A Sparse Stress Model

Force-directed layout methods constitute the most common approach to draw general graphs. Among them, stress minimization produces layouts of comparatively high quality but also imposes comparatively high computational demands. We propose a speed-up method based on the aggregation of terms in the objective function. It is akin to aggregate repulsion from far-away nodes during spring embedding but transfers the idea from the layout space into a preprocessing phase. An initial experimental study informs a method to select representatives, and subsequent more extensive experiments indicate that our method yields better approximations of minimum-stress layouts in less time than related methods.Comment: Appears in the Proceedings of the 24th International Symposium on Graph Drawing and Network Visualization (GD 2016

First Steps towards Underdominant Genetic Transformation of Insect Populations

The idea of introducing genetic modifications into wild populations of insects to stop them from spreading diseases is more than 40 years old. Synthetic disease refractory genes have been successfully generated for mosquito vectors of dengue fever and human malaria. Equally important is the development of population transformation systems to drive and maintain disease refractory genes at high frequency in populations. We demonstrate an underdominant population transformation system in Drosophila melanogaster that has the property of being both spatially self-limiting and reversible to the original genetic state. Both population transformation and its reversal can be largely achieved within as few as 5 generations. The described genetic construct {Ud} is composed of two genes; (1) a UAS-RpL14.dsRNA targeting RNAi to a haploinsufficient gene RpL14 and (2) an RNAi insensitive RpL14 rescue. In this proof-of-principle system the UAS-RpL14.dsRNA knock-down gene is placed under the control of an Actin5c-GAL4 driver located on a different chromosome to the {Ud} insert. This configuration would not be effective in wild populations without incorporating the Actin5c-GAL4 driver as part of the {Ud} construct (or replacing the UAS promoter with an appropriate direct promoter). It is however anticipated that the approach that underlies this underdominant system could potentially be applied to a number of species. Figure

Evaluation of Phage Display Discovered Peptides as Ligands for Prostate-Specific Membrane Antigen (PSMA)

The aim of this study was to identify potential ligands of PSMA suitable for further development as novel PSMA-targeted peptides using phage display technology. The human PSMA protein was immobilized as a target followed by incubation with a 15-mer phage display random peptide library. After one round of prescreening and two rounds of screening, high-stringency screening at the third round of panning was performed to identify the highest affinity binders. Phages which had a specific binding activity to PSMA in human prostate cancer cells were isolated and the DNA corresponding to the 15-mers were sequenced to provide three consensus sequences: GDHSPFT, SHFSVGS and EVPRLSLLAVFL as well as other sequences that did not display consensus. Two of the peptide sequences deduced from DNA sequencing of binding phages, SHSFSVGSGDHSPFT and GRFLTGGTGRLLRIS were labeled with 5-carboxyfluorescein and shown to bind and co-internalize with PSMA on human prostate cancer cells by fluorescence microscopy. The high stringency requirements yielded peptides with affinities KD∼1 μM or greater which are suitable starting points for affinity maturation. While these values were less than anticipated, the high stringency did yield peptide sequences that apparently bound to different surfaces on PSMA. These peptide sequences could be the basis for further development of peptides for prostate cancer tumor imaging and therapy. © 2013 Shen et al

Niche as a determinant of word fate in online groups

Patterns of word use both reflect and influence a myriad of human activities and interactions. Like other entities that are reproduced and evolve, words rise or decline depending upon a complex interplay between {their intrinsic properties and the environments in which they function}. Using Internet discussion communities as model systems, we define the concept of a word niche as the relationship between the word and the characteristic features of the environments in which it is used. We develop a method to quantify two important aspects of the size of the word niche: the range of individuals using the word and the range of topics it is used to discuss. Controlling for word frequency, we show that these aspects of the word niche are strong determinants of changes in word frequency. Previous studies have already indicated that word frequency itself is a correlate of word success at historical time scales. Our analysis of changes in word frequencies over time reveals that the relative sizes of word niches are far more important than word frequencies in the dynamics of the entire vocabulary at shorter time scales, as the language adapts to new concepts and social groupings. We also distinguish endogenous versus exogenous factors as additional contributors to the fates of words, and demonstrate the force of this distinction in the rise of novel words. Our results indicate that short-term nonstationarity in word statistics is strongly driven by individual proclivities, including inclinations to provide novel information and to project a distinctive social identity.Comment: Supporting Information is available here: http://www.plosone.org/article/fetchSingleRepresentation.action?uri=info:doi/10.1371/journal.pone.0019009.s00

Species recovery in the united states: Increasing the effectiveness of the endangered species act

The Endangered Species Act (ESA) has succeeded in shielding hundreds of species from extinction and improving species recovery over time. However, recovery for most species officially protected by the ESA - i.e., listed species-has been harder to achieve than initially envisioned. Threats to species are persistent and pervasive, funding has been insufficient, the distribution of money among listed species is highly uneven, and at least 10 times more species than are actually listed probably qualify for listing. Moreover, many listed species will require ongoing management for the foreseeable future to protect them from persistent threats. Climate change will exacerbate this problem and increase both species risk and management uncertainty, requiring more intensive and controversial management strategies to prevent species from going extinct

