Immersive Projection for biochemical pattern matching

In all biological processes, protein molecules and other small molecules interact to function and form transient macromolecular complexes. This interaction of two or more molecules can be described by a docking event. Docking is an important phase for structure-based drug design strategies, as it can be used as a method to simulate protein-ligand interactions. Various docking programs exist that allow automated docking, but most of them have limited visualization and user interaction. It would be advantageous if scientists could visualize the molecules participating in the docking process, manipulate their structures and manually dock them before submitting the new conformations to an automated docking process in an immersive environment, which can help stimulate the design/docking process. This also could greatly reduce docking time and resources. To achieve this, we propose a new virtual modelling/docking program, whereby the advantages of virtual modelling programs and the efficiency of the algorithms in existing docking programs will be merged.

The Splitting of the Stratospheric Polar Vortex in the Southern Hemisphere, September 2002: Dynamical Evolution

The polar vortex of the Southern Hemisphere (SH) split dramatically during September 2002. The large-scale dynamical effects were manifest throughout the stratosphere and upper troposphere, corresponding to two distinct cyclonic centers in the upper troposphere–stratosphere system. High-resolution (T511) ECMWF analyses, supplemented by analyses from the Met Office, are used to present a detailed dynamical analysis of the event. First, the anomalous evolution of the SH polar vortex is placed in the context of the evolution that is usually witnessed during spring. Then high-resolution fields of potential vorticity (PV) from ECMWF are used to reveal several dynamical features of the split. Vortex fragments are rapidly sheared out into sheets of high (modulus) PV, which subsequently roll up into distinct synoptic-scale vortices. It is proposed that the stratospheric circulation becomes hydrodynamically unstable through a significant depth of the troposphere–stratosphere system as the polar vortex elongates.

Illustration of micro-scale advection using grid-pattern mini-lysimeters

Twenty-five small soil-filled perspex boxes arranged in a square, with dwarf sunflowers growing in them, were used to study micro-scale advection. Hydrological heterogeneity was introduced by applying two different amounts of irrigation water (low-irrigation, L, versus high-irrigation, H). The nine central boxes (4 H, 4 L and I bare box) were precision weighing lysimeters, yielding diurnal measurements of evaporation. After the onset of soil water stress, a large difference in latent heat flux (up to 4-fold) was observed between the lysimeters of the H and L treatments, mainly caused by large differences between H and L stomatal conductance values. This resulted in micro-advection, causing H soil-sunflower systems to evaporate well above equilibrium latent heat flux. The occurrence of micro-advective enhancement was reflected in large values of the Priestley-Taylor constant (often larger than 2.0) and generally negative values of sensible heat flux for the H treatment. (c) 2005 Elsevier B.V. All rights reserved.

Amygdala and ventromedial prefrontal cortex are inversely coupled during regulation of negative affect and predict the diurnal pattern of cortisol secretion among older adults

Among younger adults, the ability to willfully regulate negative affect, enabling effective responses to stressful experiences, engages regions of prefrontal cortex (PFC) and the amygdala. Because regions of PFC and the amygdala are known to influence the hypothalamic-pituitary-adrenal axis, here we test whether PFC and amygdala responses during emotion regulation predict the diurnal pattern of salivary cortisol secretion. We also test whether PFC and amygdala regions are engaged during emotion regulation in older (62- to 64-year-old) rather than younger individuals. We measured brain activity using functional magnetic resonance imaging as participants regulated (increased or decreased) their affective responses or attended to negative picture stimuli. We also collected saliva samples for 1 week at home for cortisol assay. Consistent with previous work in younger samples, increasing negative affect resulted in ventral lateral, dorsolateral, and dorsomedial regions of PFC and amygdala activation. In contrast to previous work, decreasing negative affect did not produce the predicted robust pattern of higher PFC and lower amygdala activation. Individuals demonstrating the predicted effect (decrease s attend in the amygdala), however, exhibited higher signal in ventromedial prefrontal cortex (VMPFC) for the same contrast. Furthermore, participants displaying higher VMPFC and lower amygdala signal when decreasing compared with the attention control condition evidenced steeper, more normative declines in cortisol over the course of the day. Individual differences yielded the predicted link between brain function while reducing negative affect in the laboratory and diurnal regulation of endocrine activity in the home environment.

