1,608 research outputs found
Common promoter variant in cyclooxygenase-2 represses gene expression: evidence of role in acute-phase inflammatory response
Objective: Cyclooxygenase (COX)-2 is a key regulatory enzyme in the synthesis of prostanoids associated with trauma and inflammation. We investigated the COX-2 gene for functional variants that may influence susceptibility to disease.
Methods and results: The promoter of COX-2 was screened for variants in healthy subjects by use of polymerase chain reaction-based methods. Promoter activity was investigated by using reporter expression experiments in human lung fibroblasts. Patients undergoing coronary artery bypass graft surgery, with measurements of plasma markers linked to COX-2 activity, were genotyped for association studies. A common COX-2 promoter variant, -765G>C, was found and shown to be carried by >25% of a group of healthy UK subjects. The -765C allele had significantly lower promoter activity compared with -765G, basally (28±3% lower, P<0.005) and in serum-stimulated cells (31±2% lower, P<0.005). In patients subjected to coronary artery bypass graft surgery, the magnitude of rise in levels of C-reactive protein (CRP) was strongly genotype dependent. Compared with -765G homozygotes, patients carrying the -765C allele had significantly lower plasma CRP levels at 1 to 4 days after surgery (14% lower at the peak of CRP levels on day 3, P<0.05 for all time points).
Conclusions: For several acute and chronic inflammatory diseases, -765G>C may influence the variability of response observed
Simulations of Oligomeric Intermediates in Prion Diseases
We extend our previous stochastic cellular automata based model for areal
aggregation of prion proteins on neuronal surfaces. The new anisotropic model
allow us to simulate both strong beta-sheet and weaker attachment bonds between
proteins. Constraining binding directions allows us to generate aggregate
structures with the hexagonal lattice symmetry found in recently observed in
vitro experiments. We argue that these constraints on rules may correspond to
underlying steric constraints on the aggregation process. We find that monomer
dominated growth of the areal aggregate is too slow to account for some
observed doubling time-to-incubation time ratios inferred from data, and so
consider aggregation dominated by relatively stable but non-infectious
oligomeric intermediates. We compare a kinetic theory analysis of oligomeric
aggregation to spatially explicit simulations of the process. We find that with
suitable rules for misfolding of oligomers, possibly due to water exclusion by
the surrounding aggregate, the resulting oligomeric aggregation model maps onto
our previous monomer aggregation model. Therefore it can produce some of the
same attractive features for the description of prion incubation time data. We
propose experiments to test the oligomeric aggregation model.Comment: 8 pages, 10 figures For larger versions of several figures, see
http://asaph.ucdavis.edu/~dmobley and click on the prion paper lin
Erythropoietin treatment during complement inhibition with eculizumab in a patient with paroxysmal nocturnal hemoglobinuria
Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by intravascular hemolysis leading to anemia and other clinical manifestations. Transfusions are often required to support hemoglobin at tolerable levels. A PNH patient with aplastic anemia was treated with the complement inhibitor eculizumab, followed by concurrent treatment with recombinant human erythropoietin (rHuEpo). Eculizumab alone reduced hemolysis, increased PNH red blood cell (RBC) mass, and decreased transfusions. Addition of rHuEpo during eculizumab therapy, enhanced erythropoiesis, further increased PNH RBC mass and hemoglobin levels, and rendered the patient transfusion independent for more than two years. These data show that driving erythropoiesis during eculizumab treatment provided further benefit to a patient with PNH and underlying bone marrow failure
Optical spectroscopy of the radio pulsar PSR B0656+14
We have obtained the spectrum of a middle-aged PSR B0656+14 in the 4300-9000
AA range with the ESO/VLT/FORS2. Preliminary results show that at 4600-7000 AA
the spectrum is almost featureless and flat with a spectral index $\alpha_nu ~
-0.2 that undergoes a change to a positive value at longer wavelengths.
