance scanner to define plaque-containing volumes of interest, and obtained localized water-suppressed proton spectra using a stimulated echo sequence. Twenty-five of 40 plaque-containing regions provided spectra of adequate quality. Of these, 8 spectra from 6 subjects were consistent with the presence of cholesterol or fatty acids; the remainder were similar to those obtained from white matter of normal volunteers. This early experience with regional proton spectroscopy suggests that individual plaques are distinct. These differences likely reflect dynamic stages of the evolution of the demyelinative process not previously accessible to in vivo investigation.

  7. Imaging Intelligence with Proton Magnetic Resonance Spectroscopy

    ERIC Educational Resources Information Center

    Jung, Rex E.; Gasparovic, Charles; Chavez, Robert S.; Caprihan, Arvind; Barrow, Ranee; Yeo, Ronald A.

    2009-01-01

    Proton magnetic resonance spectroscopy ([to the first power]H-MRS) is a technique for the assay of brain neurochemistry "in vivo." N-acetylaspartate (NAA), the most prominent metabolite visible within the [to the first power]H-MRS spectrum, is found primarily within neurons. The current study was designed to further elucidate NAA-cognition…

  8. Soft x-ray magnetic circular dichroism study of valence and spin states in FeT2O4 (T = V, Cr) spinel oxides

    NASA Astrophysics Data System (ADS)

    Kang, J.-S.; Hwang, Jihoon; Kim, D. H.; Lee, Eunsook; Kim, W. C.; Kim, C. S.; Lee, Han-Koo; Kim, J.-Y.; Han, S. W.; Hong, S. C.; Kim, Bongjae; Min, B. I.

    2013-05-01

    Electronic structures of spinel oxides FeT2O4 (T = V, Cr) have been investigated by employing soft x-ray magnetic circular dichroism (XMCD) and soft x-ray absorption spectroscopy (XAS). XAS reveals that Cr and V ions are trivalent, and that Fe ions are nearly divalent in FeT2O4 (T = V, Cr). Finite XMCD signals are observed in FeV2O4 at T = 80 K, while they are very weak in FeCr2O4. XMCD shows that Fe spins are antiparallel to V and Cr spins, with the V and Cr spins being canted from Fe spins, which suggests a Yafet-Kittel type triangular spin configuration in FeT2O4 (T = V, Cr).

  9. Magnetic monopole catalysis of proton decay

    SciTech Connect

    Marciano, W.J.; Salvino, D.

    1986-09-01

    Catalysis of proton decay by GUT magnetic monopoles (the Rubakov-Callan effect) is discussed. Combining a short-distance cross section calculation by Bernreuther and Craigie with the long-distance velocity dependent distortion factors of Arafune and Fukugita, catalysis rate predictions which can be compared with experiment are obtained. At present, hydrogen rich detectors such as water (H/sub 2/O) and methane (CH/sub 4/) appear to be particularly well suited for observing catalysis by very slow monopoles. 17 refs., 1 fig.

  10. Metabolite specific proton magnetic resonance imaging

    SciTech Connect

    Hurd, R.E.; Freeman, D.M.

    1989-06-01

    An imaging method is described that makes use of proton double quantum nuclear magnetic resonance (NMR) to construct images based on selected metabolites such as lactic acid. The optimization of the method is illustrated in vitro, followed by in vivo determination of lactic acid distribution in a solid tumor model. Water suppression and editing of lipid signals are such that two-dimensional spectra of lactic acid may be obtained from a radiation-induced fibrosarcoma (RIF-1) tumor in under 1 min and lactic acid images from the same tumor in under 1 hr at 2.0 T. This technique provides a fast and reproducible method at moderate magnetic field strength for mapping biologically relevant metabolites.

  11. Proton-Conducting Magnetic Coordination Polymers.

    PubMed

    Biswas, Soumava; Jena, Himanshu Sekhar; Sanda, Suresh; Konar, Sanjit

    2015-09-21

    Three isostructural lanthanide-based two- dimensional coordination polymers (CPs) {[Ln2(L)3(H2O)2]n⋅2n CH3OH)⋅2n H2O} (Ln=Gd(3+) (1), Tb(3+) (2), Dy(3+) (3); H2L=cyclobutane-1,1-dicarboxylic acid) were synthesized by using a low molecular weight dicarboxylate ligand and characterized. Single-crystal structure analysis showed that in complexes 1-3 lanthanide centers are connected by μ3-bridging cyclobutanedicarboxylate ligands along the c axis to form a rod-shaped infinite 1D coordination chain, which is further linked with nearby chains by μ4-connected cyclobutanedicarboxylate ligands to form 2D CPs in the bc plane. Viewing the packing of the complexes down the b axis reveals that the lattice methanol molecules are located in the interlayer space between the adjacent 2D layers and form H-bonds with lattice and coordinated water molecules to form 1D chains. Magnetic properties of complexes 1-3 were thoroughly investigated. Complex 1 exhibits dominant ferromagnetic interaction between two nearby gadolinium centers and also acts as a cryogenic magnetic refrigerant having a significant magnetic entropy change of -ΔSm=32.8 J kg(-1) K(-1) for ΔH=7 T at 4 K (calculated from isothermal magnetization data). Complex 3 shows slow relaxation of magnetization below 10 K. Impedance analysis revealed that the complexes show humidity-dependent proton conductivity (σ=1.5×10(-5) S cm(-1) for 1, σ=2.07×10(-4) S cm(-1) for 2, and σ=1.1×10(-3) S cm(-1) for 3) at elevated temperature (>75 °C). They retain the conductivity for up to 10 h at high temperature and high humidity. Furthermore, the proton conductivity results were correlated with the number of water molecules from the water-vapor adsorption measurements. Water-vapor adsorption studies showed hysteretic and two-step water vapor adsorption (182,000 μL g(-1) for 1, 184,000 μL g(-1) for 2, and 1,874,000 μL g(-1) for 3) in the experimental pressure range. Simulation of

  12. Antibody-Free Magnetic Cell Sorting of Genetically Modified Primary Human CD4+ T Cells by One-Step Streptavidin Affinity Purification

    PubMed Central

    Matheson, Nicholas J.; Peden, Andrew A.; Lehner, Paul J.

    2014-01-01

    Existing methods for phenotypic selection of genetically modified mammalian cells suffer disadvantages of time, cost and scalability and, where antibodies are used to bind exogenous cell surface markers for magnetic selection, typically yield cells coated with antibody-antigen complexes and beads. To overcome these limitations we have developed a method termed Antibody-Free Magnetic Cell Sorting in which the 38 amino acid Streptavidin Binding Peptide (SBP) is displayed at the cell surface by the truncated Low Affinity Nerve Growth Receptor (LNGFRF) and used as an affinity tag for one-step selection with streptavidin-conjugated magnetic beads. Cells are released through competition with the naturally occurring vitamin biotin, free of either beads or antibody-antigen complexes and ready for culture or use in downstream applications. Antibody-Free Magnetic Cell Sorting is a rapid, cost-effective, scalable method of magnetic selection applicable to either viral transduction or transient transfection of cell lines or primary cells. We have optimised the system for enrichment of primary human CD4+ T cells expressing shRNAs and exogenous genes of interest to purities of >99%, and used it to isolate cells following Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 genome editing. PMID:25360777

  13. Tracking Efficiency And Charge Sharing of 3D Silicon Sensors at Different Angles in a 1.4T Magnetic Field

    SciTech Connect

    Gjersdal, H.; Bolle, E.; Borri, M.; Da Via, C.; Dorholt, O.; Fazio, S.; Grenier, P.; Grinstein, S. Hansson, P.; Hasi, J.; Hugging, F.; Jackson, P.; Kenney, C.; Kocian, M.; La Rosa, A.; Mastroberardino, A.; Nordahl, P.; Rivero, F.; Rohne, O.; Sandaker, H.; Sjobaek, K.; /Oslo U. /Prague, Tech. U. /SLAC /Bonn U. /SUNY, Stony Brook /Bonn U. /SLAC

    2012-05-07

    A 3D silicon sensor fabricated at Stanford with electrodes penetrating throughout the entire silicon wafer and with active edges was tested in a 1.4 T magnetic field with a 180 GeV/c pion beam at the CERN SPS in May 2009. The device under test was bump-bonded to the ATLAS pixel FE-I3 readout electronics chip. Three readout electrodes were used to cover the 400 {micro}m long pixel side, this resulting in a p-n inter-electrode distance of {approx} 71 {micro}m. Its behavior was confronted with a planar sensor of the type presently installed in the ATLAS inner tracker. Time over threshold, charge sharing and tracking efficiency data were collected at zero and 15{sup o} angles with and without magnetic field. The latest is the angular configuration expected for the modules of the Insertable B-Layer (IBL) currently under study for the LHC phase 1 upgrade expected in 2014.

  14. Helical Dipole Magnets for Polarized Protons in RHIC

    NASA Astrophysics Data System (ADS)

    Syphers, M.; Courant, E.; Fischer, W.; Luccio, A.; Mariam, F.; Peggs, S.; Pilat, F.; Roser, T.; Tepikian, S.; Tsoupas, N.; Willen, E.; Katayama, T.; Hatanaka, K.; Kawaguchi, T.; Okamura, M.; Tominaka, T.; Wu, H.; Ptitsin, V.; Shatunov, Y.

    1997-05-01

    The Brookhaven Relativistic Heavy Ion Collider (RHIC) will be able to support experiments using polarized proton beams. Siberian Snakes are used to maintain polarization in this high energy superconducting collider. To make efficient use of available space while taking advantage of high field superconducting magnets, 4 Tesla helical dipole magnets will be used. These magnets generate a central dipole field in which the field direction rotates through 360^circ about the longitudinal axis over the length of the device. An arrangement of four such magnets can produce the desired change in the spin direction while keeping the proton orbit outside of the ``Snake'' unaltered. Similar magnet arrangements will be used to produce longitudinal polarization at the two major interaction points in RHIC. The basic requirements and layout of these magnets are described, as well as tolerances on field quality and integrated field strengths. First results of tests of prototype helical magnets will be discussed.

  15. Helical dipole magnets for polarized protons in RHIC

    SciTech Connect

    Syphers, M.; Courant, E.; Fischer, W.

    1997-07-01

    Superconducting helical dipole magnets will be used in the Brookhaven Relativistic Heavy Ion Collider (RHIC) to maintain polarization of proton beams and to perform localized spin rotations at the two major experimental detector regions. Requirements for the helical dipole system are discussed, and magnet prototype work is reported.

  16. Single-Plane Magnetically Focused Elongated Small Field Proton Beams.

    PubMed

    McAuley, Grant A; Slater, James M; Wroe, Andrew J

    2015-08-01

    We previously performed Monte Carlo simulations of magnetically focused proton beams shaped by a single quadrapole magnet and thereby created narrow elongated beams with superior dose delivery characteristics (compared to collimated beams) suitable for targets of similar geometry. The present study seeks to experimentally validate these simulations using a focusing magnet consisting of 24 segments of samarium cobalt permanent magnetic material adhered into a hollow cylinder. Proton beams with properties relevant to clinical radiosurgery applications were delivered through the magnet to a water tank containing a diode detector or radiochromic film. Dose profiles were analyzed and compared with analogous Monte Carlo simulations. The focused beams produced elongated beam spots with high elliptical symmetry, indicative of magnet quality. Experimental data showed good agreement with simulations, affirming the utility of Monte Carlo simulations as a tool to model the inherent complexity of a magnetic focusing system. Compared to target-matched unfocused simulations, focused beams showed larger peak to entrance ratios (26% to 38%) and focused simulations showed a two-fold increase in beam delivery efficiency. These advantages can be attributed to the magnetic acceleration of protons in the transverse plane that tends to counteract the particle outscatter that leads to degradation of peak to entrance performance in small field proton beams. Our results have important clinical implications and suggest rare earth focusing magnet assemblies are feasible and could reduce skin dose and beam number while delivering enhanced dose to narrow elongated targets (eg, in and around the spinal cord) in less time compared to collimated beams. PMID:25414143

  17. On the Importance of Exchangeable NH Protons in Creatine for the Magnetic Coupling of Creatine Methyl Protons in Skeletal Muscle

    NASA Astrophysics Data System (ADS)

    Kruiskamp, M. J.; Nicolay, K.

    2001-03-01

    The methyl protons of creatine in skeletal muscle exhibit a strong off-resonance magnetization transfer effect. The mechanism of this process is unknown. We previously hypothesized that the exchangeable amide/amino protons of creatine might be involved. To test this the characteristics of the creatine magnetization transfer effect were investigated in excised rat hindleg skeletal muscle that was equilibrated in either H2O or D2O solutions containing creatine. The efficiency of off-resonance magnetization transfer to the protons of mobile creatine in excised muscle was similar to that previously reported in intact muscle in vivo. Equilibrating the isolated muscle in D2O solution had no effect on the magnetic coupling to the immobile protons. It is concluded that exchangeable protons play a negligible role in the magnetic coupling of creatine methyl protons in muscle.

  18. Proton magnetic relaxation and internal rotations in tetramethylammonium cadmium chloride

    NASA Technical Reports Server (NTRS)

    Tsang, T.; Utton, D. B.

    1976-01-01

    Nuclear magnetic resonance (NMR) and relaxation studies of the proton spin-lattice relaxation time (PSLRT) and proton second moment (PSM) are reported. Tetramethylammonium cadmium chloride (TMCC) was selected as a diamagnetic member of the isomorphic series, and hence proton data relate directly to the motion of the tetramethylammonium ion in the absence of paramagnetic ions. In the model adopted, the correlation time for hindered motion of one of the methyl groups differs from that of the other three groups in the low-temperature phase below 104 K. PSLRT and PSM values agree closely with experimental data with this model. Crystallographic phase transitions in TMCC occur at 104 K and 119 K according to the PSLRT measurements. Dipolar interactions between adjacent protons account for the PSLR rates below 104 K.

  19. Mercury's Surface Magnetic Field Determined from Proton-Reflection Magnetometry

    NASA Technical Reports Server (NTRS)

    Winslow, Reka M.; Johnson, Catherine L.; Anderson, Brian J.; Gershman, Daniel J.; Raines, Jim M.; Lillis, Robert J.; Korth, Haje; Slavin, James A.; Solomon, Sean C.; Zurbuchen, Thomas H.; Zuber, Maria T.

    2014-01-01

    Solar wind protons observed by the MESSENGER spacecraft in orbit about Mercury exhibit signatures of precipitation loss to Mercury's surface. We apply proton-reflection magnetometry to sense Mercury's surface magnetic field intensity in the planet's northern and southern hemispheres. The results are consistent with a dipole field offset to the north and show that the technique may be used to resolve regional-scale fields at the surface. The proton loss cones indicate persistent ion precipitation to the surface in the northern magnetospheric cusp region and in the southern hemisphere at low nightside latitudes. The latter observation implies that most of the surface in Mercury's southern hemisphere is continuously bombarded by plasma, in contrast with the premise that the global magnetic field largely protects the planetary surface from the solar wind.

  20. Polarization Status of Magnetic Fluctuations at Proton Scales

    NASA Astrophysics Data System (ADS)

    Bruno, Roberto; Telloni, Daniele; D'Amicis, Raffaella; DeMarco, Rossana; Marcucci, Federica

    2016-04-01

    We study the polarization status of magnetic field fluctuations at proton scales looking for possible links between the large-scale and small-scale features of solar wind fluctuations across the frequency break separating fluid and kinetic regimes. The main goal is to correlate the occurrence of proton temperature anisotropy, low proton β∥ values and, magnetic field fluctuations polarization to the particular state of turbulence found within the inertial range. We found clear correlations between each type of polarization, either left or right, and turbulence status. Moreover, for the first time in literature, we show that left-handed and right handed polarized fluctuations occupy different areas of the temperature anisotropy-β∥ plot, as expected for Alfvén Ion Cyclotron and Kinetic Alfvén waves, respectively.

  1. Insulating behavior of magnetic spots in proton-bombarded graphite

    NASA Astrophysics Data System (ADS)

    Schindler, K.; García, N.; Esquinazi, P.; Ohldag, H.

    2008-07-01

    Kelvin probe force microscopy measurements on micrometer small magnetic spots produced by proton bombardment on bulk graphite reveal a charge transfer from the center of the spot to an external ring with potential variation on the order of 50 mV. The total charge in the spot is neutral. The results can be well understood in terms of practically unscreened potentials, an insulating property, although the nonbombarded, surrounding graphite region exhibits good conductance. Scanning transmission x-ray microscopy measurements on magnetic spots prepared on graphitic films reveal similar charge distribution. The insulating behavior is fundamental to understand the magnetism in graphite.

  2. Experimental validation of a Monte Carlo proton therapy nozzle model incorporating magnetically steered protons

    NASA Astrophysics Data System (ADS)

    Peterson, S. W.; Polf, J.; Bues, M.; Ciangaru, G.; Archambault, L.; Beddar, S.; Smith, A.

    2009-05-01

    The purpose of this study is to validate the accuracy of a Monte Carlo calculation model of a proton magnetic beam scanning delivery nozzle developed using the Geant4 toolkit. The Monte Carlo model was used to produce depth dose and lateral profiles, which were compared to data measured in the clinical scanning treatment nozzle at several energies. Comparisons were also made between measured and simulated off-axis profiles to test the accuracy of the model's magnetic steering. Comparison of the 80% distal dose fall-off values for the measured and simulated depth dose profiles agreed to within 1 mm for the beam energies evaluated. Agreement of the full width at half maximum values for the measured and simulated lateral fluence profiles was within 1.3 mm for all energies. The position of measured and simulated spot positions for the magnetically steered beams agreed to within 0.7 mm of each other. Based on these results, we found that the Geant4 Monte Carlo model of the beam scanning nozzle has the ability to accurately predict depth dose profiles, lateral profiles perpendicular to the beam axis and magnetic steering of a proton beam during beam scanning proton therapy.

  3. Experimental validation of a Monte Carlo proton therapy nozzle model incorporating magnetically steered protons.

    PubMed

    Peterson, S W; Polf, J; Bues, M; Ciangaru, G; Archambault, L; Beddar, S; Smith, A

    2009-05-21

    The purpose of this study is to validate the accuracy of a Monte Carlo calculation model of a proton magnetic beam scanning delivery nozzle developed using the Geant4 toolkit. The Monte Carlo model was used to produce depth dose and lateral profiles, which were compared to data measured in the clinical scanning treatment nozzle at several energies. Comparisons were also made between measured and simulated off-axis profiles to test the accuracy of the model's magnetic steering. Comparison of the 80% distal dose fall-off values for the measured and simulated depth dose profiles agreed to within 1 mm for the beam energies evaluated. Agreement of the full width at half maximum values for the measured and simulated lateral fluence profiles was within 1.3 mm for all energies. The position of measured and simulated spot positions for the magnetically steered beams agreed to within 0.7 mm of each other. Based on these results, we found that the Geant4 Monte Carlo model of the beam scanning nozzle has the ability to accurately predict depth dose profiles, lateral profiles perpendicular to the beam axis and magnetic steering of a proton beam during beam scanning proton therapy. PMID:19420426

  4. Protein conformation and proton nuclear-magnetic-resonance chemical shifts.

    PubMed

    Pardi, A; Wagner, G; Wüthrich, K

    1983-12-15

    The nuclear magnetic resonance (NMR) chemical shifts of the polypeptide backbone protons in basic pancreatic trypsin inhibitor from bovine organs and the inhibitors E and K from the venom of Dendroaspis polylepis polylepis have been analyzed. Using the corresponding shifts in model peptides, the chemical shifts observed in the proteins were decomposed into random-coil shifts and conformation-dependent shifts. Correlations between contributions to the latter term and the polypeptide conformation were investigated by using the crystal structure of the bovine inhibitor. In addition to the well-known ring-current effects, a correlation was found between chemical shifts of amide and C alpha protons and the length of the hydrogen bonds formed by these protons with nearby oxygen atoms as acceptor groups. There remain sizeable and as yet unexplained residual conformation shifts. Overall, the present treatment provides a satisfactory qualitative explanation for the outstandingly large shifts of backbone hydrogen atoms in these diamagnetic proteins. PMID:6198174

  5. An improved proton magnetometer for Earth's magnetic field observation

    NASA Astrophysics Data System (ADS)

    Xiao, Chengyu; Zhang, Shuang; Guo, Xin; Fu, Haoyang

    2015-09-01

    As a precision instrument to measure the earth magnetic field, proton magnetometer is widely used in different fields such as geological survey, buried objects detection and earth field variations. Due to poor signal to noise ratio (SNR) of the system, proton magnetometer suffers from low sensitivity which directly affects the performance. In order to increase the sensitivity, we present an improved proton magnetometer. First, the effect of matching resistance on Q value is discussed to enhance SNR, and high matching resistance has been chosen to improve the Q value of the resonant circuit. Second, noise induced by pre-amplifier is investigated in order to obtain low noise signal, and we adopt the JFET with noise figure less than 0.5dB as the pre-amplifier. Third, by using band-pass filter, low-noise output signal is obtained. Fourth, the method of period measurement based on CPLD is employed to measure frequency of the square wave shaped from the output sinusoidal signal. High precision temperature compensate crystal oscillator (TCXO) has been used to improve the frequency measurement accuracy. Last, experimental data is obtained through field measurements. By calculating the standard deviation, the sensitivity of the improved proton magnetometer is 0.15nT for Earth's magnetic field observation. Experimental results show that the new magnetometer is sensitive to earth field measurement.

  6. Magnetic Moment of Proton Drip-Line Nucleus (9)C

    NASA Technical Reports Server (NTRS)

    Matsuta, K.; Fukuda, M.; Tanigaki, M.; Minamisono, T.; Nojiri, Y.; Mihara, M.; Onishi, T.; Yamaguchi, T.; Harada, A.; Sasaki, M.

    1994-01-01

    The magnetic moment of the proton drip-line nucleus C-9(I(sup (pi)) = 3/2, T(sub 1/2) = 126 ms) has been measured for the first time, using the beta-NMR detection technique with polarized radioactive beams. The measure value for the magnetic moment is 1mu(C-9)! = 1.3914 +/- 0.0005 (mu)N. The deduced spin expectation value of 1.44 is unusually larger than any other ones of even-odd nuclei.

  7. Magnetic properties of point defects in proton irradiated diamond

    NASA Astrophysics Data System (ADS)

    Makgato, T. N.; Sideras-Haddad, E.; Ramos, M. A.; García-Hernández, M.; Climent-Font, A.; Zucchiatti, A.; Muñoz-Martin, A.; Shrivastava, S.; Erasmus, R.

    2016-09-01

    We investigate the magnetic properties of ultra-pure type-IIa diamond following irradiation with proton beams of ≈1-2 MeV energy. SQUID magnetometry indicate the formation of Curie type paramagnetism according to the Curie law. Raman and Photoluminescence spectroscopy measurements show that the primary structural features created by proton irradiation are the centers: GR1, ND1, TR12 and 3H. The Stopping and Range of Ions in Matter (SRIM) Monte Carlo simulations together with SQUID observations show a strong correlation between vacancy production, proton fluence and the paramagnetic factor. At an average surface vacancy spacing of ≈1-1.6 nm and bulk (peak) vacancy spacing of ≈0.3-0.5 nm Curie paramagnetism is induced by formation of ND1 centres with an effective magnetic moment μeff~(0.1-0.2)μB. No evidence of long range magnetic ordering is observed in the temperature range 4.2-300 K.

  8. Proton magnetic resonance spectroscopy in oncology: the fingerprints of cancer?

    PubMed Central

    García-Figueiras, Roberto; Baleato-González, Sandra; Padhani, Anwar R; Oleaga, Laura; Vilanova, Joan C; Luna, Antonio; Gómez, Juan Carlos Cobas

    2016-01-01

    Abnormal metabolism is a key tumor hallmark. Proton magnetic resonance spectroscopy (1H-MRS) allows measurement of metabolite concentration that can be utilized to characterize tumor metabolic changes. 1H-MRS measurements of specific metabolites have been implemented in the clinic. This article performs a systematic review of image acquisition and interpretation of 1H-MRS for cancer evaluation, evaluates its strengths and limitations, and correlates metabolite peaks at 1H-MRS with diagnostic and prognostic parameters of cancer in different tumor types. PMID:26712681

  9. Electric and magnetic form factors of the proton

    NASA Astrophysics Data System (ADS)

    Bernauer, J. Â. C.; Distler, M. Â. O.; Friedrich, J.; Walcher, Th.; Achenbach, P.; Ayerbe Gayoso, C.; Böhm, R.; Bosnar, D.; Debenjak, L.; Doria, L.; Esser, A.; Fonvieille, H.; Gómez Rodríguez de la Paz, M.; Friedrich, J. Â. M.; Makek, M.; Merkel, H.; Middleton, D. Â. G.; Müller, U.; Nungesser, L.; Pochodzalla, J.; Potokar, M.; Sánchez Majos, S.; Schlimme, B. Â. S.; Širca, S.; Weinriefer, M.; A1 Collaboration

    2014-07-01

    This paper describes a precise measurement of electron scattering off the proton at momentum transfers of 0.003≲Q2≲1 GeV2. The average point-to-point error of the cross sections in this experiment is ˜0.37%. These data are used for a coherent new analysis together with all world data of unpolarized and polarized electron scattering from the very smallest to the highest momentum transfers so far measured. The extracted electric and magnetic form factors provide new insight into their exact shape, deviating from the classical dipole form, and of structure on top of this gross shape. The data reaching very low Q2 values are used for a new determination of the electric and magnetic radii. An empirical determination of the two-photon-exchange correction is presented. The implications of this correction on the radii and the question of a directly visible signal of the pion cloud are addressed.

  10. ENERGETIC PROTONS, RADIONUCLIDES, AND MAGNETIC ACTIVITY IN PROTOSTELLAR DISKS

    SciTech Connect

    Turner, N. J.; Drake, J. F.

    2009-10-01

    We calculate the location of the magnetically inactive dead zone in the minimum-mass protosolar disk, under ionization scenarios including stellar X-rays, long- or short-lived radionuclide decay, and energetic protons arriving from the general interstellar medium, from a nearby supernova explosion, from the disk corona, or from the corona of the young star. The disk contains a dead zone in all scenarios except those with small dust grains removed and a fraction of the short-lived radionuclides remaining in the gas. All the cases without exception have an 'undead zone' where intermediate resistivities prevent magneto-rotational turbulence while allowing shear-generated large-scale magnetic fields. The mass column in the undead zone is typically greater than the column in the turbulent surface layers. The results support the idea that the dead and undead zones are robust consequences of cold, dusty gas with mass columns exceeding 1000 g cm{sup -2}.

  11. Magnetic Resonance Detection of Individual Proton Spins Using Quantum Reporters

    NASA Astrophysics Data System (ADS)

    Sushkov, A. O.; Lovchinsky, I.; Chisholm, N.; Walsworth, R. L.; Park, H.; Lukin, M. D.

    2014-11-01

    We demonstrate a method of magnetic resonance imaging with single nuclear-spin sensitivity under ambient conditions. Our method employs isolated electronic-spin quantum bits (qubits) as magnetic resonance "reporters" on the surface of high purity diamond. These spin qubits are localized with nanometer-scale uncertainty, and their quantum state is coherently manipulated and measured optically via a proximal nitrogen-vacancy color center located a few nanometers below the diamond surface. This system is then used for sensing, coherent coupling, and imaging of individual proton spins on the diamond surface with angstrom resolution. Our approach may enable direct structural imaging of complex molecules that cannot be accessed from bulk studies. It realizes a new platform for probing novel materials, monitoring chemical reactions, and manipulation of complex systems on surfaces at a quantum level.

  12. Estimation of changes in fitness components and antioxidant defense of Drosophila subobscura (Insecta, Diptera) after exposure to 2.4 T strong static magnetic field.

    PubMed

    Todorović, Dajana; Perić-Mataruga, Vesna; Mirčić, Dejan; Ristić-Djurović, Jasna; Prolić, Zlatko; Petković, Branka; Savić, Tatjana

    2015-04-01

    As an ecological factor, a magnetic field can affect insects causing a wide range of responses. The main purpose of this study was to analyze the fitness components (postembryonic development and viability of individuals) and the antioxidant defense (superoxide dismutase, catalase, and total glutathione) in laboratory strains of Drosophila subobscura, originating from oak and beech forests after exposure to the strong static magnet (2.4 T, VINCY Cyclotron magnet). The first instar larvae were placed near the north pole (N group) or the south pole (S group) of the magnet for 2 h. Oak and beech populations of D. subobscura had longer development time and lower viability in N and S groups compared to controls. These differences were significant only in S group of oak population and in N group of beech population. Total glutathione content was significantly decreased in both exposed groups of oak population, while catalase activity was significantly increased in both exposed groups of beech population. Being significantly decreased in both exposed groups of oak population and significantly increased in S group of beech population in comparison to controls, superoxide dismutase activity was observed in different values. According to the results, it can be stated that applied static magnetic field could be considered a potential stressor influencing the fitness components and antioxidant defense in Drosophila flies. PMID:25475617

  13. Capture and Transport of Laser Accelerated Protons by Pulsed Magnetic Fields: Advancements Toward Laser-Based Proton Therapy

    NASA Astrophysics Data System (ADS)

    Burris-Mog, Trevor J.

    The interaction of intense laser light (I > 10 18 W/cm2) with a thin target foil leads to the Target Normal Sheath Acceleration mechanism (TNSA). TNSA is responsible for the generation of high current, ultra-low emittance proton beams, which may allow for the development of a compact and cost effective proton therapy system for the treatment of cancer. Before this application can be realized, control is needed over the large divergence and the 100% kinetic energy spread that are characteristic of TNSA proton beams. The work presented here demonstrates control over the divergence and energy spread using strong magnetic fields generated by a pulse power solenoid. The solenoidal field results in a parallel proton beam with a kinetic energy spread DeltaE/E = 10%. Assuming that next generation lasers will be able to operate at 10 Hz, the 10% spread in the kinetic energy along with the 23% capture efficiency of the solenoid yield enough protons per laser pulse to, for the first time, consider applications in Radiation Oncology. Current lasers can generate proton beams with kinetic energies up to 67.5 MeV, but for therapy applications, the proton kinetic energy must reach 250 MeV. Since the maximum kinetic energy Emax of the proton scales with laser light intensity as Emax ∝ I0.5, next generation lasers may very well accelerate 250 MeV protons. As the kinetic energy of the protons is increased, the magnetic field strength of the solenoid will need to increase. The scaling of the magnetic field B with the kinetic energy of the protons follows B ∝ E1/2. Therefor, the field strength of the solenoid presented in this work will need to be increased by a factor of 2.4 in order to accommodate 250 MeV protons. This scaling factor seems reasonable, even with present technology. This work not only demonstrates control over beam divergence and energy spread, it also allows for us to now perform feasibility studies to further research what a laser-based proton therapy system

  14. On the outer limit for the expansion of magnetic bottles ejected by solar proton flares

    NASA Technical Reports Server (NTRS)

    Sakurai, K.

    1973-01-01

    Pioneer 6 observations of proton flare ejected magnetic bottles are reported. The SSC geomagnetic storms, electron density distribution near the sun, and Faraday rotation induced by the flares are included. Magnetic bottle speed is discussed.

  15. High latitude proton precipitation and light-ion density profiles during the magnetic storm initial phase

    NASA Technical Reports Server (NTRS)

    Burch, J. L.

    1973-01-01

    Measurements of precipitating protons and light ion densities by experiments on OGO-4 indicate that widespread proton precipitation occurs in predawn hours during the magnetic storm initial phase from the latitude of the high-latitude ion trough, or plasmapause , up to Lambda 75 deg. A softening of the proton spectrum is apparent as the plasmapause is approached. The separation of the low-latitude precipitation boundaries for 7.3 kev and 23.8 kev protons is approximately 1 deg, compared with a 3.6 deg separation which has been computed using the formulas of Gendrin and Eather and Carovillano. Consideration of probable proton drift morphology leads to the conclusion that protons ase injected in predawn hours, with widespread precipitation occurring in the region outside the plasmapause. Protons less energetic than approximately 7 kev drift eastward, while the more energetic protons drift westward, producing the observed dawn-dusk asymmetry for the lower-energy protons.

  16. Quantitative Proton Magnetic Resonance Techniques for Measuring Fat

    PubMed Central

    Harry, Houchun; Kan, Hermien E.

    2014-01-01

    Accurate, precise, and reliable techniques for quantifying body and organ fat distributions are important tools in physiology research. They are critically needed in studies of obesity and diseases involving excess fat accumulation. Proton magnetic resonance methods address this need by providing an array of relaxometry-based (T1, T2) and chemical-shift-based approaches. These techniques can generate informative visualizations of regional and whole-body fat distributions, yield measurements of fat volumes within specific body depots, and quantify fat accumulation in abdominal organs and muscles. MR methods are commonly used to investigate the role of fat in nutrition and metabolism, to measure the efficacy of short and long-term dietary and exercise interventions, to study the implications of fat in organ steatosis and muscular dystrophies, and to elucidate pathophysiological mechanisms in the context of obesity and its comorbidities. The purpose of this review is to provide a summary of mainstream MR strategies for fat quantification. The article will succinctly describe the principles that differentiate water and fat proton signals, summarize advantages and limitations of various techniques, and offer a few illustrative examples. The article will also highlight recent efforts in MR of brown adipose tissue and conclude by briefly discussing some future research directions. PMID:24123229

  17. Proton Nuclear Magnetic Resonance Relaxation Measurements in Frog Muscle

    PubMed Central

    Finch, Edward D.; Homer, Louis D.

    1974-01-01

    Proton nuclear magnetic resonance (NMR) relaxation measurements are reported for frog muscle as a function of temperature and Larmor frequency. Each T1ρ, T2, and T1 measurement covered a time domain sufficient to identify the average relaxation time for most intracellular water. Using regression analysis the data were fit with a model where intracellular water molecules are exchanging between a large compartment in which mobility is similar to ordinary water and a small compartment in which motion is restricted. The regression results suggest that: the restricted compartment exhibits a distribution of motions skewed toward that of free water; the residence time of water molecules in the restricted compartment is approximately 1 ms; and, the activation entropy for some water molecules in the restricted compartment is negative. PMID:4547668

  18. Cross relaxation of the proton magnetization in ammonium compounds

    NASA Astrophysics Data System (ADS)

    Punkkinen, M.; Vuorimäki, A. H.; Ylinen, E. E.

    1990-01-01

    Expressions are derived for the time constants T1D and TSD of the NH 4 protons in tunneling ammonium compounds below the line-width transition temperature. T1D characterizes the speed of the spin-lattice relaxation of the dipolar energy and TSD the speed of the cross relaxation between the A and T symmetry species. The expressions should be valid if all the tunnel splittings between the T species levels are larger than the magnetic dipolar interaction. Predictions are compared with new experimental results on TSD in (NH 4) 2PbCl 6 and with some earlier results on TSD and T1D in (NH 4) 2 SnBr 6 and NH 4ClO 4. They support the conclusion that for T1D> TSD the T levels are nondegenerate, while the condition T1D< TSD refers to at least a partial degeneracy.

  19. Calibration of a compact magnetic proton recoil neutron spectrometer

    NASA Astrophysics Data System (ADS)

    Zhang, Jianfu; Ouyang, Xiaoping; Zhang, Xianpeng; Ruan, Jinlu; Zhang, Guoguang; Zhang, Xiaodong; Qiu, Suizheng; Chen, Liang; Liu, Jinliang; Song, Jiwen; Liu, Linyue; Yang, Shaohua

    2016-04-01

    Magnetic proton recoil (MPR) neutron spectrometer is considered as a powerful instrument to measure deuterium-tritium (DT) neutron spectrum, as it is currently used in inertial confinement fusion facilities and large Tokamak devices. The energy resolution (ER) and neutron detection efficiency (NDE) are the two most important parameters to characterize a neutron spectrometer. In this work, the ER calibration for the MPR spectrometer was performed by using the HI-13 tandem accelerator at China Institute of Atomic Energy (CIAE), and the NDE calibration was performed by using the neutron generator at CIAE. The specific calibration techniques used in this work and the associated accuracies were discussed in details in this paper. The calibration results were presented along with Monte Carlo simulation results.

  20. Brain proton magnetic resonance spectroscopy of alcohol use disorders.

    PubMed

    Meyerhoff, Dieter J

    2014-01-01

    This chapter critically reviews brain proton magnetic resonance spectroscopy ((1)H MRS) studies performed since 1994 in individuals with alcohol use disorders (AUD). We describe the neurochemicals that can be measured in vivo at the most common magnetic field strengths, summarize our knowledge about their general brain functions, and briefly explain some basic human (1)H MRS methods. Both cross-sectional and longitudinal research of individuals in treatment and of treatment-naïve individuals with AUD are discussed and interpreted on the basis of reported neuropathology. As AUDs are highly comorbid with chronic cigarette smoking and illicit substance abuse, we also summarize reports on their respective influences on regional proton metabolite levels. After reviewing research on neurobiologic correlates of relapse and genetic influences on brain metabolite levels, we finish with suggestions on future directions for (1)H MRS studies in AUDs. The review demonstrates that brain metabolic alterations associated with AUDs as well as their cognitive correlates are not simply a consequence of chronic alcohol consumption. Future MR research of AUDs in general has to be better prepared - and supported - to study clinically complex relationships between personality characteristics, comorbidities, neurogenetics, lifestyle, and living environment, as all these factors critically affect an individual's neurometabolic profile. (1)H MRS is uniquely positioned to tackle these complexities by contributing to a comprehensive biopsychosocial profile of individuals with AUD: it can provide non-invasive biochemical information on select regions of the brain at comparatively low overall cost for the ultimate purpose of informing more efficient treatments of AUDs. PMID:25307583

  1. Rabi, the proton magnetic moment, and the ¡2-wire¢ magnet, 1931-34

    NASA Astrophysics Data System (ADS)

    Forman, Paul

    2001-04-01

    With the assistance of Gregory Breit, I.I. Rabi, at Columbia University, worked out in 1931 a method to determine the spin (not the magnetic moment) of atomic nuclei by deflecting an atomic beam of the isotope in question in a weak, but long, inhomogeneous magnetic field. Crucial to this method was that it required no exact knowledge of that field. When the sensational result: p = 2.5:_Bohr(m_e/m_p) from Otto Stern's deflection of a beam of hydrogen molecules in a strong magnetic field became known late in 1932, its confirmation by another laboratory, preferably by another method, seemed urgent. No one else had the refined technique to reproduce Stern's experiment. But because the hydrogen electronic wave function was known, the Breit Rabi technique was susceptible of extension in this case to the measurement of the magnetic moment of the proton but only with accurate knowledge of the magnetic field and field gradient traversed by the atomic hydrogen beam. To this end Rabi introduced the '2 wire' magnet, producing a weak field and uniform gradient that could be calculated rather than measured. This field configuration quickly came to be used in all magnetic deflection experiments in Rabi's laboratory, first as produced directly by electric currents, and subsequently as emulated in iron electromagnets in order to achieve the higher magnetic fields required by molecular beam magnetic resonance experiments from 1937 onward.

  2. Rabi, the proton magnetic moment, and the ‘2-wire' magnet, 1931-34

    NASA Astrophysics Data System (ADS)

    Forman, Paul

    2001-04-01

    With the assistance of Gregory Breit, I.I. Rabi, at Columbia University, worked out in 1931 a method to determine the spin (not the magnetic moment) of atomic nuclei by deflecting an atomic beam of the isotope in question in a weak, but long, inhomogeneous magnetic field. Crucial to this method was that it required no exact knowledge of that field. When the sensational result -- µp = 2.5µ_Bohr(m_e/m_p) -- from Otto Stern's deflection of a beam of hydrogen molecules in a strong magnetic field became known late in 1932, its confirmation by another laboratory, preferably by another method, seemed urgent. No one else had the refined technique to reproduce Stern's experiment. But because the hydrogen electronic wave function was known, the Breit-Rabi technique was susceptible of extension in this case to the measurement of the magnetic moment of the proton - - but only with accurate knowledge of the magnetic field and field gradient traversed by the atomic hydrogen beam. To this end Rabi introduced the '2-wire' magnet, producing a weak field and uniform gradient that could be calculated rather than measured. This field configuration quickly came to be used in all magnetic deflection experiments in Rabi's laboratory, first as produced directly by electric currents, and subsequently as emulated in iron electromagnets in order to achieve the higher magnetic fields required by molecular beam magnetic resonance experiments from 1937 onward.

  3. Proton Magnetic Resonance Spectroscopy in Adults with Childhood Lead Exposure

    PubMed Central

    Cecil, Kim M.; Dietrich, Kim N.; Altaye, Mekibib; Egelhoff, John C.; Lindquist, Diana M.; Brubaker, Christopher J.; Lanphear, Bruce P.

    2011-01-01

    Background Childhood lead exposure adversely affects neurodevelopment. However, few studies have examined changes in human brain metabolism that may underlie known adverse cognitive and behavioral outcomes. Objective We examined the association between mean childhood blood lead levels and in vivo brain metabolite concentrations as adults, determined by proton magnetic resonance spectroscopy (MRS) in a birth cohort with documented low-to-moderate lead exposure. Methods Adult participants from the Cincinnati Lead Study [n = 159; mean age (± SD), 20.8 ± 0.9 years] completed a quantitative, short-echo proton MRS protocol evaluating seven regions to determine brain concentrations of N-acetyl aspartate (NAA), creatine and phosphocreatine (Cr), cholines (Cho), myo-inositol, and a composite of glutamate and glutamine (GLX). Correlation and multiple linear regression analyses were conducted. Results Mean childhood blood lead levels were associated with regionally specific brain metabolite concentrations adjusted for age at imaging and Full-Scale intelligence quotient. Adjusted analyses estimated for a unit (micrograms per deciliter) increase in mean childhood blood lead concentrations, a decrease of NAA and Cr concentration levels in the basal ganglia, a decrease of NAA and a decrease of Cho concentration levels in the cerebellar hemisphere, a decrease of GLX concentration levels in vermis, a decrease of Cho and a decrease of GLX concentration levels in parietal white matter, and a decrease of Cho concentration levels in frontal white matter. Conclusions Gray-matter NAA reductions associated with increasing childhood blood lead levels suggest that sustained childhood lead exposure produces an irreversible pattern of neuronal dysfunction, whereas associated white-matter choline declines indicate a permanent alteration to myelin architecture. PMID:20947467

  4. Proton magnetic resonance spectroscopy changes after antipsychotic treatment.

    PubMed

    Szulc, Agata; Galinska-Skok, Beata; Waszkiewicz, Napoleon; Bibulowicz, Daniel; Konarzewska, Beata; Tarasow, Eugeniusz

    2013-01-01

    Proton magnetic resonance spectroscopy ((1)H MRS) enables the observation of brain function in vivo. Several brain metabolites can be measured by the means of (1)H MRS: N-acetylaspartate (NAA), choline containing compounds (Cho), myo-inositol (mI) and glutamate (Glu), glutamine (Gln) and GABA (together as Glx complex or separately). (1)H MRS measures have been found to be abnormal in psychotic disorders such as schizophrenia. Here we specifically review the influence exerted by antipsychotic drugs on brain metabolism, as detected by (1)H MRS. We systematically reviewed the available literature and uncovered 27 studies, 16 before-after treatment and 11 cross-sectional. Most of them addressed the effects of antipsychotics in schizophrenia and mainly focusing on NAA alterations. Follow up studies indicated antipsychotic drugs may act by increasing NAA levels in selected brain areas (the frontal lobe and thalamus), especially during the short-time observation. This phenomenon seems to vanish after longer observation. Other studies indicated that glutamate measures are decreasing along with the duration of the disease, suggesting both a neurodegenerative process present in schizophrenic brain as well as an influence of antipsychotics. The above results were reviewed according to the most recent theories in the field accounting for the impact of antipsychotics (1)HMRS measures. PMID:23157634

  5. Proton nuclear magnetic resonance studies on brain edema

    SciTech Connect

    Naruse, S.; Horikawa, Y.; Tanaka, C.; Hirakawa, K.; Nishikawa, H.; Yoshizaki, K.

    1982-06-01

    The water in normal and edematous brain tissues of rats was studied by the pulse nuclear magnetic resonance (NMR) technique, measuring the longitudinal relaxation time (T1) and the transverse relaxation time (T2). In the normal brain, T1 and T2 were single components, both shorter than in pure water. Prolongation and separation of T2 into two components, one fast and one slow, were the characteristic findings in brain edema induced by both cold injury and triethyl tin (TET), although some differences between the two types of edema existed in the content of the lesion and in the degree of changes in T1 and T2 values. Quantitative analysis of T1 and T2 values in their time course relating to water content demonstrated that prolongation of T1 referred to the volume of increased water in tissues examined, and that two phases of T2 reflected the distribution and the content of the edema fluid. From the analysis of the slow component of T2 versus water content during edema formation, it was demonstrated that the increase in edema fluid was steady, and its content was constant during formation of TET-induced edema. On the contrary, during the formation of cold-injury edema, water-rich edema fluid increased during the initial few hours, and protein-rich edema fluid increased thereafter. It was concluded that proton NMR relaxation time measurements may provide new understanding in the field of brain edema research.

  6. Magnetic quadrupoles lens for hot spot proton imaging in inertial confinement fusion

    NASA Astrophysics Data System (ADS)

    Teng, J.; Gu, Y. Q.; Chen, J.; Zhu, B.; Zhang, B.; Zhang, T. K.; Tan, F.; Hong, W.; Zhang, B. H.; Wang, X. Q.

    2016-08-01

    Imaging of DD-produced protons from an implosion hot spot region by miniature permanent magnetic quadrupole (PMQ) lens is proposed. Corresponding object-image relation is deduced and an adjust method for this imaging system is discussed. Ideal point-to-point imaging demands a monoenergetic proton source; nevertheless, we proved that the blur of image induced by proton energy spread is a second order effect therefore controllable. A proton imaging system based on miniature PMQ lens is designed for 2.8 MeV DD-protons and the adjust method in case of proton energy shift is proposed. The spatial resolution of this system is better than 10 μm when proton yield is above 109 and the spectra width is within 10%.

  7. Proton flare and magnetic storm effect in the vicinity of the Earth

    NASA Technical Reports Server (NTRS)

    Nealy, J. E.; Wilson, J. W.; Shea, M. A.; Smart, D. F.

    1994-01-01

    We have developed a model and associated computational procedure for estimating energetic proton exposures during a major solar proton event that occur in combination with a large magnetic storm. Transmission functions for solar protons are computed using geomagnetic vertical cutoff data for quiescent amd disturbed conditions. Predicted exposures in low altitude polar orbit are found to be orders of magnitude greater for severe magnetic storm conditions than are corresponding exposures in the absence of major disturbances. We examine the response scenario for the events of November 1960 as an example.

  8. Carbon-13 and proton magnetic resonance of mouse muscle.

    PubMed Central

    Fung, B M

    1977-01-01

    It is shown that roughly 4 mmol carbon atoms/g mouse muscle can give rise to a "high resolution" 13C NMR spectrum. From the 13C spectrum, it is estimated that the protons from mobile organic molecules or molecular segments amount to 6-8%of total nonrigid protons (organic plus water) in muscle. Their spin-spin relaxation times (T2) are of the order of 0.4-2 ms. At 37 degrees C, the proton spin-echo decay of mouse muscle changes rapidly with time after death, while that of mouse brain does not. PMID:890043

  9. High-latitude proton precipitation and light ion density profiles during the magnetic storm initial phase.

    NASA Technical Reports Server (NTRS)

    Burch, J. L.

    1973-01-01

    Measurements of precipitating protons and light ion densities by experiments on Ogo 4 indicate that widespread proton precipitation occurs in predawn hours during the magnetic storm initial phase from the latitude of the high-latitude ion trough, or plasmapause, up to latitudes greater than 75 deg. A softening of the proton spectrum is apparent as the plasmapause is approached. The separation of the low-latitude precipitation boundaries for 7.3-keV and 23.8-keV protons is less than about 1 deg, compared with a 3.6-deg separation that has been computed by using the formulas of Gendrin and Eather and Carovillano. Consideration of probable proton drift morphology leads to the conclusion that protons are injected in predawn hours, widespread precipitation occurring in the region outside the plasmapause. Protons less energetic than 7 keV drift eastward, whereas the more energetic protons drift westward, producing the observed dawn-dusk asymmetry for the lower-energy protons.

  10. Retention of configuration in nucleophilic vinylic halide substitution - Proton magnetic resonance spectra of cis- and trans- beta-styryldiphenylphosphine oxides.

    NASA Technical Reports Server (NTRS)

    Aguiar, A. M.; Daigle, D.

    1965-01-01

    Cis- and trans-beta-bromostyrene reaction with lithium diphenylphosphide in tetrahydrofuran producing cis- and trans-beta- styryldiphenylphosphine, discussing proton magnetic resonance and configuration retention

  11. WE-D-17A-04: Magnetically Focused Proton Irradiation of Small Volume Targets

    SciTech Connect

    McAuley, G; Slater, J; Wroe, A

    2014-06-15

    Purpose: To explore the advantages of magnetic focusing for small volume proton irradiations and the potential clinical benefits for radiosurgery targets. The primary goal is to create narrow elongated proton beams of elliptical cross section with superior dose delivery characteristics compared to current delivery modalities (eg, collimated beams). In addition, more general beam shapes are also under investigation. Methods: Two prototype magnets consisting of 24 segments of samarium-cobalt (Sm2Co17) permanent magnetic material adhered into hollow cylinders were manufactured for testing. A single focusing magnet was placed on a positioning track on our Gantry 1 treatment table and 15 mm diameter proton beams with energies and modulation relevant to clinical radiosurgery applications (127 to 186 MeV, and 0 to 30 mm modulation) were delivered to a terminal water tank. Beam dose distributions were measured using a PTW diode detector and Gafchromic EBT2 film. Longitudinal and transverse dose profiles were analyzed and compared to data from Monte Carlo simulations analogous to the experimental setup. Results: The narrow elongated focused beam spots showed high elliptical symmetry indicating high magnet quality. In addition, when compared to unfocused beams, peak-to-entrance depth dose ratios were 11 to 14% larger (depending on presence or extent of modulation), and minor axis penumbras were 11 to 20% smaller (again depending on modulation) for focused beams. These results suggest that the use of rare earth magnet assemblies is practical and could improve dose-sparing of normal tissue and organs at risk while delivering enhanced dose to small proton radiosurgery targets. Conclusion: Quadrapole rare earth magnetic assemblies are a promising and inexpensive method to counteract particle out scatter that tends to degrade the peak to entrance performance of small field proton beams. Knowledge gained from current experiments will inform the design of a prototype treatment

  12. An analytical solution to proton Bragg peak deflection in a magnetic field.

    PubMed

    Wolf, Russell; Bortfeld, Thomas

    2012-09-01

    The role of MR imaging for image-guided radiation therapy (IGRT) is becoming more and more important thanks to the excellent soft tissue contrast offered by MRI. Hybrid therapy devices with integrated MRI scanners are under active development for x-ray therapy. The combination of proton therapy with MRI imaging has only been investigated at the theoretical or conceptual level. Of concern is the deflection of the proton beam in the homogeneous magnetic field. A previous publication has come to the conclusion that the impact of a 0.5 T magnetic field on the dose distribution for proton therapy is very small and lateral deflections stay well below 2 mm. The purpose of this study is to provide new insights into the effects of magnetic fields on a proton beam coming to rest in a patient. We performed an analytical calculation of the lateral deflection of protons with initial energies between 50 MeV and 250 MeV, perpendicular to the beam direction and the magnetic field. We used a power-law range-energy relationship and the Lorentz force in both relativistic and non-relativistic conditions. Calculations were done for protons coming to rest in water or soft tissue, and generalized to other uniform and non-uniform media. Results were verified by comparisons with numerical calculations and Monte Carlo simulations. A key result of our calculations is that the maximum lateral deflection at the end of range is proportional to the third power of the initial energy. Accordingly, due to the strong dependence on the energy, even a relatively small magnetic field of 0.5 T will cause a deflection of the proton beam by 1 cm at the end of range of a 200 MeV beam. The maximum deflection at 200 MeV is more than 10 times larger than that of a 90 MeV beam. Relativistic corrections of the deflection are generally small but they can become non-negligible at higher energies around 200 MeV and above. Contrary to previous findings, the lateral deflection of a proton beam can be significant (1

  13. An analytical solution to proton Bragg peak deflection in a magnetic field

    NASA Astrophysics Data System (ADS)

    Wolf, Russell; Bortfeld, Thomas

    2012-09-01

    The role of MR imaging for image-guided radiation therapy (IGRT) is becoming more and more important thanks to the excellent soft tissue contrast offered by MRI. Hybrid therapy devices with integrated MRI scanners are under active development for x-ray therapy. The combination of proton therapy with MRI imaging has only been investigated at the theoretical or conceptual level. Of concern is the deflection of the proton beam in the homogeneous magnetic field. A previous publication has come to the conclusion that the impact of a 0.5 T magnetic field on the dose distribution for proton therapy is very small and lateral deflections stay well below 2 mm. The purpose of this study is to provide new insights into the effects of magnetic fields on a proton beam coming to rest in a patient. We performed an analytical calculation of the lateral deflection of protons with initial energies between 50 MeV and 250 MeV, perpendicular to the beam direction and the magnetic field. We used a power-law range-energy relationship and the Lorentz force in both relativistic and non-relativistic conditions. Calculations were done for protons coming to rest in water or soft tissue, and generalized to other uniform and non-uniform media. Results were verified by comparisons with numerical calculations and Monte Carlo simulations. A key result of our calculations is that the maximum lateral deflection at the end of range is proportional to the third power of the initial energy. Accordingly, due to the strong dependence on the energy, even a relatively small magnetic field of 0.5 T will cause a deflection of the proton beam by 1 cm at the end of range of a 200 MeV beam. The maximum deflection at 200 MeV is more than 10 times larger than that of a 90 MeV beam. Relativistic corrections of the deflection are generally small but they can become non-negligible at higher energies around 200 MeV and above. Contrary to previous findings, the lateral deflection of a proton beam can be significant (1

  14. Magnetic field measurements in laser-produced plasmas via proton deflectometry

    SciTech Connect

    Cecchetti, C. A.; Borghesi, M.; Kar, S.; Macchi, A.; Romagnani, L.; Wilson, P. A.; Fuchs, J.; Antici, P.; Jung, R.; Osterholtz, J.; Pipahl, C. A.; Willi, O.; Schiavi, A.; Notley, M.; Neely, D.

    2009-04-15

    Large magnetic fields generated during laser-matter interaction at irradiances of {approx}5x10{sup 14} W cm{sup -2} have been measured using a deflectometry technique employing MeV laser-accelerated protons. Azimuthal magnetic fields were identified unambiguously via a characteristic proton deflection pattern and found to have an amplitude of {approx}45 T in the outer coronal region. Comparison with magnetohydrodynamic simulations confirms that in this regime the {nabla}-vectorT{sub e}x{nabla}-vectorn{sub e} source is the main field generation mechanism, while additional terms are negligible.

  15. Magnetic Resonance Studies of Proton Loss from Carotenoid Radical Cations

    SciTech Connect

    Kispert, Lowell D; Focsan, A Ligia; Konovalova, Tatyana A; Lawrence, Jesse; Bowman, Michael K; Dixon, David A; Molnar, Peter; Deli, Jozsef

    2007-06-11

    Carotenoids, intrinsic components of reaction centers and pigment-protein complexes in photosynthetic membranes, play a photoprotective role and serve as a secondary electron donor. Before optimum use of carotenoids can be made in artificial photosynthetic systems, their robust nature in living materials requires extensive characterization of their electron transfer, radical trapping ability, stability, structure in and on various hosts, and photochemical behavior. Pulsed ENDOR and 2D-HYSCORE studies combined with DFT calculations reveal that photo-oxidation of natural zeaxanthin (I) and violaxanthin (II) on silica-alumina produces not only the carotenoid radical cations (Car•+) but also neutral radicals (#Car•) by proton loss from the methyl groups at positions 5 or 5', and possibly 9 or 9' and 13 or 13'. Notably, the proton loss favored in I at the 5 position by DFT calculations, is unfavorable in II due to the epoxide at the 5, 6 position. DFT calculations predict the isotropic methyl proton couplings of 8-10 MHz for Car•+ which agree with the ENDOR for carotenoid α-conjugated radical cations. Large α-proton hyperfine coupling constants (>10 MHz) determined from HYSCORE are assigned from the DFT calculations to neutral carotenoid radicals. Proton loss upon photolysis was also examined as a function of carotenoid polarity [Lycopene (III) versus 8'-apo-β-caroten-8'-al (IV)]; hydrogen bonding [Lutein (V) versus III]; host [silica-alumina versus MCM-41 molecular sieve]; and substituted metal in MCM-41. Loss of H+ from the 5(5'), 9(9') or 13(13') methyl positions has importance in photoprotection. Photoprotection involves nonphotochemical quenching (NPQ) in which 1Ch1* decays via energy transfer to the carotenoid which returns to the ground state by thermal dissipation; or via electron transfer to form a charge transfer state (I •+…Chl•-), lower in energy than 1Chl*. Formation of I •+ results in bond lengthening, a mechanism for nonradiative energy

  16. Proton-nuclear magnetic resonance relaxation times in brain edema

    SciTech Connect

    Kamman, R.L.; Go, K.G.; Berendsen, H.J. )

    1990-01-01

    Proton relaxation times of protein solutions, bovine brain, and edematous feline brain tissue were studied as a function of water concentration, protein concentration, and temperature. In accordance with the fast proton exchange model for relaxation, a linear relation could be established between R1 and the inverse of the weight fraction of tissue water. This relation also applied to R2 of gray matter and of protein solutions. No straightforward relation with water content was found for R2 of white matter. Temperature-dependent studies indicated that in this case, the slow exchange model for relaxation had to be applied. The effect of macromolecules in physiological relevant concentrations on the total relaxation behavior of edematous tissue was weak. Total water content changes predominantly affected the relaxation rates. The linear relation may have high clinical potential for assessment of the status of cerebral edema on the basis of T1 and T2 readings from MR images.

  17. Solar wind proton reflection by lunar crustal magnetic fields observed at low altitude

    NASA Astrophysics Data System (ADS)

    Nishino, M. N.; Fujimoto, M.; Tsunakawa, H.; Saito, Y.; Yokota, S.; Shibuya, H.; Matsushima, M.; Shimizu, H.; Takahashi, F.

