Introducing the Perfect Language. Department of Computer Science, Technical Report Series. NUIM-CS-TR-2005-06

Perfect Developer is an environment that supports software development by providing a verification of the softwares correctness. Software is constructed with the Perfect language, an Object Oriented programming language that encompasses both specification and implementation features. This paper provides a general overview of the syntax of Perfect, describing a class template for Perfect. The novel features of the language are highlighted to document the uniqueness of Perfect. A small example is developed toward the end of the paper, to illustrate the process of software development on a small scale

Information-based cues at point of choice to change selection and consumption of food, alcohol and tobacco products: a systematic review.

BACKGROUND: Reducing harmful consumption of food, alcohol, and tobacco products would prevent many cancers, diabetes and cardiovascular disease. Placing information-based cues in the environments in which we select and consume these products has the potential to contribute to changing these behaviours. METHODS: In this review, information-based cues are defined as those which comprise any combination of words, symbols, numbers or pictures that convey information about a product or its use. We specifically exclude cues which are located on the products themselves. We conducted a systematic review of randomised, cluster- randomised, and non-randomised controlled trials to assess the impact of such cues on selection and consumption. Thirteen studies met the inclusion criteria, of which 12 targeted food (most commonly fruit and vegetables), one targeted alcohol sales, and none targeted tobacco products. RESULTS: Ten studies reported statistically significant effects on some or all of the targeted products, although studies were insufficiently homogenous to justify meta-analysis. Existing evidence suggests information-based cues can influence selection and consumption of food and alcohol products, although significant uncertainty remains. CONCLUSIONS: The current evidence base is limited both in quality and quantity, with relatively few, heterogeneous studies at unclear or high risk of bias. Additional, more rigorously conducted studies are warranted to better estimate the potential for these interventions to change selection and consumption of food, alcohol and tobacco products. TRIAL REGISTRATION: PROSPERO. 2016; CRD42016051884

Software Specification, Implementation and Execution with Perfect. Department of Computer Science, Technical Report Series. NUIM-CS-TR-2005-07

Perfect is an Object Oriented programming language that is supported by the Perfect Developer software development tool. The paper presents the techniques that Perfect supports for the specification and implementation of software. The executable code produced by Perfect is also discussed. A guideline to the techniques of software development is provided by the paper, illustrating the many software development mechanisms that are supported by Perfect and the Perfect Developer tool

Preparation and experimental studies into unconventional superconductivity in metallic elements and binary intermetallic alloys

In a conventional superconductor, electrons pair up in a spin-singlet s-wave state, interact through the virtual exchange of phonons, and the gauge symmetry is spontaneously broken upon transitioning into the superconducting state. But a superconductor is unconventional if a different pairing state or interaction is present, or if additional symmetries are broken. Work presented in this thesis involved the preparation of polycrystalline Re, La, La3Os, La3Ru, La3Ge, and single crystal La7Ni3, which were investigated using structural, magnetic, thermal, transport, and muon spectroscopy measurements, at low temperatures and in high magnetic fields, to search for signatures of unconventional superconductivity. Elemental rhenium exhibiting type-I superconductivity was studied with muons in zero-field to investigate time-reversal symmetry breaking. In contrast to work published on the type-II material, no unconventional behaviour is observed, in agreement with heat capacity measurements. Instead, quantum muon diffusion occurs, which can be explained quantitatively in the normal state for a clean metal and is supported by resistivity data. Energy differences between muon stopping sites produce the qualitative behaviour in the superconducting state. While the exact pairing state of this family is unknown, La3(Os, Ru, Ge) all show evidence of d-wave superconductivity and enhanced electron-electron correlations. These properties occur regardless of the tetragonal crystal structure of La3Ge, or from a reduced spin-orbit coupling strength in La3Ru, when compared with a new orthorhombic superconductor, La3Os. This suggests that the local electronic structure determines the unconventionality. In agreement with the polycrystalline material, single crystal La7Ni3 exhibits a two-gap pairing state, but also there is also evidence of a wavevector-dependent component, surface superconductivity, and anisotropy of the normal and superconducting parameters. Time-reversal symmetry is also preserved in elemental facecentred- cubic lanthanum, which infers that the unconventional behaviour seen in La7Ni3 and other isostructural compounds in this family is due to the superconducting pairing state

Morphology of small-scale submarine mass movement events across the northwest United Kingdom

A review of multibeam echo sounder (MBES) survey data from five locations around the United Kingdom northwest coast has led to the identification of a total of 14 separate subaqueous mass movement scars and deposits within the fjords (sea lochs) and coastal inlets of mainland Scotland, and the channels between the islands of the Inner Hebrides. In these areas, Quaternary sediment deposition was dominated by glacial and glaciomarine processes. Analysis of the morphometric parameters of each submarine mass movement has revealed that they fall into four distinct groups of subaqueous landslides; Singular Slumps, Singular Translational, Multiple Single-Type, and Complex (translational & rotational) failures. The Singular Slump Group includes discrete, individual subaqueous slumps that exhibit no evidence of modification through the merging of several scars. The Singular Translational Group comprise a single slide that displays characteristics associated with a single translational (planar) failure with no merging of multiple events. The Multiple Single-Type Group incorporates scars and deposits that displayed morphometric features consistent with the amalgamation of several failure events of the same type (e.g. debris flows or slumps). Finally, the Complex (translational & rotational) Group comprises landslides that exhibited complex styles of failures, including both translational and rotational mechanisms controlling the same slide. The submarine mass movements that comprise this dataset are then discussed in relation to global fjordic and glaciomarine nearshore settings, and slope failure trigger mechanisms associated with these environments are described with tentative links to individual submarine landslides from the database, where appropriate. It is acknowledged that additional MBES data are needed not only to expand this database, but also in order to create a more statistically robust study. However, this initial study provides the basis for a much wider investigation of subaqueous mass movements and correlations between their morphometric parameters

