Requirement for sphingosine kinase 1 in mediating phase 1 of the hypotensive response to anandamide in the anaesthetised mouse

In the isolated rat carotid artery, the endocannabinoid anandamide induces endothelium-dependent relaxation via activation of the enzyme sphingosine kinase (SK). This generates sphingosine-1-phosphate (S1P) which can be released from the cell and activates S1P receptors on the endothelium. In anaesthetised mice, anandamide has a well-characterised triphasic effect on blood pressure but the contribution of SK and S1P receptors in mediating changes in blood pressure has never been studied. Therefore, we assessed this in the current study. The peak hypotensive response to 1 and 10 mg/kg anandamide was measured in control C57BL/6 mice and in mice pretreated with selective inhibitors of SK1 (BML-258, also known as SK1-I) or SK2 ((R)-FTY720 methylether (ROMe), a dual SK1/2 inhibitor (SKi) or an S1P1 receptor antagonist (W146). Vasodilator responses to S1P were also studied in isolated mouse aortic rings. The hypotensive response to anandamide was significantly attenuated by BML-258 but not by ROMe. Antagonising S1P1 receptors with W146 completely blocked the fall in systolic but not diastolic blood pressure in response to anandamide. S1P induced vasodilation in denuded aortic rings was blocked by W146 but caused no vasodilation in endothelium-intact rings. This study provides evidence that the SK1/S1P regulatory-axis is necessary for the rapid hypotension induced by anandamide. Generation of S1P in response to anandamide likely activates S1P1 to reduce total peripheral resistance and lower mean arterial pressure. These findings have important implications in our understanding of the hypotensive and cardiovascular actions of cannabinoids

Validation of a skinfold based index for tracking proportional changes in lean mass

BACKGROUND: The lean mass index (LMI) is a new empirical measure that tracks within‐subject proportional changes in body mass adjusted for changes in skinfold thickness. OBJECTIVE: To compare the ability of the LMI and other skinfold derived measures of lean mass to monitor changes in lean mass. METHODS: 20 elite rugby union players undertook full anthropometric profiles on two occasions 10 weeks apart to calculate the LMI and five skinfold based measures of lean mass. Hydrodensitometry, deuterium dilution, and dual energy x ray absorptiometry provided a criterion choice, four compartment (4C) measure of lean mass for validation purposes. Regression based measures of validity, derived for within‐subject proportional changes through log transformation, included correlation coefficients and standard errors of the estimate. RESULTS: The correlation between change scores for the LMI and 4C lean mass was moderate (0.37, 90% confidence interval −0.01 to 0.66) and similar to the correlations for the other practical measures of lean mass (range 0.26 to 0.42). Standard errors of the estimate for the practical measures were in the range of 2.8–2.9%. The LMI correctly identified the direction of change in 4C lean mass for 14 of the 20 athletes, compared with 11 to 13 for the other practical measures of lean mass. CONCLUSIONS: The LMI is probably as good as other skinfold based measures for tracking lean mass and is theoretically more appropriate. Given the impracticality of the 4C criterion measure for routine field use, the LMI may offer a convenient alternative for monitoring physique changes, provided its utility is established under various conditions

Iterative Approach to Gravitational Lensing Theory

We develop an iterative approach to gravitational lensing theory based on approximate solutions of the null geodesic equations. The approach can be employed in any space-time which is ``close'' to a space-time in which the null geodesic equations can be completely integrated, such as Minkowski space-time, Robertson-Walker cosmologies, or Schwarzschild-Kerr geometries. To illustrate the method, we construct the iterative gravitational lens equations and time of arrival equation for a single Schwarzschild lens. This example motivates a discussion of the relationship between the iterative approach, the standard thin lens formulation, and an exact formulation of gravitational lensing.Comment: 27 pages, 2 figures, submitted to Phys.Rev.D, minor revisions, new reference

Quasar Proper Motions and Low-Frequency Gravitational Waves

We report observational upper limits on the mass-energy of the cosmological gravitational-wave background, from limits on proper motions of quasars. Gravitational waves with periods longer than the time span of observations produce a simple pattern of apparent proper motions over the sky, composed primarily of second-order transverse vector spherical harmonics. A fit of such harmonics to measured motions yields a 95%-confidence limit on the mass-energy of gravitational waves with frequencies <2e-9 Hz, of <0.11/h*h times the closure density of the universe.Comment: 15 pages, 1 figure. Also available at http://charm.physics.ucsb.edu:80/people/cgwinn/cgwinn_group/index.htm

Deep Drilling with the ANDRILL Program in Antarctica

ANDRILL (ANtarctic geological DRILLing) is a new international, multi-disciplinary drilling program that targets geological records that lie hidden beneath the icy blanket of Antarctica. The primary objective is to investigate Antarctica’s role in global environmental change over the past sixty-fi ve million years, at various scales of age resolution, and thereby enhance our understanding of Antarctica’s potential response to future global changes. Efforts to understand the infl uence of Antarctica on global climate change require a fundamental knowledge of how the Antarctic cryosphere (ice sheets, ice shelves, and sea ice) has evolved, not only in recent times but also during earlier geological periods when global temperature and atmospheric CO2 levels were similar to what might be reached by the end of this century. ANDRILL’s integrated science approach will use stratigraphic drilling, coring, and multi-proxy core analysis combined with geophysical surveys and numerical modeling to study the Cenozoic history of Antarctic climate and ice sheets, the evolution of polar biota, Antarctic tectonism, and Antarctica’s role in the evolution of Earth’s ocean–climate system

