A single amino acid determines preference between phospholipids and reveals length restriction for activation ofthe S1P₄ receptor

Background<br/><br/> Sphingosine-1-phosphate and lysophosphatidic acid (LPA) are ligands for two related families of G protein-coupled receptors, the S1P and LPA receptors, respectively. The lysophospholipid ligands of these receptors are structurally similar, however recognition of these lipids by these receptors is highly selective. A single residue present within the third transmembrane domain (TM) of S1P receptors is thought to determine ligand selectivity; replacement of the naturally occurring glutamic acid with glutamine (present at this position in the LPA receptors) has previously been shown to be sufficient to change the specificity of S1P<sub>1</sub> from S1P to 18:1 LPA.<br/><br/> Results<br/><br/> We tested whether mutation of this "ligand selectivity" residue to glutamine could confer LPA-responsiveness to the related S1P receptor, S1P<sub>4</sub>. This mutation severely affected the response of S1P<sub>4</sub> to S1P in a [<sup>35</sup>S]GTPγS binding assay, and imparted sensitivity to LPA species in the order 14:0 LPA > 16:0 LPA > 18:1 LPA. These results indicate a length restriction for activation of this receptor and demonstrate the utility of using LPA-responsive S1P receptor mutants to probe binding pocket length using readily available LPA species. Computational modelling of the interactions between these ligands and both wild type and mutant S1P<sub>4</sub> receptors showed excellent agreement with experimental data, therefore confirming the fundamental role of this residue in ligand recognition by S1P receptors.<br/><br/> Conclusions<br/><br/> Glutamic acid in the third transmembrane domain of the S1P receptors is a general selectivity switch regulating response to S1P over the closely related phospholipids, LPA. Mutation of this residue to glutamine confers LPA responsiveness with preference for short-chain species. The preference for short-chain LPA species indicates a length restriction different from the closely related S1P<sub>1</sub> receptor

Optimal query complexity for estimating the trace of a matrix

Given an implicit $n\times n$ matrix $A$ with oracle access $x^TA x$ for any $x\in \mathbb{R}^n$, we study the query complexity of randomized algorithms for estimating the trace of the matrix. This problem has many applications in quantum physics, machine learning, and pattern matching. Two metrics are commonly used for evaluating the estimators: i) variance; ii) a high probability multiplicative-approximation guarantee. Almost all the known estimators are of the form $\frac{1}{k}\sum_{i=1}^k x_i^T A x_i$ for $x_i\in \mathbb{R}^n$ being i.i.d. for some special distribution. Our main results are summarized as follows. We give an exact characterization of the minimum variance unbiased estimator in the broad class of linear nonadaptive estimators (which subsumes all the existing known estimators). We also consider the query complexity lower bounds for any (possibly nonlinear and adaptive) estimators: (1) We show that any estimator requires $\Omega(1/\epsilon)$ queries to have a guarantee of variance at most $\epsilon$. (2) We show that any estimator requires $\Omega(\frac{1}{\epsilon^2}\log \frac{1}{\delta})$ queries to achieve a $(1\pm\epsilon)$-multiplicative approximation guarantee with probability at least $1 - \delta$. Both above lower bounds are asymptotically tight. As a corollary, we also resolve a conjecture in the seminal work of Avron and Toledo (Journal of the ACM 2011) regarding the sample complexity of the Gaussian Estimator.Comment: full version of the paper in ICALP 201

On the asymptotic magnitude of subsets of Euclidean space

Magnitude is a canonical invariant of finite metric spaces which has its origins in category theory; it is analogous to cardinality of finite sets. Here, by approximating certain compact subsets of Euclidean space with finite subsets, the magnitudes of line segments, circles and Cantor sets are defined and calculated. It is observed that asymptotically these satisfy the inclusion-exclusion principle, relating them to intrinsic volumes of polyconvex sets.Comment: 23 pages. Version 2: updated to reflect more recent work, in particular, the approximation method is now known to calculate (rather than merely define) the magnitude; also minor alterations such as references adde

Thermodynamics of a Trapped Bose-Fermi Mixture

By using the Hartree-Fock-Bogoliubov equations within the Popov approximation, we investigate the thermodynamic properties of a dilute binary Bose-Fermi mixture confined in an isotropic harmonic trap. For mixtures with an attractive Bose-Fermi interaction we find a sizable enhancement of the condensate fraction and of the critical temperature of Bose-Einstein condensation with respect to the predictions for a pure interacting Bose gas. Conversely, the influence of the repulsive Bose-Fermi interaction is less pronounced. The possible relevance of our results in current experiments on trapped $^{87}{\rm Rb}-^{40}${\rm K} mixtures is discussed.Comment: 5 pages + 4 figures; minor changes, final version to appear in Phys. Rev. A; the extension work on the finite-temperature low-lying excitations can be found in cond-mat/030763