Combining with available multiwavelength data suggests two wide, red and blue,
flux depressions whose frequency ratio is about 2 and which could be the 1st
and 2nd harmonics of electron/positron cyclotron absorption formed at magnetic
fields ~10^8G in upper magnetosphere of the pulsar.Comment: 4 pages, 4 figures, To appear in Astrophysics and Space Science,
Proceedings of "Isolated Neutron Stars: from the Interior to the Surface",
eds. D. Page, R. Turolla and S. Zan
Role of dipolar and exchange interactions in the positions and widths of EPR transitions for the single-molecule magnets Fe8 and Mn12
We examine quantitatively the temperature dependence of the linewidths and
line shifts in electron paramagnetic resonance experiments on single crystals
of the single-molecule magnets Fe and Mn, at fixed frequency, with
an applied magnetic field along the easy axis. We include inter-molecular
spin-spin interactions (dipolar and exchange) and distributions in both the
uniaxial anisotropy parameter and the Land\'{e} -factor. The temperature
dependence of the linewidths and the line shifts are mainly caused by the
spin-spin interactions. For Fe and Mn, the temperature dependence of
the calculated line shifts and linewidths agrees well with the trends of the
experimental data. The linewidths for Fe reveal a stronger temperature
dependence than those for Mn, because for Mn a much wider
distribution in overshadows the temperature dependence of the spin-spin
interactions. For Fe, the line-shift analysis suggests two competing
interactions: a weak ferromagnetic exchange coupling between neighboring
molecules and a longer-ranged dipolar interaction. This result could have
implications for ordering in Fe at low temperatures.Comment: published versio
Geometric Strategy for the Optimal Quantum Search
We explore quantum search from the geometric viewpoint of a complex
projective space , a space of rays. First, we show that the optimal quantum
search can be geometrically identified with the shortest path along the
geodesic joining a target state, an element of the computational basis, and
such an initial state as overlaps equally, up to phases, with all the elements
of the computational basis. Second, we calculate the entanglement through the
algorithm for any number of qubits as the minimum Fubini-Study distance to
the submanifold formed by separable states in Segre embedding, and find that
entanglement is used almost maximally for large . The computational time
seems to be optimized by the dynamics as the geodesic, running across entangled
states away from the submanifold of separable states, rather than the amount of
entanglement itself.Comment: revtex, 10 pages, 7 eps figures, uses psfrag packag
Observations of quasi-periodic solar X-ray emission as a result of MHD oscillations in a system of multiple flare loops
We investigate the solar flare of 20 October 2002. The flare was accompanied
by quasi-periodic pulsations (QPP) of both thermal and nonthermal hard X-ray
emissions (HXR) observed by RHESSI in the 3-50 keV energy range. Analysis of
the HXR time profiles in different energy channels made with the Lomb
periodogram indicates two statistically significant time periods of about 16
and 36 seconds. The 36-second QPP were observed only in the nonthermal HXR
emission in the impulsive phase of the flare. The 16-second QPP were more
pronounced in the thermal HXR emission and were observed both in the impulsive
and in the decay phases of the flare. Imaging analysis of the flare region, the
determined time periods of the QPP and the estimated physical parameters of
magnetic loops in the flare region allow us to interpret the observations as
follows. 1) In the impulsive phase energy was released and electrons were
accelerated by successive acts with the average time period of about 36 seconds
in different parts of two spatially separated, but interacting loop systems of
the flare region. 2) The 36-second periodicity of energy release could be
caused by the action of fast MHD oscillations in the loops connecting these
flaring sites. 3) During the first explosive acts of energy release the MHD
oscillations (most probably the sausage mode) with time period of 16 seconds
were excited in one system of the flare loops. 4) These oscillations were
maintained by the subsequent explosive acts of energy release in the impulsive
phase and were completely damped in the decay phase of the flare.Comment: 14 pages, 4 figure
Energy Release During Slow Long Duration Flares Observed by RHESSI
Slow Long Duration Events (SLDEs) are flares characterized by long duration
of rising phase. In many such cases impulsive phase is weak with lack of
typical short-lasting pulses. Instead of that smooth, long-lasting Hard X-ray
(HXR) emission is observed. We analysed hard X-ray emission and morphology of
six selected SLDEs. In our analysis we utilized data from RHESSI and GOES
satellites. Physical parameters of HXR sources were obtained from imaging
spectroscopy and were used for the energy balance analysis. Characteristic time
of heating rate decrease, after reaching its maximum value, is very long, which
explains long rising phase of these flares.Comment: Accepted for publication in Solar Physic
The Intentional Use of Service Recovery Strategies to Influence Consumer Emotion, Cognition and Behaviour
Service recovery strategies have been identified as a critical factor in the success of. service organizations. This study develops a conceptual frame work to investigate how specific service recovery strategies influence the emotional, cognitive and negative behavioural responses of . consumers., as well as how emotion and cognition influence negative behavior. Understanding the impact of specific service recovery strategies will allow service providers' to more deliberately and intentionally engage in strategies that result in positive organizational outcomes. This study was conducted using a 2 x 2 between-subjects quasi-experimental design. The results suggest that service recovery has a significant impact on emotion, cognition and negative behavior. Similarly, satisfaction, negative emotion and positive emotion all influence negative behavior but distributive justice has no effect
- …