1,093 research outputs found
Biliverdin Reductase: More than a Namesake – The Reductase, Its Peptide Fragments, and Biliverdin Regulate Activity of the Three Classes of Protein Kinase C
The expanse of human biliverdin reductase (hBVR) functions in the cells is arguably unmatched by any single protein. hBVR is a Ser/Thr/Tyr-kinase, a scaffold protein, a transcription factor, and an intracellular transporter of gene regulators. hBVR is an upstream activator of the insulin/IGF-1 signaling pathway and of protein kinase C (PKC) kinases in the two major arms of the pathway. In addition, it is the sole means for generating the antioxidant bilirubin-IXα. hBVR is essential for activation of ERK1/2 kinases by upstream MAPKK-MEK and by PKCδ, as well as the nuclear import and export of ERK1/2. Small fragments of hBVR are potent activators and inhibitors of the ERK kinases and PKCs: as such, they suggest the potential application of BVR-based technology in therapeutic settings. Presently, we have reviewed the function of hBVR in cell signaling with an emphasis on regulation of PKCδ activity
Test of classical nucleation theory on deeply supercooled high-pressure simulated silica
We test classical nucleation theory (CNT) in the case of simulations of
deeply supercooled, high density liquid silica, as modelled by the BKS
potential. We find that at density ~g/cm, spontaneous nucleation
of crystalline stishovite occurs in conventional molecular dynamics simulations
at temperature T=3000 K, and we evaluate the nucleation rate J directly at this
T via "brute force" sampling of nucleation events. We then use parallel,
constrained Monte Carlo simulations to evaluate , the free energy
to form a crystalline embryo containing n silicon atoms, at T=3000, 3100, 3200
and 3300 K. We find that the prediction of CNT for the n-dependence of fits reasonably well to the data at all T studied, and at 3300 K yields a
chemical potential difference between liquid and stishovite that matches
independent calculation. We find that , the size of the critical nucleus,
is approximately 10 silicon atoms at T=3300 K. At 3000 K, decreases to
approximately 3, and at such small sizes methodological challenges arise in the
evaluation of when using standard techniques; indeed even the
thermodynamic stability of the supercooled liquid comes into question under
these conditions. We therefore present a modified approach that permits an
estimation of at 3000 K. Finally, we directly evaluate at T=3000
K the kinetic prefactors in the CNT expression for J, and find physically
reasonable values; e.g. the diffusion length that Si atoms must travel in order
to move from the liquid to the crystal embryo is approximately 0.2 nm. We are
thereby able to compare the results for J at 3000 K obtained both directly and
based on CNT, and find that they agree within an order of magnitude.Comment: corrected calculation, new figure, accepted in JC
Chelator free gallium-68 radiolabelling of silica coated iron oxide nanorods via surface interactions
The commercial availability of combined magnetic resonance imaging (MRI)/positron emission tomography (PET) scanners for clinical use has increased demand for easily prepared agents which offer signal or contrast in both modalities. Herein we describe a new class of silica coated iron–oxide nanorods (NRs) coated with polyethylene glycol (PEG) and/or a tetraazamacrocyclic chelator (DO3A). Studies of the coated NRs validate their composition and confirm their properties as in vivo T₂ MRI contrast agents. Radiolabelling studies with the positron emitting radioisotope gallium-68 (t1/2 = 68 min) demonstrate that, in the presence of the silica coating, the macrocyclic chelator was not required for preparation of highly stable radiometal-NR constructs. In vivo PET-CT and MR imaging studies show the expected high liver uptake of gallium-68 radiolabelled nanorods with no significant release of gallium-68 metal ions, validating our innovation to provide a novel simple method for labelling of iron oxide NRs with a radiometal in the absence of a chelating unit that can be used for high sensitivity liver imaging
Potential Use of Quantum Dots in Flow Cytometry
QDs may offer significant advantages in environmental and bead-based applications where the target cells need to be discriminated above background fluorescence. We have examined the possible applications of QDs for flow cytometric measurements (FCM) by studying their excitation - emission spectra and their binding to paramagnetic beads. We labelled beads with either QDs or a commonly-used fluorochrome (FITC) and studied their fluorescence intensity by FCM. Flow cytometric comparisons indicated that the minimum fluorophore concentration required for detection of QDs above autofluorescent background was 100-fold less than for FITC
Simulation of fluid-solid coexistence in finite volumes: A method to study the properties of wall-attached crystalline nuclei
The Asakura-Oosawa model for colloid-polymer mixtures is studied by Monte
Carlo simulations at densities inside the two-phase coexistence region of fluid
and solid. Choosing a geometry where the system is confined between two flat
walls, and a wall-colloid potential that leads to incomplete wetting of the
crystal at the wall, conditions can be created where a single nanoscopic
wall-attached crystalline cluster coexists with fluid in the remainder of the
