Sphingosine kinases : emerging structure function insights

Sphingosine kinases (SK1 and SK2) catalyse the conversion of sphingosine into sphingosine 1-phosphate and control fundamental cellular processes, including cell survival, proliferation, differentiation, migration, and immune function. In this review, we highlight recent breakthroughs in the structural and functional characterisation of SK1 and these are contextualised by analysis of crystal structures for closely related prokaryotic lipid kinases. We identify a putative dimerisation interface and propose novel regulatory mechanisms governing structural plasticity induced by phosphorylation and interaction with phospholipids and proteins. Our analysis suggests that the catalytic function and regulation of the enzymes might be dependent on conformational mobility and it provides a roadmap for future interrogation of SK1 function and its role in physiology and disease

Second Order Perturbations of Flat Dust FLRW Universes with a Cosmological Constant

We summarize recent results concerning the evolution of second order perturbations in flat dust irrotational FLRW models with $\Lambda\ne 0$. We show that asymptotically these perturbations tend to constants in time, in agreement with the cosmic no-hair conjecture. We solve numerically the second order scalar perturbation equation, and very briefly discuss its all time behaviour and some possible implications for the structure formation.Comment: 6 pages, 1 figure. to be published in "Proceedings of the 5th Alexander Friedmann Seminar on Gravitation and Cosmology", Int. Journ. Mod. Phys. A (2002). Macros: ws-ijmpa.cls, ws-p9-75x6-50.cl

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

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

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.

Nonlinear Effects in the Cosmic Microwave Background

Major advances in the observation and theory of cosmic microwave background anisotropies have opened up a new era in cosmology. This has encouraged the hope that the fundamental parameters of cosmology will be determined to high accuracy in the near future. However, this optimism should not obscure the ongoing need for theoretical developments that go beyond the highly successful but simplified standard model. Such developments include improvements in observational modelling (e.g. foregrounds, non-Gaussian features), extensions and alternatives to the simplest inflationary paradigm (e.g. non-adiabatic effects, defects), and investigation of nonlinear effects. In addition to well known nonlinear effects such as the Rees-Sciama and Ostriker-Vishniac effects, further nonlinear effects have recently been identified. These include a Rees-Sciama-type tensor effect, time-delay effects of scalar and tensor lensing, nonlinear Thomson scattering effects and a nonlinear shear effect. Some of the nonlinear effects and their potential implications are discussed.Comment: Invited contribution to Relativistic Cosmology Symposium (celebrating the 60th year of GFR Ellis); to appear Gen. Rel. Gra

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

Was Sinn Féin dying? A quantitative post-mortem of the party's decline and the emergence of Fianna Fáil

This article calls for a reappraisal of the consensus surrounding the split within Sinn Féin in 1926 that led to the foundation of Fianna Fáil. It demonstrates that quantitative factors cited to demonstrate Sinn Féin’s “terminal” decline – finances, cumann numbers, and election results – and to explain de Valera’s decision to leave Sinn Féin and establish a rival republican organisation, Fianna Fáil, do not provide sufficient objective grounds to explain the republican leader’s actions. This article demonstrates that Sinn Féin’s election results during the period in question (1923-1926) were encouraging and the decline in finances and cumann numbers can be explained by the fact that the base year used to compare progress was 1923, an election year. Moreover, this article compares the performance of Sinn Féin to the first five years of Fianna Fáil (1926-1931) to show that what has been interpreted as terminal decline can also be attributed to normal inter-election lulls in party activity. Correspondingly, subjective factors – e.g. personal rivalries, differences in ideology, organisational style and levels of patience in terms of achieving political power – were most likely the determining factors rather than organisational decline

A Texture Bestiary

Textures are topologically nontrivial field configurations which can exist in a field theory in which a global symmetry group $G$ is broken to a subgroup $H$, if the third homotopy group \p3 of $G/H$ is nontrivial. We compute this group for a variety of choices of $G$ and $H$, revealing what symmetry breaking patterns can lead to texture. We also comment on the construction of texture configurations in the different models.Comment: 34 pages, plain Tex. (Minor corrections to an old paper.

Skewness in the Cosmic Microwave Background Anisotropy from Inflationary Gravity Wave Background

In the context of inflationary scenarios, the observed large angle anisotropy of the Cosmic Microwave Background (CMB) temperature is believed to probe the primordial metric perturbations from inflation. Although the perturbations from inflation are expected to be gaussian random fields, there remains the possibility that nonlinear processes at later epochs induce ``secondary'' non-gaussian features in the corresponding CMB anisotropy maps. The non-gaussianity induced by nonlinear gravitational instability of scalar (density) perturbations has been investigated in existing literature. In this paper, we highlight another source of non-gaussianity arising out of higher order scattering of CMB photons off the metric perturbations. We provide a simple and elegant formalism for deriving the CMB temperature fluctuations arising due to the Sachs-Wolfe effect beyond the linear order. In particular, we derive the expression for the second order CMB temperature fluctuations. The multiple scattering effect pointed out in this paper leads to the possibility that tensor metric perturbation, i.e., gravity waves (GW) which do not exhibit gravitational instability can still contribute to the skewness in the CMB anisotropy maps. We find that in a flat $\Omega =1$ universe, the skewness in CMB contributed by gravity waves via multiple scattering effect is comparable to that from the gravitational instability of scalar perturbations for equal contribution of the gravity waves and scalar perturbations to the total rms CMB anisotropy. The secondary skewness is found to be smaller than the cosmic variance leading to the conclusion that inflationary scenarios do predict that the observed CMB anisotropy should be statistically consistent with a gaussian random distribution.Comment: 10 pages, Latex (uses revtex), 1 postscript figure included. Accepted for publication in Physical Review