Orphan receptor IL-17RD tunes IL-17A signalling and is required for neutrophilia

Interleukin-17A, the prototypical member of the interleukin-17 cytokine family, coordinates local tissue inflammation by recruiting neutrophils to sites of infection. Dysregulation of interleukin-17 signalling has been linked to the pathogenesis of inflammatory diseases and autoimmunity. The interleukin-17 receptor family members (A-E) have a broad range of functional effects in immune signalling yet no known role has been described for the remaining orphan receptor, interleukin-17 receptor D, in regulating interleukin-17A-induced signalling pathways. Here we demonstrate that interleukin-17 receptor D can differentially regulate the various pathways employed by interleukin-17A. Neutrophil recruitment, in response to in vivo administration of interleukin-17A, is abolished in interleukin-17 receptor D-deficient mice, correlating with reduced interleukin-17A-induced activation of p38 mitogen-activated protein kinase and expression of the neutrophil chemokine MIP-2. In contrast, interleukin-17 receptor D deficiency results in enhanced interleukin-17A-induced activation of nuclear factor-kappa B and interleukin-6 and keratinocyte chemoattractant expression. Interleukin-17 receptor D disrupts the interaction of Act1 and TRAF6 causing differential regulation of nuclear factor-kappa B and p38 mitogen-activated protein kinase signalling pathways. © 2012 Macmillan Publishers Limited. All rights reserved.

The nucleus of Comet 67P/Churyumov-Gerasimenko. A new shape model and thermophysical analysis

Context. Comet 67P/Churyumov-Gerasimenko is the target of the European Space Agency Rosetta spacecraft rendez-vous mission. Detailed physical characteristation of the comet before arrival is important for mission planning as well as providing a test bed for ground-based observing and data-analysis methods. Aims: To conduct a long-term observational programme to characterize the physical properties of the nucleus of the comet, via ground-based optical photometry, and to combine our new data with all available nucleus data from the literature. Methods: We applied aperture photometry techniques on our imaging data and combined the extracted rotational lightcurves with data from the literature. Optical lightcurve inversion techniques were applied to constrain the spin state of the nucleus and its broad shape. We performed a detailed surface thermal analysis with the shape model and optical photometry by incorporating both into the new Advanced Thermophysical Model (ATPM), along with all available Spitzer 8-24 μm thermal-IR flux measurements from the literature. Results: A convex triangular-facet shape model was determined with axial ratios b/a = 1.239 and c/a = 0.819. These values can vary by as much as 7% in each axis and still result in a statistically significant fit to the observational data. Our best spin state solution has Psid = 12.76137 ± 0.00006 h, and a rotational pole orientated at Ecliptic coordinates λ = 78°(±10°), β = + 58°(±10°). The nucleus phase darkening behaviour was measured and best characterized using the IAU HG system. Best fit parameters are: G = 0.11 ± 0.12 and HR(1,1,0) = 15.31 ± 0.07. Our shape model combined with the ATPM can satisfactorily reconcile all optical and thermal-IR data, with the fit to the Spitzer 24 μm data taken in February 2004 being exceptionally good. We derive a range of mutually-consistent physical parameters for each thermal-IR data set, including effective radius, geometric albedo, surface thermal inertia and roughness fraction. Conclusions: The overall nucleus dimensions are well constrained and strongly imply a broad nucleus shape more akin to comet 9P/Tempel 1, rather than the highly elongated or "bi-lobed" nuclei seen for comets 103P/Hartley 2 or 8P/Tuttle. The derived low thermal inertia of

Status of GPCR modeling and docking as reflected by community-wide GPCR Dock 2010 assessment

The community-wide GPCR Dock assessment is conducted to evaluate the status of molecular modeling and ligand docking for human G protein-coupled receptors. The present round of the assessment was based on the recent structures of dopamine D3 and CXCR4 chemokine receptors bound to small molecule antagonists and CXCR4 with a synthetic cyclopeptide. Thirty-five groups submitted their receptor-ligand complex structure predictions prior to the release of the crystallographic coordinates. With closely related homology modeling templates, as for dopamine D3 receptor, and with incorporation of biochemical and QSAR data, modern computational techniques predicted complex details with accuracy approaching experimental. In contrast, CXCR4 complexes that had less-characterized interactions and only distant homology to the known GPCR structures still remained very challenging. The assessment results provide guidance for modeling and crystallographic communities in method development and target selection for further expansion of the structural coverage of the GPCR universe.

