The use of informal resolution approaches by ombudsmen in the UK and Ireland: A mapping study

This report presents findings of an empirical research project, funded by the Nuffield Foundation, designed to produce a descriptive mapping study on the use of informal resolution by ombudsmen. Its focus is on the use of informal resolution approaches as alternatives to investigation and determination/decision. The use of informal and early resolution techniques by ombudsmen and other complaint handlers is an under-studied area but one which is gaining importance in light of several developments in the field of administrative justice generally, and the European Union ADR Directive, to be implemented by 2015. This directive looks set to overhaul complaint handling in the private sector by requiring the government to ensure that an ADR scheme is available in all contractual disputes between a consumer and a business (although neither consumer nor business will be obliged to use the service). This report sets out the analysis of the responses received from 48 ombudsman and complaint-handling organisations in UK and Ireland that are (or were at the relevant time) members of the Ombudsman Association

Module-Based Analysis of Robustness Tradeoffs in the Heat Shock Response System

Biological systems have evolved complex regulatory mechanisms, even in situations where much simpler designs seem to be sufficient for generating nominal functionality. Using module-based analysis coupled with rigorous mathematical comparisons, we propose that in analogy to control engineering architectures, the complexity of cellular systems and the presence of hierarchical modular structures can be attributed to the necessity of achieving robustness. We employ the Escherichia coli heat shock response system, a strongly conserved cellular mechanism, as an example to explore the design principles of such modular architectures. In the heat shock response system, the sigma-factor σ(32) is a central regulator that integrates multiple feedforward and feedback modules. Each of these modules provides a different type of robustness with its inherent tradeoffs in terms of transient response and efficiency. We demonstrate how the overall architecture of the system balances such tradeoffs. An extensive mathematical exploration nevertheless points to the existence of an array of alternative strategies for the existing heat shock response that could exhibit similar behavior. We therefore deduce that the evolutionary constraints facing the system might have steered its architecture toward one of many robustly functional solutions

Co-evolution of density and topology in a simple model of city formation

We study the influence that population density and the road network have on each others' growth and evolution. We use a simple model of formation and evolution of city roads which reproduces the most important empirical features of street networks in cities. Within this framework, we explicitely introduce the topology of the road network and analyze how it evolves and interact with the evolution of population density. We show that accessibility issues -pushing individuals to get closer to high centrality nodes- lead to high density regions and the appearance of densely populated centers. In particular, this model reproduces the empirical fact that the density profile decreases exponentially from a core district. In this simplified model, the size of the core district depends on the relative importance of transportation and rent costs.Comment: 13 pages, 13 figure

The Main Belt Comets and ice in the Solar System

We review the evidence for buried ice in the asteroid belt; specifically the questions around the so-called Main Belt Comets (MBCs). We summarise the evidence for water throughout the Solar System, and describe the various methods for detecting it, including remote sensing from ultraviolet to radio wavelengths. We review progress in the first decade of study of MBCs, including observations, modelling of ice survival, and discussion on their origins. We then look at which methods will likely be most effective for further progress, including the key challenge of direct detection of (escaping) water in these bodies

The Aspergillus fumigatus transcription factor RglT is important for gliotoxin biosynthesis and self-protection, and virulence

This is the final version (corrected proof). The final published version is available from Public Library of Science via the DOI in this recordData Availability: Short reads were submitted to the NCBI’s Sequence Read Archive under accession number SRP154617 (https://www.ncbi.nlm.nih.gov/sra/?term=SRP154617). The ChIPseq data are available from NCBI SRA (sequence read archive) database under accession number PRJNA574873 (https://www.ncbi.nlm.nih.gov/Traces/study/?acc=PRJNA574873&o=acc_s%3Aa).Aspergillus fumigatus is an opportunistic fungal pathogen that secretes an array of immune-modulatory molecules, including secondary metabolites (SMs), which contribute to enhancing fungal fitness and growth within the mammalian host. Gliotoxin (GT) is a SM that interferes with the function and recruitment of innate immune cells, which are essential for eliminating A. fumigatus during invasive infections. We identified a C6 Zn cluster-type transcription factor (TF), subsequently named RglT, important for A. fumigatus oxidative stress resistance, GT biosynthesis and self-protection. RglT regulates the expression of several gli genes of the GT biosynthetic gene cluster, including the oxidoreductase-encoding gene gliT, by directly binding to their respective promoter regions. Subsequently, RglT was shown to be important for virulence in a chemotherapeutic murine model of invasive pulmonary aspergillosis (IPA). Homologues of RglT and GliT are present in eurotiomycete and sordariomycete fungi, including the non-GT-producing fungus A. nidulans, where a conservation of function was described. Phylogenetically informed model testing led to an evolutionary scenario in which the GliT-based resistance mechanism is ancestral and RglT-mediated regulation of GliT occurred subsequently. In conclusion, this work describes the function of a previously uncharacterised TF in oxidative stress resistance, GT biosynthesis and self-protection in both GT-producing and non-producing Aspergillus species.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESPConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior – Brasil (CAPES)Wellcome TrustUniversity of MacauNational Science Foundation (NSF)Vanderbilt UniversityHoward Hughes Medical Institut

The regions within the N-terminus critical for human glucagon like peptide-1 receptor (hGLP-1R) cell Surface expression