Relaxation rates and collision integrals for Bose-Einstein condensates

Near equilibrium, the rate of relaxation to equilibrium and the transport properties of excitations (bogolons) in a dilute Bose-Einstein condensate (BEC) are determined by three collision integrals, $\mathcal{G}^{12}$, $\mathcal{G}^{22}$, and $\mathcal{G}^{31}$. All three collision integrals conserve momentum and energy during bogolon collisions, but only $\mathcal{G}^{22}$ conserves bogolon number. Previous works have considered the contribution of only two collision integrals, $\mathcal{G}^{22}$ and $\mathcal{G}^{12}$. In this work, we show that the third collision integral $\mathcal{G}^{31}$ makes a significant contribution to the bogolon number relaxation rate and needs to be retained when computing relaxation properties of the BEC. We provide values of relaxation rates in a form that can be applied to a variety of dilute Bose-Einstein condensates.Comment: 18 pages, 4 figures, accepted by Journal of Low Temperature Physics 7/201

Experimental vertical stability studies for ITER performance and design

Operating experimental devices have provided key inputs to the design process for ITER axisymmetric control. In particular, experiments have quantified controllability and robustness requirements in the presence of realistic noise and disturbance environments, which are difficult or impossible to characterize with modelling and simulation alone. This kind of information is particularly critical for ITER vertical control, which poses the highest demands on poloidal field system performance, since the consequences of loss of vertical control can be severe. This work describes results of multi-machine studies performed under a joint ITPA experiment (MDC-13) on fundamental vertical control performance and controllability limits. We present experimental results from Alcator C-Mod, DIII-D, NSTX, TCV and JET, along with analysis of these data to provide vertical control performance guidance to ITER. Useful metrics to quantify this control performance include the stability margin and maximum controllable vertical displacement. Theoretical analysis of the maximum controllable vertical displacement suggests effective approaches to improving performance in terms of this metric, with implications for ITER design modifications. Typical levels of noise in the vertical position measurement and several common disturbances which can challenge the vertical control loop are assessed and analysed.United States Department of Energy (DE-FC02-04ER54698, DEAC52- 07NA27344, and DE-FG02-04ER54235

Finite temperature effects on the collapse of trapped Bose-Fermi mixtures

By using the self-consistent Hartree-Fock-Bogoliubov-Popov theory, we present a detailed study of the mean-field stability of spherically trapped Bose-Fermi mixtures at finite temperature. We find that, by increasing the temperature, the critical particle number of bosons (or fermions) and the critical attractive Bose-Fermi scattering length increase, leading to a significant stabilization of the mixture.Comment: 5 pages, 4 figures; minor changes, proof version, to appear in Phys. Rev. A (Nov. 1, 2003

Finite temperature excitations of a trapped Bose-Fermi mixture

We present a detailed study of the low-lying collective excitations of a spherically trapped Bose-Fermi mixture at finite temperature in the collisionless regime. The excitation frequencies of the condensate are calculated self-consistently using the static Hartree-Fock-Bogoliubov theory within the Popov approximation. The frequency shifts and damping rates due to the coupled dynamics of the condensate, noncondensate, and degenerate Fermi gas are also taken into account by means of the random phase approximation and linear response theory. In our treatment, the dipole excitation remains close to the bare trapping frequency for all temperatures considered, and thus is consistent with the generalized Kohn theorem. We discuss in some detail the behavior of monopole and quadrupole excitations as a function of the Bose-Fermi coupling. At nonzero temperatures we find that, as the mixture moves towards spatial separation with increasing Bose-Fermi coupling, the damping rate of the monopole (quadrupole) excitation increases (decreases). This provides us a useful signature to identify the phase transition of spatial separation.Comment: 10 pages, 8 figures embedded; to be published in Phys. Rev.

Precision charging of microparticles in plasma via the Rayleigh instability for evaporating charged liquid droplets

In this paper we describe a novel method for delivering a precise, known amount of electric charge to a micron-sized solid target. Aerosolised microparticles passed through a plasma discharge will acquire significant electric charge. The fluid stability under evaporative stress is a key aspect that is core to the research. Initially stable charged aerosols subject to evaporation (i.e. a continually changing radius) may encounter the Rayleigh stability limit. This limit arises from the electrostatic and surface tension forces and determines the maximum charge a stable droplet can retain, as a function of radius. We demonstrate that even if the droplet charge is initially much less than the Rayleigh limit, the stability limit will be encountered as the droplet evaporates. The instability emission mechanism is strongly linked to the final charge deposited on the target, providing a mechanism that can be used to ensure a predictable charge deposit on a known encapsulated microparticle

Dark soliton states of Bose-Einstein condensates in anisotropic traps

Dark soliton states of Bose-Einstein condensates in harmonic traps are studied both analytically and computationally by the direct solution of the Gross-Pitaevskii equation in three dimensions. The ground and self-consistent excited states are found numerically by relaxation in imaginary time. The energy of a stationary soliton in a harmonic trap is shown to be independent of density and geometry for large numbers of atoms. Large amplitude field modulation at a frequency resonant with the energy of a dark soliton is found to give rise to a state with multiple vortices. The Bogoliubov excitation spectrum of the soliton state contains complex frequencies, which disappear for sufficiently small numbers of atoms or large transverse confinement. The relationship between these complex modes and the snake instability is investigated numerically by propagation in real time.Comment: 11 pages, 8 embedded figures (two in color