Geometry-controlled kinetics

It has long been appreciated that transport properties can control reaction kinetics. This effect can be characterized by the time it takes a diffusing molecule to reach a target -- the first-passage time (FPT). Although essential to quantify the kinetics of reactions on all time scales, determining the FPT distribution was deemed so far intractable. Here, we calculate analytically this FPT distribution and show that transport processes as various as regular diffusion, anomalous diffusion, diffusion in disordered media and in fractals fall into the same universality classes. Beyond this theoretical aspect, this result changes the views on standard reaction kinetics. More precisely, we argue that geometry can become a key parameter so far ignored in this context, and introduce the concept of "geometry-controlled kinetics". These findings could help understand the crucial role of spatial organization of genes in transcription kinetics, and more generally the impact of geometry on diffusion-limited reactions.Comment: Submitted versio

South American Spider Mites: New Hosts and Localities

In order to contribute to taxonomic information on Tetranychid mites (Acari: Tetranychidae) in South America, surveys were conducted in Brazil (15 States and the Federal District) and Uruguay (one Department); 550 samples of 120 plant species were collected. Tetranychid mite infestations were confirmed in 204 samples, and 22 species belonging to seven genera of the Bryobiinae and Tetranychinae subfamilies were identified on 58 different host plants. Thirty-six new plant hosts were found in Brazil, South America, and worldwide for the following species: Eutetranychus banksi (McGregor); Mononychellus tanajoa (Bondar); Oligonychus anonae Paschoal; O. mangiferus (Rahman and Sapra); Tetranychus bastosi Tuttle, Baker and Sales; T. desertorum Banks, 1900, T. evansi Baker and Pritchard; T. ludeni Zacher; T. mexicanus (McGregor); T. neocaledonicus André; and T. urticae Koch. Four new localities in Brazil were reported for Eotetranychus tremae De Leon; O. anonae; Panonychus ulmi (Koch); and T. gloveri Baker and Pritchard

N-player quantum games in an EPR setting

The $N$-player quantum game is analyzed in the context of an Einstein-Podolsky-Rosen (EPR) experiment. In this setting, a player's strategies are not unitary transformations as in alternate quantum game-theoretic frameworks, but a classical choice between two directions along which spin or polarization measurements are made. The players' strategies thus remain identical to their strategies in the mixed-strategy version of the classical game. In the EPR setting the quantum game reduces itself to the corresponding classical game when the shared quantum state reaches zero entanglement. We find the relations for the probability distribution for $N$-qubit GHZ and W-type states, subject to general measurement directions, from which the expressions for the mixed Nash equilibrium and the payoffs are determined. Players' payoffs are then defined with linear functions so that common two-player games can be easily extended to the $N$-player case and permit analytic expressions for the Nash equilibrium. As a specific example, we solve the Prisoners' Dilemma game for general $N \ge 2$. We find a new property for the game that for an even number of players the payoffs at the Nash equilibrium are equal, whereas for an odd number of players the cooperating players receive higher payoffs.Comment: 26 pages, 2 figure

Improving delirium care in the intensive care unit: The design of a pragmatic study

<p>Abstract</p> <p>Background</p> <p>Delirium prevalence in the intensive care unit (ICU) is high. Numerous psychotropic agents are used to manage delirium in the ICU with limited data regarding their efficacy or harms.</p> <p>Methods/Design</p> <p>This is a randomized controlled trial of 428 patients aged 18 and older suffering from delirium and admitted to the ICU of Wishard Memorial Hospital in Indianapolis. Subjects assigned to the intervention group will receive a multicomponent pharmacological management protocol for delirium (PMD) and those assigned to the control group will receive no change in their usual ICU care. The primary outcomes of the trial are (1) delirium severity as measured by the Delirium Rating Scale revised-98 (DRS-R-98) and (2) delirium duration as determined by the Confusion Assessment Method for the ICU (CAM-ICU). The PMD protocol targets the three neurotransmitter systems thought to be compromised in delirious patients: dopamine, acetylcholine, and gamma-aminobutyric acid. The PMD protocol will target the reduction of anticholinergic medications and benzodiazepines, and introduce a low-dose of haloperidol at 0.5-1 mg for 7 days. The protocol will be delivered by a combination of computer (artificial intelligence) and pharmacist (human intelligence) decision support system to increase adherence to the PMD protocol.</p> <p>Discussion</p> <p>The proposed study will evaluate the content and the delivery process of a multicomponent pharmacological management program for delirium in the ICU.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00842608">NCT00842608</a></p

Environment Orientation : a structured simulation approach for agent-based complex systems

Complex systems are collections of independent agents interacting with each other and with their environment to produce emergent behaviour. Agent-based computer simulation is one of the main ways of studying complex systems. A naive approach to such simulation can fare poorly, due to large communication overhead, and due to the scope for deadlock between the interacting agents sharing a computational platform. Agent interaction can instead be considered entirely from the point of view of the environment(s) within which the agents interact. Structuring a simulation using such Environment Orientation leads to a simulation that reduces communication overhead, that is effectively deadlock-free, and yet still behaves in the manner required. Additionally the Environment Orientation architecture eases the development of more sophisticated large-scale simulations, with multiple kinds of complex agents, situated in and interacting with multiple kinds of environments. We describe the Environment Orientation simulation architecture. We report on a number of experiments that demonstrate the effectiveness of the Environment Orientation approach: a simple flocking system, a flocking system with multiple sensory environments, and a flocking system in an external environment

