Motivated proteins: a web application for studying small three-dimensional protein motifs

<b>BACKGROUND:</b> Small loop-shaped motifs are common constituents of the three-dimensional structure of proteins. Typically they comprise between three and seven amino acid residues, and are defined by a combination of dihedral angles and hydrogen bonding partners. The most abundant of these are alphabeta-motifs, asx-motifs, asx-turns, beta-bulges, beta-bulge loops, beta-turns, nests, niches, Schellmann loops, ST-motifs, ST-staples and ST-turns.We have constructed a database of such motifs from a range of high-quality protein structures and built a web application as a visual interface to this. <b>DESCRIPTION:</b> The web application, Motivated Proteins, provides access to these 12 motifs (with 48 sub-categories) in a database of over 400 representative proteins. Queries can be made for specific categories or sub-categories of motif, motifs in the vicinity of ligands, motifs which include part of an enzyme active site, overlapping motifs, or motifs which include a particular amino acid sequence. Individual proteins can be specified, or, where appropriate, motifs for all proteins listed. The results of queries are presented in textual form as an (X)HTML table, and may be saved as parsable plain text or XML. Motifs can be viewed and manipulated either individually or in the context of the protein in the Jmol applet structural viewer. Cartoons of the motifs imposed on a linear representation of protein secondary structure are also provided. Summary information for the motifs is available, as are histograms of amino acid distribution, and graphs of dihedral angles at individual positions in the motifs. <b>CONCLUSION:</b> Motivated Proteins is a publicly and freely accessible web application that enables protein scientists to study small three-dimensional motifs without requiring knowledge of either Structured Query Language or the underlying database schem

Microservice Transition and its Granularity Problem: A Systematic Mapping Study

Microservices have gained wide recognition and acceptance in software industries as an emerging architectural style for autonomic, scalable, and more reliable computing. The transition to microservices has been highly motivated by the need for better alignment of technical design decisions with improving value potentials of architectures. Despite microservices' popularity, research still lacks disciplined understanding of transition and consensus on the principles and activities underlying "micro-ing" architectures. In this paper, we report on a systematic mapping study that consolidates various views, approaches and activities that commonly assist in the transition to microservices. The study aims to provide a better understanding of the transition; it also contributes a working definition of the transition and technical activities underlying it. We term the transition and technical activities leading to microservice architectures as microservitization. We then shed light on a fundamental problem of microservitization: microservice granularity and reasoning about its adaptation as first-class entities. This study reviews state-of-the-art and -practice related to reasoning about microservice granularity; it reviews modelling approaches, aspects considered, guidelines and processes used to reason about microservice granularity. This study identifies opportunities for future research and development related to reasoning about microservice granularity.Comment: 36 pages including references, 6 figures, and 3 table

A Vast Thin Plane of Co-rotating Dwarf Galaxies Orbiting the Andromeda Galaxy

Dwarf satellite galaxies are thought to be the remnants of the population of primordial structures that coalesced to form giant galaxies like the Milky Way. An early analysis noted that dwarf galaxies may not be isotropically distributed around our Galaxy, as several are correlated with streams of HI emission, and possibly form co-planar groups. These suspicions are supported by recent analyses, and it has been claimed that the apparently planar distribution of satellites is not predicted within standard cosmology, and cannot simply represent a memory of past coherent accretion. However, other studies dispute this conclusion. Here we report the existence (99.998% significance) of a planar sub-group of satellites in the Andromeda galaxy, comprising approximately 50% of the population. The structure is vast: at least 400 kpc in diameter, but also extremely thin, with a perpendicular scatter <14.1 kpc (99% confidence). Radial velocity measurements reveal that the satellites in this structure have the same sense of rotation about their host. This finding shows conclusively that substantial numbers of dwarf satellite galaxies share the same dynamical orbital properties and direction of angular momentum, a new insight for our understanding of the origin of these most dark matter dominated of galaxies. Intriguingly, the plane we identify is approximately aligned with the pole of the Milky Way's disk and is co-planar with the Milky Way to Andromeda position vector. The existence of such extensive coherent kinematic structures within the halos of massive galaxies is a fact that must be explained within the framework of galaxy formation and cosmology.Comment: Published in the 3rd Jan 2013 issue of Nature. 19 pages, 4 figures, 1 three-dimensional interactive figure. To view and manipulate the 3-D figure, an Adobe Reader browser plug-in is required; alternatively save to disk and view with Adobe Reade