Power Modeling and Capping for Heterogeneous ARM/FPGA SoCs

Low-power processors and accelerators that were originally designed for the embedded systems market are emerging as building blocks for servers. Power capping has been actively explored as a technique to reduce the energy footprint of high-performance processors. The opportunities and limitations of power capping on the new low-power processor and accelerator ecosystem are less understood. This paper presents an efficient power capping and management infrastructure for heterogeneous SoCs based on hybrid ARM/FPGA designs. The infrastructure coordinates dynamic voltage and frequency scaling with task allocation on a customised Linux system for the Xilinx Zynq SoC. We present a compiler-assisted power model to guide voltage and frequency scaling, in conjunction with workload allocation between the ARM cores and the FPGA, under given power caps. The model achieves less than 5% estimation bias to mean power consumption. In an FFT case study, the proposed power capping schemes achieve on average 97.5% of the performance of the optimal execution and match the optimal execution in 87.5% of the cases, while always meeting power constraints.

A Lagrangian approach for modeling road collisions using second-order models of traffic flow

In [M. Herty, A. Klein, S. Moutari, V. Schleper, and G. Steinaur, IMA J. Appl. Math., 78(5), 1087–1108, 2013] and [M. Herty and V. Schleper, ZAMM J. Appl. Math. Mech., 91, 763–776, 2011], a macroscopic approach, derived from fluid-dynamics models, has been introduced to infer traffic conditions prone to road traffic collisions along highways’ sections. In these studies, the governing equations are coupled within an Eulerian framework, which assumes fixed interfaces between the models. A coupling in Lagrangian coordinates would enable us to get rid of this (not very realistic) assumption. In this paper, we investigate the well-posedness and the suitability of the coupling of the governing equations within the Lagrangian framework. Further, we illustrate some features of the proposed approach through some numerical simulations.

Predicting forest attributes In southeast Alaska using artificial neural networks

Artificial neural network (ANN) methods are used to predict forest characteristics. The data source is the Southeast Alaska (SEAK) Grid Inventory, a ground survey compiled by the USDA Forest Service at several thousand sites. The main objective of this article is to predict characteristics at unsurveyed locations between grid sites. A secondary objective is to evaluate the relative performance of different ANNs. Data from the grid sites are used to train six ANNs: multilayer perceptron, fuzzy ARTMAP, probabilistic, generalized regression, radial basis function, and learning vector quantization. A classification and regression tree method is used for comparison. Topographic variables are used to construct models: latitude and longitude coordinates, elevation, slope, and aspect. The models classify three forest characteristics: crown closure, species land cover, and tree size/structure. Models are constructed using n-fold cross-validation. Predictive accuracy is calculated using a method that accounts for the influence of misclassification as well as measuring correct classifications. The probabilistic and generalized regression networks are found to be the most accurate. The predictions of the ANN models are compared with a classification of the Tongass national forest in southeast Alaska based on the interpretation of satellite imagery and are found to be of similar accuracy.

Are Alaskan trees found in locally more favourable sites in marginal areas?

Aim Species generally become rarer and more patchily distributed as the margins of their ranges are approached. We predicted that in such marginal sites, tree species would tend to occur where some key environmental factors are at particularly favourable levels, compensating in part for the low overall suitability of marginal sites.

Location The article considers the spatial distributions of trees in Southeast Alaska (the Alaskan 'panhandle').

Methods We quantified range marginality using spatial distributions of eight tree species across more than one thousand surveyed sites in Southeast Alaska. For each species we derived a site core/margin index using a three-dimensional trend surface generated from logistic regression on site coordinates. For each species, the relationships between the environmental factors slope, aspect and site marginality were then compared for occupied and unoccupied sets of sites.

Results We found that site slope is important for more Alaskan tree species than aspect. Three out of eight had a significant core/margin by occupied/unoccupied interaction, tending to be present in significantly shallower-sloped (more favourable) sites in the marginal areas than the simple core/margin trend predicted. For site aspect, one species had a significant interaction, selecting potentially more favourable northerly aspects in marginal areas. A finer-scale analysis based on the same data came to the same overall conclusions.

Conclusions There is evidence that several tree species in Alaska tend to occur in especially favourable sites in marginal areas. In these marginal areas, these species amplify habitat preferences shown in core areas.

