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

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$_8$ and Mn$_{12}$, 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 $D$ and the Land\'{e} $g$-factor. The temperature dependence of the linewidths and the line shifts are mainly caused by the spin-spin interactions. For Fe$_8$ and Mn$_{12}$, the temperature dependence of the calculated line shifts and linewidths agrees well with the trends of the experimental data. The linewidths for Fe$_8$ reveal a stronger temperature dependence than those for Mn$_{12}$, because for Mn$_{12}$ a much wider distribution in $D$ overshadows the temperature dependence of the spin-spin interactions. For Fe$_8$, 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$_8$ 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 $CP$, 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 $n$ 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 $n$. 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

Force and Motion Generation of Molecular Motors: A Generic Description

We review the properties of biological motor proteins which move along linear filaments that are polar and periodic. The physics of the operation of such motors can be described by simple stochastic models which are coupled to a chemical reaction. We analyze the essential features of force and motion generation and discuss the general properties of single motors in the framework of two-state models. Systems which contain large numbers of motors such as muscles and flagella motivate the study of many interacting motors within the framework of simple models. In this case, collective effects can lead to new types of behaviors such as dynamic instabilities of the steady states and oscillatory motion.Comment: 29 pages, 9 figure