Collaborative Gaze Channelling for Improved Cooperation During Robotic Assisted Surgery

The use of multiple robots for performing complex tasks is becoming a common practice for many robot applications. When different operators are involved, effective cooperation with anticipated manoeuvres is important for seamless, synergistic control of all the end-effectors. In this paper, the concept of Collaborative Gaze Channelling (CGC) is presented for improved control of surgical robots for a shared task. Through eye tracking, the fixations of each operator are monitored and presented in a shared surgical workspace. CGC permits remote or physically separated collaborators to share their intention by visualising the eye gaze of their counterparts, and thus recovers, to a certain extent, the information of mutual intent that we rely upon in a vis-à-vis working setting. In this study, the efficiency of surgical manipulation with and without CGC for controlling a pair of bimanual surgical robots is evaluated by analysing the level of coordination of two independent operators. Fitts' law is used to compare the quality of movement with or without CGC. A total of 40 subjects have been recruited for this study and the results show that the proposed CGC framework exhibits significant improvement (p<0.05) on all the motion indices used for quality assessment. This study demonstrates that visual guidance is an implicit yet effective way of communication during collaborative tasks for robotic surgery. Detailed experimental validation results demonstrate the potential clinical value of the proposed CGC framework. © 2012 Biomedical Engineering Society.link_to_subscribed_fulltex

Energy- and flux-budget (EFB) turbulence closure model for the stably stratified flows. Part I: Steady-state, homogeneous regimes

We propose a new turbulence closure model based on the budget equations for the key second moments: turbulent kinetic and potential energies: TKE and TPE (comprising the turbulent total energy: TTE = TKE + TPE) and vertical turbulent fluxes of momentum and buoyancy (proportional to potential temperature). Besides the concept of TTE, we take into account the non-gradient correction to the traditional buoyancy flux formulation. The proposed model grants the existence of turbulence at any gradient Richardson number, Ri. Instead of its critical value separating - as usually assumed - the turbulent and the laminar regimes, it reveals a transition interval, 0.1< Ri <1, which separates two regimes of essentially different nature but both turbulent: strong turbulence at Ri<<1; and weak turbulence, capable of transporting momentum but much less efficient in transporting heat, at Ri>1. Predictions from this model are consistent with available data from atmospheric and lab experiments, direct numerical simulation (DNS) and large-eddy simulation (LES).Comment: 40 pages, 6 figures, Boundary-layer Meteorology, resubmitted, revised versio

Genetic contributions to visuospatial cognition in Williams syndrome: insights from two contrasting partial deletion patients

Background Williams syndrome (WS) is a rare neurodevelopmental disorder arising from a hemizygotic deletion of approximately 27 genes on chromosome 7, at locus 7q11.23. WS is characterised by an uneven cognitive profile, with serious deficits in visuospatial tasks in comparison to relatively proficient performance in some other cognitive domains such as language and face processing. Individuals with partial genetic deletions within the WS critical region (WSCR) have provided insights into the contribution of specific genes to this complex phenotype. However, the combinatorial effects of different genes remain elusive. Methods We report on visuospatial cognition in two individuals with contrasting partial deletions in the WSCR: one female (HR), aged 11 years 9 months, with haploinsufficiency for 24 of the WS genes (up to GTF2IRD1), and one male (JB), aged 14 years 2 months, with the three most telomeric genes within the WSCR deleted, or partially deleted. Results Our in-depth phenotyping of the visuospatial domain from table-top psychometric, and small- and large-scale experimental tasks reveal a profile in HR in line with typically developing controls, albeit with some atypical features. These data are contrasted with patient JB’s atypical profile of strengths and weaknesses across the visuospatial domain, as well as with more substantial visuospatial deficits in individuals with the full WS deletion. Conclusions Our findings point to the contribution of specific genes to spatial processing difficulties associated with WS, highlighting the multifaceted nature of spatial cognition and the divergent effects of genetic deletions within the WSCR on different components of visuospatial ability. The importance of general transcription factors at the telomeric end of the WSCR, and their combinatorial effects on the WS visuospatial phenotype are also discussed