The hGLP-1R is a target for the treatment of type 2 diabetes and belongs to the class B family of GPCRs. Like other class B GPCRs, the GLP-1R contains an N-terminal signal peptide (SP) and undergoes N-linked glycosylation, which are important for its trafficking and maturation. This study analysed the role of the SP, the hydrophobic region after the SP (HRASP), glycosylation and the conserved residues within the N-terminus in GLP-1R trafficking. HGLP-1R targeted to the cell surface showed no SP, and the SP deleted mutant, but not the mutants defective in SP cleavage, showed cell surface expression, demonstrating the importance of SP cleavage for hGLP-1R cell surface expression. The N-terminal deletions of hGLP-1R revealed that the HRASP, not the SP, is essential for cell surface expression of GLP-1R. Further, inhibition of hGLP-1R glycosylation prevented cell surface expression of the receptor. Mutation of Trp39, Tyr69 and Tyr88, which are required for agonist binding, in the GLP-1R abolished cell surface expression of the receptor independent of the SP cleavage or N-linked glycosylation. In conclusion, the N-terminus of hGLP-1R regulates receptor trafficking and maturation. Therefore this study provides insight into the role of hGLP-1R N-terminus on the receptor cell surface expression

The influence of the accessory genome on bacterial pathogen evolution

Bacterial pathogens exhibit significant variation in their genomic content of virulence factors. This reflects the abundance of strategies pathogens evolved to infect host organisms by suppressing host immunity. Molecular arms-races have been a strong driving force for the evolution of pathogenicity, with pathogens often encoding overlapping or redundant functions, such as type III protein secretion effectors and hosts encoding ever more sophisticated immune systems. The pathogens’ frequent exposure to other microbes, either in their host or in the environment, provides opportunities for the acquisition or interchange of mobile genetic elements. These DNA elements accessorise the core genome and can play major roles in shaping genome structure and altering the complement of virulence factors. Here, we review the different mobile genetic elements focusing on the more recent discoveries and highlighting their role in shaping bacterial pathogen evolution

The Rossiter-McLaughlin effect in Exoplanet Research

The Rossiter-McLaughlin effect occurs during a planet's transit. It provides the main means of measuring the sky-projected spin-orbit angle between a planet's orbital plane, and its host star's equatorial plane. Observing the Rossiter-McLaughlin effect is now a near routine procedure. It is an important element in the orbital characterisation of transiting exoplanets. Measurements of the spin-orbit angle have revealed a surprising diversity, far from the placid, Kantian and Laplacian ideals, whereby planets form, and remain, on orbital planes coincident with their star's equator. This chapter will review a short history of the Rossiter-McLaughlin effect, how it is modelled, and will summarise the current state of the field before describing other uses for a spectroscopic transit, and alternative methods of measuring the spin-orbit angle.Comment: Review to appear as a chapter in the "Handbook of Exoplanets", ed. H. Deeg & J.A. Belmont

Influence of adding multiwalled carbon nanotubes on the adhesive strength of composite epoxy/sol–gel materials

The tensile shear strength of a composite epoxy/sol–gel system modified with different ratios of multiwall carbon nanotubes (MWCNTs) was evaluated using a mechanical testing machine. The experimental results showed that the shear strength increased when lower than ~0.07 wt% of MWCNTs were added in the composite solution. The increase of the shear strength was attributed to both the mechanical load transfer from the matrix to the MWCNTs and the high specific surface area of this material that increased the degree of crosslinking with other inorganic fillers in the formulation. However, a decrease in the adhesive shear strength was observed after more than ~0.07 wt% MWCNTs were added to the composite. The reason for this may be related to the high concentration of MWCNTs within the matrix leading to excessively high viscosity, dewetting of the substrate surfaces, and reduced bonding of MWCNTs with the matrix, thereby limiting the strength. SEM observation of the fracture surfaces for composite epoxy/sol–gel adhesive materials with 0.01 wt% MWCNTs showed a mixed interfacial/cohesive fracture mode. This fracture mode indicated strong links at the adhesive/substrate interface, and interaction between CNTs and the matrix was achieved; therefore, adhesion performance of the composite epoxy/sol–gel material to the substrate was improved. An increase of a strong peak related to the C–O bond at ~1733 cm-1 in the FTIR spectra was observed. This peak represented crosslinking between the CNT surface and the organosilica nanoparticles in the MWCNTs-doped composite adhesive. Raman spectroscopy was also used to identify MWCNTs within the adhesive material. The Raman spectra exhibit peaks at ~1275 cm-1 and in the range of ~1549–1590 cm-1. The former is the graphite G-band, while the latter is the diamond D-band. The D-band and G-band represent the C–C single bond and C=C double bond in carbon nanotubes, respectively

Isolation of microplastics in biota-rich seawater samples and marine organisms.

notes: PMCID: PMC3970126types: Journal Article; Research Support, Non-U.S. Gov'tThis is an open access article that is freely available in ORE or from the publisher's web site. Please cite the published version.Microplastic litter is a pervasive pollutant present in aquatic systems across the globe. A range of marine organisms have the capacity to ingest microplastics, resulting in adverse health effects. Developing methods to accurately quantify microplastics in productive marine waters, and those internalized by marine organisms, is of growing importance. Here we investigate the efficacy of using acid, alkaline and enzymatic digestion techniques in mineralizing biological material from marine surface trawls to reveal any microplastics present. Our optimized enzymatic protocol can digest >97% (by weight) of the material present in plankton-rich seawater samples without destroying any microplastic debris present. In applying the method to replicate marine samples from the western English Channel, we identified 0.27 microplastics m(-3). The protocol was further used to extract microplastics ingested by marine zooplankton under laboratory conditions. Our findings illustrate that enzymatic digestion can aid the detection of microplastic debris within seawater samples and marine biota.Natural Environment Research Council (NERC