simulation box. Following related ideas that have been useful to study
heterogeneous nucleation of liquid droplets at the vapor-liquid coexistence, we
estimate the contact angles from observations of the crystalline clusters in
thermal equilibrium. We find fair agreement with a prediction based on Young's
equation, using estimates of interface and wall tension from the study of flat
surfaces. It is shown that the pressure versus density curve of the finite
system exhibits a loop, but the pressure maximum signifies the "droplet
evaporation-condensation" transition and thus has nothing in common with a van
der Waals-like loop. Preparing systems where the packing fraction is deep
inside the two-phase coexistence region, the system spontaneously forms a "slab
state", with two wall-attached crystalline domains separated by (flat)
interfaces from liquid in full equilibrium with the crystal in between;
analysis of such states allows a precise estimation of the bulk equilibrium
properties at phase coexistence
Curvature Dependence of Surface Free Energy of Liquid Drops and Bubbles: A Simulation Study
We study the excess free energy due to phase coexistence of fluids by Monte
Carlo simulations using successive umbrella sampling in finite LxLxL boxes with
periodic boundary conditions. Both the vapor-liquid phase coexistence of a
simple Lennard-Jones fluid and the coexistence between A-rich and B-rich phases
of a symmetric binary (AB) Lennard-Jones mixture are studied, varying the
density rho in the simple fluid or the relative concentration x_A of A in the
binary mixture, respectively. The character of phase coexistence changes from a
spherical droplet (or bubble) of the minority phase (near the coexistence
curve) to a cylindrical droplet (or bubble) and finally (in the center of the
miscibility gap) to a slab-like configuration of two parallel flat interfaces.
Extending the analysis of M. Schrader, P. Virnau, and K. Binder [Phys. Rev. E
79, 061104 (2009)], we extract the surface free energy gamma (R) of both
spherical and cylindrical droplets and bubbles in the vapor-liquid case, and
present evidence that for R -> Infinity the leading order (Tolman) correction
for droplets has sign opposite to the case of bubbles, consistent with the
Tolman length being independent on the sign of curvature. For the symmetric
binary mixture the expected non-existence of the Tolman length is confirmed. In
all cases {and for a range of radii} R relevant for nucleation theory, gamma(R)
deviates strongly from gamma (Infinity) which can be accounted for by a term of
order gamma(Infinity)/gamma(R)-1 ~ 1/R^2. Our results for the simple
Lennard-Jones fluid are also compared to results from density functional theory
and we find qualitative agreement in the behavior of gamma(R) as well as in the
sign and magnitude of the Tolman length.Comment: 25 pages, submitted to J. Chem. Phy
Determinants of carotid microembolization
AbstractPurpose: Earlier studies have highlighted risk factors for perioperative stroke after carotid endarterectomy, such as female sex, preoperative symptoms, and cerebral infarction. In this study, we investigated the relationship between these factors and perioperative microembolization. Methods: A total of 235 patients were entered in the study at two centers. Transcranial Doppler ultrasound scanning was possible in 190 patients (81%) and was performed for 1 hour preoperatively and continuously intraoperatively as a means of detecting microemboli and monitoring mean middle cerebral artery velocity. The findings of transcranial Doppler ultrasound scanning were related to perioperative risk factors by means of univariate analysis. Results: Microemboli were detected in 28 (15%), 79 (42%), and 98 (52%) patients preoperatively, during carotid artery dissection, and after closure of the artery, respectively. Having 10 or more emboli after carotid artery closure was more common in women (P =.04) and in patients with symptomatic carotid artery disease (P =.04) and was demonstrated in three of the six patients who had a perioperative stroke. These three patients also had preoperative evidence of cerebral infarction and an intraoperative middle cerebral artery velocity less than 40 cm/s. Conclusion: In this study, perioperative microembolization was more common in women and patients with symptomatic carotid artery disease. These findings may explain the increased risk of carotid surgery in these patients. (J Vasc Surg 2001;34:1060-4.
Anomalous layering at the liquid Sn surface
X-ray reflectivity measurements on the free surface of liquid Sn are
presented. They exhibit the high-angle peak, indicative of surface-induced
layering, also found for other pure liquid metals (Hg, Ga and In). However, a
low-angle peak, not hitherto observed for any pure liquid metal, is also found,
indicating the presence of a high-density surface layer. Fluorescence and
resonant reflectivity measurements rule out the assignment of this layer to
surface-segregation of impurities. The reflectivity is modelled well by a 10%
contraction of the spacing between the first and second atomic surface layers,
relative to that of subsequent layers. Possible reasons for this are discussed.Comment: 8 pages, 9 figures; to be submitted to Phys. Rev. B; updated
references, expanded discussio
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