Optimising drug solubilisation in amorphous polymer dispersions: rational selection of hot-melt extrusion processing parameters

The aim of this article was to construct a T–ϕ phase diagram for a model drug (FD) and amorphous polymer (Eudragit® EPO) and to use this information to understand the impact of how temperature–composition coordinates influenced the final properties of the extrudate. Defining process boundaries and understanding drug solubility in polymeric carriers is of utmost importance and will help in the successful manufacture of new delivery platforms for BCS class II drugs. Physically mixed felodipine (FD)–Eudragit® EPO (EPO) binary mixtures with pre-determined weight fractions were analysed using DSC to measure the endset of melting and glass transition temperature. Extrudates of 10 wt% FD–EPO were processed using temperatures (110°C, 126°C, 140°C and 150°C) selected from the temperature–composition (T–ϕ) phase diagrams and processing screw speed of 20, 100 and 200rpm. Extrudates were characterised using powder X-ray diffraction (PXRD), optical, polarised light and Raman microscopy. To ensure formation of a binary amorphous drug dispersion (ADD) at a specific composition, HME processing temperatures should at least be equal to, or exceed, the corresponding temperature value on the liquid–solid curve in a F–H T–ϕ phase diagram. If extruded between the spinodal and liquid–solid curve, the lack of thermodynamic forces to attain complete drug amorphisation may be compensated for through the use of an increased screw speed. Constructing F–H T–ϕ phase diagrams are valuable not only in the understanding drug–polymer miscibility behaviour but also in rationalising the selection of important processing parameters for HME to ensure miscibility of drug and polymer.

Assessment Work of Paramedics on the Front lines of Emergency Health Services

This article draws on an institutional ethnographic inquiry into the work of paramedics and the institutional setting that organizes and coordinates their work processes. Drawing on over 200 hours of observations and over 100 interviews with paramedics (average length of 18 minutes) and other emergency medical personnel, this article explores the standard and not so standard work of paramedics as they assess and care for their patients on the front lines of emergency health services. More specifically, I focus on the multiplicity of interfacing social, demographic, locational, situational, and institutional factors that shape and organize the work of paramedics. In doing so, this article provides insights into how paramedics orient to the social context in which their work occurs and contrasts this actual work with how their work is institutionally reported and made visible; what gets counted institutionally is not necessarily the same as what counts for the paramedics. This article problematizes this demarcation between what is known institutionally and “systematic practices of ‘not knowing’” (DeVault, 2008, p. 290).

Street Medicine – Assessment Work Strategies of Paramedics on the Front lines of Emergency Health Services

This article is based on an institutional ethnographic inquiry into the work of paramedics and the institutional setting that organizes and coordinates their work processes in a major City in Canada. Drawing on over 200 hours of observations and over 100 interviews with paramedics (average length of 18 minutes) and other emergency medical personnel, this article explores the standard and not so standard work of paramedics as they assess and care for their patients on the front lines of emergency health services. The multiplicity of interfacing social, demographic, locational, and situational factors that shape and organize the work of paramedics are analyzed. In doing so, this article provides insights into the complex work of an understudied yet ever-important profession in healthcare.

General, PDB-based collective variables for protein folding

New, automated forms of data-analysis are required in order to understand the high-dimensional trajectories that are obtained from molecular dynamics simulations on proteins. Dimensionality reduction algorithms are particularly appealing in this regard as they allow one to construct unbiased, low-dimensional representations of the trajectory using only the information encoded in the trajectory. The downside of this approach is that different sets of coordinates are required for each different chemical systems under study precisely because the coordinates are constructed using information from the trajectory. In this paper we show how one can resolve this problem by using the sketch-map algorithm that we recently proposed to construct a low-dimensional representation of the structures contained in the protein data bank (PDB). We show that the resulting coordinates are as useful for analysing trajectory data as coordinates constructed using landmark configurations taken from the trajectory and that these coordinates can thus be used for understanding protein folding across a range of systems.

EFFECT OF DIFFERENT STORAGE CONDITIONS ON NUTRITIONAL AND QUALITY PARAMETERS OF 'SWEETHEART' CHERRY.

Abstract The sweet cherry ‘Sweetheart’, although having a short shelf life, is highly appreciated by consumers due to its organoleptic characteristics. Different storage methods were tested to study the maintenance of quality during a period of 27 days: 1) cold (air at 1°C and 95% relative humidity) (CC), 2) cold and polypropylene film bags (1°C and 95% relative humidity) (MA) and 3) cold and controlled atmosphere (1°C, 95% RH, 10% CO2 and 8% O2) (CA). Quality parameters tested included external colour (L*, a*, b*), total soluble solids (TSS), and titratable acidity (TA). To evaluate nutritional quality anthocyanins, total antioxidant activity, and total phenolics were measured. Results allow us to say that phenolic compounds were relatively stable and similar during storage in CC and MA. Cherries stored under CA conditions presented lowest concentrations of phenolic compounds. Phenolic compounds, total anthocyanins and antioxidant activity were inversely correlated with values of colour coordinates. Considering all the evaluations done during this work it is unquestionable that fruits stored in controlled atmosphere conditions had significantly different quality.

