Use of a distant reporter group as evidence for a conformational change in a sensory receptor

A highly sensitive method for demonstrating ligand-induced conformational changes in protein molecules in solution is described. The method utilizes an environmentally sensitive reporter group that is known to be distant from the active site. In the present application a conformational change is demonstrated in the galactose receptor of Salmonella typhimurium, involved in bacterial sensing and transport, by means of an extrinsic fluorophore, 5-iodoacetamidofluorescein, attached at a single methionine residue, and the intrinsic tryptophan fluorophore. Binding of the ligand galactose perturbs the microenvironment of both the fluorescein and tryptophan, as shown by both spectral and potassium iodide quenching changes. The distance between the two dyes is established by fluorescence energy transfer methods to be 41 ± 10 angstrom. Since only one molecule of galactose binds per molecule of receptor and since the galactose molecule is only about 5 angstrom in length, changes at one of these sites reflect the result of an indirect effect. Hence, there must be a ligand-induced conformational change that is propagated a minimum of 30 angstrom through the receptor molecule

The Gremlin Graph Traversal Machine and Language

Gremlin is a graph traversal machine and language designed, developed, and distributed by the Apache TinkerPop project. Gremlin, as a graph traversal machine, is composed of three interacting components: a graph $G$, a traversal $\Psi$, and a set of traversers $T$. The traversers move about the graph according to the instructions specified in the traversal, where the result of the computation is the ultimate locations of all halted traversers. A Gremlin machine can be executed over any supporting graph computing system such as an OLTP graph database and/or an OLAP graph processor. Gremlin, as a graph traversal language, is a functional language implemented in the user's native programming language and is used to define the $\Psi$ of a Gremlin machine. This article provides a mathematical description of Gremlin and details its automaton and functional properties. These properties enable Gremlin to naturally support imperative and declarative querying, host language agnosticism, user-defined domain specific languages, an extensible compiler/optimizer, single- and multi-machine execution models, hybrid depth- and breadth-first evaluation, as well as the existence of a Universal Gremlin Machine and its respective entailments.Comment: To appear in the Proceedings of the 2015 ACM Database Programming Languages Conferenc

Wide-Field Multi-Parameter FLIM: Long-Term Minimal Invasive Observation of Proteins in Living Cells.

Time-domain Fluorescence Lifetime Imaging Microscopy (FLIM) is a remarkable tool to monitor the dynamics of fluorophore-tagged protein domains inside living cells. We propose a Wide-Field Multi-Parameter FLIM method (WFMP-FLIM) aimed to monitor continuously living cells under minimum light intensity at a given illumination energy dose. A powerful data analysis technique applied to the WFMP-FLIM data sets allows to optimize the estimation accuracy of physical parameters at very low fluorescence signal levels approaching the lower bound theoretical limit. We demonstrate the efficiency of WFMP-FLIM by presenting two independent and relevant long-term experiments in cell biology: 1) FRET analysis of simultaneously recorded donor and acceptor fluorescence in living HeLa cells and 2) tracking of mitochondrial transport combined with fluorescence lifetime analysis in neuronal processes

HST/ACS Images of the GG Tauri Circumbinary Disk

Hubble Space Telescope Advanced Camera for Surveys images of the young binary GG Tauri and its circumbinary disk in V and I bandpasses were obtained in 2002 and are the most detailed of this system to date. The confirm features previously seen in the disk including: a "gap" apparently caused by shadowing from circumstellar material; an asymmetrical distribution of light about the line of sight on the near edge of the disk; enhanced brightness along the near edge of the disk due to forward scattering; and a compact reflection nebula near the secondary star. New features are seen in the ACS images: two short filaments along the disk; localized but strong variations in disk intensity ("gaplets"); and a "spur" or filament extending from the reflection nebulosity near the secondary. The back side of the disk is detected in the V band for the first time. The disk appears redder than the combined light from the stars, which may be explained by a varied distribution of grain sizes. The brightness asymmetries along the disk suggest that it is asymmetrically illuminated by the stars due to extinction by nonuniform circumstellar material or the illuminated surface of the disk is warped by tidal effects (or perhaps both). Localized, time-dependent brightness variations in the disk are also seen.Comment: 28 pages, 7 figures, accepted for publication in the Astronomical Journa

Rocket and FUSE Observations of IC 405: Differential Extinction and Fluorescent Molecular Hydrogen