The H-band Emitting Region of the Luminous Blue Variable P Cygni: Spectrophotometry and Interferometry of the Wind

This is the final version of the article. Available from American Astronomical Society / IOP Publishing via the DOI in this record.We present the first high angular resolution observations in the near-infrared H band (1.6 μm) of the luminous blue variable star P Cygni. We obtained six-telescope interferometric observations with the CHARA Array and the MIRC beam combiner. These show that the spatial flux distribution is larger than expected for the stellar photosphere. A two-component model for the star (uniform disk) plus a halo (two-dimensional Gaussian) yields an excellent fit of the observations, and we suggest that the halo corresponds to flux emitted from the base of the stellar wind. This wind component contributes about 45% of the H-band flux and has an angular FWHM = 0.96 mas, compared to the predicted stellar diameter of 0.41 mas. We show several images reconstructed from the interferometric visibilities and closure phases, and they indicate a generally spherical geometry for the wind. We also obtained near-infrared spectrophotometry of P Cygni from which we derive the flux excess compared to a purely photospheric spectral energy distribution. The H-band flux excess matches that from the wind flux fraction derived from the two-component fits to the interferometry. We find evidence of significant near-infrared flux variability over the period from 2006 to 2010 that appears similar to the variations in the Hα emission flux from the wind.We acknowledge with thanks the variable star observations from the AAVSO International Database contributed by observers worldwide and used in this research. Support for Ritter Astrophysical Research Center during the time of the observations was provided by the National Science Foundation Program for Research and Education with Small Telescopes (NSF-PREST) under grant AST-0440784 (N.D.M.). This work was also supported by the National Science Foundation under grants AST-0606861 and AST-1009080 (D.R.G.). N.D.R. gratefully acknowledges his current CRAQ postdoctoral fellowship. We are grateful for the insightful comments of A. F. J. Moffat that improved portions of the paper, discussions with Paco Najarro and Luc Dessart about spectroscopic modeling of P Cygni, and support of the MIRC 6 telescope beam combiner by Ettore Pedretti. Institutional support has been provided by the GSU College of Arts and Sciences and by the Research Program Enhancement fund of the Board of Regents of the University System of Georgia, administered through the GSU Office of the Vice President for Research. Operational funding for the CHARA Array is provided by the GSU College of Arts and Sciences, by the National Science Foundation through grants AST-0606958 and AST-0908253, by the W. M. Keck Foundation, and by the NASA Exoplanet Science Institute. We thank the Mount Wilson Institute for providing infrastructure support at Mount Wilson Observatory. The CHARA Array, operated by Georgia State University, was built with funding provided by the National Science Foundation, Georgia State University, the W. M. Keck Foundation, and the David and Lucile Packard Foundation. This research was conducted in part using the Mimir instrument, jointly developed at Boston University and Lowell Observatory and supported by NASA, NSF, and the W. M. Keck Foundation. J.D.M. acknowledges University of Michigan and NSF AST-0707927 for support of MIRC construction and observations. D.P.C. acknowledges support under NSF AST-0907790 to Boston University. We gratefully acknowledge all of this support. This research has made use of the SIMBAD database operated at CDS, Strasbourg, France