The Epstein-Barr Virus G-Protein-Coupled Receptor Contributes to Immune Evasion by Targeting MHC Class I Molecules for Degradation

Epstein-Barr virus (EBV) is a human herpesvirus that persists as a largely subclinical infection in the vast majority of adults worldwide. Recent evidence indicates that an important component of the persistence strategy involves active interference with the MHC class I antigen processing pathway during the lytic replication cycle. We have now identified a novel role for the lytic cycle gene, BILF1, which encodes a glycoprotein with the properties of a constitutive signaling G-protein-coupled receptor (GPCR). BILF1 reduced the levels of MHC class I at the cell surface and inhibited CD8+ T cell recognition of endogenous target antigens. The underlying mechanism involves physical association of BILF1 with MHC class I molecules, an increased turnover from the cell surface, and enhanced degradation via lysosomal proteases. The BILF1 protein of the closely related CeHV15 c1-herpesvirus of the Rhesus Old World primate (80% amino acid sequence identity) downregulated surface MHC class I similarly to EBV BILF1. Amongst the human herpesviruses, the GPCR encoded by the ORF74 of the KSHV c2-herpesvirus is most closely related to EBV BILF1 (15% amino acid sequence identity) but did not affect levels of surface MHC class I. An engineered mutant of BILF1 that was unable to activate G protein signaling pathways retained the ability to downregulate MHC class I, indicating that the immune-modulating and GPCR-signaling properties are two distinct functions of BILF1. These findings extend our understanding of the normal biology of an important human pathogen. The discovery of a third EBV lytic cycle gene that cooperates to interfere with MHC class I antigen processing underscores the importance of the need for EBV to be able to evade CD8+ T cell responses during the lytic replication cycle, at a time when such a large number of potential viral targets are expressed

Tool Support for Correctness-by-Construction

Correctness-by-Construction (CbC) is an approach to incrementally create formally correct programs guided by pre- and postcondition specifications. A program is created using refinement rules that guarantee the resulting implementation is correct with respect to the specification. Although CbC is supposed to lead to code with a low defect rate, it is not prevalent, especially because appropriate tool support is missing. To promote CbC, we provide tool support for CbC-based program development. We present CorC, a graphical and textual IDE to create programs in a simple while-language following the CbC approach. Starting with a specification, our open source tool supports CbC developers in refining a program by a sequence of refinement steps and in verifying the correctness of these refinement steps using the theorem prover KeY. We evaluated the tool with a set of standard examples on CbC where we reveal errors in the provided specification. The evaluation shows that our tool reduces the verification time in comparison to post-hoc verification

Interactive metagenomic visualization in a Web browser

<p>Abstract</p> <p>Background</p> <p>A critical output of metagenomic studies is the estimation of abundances of taxonomical or functional groups. The inherent uncertainty in assignments to these groups makes it important to consider both their hierarchical contexts and their prediction confidence. The current tools for visualizing metagenomic data, however, omit or distort quantitative hierarchical relationships and lack the facility for displaying secondary variables.</p> <p>Results</p> <p>Here we present Krona, a new visualization tool that allows intuitive exploration of relative abundances and confidences within the complex hierarchies of metagenomic classifications. Krona combines a variant of radial, space-filling displays with parametric coloring and interactive polar-coordinate zooming. The HTML5 and JavaScript implementation enables fully interactive charts that can be explored with any modern Web browser, without the need for installed software or plug-ins. This Web-based architecture also allows each chart to be an independent document, making them easy to share via e-mail or post to a standard Web server. To illustrate Krona's utility, we describe its application to various metagenomic data sets and its compatibility with popular metagenomic analysis tools.</p> <p>Conclusions</p> <p>Krona is both a powerful metagenomic visualization tool and a demonstration of the potential of HTML5 for highly accessible bioinformatic visualizations. Its rich and interactive displays facilitate more informed interpretations of metagenomic analyses, while its implementation as a browser-based application makes it extremely portable and easily adopted into existing analysis packages. Both the Krona rendering code and conversion tools are freely available under a BSD open-source license, and available from: <url>http://krona.sourceforge.net</url>.</p

Long-term (trophic) purinergic signalling: purinoceptors control cell proliferation, differentiation and death

The purinergic signalling system, which uses purines and pyrimidines as chemical transmitters, and purinoceptors as effectors, is deeply rooted in evolution and development and is a pivotal factor in cell communication. The ATP and its derivatives function as a 'danger signal' in the most primitive forms of life. Purinoceptors are extraordinarily widely distributed in all cell types and tissues and they are involved in the regulation of an even more extraordinary number of biological processes. In addition to fast purinergic signalling in neurotransmission, neuromodulation and secretion, there is long-term (trophic) purinergic signalling involving cell proliferation, differentiation, motility and death in the development and regeneration of most systems of the body. In this article, we focus on the latter in the immune/defence system, in stratified epithelia in visceral organs and skin, embryological development, bone formation and resorption, as well as in cancer. Cell Death and Disease (2010) 1, e9; doi:10.1038/cddis.2009.11; published online 14 January 201