    2012-12-01

    We study interaction between the solar wind flow and lunar crustal magnetic fields observed at lower altitudes by SELENE (Kaguya), predominantly focusing on proton reflection above strong crustal fields. Several studies revealed interaction between the solar wind and the Moon, while detailed observation at low altitude including ion measurements has been hardly reported yet. Previous observations at higher altitude revealed that the solar wind protons are not reflected toward the sun but deflected downstream around the solar wind flow direction. Here we report detailed observations of solar wind proton reflection/deflection observed above South Pole-Aitken (SPA) basin at low altitude (typically, lower than 30 km) and at several solar zenith angles. Above wide crustal fields inside the SPA basin, a large amount of incident solar wind protons are deflected and sometimes reflected to come back sunward; in particular, the sunward proton beams are observed at lower solar zenith angle regions. The reflected/deflected protons at times consist of two (or more-than-two) separate components that have been mirror-reflected at different crustal fields. Our result shows that the mirror reflection of incident protons takes place at the altitude much lower than the spacecraft orbit, and suggests that strong compression of the crustal fields at lower solar zenith angle and at lower altitude by the solar wind dynamic pressure is essential.

  18. The proton nuclear magnetic shielding tensors in biphenyl: experiment and theory.

    PubMed

    Schönborn, Frank; Schmitt, Heike; Zimmermann, Herbert; Haeberlen, Ulrich; Corminboeuf, Clémence; Grossmann, Gisbert; Heine, Thomas

    2005-07-01

    Line-narrowing multiple pulse techniques are applied to a spherical sample crystal of biphenyl. The 10 different proton shielding tensors in this compound are determined. The accuracy level for the tensor components is 0.3 ppm. The assignment of the measured tensors to the corresponding proton sites is given careful attention. Intermolecular shielding contributions are calculated by the induced magnetic point dipole model with empirical atom and bond susceptibilities (distant neighbours) and by a new quantum chemical method (near neighbours). Subtracting the intermolecular contributions from the (correctly assigned) measured shielding tensors leads to isolated-molecule shielding tensors for which there are symmetry relations. Compliance to these relations is the criterion for the correct assignment. The success of this program indicates that intermolecular proton shielding contributions can be calculated to better than 0.5 ppm. The isolated-molecule shielding tensors obtained from experiment and calculated intermolecular contributions are compared with isolated-molecule quantum chemical results. Expressed in the icosahedral tensor representation, the rms differences of the respective tensor components are below 0.5 ppm for all proton sites in biphenyl. In the isolated molecule, the least shielded direction of all protons is the perpendicular to the molecular plane. For the para proton, the intermediate principal direction is along the C-H bond. It is argued that these relations also hold for the protons in the isolated benzene molecule. PMID:15949748

  19. Fundamental investigations of supported monometallic and bimetallic catalysts by proton magnetic resonance spectroscopy

    SciTech Connect

    Wu, Xi.

    1990-09-21

    Proton magnetic resonance spectroscopy, or nuclear magnetic resonance (NMR) of hydrogen, has been applied to investigate silica-supported Group VIII monometallic and Group VIII-Group IB bimetallic catalysts and alumina- and silica-supported platinum-rhenium bimetallic catalysts. Two adsorbed states of hydrogen, i.e., irreversible and reversible hydrogen, on the surfaces of monometallic Ru, Pt, and Cu particles and bimetallic Ru-Group Ib, Pt-Group Ib, and Pt-Re particles were observed directly via proton NMR. The same amounts of the irreversible hydrogen adsorbed on pure Ru catalysts were measured by both proton NMR and the volumetric technique. The electronic environments on surfaces of monometallic catalysts are sensitive to changes in metal dispersion, state of adsorbed hydrogen, and residual chlorine. Surface compositions for the Ru--Cu and Pt--Cu bimetallic catalysts were determined by NMR of adsorbed hydrogen. 297 refs., 96 figs., 19 tabs.

  20. In vivo1H NMR spectroscopy of the human brain at 9.4 T: Initial results

    NASA Astrophysics Data System (ADS)

    Deelchand, Dinesh Kumar; Moortele, Pierre-François Van de; Adriany, Gregor; Iltis, Isabelle; Andersen, Peter; Strupp, John P.; Thomas Vaughan, J.; Uğurbil, Kâmil; Henry, Pierre-Gilles

    2010-09-01

    In vivo proton NMR spectroscopy allows non-invasive detection and quantification of a wide range of biochemical compounds in the brain. Higher field strength is generally considered advantageous for spectroscopy due to increased signal-to-noise and increased spectral dispersion. So far 1H NMR spectra have been reported in the human brain up to 7 T. In this study we show that excellent quality short echo time STEAM and LASER 1H NMR spectra can be measured in the human brain at 9.4 T. The information content of the human brain spectra appears very similar to that measured in the past decade in rodent brains at the same field strength, in spite of broader linewidth in human brain. Compared to lower fields, the T1 relaxation times of metabolites were slightly longer while T2 relaxation values of metabolites were shorter (<100 ms) at 9.4 T. The linewidth of the total creatine (tCr) resonance at 3.03 ppm increased linearly with magnetic field (1.35 Hz/T from 1.5 T to 9.4 T), with a minimum achievable tCr linewidth of around 12.5 Hz at 9.4 T. At very high field, B0 microsusceptibility effects are the main contributor to the minimum achievable linewidth.

  1. Glutamatergic Effects of Divalproex in Adolescents with Mania: A Proton Magnetic Resonance Spectroscopy Study

    ERIC Educational Resources Information Center

    Strawn, Jeffrey R.; Patel, Nick C.; Chu, Wen-Jang; Lee, Jing-Huei; Adler, Caleb M.; Kim, Mi Jung; Bryan, Holly S.; Alfieri, David C.; Welge, Jeffrey A.; Blom, Thomas J.; Nandagopal, Jayasree J.; Strakowski, Stephen M.; DelBello, Melissa P.

    2012-01-01

    Objectives: This study used proton magnetic resonance spectroscopy ([superscript 1]H MRS) to evaluate the in vivo effects of extended-release divalproex sodium on the glutamatergic system in adolescents with bipolar disorder, and to identify baseline neurochemical predictors of clinical remission. Method: Adolescents with bipolar disorder who were…

  2. Evaluation of brain edema using magnetic resonance proton relaxation times

    SciTech Connect

    Fu, Y.; Tanaka, K.; Nishimura, S. )

    1990-01-01

    Experimental and clinical studies on the evaluation of water content in cases of brain edema were performed in vivo, using MR proton relaxation times (longitudinal relaxation time, T1; transverse relaxation time, T2). Brain edema was produced in the white matter of cats by the direct infusion method. The correlations between proton relaxation times obtained from MR images and the water content of white matter were studied both in autoserum-infused cats and in saline-infused cats. The correlations between T1 as well as T2 and the water content in human vasogenic brain edema were also examined and compared with the data obtained from the serum group. T1 and T2 showed good correlations with the water content of white matter not only in the experimental animals but also in the clinical cases. The quality of the edema fluid did not influence relaxation time and T1 seemed to represent almost solely the water content of the tissue. T2, however, was affected by the nature of existence of water and was more sensitive than T1 in detecting extravasated edema fluid. It seems feasible therefore to evaluate the water content of brain edema on the basis of T1 values.

  3. The effect of magnetically induced linear aggregates on proton transverse relaxation rates of aqueous suspensions of polymer coated magnetic nanoparticles

    NASA Astrophysics Data System (ADS)

    Saville, Steven L.; Woodward, Robert C.; House, Michael J.; Tokarev, Alexander; Hammers, Jacob; Qi, Bin; Shaw, Jeremy; Saunders, Martin; Varsani, Rahi R.; St Pierre, Tim G.; Mefford, O. Thompson

    2013-02-01

    It has been recently reported that for some suspensions of magnetic nanoparticles the transverse proton relaxation rate, R2, is dependent on the time that the sample is exposed to an applied magnetic field. This time dependence has been linked to the formation of linear aggregates or chains in an applied magnetic field via numerical modeling. It is widely known that chain formation occurs in more concentrated ferrofluids systems and that this has an affect on the ferrofluid properties. In this work we examine the relationships between colloidal stability, the formation of these linear structures, and changes observed in the proton transverse relaxation rate of aqueous suspensions of magnetic particles. A series of iron oxide nanoparticles with varying stabilizing ligand brush lengths were synthesized. These systems were characterized with dynamic light scattering, transmission electron microscopy, dark-field optical microscopy, and proton transverse relaxation rate measurements. The dark field optical microscopy and R2 measurements were made in similar magnetic fields over the same time scale so as to correlate the reduction of the transverse relaxivity with the formation of linear aggregates. Our results indicate that varying the ligand length has a direct effect on the colloidal arrangement of the system in a magnetic field, producing differences in the rate and size of chain formation, and hence systematic changes in transverse relaxation rates over time. With increasing ligand brush length, attractive inter-particle interactions are reduced, which results in slower aggregate formation and shorter linear aggregate length. These results have implications for the stabilization, characterization and potentially the toxicity of magnetic nanoparticle systems used in biomedical applications.It has been recently reported that for some suspensions of magnetic nanoparticles the transverse proton relaxation rate, R2, is dependent on the time that the sample is exposed to

  4. Ultrafast proton radiography of the magnetic fields generated by a laser-driven coil current

    NASA Astrophysics Data System (ADS)

    Gao, Lan; Ji, Hantao; Fiksel, Gennady; Fox, William; Evans, Michelle; Alfonso, Noel

    2016-04-01

    Magnetic fields generated by a current flowing through a U-shaped coil connecting two copper foils were measured using ultrafast proton radiography. Two ˜1.25 kJ, 1-ns laser pulses propagated through laser entrance holes in the front foil and were focused to the back foil with an intensity of ˜3 × 1016 W/cm2. The intense laser-solid interaction induced a high voltage between the copper foils and generated a large current in the connecting coil. The proton data show ˜40-50 T magnetic fields at the center of the coil ˜3-4 ns after laser irradiation. The experiments provide significant insight for future target designs that aim to develop a powerful source of external magnetic fields for various applications in high-energy-density science.

  5. Development of a compact magnetic proton recoil spectrometer for measurement of deuterium-tritium neutrons.

    PubMed

    Zhang, Jianfu; Ouyang, Xiaoping; Qiu, Suizheng; Zhang, Guoguang; Ruan, Jinlu; Zhang, Xiaodong; Zhang, Xianpeng; Yang, Shaohua; Song, Jiwen; Liu, Linyue; Li, Hongyun

    2015-12-01

    A new compact magnetic proton recoil (MPR) neutron spectrometer has been designed for precise measurement of deuterium-tritium (DT) neutrons. This design is presented emphasizing the magnetic analyzing system, which is based on a compact quadrupole-dipole (QD) electromagnet. The focal plane detector (FPD) is also discussed with respect to application for the next step. The characteristics of the MPR spectrometer were calculated by using Monte Carlo simulation. A preliminary experiment was performed to test the magnetic analyzing system and the proton images of the FPD. Since the QD electromagnet design allows for a larger foil thickness and solid angle to be utilized, the MPR spectrometer defined in this paper can achieve neutron detection efficiency more than 5 × 10(-7) at an energy resolution of 1.5% for measuring DT neutrons. PMID:26724081

  6. Development of a compact magnetic proton recoil spectrometer for measurement of deuterium-tritium neutrons

    NASA Astrophysics Data System (ADS)

    Zhang, Jianfu; Ouyang, Xiaoping; Qiu, Suizheng; Zhang, Guoguang; Ruan, Jinlu; Zhang, Xiaodong; Zhang, Xianpeng; Yang, Shaohua; Song, Jiwen; Liu, Linyue; Li, Hongyun

    2015-12-01

    A new compact magnetic proton recoil (MPR) neutron spectrometer has been designed for precise measurement of deuterium-tritium (DT) neutrons. This design is presented emphasizing the magnetic analyzing system, which is based on a compact quadrupole-dipole (QD) electromagnet. The focal plane detector (FPD) is also discussed with respect to application for the next step. The characteristics of the MPR spectrometer were calculated by using Monte Carlo simulation. A preliminary experiment was performed to test the magnetic analyzing system and the proton images of the FPD. Since the QD electromagnet design allows for a larger foil thickness and solid angle to be utilized, the MPR spectrometer defined in this paper can achieve neutron detection efficiency more than 5 × 10-7 at an energy resolution of 1.5% for measuring DT neutrons.

  7. Ultrafast proton radiography of the magnetic fields generated by a laser-driven coil current

    DOE PAGESBeta

    Gao, Lan; Ji, Hantao; Fiksel, Gennady; Fox, William; Evans, Michelle; Alfonso, Noel

    2016-04-15

    Magnetic fields generated by a current flowing through a U-shaped coil connecting two copper foils were measured using ultrafast proton radiography. Two ~ 1.25 kJ, 1-ns laser pulses propagated through laser entrance holes in the front foil and were focused to the back foil with an intensity of ~ 3 x 1016 W/cm2. The intense laser-solid interaction induced a high voltage between the copper foils and generated a large current in the connecting coil. The proton data show ~ 40-50 T magnetic fields at the center of the coil ~ 3-4 ns after laser irradiation. In conclusion, the experiments providemore » significant insight for future target designs that aim to develop a powerful source of external magnetic fields for various applications in high-energy-density science.« less

  8. Development of a compact magnetic proton recoil spectrometer for measurement of deuterium-tritium neutrons

    SciTech Connect

    Zhang, Jianfu Ouyang, Xiaoping; Zhang, Xianpeng; Qiu, Suizheng; Zhang, Guoguang; Ruan, Jinlu; Zhang, Xiaodong; Yang, Shaohua; Song, Jiwen; Liu, Linyue; Li, Hongyun

    2015-12-15

    A new compact magnetic proton recoil (MPR) neutron spectrometer has been designed for precise measurement of deuterium-tritium (DT) neutrons. This design is presented emphasizing the magnetic analyzing system, which is based on a compact quadrupole-dipole (QD) electromagnet. The focal plane detector (FPD) is also discussed with respect to application for the next step. The characteristics of the MPR spectrometer were calculated by using Monte Carlo simulation. A preliminary experiment was performed to test the magnetic analyzing system and the proton images of the FPD. Since the QD electromagnet design allows for a larger foil thickness and solid angle to be utilized, the MPR spectrometer defined in this paper can achieve neutron detection efficiency more than 5 × 10{sup −7} at an energy resolution of 1.5% for measuring DT neutrons.

  9. The effect of magnetically induced linear aggregates on proton transverse relaxation rates of aqueous suspensions of polymer coated magnetic nanoparticles.

    PubMed

    Saville, Steven L; Woodward, Robert C; House, Michael J; Tokarev, Alexander; Hammers, Jacob; Qi, Bin; Shaw, Jeremy; Saunders, Martin; Varsani, Rahi R; St Pierre, Tim G; Mefford, O Thompson

    2013-03-01

    It has been recently reported that for some suspensions of magnetic nanoparticles the transverse proton relaxation rate, R(2), is dependent on the time that the sample is exposed to an applied magnetic field. This time dependence has been linked to the formation of linear aggregates or chains in an applied magnetic field via numerical modeling. It is widely known that chain formation occurs in more concentrated ferrofluids systems and that this has an affect on the ferrofluid properties. In this work we examine the relationships between colloidal stability, the formation of these linear structures, and changes observed in the proton transverse relaxation rate of aqueous suspensions of magnetic particles. A series of iron oxide nanoparticles with varying stabilizing ligand brush lengths were synthesized. These systems were characterized with dynamic light scattering, transmission electron microscopy, dark-field optical microscopy, and proton transverse relaxation rate measurements. The dark field optical microscopy and R(2) measurements were made in similar magnetic fields over the same time scale so as to correlate the reduction of the transverse relaxivity with the formation of linear aggregates. Our results indicate that varying the ligand length has a direct effect on the colloidal arrangement of the system in a magnetic field, producing differences in the rate and size of chain formation, and hence systematic changes in transverse relaxation rates over time. With increasing ligand brush length, attractive inter-particle interactions are reduced, which results in slower aggregate formation and shorter linear aggregate length. These results have implications for the stabilization, characterization and potentially the toxicity of magnetic nanoparticle systems used in biomedical applications. PMID:23389324

  10. Controlled transport and focusing of laser-accelerated protons with miniature magnetic devices.

    PubMed

    Schollmeier, M; Becker, S; Geissel, M; Flippo, K A; Blazević, A; Gaillard, S A; Gautier, D C; Grüner, F; Harres, K; Kimmel, M; Nürnberg, F; Rambo, P; Schramm, U; Schreiber, J; Schütrumpf, J; Schwarz, J; Tahir, N A; Atherton, B; Habs, D; Hegelich, B M; Roth, M

    2008-08-01

    This Letter demonstrates the transporting and focusing of laser-accelerated 14 MeV protons by permanent magnet miniature quadrupole lenses providing field gradients of up to 500 T/m. The approach is highly reproducible and predictable, leading to a focal spot of (286 x 173) microm full width at half maximum 50 cm behind the source. It decouples the relativistic laser-proton acceleration from the beam transport, paving the way to optimize both separately. The collimation and the subsequent energy selection obtained are perfectly applicable for upcoming high-energy, high-repetition rate laser systems. PMID:18764401

  11. New method to determine proton trajectories in the equatorial plane of a dipole magnetic field.

    PubMed

    Ioanoviciu, Damaschin

    2015-01-01

    A parametric description of proton trajectories in the equatorial plane of Earth's dipole magnetic field has been derived. The exact expression of the angular coordinate contains an integral to be performed numerically. The radial coordinate results from the initial conditions by basic mathematical operations and by using trigonometric functions. With the approximate angular coordinate formula, applicable for a wide variety of cases of protons trapped in Earth's radiation belts, no numerical integration is needed. The results of exact and approximate expressions were compared for a specific case and small differences were found. PMID:25815248

  12. Alternating-gradient canted cosine theta superconducting magnets for future compact proton gantries

    NASA Astrophysics Data System (ADS)

    Wan, Weishi; Brouwer, Lucas; Caspi, Shlomo; Prestemon, Soren; Gerbershagen, Alexander; Schippers, Jacobus Maarten; Robin, David

    2015-10-01

    We present a design of superconducting magnets, optimized for application in a gantry for proton therapy. We have introduced a new magnet design concept, called an alternating-gradient canted cosine theta (AG-CCT) concept, which is compatible with an achromatic layout. This layout allows a large momentum acceptance. The 15 cm radius of the bore aperture enables the application of pencil beam scanning in front of the SC-magnet. The optical and dynamic performance of a gantry based on these magnets has been analyzed using the fields derived (via Biot-Savart law) from the actual windings of the AG-CCT combined with the full equations of motion. The results show that with appropriate higher order correction, a large 3D volume can be rapidly scanned with little beam shape distortion. A very big advantage is that all this can be done while keeping the AG-CCT fields fixed. This reduces the need for fast field ramping of the superconducting magnets between the successive beam energies used for the scanning in depth and it is important for medical application since this reduces the technical risk (e.g., a quench) associated with fast field changes in superconducting magnets. For proton gantries the corresponding superconducting magnet system holds promise of dramatic reduction in weight. For heavier ion gantries there may furthermore be a significant reduction in size.

  13. Nuclear magnetic resonance multiwindow analysis of proton local fields and magnetization distribution in natural and deuterated mouse muscle.

    PubMed Central

    Peemoeller, H; Pintar, M M

    1979-01-01

    The proton free-induction decays, spin-spin relaxation times, local fields in the rotating frame, and spin-lattice relaxation times in the laboratory and rotating frames, in natural and fully deuterated mouse muscle, are reported. Measurements were taken above and below freezing temperature and at two time windows on the free-induction decay. A comparative analysis show that the magnetization fractions deduced from the different experiments are in good agreement. The main conclusion is that the resolution of the (heterogeneous) muscle nuclear magnetic resonance (NMR) response is improved by the multiwindow analysis. PMID:262554

  14. SU-D-304-02: Magnetically Focused Proton Irradiation of Small Field Targets

    SciTech Connect

    McAuley, GA; Slater, JM; Slater, JD; Wroe, AJ

    2015-06-15

    Purpose: To investigate the use of magnetic focusing for small field proton irradiations. It is hypothesized that magnetic focusing will provide significant dose distribution benefits over standard collimated beams for fields less than 10 mm diameter. Methods: Magnets consisting of 24 segments of radiation hard samarium-cobalt adhered into hollow cylinders were designed and manufactured. Two focusing magnets were placed on a positioning track on our Gantry 1 treatment table. Proton beams with energies of 127 and 157 MeV, 15 and 30 mm modulation, and 8 mm initial diameters were delivered to a water tank using single-stage scattering. Depth dose distributions were measured using a PTW PR60020 diode detector and transverse profiles were measured with Gafchromic EBT3 film. Monte Carlo simulations were also performed - both for comparison with experimental data and to further explore the potential of magnetic focusing in silica. For example, beam spot areas (based on the 90% dose contour) were matched at Bragg depth between simulated 100 MeV collimated beams and simulated beams focused by two 400 T/m gradient magnets. Results: Preliminary experimental results show 23% higher peak to entrance dose ratios and flatter spread out Bragg peak plateaus for 8 mm focused beams compared with uncollimated beams. Monte Carlo simulations showed 21% larger peak to entrance ratios and a ∼9 fold more efficient dose to target delivery compared to spot-sized matched collimated beams. Our latest results will be presented. Conclusion: Our results suggest that rare earth focusing magnet assemblies could reduce skin dose and beam number while delivering dose to nominally spherical radiosurgery targets over a much shorter time compared to unfocused beams. Immediate clinical applications include those associated with proton radiosurgery and functional radiosurgery of the brain and spine, however expanded treatment sites can be also envisaged.

  15. The haem-accessibility in leghaemoglobin of Lupinus luteus as observed by proton magnetic relaxation.

    PubMed

    Vuk-pavlović, S; Benko, B; Maricić, S; Lahajnar, G; Kuranova, I P; Vainshtein, B K

    1976-01-01

    Using the solvent-protons' longitudinal magnetic relaxation rates (p.m.r.) for Lupinus luteus leghaemoglobin derivatives the accessibility of the haem has been evaluated by our "stereo-chemical p.m.r. titration" method with nonexchangeable protons of aliphatic lower alcohols in otherwise deuterated solutions. The haem in leghaemoglobin is more accessible and its protein environment more flexible compared with vertebrate haemoglobins. The correlation time in aquometleghaemglobin aqueous solution has been determined by measuring the frequency dispersion of the p.m.r. rates between 6.1 and 93 MHZ. Taking into account the measured value of tauc = (7.7 +/- 0.5 x 10(-10) s the iron-to-proton inter-spin distances have been calculated. The significance of these distances as well as the electronic g-factor anisotrophy for elucidation of fine structural details of the haem-environment are discussed. PMID:965150

  16. Measuring N-acetyl aspartate synthesis in vivo using proton magnetic resonance spectroscopy

    PubMed Central

    Xu, Su; Yang, Jehoon; Shen, Jun

    2008-01-01

    N-acetyl aspartate (NAA) is an important marker of neuronal function and viability that can be measured using magnetic resonance spectroscopy (MRS). In this paper, we proposed a method to measure NAA synthesis using proton MRS with infusion of uniformly 13C-labeled glucose, and demonstrated its feasibility in an in vivo study of the rat brain. The rate of 13C-label incorporation into the acetyl group of NAA was measured using a localized, long echo-time proton MRS method. Signals from the 13C satellites of the main NAA methyl protons at 2.02 ppm were continuously monitored for 10 hours. Quantification of the data based on a linear kinetic model showed that NAA synthesis rate in isoflurane-anesthetized rats was 0.19 ± 0.02 µmol/g/h (mean ± standard deviation, n = 12). PMID:18486230

  17. Magnetic properties of proton irradiated BiFeO{sub 3}

    SciTech Connect

    Han, Seungkyu; Jin Kim, Sam; Sung Kim, Chul

    2013-05-07

    The crystal structure and magnetic properties of BiFeO{sub 3} samples, proton-irradiated with 0, 10, and 20 pC/{mu}m{sup 2}, were investigated with x-ray diffraction (XRD), vibrating sample magnetometer, and Moessbauer spectroscopy measurements. From the Rietveld refinement analysis of the XRD patterns, the crystal structure of BiFeO{sub 3} is determined to be rhombohedral with the space group of R3c. We have observed the decrease in the lattice constant and oxygen occupancy with proton irradiation. The magnetization hysteresis (M-H) curves show the appearance of the weak ferromagnetic behavior in the proton irradiated BiFeO{sub 3} samples. The Moessbauer spectra of proton irradiated BiFeO{sub 3} samples at 295 K were analyzed with two-sextets (B{sub 1} and B{sub 2}) and doublet. From the isomer shift ({delta}) values, ionic states were determined to be Fe{sup 3+}. Compared to non-irradiated sample, having the antiferromagnetic area ratio (two-sextets) of 45.47, 54.53% the antiferromagnetic and paramagnetic area ratios (doublet) of 10 and 20 pC/{mu}m{sup 2} proton irradiated BiFeO{sub 3} samples are 41.36, 51.26, and 7.38% and 41.03, 50.90, and 8.07%, respectively. Our experimental observation suggests that the increase in the paramagnetic area ratio is due to the disappearance of superexchange interaction, resulted from the removal of the oxygen with proton irradiation. Also, the appearance of the weak ferromagnetic behavior is caused by the breaking of the antiferromagnetic coupling.

  18. High-field proton magnetic resonance spectroscopy reveals metabolic effects of normal brain aging

    PubMed Central

    Harris, Janna L.; Yeh, Hung-Wen; Swerdlow, Russell H.; Choi, In-Young; Lee, Phil; Brooks, William M.

    2014-01-01

    Altered brain metabolism is likely to be an important contributor to normal cognitive decline and brain pathology in elderly individuals. To characterize the metabolic changes associated with normal brain aging, we used high-field proton magnetic resonance spectroscopy in vivo to quantify 20 neurochemicals in the hippocampus and sensorimotor cortex of young adult and aged rats. We found significant differences in the neurochemical profile of the aged brain when compared with younger adults, including lower aspartate, ascorbate, glutamate, and macromolecules, and higher glucose, myo-inositol, N-acetylaspartylglutamate, total choline, and glutamine. These neurochemical biomarkers point to specific cellular mechanisms that are altered in brain aging, such as bioenergetics, oxidative stress, inflammation, cell membrane turnover, and endogenous neuroprotection. Proton magnetic resonance spectroscopy may be a valuable translational approach for studying mechanisms of brain aging and pathology, and for investigating treatments to preserve or enhance cognitive function in aging. PMID:24559659

  19. High-precision determination of the electric and magnetic form factors of the proton.

    PubMed

    Bernauer, J C; Achenbach, P; Ayerbe Gayoso, C; Böhm, R; Bosnar, D; Debenjak, L; Distler, M O; Doria, L; Esser, A; Fonvieille, H; Friedrich, J M; Friedrich, J; Gómez Rodríguez de la Paz, M; Makek, M; Merkel, H; Middleton, D G; Müller, U; Nungesser, L; Pochodzalla, J; Potokar, M; Sánchez Majos, S; Schlimme, B S; Sirca, S; Walcher, Th; Weinriefer, M

    2010-12-10

    New precise results of a measurement of the elastic electron-proton scattering cross section performed at the Mainz Microtron MAMI are presented. About 1400 cross sections were measured with negative four-momentum transfers squared up to Q² = 1 (GeV/c)² with statistical errors below 0.2%. The electric and magnetic form factors of the proton were extracted by fits of a large variety of form factor models directly to the cross sections. The form factors show some features at the scale of the pion cloud. The charge and magnetic radii are determined to be ½ = 0.879(5)stat(4)syst(2)model(4)group fm and ½ = 0.777(13)stat(9)syst(5)model(2)group fm. PMID:21231520

  20. High-Precision Determination of the Electric and Magnetic Form Factors of the Proton

    SciTech Connect

    Bernauer, J. C.; Achenbach, P.; Ayerbe Gayoso, C.; Boehm, R.; Distler, M. O.; Doria, L.; Esser, A.; Friedrich, J.; Gomez Rodriguez de la Paz, M.; Merkel, H.; Middleton, D. G.; Mueller, U.; Nungesser, L.; Pochodzalla, J.; Sanchez Majos, S.; Schlimme, B. S.; Walcher, Th.; Weinriefer, M.; Bosnar, D.; Makek, M.

    2010-12-10

    New precise results of a measurement of the elastic electron-proton scattering cross section performed at the Mainz Microtron MAMI are presented. About 1400 cross sections were measured with negative four-momentum transfers squared up to Q{sup 2}=1 (GeV/c){sup 2} with statistical errors below 0.2%. The electric and magnetic form factors of the proton were extracted by fits of a large variety of form factor models directly to the cross sections. The form factors show some features at the scale of the pion cloud. The charge and magnetic radii are determined to be {sup 1/2}=0.879(5){sub stat}(4){sub syst}(2){sub model}(4){sub group} fm and {sup 1/2}=0.777(13){sub stat}(9){sub syst}(5){sub model}(2){sub group} fm.

  1. NuMI proton kicker extraction magnet termination resistor system

    SciTech Connect

    Reeves, S.R.; Jensen, C.C.; /Fermilab

    2005-05-01

    The temperature stability of the kicker magnet termination resistor assembly directly affects the field flatness and amplitude stability. Comprehensive thermal enhancements were made to the existing Main Injector resistor assembly design to satisfy NuMI performance specifications. Additionally, a fluid-processing system utilizing Fluorinert{reg_sign} FC-77 high-voltage dielectric was built to precisely control the setpoint temperature of the resistor assembly from 70 to 120F, required to maintain constant resistance during changing operational modes. The Fluorinert{reg_sign} must be continually processed to remove hazardous breakdown products caused by radiation exposure to prevent chemical attack of system components. Design details of the termination resistor assembly and Fluorinert{reg_sign} processing system are described. Early performance results will be presented.

  2. High-Resolution Proton Nuclear Magnetic Resonance Analysis of Metastatic Cancer Cells

    NASA Astrophysics Data System (ADS)

    Mountford, Carolyn E.; Wright, Lesley C.; Holmes, Kerry T.; MacKinnon, Wanda B.; Gregory, Patricia; Fox, Richard M.

    1984-12-01

    High-resolution proton nuclear magnetic resonance (NMR) studies of intact cancer cells revealed differences between cells with the capacity to metastasize and those that produce locally invasive tumors. The NMR resonances that characterize the metastatic cells were associated with an increased ratio of cholesterol to phospholipid and an increased amount of plasma membrane--bound cholesterol ester. High-resolution NMR spectroscopy could therefore be used to assess the metastatic potential of primary tumors.

  3. Design summary of the magnet support structures for the proton storage ring injection line upgrade

    SciTech Connect

    Bernardin, J.D.; Ledford, J.E.; Smith, B.G.

    1997-05-01

    This report summarizes the technical engineering and design issues associated with the Proton Storage Ring (PSR) Injection Line upgrade of the Los Alamos Neutron Science Center (LANSCE). The main focus is on the engineering design calculations of several magnet support structures. The general procedure based upon a set number of design criteria is outlined, followed by a case-by-case summary of the engineering design analyses, reutilization or fabrication callouts and design safety factors.

  4. Measurement of pulsed-power-driven magnetic fields via proton deflectometry

    NASA Astrophysics Data System (ADS)

    Mariscal, D.; McGuffey, C.; Valenzuela, J.; Wei, M. S.; Chittenden, J. P.; Niasse, N.; Presura, R.; Haque, S.; Wallace, M.; Arias, A.; Covington, A.; Sawada, H.; Wiewior, P.; Beg, F. N.

    2014-12-01

    Measuring magnetic field and current distribution in Z-pinch plasma systems is crucial to the validation of Z-pinch theory. In this letter, the demonstration of proton deflectometry to pulsed-power-driven loads at the mega-amp scale is presented, which is capable of making more detailed field maps in high-density regions of plasmas. In this method, a laser-driven, broad-spectrum, MeV-energy proton beam is directed through a pulsed-power-driven plasma system, and the resulting deflections are measured to examine configuration of magnetic fields and to infer the currents that support them. The technique was first demonstrated on simple short-circuit loads, and the results are in excellent agreement with numerical simulations providing reliable estimates of the field and current configurations. It was then applied to a more complex—radial foil—plasma load. The measurements show unexpected proton deflections that exhibit the complexity of the plasma load and that with further analysis will reveal details about the current and magnetic field topology in this complex configuration.

  5. Ulysses observations of electron and proton components in a magnetic cloud and related wave activity

    NASA Technical Reports Server (NTRS)

    Osherovich, V. A.; Fainberg, J.; Stone, R. G.; MacDowall, R. J.; Phillips, J. L.; Balogh, A.

    1995-01-01

    In addition to a smooth rotation of the magnetic field vector, magnetic clouds have a low proton temperature T(sub p). Their expansion in the solar wind leads to depletion and therefore the ion component cools down. It has been shown recently that the electron component in magnetic clouds behaves differently: when the cloud expands, electron temperature Te anti correlates with density and therefore Te increases in the cloud, creating favorable conditions for the rise of ion-acoustic waves. For the magnetic cloud observed by Ulysses on June 10 - 12, 1993 at 4.64 AU at S 32.5 deg, we present observations for both electron and proton components and related plasma wave activity. Our results confirm the anti correlation between T(sub e) and electron density and also exhibit a high ratio of T(sub e)/T(sub P) in the cloud. Since Landau damping is not effective for T(sub e)/T(sub p) much greater than 1, Doppler shifted ion acoustic waves are expected in the cloud. Calculation of ion acoustic wave frequencies in the cloud and comparison with observed wave activity confirm this expectation. As in our previous work, we show that the electron component in the cloud obeys a polytropic law with gamma is less than 1 (gamma approximately equals 0.3-0.4). The dynamics of the magnetic cloud are determined to a large degree by the dominating electron pressure.

  6. Nuclear magnetic resonance proton imaging of bone pathology

    SciTech Connect

    Atlan, H.; Sigal, R.; Hadar, H.; Chisin, R.; Cohen, I.; Lanir, A.; Soudry, M.; Machtey, Y.; Schreiber, R.; Benmair, J.

    1986-02-01

    Thirty-two patients with diversified pathology were examined with a supraconductive NMR imager using spin echo with different TR and TE to obtain T1 and T2 weighted images. They included 20 tumors (12 primary, eight metastasis), six osteomyelitis, three fractures, two osteonecrosis, and one diffuse metabolic (Gaucher) disease. In all cases except for the stress fractures, the bone pathology was clearly visualized in spite of the normal lack of signal from the compact cortical bone. Nuclear magnetic resonance (NMR) imaging proved to be at least as sensitive as radionuclide scintigraphy but much more accurate than all other imaging procedures including computed tomography (CT) and angiography to assess the extension of the lesions, especially in tumors extended to soft tissue. This is due both to easy acquisition of sagittal and coronal sections and to different patterns of pathologic modifications of T1 and T2 which are beginning to be defined. It is hoped that more experience in clinical use of these patterns will help to discriminate between tumor extension and soft-tissue edema. We conclude that while radionuclide scintigraphy will probably remain the most sensitive and easy to perform screening test for bone pathology, NMR imaging, among noninvasive diagnostic procedures, appears to be at least as specific as CT. In addition, where the extension of the lesions is concerned, NMR imaging is much more informative than CT. In pathology of the spine, the easy visualization of the spinal cord should decrease the need for myelography.

  7. Memory CD4 T cells in influenza.

    PubMed

    Zens, Kyra D; Farber, Donna L

    2015-01-01

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

  8. Measuring the strong electrostatic and magnetic fields with proton radiography for ultra-high intensity laser channeling on fast ignition

    SciTech Connect

    Uematsu, Y.; Iwawaki, T.; Habara, H. Tanaka, K. A.; Ivancic, S.; Theobald, W.; Lei, A. L.

    2014-11-15

    In order to investigate the intense laser propagation and channel formation in dense plasma, we conducted an experiment with proton deflectometry on the OMEGA EP Laser facility. The proton image was analyzed by tracing the trajectory of mono-energetic protons, which provides understanding the electric and magnetic fields that were generated around the channel. The estimated field strengths (E ∼ 10{sup 11} V/m and B ∼ 10{sup 8} G) agree with the predictions from 2D-Particle-in-cell (PIC) simulations, indicating the feasibility of the proton deflectometry technique for over-critical density plasma.

  9. Measuring the strong electrostatic and magnetic fields with proton radiography for ultra-high intensity laser channeling on fast ignitiona)

    NASA Astrophysics Data System (ADS)

    Uematsu, Y.; Ivancic, S.; Iwawaki, T.; Habara, H.; Lei, A. L.; Theobald, W.; Tanaka, K. A.

    2014-11-01

    In order to investigate the intense laser propagation and channel formation in dense plasma, we conducted an experiment with proton deflectometry on the OMEGA EP Laser facility. The proton image was analyzed by tracing the trajectory of mono-energetic protons, which provides understanding the electric and magnetic fields that were generated around the channel. The estimated field strengths (E ˜ 1011 V/m and B ˜ 108 G) agree with the predictions from 2D-Particle-in-cell (PIC) simulations, indicating the feasibility of the proton deflectometry technique for over-critical density plasma.

  10. Measuring the strong electrostatic and magnetic fields with proton radiography for ultra-high intensity laser channeling on fast ignition.

    PubMed

    Uematsu, Y; Ivancic, S; Iwawaki, T; Habara, H; Lei, A L; Theobald, W; Tanaka, K A

    2014-11-01

    In order to investigate the intense laser propagation and channel formation in dense plasma, we conducted an experiment with proton deflectometry on the OMEGA EP Laser facility. The proton image was analyzed by tracing the trajectory of mono-energetic protons, which provides understanding the electric and magnetic fields that were generated around the channel. The estimated field strengths (E ∼ 10(11) V/m and B ∼ 10(8) G) agree with the predictions from 2D-Particle-in-cell (PIC) simulations, indicating the feasibility of the proton deflectometry technique for over-critical density plasma. PMID:25430358

  11. Proton magnetic resonance imaging using a nitrogen-vacancy spin sensor.

    PubMed

    Rugar, D; Mamin, H J; Sherwood, M H; Kim, M; Rettner, C T; Ohno, K; Awschalom, D D

    2015-02-01

    Magnetic resonance imaging, with its ability to provide three-dimensional, elementally selective imaging without radiation damage, has had a revolutionary impact in many fields, especially medicine and the neurosciences. Although challenging, its extension to the nanometre scale could provide a powerful new tool for the nanosciences, especially if it can provide a means for non-destructively visualizing the full three-dimensional morphology of complex nanostructures, including biomolecules. To achieve this potential, innovative new detection strategies are required to overcome the severe sensitivity limitations of conventional inductive detection techniques. One successful example is magnetic resonance force microscopy, which has demonstrated three-dimensional imaging of proton NMR with resolution on the order of 10 nm, but with the requirement of operating at cryogenic temperatures. Nitrogen-vacancy (NV) centres in diamond offer an alternative detection strategy for nanoscale magnetic resonance imaging that is operable at room temperature. Here, we demonstrate two-dimensional imaging of (1)H NMR from a polymer test sample using a single NV centre in diamond as the sensor. The NV centre detects the oscillating magnetic field from precessing protons as the sample is scanned past the NV centre. A spatial resolution of ∼12 nm is shown, limited primarily by the scan resolution. PMID:25531089

  12. Proton magnetic resonance imaging using a nitrogen-vacancy spin sensor

    NASA Astrophysics Data System (ADS)

    Rugar, D.; Mamin, H. J.; Sherwood, M. H.; Kim, M.; Rettner, C. T.; Ohno, K.; Awschalom, D. D.

    2015-02-01

    Magnetic resonance imaging, with its ability to provide three-dimensional, elementally selective imaging without radiation damage, has had a revolutionary impact in many fields, especially medicine and the neurosciences. Although challenging, its extension to the nanometre scale could provide a powerful new tool for the nanosciences, especially if it can provide a means for non-destructively visualizing the full three-dimensional morphology of complex nanostructures, including biomolecules. To achieve this potential, innovative new detection strategies are required to overcome the severe sensitivity limitations of conventional inductive detection techniques. One successful example is magnetic resonance force microscopy, which has demonstrated three-dimensional imaging of proton NMR with resolution on the order of 10 nm, but with the requirement of operating at cryogenic temperatures. Nitrogen-vacancy (NV) centres in diamond offer an alternative detection strategy for nanoscale magnetic resonance imaging that is operable at room temperature. Here, we demonstrate two-dimensional imaging of 1H NMR from a polymer test sample using a single NV centre in diamond as the sensor. The NV centre detects the oscillating magnetic field from precessing protons as the sample is scanned past the NV centre. A spatial resolution of ˜12 nm is shown, limited primarily by the scan resolution.

  13. A nested phosphorus and proton coil array for brain magnetic resonance imaging and spectroscopy.

    PubMed

    Brown, Ryan; Lakshmanan, Karthik; Madelin, Guillaume; Parasoglou, Prodromos

    2016-01-01

    A dual-nuclei radiofrequency coil array was constructed for phosphorus and proton magnetic resonance imaging and spectroscopy of the human brain at 7T. An eight-channel transceive degenerate birdcage phosphorus module was implemented to provide whole-brain coverage and significant sensitivity improvement over a standard dual-tuned loop coil. A nested eight-channel proton module provided adequate sensitivity for anatomical localization without substantially sacrificing performance on the phosphorus module. The developed array enabled phosphorus spectroscopy, a saturation transfer technique to calculate the global creatine kinase forward reaction rate, and single-metabolite whole-brain imaging with 1.4cm nominal isotropic resolution in 15min (2.3cm actual resolution), while additionally enabling 1mm isotropic proton imaging. This study demonstrates that a multi-channel array can be utilized for phosphorus and proton applications with improved coverage and/or sensitivity over traditional single-channel coils. The efficient multi-channel coil array, time-efficient pulse sequences, and the enhanced signal strength available at ultra-high fields can be combined to allow volumetric assessment of the brain and could provide new insights into the underlying energy metabolism impairment in several neurodegenerative conditions, such as Alzheimer's and Parkinson's diseases, as well as mental disorders such as schizophrenia. PMID:26375209

  14. Monitoring lactic acid production during milk fermentation by in situ quantitative proton nuclear magnetic resonance spectroscopy.

    PubMed

    Bouteille, R; Gaudet, M; Lecanu, B; This, H

    2013-04-01

    When fermenting milk, lactic bacteria convert part of α- and β-lactoses into d- and l- lactic acids, causing a pH decrease responsible for casein coagulation. Lactic acid monitoring during fermentation is essential for the control of dairy gel textural and organoleptic properties, and is a way to evaluate strain efficiency. Currently, titrations are used to follow the quantity of acids formed during jellification of milk but they are not specific to lactic acid. An analytical method without the use of any reagent was investigated to quantify lactic acid during milk fermentation: in situ quantitative proton nuclear magnetic resonance spectroscopy. Two methods using in situ quantitative proton nuclear magnetic resonance spectroscopy were compared: (1) d- and l-lactic acids content determination, using the resonance of their methyl protons, showing an increase from 2.06 ± 0.02 to 8.16 ± 0.74 g/L during 240 min of fermentation; and (2) the determination of the α- and β-lactoses content, decreasing from 42.68 ± 0.02 to 30.76 ± 1.75 g/L for the same fermentation duration. The ratio between the molar concentrations of produced lactic acids and consumed lactoses enabled cross-validation, as the value (2.02 ± 0.18) is consistent with lactic acid bacteria metabolism. PMID:23403188

  15. Fast method for brain image segmentation: application to proton magnetic resonance spectroscopic imaging.

    PubMed

    Bonekamp, David; Horská, Alena; Jacobs, Michael A; Arslanoglu, Atilla; Barker, Peter B

    2005-11-01

    The interpretation of brain metabolite concentrations measured by quantitative proton magnetic resonance spectroscopic imaging (MRSI) is assisted by knowledge of the percentage of gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF) within each MRSI voxel. Usually, this information is determined from T(1)-weighted magnetic resonance images (MRI) that have a much higher spatial resolution than the MRSI data. While this approach works well, it is time-consuming. In this article, a rapid data acquisition and analysis procedure for image segmentation is described, which is based on collection of several, thick slice, fast spin echo images (FSE) of different contrast. Tissue segmentation is performed with linear "Eigenimage" filtering and normalization. The method was compared to standard segmentation techniques using high-resolution 3D T(1)-weighted MRI in five subjects. Excellent correlation between the two techniques was obtained, with voxel-wise regression analysis giving GM: R2 = 0.893 +/- 0.098, WM: R2 = 0.892 +/- 0.089, ln(CSF): R2 = 0.831 +/- 0.082). Test-retest analysis in one individual yielded an excellent agreement of measurements with R2 higher than 0.926 in all three tissue classes. Application of FSE/EI segmentation to a sample proton MRSI dataset yielded results similar to prior publications. It is concluded that FSE imaging in conjunction with Eigenimage analysis is a rapid and reliable way of segmenting brain tissue for application to proton MRSI. PMID:16187272

  16. Water confined in carbon nanotubes: Magnetic response and proton chemical shieldings

    SciTech Connect

    Huang, P; Schwegler, E; Galli, G

    2008-11-14

    We study the proton nuclear magnetic resonance ({sup 1}H-NMR) of a model system consisting of liquid water in infinite carbon nanotubes (CNT). Chemical shieldings are evaluated from linear response theory, where the electronic structure is derived from density functional theory (DFT) with plane-wave basis sets and periodic boundary conditions. The shieldings are sampled from trajectories generated via first-principles molecular dynamics simulations at ambient conditions, for water confined in (14,0) and (19,0) CNTs with diameters d = 11 {angstrom} and 14.9 {angstrom}, respectively. We find that confinement within the CNT leads to a large ({approx} -23 ppm) upfield shift relative to bulk liquid water. This shift is a consequence of strongly anisotropic magnetic fields induced in the CNT by an applied magnetic field.

  17. Low energy proton bidirectional anisotropies and their relation to transient interplanetary magnetic structures: ISEE-3 observations

    NASA Technical Reports Server (NTRS)

    Marsden, R. G.; Sanderson, T. R.; Wenzel, K. P.; Smith, E. J.

    1985-01-01

    It is known that the interplanetary medium in the period approaching solar maximum is characterized by an enhancement in the occurrence of transient solar wind streams and shocks and that such systems are often associated with looplike magnetic structures or clouds. There is observational evidence that bidirectional, field aligned flows of low energy particles could be a signature of such looplike structures, although detailed models for the magnetic field configuration and injection mechanisms do not exist at the current time. Preliminary results of a survey of low energy proton bidirectional anisotropies measured on ISEE-3 in the interplanetary medium between August 1978 and May 1982, together with magnetic field data from the same spacecraft are presented.

  18. A superconducting magnet mandrel with minimum symmetry laminations for proton therapy

    NASA Astrophysics Data System (ADS)

    Caspi, S.; Arbelaez, D.; Brouwer, L.; Dietderich, D. R.; Felice, H.; Hafalia, R.; Prestemon, S.; Robin, D.; Sun, C.; Wan, W.

    2013-08-01

    The size and weight of ion-beam cancer therapy gantries are frequently determined by a large aperture, curved, ninety degree, dipole magnet. The higher fields achievable with superconducting technology promise to greatly reduce the size and weight of this magnet and therefore also the gantry as a whole. This paper reports advances in the design of winding mandrels for curved, canted cosine-theta (CCT) magnets in the context of a preliminary magnet design for a proton gantry. The winding mandrel is integral to the CCT design and significantly affects the construction cost, stress management, winding feasibility, eddy current power losses, and field quality of the magnet. A laminated mandrel design using a minimum symmetry in the winding path is introduced and its feasibility demonstrated by a rapid prototype model. Piecewise construction of the mandrel using this laminated approach allows for increased manufacturing techniques and material choices. Sectioning the mandrel also reduces eddy currents produced during field changes accommodating the scan of beam energies during treatment. This symmetry concept can also greatly reduce the computational resources needed for 3D finite element calculations. It is shown that the small region of symmetry forming the laminations combined with periodic boundary conditions can model the entire magnet geometry disregarding the ends.

  19. Initial test results of the Los Alamos proton-storage-ring bump-magnet system

    SciTech Connect

    Rose, C.R.; Barlow, D.B.; Redd, D.B.

    1997-09-01

    An upgrade program for increasing the stored beam current in the LANSCE Proton Storage is presently under way. Part of the upgrade effort has been to design, specify, and add four bump-magnet/modulator systems to the ring. This paper describes the initial test results of the first bump-magnet/modulator system. The paper begins with an overview of the pulsed-power system including important specifications of the modulator, magnet, cabling, and control system. In the main portion of the paper, waveforms and test data are included showing the accuracy, repeatability, and stability of the magnet-current pulses. These magnet pulses are programmable both in rise and fall time as well as in amplitude. The amplitude can be set between 50 and 300 A, the rise-time is fixed at 1 ms, and the linear fall-time can be varied between 500 {mu}s and 1500 {mu}s. Other issues such as loading effects and power dissipation in the magnet-bore beamtube are examined and reported.

  20. Strange magnetic form factor of the proton at $Q^2 = 0.23$ GeV$^2$

    SciTech Connect

    Wang, Ping; Leinweber, Derek; Thomas, Anthony; Young, Ross

    2009-06-01

    We determine the $u$ and $d$ quark contributions to the proton magnetic form factor at finite momentum transfer by applying chiral corrections to quenched lattice data. Heavy baryon chiral perturbation theory is applied at next to leading order in the quenched, and full QCD cases for the valence sector using finite range regularization. Under the assumption of charge symmetry these values can be combined with the experimental values of the proton and neutron magnetic form factors to deduce a relatively accurate value for the strange magnetic form factor at $Q^2=0.23$ GeV$^2$, namely $G_M^s=-0.034 \\pm 0.021$ $\\mu_N$.

  1. Analyzing power in pion-proton bremsstrahlung, and the. Delta. sup ++ (1232) magnetic moment

    SciTech Connect

    Bosshard, A.; Amsler, C.; Doebeli, M.; Doser, M.; Schaad, M.; Riedlberger, J.; Truoel, P. ); Bistirlich, J.A.; Crowe, K.M.; Ljungfelt, S.; Meyer, C.A. ); van den Brandt, B.; Konter, J.A.; Mango, S.; Renker, D. ); Loude, J.F.; Perroud, J.P. ); Haddock, R.P. ); Sober, D.I. )

    1991-10-01

    We report on a first measurement of the polarized-target asymmetry of the pion-proton bremsstrahlung cross section ({pi}{sup +}{ital p}{r arrow}{pi}{sup {minus}}{ital p}{gamma}). As in previous cross section measurements the pion energy (298 MeV) and the detector geometry for this experiment was chosen to optimize the sensitivity to the radiation from the magnetic dipole moment of the {Delta}{sup ++}(1232) resonance {mu}{sub {Delta}}. Comparison to a recent isobar model for pion-nucleon bremsstrahlung yields {mu}{sub {Delta}}=(1.62{plus minus}0.18){mu}{sub {ital p}}, where {mu}{sub {ital p}} is the proton magnetic moment. Since the asymmetry depends less than the cross section on the choice of the other input parameters for the model, their uncertainties affect this analysis by less than the experimental error. However the theory fails to represent both the cross section and the asymmetry data at the highest photon energies. Hence further improvements in the calculations are needed before the model dependence of the magnetic moment analysis can be fully assessed. The present result agrees with bag-model corrections to the SU(6) prediction {mu}{sub {Delta}}=2{mu}{sub {ital p}}. As a by-product, the analyzing power for elastic {pi}{sup +}{ital p} scattering at 415 MeV/{ital c} was also measured. This second result is in good agreement with phase shift calculations.

  2. Temperature dependence of proton NMR relaxation times at earth's magnetic field

    NASA Astrophysics Data System (ADS)

    Niedbalski, Peter; Kiswandhi, Andhika; Parish, Christopher; Ferguson, Sarah; Cervantes, Eduardo; Oomen, Anisha; Krishnan, Anagha; Goyal, Aayush; Lumata, Lloyd

    The theoretical description of relaxation processes for protons, well established and experimentally verified at conventional nuclear magnetic resonance (NMR) fields, has remained untested at low fields despite significant advances in low field NMR technology. In this study, proton spin-lattice relaxation (T1) times in pure water and water doped with varying concentrations of the paramagnetic agent copper chloride have been measured from 6 to 92oC at earth's magnetic field (1700 Hz). Results show a linear increase of T1 with temperature for each of the samples studied. Increasing the concentration of the copper chloride greatly reduced T1 and reduced dependence on temperature. The consistency of the results with theory is an important confirmation of past results, while the ability of an ultra-low field NMR system to do contrast-enhanced magnetic resonance imaging (MRI) is promising for future applicability to low-cost medical imaging and chemical identification. This work is supported by US Dept of Defense Award No. W81XWH-14-1-0048 and the Robert A. Welch Foundation Grant No. AT-1877.

  3. Proton NMR and {mu}SR in Mn{sub 12}O{sub 12} acetate: A mesoscopic magnetic molecular cluster

    SciTech Connect

    Lascialfari, A.; Gatteschi, D.; Borsa, F. |; Shastri, A.; Jang, Z.H.; Carretta, P.

    1998-01-01

    The spin dynamics of Mn spins in the dodecanuclear manganese cluster of formula [Mn{sub 12}O{sub 12}(CH{sub 3}COO){sub 16}(H{sub 2}O){sub 4}]{center_dot}2CH{sub 3}-COOH{center_dot}4H{sub 2}O(Mn{sub 12}) has been investigated by {sup 1}HNMR and muon spin-lattice relaxation rate 1/T{sub 1} as a function of temperature (10{endash}400 K) and external magnetic field (0{endash}9.4 T). At room temperature, the proton 1/T{sub 1} depends on the measuring frequency. The results can be interpreted in terms of a slow decay of the Mn electronic-spin autocorrelation function, a feature characteristic of the almost zero dimensionality of the system. As the temperature is lowered, 1/T{sub 1} displays a critical enhancement that can be related to the slowing down of the local spin fluctuations as the cluster approaches the condensation into the total spin S=10 ground-state configuration. It is found that the application of an external magnetic field greatly depresses the enhancement of 1/T{sub 1} an effect that could be related to the superparamagnetic behavior of the Mn{sub 12} molecule. {copyright} {ital 1998} {ital The American Physical Society}

  4. Characterization of the ELIMED Permanent Magnets Quadrupole system prototype with laser-driven proton beams

    NASA Astrophysics Data System (ADS)

    Schillaci, F.; Pommarel, L.; Romano, F.; Cuttone, G.; Costa, M.; Giove, D.; Maggiore, M.; Russo, A. D.; Scuderi, V.; Malka, V.; Vauzour, B.; Flacco, A.; Cirrone, G. A. P.

    2016-07-01

    Laser-based accelerators are gaining interest in recent years as an alternative to conventional machines [1]. In the actual ion acceleration scheme, energy and angular spread of the laser-driven beams are the main limiting factors for beam applications and different solutions for dedicated beam-transport lines have been proposed [2,3]. In this context a system of Permanent Magnet Quadrupoles (PMQs) has been realized [2] by INFN-LNS (Laboratori Nazionali del Sud of the Instituto Nazionale di Fisica Nucleare) researchers, in collaboration with SIGMAPHI company in France, to be used as a collection and pre-selection system for laser driven proton beams. This system is meant to be a prototype to a more performing one [3] to be installed at ELI-Beamlines for the collection of ions. The final system is designed for protons and carbons up to 60 MeV/u. In order to validate the design and the performances of this large bore, compact, high gradient magnetic system prototype an experimental campaign have been carried out, in collaboration with the group of the SAPHIR experimental facility at LOA (Laboratoire d'Optique Appliquée) in Paris using a 200 TW Ti:Sapphire laser system. During this campaign a deep study of the quadrupole system optics has been performed, comparing the results with the simulation codes used to determine the setup of the PMQ system and to track protons with realistic TNSA-like divergence and spectrum. Experimental and simulation results are good agreement, demonstrating the possibility to have a good control on the magnet optics. The procedure used during the experimental campaign and the most relevant results are reported here.

  5. Pion-proton bremsstrahlung calculation and the ``experimental'' magnetic moment of Δ++(1232)

    NASA Astrophysics Data System (ADS)

    Lin, Dahang; Liou, M. K.; Ding, Z. M.

    1991-11-01

    A bremsstrahlung amplitude in the special two-energy-two-angle (TETAS) approximation, which is relativistic, gauge invariant, and consistent with the soft-photon theorem, is derived for the pion-proton bremsstrahlung (π+pγ) process near the Δ++(1232) resonance. In order to take into account bremsstrahlung emission from an internal Δ++ line with both charge and the anomalous magnetic moment λΔ, we have applied a radiation decomposition identity to modify Low's standard prescription for constructing a soft-photon amplitude. This modified procedure is very general; it can be used to derive the TETAS amplitude for any bremsstrahlung process with resonance. The derived TETAS amplitude is applied to calculate all π+pγ cross sections which can be compared with the experimental data. Treating λΔ as a free parameter in these calculations, we extract the ``experimental'' magnetic moment of the Δ++, μΔ, from recent data. The extracted values of μΔ are (3.7-4.2)e/(2mp) from the University of California, Los Angeles data and (4.6-4.9)e/(2mp) from the Paul Scherrer Institute data. Here, mp is the proton mass. These values are smaller than the value 5.58e/(2mp), the ``bare'' magnetic moment predicted by the SU(6) model or the quark model, but they are close to the value 4.25e/(2mp) predicted by the modified SU(6) model of Beg and Pais and to the value (4.41-4.89)e/(2mp) predicted by the corrected bag-model of Brown, Rho, and Vento. Using the extracted μΔ as an input for calculating π+pγ cross sections, we show that the overall agreement between the theoretical predictions calculated with the extracted μΔ and the experimental measurements is excellent. This agreement demonstrates that the TETAS amplitude can be used to describe almost all the available π+pγ data. Finally, we also treat λΔ as a complex quantity, λΔ=λR+iλI, in order to estimate the contribution from the imaginary part λI. The best fit to the data gives λI~=0, independent of the choice

  6. Isotropic proton-detected local-field nuclear magnetic resonancein solids

    SciTech Connect

    Havlin, Robert H.; Walls, Jamie D.; Pines, Alexander

    2004-08-04

    A new nuclear magnetic resonance (NMR) method is presented which produces linear, isotropic proton-detected local-field spectra for InS spin systems in powdered samples. The method, HETeronuclear Isotropic Evolution (HETIE), refocuses the anisotropic portion of the heteronuclear dipolar coupling frequencies by evolving the system under a series of specially designed Hamiltonians and evolution pathways. The theory behind HETIE is represented along with experimental studies conducted on a powdered sample of ferrocene, demonstrating the methodology outlined in this paper. Applications of HETIE for structural determination in solid-state NMR are discussed.

