PinR mediates the generation of reversible population diversity in Streptococcus zooepidemicus

Opportunistic pathogens must adapt to and survive in a wide range of complex ecosystems. Streptococcus zooepidemicus is an opportunistic pathogen of horses and many other animals, including humans. The assembly of different surface architecture phenotypes from one genotype is likely to be crucial to the successful exploitation of such an opportunistic lifestyle. Construction of a series of mutants revealed that a serine recombinase, PinR, inverts 114 bp of the promoter of SZO_08560, which is bordered by GTAGACTTTA and TAAAGTCTAC inverted repeats. Inversion acts as a switch, controlling the transcription of this sortase-processed protein, which may enhance the attachment of S. zooepidemicus to equine trachea. The genome of a recently sequenced strain of S. zooepidemicus, 2329 (Sz2329), was found to contain a disruptive internal inversion of 7 kb of the FimIV pilus locus, which is bordered by TAGAAA and TTTCTA inverted repeats. This strain lacks pinR and this inversion may have become irreversible following the loss of this recombinase. Active inversion of FimIV was detected in three strains of S. zooepidemicus, 1770 (Sz1770), B260863 (SzB260863) and H050840501 (SzH050840501), all of which encoded pinR. A deletion mutant of Sz1770 that lacked pinR was no longer capable of inverting its internal region of FimIV. The data highlight redundancy in the PinR sequence recognition motif around a short TAGA consensus and suggest that PinR can reversibly influence the wider surface architecture of S. zooepidemicus, providing this organism with a bet-hedging solution to survival in fluctuating environments

Verbs, times and objects

The aim of the paper is to demonstrate the fruitfulness of the influential verb typology developed by Zeno Vendler for recent debates in the philosophy of perception. Section one explains the verb typology and explains how Vendler applies it to different perceptual notions. Section two identifies various questions that arise from observations in Vendler’s paper that suggest that there is a match between the temporal properties of perceptual verb objects and the complex verb phrases of which they are a part. Subsequent discussion focuses on just one of these questions. Section three identifies and rejects a simple proposal about how to answer this question. Section four develops a ‘limited matching’ account. In the visual perception of events and processes there seems to be a match between the temporal duration, order and location of the events and processes which are the objects of perception and the subject’s perceiving them. But this matching is absent in cases of the perception of primary substances; objects which manifestly endure over time. Section five identifies and responds to some criticisms of this matching account. The conclusion notes some consequences of the discussion for contemporary debates about the temporal characteristics of perception

Integrated engineering environments for large complex products

An introduction is given to the Engineering Design Centre at the University of Newcastle upon Tyne, along with a brief explanation of the main focus towards large made-to-order products. Three key areas of research at the Centre, which have evolved as a result of collaboration with industrial partners from various sectors of industry, are identified as (1) decision support and optimisation, (2) design for lifecycle, and (3) design integration and co-ordination. A summary of the unique features of large made-to-order products is then presented, which includes the need for integration and co-ordination technologies. Thus, an overview of the existing integration and co-ordination technologies is presented followed by a brief explanation of research in these areas at the Engineering Design Centre. A more detailed description is then presented regarding the co-ordination aspect of research being conducted at the Engineering Design Centre, in collaboration with the CAD Centre at the University of Strathclyde. Concurrent Engineering is acknowledged as a strategy for improving the design process, however design coordination is viewed as a principal requirement for its successful implementation. That is, design co-ordination is proposed as being the key to a mechanism that is able to maximise and realise any potential opportunity of concurrency. Thus, an agentoriented approach to co-ordination is presented, which incorporates various types of agents responsible for managing their respective activities. The co-ordinated approach, which is implemented within the Design Co-ordination System, includes features such as resource management and monitoring, dynamic scheduling, activity direction, task enactment, and information management. An application of the Design Co-ordination System, in conjunction with a robust concept exploration tool, shows that the computational design analysis involved in evaluating many design concepts can be performed more efficiently through a co-ordinated approach

Essentially English : Sherlock Holmes at the BBC

Sir Arthur Conan Doyle’s Sherlock Holmes stories, currently enjoying renewed popularity on television via the BBC’s Sherlock (2010- ), have been adapted for the screen countless times around the world. Arguably best remembered are Granada’s long-running strand with Jeremy Brett (1984-94), and the Universal film series of the 1940s, featuring Basil Rathbone and Nigel Bruce. Less frequently cited, however, are the two series produced by the BBC between 1965 and 1968, in which first Douglas Wilmer and later Peter Cushing took on the mantle of the Baker Street detective. Typically for the time – but against the wishes of the Conan Doyle estate - these programmes adopted a multi-camera studio model; a mode of production which made them less attractive to US networks than the single camera 35mm film output of commercial rivals such as ITC. Drawing upon material from the BBC’s Written Archives Centre, this article investigates the motivations underpinning the Corporation’s refusal to accommodate the estate’s exhortations to seek American co-production and utilise single camera filming, not least of which was the BBC’s stated desire to maintain the ‘essentially English’ quality of Sherlock Holmes. This decision would have significant repercussions for the series’ overseas saleability, and – despite impressive viewing figures and positive audience reaction at home in the UK – helped contribute to its ‘forgotten’ status with regard to the television canon