We present far-ultraviolet spectroscopy of the emission/reflection nebula IC 405 obtained by a rocket-borne long-slit spectrograph and the Far Ultraviolet Spectroscopic Explorer. Both data sets show a rise in the ratio of the nebular surface brightness to stellar flux (S/F_*) of approximately two orders of magnitude towards the blue end of the far-UV bandpass. Scattering models using simple dust geometries fail to reproduce the observed S/F_* for realistic grain properties. The high spectral resolution of the FUSE data reveals a rich fluorescent molecular hydrogen spectrum ~1000" north of the star that is clearly distinguished from the steady blue continuum. The S/F_* remains roughly constant at all nebular pointings, showing that fluorescent molecular hydrogen is not the dominant cause for the blue rise. We discuss three possible mechanisms for the ``Blue Dust'': differential extinction of the dominant star (HD 34078), unusual dust grain properties, and emission from nebular dust. We conclude that uncertainties in the nebular geometry and the degree of dust clumping are most likely responsible for the blue rise. As an interesting consequence of this result, we consider how IC 405 would appear in a spatially unresolved observation. If IC 405 was observed with a spatial resolution of less than 0.4 pc, for example, an observer would infer a far-UV flux that was 2.5 times the true value, giving the appearance of a stellar continuum that was less extinguished than radiation from the surrounding nebula, an effect that is reminiscent of the observed ultraviolet properties of starburst galaxies.Comment: 8 pages, 9 figures, using emulateapj, ApJ - accepte

M87: A Misaligned BL LAC?

The nuclear region of M87 was observed with the Faint Object Spectrograph (FOS) on the Hubble Space Telescope (HST) at 6 epochs, spanning 18 months, after the HST image quality was improved with the deployment of the corrective optics (COSTAR) in December 1993. From the FOS target acquisition data, we have established that the flux from the optical nucleus of M87 varies by a factor ~2 on time scales of ~2.5 months and by as much as 25% over 3 weeks, and remains unchanged (<= 2.5%) on time scales of ~1 day. The changes occur in an unresolved central region <= 5 pc in diameter, with the physical size of the emitting region limited by the observed time scales to a few hundred gravitational radii. The featureless continuum spectrum becomes bluer as it brightens while emission lines remain unchanged. This variability combined with the observations of the continuum spectral shape, strong relativistic boosting and the detection of significant superluminal motions in the jet, strongly suggest that M87 belongs to the class of BL Lac objects but is viewed at an angle too large to reveal the classical BL Lac properties.Comment: 12 pages, 3 Postscript figure

Modeling of Kidney Hemodynamics: Probability-Based Topology of an Arterial Network

Through regulation of the extracellular fluid volume, the kidneys provide important long-term regulation of blood pressure. At the level of the individual functional unit (the nephron), pressure and flow control involves two different mechanisms that both produce oscillations. The nephrons are arranged in a complex branching structure that delivers blood to each nephron and, at the same time, provides a basis for an interaction between adjacent nephrons. The functional consequences of this interaction are not understood, and at present it is not possible to address this question experimentally. We provide experimental data and a new modeling approach to clarify this problem. To resolve details of microvascular structure, we collected 3D data from more than 150 afferent arterioles in an optically cleared rat kidney. Using these results together with published micro-computed tomography (μCT) data we develop an algorithm for generating the renal arterial network. We then introduce a mathematical model describing blood flow dynamics and nephron to nephron interaction in the network. The model includes an implementation of electrical signal propagation along a vascular wall. Simulation results show that the renal arterial architecture plays an important role in maintaining adequate pressure levels and the self-sustained dynamics of nephrons

GUN: An Efficient Execution Strategy for Querying the Web of Data

International audienceLocal-As-View (LAV) mediators provide a uniform interface to a federation of heterogeneous data sources, attempting to execute queries against the federation. LAV mediators rely on query rewriters to translate mediator queries into equivalent queries on the federated data sources. The query rewriting problem in LAV mediators has shown to be NP-complete, and there may be an exponential number of rewritings, making unfeasible the execution or even generation of all the rewritings for some queries. The complexity of this problem can be particularly impacted when queries and data sources are described using SPARQL conjunctive queries, for which millions of rewritings could be generated. We aim at providing an efficient solution to the problem of executing LAV SPARQL query rewritings while the gathered answer is as complete as possible. We formulate the Result-Maximal k-Execution problem (ReMakE) as the problem of maximizing the query results obtained from the execution of only k rewritings. Additionally, a novel query execution strategy called GUN is proposed to solve the ReMakE problem. Our experimental evaluation demonstrates that GUN outperforms traditional techniques in terms of answer completeness and execution time