  7. High-resolution proton nuclear magnetic resonance characterization of seminolipid from bovine spermatozoa.

    PubMed

    Alvarez, J G; Storey, B T; Hemling, M L; Grob, R L

    1990-06-01

    The high-resolution one- and two-dimensional proton nuclear magnetic resonance (1H-NMR) characterization of seminolipid from bovine spermatozoa is presented. The 1H-NMR data was confirmed by gas-liquid chromatography-mass spectrometric analysis of the partially methylated alditol acetates of the sugar unit, mild alkaline methanolysis of the glyceryl ester, mobility on normal phase and diphasic thin-layer chromatography (HPTLC), and fast atom bombardment mass spectrometry (FAB-MS). The structure of the molecule corresponds to 1-O-hexadecyl-2-O-hexadecanoyl-3-O-beta-D-(3'-sulfo)-galactopyranosyl- sn-glycerol. PMID:2373957

  8. 9.4T Human MRI: Preliminary Results

    PubMed Central

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

    2014-01-01

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

  9. CPT Test with (anti)proton Magnetic Moments Based on Quantum Logic Cooling and Readout

    NASA Astrophysics Data System (ADS)

    Niemann, M.; Paschke, A.-G.; Dubielzig, T.; Ulmer, S.; Ospelkaus, C.

    2014-01-01

    Dehmelt and VanDyck's famous 1987 measurement of the electron and positron g-factor is still the most precise g-factor comparison in the lepton sector, and a sensitive test of possible CPT violation. A complementary g-factor comparison between the proton and the antiproton is highly desirable to test CPT symmetry in the baryon sector. Current experiments, based on Dehmelt's continuous Stern-Gerlach effect and the double Penning-trap technique, are making rapid progress. They are, however, extremely difficult to carry out because ground state cooling using cryogenic techniques is virtually impossible for heavy baryons, and because the continous Stern-Gerlach effect scales as μ/m, where m is the mass of the particle and μ its magnetic moment. Both difficulties will ultimately limit the accuracy. We discuss experimental prospects of realizing an alternative approach to a g-factor comparison with single (anti)protons, based on quantum logic techniques proposed by Heinzen and Wineland and by Wineland et al. The basic idea is to cool, control and measure single (anti)protons through interaction with a well-controlled atomic ion.

  10. Proton fire hose instabilities in the expanding solar wind: Role of oblique magnetic field

    NASA Astrophysics Data System (ADS)

    Hellinger, Petr

    2016-04-01

    The double adiabatic (CGL) approximation for the ideal (Parker) interplanetary magnetic field (IMF) predicts generation of the parallel particle temperature anisotropy (T∥ > T⊥) for a nearly radial magnetic field whereas for a strongly oblique IMF generation of the opposite temperature anisotropy is expected. The transition between the two behaviours is expected at around 45o, i.e. around 1 AU in the solar wind in the ecliptic plane. We investigate properties of a proton-electron plasma system in the solar wind using hybrid expanding box simulations starting with an oblique IMF. The simulated system becomes unstable with respect to the parallel and oblique fire hose instabilities and is forced to stay around the corresponding marginal stability. Rotation of the IMF reduces the time system stays near the marginal stability regions and for a strongly transverse IMF the system moves away from the regions unstable with respect to the fire hose instabilities.

  11. Non-destructive Ripeness Sensing by Using Proton NMR [Nuclear Magnetic Resonance

    DOE R&D Accomplishments Database

    Cho, Seong In; Krutz, G. W.; Stroshine, R. L.; Bellon, V.

    1990-01-01

    More than 80 kinds of fruits and vegetables are available in the United States. But only about 6 of them have their quality standards (Dull, 1986). In the 1990 Fresh Trends survey (Zind, 1990), consumers were asked to rate 16 characteristics important to their decision to purchase fresh produce. The four top ranking factors were ripeness/freshness, taste/flavor, appearance/condition and nutritional value. Of these surveyed, 96% rated ripeness/freshness as extremely important or very important. Therefore, the development of reliable grading or sorting techniques for fresh commodities is essential. Determination of fruit quality often involves cutting and tasting. Non-destructive quality control in fruit and vegetables is a goal of growers and distributors, as well as the food processing industry. Many nondestructive techniques have been evaluated including soft x-ray, optical transmission, near infrared radiation, and machine vision. However, there are few reports of successful non-destructive measurement of sugar content directly in fruit. Higher quality fruit could be harvested and available to consumers if a nondestructive sensor that detects ripeness level directly by measuring sugar content were available. Using proton Nuclear Magnetic Resonance (NMR) principle is the possibility. A nondestructive ripeness (or sweetness) sensor for fruit quality control can be developed with the proton NMR principle (Cho, 1989). Several feasibility studies were necessary for the ripeness sensor development. Main objectives in this paper was to investigate the feasibilities (1) to detect ripeness (or sweetness level) of raw fruit tissue with an high resolution proton NMR spectroscopy (200 MHz) and (2) to measure sugar content of intact fruit with a low resolution proton NMR spectroscopy (10 MHz).

  12. Non-destructive ripeness sensing by using proton NMR (Nuclear Magnetic Resonance)

    SciTech Connect

    Cho, Seong In; Krutz, G.W.; Stroshine, R.L. . Dept. of Agricultural Engineering); Bellon, V. , 34 - Montpellier )

    1990-01-01

    More than 80 kinds of fruits and vegetables are available in the United States. But only about 6 of them have their quality standards (Dull, 1986). In the 1990 Fresh Trends survey (Zind, 1990), consumers were asked to rate 16 characteristics important to their decision to purchase fresh produce. The four top ranking factors were ripeness/freshness, taste/flavor, appearance/condition and nutritional value. Of these surveyed, 96% rated ripeness/freshness as extremely important or very important. Therefore, the development of reliable grading or sorting techniques for fresh commodities is essential. Determination of fruit quality often involves cutting and tasting. Non-destructive quality control in fruit and vegetables is a goal of growers and distributors, as well as the food processing industry. Many nondestructive techniques have been evaluated including soft x-ray, optical transmission, near infrared radiation, and machine vision. However, there are few reports of successful non-destructive measurement of sugar content directly in fruit. Higher quality fruit could be harvested and available to consumers if a nondestructive sensor that detects ripeness level directly by measuring sugar content were available. Using proton Nuclear Magnetic Resonance (NMR) principle is the possibility. A nondestructive ripeness (or sweetness) sensor for fruit quality control can be developed with the proton NMR principle (Cho, 1989). Several feasibility studies were necessary for the ripeness sensor development. Main objectives in this paper was to investigate the feasibilities (1) to detect ripeness (or sweetness level) of raw fruit tissue with an high resolution proton NMR spectroscopy (200 MHz) and (2) to measure sugar content of intact fruit with a low resolution proton NMR spectroscopy (10 MHz). 7 refs., 4 figs.

  13. Pion-proton bremsstrahlung calculation and the experimental'' magnetic moment of. Delta. sup ++ (1232)

    SciTech Connect

    Lin, D.; Liou, M.K. ); Ding, Z.M. Department of Physics, Normandale Community College, Bloomington, Minnesota )

    1991-11-01

    A bremsstrahlung amplitude in the special two-energy-two-angle (TETAS) approximation, which is relativistic, gauge invariant, and consistent with the soft-photon theorem, is derived for the pion-proton bremsstrahlung ({pi}{sup +}{ital p}{gamma}) process near the {Delta}{sup ++}(1232) resonance. In order to take into account bremsstrahlung emission from an internal {Delta}{sup ++} line with both charge and the anomalous magnetic moment {lambda}{sub {Delta}}, we have applied a radiation decomposition identity to modify Low's standard prescription for constructing a soft-photon amplitude. This modified procedure is very general; it can be used to derive the TETAS amplitude for any bremsstrahlung process with resonance. The derived TETAS amplitude is applied to calculate all {pi}{sup +}{ital p}{gamma} cross sections which can be compared with the experimental data. Treating {lambda}{sub {Delta}} as a free parameter in these calculations, we extract the experimental'' magnetic moment of the {Delta}{sup ++}, {mu}{sub {Delta}}, from recent data. The extracted values of {mu}{sub {Delta}} are (3.7--4.2){ital e}/(2{ital m}{sub {ital p}}) from the University of California, Los Angeles data and (4.6--4.9){ital e}/(2{ital m}{sub {ital p}}) from the Paul Scherrer Institute data. Here, {ital m}{sub {ital p}} is the proton mass.

  14. Proton Magnetic Form Factor from Existing Elastic e-p Cross Section Data

    NASA Astrophysics Data System (ADS)

    Ou, Longwu; Christy, Eric; Gilad, Shalev; Keppel, Cynthia; Schmookler, Barak; Wojtsekhowski, Bogdan

    2015-04-01

    The proton magnetic form factor GMp, in addition to being an important benchmark for all cross section measurements in hadron physics, provides critical information on proton structure. Extraction of GMp from e-p cross section data is complicated by two-photon exchange (TPE) effects, where available calculations still have large theoretical uncertainties. Studies of TPE contributions to e-p scattering have observed no nonlinear effects in Rosenbluth separations. Recent theoretical investigations show that the TPE correction goes to 0 when ɛ approaches 1, where ɛ is the virtual photon polarization parameter. In this talk, existing e-p elastic cross section data are reanalyzed by extrapolating the reduced cross section for ɛ approaching 1. Existing polarization transfer data, which is supposed to be relatively immune to TPE effects, are used to produce a ratio of electric and magnetic form factors. The extrapolated reduced cross section and polarization transfer ratio are then used to calculate GEp and GMp at different Q2 values.

  15. Double-proton beams and magnetic switchbacks in the solar wind

    NASA Astrophysics Data System (ADS)

    Neugebauer, Marcia; Goldstein, Bruce E.

    2013-06-01

    Previous work has led to suggestions that core-beam distributions of ions in the fast polar solar wind could be caused either by wave-particle interactions in interplanetary space or by ejections of faster material into pre-existing flows. It has also been suggested that the many-hour-long high-speed structures, or microstreams, in the polar wind could be the interplanetary manifestation of solar X-ray jets observed in supergranule boundaries. Proton distribution functions both in the microstreams and in the ambient fast polar wind are examined to test the conjecture that solar ejections may play an important role in creating double proton beams. Double-peaked distributions in the microstreams that have the peak containing most of the particles (the core) being faster than the less-dense beam are suggestive of ejection of material that may have come from a jet. It is concluded, however, that those "backwards" distributions were caused by magnetic reversals, or switchbacks, rather than by the inclusion of faster material. Other than in the switchbacks, there is no qualitative difference between the double-proton streaming in the microstreams peaks and in the ambient wind. Evidence is provided that essentially all departures of the magnetic field from the dominant polarity of the polar wind are due to such switchbacks rather than to solar fields with non-dominant polarities. It is also shown that, in the fast polar solar wind, there are more short-duration switchbacks than longer ones and that the incidence of reversed fields increases with solar distance.

  16. Intergalactic Magnetic Field and Arrival Direction of Ultra-High-Energy Protons

    NASA Astrophysics Data System (ADS)

    Ryu, Dongsu; Das, Santabrata; Kang, Hyesung

    2010-02-01

    We studied how the intergalactic magnetic field (IGMF) affects the propagation of super-Greisen-Zatsepin-Kuz'min (GZK) protons that originate from extragalactic sources within the local GZK sphere. To this end, we set up hypothetical sources of ultra-high-energy cosmic rays (UHECRs), virtual observers, and the magnetized cosmic web in a model universe constructed from cosmological structure formation simulations. We then arranged a set of reference objects mimicking active galactic nuclei (AGNs) in the local universe, with which correlations of simulated UHECR events are analyzed. With our model IGMF, the deflection angle between the arrival direction of super-GZK protons and the sky position of their actual sources is quite large with a mean value of langθrang ~ 15° and a median value of \\tilde{θ}˜ 7°-10°. On the other hand, the separation angle between the arrival direction and the sky position of nearest reference objects is substantially smaller with langSrang ~ 3fdg5-4°, which is similar to the mean angular distance in the sky to nearest neighbors among the reference objects. This is a direct consequence of our model that the sources, observers, reference objects, and the IGMF all trace the matter distribution of the universe. The result implies that extragalactic objects lying closest to the arrival direction of UHECRs are not necessarily their actual sources. With our model for the distribution of reference objects, the fraction of super-GZK proton events, whose closest AGNs are true sources, is less than 1/3. We discussed implications of our findings for correlation studies of real UHECR events.

  17. The proton temperature and the total hourly variance of the magnetic field components in different solar wind speed regions

    NASA Technical Reports Server (NTRS)

    Tu, Chuan-Yi; Freeman, John W.; Lopez, R. E.

    1989-01-01

    A comparison has been made between the predictions of the theory for radial variations of both Alfvenic fluctuations and solar wind proton temperatures proposed by Tu (1987, 1988) and the statistical results of hourly averaged plasma and magnetic field data observed by Helios 1 and 2 from launch through 1980 for different solar wind speed regimes. The comparison shows that for speed ranges between 500-800 km/s, the radial variation of the proton temperature between 0.3 and 1 AU can be explained by heating from the cascade energy which is determined by the radial variation of the total variance of magnetic field vector.

  18. An improved permanent magnet quadrupole design with larger good field region for high intensity proton linacs

    NASA Astrophysics Data System (ADS)

    Mathew, Jose V.; Rao, S. V. L. S.; Krishnagopal, S.; Singh, P.

    2013-11-01

    The Low Energy High Intensity Proton Accelerator (LEHIPA), being developed at the Bhabha Atomic Research Centre (BARC) will produce a 20 MeV, 30 mA, continuous wave (CW) proton beam. At these low velocities, space-charge forces dominate, and could lead to larger beam sizes and beam halos. Hence in the design of the focusing lattice of the LEHIPA drift tube linac (DTL) using permanent magnet quadrupoles (PMQs), a larger good field region is preferred. Here we study, using the two dimensional (2D) and three dimensional (3D) simulation codes PANDIRA and RADIA, four different types of cylindrical PMQ designs: 16-segment trapezoidal Halbach configuration, bullet-nosed geometry and 8- and 16-segment rectangular geometries. The trapezoidal Halbach geometry is used in a variety of accelerators since it provides very high field gradients in small bores, while the bullet-nosed geometry, which is a combination of the trapezoidal and rectangular designs, is used in some DTLs. This study shows that a larger good field region is possible in the 16-segment rectangular design as compared to the Halbach and bullet-nosed designs, making it more attractive for high-intensity proton linacs. An improvement in good-field region by ˜16% over the Halbach design is obtained in the optimized 16-segment rectangular design, although the field gradient is lower by ˜20%. Tolerance studies show that the rectangular segment PMQ design is substantially less sensitive to the easy axis orientation errors and hence will be a better choice for DTLs.

  19. High order magnetic optics for high dynamic range proton radiography at a kinetic energy of 800 MeV

    NASA Astrophysics Data System (ADS)

    Sjue, S. K. L.; Mariam, F. G.; Merrill, F. E.; Morris, C. L.; Saunders, A.

    2016-01-01

    Flash radiography with 800 MeV kinetic energy protons at Los Alamos National Laboratory is an important experimental tool for investigations of dynamic material behavior driven by high explosives or pulsed power. The extraction of quantitative information about density fields in a dynamic experiment from proton generated images requires a high fidelity model of the proton imaging process. It is shown that accurate calculations of the transmission through the magnetic lens system require terms beyond second order for protons far from the tune energy. The approach used integrates the correlated multiple Coulomb scattering distribution simultaneously over the collimator and the image plane. Comparison with a series of static calibration images demonstrates the model's accurate reproduction of both the transmission and blur over a wide range of tune energies in an inverse identity lens that consists of four quadrupole electromagnets.

  20. High order magnetic optics for high dynamic range proton radiography at a kinetic energy of 800 MeV.

    PubMed

    Sjue, S K L; Mariam, F G; Merrill, F E; Morris, C L; Saunders, A

    2016-01-01

    Flash radiography with 800 MeV kinetic energy protons at Los Alamos National Laboratory is an important experimental tool for investigations of dynamic material behavior driven by high explosives or pulsed power. The extraction of quantitative information about density fields in a dynamic experiment from proton generated images requires a high fidelity model of the proton imaging process. It is shown that accurate calculations of the transmission through the magnetic lens system require terms beyond second order for protons far from the tune energy. The approach used integrates the correlated multiple Coulomb scattering distribution simultaneously over the collimator and the image plane. Comparison with a series of static calibration images demonstrates the model's accurate reproduction of both the transmission and blur over a wide range of tune energies in an inverse identity lens that consists of four quadrupole electromagnets. PMID:26827356

  1. Absolute quantification for benzoic acid in processed foods using quantitative proton nuclear magnetic resonance spectroscopy.

    PubMed

    Ohtsuki, Takashi; Sato, Kyoko; Sugimoto, Naoki; Akiyama, Hiroshi; Kawamura, Yoko

    2012-09-15

    The absolute quantification method of benzoic acid (BA) in processed foods using solvent extraction and quantitative proton nuclear magnetic resonance spectroscopy was developed and validated. BA levels were determined using proton signals (δ(H) 7.53 and 7.98) referenced to 2-dimethyl-2-silapentane-5-sulfonate-d(6) sodium salt (DSS-d(6)) after simple solvent extraction from processed foods. All recoveries from several kinds of processed foods, spiked at their specified maximum Japanese usage levels (0.6-2.5 g kg(-1)) and at 0.13 g kg(-1) and 0.063 g kg(-1), were greater than 80%. The limit of quantification was confirmed as 0.063 g kg(-1) in processed foods, which was sufficiently low for the purposes of monitoring BA. The accuracy of the proposed method is equivalent to the conventional method using steam-distillation extraction and high-performance liquid chromatography. The proposed method was both rapid and simple. Moreover, it provided International System of Units traceability without the need for authentic analyte standards. Therefore, the proposed method is a useful and practical tool for determining BA levels in processed foods. PMID:22967562

  2. Carbon-13 and proton nuclear magnetic resonance spectroscopy of water-soluble porphyrins and metalloporphyrins.

    PubMed

    Goff, H M; Morgan, L O

    1978-07-01

    Carbon-13 and proton nuclear magnetic resonance (NMR) spectra have been recorded for porphyrins, zinc porphyrins, and iron(III) porphyrin complexes in aqueous media. Spectra of porphyrin-c and hemin-c confirm the structure with thioether linkages at positions alpha to the porphyrin ring. The pattern of NMR isotropic shifts has implications regarding electron transfer in cytochrome-c. Free-base porphyrin-c and meso-substituted porphyrins have been examined for pyrrole nitrogen-hydrogen tautomerism and possible aggregation in aqueous solution. Zinc porphyrin 13C NMR spectra were recorded in order to provide diamagnetic references for paramagnetic iron(III) derivatives. Low-spin iron(III) porphyrin-biscyano complexes in aqueous solution exhibit NMR isotropic shift patterns similar to those previously observed for related compounds in non-aqueous media. The first 13C NMR spectra are reported for mu-oxo-bridged iron(III) porphyrin dimers. A partially resolved spectrum of a high-spin iron(III) porphyrin has also been obtained. Patterns of 13C and proton isotropic shifts are compared, and unpaired spin delocalization mechanisms for 13C resonances are discussed in a qualitative manner. PMID:687673

  3. Spectral Analysis of Magnetic Fluctuations at Proton Scales from Fast to Slow Solar Wind

    NASA Astrophysics Data System (ADS)

    Bruno, R.; Telloni, D.

    2015-10-01

    This Letter investigates the spectral characteristics of interplanetary magnetic field fluctuations at proton scales during several time intervals chosen along the speed profile of a fast stream. The character of the fluctuations within the first frequency decade, beyond the high-frequency break located between the fluid and kinetic regimes, strongly depends on the type of wind. While the fast wind shows a clear signature of both right-handed and left-handed polarized fluctuations, possibly associated with Kinetic {Alfv}\\acute{{{e}}}{{n}} Wave (KAW) and ion-cyclotron waves, respectively, the rarefaction region, where the wind speed and the Alfvénicity of low-frequency fluctuations decrease, shows a rapid disappearance of the ion-cyclotron signature followed by a more gradual disappearance of KAWs. Moreover, the power associated with perpendicular and parallel fluctuations also experiences rapid depletion, however, retaining the power anisotropy in favor of the perpendicular spectrum.

  4. Covalency of hydrogen bonds in liquid water can be probed by proton nuclear magnetic resonance experiments

    PubMed Central

    Elgabarty, Hossam; Khaliullin, Rustam Z.; Kühne, Thomas D.

    2015-01-01

    The concept of covalency is widely used to describe the nature of intermolecular bonds, to explain their spectroscopic features and to rationalize their chemical behaviour. Unfortunately, the degree of covalency of an intermolecular bond cannot be directly measured in an experiment. Here we established a simple quantitative relationship between the calculated covalency of hydrogen bonds in liquid water and the anisotropy of the proton magnetic shielding tensor that can be measured experimentally. This relationship enabled us to quantify the degree of covalency of hydrogen bonds in liquid water using the experimentally measured anisotropy. We estimated that the amount of electron density transferred between molecules is on the order of 10  m while the stabilization energy due to this charge transfer is ∼15 kJ mol−1. The physical insight into the fundamental nature of hydrogen bonding provided in this work will facilitate new studies of intermolecular bonding in a variety of molecular systems. PMID:26370179

  5. Correction of Proton Resonance Frequency Shift Temperature Maps for Magnetic Field Disturbances Caused by Breathing

    NASA Astrophysics Data System (ADS)

    Shmatukha, Andriy V.; Bakker, Chris J. G.

    2006-05-01

    Respiratory Induced Resonance Offset (RIRO) is a periodic disturbance of the magnetic field due to breathing. Such disturbances handicap the accuracy of the Proton Resonance Frequency Shift (PRFS) method of MRI temperature mapping in anatomies situated nearby the lungs and chest wall. In this work, we propose a method capable of minimizing errors caused by RIRO in PRFS temperature maps. In this method, a set of baseline images characterizing RIRO at a variety of respiratory cycle instants is acquired before the thermal treatment starts. During the treatment, the temperature evolution is found from two successive images. Then, the calculated temperature changes are corrected for the additional contribution caused by RIRO using the pre-treatment baseline images acquired at the identical instances of the respiratory cycle. Our method is shown to improve the accuracy and stability of PRFS temperature maps in the presence of RIRO and motion in phantom and volunteer experiments.

  6. Gain stabilization control system of the upgraded magnetic proton recoil neutron spectrometer at JET

    SciTech Connect

    Sjoestrand, Henrik; Sunden, E. Andersson; Conroy, S.; Ericsson, G.; Johnson, M. Gatu; Giacomelli, L.; Hellesen, C.; Hjalmarsson, A.; Ronchi, E.; Weiszflog, M.; Gorini, G.; Tardocchi, M.; Popovichev, S. [EURATOM Collaboration: JET EFDA Contributors

    2009-06-15

    Burning plasma experiments such as ITER and DEMO require diagnostics capable of withstanding the harsh environment generated by the intense neutron flux and to maintain stable operating conditions for times longer than present day systems. For these reasons, advanced control and monitoring (CM) systems will be necessary for the reliable operation of diagnostics. This paper describes the CM system of the upgraded magnetic proton recoil neutron spectrometer installed at the Joint European Torus focusing in particular on a technique for the stabilization of the gain of the photomultipliers coupled to the neutron detectors. The results presented here show that this technique provides good results over long time scales. The technique is of general interest for all diagnostics that employ scintillators coupled to photomultiplier tubes.

  7. Covalency of hydrogen bonds in liquid water can be probed by proton nuclear magnetic resonance experiments.

    PubMed

    Elgabarty, Hossam; Khaliullin, Rustam Z; Kühne, Thomas D

    2015-01-01

    The concept of covalency is widely used to describe the nature of intermolecular bonds, to explain their spectroscopic features and to rationalize their chemical behaviour. Unfortunately, the degree of covalency of an intermolecular bond cannot be directly measured in an experiment. Here we established a simple quantitative relationship between the calculated covalency of hydrogen bonds in liquid water and the anisotropy of the proton magnetic shielding tensor that can be measured experimentally. This relationship enabled us to quantify the degree of covalency of hydrogen bonds in liquid water using the experimentally measured anisotropy. We estimated that the amount of electron density transferred between molecules is on the order of 10  m while the stabilization energy due to this charge transfer is ∼15 kJ mol(-1). The physical insight into the fundamental nature of hydrogen bonding provided in this work will facilitate new studies of intermolecular bonding in a variety of molecular systems. PMID:26370179

  8. Magnetic superbasic proton sponges are readily removed and permit direct product isolation.

    PubMed

    Schneider, Elia M; Raso, Renzo A; Hofer, Corinne J; Zeltner, Martin; Stettler, Robert D; Hess, Samuel C; Grass, Robert N; Stark, Wendelin J

    2014-11-21

    Workup in organic synthesis can be very time-consuming, particularly when using reagents with both a solubility similar to that of the desired products and a tendency not to crystallize. In this respect, reactions involving organic bases would strongly benefit from a tremendously simplified separation process. Therefore, we synthesized a derivative of the superbasic proton sponge 1,8-bis(dimethylamino)naphthalene (DMAN) and covalently linked it to the strongest currently available nanomagnets based on carbon-coated cobalt metal nanoparticles. The immobilized magnetic superbase reagent was tested in Knoevenagel- and Claisen-Schmidt-type condensations and showed conversions of up to 99%. High yields of up to 97% isolated product could be obtained by simple recrystallization without using column chromatography. Recycling the catalyst was simple and fast with an insignificant decrease in catalytic activity. PMID:25325822

  9. In vivo proton magnetic resonance spectroscopy of breast cancer: a review of the literature

    PubMed Central

    2012-01-01

    An emerging clinical modality called proton magnetic resonance spectroscopy (1H-MRS) enables the non-invasive in vivo assessment of tissue metabolism and is demonstrating applications in improving the specificity of MR breast lesion diagnosis and monitoring tumour responsiveness to neoadjuvant chemotherapies. Variations in the concentration of choline-based cellular metabolites, detectable with 1H-MRS, have shown an association with malignant transformation of tissue in in vivo and in vitro studies. 1H-MRS exists as an adjunct to the current routine clinical breast MR examination. This review serves as an introduction to the field of breast 1H-MRS, discusses modern high-field strength and quantitative approaches and technical considerations, and reviews the literature with respect to the application of 1H-MRS for breast cancer. PMID:22515594

  10. Proton Magnetic Resonance Spectroscopy and MRI Reveal No Evidence for Brain Mitochondrial Dysfunction in Children with Autism Spectrum Disorder

    ERIC Educational Resources Information Center

    Corrigan, Neva M.; Shaw, Dennis. W. W.; Richards, Todd L.; Estes, Annette M.; Friedman, Seth D.; Petropoulos, Helen; Artru, Alan A.; Dager, Stephen R.

    2012-01-01

    Brain mitochondrial dysfunction has been proposed as an etiologic factor in autism spectrum disorder (ASD). Proton magnetic resonance spectroscopic imaging ([superscript 1]HMRS) and MRI were used to assess for evidence of brain mitochondrial dysfunction in longitudinal samples of children with ASD or developmental delay (DD), and cross-sectionally…

  11. Investigation of the neuroprotective effects of bee-venom acupuncture in a mouse model of Parkinson's disease by using immunohistochemistry and In-vivo 1H magnetic resonance spectroscopy at 9.4 T

    NASA Astrophysics Data System (ADS)

    Yoon, Moon-Hyun; Lee, Do-Wan; Kim, Hyun-Jin; Chung, Jin-Yeung; Doo, Ah-Reum; Park, Hi-Joon; Kim, Seung-Nam; Choe, Bo-Young

    2013-01-01

    Neuroprotective therapeutics slows down the degeneration process in animal models of Parkinson's disease (PD). The neuronal survival in PD animal models is often measured by using immunohistochemistry. However, dynamic changes in the pathology of the brain cannot be explored with this technique. Application of in-vivo 1H magnetic resonance spectroscopy (1H MRS) can cover this shortcoming, as these techniques are non-invasive and can be repeated over time in the same animal. Thus, the sensitivity of both techniques to measure changes in the PD pathology was explored in an experiment studying the neuroprotective effects of the vigilance enhancer bee-venom (BV) in a mouse model of PD. The mice were pre-treated with 0.02-ml BV administered to the acupuncture point GB34 (Yangneungcheon) once every 3 days for 2 weeks. Three groups were classified as control, MPTP-intoxicated PD model and BV-treated mice. Outer volume suppression combined with the ultra-short echo-time STEAM (TE = 2.2 ms, TM = 20 ms, TR = 5000 ms) was used for localized in-vivo 1H MRS. Based on the 1H MRS spectral analysis, substantial changes of the neurochemical profiles were evaluated in the three investigated groups. In particular, the glutamate complex (Glx)/creatine (Cr) ratio (7.72 ± 1.25) in the PD group was significantly increased compared to that in the control group (3.93 ± 2.21, P = 0.001). Compared to the baseline values, the Glx/Cr ratio of the BV-treated group was significantly decreased 2 weeks after MPTP intoxication (one-way ANOVA, p < 0.05). In conclusion, the present study demonstrated that neurochemical alterations occurred in the three groups and that the neuroprotective effects of the BV acupuncture in a mouse model of PD could be quantified by using immunohistochemistry and 1H MRS.

  12. Temporal relationship between high-energy proton acceleration and magnetic field changes during solar flares

    NASA Astrophysics Data System (ADS)

    Kurt, Victoria; Yushkov, Boris

    Understanding of the association of the magnetic field evolution in the corona and the temporal evolution of electromagnetic emissions produced by the accelerated particles during a solar flare can provide information about the nature of the energy-release process and its location. Recent high-spatial-resolution observations in HXR, UV and radio emissions allow one to study in detail a structure of two-ribbon flare site. According to these observations, the flare process can be divided into two different intervals with different temporal evolution of morphological structure: loop contraction during impulsive phase and subsequent loop expansion. Оn the other hand, the appearance of high-energy protons (with energy >300 MeV - an energy threshold of the pion production) in the solar atmosphere can be revealed from an emerging pion-decay component of high-energy gamma-ray emission. The present work is based on comparison of measurements of high-energy gamma-rays performed with the SONG detector onboard the CORONAS-F mission and reported observations of magnetic field evolution, such as HXR foot points (FP) separation and flare shear temporal behavior, or motion of UV/radio loops. We reliably identified the pion-decay component of gamma-ray emission in the course of five events attended with suitable spatial observations, namely, 2001 August 25, 2002 August 24, 2003 October 28, 2003 October 29, and 2005 January 20, and determined its onset time. We found that in these events the pion-decay emission occurred when the distance between conjugated foot-points of flare loops ceased to decrease and began to increase, i.e. changed from shrinkage to expansion. This result leads to the conclusion that the most efficient proton acceleration up to >300 MeV coincided in time with the radical reconfiguration of the magnetic field in the flare site. Earlier we found that the pion-decay emission onset in the 2003 October 28 flare was close to the time of maximum change rate of the

  13. Particle selection and beam collimation system for laser-accelerated proton beam therapy.

    PubMed

    Luo, Wei; Fourkal, Eugene; Li, Jinsheng; Ma, Chang-Ming

    2005-03-01

    In a laser-accelerated proton therapy system, the initial protons have broad energy and angular distributions, which are not suitable for direct therapeutic applications. A compact particle selection and collimation device is needed to deliver small pencil beams of protons with desired energy spectra. In this work, we characterize a superconducting magnet system that produces a desired magnetic field configuration to spread the protons with different energies and emitting angles for particle selection. Four magnets are set side by side along the beam axis; each is made of NbTi wires which carry a current density of approximately 10(5) A/cm2 at 4.2 K, and produces a magnetic field of approximately 4.4 T in the corresponding region. Collimation is applied to both the entrance and the exit of the particle selection system to generate a desired proton pencil beam. In the middle of the magnet system, where the magnetic field is close to zero, a particle selection collimator allows only the protons with desired energies to pass through for therapy. Simulations of proton transport in the presence of the magnetic field show that the selected protons have successfully refocused on the beam axis after passing through the magnetic field with the optimal magnet system. The energy spread for any given characteristic proton energy has been obtained. It is shown that the energy spread is a function of the magnetic field strength and collimator size and reaches the full width at half maximum of 25 MeV for 230 MeV protons. Dose distributions have also been calculated with the GEANT3 Monte Carlo code to study the dosimetric properties of the laser-accelerated proton beams for radiation therapy applications. PMID:15839352

  14. Electron Cloud Generation and Trapping in a Quadrupole Magnet at the Los Alamos Proton Storage Ring

    SciTech Connect

    Macek, Robert J.; Browman, Andrew A.; Ledford, John E.; Borden, Michael J.; O'Hara, James F.; McCrady, Rodney C.; Rybarcyk, Lawrence J.; Spickermann, Thomas; Zaugg, Thomas J.; Pivi, Mauro T.F.; /SLAC

    2008-03-17

    Recent beam physics studies on the two-stream e-p instability at the LANL proton storage ring (PSR) have focused on the role of the electron cloud generated in quadrupole magnets where primary electrons, which seed beam-induced multipacting, are expected to be largest due to grazing angle losses from the beam halo. A new diagnostic to measure electron cloud formation and trapping in a quadrupole magnet has been developed, installed, and successfully tested at PSR. Beam studies using this diagnostic show that the 'prompt' electron flux striking the wall in a quadrupole is comparable to the prompt signal in the adjacent drift space. In addition, the 'swept' electron signal, obtained using the sweeping feature of the diagnostic after the beam was extracted from the ring, was larger than expected and decayed slowly with an exponential time constant of 50 to 100 {micro}s. Other measurements include the cumulative energy spectra of prompt electrons and the variation of both prompt and swept electron signals with beam intensity. Experimental results were also obtained which suggest that a good fraction of the electrons observed in the adjacent drift space for the typical beam conditions in the 2006 run cycle were seeded by electrons ejected from the quadrupole.

  15. Neurochemistry of Drug Action: Insights from Proton Magnetic Resonance Spectroscopic Imaging And Their Relevance to Addiction

    PubMed Central

    Licata, Stephanie C.; Renshaw, Perry F.

    2011-01-01

    Proton magnetic resonance spectroscopy (1H MRS) is a non-invasive imaging technique that permits measurement of particular compounds or metabolites within the tissue of interest. In the brain, 1H MRS provides a snapshot of the neurochemical environment within a defined volume of interest. A search of the literature demonstrates the widespread utility of this technique for characterizing tumors, tracking the progress of neurodegenerative disease, and for understanding the neurobiological basis of psychiatric disorders. As of relatively recently, 1H MRS has found its way into substance abuse research, and it is beginning to become recognized as a valuable complement in the brain imaging toolbox that also contains positron emission tomography (PET), single photon emission computed tomography (SPECT), and functional magnetic resonance imaging (fMRI). Drug abuse studies employing 1H MRS have identified a number biochemical changes in the brain. The most consistent alterations across drug class were reductions in N-acetylaspartate and elevations in myo-inositol, while changes in choline, creatine, and amino acid transmitters also were abundant. Together, the studies discussed herein provide evidence that drugs of abuse may have a profound impact on neuronal health, energy metabolism and maintenance, inflammatory processes, cell membrane turnover, and neurotransmission, and these biochemical changes may underlie the neuropathology within brain tissue that subsequently gives rise to the cognitive and behavioral impairments associated with drug addiction. PMID:20201852

  16. Pion production via proton synchrotron radiation in strong magnetic fields in relativistic field theory: Scaling relations and angular distributions

    NASA Astrophysics Data System (ADS)

    Maruyama, Tomoyuki; Cheoun, Myung-Ki; Kajino, Toshitaka; Mathews, Grant J.

    2016-06-01

    We study pion production by proton synchrotron radiation in the presence of a strong magnetic field when the Landau numbers of the initial and final protons are ni,f ∼104-105. We find in our relativistic field theory calculations that the pion decay width depends only on the field strength parameter which previously was only conjectured based upon semi-classical arguments. Moreover, we also find new results that the decay width satisfies a robust scaling relation, and that the polar angular distribution of emitted pion momenta is very narrow and can be easily obtained. This scaling implies that one can infer the decay width in more realistic magnetic fields of 1015 G, where ni,f ∼1012-1013, from the results for ni,f ∼104-105. The resultant pion intensity and angular distributions for realistic magnetic field strengths are presented and their physical implications discussed.

  17. Pion production via proton synchrotron radiation in strong magnetic fields in relativistic field theory: Scaling relations and angular distributions

    NASA Astrophysics Data System (ADS)

    Maruyama, Tomoyuki; Cheoun, Myung-Ki; Kajino, Toshitaka; Mathews, Grant J.

    2016-06-01

    We study pion production by proton synchrotron radiation in the presence of a strong magnetic field when the Landau numbers of the initial and final protons are ni,f ∼104-105. We find in our relativistic field theory calculations that the pion decay width depends only on the field strength parameter which previously was only conjectured based upon semi-classical arguments. Moreover, we also find new results that the decay width satisfies a robust scaling relation, and that the polar angular distribution of emitted pion momenta is very narrow and can be easily obtained. This scaling implies that one can infer the decay width in more realistic magnetic fields of 1015 G, where ni,f ∼1012-1013, from the results for ni,f ∼104-105. The resultant pion intensity and angular distributions for realistic magnetic field strengths are presented and their physical implications discussed.

  18. On the origins of chemical exchange saturation transfer (CEST) contrast in tumors at 9.4T

    PubMed Central

    Xu, Junzhong; Zaiss, Moritz; Zu, Zhongliang; Li, Hua; Xie, Jingping; Gochberg, Daniel F.; Bachert, Peter; Gore, John C.

    2014-01-01

    Chemical exchange saturation transfer (CEST) provides an indirect means to detect exchangeable protons within tissues through their effects on the water signal. Previous studies have suggested that amide proton transfer (APT) imaging, a specific form of CEST, detects endogenous amide protons with a resonance frequency offset 3.5 ppm downfield from water, and thus may be sensitive to variations of mobile proteins/peptides in tumors. However, since CEST measurements are influenced by various confounding effects, such as spillover saturation, magnetization transfer (MT) and MT asymmetry, the mechanism or degree of increased APT signal in tumors are not certain. In addition to APT, nuclear Overhauser enhancement (NOE) effects upfield from water may also provide distinct information about tissue composition. In the current study, APT, NOE and several other magnetic resonance parameters were measured and compared comprehensively in order to elucidate the origins of APT and NOE contrasts in tumors at 9.4T. In addition to conventional CEST methods, a new intrinsic inverse metric was applied to correct for relaxation and other effects. After corrections for spillover, MT and T1 effects, corrected APT in tumors was found not significantly different from normal tissues, but corrected NOE effects in tumors showed significant decreases compared with normal tissues. Biochemical measurements verified that there is no significant enhancement of protein contents in the tumors studied, consistent with corrected APT measurements and previous literature while qMT data showed decreases in the fractions of immobile macromolecules in tumors. Our results may assist better understanding the contrast depicted by CEST imaging in tumors, and the development of improved APT and NOE measurements for cancer imaging. PMID:24474497

  19. Removal of power-line harmonics from proton magnetic resonance measurements

    NASA Astrophysics Data System (ADS)

    Legchenko, Anatoly; Valla, Pierre

    2003-08-01

    The Magnetic Resonance Sounding (MRS) method is based on the resonance behaviour of proton magnetic moments in the geomagnetic field. The main distinction between MRS and other geophysical methods is that it measures the magnetic resonance signal directly from groundwater molecules, making it a selective tool sensitive to groundwater. As the signal generated by the protons is very small, the method is also sensitive to electromagnetic interference (noise) and this is one of the major limitations for practical application. The frequency of the magnetic resonance signal (the Larmor frequency) is directly proportional to the magnitude of the geomagnetic field and varies between 800 and 2800 Hz around the globe. Whilst natural noise within this frequency range is generally not very large (excepting magnetic storms or other temporary disturbances), the level of cultural noise (electrical power lines, generators, etc.) may be very high. In order to improve performance, three existing filtering techniques were adapted to processing MRS measurements: block subtraction, sinusoid subtraction and notch filtering. The first two are subtraction techniques capable of suppressing stationary power-line noise without distorting or attenuating the signal of interest, both involve subtracting an estimate of the harmonic component but differ in the way the component is estimated. The block subtraction method consists of ascertaining the power-line noise (or "noise block") from a record of the noise alone, and then subtracting this block from a record containing both the noise and the signal. The sinusoid subtraction method is based on the calculation of the amplitude, frequency and phase of power-line harmonics using noise records. The notch filtering method does not require knowledge of the power-line harmonic parameters but it may cause distortion of the measured signal. During the study, it was found that, in the investigated frequency range, the electromagnetic noise produced by

  20. A TCT and annealing study on Magnetic Czochralski silicon detectors irradiated with neutrons and 24 GeV/ c protons

    NASA Astrophysics Data System (ADS)

    Pacifico, Nicola; Creanza, Donato; de Palma, Mauro; Manna, Norman; Kramberger, Gregor; Moll, Michael

    2010-01-01

    Silicon diodes (pad detectors) were irradiated with 24 GeV/ c protons at the CERN PS IRRAD1 facility and with neutrons at the TRIGA reactor in Ljubljana (Slovenia). The diodes were realized on Magnetic Czochralski (MCz) grown silicon, of both n- and p-type. After irradiation, an annealing study with CV measurements was performed on 24 GeV/ c proton irradiated detectors, looking for hints of type inversion after irradiation and during annealing. Other pad detectors were studied using the TCT (transient current technique), to gather information about the field profile in the detector bulk and thus about the effective space charge distribution within it.

  1. 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.

  2. 26 CFR 1.846-4T - Effective dates (temporary).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 8 2010-04-01 2010-04-01 false Effective dates (temporary). 1.846-4T Section 1.846-4T Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Other Insurance Companies § 1.846-4T Effective dates (temporary). (a) . For...

  3. 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...

  4. 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...

  5. 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...

  6. 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...

  7. 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...

  8. Determination of apomorphine freebase in sublingual tablets by proton nuclear magnetic resonance spectroscopy.

    PubMed

    Tan, Li; Chin, Shook F; Miner, Virginia W; Dong, Liang; Gupta, Suneel; Fields, Steven M

    2016-09-10

    An apomorphine sublingual tablet formulation under development contains mixtures of apomorphine freebase (FB) and apomorphine hydrochloride salt. It is important to have a reliable analytical method to determine the ratio of the base and salt forms to ensure accuracy, reproducibility and robustness of the manufacturing processes as well as to meet the requirements of the quality target product profile. A Proton Nuclear Magnetic Resonance ((1)H NMR) spectroscopy method based on the proton shift of the amine methyl group (N-CH3) in apomorphine has been developed to determine the mole percentage of freebase to the total mole of freebase and hydrochloride salt in the drug product. The method was evaluated in terms of specificity, linearity, and variability. The presence of excipients does not interfere with the analysis. A standard calibration curve of the chemical shift as a function of the proportion of freebase forms of apomorphine was established, covering the range of 100% apomorphine freebase to 100% apomorhine hydrochloride. The correlation coefficient (r(2)), slope, and Y-intercept of the regression line are 0.998, -0.00596, and 3.191, respectively. The day-to-day variability of the (1)H shift in two instruments in the standard is less than 1% RSD. Three lots of the sublingual tablet drug product were examined and quantified by the standard. The mole percent apomorphine freebase was determined to be 73.8%, 75.2%, and 76.2%, respectively, within 100.0%±2.0% of the target value of 75.0%. The method is a new avenue to use the (1)H NMR technique for determination of apomorphine freebase and salt ratio in a solid drug product dosage form for release testing and in-process control. PMID:27454089

  9. The low energy magnetic spectrometer on Ulysses and ACE response to near relativistic protons

    NASA Astrophysics Data System (ADS)

    Morgado, Bruno; Filipe Maia, Dalmiro Jorge; Lanzerotti, Louis; Gonçalves, Patrícia; Patterson, J. Douglas

    2015-05-01

    Aims: We show that the Heliosphere Instrument for Spectra Composition and Anisotropy at Low Energies (HISCALE) on board the Ulysses spacecraft and the Electron Proton Alpha Monitor (EPAM) on board the Advance Composition Explorer (ACE) spacecraft can be used to measure properties for ion populations with kinetic energies in excess of 1 GeV. This previously unexplored source of information is valuable for understanding the origin of near relativistic ions of solar origin. Methods: We model the instrumental response from the low energy magnetic spectrometers from EPAM and HISCALE using a Monte Carlo approach implemented in the Geant4 toolkit to determine the response of different energy channels to energies up to 5 GeV. We compare model results with EPAM observations for 2012 May 17 ground level solar cosmic ray event, including directional fluxes. Results: For the 2012 May event, all the ion channels in EPAM show an onset more than one hour before ions with the highest nominal energy range (1.8 to 4.8 MeV) were expected to arrive. We show from Monte Carlo simulations that the timing at different channels, the ratio between counts at the different channels, and the directional fluxes within a given channel, are consistent with and can be explained by the arrival of particles with energies from 35 MeV to more than 1 GeV. Onset times for the EPAM penetrating protons are consistent with the rise seen in neutron monitor data, implying that EPAM and ground neutron monitors are seeing overlapping energy ranges and that both are consistent with GeV ions being released from the Sun at 10:38 UT.

  10. High order magnetic optics for high dynamic range proton radiography at a kinetic energy 800 MeV

    DOE PAGESBeta

    Sjue, Sky K. L.; Morris, Christopher L.; Merrill, Frank Edward; Mariam, Fesseha Gebre; Saunders, Alexander

    2016-01-14

    Flash radiography with 800 MeV kinetic energy protons at Los Alamos National Laboratory is an important experimental tool for investigations of dynamic material behavior driven by high explosives or pulsed power. The extraction of quantitative information about density fields in a dynamic experiment from proton generated images requires a high fidelity model of the protonimaging process. It is shown that accurate calculations of the transmission through the magnetic lens system require terms beyond second order for protons far from the tune energy. The approach used integrates the correlated multiple Coulomb scattering distribution simultaneously over the collimator and the image plane.more » Furthermore, comparison with a series of static calibrationimages demonstrates the model’s accurate reproduction of both the transmission and blur over a wide range of tune energies in an inverse identity lens that consists of four quadrupole electromagnets.« less

  11. Status of intense permanent magnet proton source for China-accelerator driven sub-critical system Linac

    NASA Astrophysics Data System (ADS)

    Wu, Q.; Ma, H. Y.; Yang, Y.; Sun, L. T.; Zhang, X. Z.; Zhang, Z. M.; Zhao, H. Y.; He, Y.; Zhao, H. W.

    2016-02-01

    Two compact intense 2.45 GHz permanent magnet proton sources and their corresponding low energy beam transport (LEBT) system were developed successfully for China accelerator driven sub-critical system in 2014. Both the proton sources operate at 35 kV potential. The beams extracted from the ion source are transported by the LEBT, which is composed of two identical solenoids, to the 2.1 MeV Radio-Frequency Quadrupole (RFQ). In order to ensure the safety of the superconducting cavities during commissioning, an electrostatic-chopper has been designed and installed in the LEBT line that can chop the continuous wave beam into a pulsed one. The minimum width of the pulse is less than 10 μs and the fall/rise time of the chopper is about 20 ns. The performance of the proton source and the LEBT, such as beam current, beam profile, emittance and the impact to RFQ injection will be presented.

  12. Direct measurement of kilo-tesla level magnetic field generated with laser-driven capacitor-coil target by proton deflectometry

    NASA Astrophysics Data System (ADS)

    Law, K. F. F.; Bailly-Grandvaux, M.; Morace, A.; Sakata, S.; Matsuo, K.; Kojima, S.; Lee, S.; Vaisseau, X.; Arikawa, Y.; Yogo, A.; Kondo, K.; Zhang, Z.; Bellei, C.; Santos, J. J.; Fujioka, S.; Azechi, H.

    2016-02-01

    A kilo-tesla level, quasi-static magnetic field (B-field), which is generated with an intense laser-driven capacitor-coil target, was measured by proton deflectometry with a proper plasma shielding. Proton deflectometry is a direct and reliable method to diagnose strong, mm3-scale laser-produced B-field; however, this was not successful in the previous experiment. A target-normal-sheath-accelerated proton beam is deflected by Lorentz force in the laser-produced magnetic field with the resulting deflection pattern recorded on a radiochromic film stack. A 610 ± 30 T of B-field amplitude was inferred by comparing the experimental proton pattern with Monte-Carlo calculations. The amplitude and temporal evolutions of the laser-generated B-field were also measured by a differential magnetic probe, independently confirming the proton deflectometry measurement results.

  13. Why baryons are Yang-Mills magnetic monopoles, validated by nuclear binding energies and proton and neutron masses

    NASA Astrophysics Data System (ADS)

    Yablon, Jay R.

    2013-10-01

    Evidence is summarized from four recent papers that baryons including protons and neutrons are magnetic monopoles of non-commuting Yang-Mills gauge theories: 1) Protons and neutrons are ``resonant cavities'' with binding energies determined strictly by the masses of the quarks they contain. This is proven true at parts-per million accuracy for each of the 2H, 3H,3He, 4He binding energies and the neutron minus proton mass difference. 2) Respectively, each free proton and neutron contains 7.64 MeV and 9.81 MeV of mass/energy used to confine its quarks. When these nucleons bind, some, never all, of this energy is released and the mass deficit goes into binding. The balance continues to confine quarks. 56Fe releases 99.8429% of this energy for binding, more than any other nuclide. 3) Once we consider the Fermi vev one also finds an entirely theoretical explanation of proton and neutron masses, which also connects within experimental errors to the CKM quark mixing angles. 4) A related GUT explains fermion generation replication based on generator loss during symmetry breaking, and answers Rabi's question ``who ordered this?'' 5) Nuclear physics is governed by combining Maxwell's two classical equations into one equation using non-commuting gauge fields in view of Dirac theory and Fermi-Dirac-Pauli Exclusion. 6) Atoms themselves are core magnetic charges (nucleons) paired with orbital electric charges (electrons and elusive neutrinos), with the periodic table itself revealing an electric/magnetic symmetry of Maxwell's equations often pondered but heretofore unrecognized for a century and a half.

  14. Proton and phosphorus magnetic resonance spectroscopy of a mouse model of Alzheimer's disease.

    PubMed

    Mlynárik, Vladimír; Cacquevel, Matthias; Sun-Reimer, Lili; Janssens, Sharon; Cudalbu, Cristina; Lei, Hongxia; Schneider, Bernard L; Aebischer, Patrick; Gruetter, Rolf

    2012-01-01

    The development of new diagnostic criteria for Alzheimer's disease (AD) requires new in vivo markers reflecting early pathological changes in the brain of patients. Magnetic resonance (MR) spectroscopy has been shown to provide useful information about the biochemical changes occurring in AD brain in vivo. The development of numerous transgenic mouse models of AD has facilitated the evaluation of early biomarkers, allowing researchers to perform longitudinal studies starting before the onset of the pathology. In addition, the recent development of high-field animal scanners enables the measurement of brain metabolites that cannot be reliably quantified at lower magnetic fields. In this report, we studied a new transgenic mouse model of AD, the 5xFAD model, by in vivo proton and phosphorus MR spectroscopy. This model, which is characterized by an early-onset and a robust amyloid pathology, developed changes in the neurochemical profile, which are typical in the human disease, i.e., an increase in myo-inositol and a decrease in N-acetylaspartate concentrations, as early as in the 40th week of age. In addition, a significant decrease in the γ-aminobutyrate concentration was observed in transgenic mice at this age compared to controls. The pseudo-first-order rate constant of the creatine kinase reaction as well as relative concentrations of phosphorus-containing metabolites were not changed significantly in the 36 and 72-week old transgenic mice. Overall, these results suggest that mitochondrial activity in the 5 × FAD mice is not substantially affected but that the model is relevant for studying early biomarkers of AD. PMID:22451319

  15. Quantitation of memantine hydrochloride bulk drug and its tablet formulation using proton nuclear magnetic resonance spectrometry.

    PubMed

    Sahu, Archana; Narayanam, Mallikarjun; Kurmi, Moolchand; Ladumor, Mayurbhai Kathadbhai; Singh, Saranjit

    2016-08-01

    The use of quantitative nuclear magnetic resonance spectrometry for the determination of non-UV active memantine hydrochloride with relative simplicity and precision has been demonstrated in this study. The method was developed on a 500 MHz NMR instrument and was applied to determination of the drug in a tablet formulation. The analysis was performed by taking caffeine as an internal standard and D2 O as the NMR solvent. The signal of methyl protons of memantine hydrochloride appeared at 0.75 ppm (singlet) relative to the signal of caffeine (internal standard) at 3.13 ppm (singlet). The method was found to be linear (r(2)  = 0.9989) in the drug concentration range of 0.025 to 0.80 mg/ml. The maximum relative standard deviation for accuracy and precision was <2. The limits of detection and quantification were 0.04 and 0.11 mg/ml, respectively. The robustness of the method was revealed by changing nine different parameters. The deviation for each parameter was also within the acceptable limits. The study highlighted possibility of direct determination of memantine hydrochloride in pure form and in its marketed tablet formulation by the use of quantitative NMR, without the need of derivatization, as is the requirement in HPLC studies. Copyright © 2016 John Wiley & Sons, Ltd. PMID:26923624

  16. Absolute quantification of carnosine in human calf muscle by proton magnetic resonance spectroscopy

    NASA Astrophysics Data System (ADS)

    Özdemir, Mahir S.; Reyngoudt, Harmen; DeDeene, Yves; Sazak, Hakan S.; Fieremans, Els; Delputte, Steven; D'Asseler, Yves; Derave, Wim; Lemahieu, Ignace; Achten, Eric

    2007-12-01

    Carnosine has been shown to be present in the skeletal muscle and in the brain of a variety of animals and humans. Despite the various physiological functions assigned to this metabolite, its exact role remains unclear. It has been suggested that carnosine plays a role in buffering in the intracellular physiological pHi range in skeletal muscle as a result of accepting hydrogen ions released in the development of fatigue during intensive exercise. It is thus postulated that the concentration of carnosine is an indicator for the extent of the buffering capacity. However, the determination of the concentration of this metabolite has only been performed by means of muscle biopsy, which is an invasive procedure. In this paper, we utilized proton magnetic resonance spectroscopy (1H MRS) in order to perform absolute quantification of carnosine in vivo non-invasively. The method was verified by phantom experiments and in vivo measurements in the calf muscles of athletes and untrained volunteers. The measured mean concentrations in the soleus and the gastrocnemius muscles were found to be 2.81 ± 0.57/4.8 ± 1.59 mM (mean ± SD) for athletes and 2.58 ± 0.65/3.3 ± 0.32 mM for untrained volunteers, respectively. These values are in agreement with previously reported biopsy-based results. Our results suggest that 1H MRS can provide an alternative method for non-invasively determining carnosine concentration in human calf muscle in vivo.

  17. Proton nuclear magnetic resonance of regenerating rat liver after partial hepatectomy

    SciTech Connect

    de Certaines, J.D.; Moulinoux, J.P.; Benoist, L.; Benard, A.; Rivet, P.

    1982-08-09

    Spin-lattice (T/sub 1/) and spin-spin (T/sub 2/) proton nuclear magnetic resonance relaxation times were measured over a 48-hours period of experimental liver regeneration in Wistar rats, T/sub 2/ showed an early significant increase reaching a plateau 30% above baseline from the 10th hrs onwards. Laparotomized control animals showed no change in T/sub 2/ values. The increase in T/sub 1/ occurred at a later stage but was no different from that in laparotomized controls. T/sub 1/ reached a peak, 20% above baseline, around the 30th hr. The changes observed were far less marked than those previously described for cancer tissue, which showed about a 60% increase in T/sub 1/ fluctuations followed a circadian pattern, with a minimum at night's end and a maximum around mid-day. No circadian rhythm was seen for T/sub 2/. The observed T/sub 1/ and T/sub 2/ changes are discussed with respect to mitotic and metabolic events known to occur during regeneration of the liver.

  18. A comprehensive review of proton magnetic resonance spectroscopy studies in dementia and Parkinson's disease.

    PubMed

    Firbank, M J; Harrison, R M; O'Brien, J T

    2002-01-01

    We reviewed the literature of proton magnetic resonance spectroscopy (MRS) in dementia and Parkinson's disease (PD) and quantitatively compared the reported values of the markers N-acetyl aspartate (NAA), choline, and myo-Inositol between control and disease groups. We analysed a total of 27 reports in dementia. Combining the quantitative data from these showed a relative decrease of 15% in NAA level in the temporal lobe tissue in patients with Alzheimer's disease (AD) compared with controls. The rest of the brain showed a seemingly uniform 10% decrease in NAA levels in AD compared with controls. myo-Inositol was raised by about 15%, again uniformly throughout the brain, but there was no evidence for changed levels of choline. We found 15 reports of MRS in PD, which show a small decrease (5%) in the NAA level in the lentiform nucleus compared with controls. In progressive supranuclear palsy (PSP), there is a greater decrease in NAA levels in the frontal region and the lentiform nucleus. This may aid in the diagnosis of PSP. Further research is needed to determine spectroscopic changes in other dementias, to monitor how markers change with disease progression and to establish clinical utility. PMID:12145453

  19. Probing astrocyte metabolism in vivo: proton magnetic resonance spectroscopy in the injured and aging brain.

    PubMed

    Harris, Janna L; Choi, In-Young; Brooks, William M

    2015-01-01

    Following a brain injury, the mobilization of reactive astrocytes is part of a complex neuroinflammatory response that may have both harmful and beneficial effects. There is also evidence that astrocytes progressively accumulate in the normal aging brain, increasing in both number and size. These astrocyte changes in normal brain aging may, in the event of an injury, contribute to the exacerbated injury response and poorer outcomes observed in older traumatic brain injury (TBI) survivors. Here we present our view that proton magnetic resonance spectroscopy ((1)H-MRS), a neuroimaging approach that probes brain metabolism within a defined region of interest, is a promising technique that may provide insight into astrocyte metabolic changes in the injured and aging brain in vivo. Although (1)H-MRS does not specifically differentiate between cell types, it quantifies certain metabolites that are highly enriched in astrocytes (e.g., Myo-inositol, mlns), or that are involved in metabolic shuttling between astrocytes and neurons (e.g., glutamate and glutamine). Here we focus on metabolites detectable by (1)H-MRS that may serve as markers of astrocyte metabolic status. We review the physiological roles of these metabolites, discuss recent (1)H-MRS findings in the injured and aging brain, and describe how an astrocyte metabolite profile approach might be useful in clinical medicine and clinical trials. PMID:26578948

  20. Absolute quantitative analysis for sorbic acid in processed foods using proton nuclear magnetic resonance spectroscopy.