QUALITY OF 'SWEETHEART' CHERRY UNDER DIFFERENT STORAGE CONDITIONS

Abstract: In Portalegre, Portugal, sweet cherry production is very important to the region’s economic sustainability. The sweet cherry ‘Sweetheart’ has exhibited short shelf life in spite of being highly appreciated by consumers due to its organoleptic characteristics. In this trial, we evaluated fruit quality of ‘Sweetheart’ stored under different storage conditions: 1) cold conditions (1ºC and high humidity 95%), 2) cold conditions and polypropylene film bags (MA), and 3) controlled atmosphere (CA) (1°C, 95% humidity, 10% CO2 and 8% O2). Fruit physical and chemical parameters were evaluated after 0, 6, 13, 20 and 27 days of cold storage. Quality parameters tested included weight loss, external colour (L* a* b*), visual assessment of the epidermis, epidermis and mesocarp penetration test, soluble solids content (SSC), and titratable acidity (TA). We also performed sensory analyses. The results for textural properties, colour coordinates and sensory analysis suggest that ‘Sweetheart’ fruit can be stored under cold conditions, 1°C, 95% humidity, for up to 21 days without significant loss of quality. Controlled atmosphere maintained tissue turgidity during storage; however, this was not noticed by the panelists, who consistently classified fruits stored under CA conditions with lower overall ratings than fruits under cold conditions with or without film bags.

Perception and software architecture for mobile robotics

When developing software for autonomous mobile robots, one has to inevitably tackle some kind of perception. Moreover, when dealing with agents that possess some level of reasoning for executing their actions, there is the need to model the environment and the robot internal state in a way that it represents the scenario in which the robot operates. Inserted in the ATRI group, part of the IEETA research unit at Aveiro University, this work uses two of the projects of the group as test bed, particularly in the scenario of robotic soccer with real robots. With the main objective of developing algorithms for sensor and information fusion that could be used e ectively on these teams, several state of the art approaches were studied, implemented and adapted to each of the robot types. Within the MSL RoboCup team CAMBADA, the main focus was the perception of ball and obstacles, with the creation of models capable of providing extended information so that the reasoning of the robot can be ever more e ective. To achieve it, several methodologies were analyzed, implemented, compared and improved. Concerning the ball, an analysis of ltering methodologies for stabilization of its position and estimation of its velocity was performed. Also, with the goal keeper in mind, work has been done to provide it with information of aerial balls. As for obstacles, a new de nition of the way they are perceived by the vision and the type of information provided was created, as well as a methodology for identifying which of the obstacles are team mates. Also, a tracking algorithm was developed, which ultimately assigned each of the obstacles a unique identi er. Associated with the improvement of the obstacles perception, a new algorithm of estimating reactive obstacle avoidance was created. In the context of the SPL RoboCup team Portuguese Team, besides the inevitable adaptation of many of the algorithms already developed for sensor and information fusion and considering that it was recently created, the objective was to create a sustainable software architecture that could be the base for future modular development. The software architecture created is based on a series of di erent processes and the means of communication among them. All processes were created or adapted for the new architecture and a base set of roles and behaviors was de ned during this work to achieve a base functional framework. In terms of perception, the main focus was to de ne a projection model and camera pose extraction that could provide information in metric coordinates. The second main objective was to adapt the CAMBADA localization algorithm to work on the NAO robots, considering all the limitations it presents when comparing to the MSL team, especially in terms of computational resources. A set of support tools were developed or improved in order to support the test and development in both teams. In general, the work developed during this thesis improved the performance of the teams during play and also the e ectiveness of the developers team when in development and test phases.

A three-dimensional hydrodynamic model with generic vertical coordinate

A three-dimensional primitive equation model and its application to a tidal estuary is described. The model solves the primitive equations for incompressible fluids with Boussinesq and hydrostatic approximations. The discretization is based on the finite volume method and allows a general vertical coordinate. The computational code is implemented in such a way that different vertical coordinates can be used in different parts of the domain. The model was designed to be able to simulate the flow both in the open ocean and in coastal and estuarine zones and can be coupled in a simple way to ecological models. The model was implemented successfully in several estuarine and coastal areas. Results are show for the Sado estuary in Portugal to illustrate model accuracy and potential. Quantitative validation is based on field data (water levels and velocities) while qualitative verification is based on the analysis of secondary flows.