Localisation and origin of the bacteriochlorophyll-derived photosensitizer in the retina of the deep-sea dragon fish Malacosteus niger

Most deep-sea fish have a single visual pigment maximally sensitive at short wavelengths, approximately matching the spectrum of both downwelling sunlight and bioluminescence. However, Malcosteus niger produces far-red bioluminescence and its longwave retinal sensitivity is enhanced by red-shifted visual pigments, a longwave reflecting tapetum and, uniquely, a bacteriochlorophyllderived photosensitizer. The origin of the photosensitizer, however, remains unclear. We investigated whether the bacteriochlorophyll was produced by endosymbiotic bacteria within unusual structures adjacent to the photoreceptors that had previously been described in this species. However, microscopy, elemental analysis and SYTOX green staining provided no evidence for such localised retinal bacteria, instead the photosensitizer was shown to be distributed throughout the retina. Furthermore, comparison of mRNA from the retina of Malacosteus to that of the closely related Pachystomias microdon (which does not contain a bacterichlorophyll-derived photosensitzer) revealed no genes of bacterial origin that were specifically up-regulated in Malacosteus. Instead up-regulated Malacosteus genes were associated with photosensitivity and may relate to its unique visual ecology and the chlorophyll-based visual system. We also suggest that the unusual longwave-reflecting, astaxanthin-based, tapetum of Malacosteus may protect the retina from the potential cytotoxicity of such a system

Agronomic Management of Indigenous Mycorrhizas

Many of the advantages conferred to plants by arbuscular mycorrhiza (AM) are associated to the ability of AM plants to explore a greater volume of soil through the extraradical mycelium. Sieverding (1991) estimates that for each centimetre of colonized root there is an increase of 15 cm3 on the volume of soil explored, this value can increase to 200 cm3 depending on the circumstances. Due to the enhancement of the volume of soil explored and the ability of the extraradical mycelium to absorb and translocate nutrients to the plant, one of the most obvious and important advantages resulting from mycorrhization is the uptake of nutrients. Among of which the ones that have immobilized forms in soil, such as P, assume particular significance. Besides this, many other benefits are recognized for AM plants (Gupta et al, 2000): water stress alleviation (Augé, 2004; Cho et al, 2006), protection from root pathogens (Graham, 2001), tolerance to toxic heavy metals and phytoremediation (Audet and Charest, 2006; Göhre and Paszkowski, 2006), tolerance to adverse conditions such as very high or low temperature, high salinity (Sannazzaro et al, 2006), high or low pH (Yano and Takaki, 2005) or better performance during transplantation shock (Subhan et al, 1998). The extraradical hyphae also stabilize soil aggregates by both enmeshing soil particles (Miller e Jastrow, 1992) and producing a glycoprotein, golmalin, which may act as a glue-like substance to adhere soil particles together (Wright and Upadhyaya, 1998). Despite the ubiquous distribution of mycorrhizal fungi (Smith and Read, 2000) and only a relative specificity between host plants and fungal isolates (McGonigle and Fitter, 1990), the obligate nature of the symbiosis implies the establishment of a plant propagation system, either under greenhouse conditions or in vitro laboratory propagation. These techniques result in high inoculum production costs, which still remains a serious problem since they are not competitive with production costs of phosphorus fertilizer. Even if farmers understand the significance of sustainable agricultural systems, the reduction of phosphorus inputs by using AM fungal inocula alone cannot be justified except, perhaps, in the case of high value crops (Saioto and Marumoto, 2002). Nurseries, high income horticulture farmers and no-agricultural application such as rehabilitation of degraded or devegetated landscapes are examples of areas where the use of commercial inoculum is current. Another serious problem is quality of commercial available products concerning guarantee of phatogene free content, storage conditions, most effective application methods and what types to use. Besides the information provided by suppliers about its inoculum can be deceiving, as from the usually referred total counts, only a fraction may be effective for a particular plant or in specific soil conditions. Gianinazzi and Vosátka (2004) assume that progress should be made towards registration procedures that stimulate the development of the mycorrhizal industry. Some on-farm inoculum production and application methods have been studied, allowing farmers to produce locally adapted isolates and generate a taxonomically diverse inoculum (Mohandas et al, 2004; Douds et al, 2005). However the inocula produced this way are not readily processed for mechanical application to the fields, being an obstacle to the utilization in large scale agriculture, especially row crops, moreover it would represent an additional mechanical operation with the corresponding economic and soil compaction costs. It is well recognized that inoculation of AM fungi has a potential significance in not only sustainable crop production, but also environmental conservation. However, the status quo of inoculation is far from practical technology that can be widely used in the field. Together a further basic understanding of the biology and diversity of AM fungi is needed (Abbott at al, 1995; Saito and Marumoto, 2002). Advances in ecology during the past decade have led to a much more detailed understanding of the potential negative consequences of species introductions and the potential for negative ecological consequences of invasions by mycorrhizal fungi is poorly understood. Schwartz et al, (2006) recommend that a careful assessment documenting the need for inoculation, and the likelihood of success, should be conducted prior to inoculation because inoculations are not universally beneficial. Agricultural practices such as crop rotation, tillage, weed control and fertilizer apllication all produce changes in the chemical, physical and biological soil variables and affect the ecological niches available for occupancy by the soil biota, influencing in different ways the symbiosis performance and consequently the inoculum development, shaping changes and upset balance of native populations. The molecular biology tools developed in the latest years have been very important for our perception of these changes, ensuing awareness of management choice implications in AM development. In this context, for extensive farming systems and regarding environmental and economic costs, the identification of agronomic management practices that allow controlled manipulation of the fungal community and capitalization of AM mutualistic effect making use of local inoculum, seem to be a wise option for mycorrhiza promotion and development of sustainable crop production