    PubMed

    Ohtsuki, Takashi; Sato, Kyoko; Sugimoto, Naoki; Akiyama, Hiroshi; Kawamura, Yoko

    2012-07-13

    An analytical method using solvent extraction and quantitative proton nuclear magnetic resonance (qHNMR) spectroscopy was applied and validated for the absolute quantification of sorbic acid (SA) in processed foods. The proposed method showed good linearity. The recoveries for samples spiked at the maximum usage level specified for food in Japan and at 0.13 g kg(-1) (beverage: 0.013 g kg(-1)) were larger than 80%, whereas those for samples spiked at 0.063 g kg(-1) (beverage: 0.0063 g kg(-1)) were between 56.9 and 83.5%. The limit of quantification was 0.063 g kg(-1) for foods (and 0.0063 g kg(-1) for beverages containing Lactobacillus species). Analysis of the SA content of commercial processed foods revealed quantities equal to or greater than those measured using conventional steam-distillation extraction and high-performance liquid chromatography quantification. The proposed method was rapid, simple, accurate, and precise, and provided International System of Units traceability without the need for authentic analyte standards. It could therefore be used as an alternative to the quantification of SA in processed foods using conventional method. PMID:22704472

  1. Nuclear magnetic resonance and proton relaxation times in experimental heterotopic heart transplantation

    SciTech Connect

    Eugene, M.; Lechat, P.; Hadjiisky, P.; Teillac, A.; Grosgogeat, Y.; Cabrol, C.

    1986-01-01

    It should be possible to detect heart transplant rejection by nuclear magnetic resonance (NMR) imaging if it induces myocardial T1 and T2 proton relaxation time alterations or both. We studied 20 Lewis rats after a heterotopic heart transplantation. In vitro measurement of T1 and T2 was performed on a Minispec PC20 (Bruker) 3 to 9 days after transplantation. Histologic analysis allowed the quantification of rejection process based on cellular infiltration and myocardiolysis. Water content, a major determinant of relaxation time, was also studied. T1 and T2 were significantly prolonged in heterotopic vs orthotopic hearts (638 +/- 41 msec vs 606 +/- 22 msec for T1, p less than 0.01 and 58.2 +/- 8.4 msec vs 47.4 +/- 1.9 msec for T2, p less than 0.001). Water content was also increased in heterotopic hearts (76.4 +/- 2.3 vs 73.8 +/- 1.0, p less than 0.01). Most importantly, we found close correlations between T1 and especially T2 vs water content, cellular infiltration, and myocardiolysis. We conclude that rejection reaction should be noninvasively detected by NMR imaging, particularly with pulse sequences emphasizing T2.

  2. Characterization of urban aerosol using aerosol mass spectrometry and proton nuclear magnetic resonance spectroscopy

    NASA Astrophysics Data System (ADS)

    Cleveland, M. J.; Ziemba, L. D.; Griffin, R. J.; Dibb, J. E.; Anderson, C. H.; Lefer, B.; Rappenglück, B.

    2012-07-01

    Particulate matter was measured during August and September of 2006 in Houston as part of the Texas Air Quality Study II Radical and Aerosol Measurement Project. Aerosol size and composition were determined using an Aerodyne quadrupole aerosol mass spectrometer. Aerosol was dominated by sulfate (4.1 ± 2.6 μg m-3) and organic material (5.5 ± 4.0 μg m-3), with contributions of organic material from both primary (˜32%) and secondary (˜68%) sources. Secondary organic aerosol appears to be formed locally. In addition, 29 aerosol filter samples were analyzed using proton nuclear magnetic resonance (1H NMR) spectroscopy to determine relative concentrations of organic functional groups. Houston aerosols are less oxidized than those observed elsewhere, with smaller relative contributions of carbon-oxygen double bonds. These particles do not fit 1H NMR source apportionment fingerprints for identification of secondary, marine, and biomass burning organic aerosol, suggesting that a new fingerprint for highly urbanized and industrially influenced locations be established.

  3. Proton magnetic resonance studies of 2'-,3'-, and 5'-deoxyadenosine conformations in solution.

    PubMed Central

    Westhof, E; Plach, H; Cuno, I; Lüdemann, H D

    1977-01-01

    Proton magnetic resonance studies of 2'-deoxyadenosine (2'-dA), 3'-deoxyadenosine (3'-dA), 5'-deoxyadenosine (5'-dA) and 8-bromo-5'-deoxyadenosine (8-Br-5'-dA) have been carried out in the temperature range between -60 degrees and +40 degrees C for ND3 solutios, +40 degrees and +100 degrees C for D2O solutions, and finally +10 degrees and +60 degrees C for pyridine solutions. The analysis is based on the two-state S in equilibrium N model of the ribose moiety proposed by Altona and Sundaralingam. In all solvents, 2'-dA favours slightly the S state of the ribose and the g+ conformer of the exocyclic CH2OH group. However, 3'-dA prefers strongly the N state of the ribose and the g+ conformation. Both the S and N states of the ribose are equally favoured by 5'-DA and 8-Br-5'-dA. Evidence for the existence of an intramolecular hydrogen bond between 0(5') and N3 in purine (beta)-nucleosides is presented. It is also concluded that cordycepin (3'-dA) exists in solution mainly in the anti conformation of the base relative to the ribose. PMID:301272

  4. Localized proton magnetic resonance spectroscopy of the brain differentiates the inborn metabolic encephalopathies in children.

    PubMed

    Chabrol, B; Salvan, A M; Confort-Gouny, S; Vion-Dury, J; Cozzone, P J

    1995-09-01

    Localized brain proton magnetic resonance spectroscopy (MRS) has been performed using a STEAM (stimulated echo-acquisition mode) method with a short-echo time (20 ms) in 10 children suffering from different lysosomal diseases, 6 boys with X-linked adrenoleukodystrophy (X-ALD) and 5 healthy children. Metabolic data from localized spectra were processed by principal component analysis (PCA) of 7 metabolic variables recorded on the MR spectra. PCA allows to delineate different clusters corresponding to the 2 pathological groups which are separated from each other and from the control group. The position of each spectrum on the patient map correlates with the clinical data and to the evolution of the patients subjected to a follow-up. These results also confirm the metabolic features characterizing the pathologies of the lysosome (increase in inositol) and the peroxisome (increase in choline and free lipids). PCA constitutes an alternative to the classical statistical methods to analyze and compare metabolic modifications in small populations of patients and allows to identify the most critical parameters defining the organization of the pathological populations. This analysis clearly increases the discrimination among pathologies based on the metabolic profiles obtained by MRS. PMID:8521083

  5. Production polarization and magnetic moment of Ξ¯+ antihyperons produced by 800-GeV/c protons

    NASA Astrophysics Data System (ADS)

    Ho, P. M.; Longo, M. J.; Nguyen, A.; Luk, K. B.; James, C.; Rameika, R.; Duryea, J.; Guglielmo, G.; Heller, K.; Johns, K.; Diehl, H. T.; Teige, S.; Thomson, G. B.; Zou, Y.

    1990-10-01

    The polarization of Ξ¯ + hyperons produced by 800-GeV/c protons in the inclusive reaction p+Be-->Ξ¯ ++X has been measured. The average polarization of the Ξ¯ +, at a mean xF=0.39 and pt=0.76 GeV/c, is -0.097+/-0.012+/-0.009. The magnetic moment of the Ξ¯ + is 0.657+/-0.028+/-0.020 nuclear magneton.

  6. Development of an all-permanent-magnet microwave ion source equipped with multicusp magnetic fields for high current proton beam production.

    PubMed

    Tanaka, M; Hara, S; Seki, T; Iga, T

    2008-02-01

    An all-permanent-magnet (APM) microwave hydrogen ion source was developed to reduce the size and to simplify structure of a conventional solenoid coil microwave ion source developed for reliability improvement of high current proton linac application systems. The difficulty in developing the APM source was sensitive dependence of the source performance on axial magnetic field in the microwave discharge chamber. It was difficult to produce high current proton beam stably without precise tuning of the magnetic field using solenoid coils. We lowered the sensitivity using multicusp magnetic fields for plasma confinement at the discharge chamber sidewall of the source. This enabled stable high current proton beam production with the APM microwave ion source with no tuning coil. The water cooling and the power supply for the coils are not necessary for the APM source, which leads to better reliability and system simplification. The outer diameter of the APM source was around 300 mm, which was 20% lower than the coil source. The APM source produced a maximum hydrogen ion beam current of 65 mA (high current density of 330 mA/cm(2), proton ratio of 87%, and beam energy of 30 keV) with a 5 mm diameter extraction aperture, pulse width of 400 micros, and 20 Hz repetition rate at 1.3 kW microwave power. This performance is almost the same as the best performances of the conventional coil sources. The extracted ion beams were focused with electrostatic five-grid lens to match beam to acceptance of radio-frequency quadrupole linacs. The maximum focused beam current through the orifice (5 mm radius) and the lens was 36 mA and the 90% focused beam half-width was 1-2 mm. PMID:18315183

  7. The effects of the RHIC E-lenses magnetic structure layout on the proton beam trajectory

    SciTech Connect

    Gu, X.; Pikin, A.; Luo, Y.; Okamura, M.; Fischer, W.; Gupta, R.; Hock, J.; Raparia, D.

    2011-03-28

    We are designing two electron lenses (E-lens) to compensate for the large beam-beam tune spread from proton-proton interactions at IP6 and IP8 in the Relativistic Heavy Ion Collider (RHIC). They will be installed in RHIC IR10. First, the layout of these two E-lenses is introduced. Then the effects of e-lenses on proton beam are discussed. For example, the transverse fields of the e-lens bending solenoids and the fringe field of the main solenoids will shift the proton beam. For the effects of the e-lens on proton beam trajectory, we calculate the transverse kicks that the proton beam receives in the electron lens via Opera at first. Then, after incorporating the simplified E-lens lattice in the RHIC lattice, we obtain the closed orbit effect with the Simtrack Code.

  8. -Measurement of the proton's electric to magnetic form factor ratio from 1H(over -->)(e(over -->),e'p).

    PubMed

    Crawford, C B; Sindile, A; Akdogan, T; Alarcon, R; Bertozzi, W; Booth, E; Botto, T; Calarco, J; Clasie, B; Degrush, A; Donnelly, T W; Dow, K; Dutta, D; Farkhondeh, M; Fatemi, R; Filoti, O; Franklin, W; Gao, H; Geis, E; Gilad, S; Haeberli, W; Hasell, D; Hersman, W; Holtrop, M; Karpius, P; Kohl, M; Kolster, H; Lee, T; Maschinot, A; Matthews, J; McIlhany, K; Meitanis, N; Milner, R G; Redwine, R P; Seely, J; Shinozaki, A; Sirca, S; Six, E; Smith, T; Tonguc, B; Tschalaer, C; Tsentalovich, E; Turchinetz, W; van den Brand, J F J; van der Laan, J; Wang, F; Wise, T; Xiao, Y; Xu, W; Zhang, C; Zhou, Z; Ziskin, V; Zwart, T

    2007-02-01

    We report the first precision measurement of the proton electric to magnetic form factor ratio from spin-dependent elastic scattering of longitudinally polarized electrons from a polarized hydrogen internal gas target. The measurement was performed at the MIT-Bates South Hall Ring over a range of four-momentum transfer squared Q2 from 0.15 to 0.65 (GeV/c)(2). Significantly improved results on the proton electric and magnetic form factors are obtained in combination with existing cross-section data on elastic electron-proton scattering in the same Q2 region. PMID:17358849

  9. Complete Proton and Carbon Assignment of Triclosan via One- and Two- Dimensional Nuclear Magnetic Resonance Analysis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Students from an upper-division undergraduate spectroscopy class analyzed one- and two-dimensional 400 MHz NMR spectroscopic data from triclosan in CDCl3. Guided assignment of all proton and carbon signals was completed via 1D proton and carbon, nuclear Overhauser effect (nOe), distortionless enhanc...

  10. Cell and membrane lipid analysis by proton magnetic resonance spectroscopy in five breast cancer cell lines.

    PubMed

    Le Moyec, L; Tatoud, R; Eugène, M; Gauvillé, C; Primot, I; Charlemagne, D; Calvo, F

    1992-10-01

    The lipid composition of five human breast cancer cell lines (MCF-7, T47D, ZR-75-1, SKBR3 and MDA-MB231) was assessed by proton magnetic resonance spectroscopy (MRS) in whole cells and membrane-enriched fractions. The proportions of the three main lipid resonances in 1D spectra were different for each cell line. These resonances included mobile methyl and methylene functions from fatty acids of triglycerides and phospholipids and N-trimethyl from choline of phospholipids. T47D and ZR-75-1 cells presented a high methylene/methyl ratio (6.02 +/- 0.35 and 6.28 +/- 0.90). This ratio was significantly lower for SKBR3, MCF-7 and MDA-MB231 cells (2.76 +/- 0.22, 2.27 +/- 0.57 and 1.39 +/- 0.39). The N-trimethyl/methyl ratio was high for MDA-MB231 and SKBR3 cells (1.38 +/- 0.54 and 0.86 +/- 0.32), but lower for MCF-7, T47D and ZR-75-1 cells (0.49 +/- 0.11, 0.16 +/- 0.07 and 0.07 +/- 0.03). 2D COSY spectra confirmed these different proportions in mobile lipids. From 1D spectra obtained on membrane preparations, T47D and ZR-75-1 were the only cell lines to retain a signal from mobile methylene functions. These differences might be related to the heterogeneity found for several parameters of these cells (tumorigenicity, growth rate, hormone receptors); an extended number of cases from fresh samples might enable clinical correlations. PMID:1329906

  11. Brain metabolomic profiles of lung cancer patients prior to treatment characterized by proton magnetic resonance spectroscopy

    PubMed Central

    Benveniste, Helene; Zhang, Shaonan; Reinsel, Ruth A; Li, Haifang; Lee, Hedok; Rebecchi, Mario; Moore, William; Johansen, Christoffer; Rothman, Douglas L; Bilfinger, Thomas V

    2012-01-01

    Cancer patients without evidence of brain metastases often exhibit constitutional symptoms, cognitive dysfunction and mood changes at the time of clinical diagnosis, i.e. prior to surgical and/or chemotherapy treatment. At present however, there is limited information on brain metabolic and functional status in patients with systemic cancers such as lung cancer prior to initiation of treatment. Therefore, a prospective, observational study was conducted on patients with a clinical diagnosis of lung cancer to assess the cerebral metabolic status before treatment using proton magnetic resonance spectroscopy (1HMRS). Together with neurocognitive testing, 1HMRS was performed in the parietal and occipital cortices of patients diagnosed with a lung mass (N=17) and an age-matched control group (N=15). Glutamate concentrations in the occipital cortex were found to be lower in the patients compared to controls and the concentrations of creatine and phosphocreatine were significantly lower in the parietal cortex of the patients. The lung cancer patients were also characterized by greater fatigue scores (but not depression) prior to treatment when compared to controls. In addition, the serum concentration of interleukin-6 (proinflammatory cytokine) was higher in patients compared to controls; and the concentration of tumor-necrosis factor alpha ([TNF-α]) was positively correlated to the metabolic activity of the lung tumor as defined by the 2-deoxy-2-(18F)fluoro-D-glucose (18FDG) positron emission tomography (PET) derived maximal standardized uptake values (SUVmax). Finally, multivariate statistical modeling revealed that the concentration of N-acetyl-aspartate [NAA] in the occipital cortex was negatively associated with [TNF-α]. In conclusion, our data demonstrate that the cerebral metabolic status of patients with lung cancer is changed even prior to treatment. In addition, the association between inflammatory cytokines, SUVmax and [NAA] points towards interactions

  12. Late Proton Magnetic Resonance Spectroscopy following Traumatic Brain Injury during Early Childhood: Relationship with Neurobehavioral Outcomes

    PubMed Central

    WALZ, NICOLAY CHERTKOFF; CECIL, KIM M.; WADE, SHARI L.; MICHAUD, LINDA J.

    2014-01-01

    We sought to extend previous research that demonstrates reduced neurometabolite concentrations during the chronic phase of pediatric traumatic brain injury (TBI) in children injured during early childhood. We hypothesized that young children with TBI in the chronic phase post-injury would have lower N-acetyl aspartate (NAA) metabolite concentrations in gray and white matter in comparison to controls. We also hypothesized that metabolite levels would be correlated with acute TBI severity and neurobehavioral skills. Ten children with a history of TBI between the ages of 3 and 6 years were compared to an age, gender, and race-matched group of 10 children with a history of an orthopedic injury (OI). Children completed neurobehavioral testing at 12 months post-injury. Proton magnetic resonance (MR) spectroscopy was completed at least 12 months post-injury when the children were 6–9 years old. Groups were compared on metabolite concentrations in the medial frontal gray matter and left frontal white matter. Metabolite levels were correlated with Glasgow Coma Scale (GCS) scores and neurobehavioral functioning. There was a trend for lower NAA concentrations in the medial frontal gray matter for the TBI group. Late NAA and Cr levels in the medial frontal gray matter and NAA levels in the left frontal white matter were strongly positively correlated with initial GCS score. Metabolite levels were correlated with some neurobehavioral measures differentially for children with TBI or OI. Some neurometabolite levels differed between the TBI and OI groups more than 1 year post-injury and were related to injury severity, as well as some neurobehavioral outcomes following TBI during early childhood. PMID:18260792

  13. Dosimetric feasibility of intensity modulated proton therapy in a transverse magnetic field of 1.5 T.

    PubMed

    Hartman, J; Kontaxis, C; Bol, G H; Frank, S J; Lagendijk, J J W; van Vulpen, M; Raaymakers, B W

    2015-08-01

    Proton therapy promises higher dose conformality in comparison with regular radiotherapy techniques. Also, image guidance has an increasing role in radiotherapy and MRI is a prime candidate for this imaging. Therefore, in this paper the dosimetric feasibility of Intensity Modulated Proton Therapy (IMPT) in a magnetic field of 1.5 T and the effect on the generated dose distributions compared to those at 0 T is evaluated, using the Monte Carlo software TOol for PArticle Simulation (TOPAS). For three different anatomic sites IMPT plans are generated. It is shown that the generation of an IMPT plan in a magnetic field is feasible, the impact of the magnetic field is small, and the resulting dose distributions are equivalent for 0 T and 1.5 T. Also, the framework of Monte Carlo simulation combined with an inverse optimization method can be used to generate IMPT plans. These plans can be used in future dosimetric comparisons with e.g. IMRT and conventional IMPT. Finally, this study shows that IMPT in a 1.5 T magnetic field is dosimetrically feasible. PMID:26182957

  14. Dosimetric feasibility of intensity modulated proton therapy in a transverse magnetic field of 1.5 T

    NASA Astrophysics Data System (ADS)

    Hartman, J.; Kontaxis, C.; Bol, G. H.; Frank, S. J.; Lagendijk, J. J. W.; van Vulpen, M.; Raaymakers, B. W.

    2015-08-01

    Proton therapy promises higher dose conformality in comparison with regular radiotherapy techniques. Also, image guidance has an increasing role in radiotherapy and MRI is a prime candidate for this imaging. Therefore, in this paper the dosimetric feasibility of Intensity Modulated Proton Therapy (IMPT) in a magnetic field of 1.5 T and the effect on the generated dose distributions compared to those at 0 T is evaluated, using the Monte Carlo software TOol for PArticle Simulation (TOPAS). For three different anatomic sites IMPT plans are generated. It is shown that the generation of an IMPT plan in a magnetic field is feasible, the impact of the magnetic field is small, and the resulting dose distributions are equivalent for 0 T and 1.5 T. Also, the framework of Monte Carlo simulation combined with an inverse optimization method can be used to generate IMPT plans. These plans can be used in future dosimetric comparisons with e.g. IMRT and conventional IMPT. Finally, this study shows that IMPT in a 1.5 T magnetic field is dosimetrically feasible.

  15. Predicting the outcome of grade II glioma treated with temozolomide using proton magnetic resonance spectroscopy

    PubMed Central

    Guillevin, R; Menuel, C; Taillibert, S; Capelle, L; Costalat, R; Abud, L; Habas, C; De Marco, G; Hoang-Xuan, K; Chiras, J; Vallée, J-N

    2011-01-01

    Background: This study was designed to evaluate proton magnetic resonance spectroscopy (1H-MRS) for monitoring the WHO grade II glioma (low-grade glioma (LGG)) treated with temozolomide (TMZ). Methods: This prospective study included adult patients with progressive LGG that was confirmed by magnetic resonance imaging (MRI). Temozolomide was administered at every 28 days. Response to TMZ was evaluated by monthly MRI examinations that included MRI with volumetric calculations and 1H-MRS for assessing Cho/Cr and Cho/NAA ratios. Univariate, multivariate and receiver-operating characteristic statistical analyses were performed on the results. Results: A total of 21 LGGs from 31 patients were included in the study, and followed for at least n=14 months during treatment. A total of 18 (86%) patients experienced a decrease in tumour volume with a greater decrease of metabolic ratios. Subsequently, five (28%) of these tumours resumed growth despite the continuation of TMZ administration with an earlier increase of metabolic ratios of 2 months. Three (14%) patients did not show any volume or metabolic change. The evolutions of the metabolic ratios, mean(Cho/Cr)n and mean(Cho/NAA)n, were significantly correlated over time (Spearman ρ=+0.95) and followed a logarithmic regression (P>0.001). The evolutions over time of metabolic ratios, mean(Cho/Cr)n and mean(Cho/NAA)n, were significantly correlated with the evolution of the mean relative decrease of tumour volume, mean(ΔVn/Vo), according to a linear regression (P<0.001) in the ‘response/no relapse' patient group, and with the evolution of the mean tumour volume (meanVn), according to an exponential regression (P<0.001) in the ‘response/relapse' patient group. The mean relative decrease of metabolic ratio, mean(Δ(Cho/Cr)n/(Cho/Cr)o), at n=3 months was predictive of tumour response over the 14 months of follow-up. The mean relative change between metabolic ratios, mean((Cho/NAA)n−(Cho/Cr)n)/(Cho/NAA)n, at n=4 months was

  16. MO-G-18C-07: Improving T2 Determination and Quantification of Lipid Methylene Protons in Proton Magnetic Resonance Spectroscopy at 3 T

    SciTech Connect

    Breitkreutz, D.; Fallone, B. G.; Yahya, A.

    2014-06-15

    Purpose: To improve proton magnetic resonance spectroscopy (MRS) transverse relaxation (T{sub 2}) determination and quantification of lipid methylene chain (1.3 ppm) protons by rewinding their J-coupling evolution. Methods: MRS experiments were performed on four lipid phantoms, namely, almond, corn, sunflower and oleic acid, using a 3 T Philips MRI scanner with a transmit/receive birdcage head coil. Two PRESS (Point RESolved Spectroscopy) pulse sequences were used. The first PRESS sequence employed standard bandwidth (BW) (∼550 Hz) RF (radiofrequency) refocussing pulses, while the second used refocussing pulses of narrow BW (∼50 Hz) designed to rewind J-coupling evolution of the methylene protons in the voxel of interest. Signal was acquired with each sequence from a 5×5×5 mm{sup 3} voxel, with a repetition time (TR) of 3000 ms, and with echo times (TE) of 100 to 200 ms in steps of 20 ms. 2048 sample points were measured with a 2000 Hz sampling bandwidth. Additionally, 30 mm outer volume suppression slabs were used to suppress signal outside the voxel of interest. The frequency of the RF pulses was set to that of the methylene resonance. Methylene peak areas were calculated and fitted in MATLAB to a monexponentially decaying function of the form M{sub 0}exp(-TE/T{sub 2}), where M{sub 0} is the extrapolated area when TE = 0 ms and yields a measure of concentration. Results: The determined values of M{sub 0} and T{sub 2} increased for all fatty acids when using the PRESS sequence with narrow BW refocussing pulses. M{sub 0} and T{sub 2} values increased by an average amount (over all the phantoms) of 31% and 14%, respectively. Conclusion: This investigation has demonstrated that J-coupling interactions of lipid methylene protons causes non-negligible signal losses which, if not accounted for, Result in underestimations of their levels and T{sub 2} values when performing MRS measurements. Funded by the Natural Sciences and Engineering Research Council of Canada

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

    PubMed

    Ling, Morris F; Luster, Andrew D

    2016-03-01

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

  18. A carbon-13 and proton nuclear magnetic resonance study of some experimental referee broadened-specification /ERBS/ turbine fuels

    NASA Technical Reports Server (NTRS)

    Dalling, D. K.; Pugmire, R. J.

    1982-01-01

    Preliminary results of a nuclear magnetic resonance (NMR) spectroscopy study of alternative jet fuels are presented. A referee broadened-specification (ERBS) aviation turbine fuel, a mixture of 65 percent traditional kerosene with 35 percent hydrotreated catalytic gas oil (HCGO) containing 12.8 percent hydrogen, and fuels of lower hydrogen content created by blending the latter with a mixture of HCGO and xylene bottoms were studied. The various samples were examined by carbon-13 and proton NMR at high field strength, and the resulting spectra are shown. In the proton spectrum of the 12.8 percent hydrogen fuel, no prominent single species is seen while for the blending stock, many individual lines are apparent. The ERBS fuels were fractionated by high-performance liquid chromatography and the resulting fractions analyzed by NMR. The species found are identified.

  19. Protons and electrons in Jupiter's magnetic field - Results from the University of Chicago experiment on Pioneer 10

    NASA Technical Reports Server (NTRS)

    Simpson, J. A.; Hamilton, D.; Lentz, G.; Mckibben, R. B.; Mogro-Campero, A.; Perkins, M.; Pyle, K. R.; Tuzzolino, A. J.; O'Gallagher, J. J.

    1974-01-01

    Fluxes of high energy electrons and protons are found to be highly concentrated near the magnetic equatorial plane from distances of about 30 to about 100 Jovian radii. The 10-hour period of planetary rotation is observed as an intensity variation, which indicates that the equatorial zone of high particle fluxes is inclined with respect to the rotation axis of the planet. At radial distances below 20 Jovian radii, the synchrotron-radiation-producing electrons with energies above 3 MeV rise steeply to a maximum intensity near the periapsis at 2.8 Jovian radii. The flux of protons with energies above 30 MeV reaches a maximum intensity at 3.5 Jovian radii, with the intensity decreasing inside this radial distance.

  20. Desipramine attenuates forced swim test-induced behavioral and neurochemical alterations in mice: an in vivo(1)H-MRS study at 9.4T.

    PubMed

    Kim, Sang-Young; Lee, Yun-Jung; Kim, Hyeonjin; Lee, Do-Wan; Woo, Dong-Cheol; Choi, Chi-Bong; Chae, Jeong-Ho; Choe, Bo-Young

    2010-08-12

    The forced swim test (FST) is a behavioral paradigm that is predicative of antidepressant activity in rodents. The objective of this study was to examine the effects of desipramine (DMI) pretreatment on behavioral and regional neurochemical responses in the left dorsolateral prefrontal cortex (DLPFC) and hippocampus of mice exposed to the FST using proton magnetic resonance spectroscopy ((1)H-MRS). An ultra short echo stimulated echo acquisition (STEAM) localization sequence (TR/TM/TE=5000/20/2.2ms) was used to measure in vivo proton spectra from the left DLPFC (voxel volume: 7microl) and hippocampus (6microl) of C57BL/6 mice at 9.4T and acquired proton spectra post-processed offline with LCModel. The FST induced significant increase of glutamate (Glu) and myo-inositol (mIns) concentrations in the left DLPFC and hippocampus, respectively. In addition, creatine+phosphocreatine (Cr+PCr) concentrations in the left DLPFC were significantly decreased as compared to control. The metabolic alterations induced by the FST were reverted to level similar to control by acute DMI administration. Our results suggest that glutamatergic activity and glial cell dysfunction may contribute to the pathophysiological mechanisms underlying depression and that modulation of synaptic neurotransmitter concentrations represents a potential target for antidepressant drug development. PMID:20542016

  1. 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

  2. Model for bremsstrahlung emission accompanying interactions between protons and nuclei from low energies up to intermediate energies: Role of magnetic emission

    NASA Astrophysics Data System (ADS)

    Maydanyuk, Sergei P.

    2012-07-01

    A model of the bremsstrahlung emission which accompanies proton decay and collisions of protons off nuclei in the low- to intermediate-energy region has been developed. This model includes spin formalism, a potential approach for describing the interaction between protons and nuclei, and an emission that includes a component of the magnetic emission (defined on the basis of the Pauli equation). For the problem of bremsstrahlung during proton decay the role of magnetic emission is studied by using such a model. For the 146Tm nucleus the following has been studied: (1) How much does the magnetic emission change the full bremsstrahlung spectrum? (2) At which angle is the magnetic emission the most intensive relative to the electric emission? (3) Is there some spatial region where the magnetic emission increases strongly relative to the electric emission? (4) How intensive is the magnetic emission in the tunneling region? (5) Which is the maximal probability? Which value does it equal to at the zero-energy limit of the emitted photons? It is demonstrated that the model is able to describe well enough experimental data of bremsstrahlung emission which accompanies collisions of protons off 9C, 64Cu, and 107Ag nuclei at an incident energy of Tlab=72 MeV (at a photon energy up to 60 MeV) and off 9Be, 12C, and 208Pb nuclei at an incident energy of Tlab=140 MeV (at a photon energy up to 120 MeV).

  3. Preparation of amyloid-like fibrils containing magnetic iron oxide nanoparticles: Effect of protein aggregation on proton relaxivity

    SciTech Connect

    Viktor Andersson, B.; Skoglund, Caroline; Uvdal, Kajsa; Solin, Niclas

    2012-03-23

    Highlights: Black-Right-Pointing-Pointer Preparation of amyloid materials labeled with magnetic iron oxide nanoparticles. Black-Right-Pointing-Pointer Characterization of amyloid materials by electron tomography. Black-Right-Pointing-Pointer Influence of protein aggregation on the magnetic nanoparticle properties. -- Abstract: A method to prepare amyloid-like fibrils functionalized with magnetic nanoparticles has been developed. The amyloid-like fibrils are prepared in a two step procedure, where insulin and magnetic nanoparticles are mixed simply by grinding in the solid state, resulting in a water soluble hybrid material. When the hybrid material is heated in aqueous acid, the insulin/nanoparticle hybrid material self assembles to form amyloid-like fibrils incorporating the magnetic nanoparticles. This results in magnetically labeled amyloid-like fibrils which has been characterized by Transmission Electron Microscopy (TEM) and electron tomography. The influence of the aggregation process on proton relaxivity is investigated. The prepared materials have potential uses in a range of bio-imaging applications.

  4. Pion production via proton synchrotron radiation in strong magnetic fields in relativistic field theory: Scaling relations and angular distributions

    DOE PAGESBeta

    Maruyama, Tomoyuki; Cheoun, Myung-Ki; Kajino, Toshitaka; Mathews, Grant J.

    2016-03-26

    We study pion production by proton synchrotron radiation in the presence of a strong magnetic field when the Landau numbers of the initial and final protons are n(i, f) similar to 10(4)-10(5). We find in our relativistic field theory calculations that the pion decay width depends only on the field strength parameter which previously was only conjectured based upon semi-classical arguments. Moreover, we also find new results that the decay width satisfies a robust scaling relation, and that the polar angular distribution of emitted pion momenta is very narrow and can be easily obtained. This scaling implies that one canmore » infer the decay width in more realistic magnetic fields of 10(15) G, where n(i, f) similar to 10(12)-10(13), from the results for n(i, f) similar to 10(4)-10(5). The resultant pion intensity and angular distributions for realistic magnetic field strengths are presented and their physical implications discussed. (C) 2016 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). Funded by SCOAP(3).« less

  5. Proton interrogation

    SciTech Connect

    Morris, Christopher L

    2008-01-01

    Energetic proton beams may provide an attractive alternative when compared to electromagnetic and neutron beams for active interrogation of nuclear threats because: they have large fission cross sections, long mean free paths and high penetration, and proton beams can be manipulated with magnetic optics. We have measured time-dependent cross sections for delayed neutrons and gamma-rays using the 800 MeV proton beam from the Los Alamos Neutron Science Center for a set of bare and shielded targets. The results show significant signals from both unshielded and shielded nuclear materials. Results will be presented.

  6. Monitoring of organic contaminants in sediments using low field proton nuclear magnetic resonance

    NASA Astrophysics Data System (ADS)

    Zhang, Chi; Rupert, Yuri

    2016-04-01

    The effective monitoring of soils and groundwater contaminated with organic compounds is an important goal of many environmental restoration efforts. Recent geophysical methods such as electrical resistivity, complex conductivity, and ground penetrating radar have been successfully applied to characterize organic contaminants in the subsurface and to monitor remediation process both in laboratory and in field. Low field proton nuclear magnetic resonance (NMR) is a geophysical tool sensitive to the molecular-scale physical and chemical environment of hydrogen-bearing fluids in geological materials and shows promise as a novel method for monitoring contaminant remediation. This laboratory research focuses on measurements on synthetic samples to determine the sensitivity of NMR to the presence of organic contaminants and improve understanding of relationships between NMR observables, hydrological properties of the sediments, and amount and state of contaminants in porous media. Toluene, a light non-aqueous phase liquid (LNAPL) has been selected as a representative organic contaminant. Three types of porous media (pure silica sands, montmorillonite clay, and various sand-clay mixtures with different sand/clay ratios) were prepared as synthetic sediments. NMR relaxation time (T2) and diffusion-relaxation (D ‑ T2) correlation measurements were performed in each sediment saturated with water and toluene mixed fluid at assorted concentrations (0% toluene and 100% water, 1% toluene and 99% water, 5% toluene and 95% water, 25% toluene and 75% water, and 100% toluene and 0% water) to 1) understand the effect of different porous media on the NMR responses in each fluid mixture, 2) investigate the role of clay content on T2 relaxation of each fluid, 3) quantify the amount hydrocarbons in the presence of water in each sediment, and 4) resolve hydrocarbons from water in D ‑ T2 map. Relationships between the compositions of porous media, hydrocarbon concentration, and

  7. Clinical significance of brain phenylalanine concentration assessed by in vivo proton magnetic resonance spectroscopy in phenylketonuria.

    PubMed

    Leuzzi, V; Bianchi, M C; Tosetti, M; Carducci, C L; Carducci, C A; Antonozzi, I

    2000-09-01

    Recent studies using in vivo proton magnetic resonance spectroscopy (1H MRS) have suggested that plasma phenylalanine (Phe) may not be a reliable indicator of brain Phe level in subjects with phenylketonuria (PKU). Interindividual variation in cerebral Phe can contribute to the phenotypic variability of the disease. We report the results of the direct assessment of brain Phe by 1H MRS in 10 off-diet PKU patients (aged 15.5-30.5 years), 4 detected and treated early, 6 late. In a single patient, brain Phe was evaluated before and 15 days after diet discontinuation. FLAIR MRI and 1H MRS were performed in the same setting by a 1.5 T clinical MR scanner. MR images were scored according to the extent of the lobar white-matter hyperintensity. Brain 1H MRS Phe signal (resonating at 7.36 ppm) was evaluated as a ratio to the creatine+phosphocreatine signal. Brain Phe was correlated with clinical, biochemical and MRI findings. Results were as follows. (1) An abnormal concentration of brain Phe was detected in all 10 PKU subjects (ranging from 0.030 to 0.074), associated with a wide interindividual variability of concurrent plasma Phe (ranging from 724 to 2800 micromol/L). (2) In late-detected subjects, brain Phe concentration correlated with clinical phenotype better than did plasma Phe. The discrepancy between brain and plasma Phe was relevant from a clinical point of view in two cases: in one, a late-detected patient with normal mental development, a high level of plasma Phe was associated with a relatively low concentration of brain Phe; in the other, a late-detected subject with severe neurological impairment, a very high level of brain Phe was associated with plasma Phe compatible with the diagnosis of mild PKU. (3) White-matter alterations were detected in all patients. FLAIR MRI sequences disclosed an involvement of optic chiasma and tracts in 7 subjects. No correlation was found between white-matter alterations and concurrent brain Phe concentrations. (4) In the only

  8. Sub-Proton Scale Magnetic Holes: Turbulence Simulations, Theory and Cluster Observations in the Earth's Plasma Sheet.

    NASA Astrophysics Data System (ADS)

    Haynes, C. T.; Burgess, D.; Camporeale, E.; Sundberg, T.

    2014-12-01

    We investigate the properties of a new type of nonlinear coherent structure, called electron vortex magnetic holes (EVMHs) discovered during 2-D full particle realistic mass ratio simulations of turbulence. These structures form via the interaction of magnetic depletions and the local electron population in the plasma. They are characterised by local depressions in the magnetic field strength with circular cross-sections. We use PIC and test particle simulations to show that the magnetic structure is maintained by a current carried by an electron vortex which is due to a population of electrons with pitch angles close to 90 degrees in trapped, or quasi-trapped, non-adiabatic orbits. We then compare these results to Cluster observations of electron-scale magnetic holes (MH) in the Earth's plasma sheet. MHs in the solar wind are often explained in terms of the mirror mode instability. Here, in the plasma sheet, we show MH events in mirror stable environments, with high electron perpendicular temperature anisotropy, which cannot be explained in terms of a standard mirror mode growth. We show that EVMHs may provide a theoretical explanation for a majority of the MHs observed in the plasma sheet at scales less than the proton thermal gyroradius.

  9. The protons and electrons trapped in the Jovian dipole magnetic field region and their interaction with Io

    NASA Technical Reports Server (NTRS)

    Simpson, J. A.; Hamilton, D. C.; Mckibben, R. B.; Mogro-Campero, A.; Pyle, K. R.; Tuzzolino, A. J.

    1974-01-01

    Detailed analysis of electrons equal to or greater than 3 MeV and of protons 0.5 to 1.8 MeV and equal to or greater than 35 MeV for both the inbound and the outbound passes of the Pioneer 10 spacecraft. Conclusive evidence is obtained that the trapped radiation in Jupiter's inner magnetosphere is maintained and supplied by inward diffusion from the outer regions of the trapped radiation zone. It is shown that the time required for isotropization of an anisotropic flux by pitch angle scattering inside L approximately equal to 6 is long in comparison with the time required for particles to diffuse inward from L approximately equal to 6 to L approximately equal to 3, that the high-energy protons were not injected at high energies by the Crand (cosmic ray albedo neutron decay) process but were accelerated in the magnetosphere of Jupiter, and that the main conclusions of this analysis are unaffected by use of either the D sub 1 or the D sub 2 magnetic field models. Theoretical studies of the capture of trapped electrons and protons by Io have been carried out, and it is found that the probability of capture by Io depends strongly upon the particle species and kinetic energy.

  10. Protons and Electrons in Jupiter's Magnetic Field: Results from the University of Chicago Experiment on Pioneer 10.

    PubMed

    Simpson, J A; Hamilton, D; Lentz, G; McKibben, R B; Mogro-Campero, A; Perkins, M; Pyle, K R; Tuzzolino, A J; O'gallagher, J J

    1974-01-25

    Fluxes of high energy electrons and protons are found to be highly concentrated near the magnetic equatorial plane from distances of ~ 30 to ~ 100 Jovian radii (R(J)). The 10-hour period of planetary rotation is observed as an intensity variation, which indicates that the equatorial zone of high particle fluxes is inclined with respect to the rotation axis of the planet. At radial distances [unknown] 20 R(J) the synchrotron-radiation-producing electrons with energies greater, similar 3 million electron volts rise steeply to a maximum intensity of ~ 5 x 10(8) electrons per square centimeter per second near the periapsis at 2.8 R(J). The flux of protons with energies greater, similar 30 million electron volts reaches a maximum intensity of ~ 4 x 10(6) protons per square centimeter per second at ~ 3.5 R(J) with the intensity decreasing inside this radial distance. Only for radial distances [unknown] 20 R(J) does the radiation behave in a manner which is similar to that at the earth. Burst of electrons with energies up to 30 million electron volts, each lasting about 2 days, were observed in interplanetary space beginning approximately 1 month before encounter. This radiation appears to have escaped from the Jovian bow shock or magnetosphere. PMID:17821089

  11. Effects of magnetic non-linearities on a stored proton beam and their implications for superconducting storage rings

    SciTech Connect

    Cornacchia, M.; Evans, L.

    1985-06-01

    A nonlinear lens may be used to study the effect of high-order multipolar field imperfections on a stored proton beam. Such a nonlinear lens is particulary suitable to simulate field imperfections of the types encountered in coil dominated superconducting magnets. We have studied experimentally at the SPS the effect of high order (5th and 8th) single isolated resonances driven by the nonlinear lens. The width of these resonances is of the order one expects to be caused by field errors in superconducting magnets of the SSC type. The experiment shows that, in absence of tune modulation, these resonances are harmless. Slow crossings of the resonance, on the other hand, have destructive effects on the beam, much more so than fast crossings caused by synchrotron oscillations. In the design of future storage rings, sources of low-frequency tune modulation should be avoided as a way to reduce the harmful effects of high order multipolar field imperfection.

  12. Resolution of Fundic Gland Polyposis following Laparoscopic Magnetic Sphincter Augmentation and Subsequent Cessation of Proton Pump Inhibitors

    PubMed Central

    Brockmeyer, Joel R.; Connolly, Erin E.; Wittchow, Richard J.; Kothari, Shanu N.

    2015-01-01

    Gastric polyps occur from a variety of sources and are found commonly on upper endoscopy. We present the case of a 49-year-old female who presented for evaluation for antireflux surgery with a history of fundic gland polyposis who required twice-daily proton pump inhibitors (PPIs) for control of her gastric reflux. After verifying that she met criteria for surgery, she underwent an uncomplicated laparoscopic magnetic sphincter augmentation placement. With the cessation of PPIs following surgery, the fundic gland polyposis resolved. Fundic gland polyps may occur sporadically or within certain syndromes, such as familial adenomatous polyposis. Multiple possible inciting factors exist, including the use of PPIs. This is the first reported case of the resolution of numerous fundic gland polyps following the completion of laparoscopic magnetic sphincter augmentation. PMID:26600954

  13. Quantification of N-Acetyl Aspartyl Glutamate in Human Brain using Proton Magnetic Resonance Spectroscopy at 7 T

    NASA Astrophysics Data System (ADS)

    Elywa, M.

    2015-07-01

    The separation of N-acetyl aspartyl glutamate (NAAG) from N-acetyl aspartate (NAA) and other metabolites, such as glutamate, by in vivo proton magnetic resonance spectroscopy at 7 T is described. This method is based on the stimulated echo acquisition mode (STEAM), with short and long echo time (TE) and allows quantitative measurements of NAAG in the parietal and pregenual anterior cingulate cortex (pgACC) of human brain. Two basesets for the LCModel have been established using nuclear magnetic resonance simulator software (NMR-SIM). Six healthy volunteers (age 25-35 years) have been examined at 7 T. It has been established that NAAG can be separated and quantified in the parietal location and does not get quantified in the pgACC location when using a short echo time, TE = 20 ms. On the other hand, by using a long echo time, TE = 74 ms, NAAG can be quantified in pgACC structures.

  14. Characterization of heteronuclear decoupling through proton spin dynamics in solid-state nuclear magnetic resonance spectroscopy

    NASA Astrophysics Data System (ADS)

    De Paëpe, Gaël; Eléna, Bénédicte; Emsley, Lyndon

    2004-08-01

    The work presented here aims at understanding the performance of phase modulated heteronuclear decoupling sequences such as Cosine Modulation or Two Pulse Phase Modulation. To that end we provide an analytical description of the intrinsic behavior of Cosine Modulation decoupling with respect to radio-frequency-inhomogeneity and the proton-proton dipolar coupling network. We discover through a Modulation Frame average Hamiltonian analysis that best decoupling is obtained under conditions where the heteronuclear interactions are removed but notably where homonuclear couplings are recoupled at a homonuclear Rotary Resonance (HORROR) condition in the Modulation Frame. These conclusions are supported by extensive experimental investigations, and notably through the introduction of proton nutation experiments to characterize spin dynamics in solids under decoupling conditions. The theoretical framework presented in this paper allows the prediction of the optimum parameters for a given set of experimental conditions.

  15. Nuclear magnetic resonance observation and dynamics of specific amide protons in T4 lysozyme.

    PubMed

    Griffey, R H; Redfield, A G; Loomis, R E; Dahlquist, F W

    1985-02-12

    We have produced T4 lysozyme using a bacterial expression system which allows efficient incorporation of isotopically labeled amino acids in lysozyme. By using conditions that repress the expression of various transaminases, we have incorporated 15N-labeled amino acid into the five phenylalanine residues of the protein. The relatively large spin--spin coupling (87 +/- 3 Hz) between the 15N nucleus and the phenylalanine amide protons may then be exploited in a variety of ways to selectively observe the five phenylalanine amide proton resonances. These include a simple "echo difference" technique which displays the amide proton resonances in one dimension and a "forbidden echo" technique [Bax, A., Griffey, R. H., & Hawkins, B.L. (1983) J. Magn. Reson. 55, 301-335] which gives two-dimensional information allowing the proton and 15N chemical shifts of each amide to be determined. With these approaches, all five phenylalanine amide protons give resolved resonances. Deuterium exchange experiments demonstrate that three of the five resonances are slow to exchange (half-times of about 1 week at pH 5.5 and 4 degrees C) while the other two are rapid with complete exchange in hours or less. These observations correlate well with the secondary structure of the protein which shows three residues in alpha-helical regions and two residues in surface-exposed environments. This approach of isotopic substitution on nitrogen or carbon atoms is of general utility and should allow virtually any proton on a protein of molecular weight 20 000 or thereabout to be selectively observed. PMID:3888265

  16. Investigation of Magnetic Field Geometry in Exploding Wire Z-Pinches via Proton Deflectometry

    NASA Astrophysics Data System (ADS)

    Mariscal, Derek; Beg, Farhat; Wei, Mingsheng; Chittenden, Jeremy; Presura, Radu

    2012-10-01

    It is often difficult to determine the configuration of B-fields within z-pinch plasma systems. Typical laser probing diagnostics are limited by the critical density, and electrical diagnostics are prone to failure as well as perturbation of the system. The use of proton beams launched by high intensity lasers, and the subsequent tracking of their deflected trajectories, will enable access to field measurements in previously inaccessible plasma densities.The experimental testing of this method is performed at the Nevada Test Facility (NTF) using the 10J 0.3ps Leopard laser coupled to the 1.6MA ZEBRA pulsed power generator. MHD simulations of the z-pinch plasmas are performed with the 3D resistive MHD code, GORGON. Protons are then injected and tracked through the plasma using the 3D PIC Large Scale Plasma code in order to produce possible proton image plane data. The first computational demonstration of protons propagating through single wire and x-pinch plasmas, along with comparison to recent experimental data will be presented.

  17. BNL alternating gradient synchrotron with four helical magnets to minimize the losses of the polarized proton beam

    NASA Astrophysics Data System (ADS)

    Tsoupas, N.; Huang, H.; MacKay, W. W.; Meot, F.; Roser, T.; Trbojevic, D.

    2013-04-01

    The principle of using multiple partial helical magnets to preserve the polarization of the proton beam during its acceleration was applied successfully to the alternating gradient synchrotron (AGS) which currently operates with two partial helical magnets. In this paper we further explore this idea by using four partial helical magnets placed symmetrically in the AGS ring. This provides many advantages over the present setup of the AGS, which uses two partial helical magnets. First, the symmetric placement of the four helical magnets and their relatively lower field of operation allows for better control of the AGS optics with reduced values of the beta functions especially near beam injection and allows both the vertical and horizontal tunes to be placed within the “spin tune gap,” therefore eliminating the horizontal and vertical intrinsic spin resonances of the AGS during the acceleration cycle. Second, it provides a wider spin tune gap. Third, the vertical spin direction during beam injection and extraction is closer to vertical. Although the spin tune gap, which is created with four partial helices, can also be created with a single or two partial helices, the high field strength of a single helical magnet which is required to generate such a spin tune gap makes the use of the single helical magnet impractical, and that of the two helical magnets rather difficult. In this paper we will provide results on the spin tune and on the optics of the AGS with four partial helical magnets, and compare them with those from the present setup of the AGS that uses two partial helical magnets. Although in this paper we specifically discuss the effect of the four partial helices on the AGS, this method which can eliminate simultaneously the vertical and horizontal intrinsic spin resonances is a general method and can be applied to any medium energy synchrotron which operates in similar energy range like the AGS and provides the required space to accommodate the four

  18. 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

  19. Study of anisotropy in nuclear magnetic resonance relaxation times of water protons in skeletal muscle.

    PubMed Central

    Kasturi, S R; Chang, D C; Hazlewood, C F

    1980-01-01

    The anisotropy of the spin-lattice relaxation time (T1) and the spin-spin relaxation times (T2) of water protons in skeletal muscle tissue have been studied by the spin-echo technique. Both T1 and T2 have been measured for the water protons of the tibialis anterior muscle of mature male rats for theta = 0, 55, and 90 degrees, where theta is the orientation of the muscle fiber with respect to the static field. The anisotropy in T1 and T2 has been measured at temperatures of 28, -5 and -10 degrees C. No significant anisotropy was observed in the T1 of the tissue water, while an average anisotropy of approximately 5% was observed in T2 at room temperature. The average anisotropy of T2 at -5 and -10 degrees C was found to be approximately 2 and 1.3%, respectively. PMID:6266530

  20. Transcriptional Regulatory Networks for CD4 T Cell Differentiation

    PubMed Central

    Zhu, Jinfang

    2015-01-01

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

  1. Continuous monitoring of the zinc-phosphate acid-base cement setting reaction by proton nuclear magnetic relaxation

    NASA Astrophysics Data System (ADS)

    Apih, T.; Lebar, A.; Pawlig, O.; Trettin, R.

    2001-06-01

    Proton nuclear magnetic relaxation is a well-established technique for continuous and non destructive monitoring of hydration of conventional Portland building cements. Here, we demonstrate the feasibility of nuclear magnetic resonance (NMR) monitoring of the setting reaction of zinc-phosphate acid-base dental cements, which harden in minutes as compared to days, as in the case of Portland cements. We compare the setting of cement powder (mainly, zinc oxide) prepared with clinically used aluminum-modified orthophosphoric acid solution with the setting of a model system where cement powder is mixed with pure orthophosphoric acid solution. In contrast to previously published NMR studies of setting Portland cements, where a decrease of spin-lattice relaxation time is attributed to enhanced relaxation at the growing internal surface, spin-lattice relaxation time T1 increases during the set of clinically used zinc-phosphate cement. Comparison of these results with a detailed study of diffusion, viscosity, and magnetic-field dispersion of T1 in pure and aluminum-modified orthophosphoric acid demonstrates that the increase of T1 in the setting cement is connected with the increase of molecular mobility in the residual phosphoric acid solution. Although not taken into account so far, such effects may also significantly influence the relaxation times in setting Portland cements, particularly when admixtures with an effect on water viscosity are used.

  2. Comparative proton nuclear magnetic resonance studies of amantadine complexes formed in aqueous solutions with three major cyclodextrins.

    PubMed

    Lis-Cieplak, Agnieszka; Sitkowski, Jerzy; Kolodziejski, Waclaw

    2014-01-01

    Host-guest complexes of alpha-, beta-, and gamma-cyclodextrins (α-CD, β-CD, and γ-CD, respectively) with amantadine (1-aminoadamantane, AMA; an antiviral agent) were characterized in aqueous solutions using proton nuclear magnetic resonance (NMR) spectroscopy. Host-guest molecular interactions were manifested by changes in the chemical shifts of AMA protons. NMR Job's plots showed that the stoichiometry of all the studied complexes was 1:1. Two-dimensional T-ROESY experiments demonstrated that the complexes were formed by different degrees of incorporation of the adamantyl group of AMA into the CD cavity. The mode of AMA binding was proposed. The AMA molecule came into the α-CD cavity (the smallest size) or β-CD cavity (the intermediate size) through its wide entrance to become shallowly or deeply accommodated, respectively. In the complex of AMA with γ-CD (the largest cavity size), the adamantyl group was also quite deeply inserted into the CD cavity, but it arrived there through the narrow cavity entrance. It was found that the adamantyl group of AMA was best accommodated by the β-CD cavity. The binding constants Kaa of the studied complexes (in M(-1) ), determined from DOSY NMR, were fairly high; their values in an ascending order were: α-CD (183) < γ-CD (306) ≪ β-CD (5150). PMID:24282085

  3. EXOTIC MAGNETS FOR ACCELERATORS.

    SciTech Connect

    WANDERER, P.

    2005-09-18

    Over the last few years, several novel magnet designs have been introduced to meet the requirements of new, high performance accelerators and beam lines. For example, the FAIR project at GSI requires superconducting magnets ramped at high rates ({approx} 4 T/s) in order to achieve the design intensity. Magnets for the RIA and FAIR projects and for the next generation of LHC interaction regions will need to withstand high doses of radiation. Helical magnets are required to maintain and control the polarization of high energy protons at RHIC. In other cases, novel magnets have been designed in response to limited budgets and space. For example, it is planned to use combined function superconducting magnets for the 50 GeV proton transport line at J-PARC to satisfy both budget and performance requirements. Novel coil winding methods have been developed for short, large aperture magnets such as those used in the insertion region upgrade at BEPC. This paper will highlight the novel features of these exotic magnets.

  4. Proton nuclear magnetic resonance studies on the variant-3 neurotoxin from Centruroides sculpturatus Ewing: Sequential assignment of resonances

    SciTech Connect

    Nettesheim, D.G.; Klevit, R.E.; Drobny, G.; Watt, D.D.; Krishna, N.R. )

    1989-02-21

    The authors report the sequential assignment of resonances to specific residues in the proton nuclear magnetic resonance spectrum of the variant-3 neurotoxin from the scorpion Centruroides sculpturatus Ewing (range southwestern U.S.A.). A combination of two-dimensional NMR experiments such as 2D-COSY, 2D-NOESY, and single- and double-RELAY coherence transfer spectroscopy has been employed on samples of the protein dissolved in D{sub 2}O and in H{sub 2}O for assignment purposes. These studies provide a basis for the determination of the solution-phase conformation of this protein and for undertaking detailed structure-function studies of these neurotoxins that modulate the flow of sodium current by binding to the sodium channels of excitable membranes.

  5. Increase in amino acids in the pons after sleep deprivation: a pilot study using proton magnetic resonance spectroscopy.

    PubMed

    Murck, Harald; Struttmann, Tobias; Czisch, Michael; Wetter, Thomas; Steiger, Axel; Auer, Dorothee P

    2002-01-01

    Total sleep deprivation (TSD) is an efficient method to relieve depression. An involvement of GABAergic and glutamatergic neurotransmission in the pathophysiology of depression and the mechanism of action of TSD has been suggested. To directly assess the content of GABA, glutamate (Glu) and glutamine (Gln) before and after TSD, we estimated their concentrations in four brain regions in six healthy subjects using proton magnetic resonance spectroscopy. The unresolved estimate of GABA, Glu and Gln, as well as GABA and Gln were increased in the pons after 24 h of TSD, the effect being prominent in three subjects. There were no significant changes in the hypothalamus, thalamus or parietooccipital cortex. These preliminary data support earlier animal data and indirect findings in humans suggesting that GABA and Gln, especially in the pontine structures, may play a key role in the mechanism of TSD. PMID:11979059

  6. Proton radiography of dynamic electric and magnetic fields in laser-produced high-energy-density plasmas

    SciTech Connect

    Li, C. K.; Seguin, F. H.; Frenje, J. A.; Manuel, M.; Casey, D.; Sinenian, N.; Petrasso, R. D.; Amendt, P. A.; Landen, O. L.; Rygg, J. R.; Town, R. P. J.; Betti, R.; Meyerhofer, D. D.; Delettrez, J.; Knauer, J. P.; Marshall, F.; Sangster, T. C.; Smalyuk, V. A.; Soures, J. M.; Shvarts, D.

    2009-05-15

    Time-gated, monoenergetic-proton radiography provides unique measurements of the electric (E) and magnetic (B) fields produced in laser-foil interactions and during the implosion of inertial-confinement-fusion capsules. These experiments resulted in the first observations of several new and important features: (1) observations of the generation, decay dynamics, and instabilities of megagauss B fields in laser-driven planar plastic foils, (2) the observation of radial E fields inside an imploding capsule, which are initially directed inward, reverse direction during deceleration, and are likely related to the evolution of the electron pressure gradient, and (3) the observation of many radial filaments with complex electromagnetic field striations in the expanding coronal plasmas surrounding the capsule. The physics behind and implications of such observed fields are discussed.

  7. Proton radiography of dynamic electric and magnetic fields in laser-produced high-energy-density plasmas

    SciTech Connect

    Li, C. K.; Séguin, F. H.; Frenje, J. A.; Manuel, M.; Casey, D.; Sinenian, N.; Petrasso, R. D.; Amendt, P. A.; Landen, O. L.; Rygg, J. R.; Town, R. P. J.; Betti, R.; Delettrez, J.; Knauer, J. P.; Marshall, F.; Meyerhofer, D. D.; Sangster, T. C.; Shvarts, D.; Smalyuk, V. A.; Soures, J. M.; Back, C. A.; Kilkenny, J. D.; Nikroo, A.

    2009-01-01

    Time-gated, monoenergetic-proton radiography provides unique measurements of the electric (E) and magnetic (B) fields produced in laser-foil interactions and during the implosion of inertial-confinement-fusion capsules. These experiments resulted in the first observations of several new and important features: (1) observations of the generation, decay dynamics, and instabilities of megagauss B fields in laser-driven planar plastic foils, (2) the observation of radial E fields inside an imploding capsule, which are initially directed inward, reverse direction during deceleration, and are likely related to the evolution of the electron pressure gradient, and (3) the observation of many radial filaments with complex electromagnetic field striations in the expanding coronal plasmas surrounding the capsule. The physics behind and implications of such observed fields are discussed.