Why is it difficult to implement e-health initiatives? A qualitative study

<b>Background</b> The use of information and communication technologies in healthcare is seen as essential for high quality and cost-effective healthcare. However, implementation of e-health initiatives has often been problematic, with many failing to demonstrate predicted benefits. This study aimed to explore and understand the experiences of implementers - the senior managers and other staff charged with implementing e-health initiatives and their assessment of factors which promote or inhibit the successful implementation, embedding, and integration of e-health initiatives.<p></p> <b>Methods</b> We used a case study methodology, using semi-structured interviews with implementers for data collection. Case studies were selected to provide a range of healthcare contexts (primary, secondary, community care), e-health initiatives, and degrees of normalization. The initiatives studied were Picture Archiving and Communication System (PACS) in secondary care, a Community Nurse Information System (CNIS) in community care, and Choose and Book (C&B) across the primary-secondary care interface. Implementers were selected to provide a range of seniority, including chief executive officers, middle managers, and staff with 'on the ground' experience. Interview data were analyzed using a framework derived from Normalization Process Theory (NPT).<p></p> <b>Results</b> Twenty-three interviews were completed across the three case studies. There were wide differences in experiences of implementation and embedding across these case studies; these differences were well explained by collective action components of NPT. New technology was most likely to 'normalize' where implementers perceived that it had a positive impact on interactions between professionals and patients and between different professional groups, and fit well with the organisational goals and skill sets of existing staff. However, where implementers perceived problems in one or more of these areas, they also perceived a lower level of normalization.<p></p> <b>Conclusions</b> Implementers had rich understandings of barriers and facilitators to successful implementation of e-health initiatives, and their views should continue to be sought in future research. NPT can be used to explain observed variations in implementation processes, and may be useful in drawing planners' attention to potential problems with a view to addressing them during implementation planning

Enabling comparative modeling of closely related genomes: Example genus Brucella

For many scientific applications, it is highly desirable to be able to compare metabolic models of closely related genomes. In this short report, we attempt to raise awareness to the fact that taking annotated genomes from public repositories and using them for metabolic model reconstructions is far from being trivial due to annotation inconsistencies. We are proposing a protocol for comparative analysis of metabolic models on closely related genomes, using fifteen strains of genus Brucella, which contains pathogens of both humans and livestock. This study lead to the identification and subsequent correction of inconsistent annotations in the SEED database, as well as the identification of 31 biochemical reactions that are common to Brucella, which are not originally identified by automated metabolic reconstructions. We are currently implementing this protocol for improving automated annotations within the SEED database and these improvements have been propagated into PATRIC, Model-SEED, KBase and RAST. This method is an enabling step for the future creation of consistent annotation systems and high-quality model reconstructions that will support in predicting accurate phenotypes such as pathogenicity, media requirements or type of respiration.We thank Jean Jacques Letesson, Maite Iriarte, Stephan Kohler and David O'Callaghan for their input on improving specific annotations. This project has been funded by the United States National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under Contract No. HHSN272200900040C, awarded to BW Sobral, and from the United States National Science Foundation under Grant MCB-1153357, awarded to CS Henry. J.P.F. acknowledges funding from [FRH/BD/70824/2010] of the FCT (Portuguese Foundation for Science and Technology) Ph.D. scholarship

Double differentiation in a cross-national comparison of populist political movements and online media uses in the United States and the Netherlands

In a context of highly visible and politically influential populist movements, this study considers the online self-representation of the Tea Party Patriots (TPP) in the United States and the Party for Freedom (PVV) in the Netherlands. A multi-methodological approach was adopted to compare the discursive manifestation of key populism concepts: leadership characteristics, adversary definition and mobilizing information. Analyses reconstruct and account for similarities and differences in discursive framing strategies of 'double differentiation' through which both movements attempt inclusion in and exclusion from the political establishment, and, in doing so, mobilize communities of support. Altogether, this study advances the understanding of what constitutes 'unmediated' content that is presented through user-generated media production, and how self-determined media spaces have facilitated shifts in populist media legitimation and political representation in two politically unique countries

The role of government co-investment funds in the supply of entrepreneurial finance: An assessment of the early operation of the UK Angel Co-investment Fund

Co-investment funds – which invest alongside private investors, especially business angels – thereby leveraging their networks and experience and minimizing public sector transaction costs – are a recent approach by governments in various countries to address the early stage entrepreneurial funding gap which is perceived as a barrier to the ability of firms to scale-up. However, little literature exists on their operation, impact and effectiveness. This paper assesses the early operation of the UK’s Angel Co-investment Fund, established in 2011. Interview evidence from angels and business managers suggests that the Angel Co-investment Fund is improving the availability of finance by enabling firms to raise funding rounds of between £500,000 and £2 m, hence addressing some aspects of the broken finance escalator model. However, our evidence suggests that it is not yet impacting the supply side, either in terms of stimulating the formation of new angel groups or enhancing learning amongst less experienced angels. Some aspects of the operation of the investment process have attracted criticism from angels and entrepreneurs which need to be addressed. Nevertheless, there is sufficient evidence for positive impact to justify the scheme’s expansion

Gross-Neveu Models, Nonlinear Dirac Equations, Surfaces and Strings

Recent studies of the thermodynamic phase diagrams of the Gross-Neveu model (GN2), and its chiral cousin, the NJL2 model, have shown that there are phases with inhomogeneous crystalline condensates. These (static) condensates can be found analytically because the relevant Hartree-Fock and gap equations can be reduced to the nonlinear Schr\"odinger equation, whose deformations are governed by the mKdV and AKNS integrable hierarchies, respectively. Recently, Thies et al have shown that time-dependent Hartree-Fock solutions describing baryon scattering in the massless GN2 model satisfy the Sinh-Gordon equation, and can be mapped directly to classical string solutions in AdS3. Here we propose a geometric perspective for this result, based on the generalized Weierstrass spinor representation for the embedding of 2d surfaces into 3d spaces, which explains why these well-known integrable systems underlie these various Gross-Neveu gap equations, and why there should be a connection to classical string theory solutions. This geometric viewpoint may be useful for higher dimensional models, where the relevant integrable hierarchies include the Davey-Stewartson and Novikov-Veselov systems.Comment: 27 pages, 1 figur