Preeclampsia is associated with compromized maternal synthesis of long chain polyunsaturated fatty acids leading to offspring deficiency

Obesity and excessive lipolysis are implicated in preeclampsia (PE). Intrauterine growth restriction is associated with low maternal body mass index and decreased lipolysis. Our aim was to assess how maternal and offspring fatty acid metabolism is altered in mothers in the third trimester of pregnancy with PE (n=62) or intrauterine growth restriction (n=23) compared with healthy pregnancies (n=164). Markers of lipid metabolism and erythrocyte fatty acid concentrations were measured. Maternal adipose tissue fatty acid composition and mRNA expression of adipose tissue fatty acid–metabolizing enzymes and placental fatty acid transporters were compared. Mothers with PE had higher plasma triglyceride (21%, P<0.001) and nonesterified fatty acid (50%, P<0.001) concentrations than controls. Concentrations of major n−6 and n−3 long-chain polyunsaturated fatty acids in erythrocytes were 23% to 60% lower (all P<0.005) in PE and intrauterine growth restriction mothers and offspring compared with controls. Subcutaneous adipose tissue Δ−5 and Δ−6 desaturase and very long-chain fatty acid elongase mRNA expression was lower in PE than controls (respectively, mean [SD] control 3.38 [2.96] versus PE 1.83 [1.91], P=0.030; 3.33 [2.25] versus 1.03 [0.96], P<0.001; 0.40 [0.81] versus 0.00 [0.00], P=0.038 expression relative to control gene [square root]). Low maternal and fetal long-chain polyunsaturated fatty acid concentrations in PE may be the result of decreased maternal synthesis

Formal change impact analyses for emulated control software

Processor emulators are a software tool for allowing legacy computer programs to be executed on a modern processor. In the past emulators have been used in trivial applications such as maintenance of video games. Now, however, processor emulation is being applied to safety-critical control systems, including military avionics. These applications demand utmost guarantees of correctness, but no verification techniques exist for proving that an emulated system preserves the original system’s functional and timing properties. Here we show how this can be done by combining concepts previously used for reasoning about real-time program compilation, coupled with an understanding of the new and old software architectures. In particular, we show how both the old and new systems can be given a common semantics, thus allowing their behaviours to be compared directly

Nonlocal Equation of State in Anisotropic Static Fluid Spheres in General Relativity

We show that it is possible to obtain credible static anisotropic spherically symmetric matter configurations starting from known density profiles and satisfying a nonlocal equation of state. These particular types of equation of state describe, at a given point, the components of the corresponding energy-momentum tensor not only as a function at that point, but as a functional throughout the enclosed configuration. To establish the physical plausibility of the proposed family of solutions satisfying nonlocal equation of state, we study the constraints imposed by the junction and energy conditions on these bounded matter distributions. We also show that it is possible to obtain physically plausible static anisotropic spherically symmetric matter configurations, having nonlocal equations of state\textit{,}concerning the particular cases where the radial pressure vanishes and, other where the tangential pressures vanishes. The later very particular type of relativistic sphere with vanishing tangential stresses is inspired by some of the models proposed to describe extremely magnetized neutron stars (magnetars) during the transverse quantum collapse.Comment: 21 pages, 1 figure, minor changes in the text, references added, two new solutions studie

Modelling non-dust fluids in cosmology

Currently, most of the numerical simulations of structure formation use Newtonian gravity. When modelling pressureless dark matter, or `dust', this approach gives the correct results for scales much smaller than the cosmological horizon, but for scenarios in which the fluid has pressure this is no longer the case. In this article, we present the correspondence of perturbations in Newtonian and cosmological perturbation theory, showing exact mathematical equivalence for pressureless matter, and giving the relativistic corrections for matter with pressure. As an example, we study the case of scalar field dark matter which features non-zero pressure perturbations. We discuss some problems which may arise when evolving the perturbations in this model with Newtonian numerical simulations and with CMB Boltzmann codes.Comment: 5 pages; v2: typos corrected and refs added, submitted version; v3: version to appear in JCA

Oscillations During Inflation and the Cosmological Density Perturbations

Adiabatic (curvature) perturbations are produced during a period of cosmological inflation that is driven by a single scalar field, the inflaton. On particle physics grounds -- though -- it is natural to expect that this scalar field is coupled to other scalar degrees of freedom. This gives rise to oscillations between the perturbation of the inflaton field and the perturbations of the other scalar degrees of freedom, similar to the phenomenon of neutrino oscillations. Since the degree of the mixing is governed by the squared mass matrix of the scalar fields, the oscillations can occur even if the energy density of the extra scalar fields is much smaller than the energy density of the inflaton field. The probability of oscillation is resonantly amplified when perturbations cross the horizon and the perturbations in the inflaton field may disappear at horizon crossing giving rise to perturbations in scalar fields other than the inflaton. Adiabatic and isocurvature perturbations are inevitably correlated at the end of inflation and we provide a simple expression for the cross-correlation in terms of the slow-roll parameters.Comment: 23 pages, uses LaTeX, added few reference