  8. Measurement of the polarization and magnetic moment of Ξ¯+ antihyperons produced by 800-GeV/c protons

    NASA Astrophysics Data System (ADS)

    Ho, P. M.; Longo, M. J.; Nguyen, A.; Luk, K. B.; James, C.; Rameika, R.; Duryea, J.; Guglielmo, G.; Heller, K.; Johns, K.; Diehl, H. T.; Teige, S.; Thomson, G. B.; Zou, Y.

    1991-12-01

    The polarization of Ξ¯ + hyperons produced by 800-GeV/c protons in the inclusive reaction p+Be-->Ξ¯ ++X has been measured using a sample of 70 000 Ξ¯ + decays. The average polarization of the Ξ¯ +, at a mean xF=0.39 and pt=0.76 GeV/c, is -0.097+/-0.012+/-0.009, compared to -0.102+/-0.012+/-0.010 for the Ξ-. The large polarization found for the Ξ¯ + is not expected in any model for polarization of inclusively produced hyperons. The magnetic moment of the Ξ¯ + was measured to be 0.657+/-0.028+/-0.020 nuclear magnetons (μN), compared to (-0.674+/-0.021+/-0.020)μN for the Ξ-, in good agreement with CPT invariance.

  9. Proton magnetic resonance spectroscopy and MRI reveal no evidence for brain mitochondrial dysfunction in children with autism spectrum disorder.

    PubMed

    Corrigan, Neva M; Shaw, Dennis W W; Richards, Todd L; Estes, Annette M; Friedman, Seth D; Petropoulos, Helen; Artru, Alan A; Dager, Stephen R

    2012-01-01

    Brain mitochondrial dysfunction has been proposed as an etiologic factor in autism spectrum disorder (ASD). Proton magnetic resonance spectroscopic imaging ((1)HMRS) and MRI were used to assess for evidence of brain mitochondrial dysfunction in longitudinal samples of children with ASD or developmental delay (DD), and cross-sectionally in typically developing (TD) children at 3-4, 6-7 and 9-10 years-of-age. A total of 239 studies from 130 unique participants (54ASD, 22DD, 54TD) were acquired. (1)HMRS and MRI revealed no evidence for brain mitochondrial dysfunction in the children with ASD. Findings do not support a substantive role for brain mitochondrial abnormalities in the etiology or symptom expression of ASD, nor the widespread use of hyperbaric oxygen treatment that has been advocated on the basis of this proposed relationship. PMID:21404085

  10. Experimental Study of Calculated t1 Images Under Flow Conditions Using Protons and FLUORINE-19 in Magnetic Resonance Imaging

    NASA Astrophysics Data System (ADS)

    Zheng, Jie

    A gradient refocused echo (GRE) pulse protocol has been developed and implemented to obtain calculated T1 images under flow conditions. This sequence acquires multiple images with different flip angles and uses a least -square fit to obtain calculated T1 images. A theoretical analysis of imprecision in the calculated T1 images is discussed. In accordance with Wang (49), the optimal parameters as determined by computer simulation were found to be 20 ^circ and 100^ circ for the flip angles in a two point fit for TR falling in the range 0.3 to 1.0 T1. Flow compensation was added to the pulse sequence for imaging flow phantoms containing GD-DTPA doped water and perfluorocarbon (PFC) compounds for a range of flow rates (0-55 cm/s). Flow compensation was found to effectively recover signal loss due to flow related dephasing. Experimental testing of this protocol has been performed on stationary proton and PFC compound phantoms utilizing ^1H and ^{19}F magnetic resonance imaging respectively. There is good agreement between the experimental results and the theoretical predictions about imprecision in the calculated T1 images. Analysis of variance of the mean T1 values of the calculated T1 images of the proton and PFC flow phantoms indicated that for the flow phantom geometry used in this study, there was no statistical difference among these mean T1 values from flow phantoms with different flow rates (including stationary status). It is believed that this protocol may provide an imaging method for mapping the pO _2 distribution in the vascular space in vivo utilizing perfluorocarbon compounds and ^ {19}F magnetic resonance imaging.

  11. Glutamine and Glutamate Levels in Children and Adolescents with Bipolar Disorder: A 4.0-T Proton Magnetic Resonance Spectroscopy Study of the Anterior Cingulate Cortex

    ERIC Educational Resources Information Center

    Moore, Constance M.; Frazier, Jean A.; Glod, Carol A.; Breeze, Janis L.; Dieterich, Megan; Finn, Chelsea T.; deB. Frederick, Blaise; Renshaw, Perry F.

    2007-01-01

    Objective: The purpose of this study was to use proton magnetic resonance spectroscopy, at 4.0 T, to explore the glutamine and glutamate levels in the anterior cingulate cortex of children and adolescents with bipolar disorder (BPD; medicated and unmedicated) and healthy comparison subjects (HCSs). We hypothesized that unmedicated children with…

  12. Proton NMR study of spin dynamics in the magnetic organic chains M (hfac)3 NITEt (M =Eu3 +,Gd3 + )

    NASA Astrophysics Data System (ADS)

    Mariani, M.; Lascialfari, A.; Caneschi, A.; Ammannato, L.; Gatteschi, D.; Rettori, A.; Pini, M. G.; Cucci, C.; Borsa, F.

    2016-04-01

    In this work, we present a nuclear magnetic resonance (NMR) study of the spin dynamics in the rare-earth-based low-dimensional molecular magnetic chains Eu (hfac) 3NITEt and Gd (hfac) 3NITEt (in short, Eu-Et and Gd-Et). Although both samples are based on the same chemical building block, [(hfac) 3NITEt ] , their magnetic properties change dramatically when the Eu3 + ion, which is nonmagnetic at low temperatures, is substituted by the magnetic Gd3 + ion. The present proton NMR investigation shows that, down to the lowest investigated temperature (T =1.5 K for Gd-Et and T =3 K for Eu-Et), the Eu-Et chain behaves as a one-dimensional Heisenberg model with antiferromagnetic exchange coupling (J =-20 K) between s =1 /2 organic radicals, and has a T -independent exchange frequency (ωe=2.6 ×1012 rad/s). In the Gd-Et chain, in contrast, a competition arises between nearest-neighbor ferromagnetic coupling and next-nearest-neighbor antiferromagnetic coupling; moreover, two phase transitions have previously been found, in agreement with Villain's conjecture: a first transition, at T0=2.2 K, from a high temperature paramagnetic phase to a chiral spin liquid phase, and a second transition, at TN=1.9 K, to a three-dimensional helical spin solid phase. Contrary to the Eu-Et chain (whose three-dimensional ordering temperature is estimated to insurge at very low, TN≈0.3 K), critical spin dynamics effects have been measured in the Gd-Et chain on approaching TN=1.9 K: namely, a divergence of the proton nuclear spin-lattice relaxation rate 1 /T1 , which in turn produces a sudden wipe-out of the NMR signal in a very narrow (Δ T ˜0.04 K) temperature range above TN. Below TN, an inhomogeneous broadening of the NMR line indicates a complete spin freezing. At T0=2.2 K, instead, such critical effects are not observed because NMR measurements probe the two-spin correlation function, while the chiral spin liquid phase transition is associated with a divergence of the four

  13. Detection and characterization of hyperfine-shifted resonances in the proton nuclear magnetic resonance spectrum of Anabaena 7120 ferredoxin at high magnetic fields.

    PubMed

    Skjeldal, L; Westler, W M; Markley, J L

    1990-05-01

    This paper presents previously unobserved signals in the 1H NMR spectra of oxidized and reduced [2Fe-2S]-ferredoxin from Anabaena 7120 detected at 400, 500, and 600 MHz. The signals shifted to low field exhibited longitudinal relaxation (T1) values in the range of 100-400 microseconds and line widths in the range of 1-10 kHz (at 400 MHz), and the chemical shifts of all signals showed strong temperature dependence. Although the line widths were smaller at lower magnetic fields, the resolution was better at higher magnetic fields. In the oxidized state, a broad signal was detected at 37 ppm, which corresponds to at least 6 protons, and whose chemical shift exhibits positive temperature dependence. This signal also was found in oxidized ferredoxin reconstituted in 2H2O, which excludes the signal as arising from solvent-exchangeable amide protons. In the reduced state, four signals detected between 90 and 140 ppm exhibited negative temperature dependence. These consisted of two pairs of signals, each pair having one component with half the linewidth of the other. On the basis of their chemical shifts, linewidths, longitudinal relaxation properties, and temperature dependence we assigned these resonances to four of the beta hydrogens of the ligated cysteines. Two solvent-exchangeable hyperfine-shifted signals were found in the reduced state; these are located upfield of the diamagnetic region. The low-field hyperfine resonances of half-reduced ferredoxin in the presence of sodium dithionite showed a self electron transfer exchange rate that was slow on the NMR scale as observed earlier (Chan, T., and Markley, J. L. (1983) Biochemistry 22, 5982-5987), but the exchange rate was accelerated in the presence of methyl viologen. PMID:2327800

  14. Effect of magnetic field and iron content on NMR proton relaxation of liver, spleen and brain tissues.

    PubMed

    Hocq, Aline; Luhmer, Michel; Saussez, Sven; Louryan, Stéphane; Gillis, Pierre; Gossuin, Yves

    2015-01-01

    Iron accumulation is observed in liver and spleen during hemochromatosis and important neurodegenerative diseases involve iron overload in brain. Storage of iron is ensured by ferritin, which contains a magnetic core. It causes a darkening on T2 -weighted MR images. This work aims at improving the understanding of the NMR relaxation of iron-loaded human tissues, which is necessary to develop protocols of iron content measurements by MRI. Relaxation times measurements on brain, liver and spleen samples were realized at different magnetic fields. Iron content was determined by atomic emission spectroscopy. For all samples, the longitudinal relaxation rate (1/T1 ) of tissue protons decreases with the magnetic field up to 1 T, independently of iron content, while their transverse relaxation rate (1/T2 ) strongly increases with the field, either linearly or quadratically, or a combination thereof. The extent of the inter-echo time dependence of 1/T2 also varies according to the sample. A combination of theoretical models is necessary to describe the relaxation of iron-containing tissues. This can be due to the presence, inside tissues, of ferritin clusters of different sizes and densities. When considering all samples, a correlation (r(2)  = 0.6) between 1/T1 and iron concentration is observed at 7.0 T. In contrast the correlation between 1/T2 and iron content is poor, even at high field (r(2)  = 0.14 at 7.0 T). Our results show that MRI methods based on T1 or T2 measurements will easily detect an iron overloading at high magnetic field, but will not provide an accurate quantification of tissue iron content at low iron concentrations. PMID:24954138

  15. Seasonal and temporal characterization of dissolved organic matter in rainwater by proton nuclear magnetic resonance spectroscopy

    NASA Astrophysics Data System (ADS)

    Seaton, Pamela J.; Kieber, Robert J.; Willey, Joan D.; Avery, G. Brooks; Dixon, Joshua L.

    2013-02-01

    Dissolved organic carbon in rainwater was concentrated by two separate techniques and characterized by 1H-NMR. The total 1H-NMR integral of lyophilized rainwater was higher in every rain sample than that of C18 solid phase extracted samples and always contained a higher percentage integral in the region of protons bound to carbon atoms singly bound to oxygen (H-C-O), such as alcohols, polyols and carbohydrate-like compounds. C18 extracted samples had higher % integral in the alkyl region, consistent with reverse phase extraction of more hydrophobic components in rainwater. Differences in both the 1H-NMR integration and spectral pattern of lyophilized rainwater samples were especially apparent between spring and winter rains, with spring samples having higher percent carbohydrate (H-C-O) signal and winter rains having higher percent alkyl protons and a spectral pattern consistent with the presence of saturated fatty acids. Spring rains are characterized by lower % Alkyl signal coupled with higher % H-C-O than all other events while marine winter events appear in regions characterized by relatively high % Alkyl and average % H-C-O, consistent with increased abundance of fatty acids or fatty acid oxidation products. The 1H-NMR data presented in this manuscript are important because they provide spectral data relating to the source and chemical characteristics of dissolved organic carbon in rainwater as a function of season and air mass back trajectory.

  16. Type-II entry of solar wind protons into the lunar wake: Effects of magnetic connection to the night-side surface

    NASA Astrophysics Data System (ADS)

    Nishino, Masaki N.; Fujimoto, Masaki; Saito, Yoshifumi; Tsunakawa, Hideo; Kasahara, Yoshiya; Kawamura, Mariko; Matsushima, Masaki; Takahashi, Futoshi; Shibuya, Hidetoshi; Shimizu, Hisayoshi; Goto, Yoshitaka; Hashimoto, Kozo; Omura, Yoshiharu; Kumamoto, Atsushi; Ono, Takayuki; Yokota, Shoichiro

    2014-05-01

    Our recent observations around the Moon revealed that so-called type-II (T2) entry of the solar wind protons into the near-Moon wake occurs when the IMF is dominated by the non-radial components (i.e. BY and/or BZ). Under this condition a part of the solar wind protons scattered/reflected at the lunar dayside surface subsequently enters the central region of the near-Moon wake after a large-scale cycloid motion, which accelerates electrons along the filed line into the wake. The situation handled in the previous studies is that the relevant magnetic field line is detached from the lunar surface, leaving a possibility of the T2 entry under magnetic connection left open. Here we report that the protons can access the central wake region that is magnetically connected to the lunar nightside surface, which we categorize into the T2 entry with magnetic connection to the lunar surface (T2MC). Furthermore we show that the energy of the electron beams induced by the proton entry into the wake depends on the magnetic connectivity. Strong electron acceleration (up to several hundred eV to 1 keV) along the magnetic field associated with the T2 entry is prominent when the field line has its both ends in the solar wind, that is, when the magnetic field is detached from the lunar surface (i.e. the previously-reported T2 entry that we rename to T2MD). On the other hand, no significant electron acceleration is found in the T2MC cases, although an enhancement of the electron flux associated with the T2 proton entry is evident. We also report that the T2 entry process takes place even under radial (BX-dominated) IMF condition. Our results indicate that, while the T2 entry of solar wind protons into the wake itself does not require a special IMF condition but is a rather general phenomenon, the characteristic energy of associated electrons does show a strong dependence on the magnetic connectivity to the lunar surface.

  17. SU-E-J-229: Magnetic Resonance Imaging of Small Fiducial Markers for Proton Beam Therapy

    SciTech Connect

    Hu, Y; James, J; Panda, A; Vargas, C; Silva, A; Liu, W; Shen, J; Ding, X; Paden, R; Hanson, J; Wong, W; Schild, S; Bues, M

    2015-06-15

    Purpose: For proton beam therapy, small fiducial markers are preferred for patient alignment due to less interference with the proton beam. Visualizing small fiducial markers can be challenging in MRI. This study intends to investigate MRI imaging protocols for better visualization of small fiducial markers. Methods: Two carbon and two coil-shaped gold markers were placed into a gel phantom. Both carbon markers had a diameter of 1mm and a length of 3mm. Both gold markers had a length of 5mm. One gold marker had a diameter of 0.5mm and the other had a diameter of 0.75mm. T1 VIBE, T2 SPACE, TrueFISP and susceptibility weighted (SW) images were acquired. To improve marker contrast, high spatial resolution was used to reduce partial volume effect. Slice thickness was 1.5mm for all four sequences and in-plane resolution was 0.6mm for TrueFISP, 0.7mm for T1 VIBE, and 0.8mm for T2 SPACE and SW. For comparison purpose, a 3D T1 VIBE image set at 3mm slice thickness and 1.2mm in-plane resolution was also acquired. Results: All markers were visible in all high-resolution image sets. In each image set, marker-induced signal void was the smallest (in diameter) for carbon markers, followed by the 0.5mm gold marker and the largest for the 0.75mm gold marker. The SW images had the largest marker-induced signal void. However, those might be confused by susceptibility-gradient-induced signal voids. T1 VIBE had good visualization of markers with nicely defined edges. T2 SPACE had reasonable visualization of markers but edges were slightly blurred. TrueFISP had good visualization of markers only if they were not masked by banding artifacts. As a comparison, all markers were hardly visible in the standard resolution T1 VIBE images. Conclusion: 3D high-resolution T1 VIBE and SW have great potential in providing good visualization of small fiducial markers for proton beam therapy.

  18. Effect of mica content on pore-size distribution and porosity of sandy sediment using proton nuclear magnetic resonance measurement

    NASA Astrophysics Data System (ADS)

    Kimura, S.

    2015-12-01

    As a part of a Japanese National hydrate research program (MH21, funded by METI), we performed a study on effect of mica content on pore size distribution and porosity of sandy sediment. This study used proton nuclear magnetic resonance (NMR) to measure the pore-size distribution and porosity of specimen to investigate mica content effect in sandy sediment. A mixture of silica sand No. 7 and mica (mica of 0 wt. %, 5 wt. % and 20 wt. %) was used in this study. The median D50 by laser diffraction method was obtained as 215.7 μm of silica sand No. 7 and 278.9 μm of mica. Pore-size distributions of specimens by the distribution of transverse magnetic relaxation time (T2) measurement by NMR were performed for the water-saturated sample under effective confining pressure of 1.0 MPa. The peaks of pore-size distribution curves decreased and showed finer shifts with increasing of mica content. The porosity of silica sand No. 7 specimen was 46.3%, and that of mica 5% and 20 % were 45.9% and 42.2%m, respectively. A change in pore-size distribution and porosity were observed with an increasing ratio of mica.

  19. Proton magnetic resonance spectroscopy of the kidney in renal stone disease.

    PubMed

    Mairiang, Eimorn; Hanpanich, Petcharakorn; Sriboonlue, Pote

    2002-12-01

    Previous studies of renal stone disease (RSD) in Thailand indicated abnormal urinary aggregator and inhibitor composition among farmers with excessive sweat loss. Our aim was to compare the proton MR spectra obtained from the kidneys of 32 proven cases of RSD (aged 38 to 65 yrs) with nine age-matched normal control subjects. We used the STEAM sequence with TE = 15 ms and TR = 2,000 ms. The spectra at 3.25, 3.6 and 3.9 ppm were analyzed. The results showed a correlation between the three peaks (p < 0.001), however, there was no significant difference between the RSD group and the normal control subjects. We therefore concluded that there was no overloading of these osmolytes among the renal stone patients. PMID:12591573

  20. High resolution NMR study of T{sub 1} magnetic relaxation dispersion. IV. Proton relaxation in amino acids and Met-enkephalin pentapeptide

    SciTech Connect

    Pravdivtsev, Andrey N.; Yurkovskaya, Alexandra V.; Ivanov, Konstantin L.; Vieth, Hans-Martin

    2014-10-21

    Nuclear Magnetic Relaxation Dispersion (NMRD) of protons was studied in the pentapeptide Met-enkephalin and the amino acids, which constitute it. Experiments were run by using high-resolution Nuclear Magnetic Resonance (NMR) in combination with fast field-cycling, thus enabling measuring NMRD curves for all individual protons. As in earlier works, Papers I–III, pronounced effects of intramolecular scalar spin-spin interactions, J-couplings, on spin relaxation were found. Notably, at low fields J-couplings tend to equalize the apparent relaxation rates within networks of coupled protons. In Met-enkephalin, in contrast to the free amino acids, there is a sharp increase in the proton T{sub 1}-relaxation times at high fields due to the changes in the regime of molecular motion. The experimental data are in good agreement with theory. From modelling the relaxation experiments we were able to determine motional correlation times of different residues in Met-enkephalin with atomic resolution. This allows us to draw conclusions about preferential conformation of the pentapeptide in solution, which is also in agreement with data from two-dimensional NMR experiments (rotating frame Overhauser effect spectroscopy). Altogether, our study demonstrates that high-resolution NMR studies of magnetic field-dependent relaxation allow one to probe molecular mobility in biomolecules with atomic resolution.

  1. 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

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

    PubMed

    Sallusto, Federica

    2016-05-20

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

  3. Neurodegenerative evidences during early onset of depression in CMS rats as detected by proton magnetic resonance spectroscopy at 7 T.

    PubMed

    Hemanth Kumar, B S; Mishra, Sushanta Kumar; Rana, Poonam; Singh, Sadhana; Khushu, Subash

    2012-06-15

    Depression is a complex psychiatric disorder characterized by anhedonia and feeling of sadness and chronic mild stress (CMS) seems to be a valuable animal model of depression. CMS animal model was induced and validated using behavioral studies. In the present study we investigated the neuro-metabolite changes occurring in prefrontal cortex and hippocampus during the onset of depression, in CMS rat model using in vivo proton magnetic resonance spectroscopy ((1)H MRS) at field strength of 7 T. Results showed that CMS caused depression-like behavior in rats, as indicated by the decrease in sucrose consumption and locomotor activity. (1)H MRS was performed in both control and CMS rats (n=10, in each group) and the quantitative assessment of the neurometabolites was done using LC model. Relative concentrations of all the metabolites along with the macromolecules were calculated for analysis. The results revealed a significant decrease of glutamate (Glu), glutamine (Gln), NAA+NAAG, Glx and GABA levels in both hippocampus and prefrontal cortex of CMS animals and an elevated level of myo-ionisitol (mI) and taurine (Tau) was observed only in hippocampus. These metabolite fluctuations revealed by proton MRS indicate that there might be change in the neuronal integrity of the glial cells and neurons within prefrontal cortex and hippocampus in CMS model of depression. The present study also suggests that there may be a degenerative process concerning the brain morphology in the CMS rats. The overall finding using (1)H MRS suggests that, there might be a major role of the glia and neuron in the onset of depression. PMID:22449862

  4. Hydrogenated Graphenes by Birch Reduction: Influence of Electron and Proton Sources on Hydrogenation Efficiency, Magnetism, and Electrochemistry.

    PubMed

    Eng, Alex Yong Sheng; Sofer, Zdeněk; Huber, Štěpán; Bouša, Daniel; Maryško, Miroslav; Pumera, Martin

    2015-11-16

    Interest in chemical functionalisation of graphenes today is largely driven by associated changes to its physical and material properties. Functionalisation with hydrogen was employed to obtain hydrogenated graphenes (also termed graphane if fully hydrogenated), which exhibited properties including fluorescence, magnetism and a tuneable band gap. Although the classical Birch reduction has been employed for hydrogenation of graphite oxide, variation exists between the choice of alkali metals and alcohols/water as quenching agents. A systematic study of electron (Li, Na, K, Cs) and proton sources (tBuOH, iPrOH, MeOH, H2O) has been performed to identify optimal conditions. The proton source exerted a great influence on the resulting hydrogenation with water and out-performed alcohols, and the lowest carbon-to-hydrogen ratio was observed with sodium and water with composition of C1.4H1O0.3. Although ferromagnetism at room temperature correlates well with increasing hydrogen concentrations, small contributions from trace iron impurities cannot be completely eliminated. In contrast, hydrogenated graphenes exhibit a significant paramagnetic moment at low temperatures that has no correlation with impurities, and therefore, originates from the carbon system. This is in comparison to graphene, which is strongly diamagnetic, and concentrations of paramagnetic centres in hydrogenated graphenes are one order of magnitude larger than that in graphite. Nonetheless, hydrogenation over a particular level might also excessively disrupt intrinsic sp(2) conjugation, resulting in unintended reduction of electrochemical properties. This was observed with heterogeneous electron-transfer rates and it was postulated that hydrogenated graphenes should generally have high defect densities, but only moderately high hydrogenation, should they be employed as electrode materials. PMID:26457373

  5. Multicomponent analysis of radiolytic products in human body fluids using high field proton nuclear magnetic resonance (NMR) spectroscopy

    NASA Astrophysics Data System (ADS)

    Grootveld, Martin C.; Herz, Herman; Haywood, Rachel; Hawkes, Geoffrey E.; Naughton, Declan; Perera, Anusha; Knappitt, Jacky; Blake, David R.; Claxson, Andrew W. D.

    1994-05-01

    High field proton Hahn spin-echo nuclear magnetic resonance (NMR) spectroscopy has been employed to investigate radiolytic damage to biomolecules present in intact human body fluids. γ-Radiolysis of healthy or rheumatoid human serum (5.00 kGy) in the presence of atmospheric O 2 gave rise to reproducible elevations in the concentration of NMR-detectable acetate which are predominantly ascribable to the prior oxidation of lactate to pyruvate by hydroxyl radical (·OH) followed by oxidative decarboxylation of pyruvate by radiolytically-generated hydrogen peroxide (H 2O 2) and/or further ·OH radical. Increases in the serum levels of non-protein-bound, low-molecular-mass components such as citrate and glutamine were also observed subsequent to γ-radiolysis, an observation which may reflect their mobilisation from protein binding-sites by ·OH radical, superoxide anion and/or H 2O 2. Moreover, substantial radiolytically-mediated elevations in the concentration of serum formate were also detectable. In addition to the above modifications, γ-radiolysis of inflammatory knee-joint synovial fluid (SF) generated a low-molecular-mass oligosaccharide species derived from the radiolytic fragmentation of hyaluronate. The radiolytically-mediated production of acetate in SF samples was markedly greater than that observed in serum samples, a consequence of the much higher levels of ·OH radical-scavenging lactate present. Indeed, increases in SF acetate concentration were detectable at doses as low as 48 Gy. We conclude that high field proton NMR analysis provides much useful information regarding the relative radioprotectant abilities of endogenous components and the nature, status and levels of radiolytic products generated in intact biofluids. We also suggest that NMR-detectable radiolytic products with associated toxicological properties (e.g. formate) may play a role in contributing to the deleterious effects observed following exposure of living organisms to sources of

  6. Proton Magnetic Resonance and Human Thyroid Neoplasia III. Ex VivoChemical-Shift Microimaging

    NASA Astrophysics Data System (ADS)

    Rutter, Allison; Künnecke, Basil; Dowd, Susan; Russell, Peter; Delbridge, Leigh; Mountford, Carolyn E.

    1996-03-01

    Magnetic-resonance chemical-shift microimaging, with a spatial resolution of 40 × 40 μm, is a modality which can detect alterations to cellular chemistry and hence markers of pathological processes in human tissueex vivo.This technique was used as a chemical microscope to assess follicular thyroid neoplasms, lesions which are unsatisfactorily investigated using standard histopathological techiques or water-based magnetic-resonance imaging. The chemical-shift images at the methyl frequency (0.9 ppm) identify chemical heterogeneity in follicular tumors which are histologically homogeneous. The observed changes to cellular chemistry, detectable in foci of approximately 100 cells or less, support the existence of a preinvasive state hitherto unidentified by current pathological techniques.

  7. Effect of Triplet Magnet Vibrations on RHIC Performance with High Energy Protons

    SciTech Connect

    Minty, M.

    2010-05-23

    In this report we present recent experimental data from the Relativistic Heavy Ion Collider (RHIC) illustrating effects resulting from {approx}10 Hz vibrations of the triplet quadrupole magnets in the interactions regions and evaluate the impact of these vibrations on RHIC collider performance. Measurements revealed modulation of the betatron tunes of appreciable magnitude relative to the total beam-beam parameter. Comparison of the discrete frequencies in the spectra of the measured beam positions and betatron tunes confirmed a common source. The tune modulations were shown to result from feed-down in the sextupole magnets in the interaction regions. In addition we show that the distortions to the closed orbit of the two counter-rotating beams produced a modulated crossing angle at the interaction point(s).

  8. Progressive Multifocal Leukoencephalopathy Localized in the Cerebellum and Brainstem Associated with Idiopathic CD4(+) T Lymphocytopenia.

    PubMed

    Aotsuka, Yuya; Uzawa, Akiyuki; Nishimura, Kazutaka; Kojima, Kazuho; Yamaguchi, Mika; Makino, Takahiro; Nakamichi, Kazuo; Saijo, Masayuki; Kuwabara, Satoshi

    2016-01-01

    Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease that favors the cerebrum and typically occurs in immunosuppressed patients. We herein report the case of a 66-year-old man with PML, idiopathic CD4(+) T lymphocytopenia (ICL), and chronic renal failure. Cranial magnetic resonance imaging (MRI) showed a crescent-shaped lesion in the left cerebellum, brainstem, and middle cerebellar peduncle. Although the patient did not present with HIV infection, collagen diseases, or tumors, JC virus DNA was detected in the cerebrospinal fluid. Clinicians should consider PML and ICL in the differential diagnosis if the patient develops progressive ataxia and a crescent-shaped cerebellar lesion on MRI. PMID:27301521

  9. Electron-proton spectrometer

    NASA Technical Reports Server (NTRS)

    Winckler, J. R.

    1973-01-01

    An electron-proton spectrometer was designed to measure the geomagnetically trapped radiation in a geostationary orbit at 6.6 earth radii in the outer radiation belt. This instrument is to be flown on the Applications Technology Satellite-F (ATS-F). The electron-proton spectrometer consists of two permanent magnet surface barrier detector arrays and associated electronics capable of selecting and detecting electrons in three energy ranges: (1) 30-50 keV, (2) 150-200 keV, and (3) 500 keV and protons in three energy ranges. The electron-proton spectrometer has the capability of measuring the fluxes of electrons and protons in various directions with respect to the magnetic field lines running through the satellite. One magnet detector array system is implemented to scan between EME north and south through west, sampling the directional flux in 15 steps. The other magnet-detector array system is fixed looking toward EME east.

  10. H-1 Dynamic Nuclear Polarization in Supercritical Ethylene at 1.4 T

    SciTech Connect

    Wind, Robert A. ); Shi, Bai; Hu, Jian Zhi ); Solum, Mark S.; Ellis, Paul D. ); Grant, David M.; Pugmire, Ronald J.; Taylor, Craig M.; Yonker, Clement R. )

    2000-03-01

    H1 dynamic nuclear polarization (DNP) has been measured in supercritical ethylene in the pressure range 60-300 bar and in an external field of 1.4 T. A single-cell sapphire tube was used as a high pressure cell and powdered 1,3-bisdiphenylene-2-phenyl allyl(BDPA) free radicals were added and distributed at the wall of the cell. At all pressures the dominant DNP effect was a positive Overhauser enhancement, caused by proton-electron contact interactions at the fluid/solid radical interface. The observed enhancements varied from 12 at 67 bar to 17 at 300 bar. Besides the Overhauser enhancement, also a small solid state and thermal mixing enhancement were observed, indicating that part of the ethylene is absorbed at the radical surface for a prolonged time. These data indicate that DNP-enhanced NMR has the potential of extending the impact of NMR in research areas involving supercritical fluids.

  11. Proton magnetic resonance characterization of phoratoxins and homologous proteins related to crambin.

    PubMed

    Lecomte, J T; Kaplan, D; Llinás, M; Thunberg, E; Samuelsson, G

    1987-02-24

    The mistletoe protein toxins ligatoxin, phoratoxins A and B, and viscotoxins A3 and B have been investigated by 1H NMR spectroscopy at 300 and 600 MHz. The five polypeptides define a set of closely related homologues, containing 46 amino acid residues each, in a structure constrained by three cystine bridges. Their methyl and aromatic spectra were analyzed and a number of signals identified and assigned via comparative criteria, two-dimensional chemical-shift correlated spectroscopy, acid-base titration, and proton Overhauser experiments in 1H2O. The spectra indicate a compact globular conformation and a common folding pattern for the toxins. In particular, use was made of well-resolved aliphatic and aromatic resonances in order to compare the mistletoe proteins with the thionins, a set of homologous toxins from gramineae, and with crambin, a closely related polypeptide from a crucifer, which we have previously studied by NMR. We observe that while all the investigated proteins have very similar secondary and tertiary structures, they differ widely in their dynamic characteristics as probed by the amide NH 1H-2H exchange kinetics in deuteriated solvents; thus, while crambin and the thionins exhibit very fast isotope exchange, the kinetics for the mistletoe toxins are slow, with some NH groups showing exchange half-lives that extend up to several days at pH* 5.8 or that are too long to be measurable at ambient temperature. The temperature dependence of the 1H NMR spectrum also indicates that the toxins are endowed with a thermally very stable native (ground-state) structure, with little evidence of large amplitude structural breathings up to approximately 370 K, although irreversible chemical degradation (denaturation) becomes evident at temperatures greater than or equal to 350 K. It is concluded that the mistletoe toxins afford valuable rigid structures for NMR conformational studies. PMID:3567163

  12. Proton-Enhanced 13C Nuclear Magnetic Resonance of Lipids and Biomembranes

    PubMed Central

    Urbina, Julio; Waugh, J. S.

    1974-01-01

    A recently developed nuclear double resonance technique which permits sensitive detection, together with high resolution, of rare spins in solids or other dipolar-coupled nuclear systems [Pines, Gibby, and Waugh (1973) J. Chem. Phys. 59, 569] has been applied to the study of natural abundance 13C-nuclear magnetic resonance in lipid mesophases and of selectively labeled carbon sites in bacterial membranes. Detailed microscopic information on the molecular organization and phase transitions of the lipid phases and their interaction with ions and other molecules can be obtained from the study of the chemical shift anisotropies and dynamical aspects of the 13C NMR spectra of unsonicated lipid dispersions (liposomes). Experiments are reported which demonstrated the feasibility of quantitatively observing the 13C-nuclear magnetic resonance of specifically labeled sites in unperturbed Escherichia coli membrane vesicles for the study of the physical state of the lipids with the aim of relating it to the known lipid-dependent functional properties of the membranes. PMID:4531036

  13. Nuclear magnetic resonance of external protons using continuous dynamical decoupling with shallow NV centers

    NASA Astrophysics Data System (ADS)

    de Las Casas, Charles; Ohno, Kenichi; Awschalom, David D.

    2015-03-01

    The nitrogen vacancy (NV) center in diamond is a paramagnetic defect with excellent spin properties that can reside within a few nanometers of the diamond surface, enabling atomic-scale magnetic resonance sensing of external nuclear spins. Here we use rotating frame longitudinal spin relaxation (T1ρ) based sensing schemes, known as Continuous Dynamical Decoupling (CDD), to detect external nuclear spins with shallow NV centers (<5 nm from the surface). Distinguishing neighboring nuclear spins from each other requires the NV center be near enough to create differences in the hyperfine shifts and coupling strengths of the nuclei. However, spin coherence time and consequently the sensitivity of dynamical decoupling techniques degrade sharply as NVs become shallower. We use strong continuous driving to overcome this fast decoherence and detect an ensemble of external nuclear spins using a single shallow NV center with a short T2 (<2 μs) at magnetic fields as high as 0.5 Tesla. The increased sensitivity of this method relative to pulsed dynamical decoupling techniques demonstrates the benefits of CDD for sensing with very shallow NV centers. This work was supported by DARPA, AFOSR, and the DIAMANT program.

  14. Elevated prefrontal cortex GABA in patients with major depressive disorder after TMS treatment measured with proton magnetic resonance spectroscopy

    PubMed Central

    Dubin, Marc J.; Mao, Xiangling; Banerjee, Samprit; Goodman, Zachary; Lapidus, Kyle A.B.; Kang, Guoxin; Liston, Conor; Shungu, Dikoma C.

    2016-01-01

    Background GABAergic and glutamatergic neurotransmitter systems are central to the pathophysiology of depression and are potential targets of repetitive transcranial magnetic stimulation (rTMS). We assessed the effect of 10-Hz rTMS over the left dorsolateral prefrontal cortex (DLPFC) of patients with major depressive disorder on the levels of medial prefrontal cortex (MPFC) γ-aminobutyric acid (GABA) and the combined resonance of glutamate and glutamine (Glx) as assessed in vivo with proton magnetic resonance spectroscopy (1H MRS). Methods Currently depressed individuals between the ages of 23 and 68 years participated in a 5-week naturalistic, open-label treatment study of rTMS, with 1H MRS measurements of MPFC GABA and Glx levels at baseline and following 5 weeks of the rTMS intervention. We applied rTMS pulses over the left DLPFC at 10 Hz and 80%–120% of motor threshold for 25 daily sessions, with each session consisting of 3000 pulses. We assessed therapeutic response using the 24-item Hamilton Rating Scale for Depression (HAMD24). The GABA and Glx levels are expressed as ratios of peak areas relative to the area of the synchronously acquired and similarly fitted unsuppressed voxel water signal (W). Results Twenty-three currently depressed individuals (7 men) participated in the study. GABA/W in the MPFC increased 13.8% (p = 0.013) in all depressed individuals. There were no significant effects of rTMS on Glx/W. GABA/W and Glx/W were highly correlated in severely depressed patients at baseline but not after TMS. Limitations The primary study limitations are the open-label design and the inclusion of participants currently taking stable regimens of antidepressant medications. Conclusion These results implicate GABAergic and glutamatergic systems in the mechanism of action of rTMS for major depression, warranting further investigation in larger samples. PMID:26900793

  15. Proton magnetic resonance spectroscopy as a diagnostic biomarker in mild cognitive impairment following stroke in acute phase.

    PubMed

    Meng, Ningqin; Shi, Shengliang; Su, Ying

    2016-05-25

    To investigate proton magnetic resonance spectroscopy (HMRS) as a diagnostic biomarker to identify mild cognitive impairment (MCI) following stroke in the acute phase. A total of 72 stroke patients were recruited in the acute phase of stroke from the Department of Neurology, including 36 stroke patients with MCI and 36 stroke patients without MCI. All patients underwent brain MRI/MRS examination on a 3.0 T scanner and a neuropsychological test in the acute phase of stroke. Single-voxel HMRS was performed to obtain hippocampal metabolism intensities and brain infarcts were assessed on MRI. Group difference in metabolite ratios was analyzed using a T-test. Spearman rank correlation was used to study the correlation between metabolite ratios and Montreal Cognitive Assessment scores. The hippocampal n-acetylaspartate/creatine (NAA/Cr) ratio was found to be significantly lower in stroke patients with MCI compared with stroke patients without MCI (P<0.02). However, we found no differences in the metabolite ratios between hippocampus ipsilateral to infarctions and the contralateral side (P>0.05) in stroke patients with MCI. Furthermore, a correlation was found between hippocampal NAA/Cr ratios and Montreal Cognitive Assessment scores in stroke patients with MCI (P<0.01). HMRS could be a biomarker to identify MCI following stroke in the acute phase by capturing neurodegenerative changes. PMID:26981713

  16. Three dimensional structure prediction and proton nuclear magnetic resonance analysis of toxic pesticides in human blood plasma

    PubMed Central

    Sharma, Amit Kumar; Tiwari, Rajeev Kumar; Gaur, Mulayam Singh

    2012-01-01

    The purpose of this study was to investigate the nuclear magnetic resonance (NMR) assignments of hydrolyzed products extracted from human blood plasma. The correlations between chemical, functional and structural properties of highly toxic pesticides were investigated using the PreADME analysis. We observed that toxic pesticides possessed higher molecular weight and, more hydrogen bond donors and acceptors when compared with less toxic pesticides. The occurrence of functional groups and structural properties was analyzed using 1H-NMR. The 1H-NMR spectra of the phosphomethoxy class of pesticides were characterized by methyl resonances at 3.7-3.9 ppm (δ) with the coupling constants of 11-16 Hz (JP-CH3). In phosphoethoxy pesticides, the methyl resonance was about 1.4 ppm (δ) with the coupling constant of 10 Hz (JP-CH2) and the methylene resonances was 4.2-4.4 ppm (δ) with the coupling constant of 0.8 Hz (JP-CH3), respectively. Our study shows that the values of four parameters such as chemical shift, coupling constant, integration and relaxation time correlated with the concentration of toxic pesticides, and can be used to characterise the proton groups in the molecular structures of toxic pesticides. PMID:23554747

  17. [In vitro evaluation of metabolic change in forebrain ischemia model of rat using proton magnetic resonance spectroscopy].

    PubMed

    Tanaka, N

    1997-05-01

    Metabolic disruption resulted from cerebral ischemia and post-ischemia reperfusion injury was studied using proton magnetic resonance spectroscopy (1H MRS). We also analyzed the effect of 3-methyl-1-phenyl-2-pyrazolin-5-one (MCI-186) which can scavenge free radicals induced in the brain tissue due to ischemic-reperfusion in this experiment. The ischemic model was produced using rat forebrain ischemic model (Pulsinelli's 4 vessels occlusion model). Post-ischemic reperfusion was also induced by the re-opening of the occluded common carotid arteries. The occluded time was 30 min and reperfusion time 0, 10, 30, 60 min. We obtained the specimens in the cortex under microwave fixation. Choline and acetate increased during ischemia and gradually decreased during reperfusion period. These two signals seen in 1H MRS are supposed to represent cell membrane components (products) and the increase of these signals after reperfusion seems to be related to the post ischemic reperfusion injury due to the explosive increase of free radicals. Lactate, which is induced by anaerobic glycolysis, increased during ischemia and promptly disappeared after reperfusion. The treatment of pre-ischemic administration of MCI-186 significantly suppressed increases of choline and acetate. As far as lactate is concerned, post-ischemic administration of this drug significantly reduced its increase at the point of reperfusion. Our results suggest that MCI-186 alternates changes induced by ischemic-reperfusion injury in membranous metabolism, probably due to its free radical scavenging action. PMID:9226472

  18. Hydrogen Proton Magnetic Resonance Spectroscopy in Multidomain Amnestic Mild Cognitive Impairment and Vascular Cognitive Impairment Without Dementia.

    PubMed

    Chen, Shuang-Qing; Cai, Qing; Shen, Yu-Ying; Xu, Chuan-Xiao; Zhou, Hua; Zhao, Zhong

    2016-08-01

    To investigate the value of hydrogen proton magnet resonance spectroscopy ((1)H-MRS) in the differential diagnosis of multiple-domain amnestic mild cognitive impairment (M-aMCI) and vascular cognitive impairment with no dementia (VCIND); (1)H-MRS was performed in patients with M-aMCI and VCIND. The level was determined for N-acetylaspartate (NAA), glutamate (Glu), inositol (mI), choline (Cho), and creatine (Cr). Compared with the normal control group, the NAA-Cr ratio in all regions studied was significantly lower in the M-aMCI and VCIND groups. The Glu-Cr ratio in the posterior cingulate gyrus of the M-aMCI group was significantly lower than in the VCIND. The mI-Cr ratio in the frontal white matter of the VCIND was significantly higher than in the M-aMCI group. In the white matter adjacent to the lateral ventricles, the Cho-Cr ratio was significantly higher in the VCIND than the M-aMCI. Our results suggested (1)H-MRS is an effective method in the differential diagnosis of M-aMCI and VCIND. PMID:26980718

  19. T2 relaxation effects on apparent N-acetylaspartate concentration in proton magnetic resonance studies of schizophrenia

    PubMed Central

    Bracken, Bethany K.; Rouse, Elizabeth D.; Renshaw, Perry F.; Olson, David P.

    2013-01-01

    Over the past two decades, many magnetic resonance spectroscopy (MRS) studies reported lower N-acetylaspartate (NAA) in key brain regions of patients with schizophrenia (SZ) compared to healthy subjects. A smaller number of studies report no difference in NAA. Many sources of variance may contribute to these discordant results including heterogeneity of the SZ subject populations and methodological differences such as MRS acquisition parameters, and post-acquisition analytic methods. The current study reviewed proton MRS literature reporting measurements of NAA in SZ with a focus on methodology. Studies which reported lower NAA were significantly more likely to have used longer echo times (TEs), while studies with shorter TEs reported no concentration difference. This suggests that NAA quantitation using MRS was affected by the choice of TE, and that published MRS literature reporting NAA in SZ using a long TE is confounded by apparent differential T2 relaxation effects between SZ and healthy control groups. Future MRS studies should measure T2 relaxation times. This would allow for spectral concentration measurements to be appropriately corrected for these relaxation effects. In addition, as metabolite concentration and T2 relaxation times are completely independent variables, this could offer distinct information about the metabolite of interest. PMID:23769421

  20. Comparisons of Simulated and Observed Stormtime Magnetic Intensities, Ion Plasma Parameters, and ENA Proton Flux in the Ring Current During Storms

    NASA Astrophysics Data System (ADS)

    Chen, M. W.; Lemon, C.; Guild, T. B.; Schulz, M.; Roeder, J. L.; Le, G.; Lui, T.; Goldstein, J.

    2010-12-01

    In this study we compare simulated and observed stormtime magnetic intensities, proton flux spectra and/or ENA fluxes for two storm events to test how well self-consistent simulations can simultaneously reproduce these quantities. We simulate the ring current and plasma sheet using the magnetically and electrostatically self-consistent Rice Convection Model-Equilibrium (RCM-E) [Lemon et al., JGR, 2004] with a time-varying magnetopause driven by upstream solar wind and interplanetary magnetic field (IMF) conditions. Using either in-situ data (e.g., LANL/MPA and SOPA) or the empirical IMF-dependent model of Tsyganenko and Mukai [JGR, 2003], we specify the plasma sheet pressure and density at 10 Earth radii as the plasma boundary location in the RCM-E. We compare the simulated magnetic intensity with the magnetic intensity measured by magnetometers on the GOES satellites at geosynchronous altitude (6.6 Earth radii) and any other available satellite. We simulate a larger (11 August 2000; minimum Dst = -106 nT) and a smaller (6 April 2010; minimum Dst = 73 nT) storm. For the 11 August 2000 storm, we compare simulated and observed proton spectra (LANL/MPA and SOPA and Polar/CAMMICE). For the more recent 6 April 2010 storm we compare simulated and observed proton spectra (THEMIS) and energetic neutral atom (ENA) flux (TWINS). We discuss the response of the ring current magnetic field and ion flux distribution to expansions and compressions of the magnetosphere associated with the dynamic solar wind pressure for these storm events.

  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. Proton-conductive magnetic metal-organic frameworks, {NR3(CH2COOH)}[M(a)(II)M(b)(III)(ox)3]: effect of carboxyl residue upon proton conduction.

    PubMed

    Ōkawa, Hisashi; Sadakiyo, Masaaki; Yamada, Teppei; Maesato, Mitsuhiko; Ohba, Masaaki; Kitagawa, Hiroshi

    2013-02-13

    Proton-conductive magnetic metal-organic frameworks (MOFs), {NR(3)(CH(2)COOH)}[M(a)(II)M(b)(III)(ox)(3)] (abbreviated as R-M(a)M(b): R = ethyl (Et), n-butyl (Bu); M(a)M(b) = MnCr, FeCr, FeFe) have been studied. The following six MOFs were prepared: Et-MnCr·2H(2)O, Et-FeCr·2H(2)O, Et-FeFe·2H(2)O, Bu-MnCr, Bu-FeCr, and Bu-FeFe. The structure of Bu-MnCr was determined by X-ray crystallography. Crystal data: trigonal, R3c (#161), a = 9.3928(13) Å, c = 51.0080(13) Å, Z = 6. The crystal consists of oxalate-bridged bimetallic layers interleaved by {NBu(3)(CH(2)COOH)}(+) ions. Et-MnCr·2H(2)O and Bu-MnCr (R-MnCr MOFs) show a ferromagnetic ordering with T(C) of 5.5-5.9 K, and Et-FeCr·2H(2)O and Bu-FeCr (R-FeCr MOFs) also show a ferromagnetic ordering with T(C) of 11.0-11.5 K. Et-FeFe·2H(2)O and Bu-FeFe (R-FeFe MOFs) belong to the class II of mixed-valence compounds and show the magnetism characteristic of Néel N-type ferrimagnets. The Et-MOFs (Et-MnCr·2H(2)O, Et-FeCr·2H(2)O and Et-FeFe·2H(2)O) show high proton conduction, whereas the Bu-MOFs (Bu-MnCr, Bu-FeCr, and Bu-FeFe) show moderate proton conduction. Together with water adsorption isotherm studies, the significance of the carboxyl residues as proton carriers is revealed. The R-MnCr MOFs and the R-FeCr MOFs are rare examples of coexistent ferromagnetism and proton conduction, and the R-FeFe MOFs are the first examples of coexistent Néel N-type ferrimagnetism and proton conduction. PMID:23301940

  4. Proton magnetic resonance spectroscopy of human brain in vivo in the evaluation of multiple sclerosis: Assessment of the load of disease

    SciTech Connect

    Arnold, D.L.; Matthews, P.M.; Francis, G.; Antel, J. )

    1990-04-01

    Image localized, water-suppressed proton magnetic resonance spectra were obtained from affected brain in patients with multiple sclerosis. In patients with moderate to severe chronic disease, spectra revealed a decreased ratio of N-acetylaspartate to creatine resonance intensities. A normal ratio was obtained from a large recently symptomatic MRI plaque that resolved without sequelae. We propose that the observed metabolite changes can be useful as an index of irreversible CNS injury.

  5. Non-invasive tracking of CD4+ T cells with a paramagnetic and fluorescent nanoparticle in brain ischemia.

    PubMed

    Jin, Wei-Na; Yang, Xiaoxia; Li, Zhiguo; Li, Minshu; Shi, Samuel Xiang-Yu; Wood, Kristofer; Liu, Qingwei; Fu, Ying; Han, Wei; Xu, Yun; Shi, Fu-Dong; Liu, Qiang

    2016-08-01

    Recent studies have demonstrated that lymphocytes play a key role in ischemic brain injury. However, there is still a lack of viable approaches to non-invasively track infiltrating lymphocytes and reveal their key spatiotemporal events in the inflamed central nervous system (CNS). Here we describe an in vivo imaging approach for sequential monitoring of brain-infiltrating CD4(+) T cells in experimental ischemic stroke. We show that magnetic resonance imaging (MRI) or Xenogen imaging combined with labeling of SPIO-Molday ION Rhodamine-B (MIRB) can be used to monitor the dynamics of CD4(+) T cells in a passive transfer model. MIRB-labeled CD4(+) T cells can be longitudinally visualized in the mouse brain and peripheral organs such as the spleen and liver after cerebral ischemia. Immunostaining of tissue sections showed similar kinetics of MIRB-labeled CD4(+) T cells when compared with in vivo observations. Our results demonstrated the use of MIRB coupled with in vivo imaging as a valid method to track CD4(+) T cells in ischemic brain injury. This approach will facilitate future investigations to identify the dynamics and key spatiotemporal events for brain-infiltrating lymphocytes in CNS inflammatory diseases. PMID:26661207

  6. Non-invasive tracking of CD4+ T cells with a paramagnetic and fluorescent nanoparticle in brain ischemia

    PubMed Central

    Jin, Wei-Na; Yang, Xiaoxia; Li, Zhiguo; Li, Minshu; Shi, Samuel Xiang-Yu; Wood, Kristofer; Fu, Ying; Han, Wei; Xu, Yun; Shi, Fu-Dong; Liu, Qiang

    2015-01-01

    Recent studies have demonstrated that lymphocytes play a key role in ischemic brain injury. However, there is still a lack of viable approaches to non-invasively track infiltrating lymphocytes and reveal their key spatiotemporal events in the inflamed central nervous system (CNS). Here we describe an in vivo imaging approach for sequential monitoring of brain-infiltrating CD4+ T cells in experimental ischemic stroke. We show that magnetic resonance imaging (MRI) or Xenogen imaging combined with labeling of SPIO-Molday ION Rhodamine-B (MIRB) can be used to monitor the dynamics of CD4+ T cells in a passive transfer model. MIRB-labeled CD4+ T cells can be longitudinally visualized in the mouse brain and peripheral organs such as the spleen and liver after cerebral ischemia. Immunostaining of tissue sections showed similar kinetics of MIRB-labeled CD4+ T cells when compared with in vivo observations. Our results demonstrated the use of MIRB coupled with in vivo imaging as a valid method to track CD4+ T cells in ischemic brain injury. This approach will facilitate future investigations to identify the dynamics and key spatiotemporal events for brain-infiltrating lymphocytes in CNS inflammatory diseases. PMID:26661207

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

    PubMed Central

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

    2015-01-01

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

  8. Parametric study of a variable-magnetic-field-based energy-selection system for generating a spread-out Bragg peak with a laser-accelerated proton beam

    NASA Astrophysics Data System (ADS)

    Kim, Dae-Hyun; Suh, Tae-Suk; Kang, Young Nam; Yoo, Seung Hoon; Pae, Ki-Hong; Shin, Dongho; Lee, Se Byeong

    2013-01-01

    Laser-based proton beam acceleration, which produces broad energy spectra, is unsuitable for direct clinical use. Thus, employing an energy selection system is necessary. The purpose of the present study was to investigate a method whereby a variable magnetic field could be employed with an energy selection system to generate a spread-out Bragg peak (SOBP). For energy selection, particle transport and dosimetric property measurements, the Geant4 toolkit was implemented. The energy spectrum of the laser-accelerated proton beam was acquired using a particle-in-cell simulation. The hole size and the position of the energy selection collimator were varied in order to determine the effects of those parameters on the dosimetric properties. To generate an SOBP, we changed the magnetic field in the energy selection system for each beam weighting factor during beam irradiation. The overall results of this study suggest that the use of an energy selection system with a variable magnetic field can effectively generate an SOBP suitable for proton radiation therapy applications.

  9. Investigating the Dissolution Performance of Amorphous Solid Dispersions Using Magnetic Resonance Imaging and Proton NMR.

    PubMed

    Tres, Francesco; Coombes, Steven R; Phillips, Andrew R; Hughes, Leslie P; Wren, Stephen A C; Aylott, Jonathan W; Burley, Jonathan C

    2015-01-01

    We have investigated the dissolution performance of amorphous solid dispersions of poorly water-soluble bicalutamide in a Kollidon VA64 polymeric matrix as a function of the drug loading (5% vs. 30% bicalutamide). A combined suite of state-of-the-art analytical techniques were employed to obtain a clear picture of the drug release, including an integrated magnetic resonance imaging UV-Vis flow cell system and 1H-NMR. Off-line 1H-NMR was used for the first time to simultaneously measure the dissolution profiles and rates of both the drug and the polymer from a solid dispersion. MRI and 1H-NMR data showed that the 5% drug loading compact erodes linearly, and that bicalutamide and Kollidon VA64 are released at approximately the same rate from the molecular dispersion. For the 30% extrudate, data indicated a slower water ingress into the compact which corresponds to a slower dissolution rate of both bicalutamide and Kollidon VA64. PMID:26378506

  10. Characterization of proton exchange membrane materials for fuel cells by solid state nuclear magnetic resonance

    SciTech Connect

    Kong, Zueqian

    2010-01-01

    Solid-state nuclear magnetic resonance (NMR) has been used to explore the nanometer-scale structure of Nafion, the widely used fuel cell membrane, and its composites. We have shown that solid-state NMR can characterize chemical structure and composition, domain size and morphology, internuclear distances, molecular dynamics, etc. The newly-developed water channel model of Nafion has been confirmed, and important characteristic length-scales established. Nafion-based organic and inorganic composites with special properties have also been characterized and their structures elucidated. The morphology of Nafion varies with hydration level, and is reflected in the changes in surface-to-volume (S/V) ratio of the polymer obtained by small-angle X-ray scattering (SAXS). The S/V ratios of different Nafion models have been evaluated numerically. It has been found that only the water channel model gives the measured S/V ratios in the normal hydration range of a working fuel cell, while dispersed water molecules and polymer ribbons account for the structures at low and high hydration levels, respectively.

  11. Regional Proton Magnetic Resonance Spectroscopy Patterns in Dementia with Lewy Bodies

    PubMed Central

    Graff-Radford, Jonathan; Boeve, Bradley F.; Murray, Melissa; Ferman, Tanis J.; Tosakulwong, Nirubol; Lesnick, Timothy G.; Maroney-Smith, Mandie; Senjem, Matthew L.; Gunter, Jeffrey; Smith, Glenn E.; Knopman, David S.; Jack, Clifford R.; Dickson, Dennis W.; Petersen, Ronald C.; Kantarci, Kejal

    2014-01-01

    Magnetic resonance spectroscopy (MRS) characteristics of dementia with Lewy bodies (DLB) Alzheimer’s disease (AD) and cognitively normal controls (CN) were compared. DLB (n=34), AD (n=35) and CN (n=148) participated in a MRS study from frontal, posterior cingulate and occipital voxels. We investigated DLB patients with preserved hippocampal volumes to determine the MRS changes in DLB with low probability of overlapping AD pathology. DLB patients were characterized by decreased NAA/Cr in the occipital voxel. AD patients were characterized by lower NAA/Cr in the frontal and posterior cingulate voxels. Normal NAA/Cr levels in the frontal voxel differentiated DLB patients with preserved hippocampal volumes from AD patients. DLB and AD patients had elevated Cho/Cr and mI/Cr in the posterior cingulate. MRS abnormalities associated with loss of neuronal integrity localized to the occipital lobes in DLB, and the posterior cingulate gyri and frontal lobes in AD. This pattern of MRS abnormalities may have a role in differential diagnosis of DLB and in distinguishing DLB patients with overlapping AD pathology. PMID:24468473

  12. Measurement of the axial and the strangeness magnetic form factor of the proton with a P2 backward angle setup

    SciTech Connect

    Baunack, S.; Becker, D.; Gerz, K.; Kumar, K.; Maas, F. E.

    2013-11-07

    The P2 experiment at the future accelerator facility MESA in Mainz aims for a precise determination of the weak charge of the proton at low momentum transfer. The experimental method is a measurement of the parity violating asymmetry in elastic electron-proton scattering at forward angle. This asymmetry is dominated by the weak charge, but also the proton structure plays a role. Here we consider a back angle measurement, which is more sensitive to the proton structure, and present its possible implications on the main P2 measurement.