Dynamical Instabilities of the Randall-Sundrum Model

We derive dynamical equations to describe a single 3-brane containing fluid matter and a scalar field coupling to the dilaton and the gravitational field in a five dimensional bulk. First, we show that a scalar field or an arbitrary fluid on the brane cannot evolve to cancel the cosmological constant in the bulk. Then we show that the Randall-Sundrum model is unstable under small deviations from the fine-tuning between the brane tension and the bulk cosmological constant and even under homogeneous gravitational perturbations. Implications for brane world cosmologies are discussed.Comment: 12 pages, 2 figure

'I would rather die': reasons given by 16-year-olds for not continuing their study of mathematics

Improving participation rates in specialist mathematics after the subject ceases to be compulsory at age 16 is part of government policy in England. This article provides independent and recent support for earlier findings concerning reasons for non- participation, based on free response and closed items in a questionnaire with a sample of over 1500 students in 17 schools, close to the moment of choice. The analysis supports findings that perceived difficulty and lack of confidence are important reasons for students not continuing with mathematics, and that perceived dislike and boredom, and lack of relevance, are also factors. There is a close relationship between reasons for non-participation and predicted grade, and a weaker relation to gender. An analysis of the effects of schools, demonstrates that enjoyment is the main factor differentiating schools with high and low participation indices. Building on discussion of these findings, ways of improving participation are briefly suggested

Multidisciplinary Design Optimization of an Extreme Aspect Ration HALE UAV

Development of High Altitude Long Endurance (HALE) aircraft systems is part of a vision for a low cost communications/surveillance capability. Applications of a multi payload aircraft operating for extended periods at stratospheric altitudes span military and civil genres and support battlefield operations, communications, atmospheric or agricultural monitoring, surveillance, and other disciplines that may currently require satellite-based infrastructure. The central goal of this research was the development of a multidisciplinary tool for analysis, design, and optimization of HALE UAVs, facilitating the study of a novel configuration concept. Applying design ideas stemming from a unique WWII-era project, a pinned wing HALE aircraft would employ self-supporting wing segments assembled into one overall flying wing. When wrapped in an optimization routine, the integrated design environment shows potential for a 17.3% reduction in weight when wing thickness to chord ratio, aspect ratio, wing loading, and power to weight ratio are included as optimizer-controlled design variables. Investigation of applying the sustained day/night mission requirement and improved technology factors to the design shows that there are potential benefits associated with a segmented or pinned wing. As expected, wing structural weight is reduced, but benefits diminish as higher numbers of wing segments are considered. For an aircraft consisting of six wing segments, a maximum of 14.2% reduction in gross weight over an advanced technology optimal baseline is predicted

Identifying component modules

A computer-based system for modelling component dependencies and identifying component modules is presented. A variation of the Dependency Structure Matrix (DSM) representation was used to model component dependencies. The system utilises a two-stage approach towards facilitating the identification of a hierarchical modular structure. The first stage calculates a value for a clustering criterion that may be used to group component dependencies together. A Genetic Algorithm is described to optimise the order of the components within the DSM with the focus of minimising the value of the clustering criterion to identify the most significant component groupings (modules) within the product structure. The second stage utilises a 'Module Strength Indicator' (MSI) function to determine a value representative of the degree of modularity of the component groupings. The application of this function to the DSM produces a 'Module Structure Matrix' (MSM) depicting the relative modularity of available component groupings within it. The approach enabled the identification of hierarchical modularity in the product structure without the requirement for any additional domain specific knowledge within the system. The system supports design by providing mechanisms to explicitly represent and utilise component and dependency knowledge to facilitate the nontrivial task of determining near-optimal component modules and representing product modularity

Mutations in GATA2 cause primary lymphedema associated with a predisposition to acute myeloid leukemia (Emberger syndrome).

We report an allelic series of eight mutations in GATA2 underlying Emberger syndrome, an autosomal dominant primary lymphedema associated with a predisposition to acute myeloid leukemia. GATA2 is a transcription factor that plays an essential role in gene regulation during vascular development and hematopoietic differentiation. Our findings indicate that haploinsufficiency of GATA2 underlies primary lymphedema and predisposes to acute myeloid leukemia in this syndrome

Negative Thermal Expansion Coefficient of Graphene Measured by Raman Spectroscopy

The thermal expansion coefficient (TEC) of single-layer graphene is estimated with temperature-dependent Raman spectroscopy in the temperature range between 200 and 400 K. It is found to be strongly dependent on temperature but remains negative in the whole temperature range, with a room temperature value of -8.0x10^{-6} K^{-1}. The strain caused by the TEC mismatch between graphene and the substrate plays a crucial role in determining the physical properties of graphene, and hence its effect must be accounted for in the interpretation of experimental data taken at cryogenic or elevated temperatures.Comment: 17 pagese, 3 figures, and supporting information (4 pages, 3 figures); Nano Letters, 201