Effects of monovalent and divalent ions in factor xiii activation and crosslinking.

Factor XIII (FXIII) is an emerging target for treating blood clotting and cardiovascular related diseases. FXIII can be activated non-proteolytically by the presence of elevated Ca2+ levels (2-100 mM) or proteolytically by thrombin-cleavage of the Activation Peptide along with low mM Ca2+. The studies herein utilized fluorescence to examine how monovalent and divalent ions influence the transglutaminase activity and conformation of FXIII. Monodansylcadaverine assays revealed that increasing ionic radius (Cs+ \u3e K+ \u3e Na+ \u3e Li+) and increasing ionic strength (XCl- levels and SO42- \u3e Cl-) elevated FXIII-A transglutaminase activity. Intrinsic fluorescence studies revealed that only cations influenced FXIII conformation. For divalent salts, transglutaminase activity for MgSO4 is ~3-fold higher than MgCl2. Unlike transglutaminase 2, FXIII containing a mutation in the Cab3 calcium binding site (G262V) could not exhibit an improvement in activity. A FXIII Cab3 helix is proposed to be hindered which impacts non-proteolytically activated FXIII more than proteolytically activated FXIII. Both cations and anions influence FXIII’s ability to interact with substrates

Electron and nuclear spin dynamics in the thermal mixing model of dynamic nuclear polarization

A novel mathematical treatment is proposed for computing the time evolution of dynamic nuclear polarization processes in the low temperature thermal mixing regime. Without assuming any a priori analytical form for the electron polarization, our approach provides a quantitative picture of the steady state that recovers the well known Borghini prediction based on thermodynamics arguments, as long as the electrons-nuclei transition rates are fast compared to the other relevant time scales. Substantially different final polarization levels are achieved instead when the latter assumption is relaxed in the presence of a nuclear leakage term, even though very weak, suggesting a possible explanation for the deviation between the measured steady state polarizations and the Borghini prediction. The proposed methodology also allows to calculate nuclear polarization and relaxation times, once specified the electrons/nuclei concentration ratio and the typical rates of the microscopic processes involving the two spin species. Numerical results are shown to account for the manifold dynamical behaviours of typical DNP samples.Comment: 11 pages, 11 figure

77^{77}Se and 63^{63}Cu NMR studies of the electronic correlations in Cux_xTiSe2_2 (x=0.05,0.07x=0.05, 0.07)

We report $^{77}$Se and $^{63}$Cu nuclear magnetic resonance (NMR) investigation on the charge-density-wave (CDW) superconductor Cu$_x$TiSe$_2$ ($x=0.05$ and 0.07). At high magnetic fields where superconductivity is suppressed, the temperature dependence of $^{77}$Se and $^{63}$Cu spin-lattice relaxation rates 1/T_{1}$follow a linear relation. The slope of$^{77}1/T_{1}$ vs \emph{T} increases with the Cu doping. This can be described by a modified Korringa relation which suggests the significance of electronic correlations and the Se 4\emph{p}- and Ti 3\emph{d}-band contribution to the density of states at the Fermi level in the studied compounds.Comment: Revised manuscript. Submitted to Journal of Physics: Condensed Matte

Hyperpolarized (6)Li as a probe for hemoglobin oxygenation level.

Hyperpolarization by dissolution dynamic nuclear polarization (DNP) is a versatile technique to dramatically enhance the nuclear magnetic resonance (NMR) signal intensity of insensitive long-T1 nuclear spins such as (6)Li. The (6)Li longitudinal relaxation of lithium ions in aqueous solutions strongly depends on the concentration of paramagnetic species, even if they are present in minute amounts. We herein demonstrate that blood oxygenation can be readily detected by taking advantage of the (6)Li signal enhancement provided by dissolution DNP, together with the more than 10% decrease in (6)Li longitudinal relaxation as a consequence of the presence of paramagnetic deoxyhemoglobin

Flux quanta driven by high-density currents in low-impurity V3Si and LuNi2B2C: free flux flow and flux-core size effect

High density direct currents (DC) are used to drive flux quanta via the Lorentz force towards a highly ordered "free flux flow" (FFF) dynamic state, made possible by the weak-pinning environment of high-quality, single-crystal samples of two low-Tc superconducting compounds, V3Si and LuNi2B2C. We report the effect of the magnetic field-dependent fluxon core size on flux flow resistivity rho_f. Much progress has been made in minimizing the technical challenges associated with the use of high currents. Attainment of a FFF phase is indicated by the saturation at highest currents of flux-flow dissipation levels that are well below the normal state resistance and have field-dependent values. The field dependence of the corresponding rho_f is shown to be consistent with a prediction based on a model for the decrease of flux core size at higher fields in weak-coupling BCS s-wave materials.Comment: More empirical treatment of the magnetoresistive correction of V3Si data by additional measurement and analysis (involving two new coauthors, Favreau and Henderson). End result is the same, making for a stronger manuscrip

Dynamic nuclear polarisation by thermal mixing: quantum theory and macroscopic simulations

A theory of dynamic nuclear polarisation (DNP) by thermal mixing is suggested based on purely quantum considerations. A minimal 6-level microscopic model is developed to test the theory and link it to the well known thermodynamic model. Optimal conditions for the nuclear polarization enhancement and effects of inhomogeneous broadening of the electron resonance are discussed. Macroscopic simulations of nuclear polarization spectra displaying good agreement with experiments, involving BDPA and trityl free radicals, are presented

The use of yttrium in medical imaging and therapy : historical background and future perspectives

Yttrium is a chemically versatile rare earth element that finds use in a range of applications including lasers and superconductors. In medicine, yttrium-based materials are used in medical lasers and biomedical implants. This is extended through the array of available yttrium isotopes to enable roles for 90Y complexes as radiopharmaceuticals and 86Y tracers for positron emission tomography (PET) imaging. The naturally abundant isotope 89Y is proving to be suitable for nuclear magnetic resonance investigations, where initial reports in the emerging field of hyperpolarised magnetic resonance imaging (MRI) are promising. In this review we explore the coordination and radiochemical properties of yttrium, and its role in drugs for radiotherapy, PET imaging agents and perspectives for applications in hyperpolarised MRI. This journal i

Hyperpolarization methods for MRS

© 2015 John Wiley & Sons, Ltd. This article covers the fundamental principles and practice of NMR hyperpolarization techniques, which are proving useful for in vivo magnetic resonance spectroscopy (MRS) studies of metabolism in animal models, and clinical trials with hyper-enhanced sensitivity. Fundamentally, hyperpolarization methods enhance nuclear spin polarization by orders-of-magnitude, resulting in concomitant improvement in NMR detection sensitivity. The hyperpolarization methods described here - dynamic nuclear polarization (DNP), para-hydrogen induced polarization (PHIP), signal amplification by reversible exchange (SABRE), and spin-exchange optical pumping (SEOP) - are capable of achieving nuclear spin polarization approaching the theoretical maximum of unity on nuclear spin sites of molecular or atomic agents suitable for in vivo administration. Importantly, hyperpolarization is inherently nonequilibrium in nature: The duration of the hyperpolarization is frequently shortlived, often being limited by the in vivo spin-lattice relaxation times (T 1) that are on the order of seconds to a minute. Nevertheless, sufficient amounts of nuclear spin polarization can survive the process of preparation, administration, and in vivo circulation to provide extraordinary enhancement of the hyperpolarized agent. The chemical shift dispersion of these agents at the molecular location of interest reports on functional, metabolic, and other processes at the molecular level, enabling true molecular MRS imaging