The systematic guideline review: method, rationale, and test on chronic heart failure

Background: Evidence-based guidelines have the potential to improve healthcare. However, their de-novo-development requires substantial resources-especially for complex conditions, and adaptation may be biased by contextually influenced recommendations in source guidelines. In this paper we describe a new approach to guideline development-the systematic guideline review method (SGR), and its application in the development of an evidence-based guideline for family physicians on chronic heart failure (CHF). Methods: A systematic search for guidelines was carried out. Evidence-based guidelines on CHF management in adults in ambulatory care published in English or German between the years 2000 and 2004 were included. Guidelines on acute or right heart failure were excluded. Eligibility was assessed by two reviewers, methodological quality of selected guidelines was appraised using the AGREE instrument, and a framework of relevant clinical questions for diagnostics and treatment was derived. Data were extracted into evidence tables, systematically compared by means of a consistency analysis and synthesized in a preliminary draft. Most relevant primary sources were re-assessed to verify the cited evidence. Evidence and recommendations were summarized in a draft guideline. Results: Of 16 included guidelines five were of good quality. A total of 35 recommendations were systematically compared: 25/35 were consistent, 9/35 inconsistent, and 1/35 un-rateable (derived from a single guideline). Of the 25 consistencies, 14 were based on consensus, seven on evidence and four differed in grading. Major inconsistencies were found in 3/9 of the inconsistent recommendations. We re-evaluated the evidence for 17 recommendations (evidence-based, differing evidence levels and minor inconsistencies) - the majority was congruent. Incongruity was found where the stated evidence could not be verified in the cited primary sources, or where the evaluation in the source guidelines focused on treatment benefits and underestimated the risks. The draft guideline was completed in 8.5 man-months. The main limitation to this study was the lack of a second reviewer. Conclusion: The systematic guideline review including framework development, consistency analysis and validation is an effective, valid, and resource saving-approach to the development of evidence-based guidelines