  13. Proton: the particle.

    PubMed

    Suit, Herman

    2013-11-01

    The purpose of this article is to review briefly the nature of protons: creation at the Big Bang, abundance, physical characteristics, internal components, and life span. Several particle discoveries by proton as the experimental tool are considered. Protons play important roles in science, medicine, and industry. This article was prompted by my experience in the curative treatment of cancer patients by protons and my interest in the nature of protons as particles. The latter has been stimulated by many discussions with particle physicists and reading related books and journals. Protons in our universe number ≈10(80). Protons were created at 10(-6) -1 second after the Big Bang at ≈1.37 × 10(10) years beforethe present. Proton life span has been experimentally determined to be ≥10(34) years; that is, the age of the universe is 10(-24)th of the minimum life span of a proton. The abundance of the elements is hydrogen, ≈74%; helium, ≈24%; and heavier atoms, ≈2%. Accordingly, protons are the dominant baryonic subatomic particle in the universe because ≈87% are protons. They are in each atom in our universe and thus involved in virtually every activity of matter in the visible universe, including life on our planet. Protons were discovered in 1919. In 1968, they were determined to be composed of even smaller particles, principally quarks and gluons. Protons have been the experimental tool in the discoveries of quarks (charm, bottom, and top), bosons (W(+), W(-), Z(0), and Higgs), antiprotons, and antineutrons. Industrial applications of protons are numerous and important. Additionally, protons are well appreciated in medicine for their role in radiation oncology and in magnetic resonance imaging. Protons are the dominant baryonic subatomic particle in the visible universe, comprising ≈87% of the particle mass. They are present in each atom of our universe and thus a participant in every activity involving matter. PMID:24074929

  14. Proton: The Particle

    SciTech Connect

    Suit, Herman

    2013-11-01

    The purpose of this article is to review briefly the nature of protons: creation at the Big Bang, abundance, physical characteristics, internal components, and life span. Several particle discoveries by proton as the experimental tool are considered. Protons play important roles in science, medicine, and industry. This article was prompted by my experience in the curative treatment of cancer patients by protons and my interest in the nature of protons as particles. The latter has been stimulated by many discussions with particle physicists and reading related books and journals. Protons in our universe number ≈10{sup 80}. Protons were created at 10{sup −6} –1 second after the Big Bang at ≈1.37 × 10{sup 10} years beforethe present. Proton life span has been experimentally determined to be ≥10{sup 34} years; that is, the age of the universe is 10{sup −24}th of the minimum life span of a proton. The abundance of the elements is hydrogen, ≈74%; helium, ≈24%; and heavier atoms, ≈2%. Accordingly, protons are the dominant baryonic subatomic particle in the universe because ≈87% are protons. They are in each atom in our universe and thus involved in virtually every activity of matter in the visible universe, including life on our planet. Protons were discovered in 1919. In 1968, they were determined to be composed of even smaller particles, principally quarks and gluons. Protons have been the experimental tool in the discoveries of quarks (charm, bottom, and top), bosons (W{sup +}, W{sup −}, Z{sup 0}, and Higgs), antiprotons, and antineutrons. Industrial applications of protons are numerous and important. Additionally, protons are well appreciated in medicine for their role in radiation oncology and in magnetic resonance imaging. Protons are the dominant baryonic subatomic particle in the visible universe, comprising ≈87% of the particle mass. They are present in each atom of our universe and thus a participant in every activity involving matter.

  15. Plasticity of human CD4 T cell subsets.

    PubMed

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

    2014-01-01

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

  16. 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

  17. Proton Therapy

    MedlinePlus

    ... nucleus is surrounded by electrons. In proton therapy, beams of fast-moving protons are used to destroy ... atoms to release proton, neutron, and helium ion beams. In this highly specialized form of radiosurgery , proton ...

  18. Binge Toluene Exposure Alters Glutamate, Glutamine and GABA in the Adolescent Rat Brain as Measured by Proton Magnetic Resonance Spectroscopy*

    PubMed Central

    Perrine, Shane A.; O'Leary-Moore, Shonagh K.; Galloway, Matthew P.; Hannigan, John H.; Bowen, Scott E.

    2010-01-01

    Despite the high incidence of toluene abuse in adolescents, little is known regarding the effect of binge exposure on neurochemical profiles during this developmental stage. In the current study, the effects of binge toluene exposure during adolescence on neurotransmitter levels were determined using high-resolution proton magnetic resonance spectroscopy ex vivo at 11.7 T. Adolescent male Sprague-Dawley rats were exposed to toluene (0, 8,000 , or 12,000 ppm) for 15 min twice daily from postnatal day 28 (P28) through P34 and then euthanized either one or seven days later (on P35 or P42) to assess glutamate, glutamine, and GABA levels in intact tissue punches from the medial prefrontal cortex (mPFC), anterior striatum and hippocampus. In the mPFC, toluene reduced glutamate one day after exposure, with no effect on GABA, while after seven days, glutamate was no longer affected but there was an increase in GABA levels. In the hippocampus, neither GABA nor glutamate was altered one day after exposure, whereas seven days after exposure, increases were observed in GABA and glutamate. Striatal glutamate and GABA levels measured after either one or seven days were not altered after toluene exposure. These findings show that one week of binge toluene inhalation selectively alters these neurotransmitters in the mPFC and hippocampus in adolescent rats, and that some of these effects endure at least one week after the exposure. The results suggest that age-dependent, differential neurochemical responses to toluene may contribute to the unique behavioral patterns associated with drug abuse among older children and young teens. PMID:21126832

  19. Metabonomic investigations of age- and batch-related variations in female NMRI mice using proton nuclear magnetic resonance spectroscopy.

    PubMed

    Li, Jia V; Saric, Jasmina; Yap, Ivan K S; Utzinger, Jürg; Holmes, Elaine

    2013-12-01

    The NMRI outbred mouse model is widely used for studying metabolic disease, toxicity, and infection, yet information regarding baseline metabolism of this murine strain is relatively sparse. Using different batches of female NMRI mice, we assessed the stability of the metabolic phenotype with increasing age and weight, and determined the influence of acclimatization on the metabolic profile of biofluids (urine, plasma, and faecal water). Differences in urinary concentrations of 3-ureidopropionate, 2-oxoisocaproate, trimethylamine, and glycine were detected between three batches of 9-week-old female NMRI mice using proton nuclear magnetic resonance ((1)H NMR) spectroscopy coupled with multivariate statistical analysis. An acclimatization period of 2 weeks was imposed after the mice entered the laboratory environment. Strong differences in the faecal metabolome pre- and post-acclimatization were found (reduction in amino acid concentrations), whilst the urine metabolome showed increased levels of trimethylamine-N-oxide, phenylacetyl glycine, and hippurate with decreased excretion of formate and betaine post-acclimatization. Temporal variation in the metabolite profiles over a 16-week study stabilized around 7-week-old animals. The results from this study strongly argue for inclusion of an acclimatization period prior to starting an investigative procedure, and suggest that the metabolic phenotypes of female NMRI mice are more stable at around 7 weeks of age. We have also identified a set of metabolites that are more susceptible to variation in concentration. This information can serve as a benchmark in order to establish confidence in systematic variation attributable to pathology or therapeutic intervention above the background metabolic variation in the NMRI mouse. PMID:24121299

  20. Proton Nuclear Magnetic Resonance-Spectroscopic Discrimination of Wines Reflects Genetic Homology of Several Different Grape (V. vinifera L.) Cultivars

    PubMed Central

    Zhu, Yong; Wen, Wen; Zhang, Fengmin; Hardie, Jim W.

    2015-01-01

    Background and Aims Proton nuclear magnetic resonance spectroscopy coupled multivariate analysis (1H NMR-PCA/PLS-DA) is an important tool for the discrimination of wine products. Although 1H NMR has been shown to discriminate wines of different cultivars, a grape genetic component of the discrimination has been inferred only from discrimination of cultivars of undefined genetic homology and in the presence of many confounding environmental factors. We aimed to confirm the influence of grape genotypes in the absence of those factors. Methods and Results We applied 1H NMR-PCA/PLS-DA and hierarchical cluster analysis (HCA) to wines from five, variously genetically-related grapevine (V. vinifera) cultivars; all grown similarly on the same site and vinified similarly. We also compared the semi-quantitative profiles of the discriminant metabolites of each cultivar with previously reported chemical analyses. The cultivars were clearly distinguishable and there was a general correlation between their grouping and their genetic homology as revealed by recent genomic studies. Between cultivars, the relative amounts of several of the cultivar-related discriminant metabolites conformed closely with reported chemical analyses. Conclusions Differences in grape-derived metabolites associated with genetic differences alone are a major source of 1H NMR-based discrimination of wines and 1H NMR has the capacity to discriminate between very closely related cultivars. Significance of the Study The study confirms that genetic variation among grape cultivars alone can account for the discrimination of wine by 1H NMR-PCA/PLS and indicates that 1H NMR spectra of wine of single grape cultivars may in future be used in tandem with hierarchical cluster analysis to elucidate genetic lineages and metabolomic relations of grapevine cultivars. In the absence of genetic information, for example, where predecessor varieties are no longer extant, this may be a particularly useful approach. PMID

  1. Diet-Quality Scores and Prevalence of Nonalcoholic Fatty Liver Disease: A Population Study Using Proton-Magnetic Resonance Spectroscopy

    PubMed Central

    Chan, Ruth; Wong, Vincent Wai-Sun; Chu, Winnie Chiu-Wing; Wong, Grace Lai-Hung; Li, Liz Sin; Leung, Jason; Chim, Angel Mei-Ling; Yeung, David Ka-Wai; Sea, Mandy Man-Mei; Woo, Jean; Chan, Francis Ka-Leung; Chan, Henry Lik-Yuen

    2015-01-01

    Dietary pattern analysis is an alternative approach to examine the association between diet and nonalcoholic fatty liver disease (NAFLD). This study examined the association of two diet-quality scores, namely Diet Quality Index-International (DQI-I) and Mediterranean Diet Score (MDS) with NAFLD prevalence. Apparently healthy Chinese adults (332 male, 465 female) aged 18 years or above were recruited through a population screening between 2008 and 2010 in a cross-sectional population-based study in Hong Kong. DQI-I and MDS, as well as major food group and nutrient intakes were calculated based on dietary data from a food frequency questionnaire. NAFLD was defined as intrahepatic triglyceride content at ≥5% by proton-magnetic resonance spectroscopy. Multivariate logistic regression models were used to examine the association between each diet-quality score or dietary component and prevalent NAFLD with adjustment for potential lifestyle, metabolic and genetic factors. A total of 220 subjects (27.6%) were diagnosed with NAFLD. DQI-I but not MDS was associated with the prevalence of NAFLD. A 10-unit decrease in DQI-I was associated with 24% increase in the likelihood of having NAFLD in the age and sex adjusted model (95% CI: 1.06–1.45, p = 0.009), and the association remained significant when the model was further adjusted for other lifestyle factors, metabolic and genetic factors [OR: 1.26 (95% CI: 1.03–1.54), p = 0.027]. Multivariate regression analyses showed an inverse association of the intake of vegetables and legumes, fruits and dried fruits, as well as vitamin C with the NAFLD prevalence (p<0.05). In conclusion, a better diet quality as characterized by a higher DQI-I and a higher consumption of vegetables, legumes and fruits was associated with a reduced likelihood of having NAFLD in Hong Kong Chinese. PMID:26418083

  2. Altered white matter metabolism in delayed neurologic sequelae after carbon monoxide poisoning: A proton magnetic resonance spectroscopic study.

    PubMed

    Kuroda, Hiroshi; Fujihara, Kazuo; Mugikura, Shunji; Takahashi, Shoki; Kushimoto, Shigeki; Aoki, Masashi

    2016-01-15

    Proton magnetic resonance spectroscopy ((1)H-MRS) was recently used to examine altered metabolism in the white matter (WM) of patients experiencing carbon monoxide (CO) poisoning; however, only a small number of patients with delayed neurologic sequelae (DNS) were analyzed. We aimed to detect altered metabolism in the WM of patients with DNS using (1)H-MRS; to explore its clinical relevance in the management of patients experiencing CO poisoning. Patients experiencing acute CO poisoning underwent (1)H-MRS and cerebrospinal fluid (CSF) examination within 1week and at 1month after acute poisoning. Metabolites including choline-containing compounds (Cho), creatine (Cr), N-acetylaspartate (NAA), and lactate were measured from the periventricular WM. Myelin basic protein (MBP) concentrations were measured in CSF. Fifty-two patients experiencing acute CO poisoning (15 with DNS, 37 without DNS; median age, 49years; 65% males) underwent (1)H-MRS. Within 1week, NAA/Cr ratios, reflecting neuroaxonal viability, were lower in patients with DNS than in those without DNS (P<0.05). At 1month, when 9 of 15 patients (60%) developed DNS, Cho/Cr ratios were higher, and NAA/Cr and NAA/Cho ratios lower in patients with DNS (P=0.0001, <0.0001, and <0.0001, respectively), indicating increased membrane metabolism and decreased neuroaxonal viability. (1)H-MRS parameter abnormalities correlated with the elevation of MBP in CSF. The presence of a lactate peak was a predictor for a poor long-term outcome. (1)H-MRS within 1week may be useful for predicting DNS development; (1)H-MRS at 1month may be useful for discriminating patients with DNS and predicting long-term outcomes. PMID:26723994

  3. Metabolomics by proton nuclear magnetic resonance spectroscopy of the response to chloroethylnitrosourea reveals drug efficacy and tumor adaptive metabolic pathways.

    PubMed

    Morvan, Daniel; Demidem, Aicha

    2007-03-01

    Metabolomics of tumors may allow discovery of tumor biomarkers and metabolic therapeutic targets. Metabolomics by two-dimensional proton high-resolution magic angle spinning nuclear magnetic resonance spectroscopy was applied to investigate metabolite disorders following treatment by chloroethylnitrosourea of murine B16 melanoma (n = 33) and 3LL pulmonary carcinoma (n = 31) in vivo. Treated tumors of both types resumed growth after a delay. Nitrosoureas provoke DNA damage but the metabolic consequences of genotoxic stress are little known yet. Although some differences were observed in the metabolite profile of untreated tumor types, the prominent metabolic features of the response to nitrosourea were common to both. During the growth inhibition phase, there was an accumulation of glucose (more than x10; P < 0.05), glutamine (x3 to 4; P < 0.01), and aspartate (x2 to 5; P < 0.01). This response testified to nucleoside de novo synthesis down-regulation and drug efficacy. However, this phase also involved the increase in alanine (P < 0.001 in B16 melanoma), the decrease in succinate (P < 0.001), and the accumulation of serine-derived metabolites (glycine, phosphoethanolamine, and formate; P < 0.01). This response witnessed the activation of pathways implicated in energy production and resumption of nucleotide de novo synthesis, thus metabolic pathways of DNA repair and adaptation to treatment. During the growth recovery phase, it remained polyunsaturated fatty acid accumulation (x1.5 to 2; P < 0.05) and reduced utilization of glucose compared with glutamine (P < 0.05), a metabolic fingerprint of adaptation. Thus, this study provides the proof of principle that metabolomics of tumor response to an anticancer agent may help discover metabolic pathways of drug efficacy and adaptation to treatment. PMID:17332345

  4. Proton nuclear magnetic resonance spectroscopy (NMR) methods for determining the purity of reference drug standards and illicit forensic drug seizures.

    PubMed

    Hays, Patrick A

    2005-11-01

    A rapid, sensitive, accurate, precise, reproducible, and versatile method for determining the purity of reference drug standards and the routine analysis of illicit drugs and adulterants using proton (1H) Nuclear Magnetic Resonance (NMR) Spectroscopy is presented. The methodology uses a weighed sample dissolved in a deuterated solvent or solvent mixture containing a high purity internal standard. The NMR experiment employs 8 scans using a 45 second delay and 90 degrees pulse. In the determination of purity of reference standards, the number of quantitative determinations available is equal to the number of peak groups that are baseline resolved. The relative standard deviation (RSD) of these signals is usually < 1% for pure standards, and the results agree well with other purity determining methods. This method can also aid in the determination of correct molecular weight for standards containing an unknown number of waters of hydration or an unknown number of acids per drug in salts. Because the molar response for the hydrogen nucleus is 1 for all compounds, and since no separation media are used, only one linearity study is required to test a probe. In the presented study, the linearity of the NMR probe was determined using methamphetamine HCl dissolved in deuterium oxide (D2O) with maleic acid as the internal standard (5 mg) for a range of concentrations from 0.033 to 69.18 mg/ml with a resulting correlation coefficient of >0.9999 for all 6 methamphetamine peak groups. The spectra of complex illicit heroin, methamphetamine, MDMA, and cocaine samples are presented, as well as an extensive list of compounds, their solubilities and the solvent(s) and internal standard used. PMID:16382828

  5. Accuracy and stability of measuring GABA, glutamate, and glutamine by proton magnetic resonance spectroscopy: A phantom study at 4 Tesla

    NASA Astrophysics Data System (ADS)

    Henry, Michael E.; Lauriat, Tara L.; Shanahan, Meghan; Renshaw, Perry F.; Jensen, J. Eric

    2011-02-01

    Proton magnetic resonance spectroscopy has the potential to provide valuable information about alterations in gamma-aminobutyric acid (GABA), glutamate (Glu), and glutamine (Gln) in psychiatric and neurological disorders. In order to use this technique effectively, it is important to establish the accuracy and reproducibility of the methodology. In this study, phantoms with known metabolite concentrations were used to compare the accuracy of 2D J-resolved MRS, single-echo 30 ms PRESS, and GABA-edited MEGA-PRESS for measuring all three aforementioned neurochemicals simultaneously. The phantoms included metabolite concentrations above and below the physiological range and scans were performed at baseline, 1 week, and 1 month time-points. For GABA measurement, MEGA-PRESS proved optimal with a measured-to-target correlation of R2 = 0.999, with J-resolved providing R2 = 0.973 for GABA. All three methods proved effective in measuring Glu with R2 = 0.987 (30 ms PRESS), R2 = 0.996 (J-resolved) and R2 = 0.910 (MEGA-PRESS). J-resolved and MEGA-PRESS yielded good results for Gln measures with respective R2 = 0.855 (J-resolved) and R2 = 0.815 (MEGA-PRESS). The 30 ms PRESS method proved ineffective in measuring GABA and Gln. When measurement stability at in vivo concentration was assessed as a function of varying spectral quality, J-resolved proved the most stable and immune to signal-to-noise and linewidth fluctuation compared to MEGA-PRESS and 30 ms PRESS.

  6. Relationships between LDH-A, Lactate and Metastases in 4T1 Breast Tumors

    PubMed Central

    Rizwan, Asif; Serganova, Inna; Khanin, Raya; Karabeber, Hazem; Ni, Xiaohui; Thakur, Sunitha; Zakian, Kristen L.; Blasberg, Ronald; Koutcher, Jason A.

    2013-01-01

    Purpose To investigate the relationship between LDH-A expression, lactate concentration, cell metabolism and metastases in murine 4T1 breast tumors. Experimental Design Inhibition of LDH-A expression and protein levels were achieved in a metastatic breast cancer cell line (4T1) using shRNA technology. The relationship between tumor LDH-A protein levels and lactate concentration (measured by magnetic resonance spectroscopic imaging-MRSI) and metastases was assessed. Results LDH-A knockdown cells (KD9) showed a significant reduction in LDH-A protein and LDH activity, less acid production, decreased transwell migration and invasion, lower proliferation, reduced glucose utilization and glycolysis and increase in oxygen consumption, ROS and cellular ATP levels, compared to control (NC) cells cultured in 25 mM glucose. In vivo studies showed lower lactate levels in KD9, KD5, KD317 tumors than in NC or 4T1 wild-type tumors (p<0.01), and a linear relationship between tumor LDH-A protein expression and lactate concentration. Metastases were delayed and primary tumor growth rate decreased. Conclusions We show for the first time that LDH-A knockdown inhibited the formation of metastases, and was accompanied by in vivo changes in tumor cell metabolism. Lactate MRSI can be used as a surrogate to monitor targeted inhibition of LDH-A in a pre-clinical setting and provides a non-invasive imaging strategy to monitor LDH-A targeted therapy. This imaging strategy can be translated to the clinic to identify and monitor patients who are at high risk of developing metastatic disease. PMID:23833310

  7. Protonation of carbon single-walled nanotubes studied using 13C and 1H-13C cross polarization nuclear magnetic resonance and Raman spectroscopies.

    PubMed

    Engtrakul, Chaiwat; Davis, Mark F; Gennett, Thomas; Dillon, Anne C; Jones, Kim M; Heben, Michael J

    2005-12-14

    The reversible protonation of carbon single-walled nanotubes (SWNTs) in sulfuric acid and Nafion was investigated using solid-state nuclear magnetic resonance (NMR) and Raman spectroscopies. Magic-angle spinning (MAS) was used to obtain high-resolution 13C and 1H-13C cross polarization (CP) NMR spectra. The 13C NMR chemical shifts are reported for bulk SWNTs, H2SO4-treated SWNTs, SWNT-Nafion polymer composites, SWNT-AQ55 polymer composites, and SWNTs in contact with water. Protonation occurs without irreversible oxidation of the nanotube substrate via a charge-transfer process. This is the first report of a chemically induced change in a SWNT 13C resonance brought about by a reversible interaction with an acidic proton, providing additional evidence that carbon nanotubes behave as weak bases. Cross polarization was found to be a powerful technique for providing an additional contrast mechanism for studying nanotubes in contact with other chemical species. The CP studies confirmed polarization transfer from nearby protons to nanotube carbon atoms. The CP technique was also applied to investigate water adsorbed on carbon nanotube surfaces. Finally, the degree of bundling of the SWNTs in Nafion films was probed with the 1H-13C CP-MAS technique. PMID:16332107

  8. Mechanical-property changes of structural composite materials after low-temperature proton irradiation: Implications for use in SSC magnet systems

    SciTech Connect

    Morena, J.; Snead, C.L. Jr.; Czajkowski, C.; Skaritka, J.

    1993-07-01

    Longterm physical, mechanical, electrical, and other properties of advanced composites, plastics, and other polymer materials are greatly affected by high-energy proton, neutron, electron, and gamma radiation. The effects of high-energy particles on materials is a critical design parameter to consider when choosing polymeric structural, nonstructural, and elastomeric matrix resin systems. Polymer materials used for filled resins, laminates, seals, gaskets, coatings, insulation and other nonmetallic components must be chosen carefully, and reference data viewed with caution. Most reference data collected in the high-energy physics community to date reflects material property degradation using other than proton irradiations. In most instances, the data were collected for room-temperature irradiations, not 4.2 K or other cryogenic temperatures, and at doses less than 10{sup 8}--10{sup 9} Rad. Energetic proton (and the accompanying spallation-product particles) provide good simulation fidelity to the expected radiation fields predicted for the cold-mass regions of the SSC magnets, especially the corrector magnets. The authors present here results for some structural composite materials which were part of a larger irradiation-characterization of polymeric materials for SSC applications.

  9. Graphene oxide-Fe{sub 3}O{sub 4} nanoparticle composite with high transverse proton relaxivity value for magnetic resonance imaging

    SciTech Connect

    Venkatesha, N.; Srivastava, Chandan; Poojar, Pavan; Geethanath, Sairam; Qurishi, Yasrib

    2015-04-21

    The potential of graphene oxide–Fe{sub 3}O{sub 4} nanoparticle (GO-Fe{sub 3}O{sub 4}) composite as an image contrast enhancing material in magnetic resonance imaging has been investigated. Proton relaxivity values were obtained in three different homogeneous dispersions of GO-Fe{sub 3}O{sub 4} composites synthesized by precipitating Fe{sub 3}O{sub 4} nanoparticles in three different reaction mixtures containing 0.01 g, 0.1 g, and 0.2 g of graphene oxide. A noticeable difference in proton relaxivity values was observed between the three cases. A comprehensive structural and magnetic characterization revealed discrete differences in the extent of reduction of the graphene oxide and spacing between the graphene oxide sheets in the three composites. The GO-Fe{sub 3}O{sub 4} composite framework that contained graphene oxide with least extent of reduction of the carboxyl groups and largest spacing between the graphene oxide sheets provided the optimum structure for yielding a very high transverse proton relaxivity value. It was found that the GO-Fe{sub 3}O{sub 4} composites possessed good biocompatibility with normal cell lines, whereas they exhibited considerable toxicity towards breast cancer cells.

  10. Synthesis, Magnetic Properties, Map Images, and Water Proton Relaxivities of D-Glucuronic Acid Coated Ln2O3 Nanoparticles (Ln = Ho and Er).

    PubMed

    Kattel, Krishna; Kim, Cho Rong; Xu, Wenlong; Kim, Tae Jeong; Park, Jang Woo; Chang, Yongmin; Lee, Gang Ho

    2015-09-01

    T2 MRI contrast agents cannot be synthesized by using molecules but nanoparticles because appreciable magnetic moments at room temperature are needed. Recently, some of lanthanide (Ln) oxide nanoparticles have shown decent magnetic moments at room temperature and even at ultrasmall particle diameters. In this study, we explored D-glucuronic acid coated Ln2O3 nanoparticles (Ln = Ho and Er) with ultrasmall particle diameters. They showed decent magnetic moments at room temperature and as a result, appreciable transverse water proton relaxivities (r2s) at 1.5 tesla MR field. Clear dose-dependent contrast enhancements in R2 map images were observed in both samples. These results showed that D-glucuronic acid coated Ln2O3 nanoparticles (Ln = Ho and Er) would be potential T2 MRI contrast agents at high MR fields. PMID:26716328

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

    PubMed

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

    2007-02-01

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

  12. Studies related to primitive chemistry. A proton and nitrogen-14 nuclear magnetic resonance amino acid and nucleic acid constituents and a and their possible relation to prebiotic

    NASA Technical Reports Server (NTRS)

    Manatt, S. L.; Cohen, E. A.; Shiller, A. M.; Chan, S. I.

    1973-01-01

    Preliminary proton nuclear magnetic resonance (NMR) studies were made to determine the applicability of this technique for the study of interactions between monomeric and polymeric amino acids with monomeric nucleic acid bases and nucleotides. Proton NMR results for aqueous solutions (D2O) demonstrated interactions between the bases cytosine and adenine and acidic and aromatic amino acids. Solutions of 5'-AMP admixed with amino acids exhibited more complex behavior but stacking between aromatic rings and destacking at high amino acids concentration was evident. The multisite nature of 5'-AMP was pointed out. Chemical shift changes for adenine and 5'-AMP with three water soluble polypeptides demonstrated that significant interactions exist. It was found that the linewidth-pH profile of each amino acid is unique. It is concluded that NMR techniques can give significant and quantitative data on the association of amino acid and nucleic acid constituents.

  13. Non-additive response of blends of rice and potato starch during heating at intermediate water contents: A differential scanning calorimetry and proton nuclear magnetic resonance study.

    PubMed

    Bosmans, Geertrui M; Pareyt, Bram; Delcour, Jan A

    2016-02-01

    The impact of different hydration levels, on gelatinization of potato starch (PS), rice starch (RS) and a 1:1 blend thereof, was investigated by differential scanning calorimetry and related to nuclear magnetic resonance proton distributions of hydrated samples, before and after heating. At 20% or 30% hydration, the visual appearance of all samples was that of a wet powder, and limited, if any, gelatinization occurred upon heating. At 30% hydration, changes in proton distributions were observed and related to plasticization of amorphous regions in the granules. At 50% hydration, the PS-RS blend appeared more liquid-like than other hydrated samples and showed more pronounced gelatinization than expected based on additive behavior of pure starches. This was due to an additional mobile water fraction in the unheated PS-RS blend, originating from differences in water distribution due to altered stacking of granules and/or altered hydration of PS due to presence of cations in RS. PMID:26304387

  14. Distinct Translational Control in CD4+ T Cell Subsets

    PubMed Central

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

    2013-01-01

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

  15. 2D-1H proton magnetic resonance spectroscopic imaging study on brain metabolite alterations in patients with diabetic hypertension.

    PubMed

    Cao, Zhen; Ye, Bi-Di; Shen, Zhi-Wei; Cheng, Xiao-Fang; Yang, Zhong-Xian; Liu, Yan-Yan; Wu, Ren-Hua; Geng, Kuan; Xiao, Ye-Yu

    2015-06-01

    The aim of the present study was to investigate the possible metabolic alterations in the frontal cortex and parietal white matter in patients with diabetic hypertension (DHT) using proton magnetic resonance (MR) spectroscopic imaging. A total of 33 DHT patients and 30 healthy control subjects aged between 45 and 75 were included in the present study. All subjects were right‑handed. The spectroscopy data were collected using a GE Healthcare 1.5T MR scanner. The multi‑voxels were located in the semioval center (repetition time/echo time=1,500 ms/35 ms). The area of interest was 8x10x2 cm in volume and contained the two sides of the frontal cortex and the parietal white matter. The spectra data were processed using SAGE software. The ratios of brain metabolite concentrations, particularly for N‑acetylaspartate (NAA)/creatine (Cr) and Choline (Cho)/Cr were calculated and analyzed. Statistical analyses were performed using SPSS 17.0. The NAA/Cr ratio of the bilateral prefrontal cortex of the DHT group was significantly lower than that of the control group (left t=‑7.854, P=0.000 and right t=‑5.787, P=0.000), The Cho/Cr ratio was also much lower than the control group (left t=2.422, P=0.024 and right t=2.920, P=0.007). NAA/Cr ratio of the left parietal white matter of the DHT group was extremely lower than that of the control group (t=‑4.199, P=0.000). Therefore, DHT may result in metabolic disorders in the frontal cortex and parietal white matter but the metabolic alterations are different in various regions of the brain. The alteration in cerebral metabolism is associated with diabetes and hypertension. The ratios of NAA/Cr and Cho/Cr are potential metabolic markers for the brain damage induced by DHT. PMID:25652580

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

    PubMed Central

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

    2008-01-01

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

  17. Carbon-13 and proton nuclear magnetic resonance analysis of shale-derived refinery products and jet fuels and of experimental referee broadened-specification jet fuels

    NASA Technical Reports Server (NTRS)

    Dalling, D. K.; Bailey, B. K.; Pugmire, R. J.

    1984-01-01

    A proton and carbon-13 nuclear magnetic resonance (NMR) study was conducted of Ashland shale oil refinery products, experimental referee broadened-specification jet fuels, and of related isoprenoid model compounds. Supercritical fluid chromatography techniques using carbon dioxide were developed on a preparative scale, so that samples could be quantitatively separated into saturates and aromatic fractions for study by NMR. An optimized average parameter treatment was developed, and the NMR results were analyzed in terms of the resulting average parameters; formulation of model mixtures was demonstrated. Application of novel spectroscopic techniques to fuel samples was investigated.

  18. 26 CFR 1.475(a)-4T - Valuation safe harbor (temporary).

    Code of Federal Regulations, 2012 CFR

    2012-04-01

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

  19. 26 CFR 1.905-4T - Notification of foreign tax redetermination (temporary).

    Code of Federal Regulations, 2014 CFR

    2014-04-01

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

  20. 26 CFR 1.905-4T - Notification of foreign tax redetermination (temporary).

    Code of Federal Regulations, 2013 CFR

    2013-04-01

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

  1. 26 CFR 1.905-4T - Notification of foreign tax redetermination (temporary).

    Code of Federal Regulations, 2012 CFR

    2012-04-01

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

  2. 26 CFR 1.905-4T - Notification of foreign tax redetermination (temporary).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

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

  3. 26 CFR 1.6038D-4T - Information required to be reported (temporary).

    Code of Federal Regulations, 2012 CFR

    2012-04-01

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

  4. [miR-126 knockdown enhances the activity of murine CD4(+);T cells in vivo and promotes their differentiation into Th1 cells].

    PubMed

    Cui, Panpan; Hu, Yan; Tao, Yijing; Chen, Chao; Zhao, Juanjuan; Guo, Mengmeng; Zhou, Ya; Xu, Lin

    2016-03-01

    Objective To investigate the change of CD4(+);T cell activity in microRNA-126 (miR-126) knockdown (KD) mice and explore its significance. Methods The expression level of mature miR-126 in CD4(+);CD62L(+);T cells purified by magnetic-activated cell sorting (MACS) was analyzed by real-time PCR using specific probe. Furthermore, the expression levels of CD69, CD62L and CD44 molecules, as well as intracellular proliferating nuclear antigen Ki-67, in CD4(+);T cells in miR-126 KD mice were detected by fluorescence-activated cell sorting (FACS). Moreover, the apoptosis of CD4(+);T cells was analyzed by annexin V/PI staining assay combined with flow cytometry. Finally, the relative expressions of function-related cytokines including interleukine 4 (IL-4), IL-10, IL-12, transforming growth factor (TGF-β), interferon (IFN-γ) and tumor necrosis factor (TNF-α) in CD4(+);T cells were determined by real-time PCR. Results Compared with wild-type (WT) mice, the expression level of mature miR-126 in CD4(+);T cells in miR-126 KD mice was dramatically reduced. Furthermore, the proportion of CD62L(+); in CD4(+);T cells also decreased significantly, while the proportions of CD69(+);, CD44(+); and Ki-67(+); cells were remarkably elevated. Meanwhile, the apoptosis proportion of CD4(+);T cells in vivo dropped dramatically in miR-126 KD mice. Finally, the mRNA expressions of IL-4 and IL-10 in CD4(+);T cells were significantly downregulated, but IL-12, TGF-β, TNF-α and IFN-γ mRNAs were obviously up-regulated. Conclusion miR-126 knockdown could significantly enhance the functional activity of CD4(+); T cells in vivo and promote cell differentiation into Th1 cells. PMID:26927555

  5. Severe TSH Elevation and Pituitary Enlargement After Changing Thyroid Replacement to Compounded T4/T3 Therapy

    PubMed Central

    Pappy, Adlai L.; Oyesiku, Nelson; Ioachimescu, Adriana

    2016-01-01

    We present the first case of iatrogenic hypothyroidism as a result of compounded thyroid hormone (T4/T3) therapy. The thyroid replacement was changed from 175 µg levothyroxine (LT4) to 57/13.5 µg compounded T4/T3 daily in order to improve the T3 level, despite normal thyroid-stimulating hormone (TSH). This resulted in clinical manifestations of hypothyroidism and high TSH level (150 µIU/mL). Six months later, the patient was referred to our clinic for abnormal pituitary magnetic resonance imaging. On reinitiating a physiologic dose of LT4, clinical and biochemical abnormalities resolved and the pituitary gland size decreased. Our case emphasizes the importance of using TSH level to gauge dose adjustments in primary hypothyroidism. Also, it underscores the current American Thyroid Association recommendation against routine use of compounded thyroid hormone therapy. PMID:27540557

  6. Severe TSH Elevation and Pituitary Enlargement After Changing Thyroid Replacement to Compounded T4/T3 Therapy.

    PubMed

    Pappy, Adlai L; Oyesiku, Nelson; Ioachimescu, Adriana

    2016-01-01

    We present the first case of iatrogenic hypothyroidism as a result of compounded thyroid hormone (T4/T3) therapy. The thyroid replacement was changed from 175 µg levothyroxine (LT4) to 57/13.5 µg compounded T4/T3 daily in order to improve the T3 level, despite normal thyroid-stimulating hormone (TSH). This resulted in clinical manifestations of hypothyroidism and high TSH level (150 µIU/mL). Six months later, the patient was referred to our clinic for abnormal pituitary magnetic resonance imaging. On reinitiating a physiologic dose of LT4, clinical and biochemical abnormalities resolved and the pituitary gland size decreased. Our case emphasizes the importance of using TSH level to gauge dose adjustments in primary hypothyroidism. Also, it underscores the current American Thyroid Association recommendation against routine use of compounded thyroid hormone therapy. PMID:27540557

  7. Brain Biochemical Effects of Methylphenidate Treatment Using Proton Magnetic Spectroscopy in Youth with Attention-Deficit Hyperactivity Disorder: A Controlled Pilot Study

    PubMed Central

    Hammerness, Paul; Biederman, Joseph; Petty, Carter; Henin, Aude; Moore, Constance M.

    2014-01-01

    SUMMARY Introduction This study conducted spectroscopic analyses using proton (1H) Magnetic Resonance Spectroscopy (at 4 Tesla) in a sample of adolescents with Attention Deficit Hyperactivity Disorder (ADHD), before and after treatment with extended release methylphenidate (OROS MPH), as compared to a sample of healthy comparators. Aims The main aim of this study is to use 1H MRS to measure differences in brain biochemistry between adolescents with and without ADHD, and to assess changes in cerebral biochemistry, before and after stimulant treatment in ADHD youth. Results Subjects with ADHD were medically healthy adolescents treated in an open label fashion with OROS MPH (mean dose: 54 mg/day; 0.90 mg/kg/day). Subjects with ADHD were scanned before and after OROS MPH treatment. Healthy comparators were scanned once. Magnetic resonance (MR) spectroscopy studies were performed on a 4.0 T Varian Unity/Inova MR scanner; proton spectra were acquired from the Anterior Cingulate Cortex (ACC). Data were analyzed using MANOVA and repeated measurement ANOVA. Higher metabolite ratios (Glutamate/myo-inositol, Glutamine/myo-inositol, Glutamate + Glutamine/myo-inositol) were observed in the ACC in untreated ADHD subjects as compared to controls, and to treated ADHD youth; these group differences did not reach the a priori threshold for statistical significance. Conclusions These preliminary findings suggest the presence of glutamatergic abnormalities in adolescents with ADHD, which may normalize with MPH treatment. Larger sample, controlled studies are needed to confirm these preliminary findings. PMID:21143432

  8. Alpha-Particle/Proton Differential Flow in the Solar Wind: Implications for Plasma Heating, Azimuthal Flow, and the Parker Spiral Magnetic Field

    NASA Astrophysics Data System (ADS)

    Verscharen, D.; Bourouaine, S.; Chandran, B. D. G.

    2014-12-01

    Protons and alpha particles in the fast solar wind are only weakly collisional and exhibit a number of non-equilibrium features, including temperature anisotropies and relative drifts along the direction of the background magnetic field. Two mechanisms have been proposed for limiting differential flow between alpha particles and protons: plasma instabilities and the rotational force. Both mechanisms decelerate the alpha particles - for example, the Alfvén/ion-cyclotron and fast-magnetosonic/whistler instabilities limit the drift velocity to a value comparable to the Alfvén speed, which decreases with increasing heliocentric distance r. However, while plasma instabilities transform bulk-flow kinetic energy into heat and plasma waves, the rotational force does not. We present an analytic expression for the rate Qflow at which energy is released when alpha particles are decelerated by instabilities. We find that Qflow becomes zero at a critical radius r=rcrit, where rcrit is between 1.5 AU and 2 AU in the fast solar wind in the ecliptic plane, and rcrit increases with increasing heliographic latitude. We show that instabilities control the deceleration of alpha particles at rrcrit. We compare the value of Qflow at rprotons and alpha particles deduced from in-situ measurements of fast-wind streams from the Helios and Ulysses spacecraft. We find that Qflow exceeds the empirical heating rate for alpha particles at r<1 AU. We conclude that the continuous energy input from alpha-particle deceleration at rmagnetic field.

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

    PubMed Central

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

    2013-01-01

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

  10. 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.

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

    PubMed Central

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

    2015-01-01

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

  12. Mono- and Combined Therapy of Metastasizing Breast Carcinoma 4T1 with Zoledronic Acid and Doxorubicin.

    PubMed

    Baklaushev, V P; Grinenko, N F; Yusubalieva, G M; Gubskii, I L; Burenkov, M S; Rabinovich, E Z; Ivanova, N V; Chekhonin, V P

    2016-08-01

    The efficiency of monotherapy with zoledronic acid (Resorba), doxorubicin, and their combination was studied on the model of metastasizing breast carcinoma in BALB/c mice. Doxorubicin monotherapy was accompanied by a significant increase in median survival up to 57 days (vs. 34 and 35 days in control groups); 27% animals survived for 90 days (duration of the study). Bioluminescence area of the primary tumor significantly decreased on days 21 and 28; the total number of visceral metastases also decreased according to magnetic-resonance imaging data. Resorba monotherapy produced no general toxic effect, the median survival increased to 64 days, and 90-day survival was 33%. Imaging techniques (magnetic-resonance imaging, microtomography, bioluminescent analysis) showed that Resorba delayed the development of the primary tumor (regression of luminescence area on days 21 and 28, regression of standardized bioluminescence intensity on day 28) and significantly reduced the number of visceral metastases in comparison with the control. Combination therapy was less effective than monotherapy with the same medications. Median survival was 55 days, 90-day survival was 13%, but magnetic-resonance imaging and bioluminescence analysis after combination therapy also showed delayed growth of the primary tumor and reduced number of visceral metastases. Microtomography revealed bone metastases in ~30% animals of the control group; in experimental groups, no bone metastases were found. The experiment with periosteal (distal epiphysis of the femur) injection of 4T1-Luc2 tumor cells demonstrated pronounced selective effectiveness of Resorba in relation to bone metastases. Monotherapy with Resorba can prevent the development of not only bone, but also visceral metastases of breast cancer. PMID:27590765

  13. Proton nuclear magnetic resonance characterization of the aromatic residues in the variant-3 neurotoxin from Centruroides sculpturatus Ewing

    SciTech Connect

    Krishna, N.R.; Nettesheim, D.G.; Klevit, R.E.; Drobny, G.; Watt, D.D.; Bugg, C.E. )

    1989-02-21

    The amino acid sequence for the variant-3 (CsE-v3) toxin from the venom of the scorpion Centruroides sculpturatus Ewing contains eight aromatic residues. By use of 2D NMR spectroscopic methods, the resonances from the individual protons (NH, C{sup alpha}H, C{sup beta}H{prime}, H{double prime}, and the ring) for each of the individual aromatic residues have been completely assigned. The spatial arrangement of the aromatic ring systems with respect to each other has been qualitatively analyzed by 2D-NOESY techniques. The results show that Trp-47, Tyr-4, and Tyr-42 are in close spatial proximity to each other. The NOESY contacts and the ring current induced shifts in the resonances of the individual protons of Tyr-4 and Trp-47 suggest that the aromatic ring planes of these residues are in an orthogonal arrangement. A comparison with the published crystal structure suggests that there is a minor rearrangement of the aromatic rings in the solution phase. No 2D-NOESY contacts involving Phe-44 and Tyr-14 to any other aromatic ring protons have been observed. The pH dependence of the aromatic ring proton chemical shifts has also been studied. These results suggest that the Tyr-58 phenolic group is experiencing a hydrogen-bonding interaction with a positively charged group, while Tyr-4, -14, -38, and -40 are experiencing through-space interactions with proximal negatively charged groups. These studies define the microenvironment of the aromatic residues in the variant-3 neurotoxin in aqueous solution.

  14. Proton nuclear magnetic resonance spectroscopy of horseradish peroxidase isoenzymes: correlation of distinctive spectra with isoenzyme specific activities.

    PubMed

    Gonzalez-Vergara, E; Meyer, M; Goff, H M

    1985-11-01

    High-resolution proton NMR spectra are reported for the paramagnetic ferric native and cyano complexes of the five major horseradish root peroxidase (HRP) isoenzymes (A1, A2, A3, B, and C). Axial imidazole resonances are observed in the native and cyano-complex spectra of all the isoenzymes, thus indicating the presence of a common axial histidine ligand. Proton NMR spectra outside the usual diamagnetic region are identical for sets of A1 and A2 isoenzymes and for the B and C isoenzyme set. Variation in heme residue chemical shift positions may be controlled in part by porphyrin vinyl side chain-protein interactions. Diverse upfield spectra among the isoenzymes reflect amino acid substitutions and/or conformational differences near the prosthetic group, as signals in this region must result from amino acid residues in proximity to the heme center. Acid-base dependence studies reveal an "alkaline" transition that converts the native high-spin iron (III) porphyrin to the low-spin state. The transition occurs at pH 9.3, 9.4, 9.8, and 10.9 for respective HRP A1, A2, A3, and C isoenzymes, respectively. Significantly, this ordering also reflects specific activities for the isoenzymes in the order A1 = A2 greater than A3 greater than B = C. Identical proton NMR spectra for A1/A2 and B/C isoenzyme sets parallel equivalent specific activities for members of a particular set. Proton NMR spectra thus appear to be highly sensitive to protein modifications that affect catalytic activity. PMID:4084538

  15. The Schwarzschild Proton

    SciTech Connect

    Haramein, Nassim

    2010-11-24

    We review our model of a proton that obeys the Schwarzschild condition. We find that only a very small percentage ({approx}10{sup -39}%) of the vacuum fluctuations available within a proton volume need be cohered and converted to mass-energy in order for the proton to meet the Schwarzschild condition. This proportion is equivalent to that between gravitation and the strong force where gravitation is thought to be {approx}10{sup -38} to 10{sup -40} weaker than the strong force. Gravitational attraction between two contiguous Schwarzschild protons can accommodate both nucleon and quark confinement. We calculate that two contiguous Schwarzschild protons would rotate at c and have a period of 10{sup -23} s and a frequency of 10{sup 22} Hz which is characteristic of the strong force interaction time and a close approximation of the gamma emission typically associated with nuclear decay. We include a scaling law and find that the Schwarzschild proton data point lies near the least squares trend line for organized matter. Using a semi-classical model, we find that a proton charge orbiting at a proton radius at c generates a good approximation to the measured anomalous magnetic moment.

  16. 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.

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

    PubMed

    Prasetyo, Afiono Agung; Zaini, Khilyat Ulin Nur

    2015-07-01

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

  18. Multiharmonic rf feedforward system for compensation of beam loading and periodic transient effects in magnetic-alloy cavities of a proton synchrotron

    NASA Astrophysics Data System (ADS)

    Tamura, Fumihiko; Ohmori, Chihiro; Yamamoto, Masanobu; Yoshii, Masahito; Schnase, Alexander; Nomura, Masahiro; Toda, Makoto; Shimada, Taihei; Hasegawa, Katsushi; Hara, Keigo

    2013-05-01

    Beam loading compensation is a key for acceleration of a high intensity proton beam in the main ring (MR) of the Japan Proton Accelerator Research Complex (J-PARC). Magnetic alloy loaded rf cavities with a Q value of 22 are used to achieve high accelerating voltages without a tuning bias loop. The cavity is driven by a single harmonic (h=9) rf signal while the cavity frequency response also covers the neighbor harmonics (h=8,10). Therefore the wake voltage induced by the high intensity beam consists of the three harmonics, h=8,9,10. The beam loading of neighbor harmonics is the source of periodic transient effects and a possible source of coupled bunch instabilities. In the article, we analyze the wake voltage induced by the high intensity beam. We employ the rf feedforward method to compensate the beam loading of these three harmonics (h=8,9,10). The full-digital multiharmonic feedforward system was developed for the MR. We describe the system architecture and the commissioning methodology of the feedforward patterns. The commissioning of the feedforward system has been performed by using high intensity beams with 1.0×1014 proteins per pulse. The impedance seen by the beam is successfully reduced and the longitudinal oscillations due to the beam loading are reduced. By the beam loading compensation, stable high power beam operation is achieved. We also report the reduction of the momentum loss during the debunching process for the slow extraction by the feedforward.

  19. Characterization by gas-liquid chromatography-mass spectrometry and proton-magnetic-resonance spectroscopy of pertrimethylsilyl methyl glycosides obtained in the methanolysis of glycoproteins and glycopeptides.

    PubMed

    Kamerling, J P; Gerwig, G J; Vliegenthart, J F; Clamp, J R

    1975-12-01

    The quantitative analysis by gas chromatography of monosaccharides present in glycoproteins and glycopeptides using methanolysis, followed by re-N-acetylation and trimethylsilylation, gives rise to several peaks for each monosaccharide. The identity of these peaks for xylose, fucose, mannose, galactose, glucose, N-acetylglucosamine, N-acetylgalactosamine and N-acetylneuraminic acid was established for alpha- and beta-methyl pyranosides and furanosides by combined g.l.c.-mass spectrometry and proton-magnetic-resonance spectroscopy. These data provide for the unambiguous interpretation of the gas chromatograms obtained in the application of this g.l.c. method, and supply basic information for the further application of mass spectrometry in this field. PMID:1218089

  20. In-Vivo Proton Magnetic Resonance Spectroscopy of 2-Hydroxyglutarate in Isocitrate Dehydrogenase-Mutated Gliomas: A Technical Review for Neuroradiologists

    PubMed Central

    Kim, Sungjin; Lee, Hyeong Hun; Heo, Hwon

    2016-01-01

    The diagnostic and prognostic potential of an onco-metabolite, 2-hydroxyglutarate (2HG) as a proton magnetic resonance spectroscopy (1H-MRS) detectable biomarker of the isocitrate dehydrogenase (IDH)-mutated (IDH-MT) gliomas has drawn attention of neuroradiologists recently. However, due to severe spectral overlap with background signals, quantification of 2HG can be very challenging. In this technical review for neuroradiologists, first, the biochemistry of 2HG and its significance in the diagnosis of IDH-MT gliomas are summarized. Secondly, various 1H-MRS methods used in the previous studies are outlined. Finally, wereview previous in vivo studies, and discuss the current status of 1H-MRS in the diagnosis of IDH-MT gliomas. PMID:27587950

  1. In-Vivo Proton Magnetic Resonance Spectroscopy of 2-Hydroxyglutarate in Isocitrate Dehydrogenase-Mutated Gliomas: A Technical Review for Neuroradiologists.

    PubMed

    Kim, Hyeonjin; Kim, Sungjin; Lee, Hyeong Hun; Heo, Hwon

    2016-01-01

    The diagnostic and prognostic potential of an onco-metabolite, 2-hydroxyglutarate (2HG) as a proton magnetic resonance spectroscopy (1H-MRS) detectable biomarker of the isocitrate dehydrogenase (IDH)-mutated (IDH-MT) gliomas has drawn attention of neuroradiologists recently. However, due to severe spectral overlap with background signals, quantification of 2HG can be very challenging. In this technical review for neuroradiologists, first, the biochemistry of 2HG and its significance in the diagnosis of IDH-MT gliomas are summarized. Secondly, various 1H-MRS methods used in the previous studies are outlined. Finally, wereview previous in vivo studies, and discuss the current status of 1H-MRS in the diagnosis of IDH-MT gliomas. PMID:27587950

  2. The ARTμS: a novel microfluidic CD4+ T-cell enumeration system for monitoring antiretroviral therapy in HIV patients.

    PubMed

    Liu, Qian; Chernish, Alexis; DuVall, Jacquelyn A; Ouyang, Yiwen; Li, Jingyi; Qian, Qiang; Bazydlo, Lindsay A L; Haverstick, Doris M; Landers, James P

    2016-02-01

    We report on a novel and cost-effective microfluidic platform that integrates immunomagnetic separation and cell enumeration via DNA-induced bead aggregation. Using a two-stage immunocapture microdevice, 10 μL of whole blood was processed to isolate CD4+ T-cells. The first stage involved the immuno-subtraction of monocytes by anti-CD14 magnetic beads, followed by CD4+ T-cell capture with anti-CD4 magnetic beads. The super hydrophilic surface generated during polydimethylsiloxane (PDMS) plasma treatment allowed for accurate metering of the CD4+ T-cell lysate, which then interacted with silica-coated magnetic beads under chaotropic conditions to form aggregates. Images of the resulting aggregates were captured and processed to reveal the mass of DNA, which was used to back-calculate the CD4+ T-cell number. Studies with clinical samples revealed that the analysis of blood within 24 hours of phlebotomy yielded the best results. Under these conditions, an accurate cell count was achieved (R(2) = 0.98) when compared to cell enumeration via flow cytometry, and over a functional dynamic range from 106-2337 cells per μL. PMID:26687070

  3. 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

  4. 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

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

    PubMed Central

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

    2011-01-01

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

  6. 26 CFR 1.6041-4T - Foreign-related items and other exceptions (temporary).

    Code of Federal Regulations, 2014 CFR

    2014-04-01

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

  7. 26 CFR 1.7874-4T - Disregard of certain stock related to the acquisition (temporary).

    Code of Federal Regulations, 2014 CFR

    2014-04-01

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

  8. 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...

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  10. 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...

  11. 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)

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

    PubMed

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

    2016-02-12

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

    Doitsh, Gilad; Greene, Warner C

    2016-03-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-10-20

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

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

    PubMed Central

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

    2010-01-01

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

  18. Enantioselective Protonation

    PubMed Central

    Mohr, Justin T.; Hong, Allen Y.; Stoltz, Brian M.

    2010-01-01

    Enantioselective protonation is a common process in biosynthetic sequences. The decarboxylase and esterase enzymes that effect this valuable transformation are able to control both the steric environment around the proton acceptor (typically an enolate) and the proton donor (typically a thiol). Recently, several chemical methods to achieve enantioselective protonation have been developed by exploiting various means of enantiocontrol in different mechanisms. These laboratory transformations have proven useful for the preparation of a number of valuable organic compounds. PMID:20428461

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

    PubMed

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

    2015-11-15

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

  20. Anomalous tensor magnetic moments and form factors of the proton in the self-consistent chiral quark-soliton model

    NASA Astrophysics Data System (ADS)

    Ledwig, Tim; Silva, Antonio; Kim, Hyun-Chul

    2010-09-01

    We investigate the form factors of the chiral-odd nucleon matrix element of the tensor current. In particular, we aim at the anomalous tensor magnetic form factors of the nucleon within the framework of the SU(3) and SU(2) chiral quark-soliton model. We consider 1/Nc rotational corrections and linear effects of SU(3) symmetry breaking with the symmetry-conserving quantization employed. We first obtain the results of the anomalous tensor magnetic moments for the up and down quarks: κTu=3.56 and κTd=1.83, respectively. The strange anomalous tensor magnetic moment is yielded to be κTs=0.2˜-0.2, that is compatible with zero. We also calculate the corresponding form factors κTq(Q2) up to a momentum transfer Q2≤1GeV2 at a renormalization scale of 0.36GeV2.

  1. Cerebellar Volume and Proton Magnetic Resonance Spectroscopy at Term, and Neurodevelopment at 2 Years of Age in Preterm Infants

    ERIC Educational Resources Information Center

    van Kooij, Britt J. M.; Benders, Manon J. N. L.; Anbeek, Petronella; van Haastert, Ingrid C.; de Vries, Linda S.; Groenendaal, Floris

    2012-01-01

    Aim: To assess the relation between cerebellar volume and spectroscopy at term equivalent age, and neurodevelopment at 24 months corrected age in preterm infants. Methods: Magnetic resonance imaging of the brain was performed around term equivalent age in 112 preterm infants (mean gestational age 28wks 3d [SD 1wk 5d]; birthweight 1129g [SD 324g]).…

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

    PubMed Central

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

    2013-01-01

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

  3. 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

  4. Flash Proton Radiography

    NASA Astrophysics Data System (ADS)

    Merrill, Frank E.

    Protons were first investigated as radiographic probes as high energy proton accelerators became accessible to the scientific community in the 1960s. Like the initial use of X-rays in the 1800s, protons were shown to be a useful tool for studying the contents of opaque materials, but the electromagnetic charge of the protons opened up a new set of interaction processes which complicated their use. These complications in combination with the high expense of generating protons with energies high enough to penetrate typical objects resulted in proton radiography becoming a novelty, demonstrated at accelerator facilities, but not utilized to their full potential until the 1990s at Los Alamos. During this time Los Alamos National Laboratory was investigating a wide range of options, including X-rays and neutrons, as the next generation of probes to be used for thick object flash radiography. During this process it was realized that the charge nature of the protons, which was the source of the initial difficulty with this idea, could be used to recover this technique. By introducing a magnetic imaging lens downstream of the object to be radiographed, the blur resulting from scattering within the object could be focused out of the measurements, dramatically improving the resolution of proton radiography of thick systems. Imaging systems were quickly developed and combined with the temporal structure of a proton beam generated by a linear accelerator, providing a unique flash radiography capability for measurements at Los Alamos National Laboratory. This technique has now been employed at LANSCE for two decades and has been adopted around the world as the premier flash radiography technique for the study of dynamic material properties.

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

    PubMed

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

    2016-01-15

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

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

    PubMed

    Jiménez, M; García-Carmona, F

    1996-09-13

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

  7. Amide proton signals as pH indicator for in vivo MRS and MRI of the brain-Responses to hypercapnia and hypothermia.

    PubMed

    Watanabe, Takashi; Frahm, Jens; Michaelis, Thomas

    2016-06-01

    Using proton MRS and MRI of mouse brain at 9.4T, this work provides the first in vivo evidence of pH-dependent concurrent changes of three amide signals and related metabolic responses to hypercapnia and hypothermia. During hypercapnia, amide proton MRS signals of glutamine at 6.8-6.9ppm and 7.6ppm as well as of unspecific compounds at 8.1-8.3ppm increase by at least 50% both at 37°C and 22°C. These changes reflect a reduced proton exchange with water. They are strongly correlated with intracellular pH which ranges from 6.75±0.10 to 7.13±0.06 as determined from a shift in creatine phosphokinase equilibrium. In MRI, saturation transfer from aliphatic as well as aromatic and/or amide protons alters slightly during hypercapnia and significantly during hypothermia. The asymmetry in magnetization transfer ratios decreased slightly during hypercapnia and hypothermia. Regardless of pH or temperature, saturation transfer from aliphatic protons between -2 and -4ppm frequency offset to water protons is significantly greater than that from aromatic/amide protons at corresponding offsets between +2 and +4ppm. Irradiation of aliphatic compounds at -3.5ppm frequency offset from water predominantly saturates lipids and water associated with myelin. Taken together, the results indicate that, for the B1 power used in this study, dipolar coupling between aliphatic and water protons rather than proton exchange is the dominant factor in Z-spectra and magnetization transfer ratio asymmetry of the brain in vivo. PMID:26975553

  8. Rosenbluth Award: First observations of Rayleigh-Taylor-induced magnetic fields in laser-produced plasmas using x rays and protons

    NASA Astrophysics Data System (ADS)

    Manuel, Mario

    2014-10-01

    Recent experiments [Manuel, PRL 108 (2012)] demonstrated the existence of self-generated B-fields from the Rayleigh-Taylor (RT) instability in laser-produced plasmas, as originally predicted by Mima et al. [Mima PRL 41 (1978)]. Misaligned density and temperature gradients caused by RT growth in ablatively driven targets generate B-fields in the plasma through the Biermann battery source. X-ray and proton radiography diagnosed areal-density and B-field perturbations in laser-irradiated targets with seeded sinusoidal surface perturbations. Inferred B-field strengths indicated ratios of thermal to magnetic pressures (β) near the ablation surface of 104-105, suggesting no magnetic effects on ablative RT during the linear growth phase. However, the magnitude of this self-generated field increases with the perturbation height [Srinivasan, PRL 108 (2012)] and can affect morphology in the nonlinear regime. The detailed structure of highly nonlinear RT spikes is important to understand the inner wall expansion of hohlraums in indirect-drive inertial fusion and in multiple astrophysical systems, including the explosion phase of core-collapse supernovae and formation of planetary nebulae. Numerical calculations investigating the magnetic effects on nonlinear RT-spike evolution under conditions similar to previous measurements will be covered and implications discussed. Support for this work was provided by NASA through Einstein Postdoctoral Fellowship grant number PF3-140111 awarded by the Chandra X-ray Center, which is operated by the Astrophysical Observatory for NASA under Contract NAS8-03060. This work is funded by the NNSA-DS and SC-OFES Joint Program in High-Energy-Density Laboratory Plasma under Grant Number DE-NA0001840. Previous work described here was supported in part by NLUF (DE-NA0000877), FSC/UR (415023-G), DoE (DE-FG52-09NA29553), LLE (414090-G), and LLNL (B580243).