WKB approximation for inflationary cosmological perturbations

A new method for predicting inflationary cosmological perturbations, based on the Wentzel-Kramers-Brillouin (WKB) approximation, is presented. A general expression for the WKB scalar and tensor power spectra is derived. The main advantage of the new scheme of approximation is that it is valid even if the slow-roll conditions are violated. The method is applied to power-law inflation, which allows a comparison with an exact result. It is demonstrated that the WKB approximation predicts the spectral indices exactly and the amplitude with an error lower than 10%, even in regimes far from scale-invariance. The new method of approximation is also applied to a situation where the slow-roll conditions hold. It is shown that the result obtained bears close resemblance with the standard slow-roll calculation. Finally, some possible improvements are briefly mentioned.Comment: 11 pages, 1 figure, RevTeX; minor changes, reference added (v2); typos corrected (v3

Inflation, cold dark matter, and the central density problem

A problem with high central densities in dark halos has arisen in the context of LCDM cosmologies with scale-invariant initial power spectra. Although n=1 is often justified by appealing to the inflation scenario, inflationary models with mild deviations from scale-invariance are not uncommon and models with significant running of the spectral index are plausible. Even mild deviations from scale-invariance can be important because halo collapse times and densities depend on the relative amount of small-scale power. We choose several popular models of inflation and work out the ramifications for galaxy central densities. For each model, we calculate its COBE-normalized power spectrum and deduce the implied halo densities using a semi-analytic method calibrated against N-body simulations. We compare our predictions to a sample of dark matter-dominated galaxies using a non-parametric measure of the density. While standard n=1, LCDM halos are overdense by a factor of 6, several of our example inflation+CDM models predict halo densities well within the range preferred by observations. We also show how the presence of massive (0.5 eV) neutrinos may help to alleviate the central density problem even with n=1. We conclude that galaxy central densities may not be as problematic for the CDM paradigm as is sometimes assumed: rather than telling us something about the nature of the dark matter, galaxy rotation curves may be telling us something about inflation and/or neutrinos. An important test of this idea will be an eventual consensus on the value of sigma_8, the rms overdensity on the scale 8 h^-1 Mpc. Our successful models have values of sigma_8 approximately 0.75, which is within the range of recent determinations. Finally, models with n>1 (or sigma_8 > 1) are highly disfavored.Comment: 13 pages, 6 figures. Minor changes made to reflect referee's Comments, error in Eq. (18) corrected, references updated and corrected, conclusions unchanged. Version accepted for publication in Phys. Rev. D, scheduled for 15 August 200

Large-scale pharmacogenomic study of sulfonylureas and the QT, JT and QRS intervals: CHARGE Pharmacogenomics Working Group

Sulfonylureas, a commonly used class of medication used to treat type 2 diabetes, have been associated with an increased risk of cardiovascular disease. Their effects on QT interval duration and related electrocardiographic phenotypes are potential mechanisms for this adverse effect. In 11 ethnically diverse cohorts that included 71 857 European, African-American and Hispanic/Latino ancestry individuals with repeated measures of medication use and electrocardiogram (ECG) measurements, we conducted a pharmacogenomic genome-wide association study of sulfonylurea use and three ECG phenotypes: QT, JT and QRS intervals. In ancestry-specific meta-analyses, eight novel pharmacogenomic loci met the threshold for genome-wide significance (P<5 × 10−8), and a pharmacokinetic variant in CYP2C9 (rs1057910) that has been associated with sulfonylurea-related treatment effects and other adverse drug reactions in previous studies was replicated. Additional research is needed to replicate the novel findings and to understand their biological basis

Cosmological parameter estimation and the inflationary cosmology

We consider approaches to cosmological parameter estimation in the inflationary cosmology, focussing on the required accuracy of the initial power spectra. Parametrizing the spectra, for example by power-laws, is well suited to testing the inflationary paradigm but will only correctly estimate cosmological parameters if the parametrization is sufficiently accurate, and we investigate conditions under which this is achieved both for present data and for upcoming satellite data. If inflation is favoured, reliable estimation of its physical parameters requires an alternative approach adopting its detailed predictions. For slow-roll inflation, we investigate the accuracy of the predicted spectra at first and second order in the slow-roll expansion (presenting the complete second-order corrections for the tensors for the first time). We find that within the presently-allowed parameter space, there are regions where it will be necessary to include second-order corrections to reach the accuracy requirements of MAP and Planck satellite data. We end by proposing a data analysis pipeline appropriate for testing inflation and for cosmological parameter estimation from high-precision data.Comment: 15 pages RevTeX file with figures incorporated. Slow-roll inflation module for use with the CAMB program can be found at http://astronomy.cpes.susx.ac.uk/~sleach/inflation/ This version corrects a typo in the definition of z_S (after Eq.1) and supersedes the journal versio