A computational framework to emulate the human perspective in flow cytometric data analysis

Background: In recent years, intense research efforts have focused on developing methods for automated flow cytometric data analysis. However, while designing such applications, little or no attention has been paid to the human perspective that is absolutely central to the manual gating process of identifying and characterizing cell populations. In particular, the assumption of many common techniques that cell populations could be modeled reliably with pre-specified distributions may not hold true in real-life samples, which can have populations of arbitrary shapes and considerable inter-sample variation. &lt;p/&gt;Results: To address this, we developed a new framework flowScape for emulating certain key aspects of the human perspective in analyzing flow data, which we implemented in multiple steps. First, flowScape begins with creating a mathematically rigorous map of the high-dimensional flow data landscape based on dense and sparse regions defined by relative concentrations of events around modes. In the second step, these modal clusters are connected with a global hierarchical structure. This representation allows flowScape to perform ridgeline analysis for both traversing the landscape and isolating cell populations at different levels of resolution. Finally, we extended manual gating with a new capacity for constructing templates that can identify target populations in terms of their relative parameters, as opposed to the more commonly used absolute or physical parameters. This allows flowScape to apply such templates in batch mode for detecting the corresponding populations in a flexible, sample-specific manner. We also demonstrated different applications of our framework to flow data analysis and show its superiority over other analytical methods. &lt;p/&gt;Conclusions: The human perspective, built on top of intuition and experience, is a very important component of flow cytometric data analysis. By emulating some of its approaches and extending these with automation and rigor, flowScape provides a flexible and robust framework for computational cytomics

Cosmic Microwave Background anisotropies from second order gravitational perturbations

This paper presents a complete analysis of the effects of second order gravitational perturbations on Cosmic Microwave Background anisotropies, taking explicitly into account scalar, vector and tensor modes. We also consider the second order perturbations of the metric itself obtaining them, for a universe dominated by a collision-less fluid, in the Poisson gauge, by transforming the known results in the synchronous gauge. We discuss the resulting second order anisotropies in the Poisson gauge, and analyse the possible relevance of the different terms. We expect that, in the simplest scenarios for structure formation, the main effect comes from the gravitational lensing by scalar perturbations, that is known to give a few percent contribution to the anisotropies at small angular scales.Comment: 15 pages, revtex, no figures. Version to be published in Phys. Rev.

The Angular Trispectra of CMB Temperature and Polarization

We develop the formalism necessary to study four-point functions of the cosmic microwave background (CMB) temperature and polarization fields. We determine the general form of CMB trispectra, with the constraints imposed by the assumption of statistical isotropy of the CMB fields, and derive expressions for their estimators, as well as their Gaussian noise properties. We apply these techniques to initial non-Gaussianity of a form motivated by inflationary models. Due to the large number of four-point configurations, the sensitivity of the trispectra to initial non-Gaussianity approaches that of the temperature bispectrum at high multipole moment. These trispectra techniques will also be useful in the study of secondary anisotropies induced for example by the gravitational lensing of the CMB by the large scale structure of the universe.Comment: 16 pages, 4 figures; typographical errors correcte

On Non-Gaussianity in the Curvaton Scenario

Since a positive future detection of non-linearity in the cosmic microwave background anisotropy pattern might allow to descriminate among different mechanisms giving rise to cosmological adiabatic perturbations, we study the evolution of the second-order cosmological curvature perturbation on super-horizon scales in the curvaton scenario. We provide the exact expression for the non-Gaussianity in the primordial perturbations including gravitational second-order corrections which are particularly relevant in the case in which the curvaton dominates the energy density before it decays. As a byproduct, we show that in the standard scenario where cosmological curvature perturbations are induced by the inflaton field, the second-order curvature perturbation is conserved even during the reheating stage after inflation.Comment: LaTeX file, 8 pages. Some typos corrected. In Sec. IIIA non-local gradient terms explicitly accounted for in the final non-linear parameter and references adde

Evolution of Second-Order Cosmological Perturbations and Non-Gaussianity

We present a second-order gauge-invariant formalism to study the evolution of curvature perturbations in a Friedmann-Robertson-Walker universe filled by multiple interacting fluids. We apply such a general formalism to describe the evolution of the second-order curvature perturbations in the standard one-single field inflation, in the curvaton and in the inhomogeneous reheating scenarios for the generation of the cosmological perturbations. Moreover, we provide the exact expression for the second-order temperature anisotropies on large scales, including second-order gravitational effects and extend the well-known formula for the Sachs-Wolfe effect at linear order. Our findings clarify what is the exact non-linearity parameter f_NL entering in the determination of higher-order statistics such as the bispectrum of Cosmic Microwave Background temperature anisotropies. Finally, we compute the level of non-Gaussianity in each scenario for the creation of cosmological perturbations.Comment: 14 pages, LaTeX file. Further comments adde