  9. A carbon-13 nuclear magnetic resonance spectroscopic study of inter-proton pair order parameters: a new approach to study order and dynamics in phospholipid membrane systems.

    PubMed

    Urbina, J A; Moreno, B; Arnold, W; Taron, C H; Orlean, P; Oldfield, E

    1998-09-01

    We report a simple new nuclear magnetic resonance (NMR) spectroscopic method to investigate order and dynamics in phospholipids in which inter-proton pair order parameters are derived by using high resolution 13C cross-polarization/magic angle spinning (CP/MAS) NMR combined with 1H dipolar echo preparation. The resulting two-dimensional NMR spectra permit determination of the motionally averaged interpair second moment for protons attached to each resolved 13C site, from which the corresponding interpair order parameters can be deducted. A spin-lock mixing pulse before cross-polarization enables the detection of spin diffusion amongst the different regions of the lipid molecules. The method was applied to a variety of model membrane systems, including 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC)/sterol and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC)/sterol model membranes. The results agree well with previous studies using specifically deuterium labeled or predeuterated phospholipid molecules. It was also found that efficient spin diffusion takes place within the phospholipid acyl chains, and between the glycerol backbone and choline headgroup of these molecules. The experiment was also applied to biosynthetically 13C-labeled ergosterol incorporated into phosphatidylcholine bilayers. These results indicate highly restricted motions of both the sterol nucleus and the aliphatic side chain, and efficient spin exchange between these structurally dissimilar regions of the sterol molecule. Finally, studies were carried out in the lamellar liquid crystalline (L alpha) and inverted hexagonal (HII) phases of 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE). These results indicated that phosphatidylethanolamine lamellar phases are more ordered than the equivalent phases of phosphatidylcholines. In the HII (inverted hexagonal) phase, despite the increased translational freedom, there is highly constrained packing of the lipid molecules, particularly in

  10. A Model Study of the Impact of Magnetic Field Reversal on Atmospheric Composition during Solar Proton Events

    NASA Technical Reports Server (NTRS)

    Sinnhuber, Miaiam; Jackman, Charles H.; Burrows, John P.; Chipperfield, Martyn P.; Kallenrode, May-Britt; Kunzi, Klaus F.; Quack, Manual

    2003-01-01

    During a polarity transition of the Earth's magnetic field, the structure and strength of the field change significantly from their present values. This will alter the global pattern of charged particle precipitation into the atmosphere. Thus, particle precipitation is possible into regions that are at the moment effectively shielded by the Earth's magnetic field. A two-dimensional global fbHy coupled chemistry, radiation, and transport model of the atmosphere has been used to investigate how the increased particle precipitation affects the chemical composition of the middle and lower atmosphere. Ozone losses resulting from large energetic particle events are found to increase significantly, with resultant losses similar to those observed m the Antarctic ozone hole of the 1990s. This results in significant increases in surface UV-B radiation as well as changes in stratospheric temperature and circulation over a period of several months after large particle events.

  11. Translational Approaches for Studying Neurodevelopmental Disorders Utilizing in Vivo Proton (+H) Magnetic Resonance Spectroscopic Imaging in Rats

    NASA Technical Reports Server (NTRS)

    Ronca, April E.

    2014-01-01

    Intrauterine complications have been implicated in the etiology of neuripsychiatric disorders including schizophrenia, autism and ADHD. This presentation will describe new translational studies derived from in vivo magnetic resonance imaging of developing and adult brain following perinatal asphyxia (PA). Our findings reveal significant effects of PA on neurometabolic profiles at one week of age, and significant relationships between early metabolites and later life phenotypes including behavior and brain morphometry

  12. Determining the mechanism of cusp proton aurora

    PubMed Central

    Xiao, Fuliang; Zong, Qiugang; Su, Zhenpeng; Yang, Chang; He, Zhaoguo; Wang, Yongfu; Gao, Zhonglei

    2013-01-01

    Earth's cusp proton aurora occurs near the prenoon and is primarily produced by the precipitation of solar energetic (2–10 keV) protons. Cusp auroral precipitation provides a direct source of energy for the high-latitude dayside upper atmosphere, contributing to chemical composition change and global climate variability. Previous studies have indicated that magnetic reconnection allows solar energetic protons to cross the magnetopause and enter the cusp region, producing cusp auroral precipitation. However, energetic protons are easily trapped in the cusp region due to a minimum magnetic field existing there. Hence, the mechanism of cusp proton aurora has remained a significant challenge for tens of years. Based on the satellite data and calculations of diffusion equation, we demonstrate that EMIC waves can yield the trapped proton scattering that causes cusp proton aurora. This moves forward a step toward identifying the generation mechanism of cusp proton aurora. PMID:23575366

  13. Stray-field nuclear magnetic resonance imaging in microgravity conditions

    NASA Astrophysics Data System (ADS)

    Garrido, Leoncio; Sampayo, José

    2008-03-01

    Magnetic levitation has been proposed as an alternative approach to simulate on Earth microgravity conditions encountered in space, allowing the investigation of weightlessness on materials and biological systems. In general, very strong magnetic fields, 15T or higher, are required to achieve levitation for a majority of diamagnetic substances. Here, we show that it is possible to achieve levitation of these substances in a commercial superconductive magnet operating with a nuclear magnetic resonance (NMR) spectrometer at 9.4T at ambient conditions. Furthermore, stray-field proton NMR imaging is performed in situ at the location where a sample is levitating, showing that it is feasible to obtain the corresponding one-dimensional profile. Considering that water is a diamagnetic substance and the main constituent of living systems, the outlined approach could be useful to investigate alterations in water proton NMR properties induced by low gravity and magnetic forces upon levitating, e.g., seeds, cells, etc. In addition to protons, it would also be possible to observe other nuclei (e.g., F19, P31, etc.) that may be of interest in metabolic and therapeutic investigations.

  14. Changes to Intermediary Metabolites in Sporadic and LRRK2 Parkinson's Disease Demonstrated by Proton Magnetic Resonance Spectroscopy

    PubMed Central

    Aasly, Jan O.; Sæther, Oddbjørn; Johansen, Krisztina K.; Bathen, Tone F.; Giskeødegård, Guro F.; White, Linda R.

    2015-01-01

    Background. Parkinson's disease (PD) remains a clinical diagnosis and biomarkers are needed to detect the disease as early as possible. Genetically determined PD provides an opportunity for studying metabolic differences in connection with disease development. Objectives. To study the levels of intermediary metabolites in cerebrospinal fluid (CSF) from patients with PD, either of sporadic type or in carriers of the LRRK2 p.G2019S mutation. Methods. Results from patients with sporadic PD or LRRK2-PD were compared with asymptomatic LRRK2 mutation carriers and healthy control individuals. CSF was analysed by proton MR spectroscopy (1H-MRS) giving reliable results for 16 intermediary metabolites. Partial least squares discriminant analysis (PLS-DA) was applied to study group differences. Results. PLS-DA distinguished PD patients from healthy individuals based on the metabolites identified in CSF, with 2-hydroxybutyrate, glutamine, and dimethyl sulphone largely contributing to the separations. Conclusion. Speculatively, all three metabolites could alter concentration in response to metabolic changes connected with neurodegeneration; glutamine as a means of removing excess nitrogen from brain, dimethyl sulphone as an anti-inflammatory agent, and 2-hydroxybutyrate in connection with altered glutathione metabolism. Potentially, 1H-MRS is a promising tool for identifying novel biomarkers for PD. PMID:26357583

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

    PubMed Central

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

    2014-01-01

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

  16. 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.

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

    PubMed

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

    2015-12-01

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

  18. 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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

    Walton, Senta; Mandaric, Sanja; Oxenius, Annette

    2013-01-01

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

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

    PubMed

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

    2011-04-21

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

  2. 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.

  3. 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.

  4. 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

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

    PubMed

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

    2016-09-01

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

  6. Roles of the. beta. 146 histidyl residue in the molecular basis of the Bohr Effect of hemoglobin: A proton nuclear magnetic resonance study

    SciTech Connect

    Busch, M.R.; Mace, J.E.; Ho, N.T.; Ho, Chien )

    1991-02-19

    Assessment of the roles of the carboxyl-terminal {beta}146 histidyl residues in the alkaline Bohr effect in human and normal adult hemoglobin by high-resolution proton nuclear magnetic resonance spectroscopy requires assignment of the resonances corresponding to these residues. By a careful spectroscopic study of human normal adult hemoglobin, enzymatically prepared des(His146{beta})-hemoglobin, and the mutant hemoglobins Cowtown ({beta}146His {yields} Leu) and York ({beta}146His {yields} Pro), the authors have resolved some of these conflicting results. By a close incremental variation of pH over a wide range in chloride-free 0.1 M N-(2-hydroxyethyl)piperazine-N{prime}-2-ethanesulfonic acid buffer, a single resonance has been found to be consistently missing in the proton nuclear magnetic resonance spectra of these hemoglobin variants. The results indicate that the contribution of the {beta}146 histidyl residues is 0.52 H{sup +}/hemoglobin tetramer at pH 7.6, markedly less than 0.8 H{sup +}/hemoglobin tetramer estimated by study of the mutant hemoglobin Cowtown ({beta}146His {yields} Leu) by Shih and Perutz. They have found that at least two histidyl residues in the carbonmonoxy form of this mutant have pK values that are perturbed, and they suggest that these pK differences may in part account for this discrepancy. The results show that the pK values of {beta}146 histidyl residues in the carbonmonoxy form of hemoglobin are substantially affected by the presence of chloride and other anions in the solvent, and thus, the contribution of this amino acid residue to the alkaline Bohr effect can be shown to vary widely in magnitude, depending on the solvent composition. These results demonstrate that the detailed molecular mechanisms of the alkaline Bohr effect are not unique but are affected both by the hemoglobin structure and by the interactions with the solvent components in which the hemoglobin molecule resides.

  7. Clinical brain proton magnetic resonance spectroscopy for management of Alzheimer's and sub-cortical ischemic vascular dementia in older people.

    PubMed

    Waldman, Adam D B; Rai, Gurcharan S; McConnell, James R; Chaudry, Mahera; Grant, David

    2002-01-01

    This study examined the clinical usefulness of magnetic resonance spectroscopy (MRS) performed using an automated single voxel technique at 1.0 T field strength in a district general hospital magnetic resonance (MR) scanner in the assessment of older people referred to a memory clinic with suspected dementia. Of 50 elderly subjects (M:F 20:30) examined and followed-up clinically over more than 2 years, 20 had clinical Alzheimer's disease (AD), 18 had clinical vascular dementia, six had mixed features and three were normal. Three normal volunteers were also studied. MRS was performed at the same time as structural magnetic resonance imaging (MRI), added <15 min to the examination and was well-tolerated in all patients studied. Patients with AD had significantly higher myoinositol/creatine (MI/Cr) ratios (mean +/- S.D.: 0.82 +/- 0.04) compared to those with vascular dementia (mean +/-S. D.: 0.71 +/- 0.07, P<0.00001) and normal subjects (mean +/- S.D.: 0.72 +/- 0.036, P<0.0002); there was little overlap between the AD and vascular groups. The mixed dementia group also had significantly higher MI/Cr ratios (mean +/- S.D.: 0.80 +/- 0.05) than vascular dementia (P<0.01) and normal (P<0.03) groups, but with considerable overlap. No significant differences were shown for N-acetyl aspartate or choline/creatine ratios between the different clinical groups. These data suggest that MI/Cr ratios can distinguish patients with AD from normal subjects and those with sub-cortical ischemic vascular dementia and that MRS will be useful to clinicians managing persons with AD in a district general hospital setting. PMID:14764351

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

    PubMed Central

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

    2016-01-01

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

  9. 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

  10. 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

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

    PubMed

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

    2013-05-31

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

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

    PubMed

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

    2016-09-01

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

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

    PubMed Central

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

    2010-01-01

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

  15. 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.

  16. Diagnosis of Alzheimer-type dementia: a preliminary comparison of positron emission tomography and proton magnetic resonance

    SciTech Connect

    Friedland, R.P.; Budinger, T.F.; Brant-Zawadzki, M.; Jagust, W.J.

    1984-11-16

    The use of positron emission tomography with (18F)-2-fluoro-2-deoxy-D-glucose (FDG) to study glucose metabolism in dementia is described and compared with the use of magnetic resonance imaging. These studies suggest that physiological imaging with PET may be superior to MR as it is currently used in the diagnosis of dementia-like diseases. Pet is currently limited to a few centers; however, single photon emission CT can provide regional physiological data without the need for a local cyclotron. 15 references, 2 tables.

  17. Genomewide Histone H3 Lysine 9 Acetylation Profiling in CD4+ T Cells Revealed Endoplasmic Reticulum Stress Deficiency in Patients with Acute-on-chronic Liver Failure.

    PubMed

    Jin, L; Wang, K; Liu, H; Chen, T; Yang, Y; Ma, X; Wang, J; Li, Y; Du, D; Zhao, Y; He, Y

    2015-11-01

    Acute-on-chronic liver failure (ACLF) displayed 'sepsis-like' immune paralysis. Little is known about the role of CD4+ T lymphocytes, the primary regulator of innate and adopted immune system, played in ACLF. Acetylation of histone H3 lysine 9 (H3K9ac), a key epigenetic modification, tightly controls gene transcription. Whether and how does H3K9ac modification regulate CD4+ T cells in ACLF remains unclear. PBMCs were isolated from patients with ACLF, immune tolerance of chronic hepatitis B (CHB-T) and immune active of chronic hepatitis B (CHB-A). Then, CD4+ T lymphocytes were purified by magnetic microbeads, and the purity was confirmed by flow cytometry. H3K9ac variations were analysed in CD4+ T cells using chromatin immunoprecipitation microarray and then confirmed by quantitative PCR. Whole-genome H3K9 acetylation analyses were conducted by bioinformatics. A total of 70 genes were differently modified in H3K9ac between CHB-A and ACLF groups, while 44 genes were differently modified in H3K9ac between CHB-T and ACLF groups. Clustering algorithm analysis showed patients with ACLF displayed 'sepsis-like' immune paralysis. Functional analysis showed endoplasmic reticulum (ER) stress, or downstream pathway-related genes, such as BIP, ATF4, PER1, CSNK1D, IRF3, BNIP1, AKT1 and UBC, were differentially modified in ACLF. We profiled H3K9 acetyl modification in CD4+ T lymphocytes from HBV-infected patients with three different immune states, that is ACLF, immune tolerance and immune active phases. ACLF displayed 'sepsis-like' immune paralysis. ER stress in CD4+ T lymphocytes attributed to ACLF. This study provides some useful clues for revealing the mechanisms underlying ACLF. PMID:26173605

  18. Cuprizone-induced demyelination and demyelination-associated inflammation result in different proton magnetic resonance metabolite spectra

    PubMed Central

    Praet, Jelle; Orije, Jasmien; Kara, Firat; Guglielmetti, Caroline; Santermans, Eva; Daans, Jasmijn; Hens, Niel; Verhoye, Marleen; Berneman, Zwi; Ponsaerts, Peter; Van der Linden, Annemie

    2015-01-01

    Conventional MRI is frequently used during the diagnosis of multiple sclerosis but provides only little additional pathological information. Proton MRS (1H-MRS), however, provides biochemical information on the lesion pathology by visualization of a spectrum of metabolites. In this study we aimed to better understand the changes in metabolite concentrations following demyelination of the white matter. Therefore, we used the cuprizone model, a well-established mouse model to mimic type III human multiple sclerosis demyelinating lesions. First, we identified CX3CL1/CX3CR1 signaling as a major regulator of microglial activity in the cuprizone mouse model. Compared with control groups (heterozygous CX3CR1+/− C57BL/6 mice and wild type CX3CR1+/+ C57BL/6 mice), microgliosis, astrogliosis, oligodendrocyte cell death and demyelination were shown to be highly reduced or absent in CX3CR1−/− C57BL/6 mice. Second, we show that 1H-MRS metabolite spectra are different when comparing cuprizone-treated CX3CR1−/− mice showing mild demyelination with cuprizone-treated CX3CR1+/+ mice showing severe demyelination and demyelination-associated inflammation. Following cuprizone treatment, CX3CR1+/+ mice show a decrease in the Glu, tCho and tNAA concentrations as well as an increased Tau concentration. In contrast, following cuprizone treatment CX3CR1−/− mice only showed a decrease in tCho and tNAA concentrations. Therefore, 1H-MRS might possibly allow us to discriminate demyelination from demyelination-associated inflammation via changes in Tau and Glu concentration. In addition, the observed decrease in tCho concentration in cuprizone-induced demyelinating lesions should be further explored as a possible diagnostic tool for the early identification of human MS type III lesions. Copyright © 2015 John Wiley & Sons, Ltd. PMID:25802215

  19. Naive CD4(+) T cell frequency varies for different epitopes and predicts repertoire diversity and response magnitude.

    PubMed

    Moon, James J; Chu, H Hamlet; Pepper, Marion; McSorley, Stephen J; Jameson, Stephen C; Kedl, Ross M; Jenkins, Marc K

    2007-08-01

    Cell-mediated immunity stems from the proliferation of naive T lymphocytes expressing T cell antigen receptors (TCRs) specific for foreign peptides bound to host major histocompatibility complex (MHC) molecules. Because of the tremendous diversity of the T cell repertoire, naive T cells specific for any one peptide:MHC complex (pMHC) are extremely rare. Thus, it is not known how many naive T cells of any given pMHC specificity exist in the body or how that number influences the immune response. By using soluble pMHC class II (pMHCII) tetramers and magnetic bead enrichment, we found that three different pMHCII-specific naive CD4(+) T cell populations vary in frequency from 20 to 200 cells per mouse. Moreover, naive population size predicted the size and TCR diversity of the primary CD4(+) T cell response after immunization with relevant peptide. Thus, variation in naive T cell frequencies can explain why some peptides are stronger immunogens than others. PMID:17707129

  20. Enhanced critical currents of commercial 2G superconducting coated conductors through proton irradiation

    NASA Astrophysics Data System (ADS)

    Welp, Ulrich; Leroux, M.; Kihlstrom, K. J.; Kwok, W.-K.; Koshelev, A. E.; Miller, D. J.; Rupich, M. W.; Fleshler, S.; Malozemoff, A. P.; Kayani, A.

    2015-03-01

    We report on magnetization and transport measurements of the critical current density, Jc, of commercial 2G YBCO coated conductors before and after proton irradiation. The samples were irradiated along the c-axis with 4 MeV protons. Proton irradiation produces a mixed pinning landscape composed of pre-existing rare earth particles and a uniform distribution of irradiation induced nm-sized defects. This pinning landscape strongly reduces the suppression of Jc in magnetic fields resulting in a doubling of Jc in a field of ~ 4T. The irradiation dose-dependence of Jc is characterized by a temperature and field dependent sweat spot that at 5 K and 6 T occurs around 20x1016 p/cm2. Large-scale time dependent Ginzburg-Landau simulations yield a good description of our results. This work supported by the Center for Emergent Superconductivity, an Energy Frontier Research Center funded by the U.S. D.O.E., Office of Science, Office of Basic Energy Sciences (KK, ML, AEK) and by the D.O.E, Office of Basic Energy Sciences, under Contract No. DE-AC02-06CH11357 (UW, WKK).

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

    PubMed Central

    2014-01-01

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

  2. A study of coal extraction with electron paramagnetic resonance (EPR) and proton nuclear magnetic resonance relaxation techniques. Quarterly technical progress report, April 1, 1993--June 30, 1993

    SciTech Connect

    Doetschman, D.C.; Mehlenbacher, R.C.; Ito, O.

    1993-09-01

    An electron spin and proton magnetic relaxation study is presented on the effects of the solvent extraction of coal on the macromoleculer network of the coal and on the mobile molecular species that are initially within the coal. The eight Argonne Premium coals were extracted at room temperature with a 1:1 (v/v) N-methylpyrrolidinone (NMP)-CS2 solvent mixture under an inert atmosphere. As much solvent as possible was removed from extract and residue by treatment in a vacuum. The mobilization of molecular free radicals by the solvent and the exposure of free radicals in the macromoleculer matrix to solvent or to species dissolved in the solvent, results in a preferential survival of residue radicals of types that depend on the particular coal and results in the apparently fairly uniform loss of all types of radicals in bituminous coal extracts. The surviving extract and residue free radicals are more predominantly of the odd- alternate hydrocarbon free radical type. The spin-lattice relaxation (SLR) of these coal free radicals has previously been inferred (Doetschman and Dwyer, Energy Fuels, 1992, 6, 783) to be from the modulation of the intramolecular electron-nuclear dipole-interactions of the CH groups in a magnetic field by rocldng motions of the radical in the coal matrix. Such a modulation would depend not only on the rocking amplitude and frequency but also upon the electron spin density at the CH groups in the radical. The observed SLR rates decrease with coal rank in agreement with the smaller spin densities and the lower rocidng amplitudes that are expected for the larger polycondensed ring systems in coals of higher rank. The SLR rates are found to be generally faster in the extracts (than residues) where the molecular species would be expected to have a smaller polycondensed ring system than in the macromoleculer matrix of the residue.

  3. Lithium does not alter the choline/creatine ratio in the temporal lobe of human volunteers as measured by proton magnetic resonance spectroscopy.

    PubMed Central

    Silverstone, P H; Hanstock, C C; Rotzinger, S

    1999-01-01

    OBJECTIVE: To study the effect of lithium administration on brain choline/creatine (Cho/Cr) ratios in healthy volunteers. DESIGN: Double-blind, placebo-controlled, prospective study. SETTING: The Nuclear Magnetic Resonance Research Unit at the University of Alberta. PARTICIPANTS: Sixteen healthy volunteers, recruited through advertisements. Subjects were excluded if they had a physical illness, or a personal or family history of psychiatric illness. The study period was from Feb. 6, 1996, to Mar. 21, 1996. INTERVENTIONS: Subjects received a baseline proton magnetic resonance spectroscopy (1H MRS) scan, and then were instructed to take either lithium (1,200 mg) or placebo at night for 7 days. On Day 8, the subjects returned for a second 1H MRS scan. Study participants were seen by a physician at the beginning and at the end of the experiment, and had access to the physician throughout the study period. OUTCOME MEASURES: Ratios of Cho/Cr measured in the temporal lobes by 1H MRS. RESULTS: There were no significant differences in the Cho/Cr ratios between the 2 groups on the test day (placebo 0.748 [standard deviation 0.29] versus lithium 0.811 [SD 0.25]; F = 0.147, p = 0.72), and there was no significant change from baseline in either group (0.003 above baseline for placebo; 0.056 above baseline for lithium; F = 1.21, p = 0.32). CONCLUSIONS: Lithium administration to healthy volunteers does not alter the Cho/Cr ratio in temporal lobe as measured by 1H MRS. The result concurs with reports that differences in Cho/Cr ratios observed in patients with bipolar disorder are likely specific to the illness, and are not the result of lithium therapy. Hence, alterations in choline function are not involved in the clinical effectiveness of lithium. Images Fig. 1 PMID:10354656

  4. Discrimination between neurochemical and macromolecular signals in human frontal lobes using short echo time proton magnetic resonance spectroscopy.

    PubMed

    McLean, Mary A; Simister, Robert J; Barker, Gareth J; Duncan, John S

    2004-01-01

    Magnetic resonance spectra from large (35 cm3) frontal lobe voxels in vivo were analyzed using LCModel, with and without subtraction of a "metabolite nulled" spectrum with an inversion time of 650 ms to characterize the macromolecule baseline. Baseline subtraction decreased the signal to noise ratio (SNR), but improved the reliability of LCModel quantification of most metabolites, as reflected in the Cramer-Rao lower bounds, in particular for glutamate and glutamine. The reported concentrations increased for glutamine, creatine, and lactate, and decreased for glutamate, myo-inositol and NAAG, but the sum of all metabolites remained constant, as did the standard deviation of the concentrations in the control group. Macromolecule subtraction is worthwhile when SNR is high, as in the characterization of normal-appearing tissue in the brain. PMID:14992401

  5. Glutamine and Glutamate Levels in Children and Adolescents With Bipolar Disorder: A 4.0-T Proton Magnetic Resonance Spectroscopy Study of the Anterior Cingulate Cortex

    PubMed Central

    MOORE, CONSTANCE M.; FRAZIER, JEAN A.; GLOD, CAROL A.; BREEZE, JANIS L.; DIETERICH, MEGAN; FINN, CHELSEA T.; FREDERICK, BLAISE DEB.; RENSHAW, PERRY F.

    2014-01-01

    Objective The purpose of this study was to use proton magnetic resonance spectroscopy, at 4.0 T, to explore the glutamine and glutamate levels in the anterior cingulate cortex of children and adolescents with bipolar disorder (BPD; medicated and unmedicated) and healthy comparison subjects (HCSs). We hypothesized that unmedicated children with BPD would have reduced glutamine and glutamate levels compared with HCSs and medicated children with BPD. Method Spectra were acquired from the anterior cingulate cortex in 22 children and adolescents with DSM-IV-TR BPD, type 1 (13 female: age 12.6 ± 4.4 years: 7 of the subjects with BPD were unmedicated at the time of the scan) and 10 HCSs (7 female: age 12.3 ± 2.5 years). Results Unmedicated subjects with BPD had significantly lower glutamine levels than HCSs or medicated subjects with BPD. There were no differences in glutamate levels between the three groups. Conclusions These results are consistent with there being an abnormality in anterior cingulate cortex glia in untreated children and adolescents with BPD. The results of this pilot study may be important in helping us better understand the pathophysiology of child and adolescent BPD. In addition, this observation may help to develop better and more targeted treatments, in particular those affecting the metabolism of glutamine, perhaps by regulation of glutamine synthetase activity. PMID:17420688

  6. Proton nuclear magnetic resonance and fluorescence spectroscopic studies of segmental mobility in aequorin and a green fluorescent protein from Aequorea forskalea

    SciTech Connect

    Nageswara Rao, B.D.; Kemple, M.D.; Prendergast, F.G.

    1980-10-01

    Aequorin is a protein of low molecular weight (20,000) isolated from the jellyfish Aequorea forskalea which emits blue light upon the binding of Ca/sup 2 +/ ions. This bioluminescence requires neither exogenous oxygen nor any other cofactors. The light emission occurs from an excited state of a chromophore (an imidazolopyrazinone) which is tightly and noncovalently bound to the protein. Apparently the binding of Ca/sup 2 +/ by the protein induces changes in the protein conformation which allow oxygen, already bound or otherwise held by the protein, to react with and therein oxidize the chromophore. The resulting discharged protein remains intact, with the Ca/sup 2 +/ and the chromophore still bound, but is incapable of further luminescence. The fluorescence spectrum of this discharged protein and the bioluminescence spectrum of the original charged aequorin are identical. A green fluorescent protein (GFP) of approx. 30,000 mol wt isolated from the same organism, functions in vivo as an acceptor of energy from aequorin and subsequently emits green light. We are applying proton nuclear magnetic resonance (NMR) spectroscopy and fluorescence spectroscopy to examine structural details of, and fluctuations associated with the luminescent reaction of aequorin and the in vivo energy transfer from aequorin to the GFP.

  7. Quantification of microheterogeneity in glioblastoma multiforme with ex vivo high-resolution magic-angle spinning (HRMAS) proton magnetic resonance spectroscopy.

    PubMed Central

    Cheng, L. L.; Anthony, D. C.; Comite, A. R.; Black, P. M.; Tzika, A. A.; Gonzalez, R. G.

    2000-01-01

    Microheterogeneity is a routinely observed neuropathologic characteristic in brain tumor pathology. Although microheterogeneity is readily documented by routine histologic techniques, these techniques only measure tumor status at the time of biopsy or surgery and do not indicate likely tumor progression. A biochemical screening technique calibrated against pathologic standards would greatly assist in predicting tumor progression from its biological activity. Here we demonstrate for the first time that proton magnetic resonance spectroscopy (1H MRS) with high-resolution magic-angle spinning (HRMAS), a technique introduced in 1997, can preserve tissue histopathologic features while producing well-resolved spectra of cellular metabolites in the identical intact tissue specimens. Observed biochemical alterations and tumor histopathologic characteristics can thus be correlated for the same surgical specimen, obviating the problems caused by tumor microheterogeneity. We analyzed multiple specimens of a single human glioblastoma multiforme surgically removed from a 44-year-old patient. Each specimen was first measured with HRMAS 1H MRS to determine tumor metabolites, then evaluated by quantitative histopathology. The concentrations of lactate and mobile lipids measured with HRMAS linearly reflected the percentage of tumor necrosis. Moreover, metabolic ratios of phosphorylcholine to choline correlated linearly with the percentage of the highly cellular malignant glioma. The quantification of tumor metabolic changes with HRMAS 1H MRS, in conjunction with subsequent histopathology of the same tumor specimen, has the potential to further our knowledge of the biochemistry of tumor heterogeneity during development, and thus ultimately to improve our accuracy in diagnosing, characterizing, and evaluating tumor progression. PMID:11303625

  8. Evaluation of Water Exchange Kinetics on [Ln(AAZTAPh-NO2)(H2O)q](x) Complexes Using Proton Nuclear Magnetic Resonance.

    PubMed

    Karimi, Shima; Tei, Lorenzo; Botta, Mauro; Helm, Lothar

    2016-06-20

    Water exchange kinetics on [Ln(AAZTAPh-NO2)(H2O)q](-) (Ln = Gd(3+), Dy(3+), or Tm(3+)) were determined by (1)H nuclear magnetic resonance (NMR) measurements. The number of inner-sphere water molecules was found to change from two to one when going from Dy(3+) to Tm(3+). The calculated water exchange rate constants obtained by variable-temperature proton transverse relaxation rates are 3.9 × 10(6), 0.46 × 10(6), and 0.014 × 10(6) s(-1) at 298 K for Gd(3+), Dy(3+), and Tm(3+), respectively. Variable-pressure measurements were used to assess the water exchange mechanism. The results indicate an associative and dissociative interchange mechanism for Gd(3+) and Dy(3+) complexes with ΔV(⧧) values of -1.4 and 1.9 cm(3) mol(-1), respectively. An associative activation mode (Ia or A mechanism) was obtained for the Tm(3+) complex (ΔV(⧧) = -5.6 cm(3) mol(-1)). Moreover, [Dy(AAZTAPh-NO2)(H2O)2](-) with a very high transverse relaxivity value was found as a potential candidate for negative contrast agents for high-field imaging applications. PMID:27227690

  9. Identification of endogenous metabolites in human sperm cells using proton nuclear magnetic resonance ((1) H-NMR) spectroscopy and gas chromatography-mass spectrometry (GC-MS).

    PubMed

    Paiva, C; Amaral, A; Rodriguez, M; Canyellas, N; Correig, X; Ballescà, J L; Ramalho-Santos, J; Oliva, R

    2015-05-01

    The objective of this study was to contribute to the first comprehensive metabolomic characterization of the human sperm cell through the application of two untargeted platforms based on proton nuclear magnetic resonance ((1) H-NMR) spectroscopy and gas chromatography coupled to mass spectrometry (GC-MS). Using these two complementary strategies, we were able to identify a total of 69 metabolites, of which 42 were identified using NMR, 27 using GC-MS and 4 by both techniques. The identity of some of these metabolites was further confirmed by two-dimensional (1) H-(1) H homonuclear correlation spectroscopy (COSY) and (1) H-(13) C heteronuclear single-quantum correlation (HSQC) spectroscopy. Most of the metabolites identified are reported here for the first time in mature human spermatozoa. The relationship between the metabolites identified and the previously reported sperm proteome was also explored. Interestingly, overrepresented pathways included not only the metabolism of carbohydrates, but also of lipids and lipoproteins. Of note, a large number of the metabolites identified belonged to the amino acids, peptides and analogues super class. The identification of this initial set of metabolites represents an important first step to further study their function in male gamete physiology and to explore potential reasons for dysfunction in future studies. We also demonstrate that the application of NMR and MS provides complementary results, thus constituting a promising strategy towards the completion of the human sperm cell metabolome. PMID:25854681

  10. Relationship between Proton Magnetic Resonance Spectroscopy of Frontoinsular Gray Matter and Neurodevelopmental Outcomes in Very Low Birth Weight Children at the Age of 4

    PubMed Central

    Herman-Sucharska, Izabela; Urbanik, Andrzej; Klimek, Małgorzata; Karcz, Paulina; Dutkowska, Grażyna; Nitecka, Magdalena; Kwinta, Przemko

    2016-01-01

    Very low birth weight is associated with long term neurodevelopmental complications. Macroscopic brain abnormalities in prematurity survivors have been investigated in several studies. However, there is limited data regarding local cerebral metabolic status and neurodevelopmental outcomes. The purpose of this study was to characterize the relationship between proton magnetic resonance spectra in basal ganglia, frontal white matter and frontoinsular gray matter, neurodevelopmental outcomes assessed with the Leiter scale and the Developmental Test of Visual Perception and selected socioeconomic variables in a cohort of very low birth weight children at the age of four. Children were divided in three groups based on the severity of neurodevelopmental impairment. There were no differences in spectroscopy in basal ganglia and frontal white matter between the groups. Lower concentrations of N-acetylaspartate (NAA), choline (Cho) and myoinositol (mI) were observed in the frontoinsular cortex of the left hemisphere in children with neurodevelopmental impairment compared to children with normal neurodevelopmental outcomes. Higher parental education, daycare attendance and breastfeeding after birth were associated with more favorable neurodevelopmental prognosis, whereas rural residence was more prevalent in children with moderate and severe impairment. Our study demonstrates the role of long term neurometabolic disruption in the left frontoinsular cortex and selected socioeconomic variables in determination of neurodevelopmental prognosis in prematurity survivors. PMID:27223474

  11. Differentiation of Organically and Conventionally Grown Tomatoes by Chemometric Analysis of Combined Data from Proton Nuclear Magnetic Resonance and Mid-infrared Spectroscopy and Stable Isotope Analysis.

    PubMed

    Hohmann, Monika; Monakhova, Yulia; Erich, Sarah; Christoph, Norbert; Wachter, Helmut; Holzgrabe, Ulrike

    2015-11-01

    Because the basic suitability of proton nuclear magnetic resonance spectroscopy ((1)H NMR) to differentiate organic versus conventional tomatoes was recently proven, the approach to optimize (1)H NMR classification models (comprising overall 205 authentic tomato samples) by including additional data of isotope ratio mass spectrometry (IRMS, δ(13)C, δ(15)N, and δ(18)O) and mid-infrared (MIR) spectroscopy was assessed. Both individual and combined analytical methods ((1)H NMR + MIR, (1)H NMR + IRMS, MIR + IRMS, and (1)H NMR + MIR + IRMS) were examined using principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), linear discriminant analysis (LDA), and common components and specific weight analysis (ComDim). With regard to classification abilities, fused data of (1)H NMR + MIR + IRMS yielded better validation results (ranging between 95.0 and 100.0%) than individual methods ((1)H NMR, 91.3-100%; MIR, 75.6-91.7%), suggesting that the combined examination of analytical profiles enhances authentication of organically produced tomatoes. PMID:26457410

  12. Separation of Intra- and Extramyocellular Lipid Signals in Proton MR Spectra by Determination of Their Magnetic Field Distribution

    NASA Astrophysics Data System (ADS)

    Steidle, G.; Machann, J.; Claussen, C. D.; Schick, F.

    2002-02-01

    In skeletal musculature intramyocellular (IMCL) and extramyocellular lipids (EMCL) are stored in compartments of different geometry and experience different magnetic field strengths due to geometrical susceptibility effects. The effect is strong enough to-at least partly-separate IMCL and EMCL contributions in 1H MR spectroscopy, despite IMCL and EMCL consisting of the same substances. The assessment of intramyocellular lipid stores in skeletal musculature by 1H MR spectroscopy plays an important role for studying physiological and pathological aspects of lipid metabolism. Therefore, a method using mathematical tools of Fourier analysis is developed to obtain the magnetic field distribution (MFD) from the measured spectra by deconvolution. A reference lipid spectrum is required which was recorded in tibial yellow bone marrow. It is shown that the separation of IMCL contributions can be performed more precisely-compared to other methods-based on the MFD. Examples of deconvolution in model systems elucidate the principle. Applications of the proposed approach on in vivo examinations in m. soleus and m. tibialis anterior are presented. Fitting the IMCL part of the MFD by a Gaussian lineshape with a linewidth kept fixed with respect to the linewidth of creatine and with the assumption of a smooth but not necessarily symmetrical shape for the EMCL part, the only free fit parameter, the amplitude of the IMCL part, is definite and subtraction leads to the EMCL part in the MFD. This procedure is especially justified for the soleus muscle showing a severely asymmetrical distribution which might lead to a marked overestimation of IMCL using common line fitting procedures.

  13. Separation of intra- and extramyocellular lipid signals in proton MR spectra by determination of their magnetic field distribution.

    PubMed

    Steidle, G; Machann, J; Claussen, C D; Schick, F

    2002-02-01

    In skeletal musculature intramyocellular (IMCL) and extramyocellular lipids (EMCL) are stored in compartments of different geometry and experience different magnetic field strengths due to geometrical susceptibility effects. The effect is strong enough to---at least partly---separate IMCL and EMCL contributions in (1)H MR spectroscopy, despite IMCL and EMCL consisting of the same substances. The assessment of intramyocellular lipid stores in skeletal musculature by (1)H MR spectroscopy plays an important role for studying physiological and pathological aspects of lipid metabolism. Therefore, a method using mathematical tools of Fourier analysis is developed to obtain the magnetic field distribution (MFD) from the measured spectra by deconvolution. A reference lipid spectrum is required which was recorded in tibial yellow bone marrow. It is shown that the separation of IMCL contributions can be performed more precisely---compared to other methods---based on the MFD. Examples of deconvolution in model systems elucidate the principle. Applications of the proposed approach on in vivo examinations in m. soleus and m. tibialis anterior are presented. Fitting the IMCL part of the MFD by a Gaussian lineshape with a linewidth kept fixed with respect to the linewidth of creatine and with the assumption of a smooth but not necessarily symmetrical shape for the EMCL part, the only free fit parameter, the amplitude of the IMCL part, is definite and subtraction leads to the EMCL part in the MFD. This procedure is especially justified for the soleus muscle showing a severely asymmetrical distribution which might lead to a marked overestimation of IMCL using common line fitting procedures. PMID:11846580

  14. 4T1 Murine Mammary Carcinoma Cells Enhance Macrophage-Mediated Innate Inflammatory Responses

    PubMed Central

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

    2015-01-01

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

  15. 4T1 Murine Mammary Carcinoma Cells Enhance Macrophage-Mediated Innate Inflammatory Responses.

    PubMed

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

    2015-01-01

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

  16. Development of an immune function assay by measuring intracellular adenosine triphosphate (iATP) levels in mitogen-stimulated CD4+ T lymphocytes.

    PubMed

    Naderi, Hadi; Najafi, Alireza; Khoshroo, Mohammad; Tajik, Nader

    2016-01-01

    We developed an immune function assay for monitoring CD4+ T cells activity based on changes in intracellular adenosine triphosphate (iATP) levels after phytohemagglutinin (PHA) stimulation. Blood samples were obtained from 40 healthy subjects and 30 RTRs and incubated with 5 µg/mL of PHA for 15-18 hr at 37°C and 5% CO2. Afterward, the CD4+ T cells were separated by antibody-coated magnetic beads and lysed. Then, iATP content in unstimulated and stimulated conditions was measured by luciferin-luciferase reaction using a log-log standard curve. The iATP levels showed significant increase in CD4+ T cells in both healthy persons (mean: 550 ± 142 ng/mL vs. 109 ± 54 ng/mL) and RTRs (mean: 394 ± 160 ng/mL vs. 52 ± 37 ng/mL) after PHA stimulation (P < 0.001). However, the iATP production in RTRs was significantly lower than that in healthy individuals; both prior to and after stimulation with PHA (P < 0.001). No gender-specific difference in iATP production was observed between women and men subjects. This rapid and low-cost assay reflects the degree of immune cell function through assessment of CD4+ T cells activation. Thus, it can be used for evaluation of immune system status in immunodeficient individuals as well as in immunosuppressed transplant recipients who needs drug adjustment. PMID:27089103

  17. Brain Changes in Long-Term Zen Meditators Using Proton Magnetic Resonance Spectroscopy and Diffusion Tensor Imaging: A Controlled Study

    PubMed Central

    Fayed, Nicolás; Lopez del Hoyo, Yolanda; Andres, Eva; Serrano-Blanco, Antoni; Bellón, Juan; Aguilar, Keyla; Cebolla, Ausias; Garcia-Campayo, Javier

    2013-01-01

    Introduction This work aimed to determine whether 1H magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), diffusion-weighted imaging (DWI) and diffusion tensor imaging (DTI) are correlated with years of meditation and psychological variables in long-term Zen meditators compared to healthy non-meditator controls. Materials and Methods Design. Controlled, cross-sectional study. Sample. Meditators were recruited from a Zen Buddhist monastery. The control group was recruited from hospital staff. Meditators were administered questionnaires on anxiety, depression, cognitive impairment and mindfulness. 1H-MRS (1.5 T) of the brain was carried out by exploring four areas: both thalami, both hippocampi, the posterior superior parietal lobule (PSPL) and posterior cingulate gyrus. Predefined areas of the brain were measured for diffusivity (ADC) and fractional anisotropy (FA) by MR-DTI. Results Myo-inositol (mI) was increased in the posterior cingulate gyrus and Glutamate (Glu), N-acetyl-aspartate (NAA) and N-acetyl-aspartate/Creatine (NAA/Cr) was reduced in the left thalamus in meditators. We found a significant positive correlation between mI in the posterior cingulate and years of meditation (r = 0.518; p = .019). We also found significant negative correlations between Glu (r = −0.452; p = .045), NAA (r = −0.617; p = .003) and NAA/Cr (r = −0.448; P = .047) in the left thalamus and years of meditation. Meditators showed a lower Apparent Diffusion Coefficient (ADC) in the left posterior parietal white matter than did controls, and the ADC was negatively correlated with years of meditation (r = −0.4850, p = .0066). Conclusions The results are consistent with the view that mI, Glu and NAA are the most important altered metabolites. This study provides evidence of subtle abnormalities in neuronal function in regions of the white matter in meditators. PMID:23536796

  18. 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.

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

    PubMed

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

    2013-01-01

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

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

    PubMed

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

    2013-01-01

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

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

    PubMed

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

    2013-12-15

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

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

    PubMed Central

    Chauhan, Anil K.

    2016-01-01

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

  3. 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

  4. 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

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

    PubMed Central

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

    2014-01-01

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

  6. Quantum chemical study of the enzymatic repair of T(6-4)C/C(6-4)T UV-photolesions by DNA photolyases.

    PubMed

    Faraji, Shirin; Wirz, Lukas; Dreuw, Andreas

    2013-08-26

    Several strategies have evolved to repair one of the abundant UV radiation-induced damages caused to DNA, namely the mutagenic pyrimidine (6-4) pyrimidone photolesions. DNA (6-4)-photolyases are enzymes repairing these lesions by a photoinitiated electron transfer. An important aspect of a possible repair mechanism is its generality and transferability to different (6-4) lesions. Therefore, previously suggested mechanisms for the repair of the T(6-4)T lesion are here transferred to the T(6-4)C and C(6-4)T lesions and investigated theoretically using quantum chemical methods. Despite the different functional groups of the pyrimidine bases involved, a general valid molecular mechanism was identified, in which the initial step is an electron transfer coupled to a proton transfer from the protonated HIS365 to the N3(') nitrogen of the 3(') pyrimidine, followed by an intramolecular OH/NH2 transfer in one concerted step, which does not require an oxetane/azetidine or isolated water/ammonia intermediate. PMID:23821498

  7. CHBPR Proton Magnetic Resonance Spectroscopy Detection of Neurotransmitters in Dorsomedial Medulla Correlate with Spontaneous Baroreceptor Reflex Function

    PubMed Central

    Garcia-Espinosa, Maria A.; Shaltout, Hossam A.; Olson, John; Westwood, Brian M.; Robbins, Mike E.; Link, Kerry; Diz, Debra I.

    2010-01-01

    Control of heart rate variability (HRV) via modulation of sympathovagal balance is a key function of nucleus tractus solitarii (nTS) and dorsal motor nucleus of the vagus localized in the dorsomedial medulla oblongata. Normal blood pressure regulation involves precise balance of glutamate-glutamine-GABA (Glu-Gln-GABA) transmitter systems, and angiotensin (Ang) II modulates these transmitters to produce tonic suppression of reflex function. It is not known, however, whether other brain transmitters/metabolites are indicators of baroreflex function. This study establishes the concept that comprehensive baseline transmitter/metabolite profiles obtained using in vivo 1H Magnetic Resonance Spectroscopy (1H MRS) in rats with well characterized differences in resting blood pressure and baroreflex function can be used as indices of autonomic balance or baroreflex sensitivity. Glu concentration in dorsal medulla is significantly higher in ASrAogen rats compared to either SD and (mRen2)27. Glu levels and the ratio of Glu/Gln correlated positively with indices of higher vagal tone consistent with the importance of these neurotransmitters in baroreflex function. Interestingly, the levels of choline containing metabolites showed a significant positive correlation with spontaneous baroreflex sensitivity and a negative correlation with sympathetic tone. Thus, we demonstrate the concept that non-invasive assessment of neurochemical biomarkers may be used as an index of baroreflex sensitivity. PMID:20065146

  8. Predictors of CNS injury as measured by proton magnetic resonance spectroscopy in the setting of chronic HIV infection and CART.

    PubMed

    Harezlak, J; Cohen, R; Gongvatana, A; Taylor, M; Buchthal, S; Schifitto, G; Zhong, J; Daar, E S; Alger, J R; Brown, M; Singer, E J; Campbell, T B; McMahon, D; So, Y T; Yiannoutsos, C T; Navia, B A

    2014-06-01

    The reasons for persistent brain dysfunction in chronically HIV-infected persons on stable combined antiretroviral therapies (CART) remain unclear. Host and viral factors along with their interactions were examined in 260 HIV-infected subjects who underwent magnetic resonance spectroscopy (MRS). Metabolite concentrations (NAA/Cr, Cho/Cr, MI/Cr, and Glx/Cr) were measured in the basal ganglia, the frontal white matter, and gray matter, and the best predictive models were selected using a bootstrap-enhanced Akaike information criterion (AIC). Depending on the metabolite and brain region, age, race, HIV RNA concentration, ADC stage, duration of HIV infection, nadir CD4, and/or their interactions were predictive of metabolite concentrations, particularly the basal ganglia NAA/Cr and the mid-frontal NAA/Cr and Glx/Cr, whereas current CD4 and the CPE index rarely or did not predict these changes. These results show for the first time that host and viral factors related to both current and past HIV status contribute to persisting cerebral metabolite abnormalities and provide a framework for further understanding neurological injury in the setting of chronic and stable disease. PMID:24696364

  9. Neurochemical correlates of internet game play in adolescents with attention deficit hyperactivity disorder: A proton magnetic resonance spectroscopy (MRS) study.

    PubMed

    Bae, Sujin; Han, Doug Hyun; Kim, Sun Mi; Shi, Xianfeng; Renshaw, Perry F

    2016-08-30

    Previous studies have examined the relationship of brain metabolic changes in patients with attention deficit hyperactivity disorder (ADHD) and internet gaming disorder (IGD). However, these studies have been limited by a small number of subjects, a large variance in subject age, and different brain regions of interest. The present study assessed the effects of chronic internet game play in ADHD children. Twenty eight ADHD adolescents with IGD (IGD+ADHD), 27 ADHD adolescents without problematic internet game playing (ADHD only) and 42 healthy comparison adolescents (HC) were included in the study. Magnetic resonance spectroscopy (MRS) was performed on a 3T MRI scanner. Our results indicate that the levels of NAA in both ADHD groups were lower than those observed in the HC group. The levels of Glu+Gln in the ADHD only group were increased, compared to those observed in the control group. However, Glu+Gln was not increased in the IGD+ADHD group. In addition, the levels of Glu+Gln in the IGD+ADHD group were positively correlated with K-ARS total and inattention scores. ADHD and IGD subjects were both characterized by decreased NAA levels within the frontal lobe, consistent with hypofrontality. PMID:27295400

  10. Proton Nuclear Magnetic Resonance Spectroscopy as a Technique for Gentamicin Drug Susceptibility Studies with Escherichia coli ATCC 25922

    PubMed Central

    García-Álvarez, Lara; Busto, Jesús H.; Avenoza, Alberto; Sáenz, Yolanda; Peregrina, Jesús Manuel

    2015-01-01

    Antimicrobial drug susceptibility tests involving multiple time-consuming steps are still used as reference methods. Today, there is a need for the development of new automated instruments that can provide faster results and reduce operating time, reagent costs, and labor requirements. Nuclear magnetic resonance (NMR) spectroscopy meets those requirements. The metabolism and antimicrobial susceptibility of Escherichia coli ATCC 25922 in the presence of gentamicin have been analyzed using NMR and compared with a reference method. Direct incubation of the bacteria (with and without gentamicin) into the NMR tube has also been performed, and differences in the NMR spectra were obtained. The MIC, determined by the reference method found in this study, would correspond with the termination of the bacterial metabolism observed with NMR. Experiments carried out directly into the NMR tube enabled the development of antimicrobial drug susceptibility tests to assess the effectiveness of the antibiotic. NMR is an objective and reproducible method for showing the effects of a drug on the subject bacterium and can emerge as an excellent tool for studying bacterial activity in the presence of different antibiotic concentrations. PMID:25972417

  11. Proton Transport

    NASA Technical Reports Server (NTRS)

    Pohorille, Andrew; DeVincenzi, Donald L. (Technical Monitor)

    2001-01-01

    The transport of protons across membranes is an essential process for both bioenergetics of modern cells and the origins of cellular life. All living systems make use of proton gradients across cell walls to convert environmental energy into a high-energy chemical compound, adenosine triphosphate (ATP), synthesized from adenosine diphosphate. ATP, in turn, is used as a source of energy to drive many cellular reactions. The ubiquity of this process in biology suggests that even the earliest cellular systems were relying on proton gradient for harvesting environmental energy needed to support their survival and growth. In contemporary cells, proton transfer is assisted by large, complex proteins embedded in membranes. The issue addressed in this Study was: how the same process can be accomplished with the aid of similar but much simpler molecules that could have existed in the protobiological milieu? The model system used in the study contained a bilayer membrane made of phospholipid, dimyristoylphosphatidylcholine (DMPC) which is a good model of the biological membranes forming cellular boundaries. Both sides of the bilayer were surrounded by water which simulated the environment inside and outside the cell. Embedded in the membrane was a fragment of the Influenza-A M$_2$ protein and enough sodium counterions to maintain system neutrality. This protein has been shown to exhibit remarkably high rates of proton transport and, therefore, is an excellent model to study the formation of proton gradients across membranes. The Influenza M$_2$ protein is 97 amino acids in length, but a fragment 25 amino acids long. which contains a transmembrane domain of 19 amino acids flanked by three amino acids on each side. is sufficient to transport protons. Four identical protein fragments, each folded into a helix, aggregate to form small channels spanning the membrane. Protons are conducted through a narrow pore in the middle of the channel in response to applied voltage. This

  12. 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

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

    PubMed

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

    2016-09-01

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

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

    PubMed Central

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

    2015-01-01

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

  15. 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

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

    PubMed

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

    2013-09-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2014-04-01

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

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed Central

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

    2009-01-01

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

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

    PubMed Central

    Kolls, Jay K.

    2012-01-01

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

  2. 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.

  3. Proton-Nuclear Magnetic Resonance Analyses of the Substrate Specificity of a β-Ketolase from Pseudomonas putida, Acetopyruvate Hydrolase†

    PubMed Central

    Pokorny, Diana; Brecker, Lothar; Pogorevc, Mateja; Steiner, Walter; Griengl, Herfried; Kappe, Thomas; Ribbons, Douglas W.

    1999-01-01

    A revised purification of acetopyruvate hydrolase from orcinol-grown Pseudomonas putida ORC is described. This carbon-carbon bond hydrolase, which is the last inducible enzyme of the orcinol catabolic pathway, is monomeric with a molecular size of ∼38 kDa; it hydrolyzes acetopyruvate to equimolar quantities of acetate and pyruvate. We have previously described the aqueous-solution structures of acetopyruvate at pH 7.5 and several synthesized analogues by 1H-nuclear magnetic resonance (NMR)-Fourier transform (FT) experiments. Three 1H signals (2.2 to 2.4 ppm) of the methyl group are assigned unambiguously to the carboxylate anions of 2,4-diketo, 2-enol-4-keto, and 2-hydrate-4-keto forms (40:50:10). A 1H-NMR assay for acetopyruvate hydrolase was used to study the kinetics and stoichiometries of reactions within a single reaction mixture (0.7 ml) by monitoring the three methyl-group signals of acetopyruvate and of the products acetate and pyruvate. Examination of 4-tert-butyl-2,4-diketobutanoate hydrolysis by the same method allowed the conclusion that it is the carboxylate 2-enol form(s) or carbanion(s) that is the actual substrate(s) of hydrolysis. Substrate analogues of 2,4-diketobutanoate with 4-phenyl or 4-benzyl groups are very poor substrates for the enzyme, whereas the 4-cyclohexyl analogue is readily hydrolyzed. In aqueous solution, the arene analogues do not form a stable 2-enol structure but exist principally as a delocalized π-electron system in conjugation with the aromatic ring. The effects of several divalent metal ions on solution structures were studied, and a tentative conclusion that the enol forms are coordinated to Mg2+ bound to the enzyme was made. 1H–2H exchange reactions showed the complete, fast equilibration of 2H into the C-3 of acetopyruvate chemically; this accounts for the appearance of 2H in the product pyruvate. The C-3 of the product pyruvate was similarly labelled, but this exchange was only enzyme catalyzed; the methyl group of

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

    PubMed

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

    2013-04-01

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

  5. Proton conduction in biopolymer exopolysaccharide succinoglycan

    SciTech Connect

    Kweon, Jin Jung; Lee, Kyu Won; Kim, Hyojung; Lee, Cheol Eui; Jung, Seunho; Kwon, Chanho

    2014-07-07

    Protonic currents play a vital role in electrical signalling in living systems. It has been suggested that succinoglycan plays a specific role in alfalfa root nodule development, presumably acting as the signaling molecules. In this regard, charge transport and proton dynamics in the biopolymer exopolysaccharide succinoglycan have been studied by means of electrical measurements and nuclear magnetic resonance (NMR) spectroscopy. In particular, a dielectric dispersion in the system has revealed that the electrical conduction is protonic rather electronic. Besides, our laboratory- and rotating-frame {sup 1}H NMR measurements have elucidated the nature of the protonic conduction, activation of the protonic motion being associated with a glass transition.