A pattern language for goals

Previous work has established the value of goal-oriented approaches to requirements engineering. Achieving clarity and agreement about stakeholders’ goals and assumptions is critical for building successful software systems and managing their subsequent evolution. In general, this decision-making process requires stakeholders to understand the implications of decisions outside the domains of their own expertise. Hence it is important to support goal negotiation and decision making with description languages that are both precise and expressive, yet easy to grasp. This paper presents work in progress to develop a pattern language for describing goal refinement graphs. The language has a simple graphical notation, which is supported by a prototype editor tool, and a symbolic notation based on modal logic.

Discriminative pattern mining in software fault detection

We present a method to enhance fault localization for software systems based on a frequent pattern mining algorithm. Our method is based on a large set of test cases for a given set of programs in which faults can be detected. The test executions are recorded as function call trees. Based on test oracles the tests can be classified into successful and failing tests. A frequent pattern mining algorithm is used to identify frequent subtrees in successful and failing test executions. This information is used to rank functions according to their likelihood of containing a fault. The ranking suggests an order in which to examine the functions during fault analysis. We validate our approach experimentally using a subset of Siemens benchmark programs.

Syk-Dependent Cytokine Induction by Dectin-1 Reveals a Novel Pattern Recognition Pathway for C Type Lectins

Pattern-recognition receptors (PRRs) detect molecular signatures of microbes and initiate immune responses to infection. Prototypical PRRs such as Toll-like receptors (TLRs) signal via a conserved pathway to induce innate response genes. In contrast, the signaling pathways engaged by other classes of putative PRRs remain ill defined. Here, we demonstrate that the β-glucan receptor Dectin-1, a yeast binding C type lectin known to synergize with TLR2 to induce TNFα and IL-12, can also promote synthesis of IL-2 and IL-10 through phosphorylation of the membrane proximal tyrosine in the cytoplasmic domain and recruitment of Syk kinase. syk−/− dendritic cells (DCs) do not make IL-10 or IL-2 upon yeast stimulation but produce IL-12, indicating that the Dectin-1/Syk and Dectin-1/TLR2 pathways can operate independently. These results identify a novel signaling pathway involved in pattern recognition by C type lectins and suggest a potential role for Syk kinase in regulation of innate immunity.

Analysis of the calving pattern of herds in small-scale dairy systems in central Mexico

This study sets out to find the best calving pattern for small-scale dairy systems in Michoacan State, central Mexico. Two models were built. First, a linear programming model was constructed to optimize calving pattern and herd structure according to metabolizable energy availability. Second, a Markov chain model was built to investigate three reproductive scenarios (good, average and poor) in order to suggest factors that maintain the calving pattern given by the linear programming model. Though it was not possible to maintain the optimal linear programming pattern, the Markov chain model suggested adopting different reproduction strategies according to period of the year that the cow is expected to calve. Comparing different scenarios, the Markov model indicated the effect of calving interval on calving pattern and herd structure.

Microbe-associated molecular pattern (MAMP) signatures, synergy, size and charge: influences on perception or mobility and host defence responses

Triggering of defences by microbes has mainly been investigated using single elicitors or microbe-associated molecular patterns (MAMPs), but MAMPs are released in planta as complex mixtures together with endogenous oligogalacturonan (OGA) elicitor. We investigated the early responses in Arabidopsis of calcium influx and oxidative burst induced by non-saturating concentrations of bacterial MAMPs, used singly and in combination: flagellin peptide (flg22), elongation factor peptide (elf18), peptidoglycan (PGN) and component muropeptides, lipo-oligosaccharide (LOS) and core oligosaccharides. This revealed that some MAMPs have additive (e.g. flg22 with elf18) and even synergistic (flg22 and LOS) effects, whereas others mutually interfere (flg22 with OGA). OGA suppression of flg22-induced defences was not a result of the interference with the binding of flg22 to its receptor flagellin-sensitive 2 (FLS2). MAMPs induce different calcium influx signatures, but these are concentration dependent and unlikely to explain the differential induction of defence genes [pathogenesis-related gene 1 (PR1), plant defensin gene 1.2 (PDF1.2) and phenylalanine ammonia lyase gene 1 (PAL1)] by flg22, elf18 and OGA. The peptide MAMPs are potent elicitors at subnanomolar levels, whereas PGN and LOS at high concentrations induce low and late host responses. This difference might be a result of the restricted access by plant cell walls of MAMPs to their putative cellular receptors. flg22 is restricted by ionic effects, yet rapidly permeates a cell wall matrix, whereas LOS, which forms supramolecular aggregates, is severely constrained, presumably by molecular sieving. Thus, MAMPs can interact with each other, whether directly or indirectly, and with the host wall matrix. These phenomena, which have not been considered in detail previously, are likely to influence the speed, magnitude, versatility and composition of plant defences.