  6. A Pilot In Vivo Proton Magnetic Resonance Spectroscopy Study of Amino Acid Neurotransmitter Response to Ketamine Treatment of Major Depressive Disorder

    PubMed Central

    Milak, Matthew S.; Proper, Caitlin J.; Mulhern, Stephanie T.; Parter, Amy L.; Kegeles, Lawrence S.; Ogden, R. Todd; Mao, Xiangling; Rodriguez, Carolyn I.; Oquendo, Maria A.; Suckow, Raymond F.; Cooper, Thomas B.; Keilp, John C.; Shungu, Dikoma C.; Mann, J. John

    2015-01-01

    The NMDA receptor antagonist ketamine can improve major depressive disorder (MDD) within hours. To evaluate the putative role of glutamatergic and GABAergic systems in ketamine’s antidepressant action, medial prefrontal cortical (mPFC) levels of glutamate + glutamine (Glx) and γ-aminobutyric acid (GABA) were measured before, during, and after ketamine administration using proton magnetic resonance spectroscopy. Ketamine (0.5 mg/kg i.v.) was administered to eleven depressed patients with MDD. Glx and GABA mPFC responses were measured as ratios relative to unsuppressed voxel tissue water (W) successfully in 8/11 patients. Ten of 11 patients remitted (50% reduction in 24-item Hamilton Depression Rating Scale and total ≤ 10) within 230 minutes of commencing ketamine. mPFC Glx/W and GABA/W peaked at 37.8%±7.5% and 38.0%±9.1% above baseline in ~26 minutes. Mean areas under the curve (AUC) for Glx/W (p = 0.025) and GABA/W (p = 0.005) increased and correlated (r = 0.796; p=0.018). Clinical improvement correlated with 90-minute norketamine concentration (df=6, r=−0.78, p=0.023), but no other measures. Rapid increases in Glx and GABA in MDD following ketamine administration support the postulated antidepressant role of glutamate and for the first time raises the question of GABA’s role in the antidepressant action of ketamine. These data support the hypothesis1 that ketamine administration may cause an initial increase in glutamate that potentially activates mammalian target of rapamycin (mTOR) pathway via AMPA receptors, since ketamine blocks NMDA receptors. The role of the contemporaneous surge in GABA remains to be determined.2 PMID:26283639

  7. Toxicometabolomics approach to urinary biomarkers for mercuric chloride (HgCl{sub 2})-induced nephrotoxicity using proton nuclear magnetic resonance ({sup 1}H NMR) in rats

    SciTech Connect

    Kim, Kyu-Bong; Um, So Young; Chung, Myeon Woo; Jung, Seung Chul; Oh, Ji Seon; Kim, Seon Hwa; Na, Han Sung; Lee, Byung Mu; Choi, Ki Hwan

    2010-12-01

    The primary objective of this study was to determine and characterize surrogate biomarkers that can predict nephrotoxicity induced by mercuric chloride (HgCl{sub 2}) using urinary proton nuclear magnetic resonance ({sup 1}H NMR) spectral data. A procedure for {sup 1}H NMR urinalysis using pattern recognition was proposed to evaluate nephrotoxicity induced by HgCl{sub 2} in Sprague-Dawley rats. HgCl{sub 2} at 0.1 or 0.75 mg/kg was administered intraperitoneally (i.p.), and urine was collected every 24 h for 6 days. Animals (n = 6 per group) were sacrificed 3 or 6 days post-dosing in order to perform clinical blood chemistry tests and histopathologic examinations. Urinary {sup 1}H NMR spectroscopy revealed apparent differential clustering between the control and HgCl{sub 2} treatment groups as evidenced by principal component analysis (PCA) and partial least square (PLS)-discriminant analysis (DA). Time- and dose-dependent separation of HgCl{sub 2}-treated animals from controls was observed by PCA of {sup 1}H NMR spectral data. In HgCl{sub 2}-treated rats, the concentrations of endogenous urinary metabolites of glucose, acetate, alanine, lactate, succinate, and ethanol were significantly increased, whereas the concentrations of 2-oxoglutarate, allantoin, citrate, formate, taurine, and hippurate were significantly decreased. These endogenous metabolites were selected as putative biomarkers for HgCl{sub 2}-induced nephrotoxicity. A dose response was observed in concentrations of lactate, acetate, succinate, and ethanol, where severe disruption of the concentrations of 2-oxoglutarate, citrate, formate, glucose, and taurine was observed at the higher dose (0.75 mg/kg) of HgCl{sub 2}. Correlation of urinary {sup 1}H NMR PLS-DA data with renal histopathologic changes suggests that {sup 1}H NMR urinalysis can be used to predict or screen for HgCl{sub 2}-induced nephrotoxicity{sub .}

  8. Neurochemical Alterations in Methamphetamine-Dependent Patients Treated with Cytidine-5′-Diphosphate Choline: A Longitudinal Proton Magnetic Resonance Spectroscopy Study

    PubMed Central

    Yoon, Sujung J; Lyoo, In Kyoon; Kim, Hengjun J; Kim, Tae-Suk; Sung, Young Hoon; Kim, Namkug; Lukas, Scott E; Renshaw, Perry F

    2010-01-01

    Cytidine-5′-diphosphate choline (CDP-choline), as an important intermediate for major membrane phospholipids, may exert neuroprotective effects in various neurodegenerative disorders. This longitudinal proton magnetic resonance spectroscopy (1H-MRS) study aimed to examine whether a 4-week CDP-choline treatment could alter neurometabolite levels in patients with methamphetamine (MA) dependence and to investigate whether changes in neurometabolite levels would be associated with MA use. We hypothesized that the prefrontal levels of N-acetyl-aspartate (NAA), a neuronal marker, and choline-containing compound (Cho), which are related to membrane turnover, would increase with CDP-choline treatment in MA-dependent patients. We further hypothesized that this increase would correlate with the total number of negative urine results. Thirty-one treatment seekers with MA dependence were randomly assigned to receive CDP-choline (n=16) or placebo (n=15) for 4 weeks. Prefrontal NAA and Cho levels were examined using 1H-MRS before medication, and at 2 and 4 weeks after treatment. Generalized estimating equation regression analyses showed that the rate of change in prefrontal NAA (p=0.005) and Cho (p=0.03) levels were greater with CDP-choline treatment than with placebo. In the CDP-choline-treated patients, changes in prefrontal NAA levels were positively associated with the total number of negative urine results (p=0.03). Changes in the prefrontal Cho levels, however, were not associated with the total number of negative urine results. These preliminary findings suggest that CDP-choline treatment may exert potential neuroprotective effects directly or indirectly because of reductions in drug use by the MA-dependent patients. Further studies with a larger sample size of MA-dependent patients are warranted to confirm a long-term efficacy of CDP-choline in neuroprotection and abstinence. PMID:20043005

  9. Metabolic Characterization of All-Trans-Retinoic Acid (ATRA)–Induced Craniofacial Development of Murine Embryos Using In Vivo Proton Magnetic Resonance Spectroscopy

    PubMed Central

    Peng, Lihong; Wu, Renhua; Hu, Xiao; Zhang, Guishan; Tang, Shijie

    2014-01-01

    Aim To characterize the abnormal metabolic profile of all-trans-retinoic acid (ATRA)–induced craniofacial development in mouse embryos using proton magnetic resonance spectroscopy (1H-MRS). Methods Timed-pregnant mice were treated by oral gavage on the morning of embryonic gestation day 11 (E11) with all-trans-retinoic acid (ATRA). Dosing solutions were adjusted by maternal body weight to provide 30, 70, or 100 mg/kg RA. The control group was given an equivalent volume of the carrier alone. Using an Agilent 7.0 T MR system and a combination of surface coil coils, a 3 mm×3 mm×3 mm 1H-MRS voxel was selected along the embryonic craniofacial tissue. 1H-MRS was performed with a single-voxel method using PRESS sequence and analyzed using LCModel software. Hematoxylin and eosin was used to detect and confirm cleft palate. Result 1H-MRS revealed elevated choline levels in embryonic craniofacial tissue in the RA70 and RA100 groups compared to controls (P<0.05). Increased choline levels were also found in the RA70 and RA100 groups compared with the RA30 group (P<0.01). High intra-myocellular lipids at 1.30 ppm (IMCL13) in the RA100 group compared to the RA30 group were found (P<0.01). There were no significant changes in taurine, intra-myocellular lipids at 2.10 ppm (IMCL21), and extra-myocellular lipids at 2.30 ppm (EMCL23). Cleft palate formation was observed in all fetuses carried by mice administered 70 and 100 mg/kg RA. Conclusions This novel study suggests that the elevated choline and lipid levels found by 1H-MRS may represent early biomarkers of craniofacial defects. Further studies will determine performance of this test and pathogenetic mechanisms of craniofacial malformation. PMID:24816763

  10. Analysis of brain metabolism by proton magnetic resonance spectroscopy (1H-MRS) in attention-deficit/hyperactivity disorder suggests a generalized differential ontogenic pattern from controls.

    PubMed

    Arcos-Burgos, Mauricio; Londoño, Ana C; Pineda, David A; Lopera, Francisco; Palacio, Juan David; Arbelaez, Andres; Acosta, Maria T; Vélez, Jorge I; Castellanos, Francisco Xavier; Muenke, Maximilian

    2012-12-01

    Attention-deficit/hyperactivity disorder (ADHD) is the most common behavioral disorder of childhood. Preliminary studies with proton magnetic resonance spectroscopy ((1)H-MRS) of the brain have reported differences in brain metabolite concentration-to-Cr ratios between individuals with ADHD and unaffected controls in several frontal brain regions including anterior cingulate cortex. Using multivoxel (1)H-MRS, we compared 14 individuals affected with ADHD to 20 individuals without ADHD from the same genetic isolate. After controlling by sex, age, and multiple testing, we found significant differences at the right posterior cingulate of the Glx/Cr ratio density distribution function between ADHD cases and controls (P < 0.05). Furthermore, we found several interactions of metabolite concentration-to-Cr ratio, age, and ADHD status: Ins/Cr and Glx/Cr ratios at the left posterior cingulate, and NAA/Cr at the splenius, right posterior cingulate, and at the left posterior cingulate. We also found a differential metabolite ratio interaction between ADHD cases and controls for Ins/Cr and NAA/Cr at the right striatum. These results show that: (1) NAA/Cr, Glx/Cr, and Ins/Cr ratios, as reported in other studies, exhibit significant differences between ADHD cases and controls; (2) differences of these metabolite ratios between ADHD cases and controls evolve in specific and recognizable patterns throughout age, a finding that replicates previous results obtained by structural MRI, where is demonstrated that brain ontogeny follows a different program in ADHD cases and controls; (3) Ins/Cr and NAA/Cr ratios, at the right striatum, interact in a differential way between ADHD cases and controls. As a whole, these results replicate previous 1H-MRS findings and add new intriguing differential metabolic and ontogeny patterns between ADHD cases and controls that warrant further pursue. PMID:23012086

  11. Cortico-Striatal GABAergic and Glutamatergic Dysregulations in Subjects at Ultra-High Risk for Psychosis Investigated with Proton Magnetic Resonance Spectroscopy

    PubMed Central

    Reyes-Madrigal, Francisco; Mao, Xiangling; León-Ortiz, Pablo; Rodríguez-Mayoral, Oscar; Solís-Vivanco, Rodolfo; Favila, Rafael; Graff-Guerrero, Ariel; Shungu, Dikoma C.

    2016-01-01

    Background: Dysregulations of the major inhibitory and excitatory amino neurotransmitter systems of γ-aminobutyric acid and glutamate, respectively, have been described in patients with schizophrenia. However, it is unclear whether these abnormalities are present in subjects at ultra-high risk for psychosis. Methods: Twenty-three antipsychotic naïve subjects at ultra-high risk and 24 healthy control subjects, matched for age, sex, handedness, cigarette smoking, and parental education, underwent proton magnetic resonance spectroscopy scans in the dorsal caudate bilaterally and the medial prefrontal cortex at 3T. Levels of γ-aminobutyric acid and of the combined resonance of glutamate and glutamine (Glx) were obtained using the standard J-editing technique and expressed as peak area ratios relative to the synchronously acquired unsuppressed voxel water signal. Results: Higher levels of γ-aminobutyric acid (P<.001) and Glx (P=.007) were found in the dorsal caudate of the subjects at ultra-high risk than in the healthy controls. In the medial prefrontal cortex, likewise, both γ-aminobutyric acid (P=.03) and Glx (P=.006) levels were higher in the ultra-high risk group than in the healthy controls. No group differences were found for any of the other metabolites (N-acetylaspartate, total choline, or total creatine) in the 2 regions of interest. Conclusions: This study presents the first evidence of abnormal elevations, in subjects at ultra-high risk, of γ-aminobutyric acid and Glx in 2 brain regions that have been implicated in the pathophysiology of psychosis, warranting longitudinal studies to assess whether these neurotransmitter abnormalities can serve as noninvasive biomarkers of conversion risk to psychosis as well as of illness progression and treatment response. PMID:26364273

  12. Evaluation of intracranial neoplasia and noninfectious meningoencephalitis in dogs by use of short echo time, single voxel proton magnetic resonance spectroscopy at 3.0 Tesla.

    PubMed

    Carrera, Inés; Richter, Henning; Beckmann, Katrin; Meier, Dieter; Dennler, Matthias; Kircher, Patrick R

    2016-05-01

    OBJECTIVE To investigate metabolite concentrations of the brains of dogs with intracranial neoplasia or noninfectious meningoencephalitis by use of short echo time, single voxel proton magnetic resonance spectroscopy ((1)H MRS) at 3.0 T. ANIMALS 29 dogs with intracranial lesions (14 with neoplasia [3 oligodendromas, 3 glioblastomas multiformes, 3 astrocytomas, 2 lymphomas, and 3 meningiomas] and 15 is with noninfectious meningoencephalitis) and 10 healthy control dogs. PROCEDURES Short echo time, single voxel (1)H-MRS at 3.0 T was performed on neoplastic and noninfectious inflammatory intracranial lesions identified with conventional MRI. Metabolites of interest included N-acetyl aspartate (NAA), total choline, creatine, myoinositol, the glutamine-glutamate complex (Glx), glutathione, taurine, lactate, and lipids. Data were analyzed with postprocessing fitting algorithm software. Metabolite concentrations relative to brain water content were calculated and compared with results for the healthy control dogs, which had been previously evaluated with the same (1)H MRS technique. RESULTS NAA, creatine, and Glx concentrations were reduced in the brains of dogs with neoplasia and noninfectious meningoencephalitis, whereas choline concentration was increased. Concentrations of these metabolites differed significantly between dogs with neoplasia and dogs with noninfectious meningoencephalitis. Concentrations of NAA, creatine, and Glx were significantly lower in dogs with neoplasia, whereas the concentration of choline was significantly higher in dogs with neoplasia. Lipids were predominantly found in dogs with high-grade intra-axial neoplasia, meningioma, and necrotizing meningoencephalitis. A high concentration of taurine was found in 10 of 15 dogs with noninfectious meningoencephalitis. CONCLUSIONS AND CLINICAL RELEVANCE (1)H MRS provided additional metabolic information about intracranial neoplasia and noninfectious meningoencephalitis in dogs. PMID:27111012

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2014-09-22

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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2005-05-01

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

  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, 2013 CFR

    2013-04-01

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

  20. 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...

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

    Code of Federal Regulations, 2012 CFR

    2012-04-01

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

  2. 26 CFR 1.883-4T - Qualified shareholder stock ownership test (temporary).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

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

  3. 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

  4. 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...

  5. 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...

  6. 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...

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

    PubMed Central

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

    2013-01-01

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

  8. 26 CFR 1.509(a)-4T - Supporting organizations (temporary).

    Code of Federal Regulations, 2014 CFR

    2014-04-01

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

  9. 26 CFR 1.509(a)-4T - Supporting organizations (temporary).

    Code of Federal Regulations, 2013 CFR

    2013-04-01

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

  10. 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

  11. 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.

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

    PubMed

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

    2011-01-01

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

  13. 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.

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

    PubMed Central

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

    2015-01-01

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

  15. 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

  16. 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

  17. 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

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

    PubMed Central

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

    2009-01-01

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

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

    PubMed

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

    2016-01-01

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

  20. 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

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

    PubMed

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

    2015-01-01

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

  2. Improvement of persistent magnetic field trapping in bulk Y-Ba-Cu-O superconductors

    NASA Technical Reports Server (NTRS)

    Chen, In-Gann; Weinstein, Roy

    1993-01-01

    For type-II superconductors, magnetic field can be trapped due to persistent internal supercurrent. Quasi-persistent magnetic fields near 2 T at 60 K (and 1.4 T at 77 K) have been measured in minimagnets made of proton-irradiated melt-textured Y-Ba-Cu-O (MT-Y123) samples. Using the trapping effect, high-field permanent magnets with dipole, quadrupole, or more complicated configurations can be made of existing MT-Y123 material, thus bypassing the need for high-temperature superconductor (HTS) wires. A phenomenological current model has been developed to account for the trapped field intensity and profile in HTS samples. This model is also a guide to select directions of materials development to further improve field trapping properties. General properties such as magnetic field intensities, spatial distributions, stabilities, and temperature dependence of trapped field are discussed.

  3. Pulse magnetic-induction regulator

    SciTech Connect

    Vainman, B.N.; Kuprin, A.P.

    1986-04-01

    To create magnetic fields with inductions of ca 4 T, the current in the electromagnet windings must reach tens of amperes, with a power consumptin of several kilowatts. This paper describes a variable pulse regulator of magnetic induction to 4 T in the gap of an electromagnet. The long-term relative magnetic-induction instability is ca 10/sup -4/ V/sup -1/. The low power dissipated by the switch allows natural air cooling to be used.

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

    PubMed Central

    Février, Michèle; Dorgham, Karim; Rebollo, Angelita

    2011-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

    Layman, Awo A K; Oliver, Paula M

    2016-05-15

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

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

    PubMed Central

    Ciabattini, Annalisa; Pettini, Elena; Medaglini, Donata

    2013-01-01

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

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

    PubMed

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

    2016-04-01

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

  11. Supplementation of Antipsychotic Treatment with the Amino Acid Sarcosine Influences Proton Magnetic Resonance Spectroscopy Parameters in Left Frontal White Matter in Patients with Schizophrenia

    PubMed Central

    Strzelecki, Dominik; Podgórski, Michał; Kałużyńska, Olga; Gawlik-Kotelnicka, Oliwia; Stefańczyk, Ludomir; Kotlicka-Antczak, Magdalena; Gmitrowicz, Agnieszka; Grzelak, Piotr

    2015-01-01

    Dysfunction of the glutamatergic system, the main stimulating system in the brain, has a major role in pathogenesis of schizophrenia. The frontal white matter (WM) is partially composed of axons from glutamatergic pyramidal neurons and glia with glutamatergic receptors. The natural amino acid sarcosine, a component of a normal diet, inhibits the glycine type 1 transporter, increasing the glycine level. Thus, it modulates glutamatergic transmission through the glutamatergic ionotropic NMDA (N-methyl-d-aspartate) receptor, which requires glycine as a co-agonist. To evaluate the concentrations of brain metabolites (NAA, N-acetylaspartate; Glx, complex of glutamate, glutamine, and γ-aminobutyric acid (GABA); mI, myo-inositol; Cr, creatine; Cho, choline) in the left frontal WM, Proton Nuclear Magnetic Resonance (1H-NMR) spectroscopy was used. Twenty-five patients randomly chosen from a group of fifty with stable schizophrenia (DSM-IV-TR) and dominant negative symptoms, who were receiving antipsychotic therapy, were administered 2 g of sarcosine daily for six months. The remaining 25 patients received placebo. Assignment was double blinded. 1H-NMR spectroscopy (1.5 T) was performed twice: before and after the intervention. NAA, Glx and mI were evaluated as Cr and Cho ratios. All patients were also assessed twice with the Positive and Negative Syndrome Scale (PANSS). Results were compared between groups and in two time points in each group. The sarcosine group demonstrated a significant decrease in WM Glx/Cr and Glx/Cho ratios compared to controls after six months of therapy. In the experimental group, the final NAA/Cr ratio significantly increased and Glx/Cr ratio significantly decreased compared to baseline values. Improvement in the PANSS scores was significant only in the sarcosine group. In patients with schizophrenia, sarcosine augmentation can reverse the negative effect of glutamatergic system overstimulation, with a simultaneous beneficial increase of NAA

  12. Supplementation of Antipsychotic Treatment with the Amino Acid Sarcosine Influences Proton Magnetic Resonance Spectroscopy Parameters in Left Frontal White Matter in Patients with Schizophrenia.

    PubMed

    Strzelecki, Dominik; Podgórski, Michał; Kałużyńska, Olga; Gawlik-Kotelnicka, Oliwia; Stefańczyk, Ludomir; Kotlicka-Antczak, Magdalena; Gmitrowicz, Agnieszka; Grzelak, Piotr

    2015-10-01

    Dysfunction of the glutamatergic system, the main stimulating system in the brain, has a major role in pathogenesis of schizophrenia. The frontal white matter (WM) is partially composed of axons from glutamatergic pyramidal neurons and glia with glutamatergic receptors. The natural amino acid sarcosine, a component of a normal diet, inhibits the glycine type 1 transporter, increasing the glycine level. Thus, it modulates glutamatergic transmission through the glutamatergic ionotropic NMDA (N-methyl-d-aspartate) receptor, which requires glycine as a co-agonist. To evaluate the concentrations of brain metabolites (NAA, N-acetylaspartate; Glx, complex of glutamate, glutamine, and γ-aminobutyric acid (GABA); mI, myo-inositol; Cr, creatine; Cho, choline) in the left frontal WM, Proton Nuclear Magnetic Resonance (¹H-NMR) spectroscopy was used. Twenty-five patients randomly chosen from a group of fifty with stable schizophrenia (DSM-IV-TR) and dominant negative symptoms, who were receiving antipsychotic therapy, were administered 2 g of sarcosine daily for six months. The remaining 25 patients received placebo. Assignment was double blinded. ¹H-NMR spectroscopy (1.5 T) was performed twice: before and after the intervention. NAA, Glx and mI were evaluated as Cr and Cho ratios. All patients were also assessed twice with the Positive and Negative Syndrome Scale (PANSS). Results were compared between groups and in two time points in each group. The sarcosine group demonstrated a significant decrease in WM Glx/Cr and Glx/Cho ratios compared to controls after six months of therapy. In the experimental group, the final NAA/Cr ratio significantly increased and Glx/Cr ratio significantly decreased compared to baseline values. Improvement in the PANSS scores was significant only in the sarcosine group. In patients with schizophrenia, sarcosine augmentation can reverse the negative effect of glutamatergic system overstimulation, with a simultaneous beneficial increase of NAA

  13. PERFORMANCE SUMMARY OF THE HELICAL MAGNETS FOR RHIC.

    SciTech Connect

    WILLEN,E.; ANERELLA,M.; ESCALLIER,J.; GANETIS,G.; GHOSH,A.; GUPTA,R.; HARRISON,M.; JAIN,A.; MACKAY,W.; MARONE,A.; MURATORE,J.; PLATE,S.; THOMAS,R.; WANDERER,P.; WU,K.C.; OKAMURA,M.

    2003-05-12

    A series of four Snake and eight Rotator superconducting helical magnet assemblies has been built and installed in RHIC to control the polarization of protons during acceleration and storage in that machine. Each of these assemblies consists of four 2.4 m long dipole magnets in each of which the field rotates through 360 degrees along the magnet's length. The magnets were made by winding one millimeter diameter superconducting 7-strand cable into slots milled into thick-walled aluminum tubes. The magnets produce 4 Tesla field at a current of 320 amperes and are quench-protected with 0.050 ohm resistors placed across the winding in each slot. A total of 48 of these 2.4 m magnets has been built, tested and installed. This paper summarizes their quench performance as well as their field uniformity, of which the integral field is the most critical. All magnets reached the required operating field level of 4 T, and the integral field of the magnets was generally about half of the maximum permissible level of 0.050 Tesla meters.

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

    PubMed Central

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

    2014-01-01

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

  15. 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

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

    PubMed

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

    2014-05-27

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

  17. 26 CFR 1.905-4T - Notification of foreign tax redetermination (temporary).

    Code of Federal Regulations, 2011 CFR

    2011-04-01

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

  18. 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

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

    PubMed

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

    2014-11-01

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

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

    PubMed

    Aman, M J; Tretter, T; Eisenbeis, I; Bug, G; Decker, T; Aulitzky, W E; Tilg, H; Huber, C; Peschel, C

    1996-06-01

    In the present study, we investigated the effect of interferon-alpha (IFN-alpha) on the expression of interleukin-10 (IL-10) mRNA and protein synthesis in human monocytes and CD4+ T cells. In mononuclear cells, IFN-alpha induced expression of IL-10 mRNA and further enhanced lipopolysaccharide (LPS)-stimulated IL-10 expression. In purified monocytes, a strong expression of IL-10 mRNA induced by LPS was not further enhanced by IFN-alpha. In highly purified CD4+ T cells, IFN-alpha upregulated IL-10 mRNA upon activation with phytohemagglutinin and phorbol myristate acetate. In purified monocytes, an effect of IFN-alpha on IL-10 protein synthesis was dependent on costimulation with LPS. Maximal stimulation of IL-10 protein by IFN-alpha was seen after prolonged incubation periods of 48 to 96 hours, whereas IFN-gamma reduced IL-10 production in the early incubation period. Similar effects of IFN-alpha were observed in CD4+ T cells activated with CD3 and CD28 monoclonal antibodies. Addition of IFN-alpha caused an increase of IL-10 in culture supernatants of activated T-helper cells of more than 100% after 96 hours of incubation. In contrast, other cytokines, including IFN-gamma and IL-4, had no influence on IL-10 secretion stimulated by CD3 and CD28 in CD4+ T cells. In serum samples of IFN-alpha-treated individuals, we failed to detect an influence of cytokine treatment on IL-10 serum levels, confirming the requirement of additional activating signals for IFN-alpha-mediated effects on IL-10 synthesis. In conclusion, IFN-alpha enhances the late induction of IL-10, which physiologically occurs upon stimulation of monocytes and T cells. Biologically, this effect might enhance the negative-feedback mechanism ascribed to IL-10, which limits inflammatory reactions. PMID:8639843

  1. E4BP4 overexpression: a protective mechanism in CD4+ T cells from SLE patients.

    PubMed

    Zhao, Ming; Liu, Qian; Liang, Gongping; Wang, Litao; Luo, Shuangyan; Tang, Qian; Zhao, Hongjun; Su, Yuwen; Yung, Susan; Chan, Tak Mao; Lu, Qianjin

    2013-03-01

    Systemic lupus erythematosus (SLE) is a prototype autoimmune disease characterized by various immunological abnormalities, including dysregulated activation of T and B lymphocytes, which trigger autoantibody production and immune-complex deposition. E4BP4, also known as NFIL3, has emerged as a major transcription factor that regulates the development and function of immune cells in a number of lineages. E4BP4 has been shown to regulate cytokines expression, and its synthesis is in turn controlled by various cytokines. To date, the roles of E4BP4 in immune dysregulation and autoimmune disorders are unclear. In this study, we demonstrated that E4BP4 expression is increased in CD4(+) T cells isolated from patients with active systemic lupus erythematosus (SLE), especially in patients treated with glucocorticoid (GC). Increased expression of E4BP4 inhibited the activation and self-reactivity of T cells stimulated by anti-CD3/CD28 antibodies. In contrast, the self-reactivity was enhanced in CD4(+) T cells from SLE patients following E4BP4 gene silencing and the production of autoantibody was increased in autologous B cells. We further demonstrated that E4BP4 directly regulated CD40L expression by binding to the promoter region and altering histone acetylation and methylation of the CD40L loci. Taken together, our data provide evidence that E4BP4 can inhibit CD40L expression through epigenetic modifications in the promoter region of CD40L, thus negatively regulating self-reactivity of SLE CD4(+) T cells. Furthermore, our data demonstrate that overexpression of E4BP4 initiates a protective mechanism in SLE CD4(+) T cells, which may be a promising target in the therapy for SLE. PMID:23340290

  2. CD4+ T cell responses to self- and mutated p53 determinants during tumorigenesis in mice.

    PubMed

    Fedoseyeva, E V; Boisgérault, F; Anosova, N G; Wollish, W S; Arlotta, P; Jensen, P E; Ono, S J; Benichou, G

    2000-06-01

    We analyzed CD4+ T helper responses to wild-type (wt) and mutated (mut) p53 protein in normal and tumor-bearing mice. In normal mice, we observed that although some self-p53 determinants induced negative selection of p53-reactive CD4+ T cells, other p53 determinants (cryptic) were immunogenic. Next, BALB/c mice were inoculated with J774 syngeneic tumor cell line expressing mut p53. BALB/c tumor-bearing mice mounted potent CD4+ T cell responses to two formerly cryptic peptides on self-p53. This response was characterized by massive production of IL-5, a Th2-type lymphokine. Interestingly, we found that T cell response was induced by different p53 peptides depending upon the stage of cancer. Mut p53 gene was shown to contain a single mutation resulting in the substitution of a tyrosine by a histidine at position 231 of the protein. Two peptides corresponding to wt and mutated sequences of this region were synthesized. Both peptides bound to the MHC class II-presenting molecule (Ed) with similar affinities. However, only mut p53.225-239 induced T cell responses in normal BALB/c mice, a result strongly suggesting that high-affinity wt p53.225-239 autoreactive T cells had been eliminated in these mice. Surprisingly, CD4+ T cell responses to both mut and wt p53.225-239 peptides were recorded in J774 tumor-bearing mice, a phenomenon attributed to the recruitment of low-avidity p53.225-239 self-reactive T cells. PMID:10820239

  3. Innate lymphoid cells regulate CD4+ T-cell responses to intestinal commensal bacteria.

    PubMed

    Hepworth, Matthew R; Monticelli, Laurel A; Fung, Thomas C; Ziegler, Carly G K; Grunberg, Stephanie; Sinha, Rohini; Mantegazza, Adriana R; Ma, Hak-Ling; Crawford, Alison; Angelosanto, Jill M; Wherry, E John; Koni, Pandelakis A; Bushman, Frederic D; Elson, Charles O; Eberl, Gérard; Artis, David; Sonnenberg, Gregory F

    2013-06-01

    Innate lymphoid cells (ILCs) are a recently characterized family of immune cells that have critical roles in cytokine-mediated regulation of intestinal epithelial cell barrier integrity. Alterations in ILC responses are associated with multiple chronic human diseases, including inflammatory bowel disease, implicating a role for ILCs in disease pathogenesis. Owing to an inability to target ILCs selectively, experimental studies assessing ILC function have predominantly used mice lacking adaptive immune cells. However, in lymphocyte-sufficient hosts ILCs are vastly outnumbered by CD4(+) T cells, which express similar profiles of effector cytokines. Therefore, the function of ILCs in the presence of adaptive immunity and their potential to influence adaptive immune cell responses remain unknown. To test this, we used genetic or antibody-mediated depletion strategies to target murine ILCs in the presence of an adaptive immune system. We show that loss of retinoic-acid-receptor-related orphan receptor-γt-positive (RORγt(+)) ILCs was associated with dysregulated adaptive immune cell responses against commensal bacteria and low-grade systemic inflammation. Remarkably, ILC-mediated regulation of adaptive immune cells occurred independently of interleukin (IL)-17A, IL-22 or IL-23. Genome-wide transcriptional profiling and functional analyses revealed that RORγt(+) ILCs express major histocompatibility complex class II (MHCII) and can process and present antigen. However, rather than inducing T-cell proliferation, ILCs acted to limit commensal bacteria-specific CD4(+) T-cell responses. Consistent with this, selective deletion of MHCII in murine RORγt(+) ILCs resulted in dysregulated commensal bacteria-dependent CD4(+) T-cell responses that promoted spontaneous intestinal inflammation. These data identify that ILCs maintain intestinal homeostasis through MHCII-dependent interactions with CD4(+) T cells that limit pathological adaptive immune cell responses to commensal

  4. Analysis of Virus-Specific CD4+ T Cells during Long-Term Gammaherpesvirus Infection

    PubMed Central

    Flaño, Emilio; Woodland, David L.; Blackman, Marcia A.; Doherty, Peter C.

    2001-01-01

    Major histocompatibility complex class II-mediated antigen presentation after intranasal infection with murine gammaherpesvirus 68 differs in mediastinal lymph nodes and spleen. Evidence that virus-specific CD4+ T cells were being stimulated was found as late as 6 to 8 months after infection, and cells specific for the viral gp15067–83 and ORF11168–180 peptides were maintained as a fairly stable proportion of the total response. PMID:11462049

  5. Memory CD4 T cells emerge from effector T-cell progenitors.

    PubMed

    Harrington, Laurie E; Janowski, Karen M; Oliver, James R; Zajac, Allan J; Weaver, Casey T

    2008-03-20

    A hallmark of adaptive immunity is the generation of memory T cells that confer long-lived, antigen-specific protection against repeat challenges by pathogens. Understanding the mechanisms by which memory T cells arise is important for rational vaccination strategies and improved therapeutic interventions for chronic infections and autoimmune disorders. The large clonal expansion of CD8 T cells in response to some infections has made the development of CD8 T-cell memory more amenable to study, giving rise to a model of memory cell differentiation in which a fraction of fully competent effector T cells transition into long-lived memory T cells. Delineation of CD4 T-cell memory development has proved more difficult as a result of limitations on tracking the smaller populations of CD4 effector T cells generated during a pathogenic challenge, complicating efforts to determine whether CD4 memory T cells are direct descendants of effector T cells or whether they develop by alternative pathways. Here, using two complementary cytokine reporter mouse models to identify interferon (IFN)-gamma-positive effector T cells and track their fate, we show that the lineage relationship between effector and memory CD4 T cells resembles that for CD8 T cells responding to the same pathogen. We find that, in parallel with effector CD8 T cells, IFN-gamma-positive effector CD4 T cells give rise to long-lived memory T cells capable of anamnestic responses to antigenic rechallenge. PMID:18322463

  6. 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

  7. Expanding Roles for CD4 T Cells and Their Subpopulations in Tumor Immunity and Therapy

    PubMed Central

    Dobrzanski, Mark J.

    2013-01-01

    The importance of CD4 T cells in orchestrating the immune system and their role in inducing effective T cell-mediated therapies for the treatment of patients with select established malignancies are undisputable. Through a complex and balanced array of direct and indirect mechanisms of cellular activation and regulation, this functionally diverse family of lymphocytes can potentially promote tumor eradication, long-term tumor immunity, and aid in establishing and/or rebalancing immune cell homeostasis through interaction with other immune cell populations within the highly dynamic tumor environment. However, recent studies have uncovered additional functions and roles for CD4 T cells, some of which are independent of other lymphocytes, that can not only influence and contribute to tumor immunity but paradoxically promote tumor growth and progression. Here, we review the recent advances in our understanding of the various CD4 T cell lineages and their signature cytokines in disease progression and/or regression. We discuss their direct and indirect mechanistic interplay among themselves and with other responding cells of the antitumor response, their potential roles and abilities for “plasticity” and memory cell generation within the hostile tumor environment, and their potentials in cancer treatment and immunotherapy. PMID:23533029

  8. NAFLD causes selective CD4(+) T lymphocyte loss and promotes hepatocarcinogenesis.

    PubMed

    Ma, Chi; Kesarwala, Aparna H; Eggert, Tobias; Medina-Echeverz, José; Kleiner, David E; Jin, Ping; Stroncek, David F; Terabe, Masaki; Kapoor, Veena; ElGindi, Mei; Han, Miaojun; Thornton, Angela M; Zhang, Haibo; Egger, Michèle; Luo, Ji; Felsher, Dean W; McVicar, Daniel W; Weber, Achim; Heikenwalder, Mathias; Greten, Tim F

    2016-03-10

    Hepatocellular carcinoma (HCC) is the second most common cause of cancer-related death. Non-alcoholic fatty liver disease (NAFLD) affects a large proportion of the US population and is considered to be a metabolic predisposition to liver cancer. However, the role of adaptive immune responses in NAFLD-promoted HCC is largely unknown. Here we show, in mouse models and human samples, that dysregulation of lipid metabolism in NAFLD causes a selective loss of intrahepatic CD4(+) but not CD8(+) T lymphocytes, leading to accelerated hepatocarcinogenesis. We also demonstrate that CD4(+) T lymphocytes have greater mitochondrial mass than CD8(+) T lymphocytes and generate higher levels of mitochondrially derived reactive oxygen species (ROS). Disruption of mitochondrial function by linoleic acid, a fatty acid accumulated in NAFLD, causes more oxidative damage than other free fatty acids such as palmitic acid, and mediates selective loss of intrahepatic CD4(+) T lymphocytes. In vivo blockade of ROS reversed NAFLD-induced hepatic CD4(+) T lymphocyte decrease and delayed NAFLD-promoted HCC. Our results provide an unexpected link between lipid dysregulation and impaired anti-tumour surveillance. PMID:26934227

  9. Endogenous antigen processing drives the primary CD4+ T cell response to influenza

    PubMed Central

    Miller, Michael A.; Ganesan, Asha Purnima V.; Luckashenak, Nancy; Mendonca, Mark; Eisenlohr, Laurence C.

    2015-01-01

    By convention, CD4+ T lymphocytes recognize foreign and self peptides derived from internalized antigens in combination with MHC class II molecules. Alternative pathways of epitope production have been identified but their contributions to host defense have not been established. We show here in a mouse infection model that the CD4+ T cell response to influenza, critical for durable protection from the virus, is driven principally by unconventional processing of antigen synthesized within the infected antigen-presenting cell, not by classical processing of endocytosed virions or material from infected cells. Investigation of the cellular components involved, including the H2-M molecular chaperone, the proteasome, and gamma-interferon inducible lysosomal thiol reductase revealed considerable heterogeneity in the generation of individual epitopes, an arrangement that ensures peptide diversity and broad CD4+ T cell engagement. These results could fundamentally revise strategies for rational vaccine design and may lead to key insights into the induction of autoimmune and anti-tumor responses. PMID:26413780

  10. 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

  11. 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

  12. 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

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

    PubMed

    Warth, Sebastian C; Heissmeyer, Vigo

    2013-01-01

    Regulatory T cells (Tregs) are essential to provide immune tolerance to self as well as to certain foreign antigens. Tregs can be generated from naive CD4 T cells in vitro with TCR- and co-stimulation in the presence of TGFβ and IL-2. This bears enormous potential for future therapies, however, the molecules and signaling pathways that control differentiation are largely unknown. Primary T cells can be manipulated through ectopic gene expression, but common methods fail to target the most important naive state of the T cell prior to primary antigen recognition. Here, we provide a protocol to express ectopic genes in naive CD4 T cells in vitro before inducing Treg differentiation. It applies transduction with the replication-deficient adenovirus and explains its generation and production. The adenovirus can take up large inserts (up to 7 kb) and can be equipped with promoters to achieve high and transient overexpression in T cells. It effectively transduces naive mouse T cells if they express a transgenic Coxsackie adenovirus receptor (CAR). Importantly, after infection the T cells remain naive (CD44(low), CD62L(high)) and resting (CD25(-), CD69(-)) and can be activated and differentiated into Tregs similar to non-infected cells. Thus, this method enables manipulation of CD4 T cell differentiation from its very beginning. It ensures that ectopic gene expression is already in place when early signaling events of the initial TCR stimulation induces cellular changes that eventually lead into Treg differentiation. PMID:23979424

  14. Transcription regulates HIF-1α expression in CD4(+) T cells.

    PubMed

    Bollinger, Thomas; Bollinger, Annalena; Gies, Sydney; Feldhoff, Lea; Solbach, Werner; Rupp, Jan

    2016-01-01

    The transcription factor hypoxia inducible factor-1α (HIF-1α) mediates the metabolic adaptation of cells to hypoxia and T-helper cell fate. However, HIF-1α regulation in CD4(+) T cells (T cells) remains elusive. Here we observed that depletion of oxygen (O2⩽2%) alone was not sufficient to induce HIF-1α expression in T cells. However, when hypoxic T cells were stimulated, HIF-1α was expressed and this was dependent on nuclear factor-κB- and nuclear factor of activated T cell (NFAT)-mediated transcriptional upregulation of Hif-1α mRNA. HIF-1α upregulation could be blocked by drugs inhibiting NF-κB, NFAT or mammalian target of rapamycin precluding CD4(+) T-cell stimulation or translation in T cells, as well as by blocking transcription. CD3, CD28, phorbol-12-myristat-13-acetat (PMA) or ionomycin-stimulated T cells did not express HIF-1α under normoxic conditions. In conclusion, regulation of HIF-1α expression in CD4(+) T cells in hypoxia gravely relies on its transcriptional upregulation and subsequent enhanced protein stabilization. PMID:26150319

  15. NK cell regulation of CD4 T cell-mediated graft-versus-host disease.

    PubMed

    Noval Rivas, Magali; Hazzan, Marc; Weatherly, Kathleen; Gaudray, Florence; Salmon, Isabelle; Braun, Michel Y

    2010-06-15

    CD3-negative NK cells are granular lymphocytes capable of producing inflammatory cytokines and killing malignant, infected, or stressed cells. We have recently observed a new role for NK cells in the control of the proliferation of CD4 T cells under persistent antigenic stimulation. Monoclonal anti-male CD4 T cells transferred into Rag2-/- male recipients did not expand or were rapidly eliminated. Remarkably, T cells transferred into NK cell-deficient Rag2-/- Il-2Rgammac-/- male hosts expanded extensively and mediated tissue lesions usually observed in chronic graft-versus-host disease (GVHD). T cell failure to proliferate and to induce chronic GVHD was the result of NK cell activity, because depletion of the recipient's NK1.1+ cells by Ab treatment induced T cell expansion and chronic GVHD. T cells under chronic Ag stimulation upregulated ligands of the activating receptor NKG2D, and regulatory activity of NK cells was inhibited by the injection of Abs directed to NKG2D. On the contrary, blocking NKG2A inhibitory receptors did not increase NK cell regulatory activity. Finally, we show that NK regulation of T cell expansion did not involve perforin-mediated lytic activity of NK cells, but depended on T cell surface expression of a functional Fas molecule. These results highlight the potential role played by NK cells in controlling the Ag-specific CD4+ T cells responsible for chronic GVHD. PMID:20488796

  16. Role of acid sphingomyelinase bioactivity in human CD4+ T-cell activation and immune responses

    PubMed Central

    Bai, A; Kokkotou, E; Zheng, Y; Robson, S C

    2015-01-01

    Acid sphingomyelinase (ASM), a lipid hydrolase enzyme, has the potential to modulate various cellular activation responses via the generation of ceramide and by interaction with cellular receptors. We have hypothesized that ASM modulates CD4+ T-cell receptor activation and impacts immune responses. We first observed interactions of ASM with the intracellular domains of both CD3 and CD28. ASM further mediates T-cell proliferation after anti-CD3/CD28 antibody stimulation and alters CD4+ T-cell activation signals by generating ceramide. We noted that various pharmacological inhibitors of ASM or knockdown of ASM using small hairpin RNA inhibit CD3/CD28-mediated CD4+ T-cell proliferation and activation. Furthermore, such blockade of ASM bioactivity by biochemical inhibitors and/or molecular-targeted knockdown of ASM broadly abrogate T-helper cell responses. In conclusion, we detail immune, pivotal roles of ASM in adaptive immune T-cell responses, and propose that these pathways might provide novel targets for the therapy of autoimmune and inflammatory diseases. PMID:26203857

  17. Coordinated Changes in DNA Methylation in Antigen-Specific Memory CD4 T Cells

    PubMed Central

    Ogoshi, Katsumi; Sasaki, Atsushi; Abe, Jun; Qu, Wei; Nakatani, Yoichiro; Ahsan, Budrul; Oshima, Kenshiro; Shand, Francis H. W.; Ametani, Akio; Suzuki, Yutaka; Kaneko, Shuichi; Wada, Takashi; Hattori, Masahira; Sugano, Sumio; Morishita, Shinichi; Matsushima, Kouji

    2013-01-01

    Memory CD4+ T cells are central regulators of both humoral and cellular immune responses. T cell differentiation results in specific changes in chromatin structure and DNA methylation of cytokine genes. Although the methylation status of a limited number of gene loci in T cells has been examined, the genome-wide DNA methylation status of memory CD4+ T cells remains unexplored. To further elucidate the molecular signature of memory T cells, we conducted methylome and transcriptome analyses of memory CD4+ T cells generated using T cells from TCR-transgenic mice. The resulting genome-wide DNA methylation profile revealed 1144 differentially methylated regions (DMRs) across the murine genome during the process of T cell differentiation, 552 of which were associated with gene loci. Interestingly, the majority of these DMRs were located in introns. These DMRs included genes such as CXCR6, Tbox21, Chsy1, and Cish, which are associated with cytokine production, homing to bone marrow, and immune responses. Methylation changes in memory T cells exposed to specific Ag appeared to regulate enhancer activity rather than promoter activity of immunologically relevant genes. In addition, methylation profiles differed between memory T cell subsets, demonstrating a link between T cell methylation status and T cell differentiation. By comparing DMRs between naive and Ag-specific memory T cells, this study provides new insights into the functional status of memory T cells. PMID:23509353

  18. 26 CFR 1.103(n)-4T - Elective carryforward of unused private activity bond limit (temporary).

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... carryforward for any one or more projects described in A-5 of this § 1.103(n)-4T (carryforward projects). Q-2... titled “Carryforward election under section 103(n)”. (ii) The statement required by (i) of this A-2 shall... bond limit (temporary). 1.103(n)-4T Section 1.103(n)-4T Internal Revenue INTERNAL REVENUE...

  19. 26 CFR 1.103(n)-4T - Elective carryforward of unused private activity bond limit (temporary).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... carryforward for any one or more projects described in A-5 of this § 1.103(n)-4T (carryforward projects). Q-2... titled “Carryforward election under section 103(n)”. (ii) The statement required by (i) of this A-2 shall... bond limit (temporary). 1.103(n)-4T Section 1.103(n)-4T Internal Revenue INTERNAL REVENUE...

  20. Numerical study of remote detection outside the magnet with travelling wave Magnetic Resonance Imaging at 3T

    NASA Astrophysics Data System (ADS)

    López, M.; Vázquez, F.; Solís-Nájera, S.; Rodriguez, A. O.

    2015-01-01

    The use of the travelling wave approach for high magnetic field magnetic resonance imaging has been used recently with very promising results. This approach offer images one with greater field-of-view and a reasonable signal-to-noise ratio using a circular waveguide. This scheme has been proved to be successful at 7 T and 9.4 T with whole-body imager. Images have also been acquired with clinical magnetic resonance imaging systems whose resonant frequencies were 64 MHz and 128 MHz. These results motivated the use of remote detection of the magnetic resonance signal using a parallel-plate waveguide together with 3 T clinical scanners, to acquired human leg images. The cut-off frequency of this waveguide is zero for the principal mode, allowing us to overcome the barrier of transmitting waves at lower frequency than 300 MHz or 7 T for protons. These motivated the study of remote detection outside the actual magnet. We performed electromagnetic field simulations of a parallel-plate waveguide and a phantom. The signal transmission was done at 128 MHz and using a circular surface coil located almost 200 cm away for the magnet isocentre. Numerical simulations demonstrated that the magnetic field of the principal mode propagate inside a waveguide outside the magnet. Numerical results were compared with previous experimental-acquired image data under similar conditions.

  1. Proton therapy

    MedlinePlus

    ... skin redness in the radiation area, and temporary hair loss. AFTER THE PROCEDURE Following proton therapy, you should be able to resume your normal activities. You will likely see your doctor every 3 to 4 months for a follow-up exam.

  2. 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

  3. Autophagy Restricts HIV-1 Infection by Selectively Degrading Tat in CD4+ T Lymphocytes

    PubMed Central

    Sagnier, Sophie; Daussy, Coralie F.; Borel, Sophie; Robert-Hebmann, Véronique; Faure, Mathias; Blanchet, Fabien P.; Beaumelle, Bruno; Biard-Piechaczyk, Martine

    2014-01-01

    ABSTRACT Autophagy is a ubiquitous mechanism involved in the lysosomal-mediated degradation of cellular components when they are engulfed in vacuoles called autophagosomes. Autophagy is also recognized as an important regulator of the innate and adaptive immune responses against numerous pathogens, which have, therefore, developed strategies to block or use the autophagy machinery to their own benefit. Upon human immunodeficiency virus type 1 (HIV-1) infection, viral envelope (Env) glycoproteins induce autophagy-dependent apoptosis of uninfected bystander CD4+ T lymphocytes, a mechanism likely contributing to the loss of CD4+ T cells. In contrast, in productively infected CD4+ T cells, HIV-1 is able to block Env-induced autophagy in order to avoid its antiviral effect. To date, nothing is known about how autophagy restricts HIV-1 infection in CD4+ T lymphocytes. Here, we report that autophagy selectively degrades the HIV-1 transactivator Tat, a protein essential for viral transcription and virion production. We demonstrated that this selective autophagy-mediated degradation of Tat relies on its ubiquitin-independent interaction with the p62/SQSTM1 adaptor. Taken together, our results provide evidence that the anti-HIV effect of autophagy is specifically due to the degradation of the viral transactivator Tat but that this process is rapidly counteracted by the virus to favor its replication and spread. IMPORTANCE Autophagy is recognized as one of the most ancient and conserved mechanisms of cellular defense against invading pathogens. Cross talk between HIV-1 and autophagy has been demonstrated depending on the virally challenged cell type, and HIV-1 has evolved strategies to block this process to replicate efficiently. However, the mechanisms by which autophagy restricts HIV-1 infection remain to be elucidated. Here, we report that the HIV-1 transactivator Tat, a protein essential for viral replication, is specifically degraded by autophagy in CD4+ T lymphocytes

  4. Effect of Carr-Purcell refocusing pulse trains on transverse relaxation times of metabolites in rat brain at 9.4 T

    PubMed Central

    Deelchand, Dinesh Kumar; Henry, Pierre-Gilles; Marjańska, Małgorzata

    2014-01-01

    Purpose To investigate the effect of Carr-Purcell (CP) pulse trains on transverse relaxation times, T2, of tissue water and metabolites (both non-coupled and J-coupled spins) in the rat brain at 9.4 T using LASER, CP-LASER and T2ρ-LASER sequences. Methods Proton NMR spectra were measured in rat brain in vivo at 9.4 T. Spectra were acquired at multiple echo times ranging from 18 to 402 ms. All spectra were analyzed using LCModel with simulated basis sets. Signals of metabolites as a function of echo time were fitted using a mono-exponential function to determine their T2 relaxation times. Results Measured T2s for tissue water and all metabolites were significantly longer with CP-LASER and T2ρ-LASER compared to LASER. The T2 increased by a factor of ~1.3 for non-coupled and weakly coupled spins (e.g., N-acetylaspartate and total creatine) and by a factor of ~2 (e.g., glutamine and taurine) to ~4 (e.g., glutamate and myo-inositol) for strongly coupled spins. Conclusion Application of a CP pulse train results in a larger increase in T2 relaxation times for strongly coupled spins than for non-coupled (singlet) and weakly coupled spins. This needs to be taken into account when correcting for T2 relaxation in CP-like sequences such as LASER. PMID:24436256

  5. 800-MeV magnetic-focused flash proton radiography for high-contrast imaging of low-density biologically-relevant targets using an inverse-scatter collimator

    NASA Astrophysics Data System (ADS)

    Freeman, Matthew S.; Allison, Jason; Espinoza, Camilo; Goett, John Jerome; Hogan, Gary; Hollander, Brian; Kwiatkowski, Kris; Lopez, Julian; Mariam, Fesseha; Martinez, Michael; Medina, Jason; Medina, Patrick; Merrill, Frank E.; Morley, Deborah; Morris, Chris; Murray, Matthew; Nedrow, Paul; Saunders, Alexander; Schurman, Tamsen; Sisneros, Thomas; Tainter, Amy; Trouw, Frans; Tupa, Dale; Tybo, Josh; Wilde, Carl

    2016-03-01

    Proton radiography shows great promise as a tool to guide proton beam therapy (PBT) in real time. Here, we demonstrate two ways in which the technology may progress towards that goal. Firstly, with a proton beam that is 800 MeV in energy, target tissue receives a dose of radiation with very tight lateral constraint. This could present a benefit over the traditional treatment energies of ~200 MeV, where up to 1 cm of lateral tissue receives scattered radiation at the target. At 800 MeV, the beam travels completely through the object with minimal deflection, thus constraining lateral dose to a smaller area. The second novelty of this system is the utilization of magnetic quadrupole refocusing lenses that mitigate the blur caused by multiple Coulomb scattering within an object, enabling high resolution imaging of thick objects, such as the human body. This system is demonstrated on ex vivo salamander and zebrafish specimens, as well as on a realistic hand phantom. The resulting images provide contrast sufficient to visualize thin tissue, as well as fine detail within the target volumes, and the ability to measure small changes in density. Such a system, combined with PBT, would enable the delivery of a highly specific dose of radiation that is monitored and guided in real time.

  6. Vaccine-Induced CD107a+ CD4+ T Cells Are Resistant to Depletion following AIDS Virus Infection

    PubMed Central

    Terahara, Kazutaka; Ishii, Hiroshi; Nomura, Takushi; Takahashi, Naofumi; Takeda, Akiko; Shiino, Teiichiro; Tsunetsugu-Yokota, Yasuko

    2014-01-01

    ABSTRACT CD4+ T-cell responses are crucial for effective antibody and CD8+ T-cell induction following virus infection. However, virus-specific CD4+ T cells can be preferential targets for human immunodeficiency virus (HIV) infection. HIV-specific CD4+ T-cell induction by vaccination may thus result in enhancement of virus replication following infection. In the present study, we show that vaccine-elicited CD4+ T cells expressing CD107a are relatively resistant to depletion in a macaque AIDS model. Comparison of virus-specific CD107a, macrophage inflammatory protein-1β, gamma interferon, tumor necrosis factor alpha, and interleukin-2 responses in CD4+ T cells of vaccinated macaques prechallenge and 1 week postchallenge showed a significant reduction in the CD107a− but not the CD107a+ subset after virus exposure. Those vaccinees that failed to control viremia showed a more marked reduction and exhibited significantly higher viral loads at week 1 than unvaccinated animals. Our results indicate that vaccine-induced CD107a− CD4+ T cells are depleted following virus infection, suggesting a rationale for avoiding virus-specific CD107a− CD4+ T-cell induction in HIV vaccine design. IMPORTANCE Induction of effective antibody and/or CD8+ T-cell responses is a principal vaccine strategy against human immunodeficiency virus (HIV) infection. CD4+ T-cell responses are crucial for effective antibody and CD8+ T-cell induction. However, virus-specific CD4+ T cells can be preferential targets for HIV infection. Here, we show that vaccine-induced virus-specific CD107a− CD4+ T cells are largely depleted following infection in a macaque AIDS model. While CD4+ T-cell responses are important in viral control, our results indicate that virus-specific CD107a− CD4+ T-cell induction by vaccination may not lead to efficient CD4+ T-cell responses following infection but rather be detrimental and accelerate viral replication in the acute phase. This suggests that HIV vaccine design

  7. Low-temperature dynamic nuclear polarization at 9.4 T with a 30 mW microwave source

    NASA Astrophysics Data System (ADS)

    Thurber, Kent R.; Yau, Wai-Ming; Tycko, Robert

    2010-06-01

    Dynamic nuclear polarization (DNP) can provide large signal enhancements in nuclear magnetic resonance (NMR) by transfer of polarization from electron spins to nuclear spins. We discuss several aspects of DNP experiments at 9.4 T (400 MHz resonant frequency for 1H, 264 GHz for electron spins in organic radicals) in the 7-80 K temperature range, using a 30 mW, frequency-tunable microwave source and a quasi-optical microwave bridge for polarization control and low-loss microwave transmission. In experiments on frozen glycerol/water doped with nitroxide radicals, DNP signal enhancements up to a factor of 80 are observed (relative to 1H NMR signals with thermal equilibrium spin polarization). The largest sensitivity enhancements are observed with a new triradical dopant, DOTOPA-TEMPO. Field modulation with a 10 G root-mean-squared amplitude during DNP increases the nuclear spin polarizations by up to 135%. Dependencies of 1H NMR signal amplitudes, nuclear spin relaxation times, and DNP build-up times on the dopant and its concentration, temperature, microwave power, and modulation frequency are reported and discussed. The benefits of low-temperature DNP can be dramatic: the 1H spin polarization is increased approximately 1000-fold at 7 K with DNP, relative to thermal polarization at 80 K.

  8. Magnetic penetration-depth measurements of a suppressed superfluid density of superconducting Ca0.5Na0.5Fe2As2 single crystals by proton irradiation

    NASA Astrophysics Data System (ADS)

    Kim, Jeehoon; Haberkorn, N.; Graf, M. J.; Usov, I.; Ronning, F.; Civale, L.; Nazaretski, E.; Chen, G. F.; Yu, W.; Thompson, J. D.; Movshovich, R.

    2012-10-01

    We report on the dramatic effect of random point defects, produced by proton irradiation, on the superfluid density ρs in superconducting Ca0.5Na0.5Fe2As2 single crystals. The magnitude of the suppression is inferred from measurements of the temperature-dependent magnetic penetration depth λ(T) using magnetic force microscopy. Our findings indicate that a radiation dose of 2×1016 cm-2 produced by 3 MeV protons results in a reduction of the superconducting critical temperature Tc by approximately 10%. In contrast, ρs(0) is suppressed by approximately 60%. This breakdown of the Abrikosov-Gorkov theory may be explained by the so-called “Swiss cheese model,” which accounts for the spatial suppression of the order parameter near point defects similar to holes in Swiss cheese. Both the slope of the upper critical field and the penetration depth λ(T/Tc)/λ(0) exhibit similar temperature dependences before and after irradiation. This may be due to a combination of the highly disordered nature of Ca0.5Na0.5Fe2As2 with large intraband and simultaneous interband scattering as well as the s±-wave nature of short coherence length superconductivity.

  9. 26 CFR 1.6664-4T - Reasonable cause and good faith exception to section 6662 penalties.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 13 2010-04-01 2010-04-01 false Reasonable cause and good faith exception to section 6662 penalties. 1.6664-4T Section 1.6664-4T Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Additions to the Tax,...

  10. 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...

  11. 26 CFR 1.79-4T - Questions and answers relating to the nondiscrimination requirements for group-term life...

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... nondiscrimination requirements for group-term life insurance (temporary). 1.79-4T Section 1.79-4T Internal Revenue... nondiscrimination requirements for group-term life insurance (temporary). Q-1: When does section 79, as amended by..., however, several exceptions to this effective date where there is coverage under a group-term...

  12. 26 CFR 1.79-4T - Questions and answers relating to the nondiscrimination requirements for group-term life...

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... nondiscrimination requirements for group-term life insurance (temporary). 1.79-4T Section 1.79-4T Internal Revenue... nondiscrimination requirements for group-term life insurance (temporary). Q-1: When does section 79, as amended by..., however, several exceptions to this effective date where there is coverage under a group-term...

  13. 26 CFR 1.79-4T - Questions and answers relating to the nondiscrimination requirements for group-term life...

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... nondiscrimination requirements for group-term life insurance (temporary). 1.79-4T Section 1.79-4T Internal Revenue... nondiscrimination requirements for group-term life insurance (temporary). Q-1: When does section 79, as amended by..., however, several exceptions to this effective date where there is coverage under a group-term...

  14. 26 CFR 1.79-4T - Questions and answers relating to the nondiscrimination requirements for group-term life...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... nondiscrimination requirements for group-term life insurance (temporary). 1.79-4T Section 1.79-4T Internal Revenue... nondiscrimination requirements for group-term life insurance (temporary). Q-1: When does section 79, as amended by..., however, several exceptions to this effective date where there is coverage under a group-term...

  15. 26 CFR 1.79-4T - Questions and answers relating to the nondiscrimination requirements for group-term life...

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... nondiscrimination requirements for group-term life insurance (temporary). 1.79-4T Section 1.79-4T Internal Revenue... nondiscrimination requirements for group-term life insurance (temporary). Q-1: When does section 79, as amended by..., however, several exceptions to this effective date where there is coverage under a group-term...

  16. Elevated expression of T-bet in mycobacterial antigen-specific CD4(+) T cells from patients with tuberculosis.

    PubMed

    Yang, Bingfen; Zhai, Fei; Jiang, Jing; Wang, Xinjing; Cao, Zhihong; Cheng, Xiaoxing

    2015-01-01

    T-bet is a T-box transcriptional factor that controls the differentiation and effector functions of CD4 T cells. In this study, we studied the role of T-bet in regulating CD4(+) T cell immunity against tuberculosis (TB). T-bet expression in Mycobacterium tuberculosis antigen-specific CD4(+) T cells was significantly higher in patients with active TB than in individuals with latent TB infection (p<0.0001). Comparison of T-bet expression in TCM and TEM subsets showed that CD4(+)T-bet(+)M. tuberculosis antigen-specific CD4(+) T cells had significantly lower frequency of TCM (p=0.003) and higher frequency of TEM (p=0.003) than CD4(+)T-bet(-) cells. The expression of PD-1 in antigen-specific CD4(+) T cells was significantly higher in patients with TB than in individuals with latent TB infection (p=0.006). CD4(+)CD154(+)T-bet(+) T cells had significantly higher expression of PD-1 than CD4(+)CD154(+)T-bet(-) T cells (p=0.0028). It is concluded that T-bet expression might be associated with differentiation into effector memory cells and PD-1 expression in mycobacterial antigen-specific CD4(+) T cells. PMID:26302932

  17. Genome Sequence of Anaerobacillus macyae JMM-4T (DSM 16346), the First Genomic Information of the Newly Established Genus Anaerobacillus