Interference of the T cell and antigen-presenting cell costimulatory pathway using CTLA4-Ig (abatacept) prevents Staphylococcal enterotoxin B pathology

Abstract Staphylococcal enterotoxin B (SEB) is a bacterial superantigen that binds the receptors in the APC/T cell synapse and causes increased proliferation of T cells and a cytokine storm syndrome in vivo. Exposure to the toxin can be lethal and cause significant pathology in humans. The lack of effective therapies for SEB exposure remains an area of concern, particularly in scenarios of acute mass casualties. We hypothesized that blockade of the T cell costimulatory signal by the CTLA4-Ig synthetic protein (abatacept) could prevent SEB-dependent pathology. In this article, we demonstrate mice treated with a single dose of abatacept 8 h post SEB exposure had reduced pathology compared with control SEB-exposed mice. SEB-exposed mice showed significant reductions in body weight between days 4 and 9, whereas mice exposed to SEB and also treated with abatacept showed no weight loss for the duration of the study, suggesting therapeutic mitigation of SEB-induced morbidity. Histopathology and magnetic resonance imaging demonstrated that SEB mediated lung damage and edema, which were absent after treatment with abatacept. Analysis of plasma and lung tissues from SEB-exposed mice treated with abatacept demonstrated significantly lower levels of IL-6 and IFN-γ (p &amp;lt; 0.0001), which is likely to have resulted in less pathology. In addition, exposure of human and mouse PBMCs to SEB in vitro showed a significant reduction in levels of IL-2 (p &amp;lt; 0.0001) after treatment with abatacept, indicating that T cell proliferation is the main target for intervention. Our findings demonstrate that abatacept is a robust and potentially credible drug to prevent toxic effects from SEB exposure.</jats:p

Differential splicing of neuronal genes in a Trem2*R47H mouse model mimics alterations associated with Alzheimer\u27s disease.

BACKGROUND: Molecular characterization of late-onset Alzheimer\u27s disease (LOAD), the leading cause of age-related dementia, has revealed transcripts, proteins, and pathway alterations associated with disease. Assessing these postmortem signatures of LOAD in experimental model systems can further elucidate their relevance to disease origins and progression. Model organisms engineered with human genetic factors further link these signatures to disease-associated variants, especially when studies are designed to leverage homology across species. Here we assess differential gene splicing patterns in aging mouse models carrying humanized APOE4 and/or the Trem2*R47H variant on a C57BL/6J background. We performed a differential expression of gene (DEG) and differential splicing analyses on whole brain transcriptomes at multiple ages. To better understand the difference between differentially expressed and differentially spliced genes, we evaluated enrichment of KEGG pathways and cell-type specific gene signatures of the adult brain from each alteration type. To determine LOAD relevance, we compared differential splicing results from mouse models with multiple human AD splicing studies. RESULTS: We found that differentially expressed genes in Trem2*R47H mice were significantly enriched in multiple AD-related pathways, including immune response, osteoclast differentiation, and metabolism, whereas differentially spliced genes were enriched for neuronal related functions, including GABAergic synapse and glutamatergic synapse. These results were reinforced by the enrichment of microglial genes in DEGs and neuronal genes in differentially spliced genes in Trem2*R47H mice. We observed significant overlap between differentially spliced genes in Trem2*R47H mice and brains from human AD subjects. These effects were absent in APOE4 mice and suppressed in APOE4.Trem2*R47H double mutant mice relative to Trem2*R47H mice. CONCLUSIONS: The cross-species observation that alternative splicing observed in LOAD are present in Trem2*R47H mouse models suggests a novel link between this candidate risk gene and molecular signatures of LOAD in neurons and demonstrates how deep molecular analysis of new genetic models links molecular disease outcomes to a human candidate gene

Genetic perturbations of disease risk genes in mice capture transcriptomic signatures of late-onset Alzheimer\u27s disease.

BACKGROUND: New genetic and genomic resources have identified multiple genetic risk factors for late-onset Alzheimer\u27s disease (LOAD) and characterized this common dementia at the molecular level. Experimental studies in model organisms can validate these associations and elucidate the links between specific genetic factors and transcriptomic signatures. Animal models based on LOAD-associated genes can potentially connect common genetic variation with LOAD transcriptomes, thereby providing novel insights into basic biological mechanisms underlying the disease. METHODS: We performed RNA-Seq on whole brain samples from a panel of six-month-old female mice, each carrying one of the following mutations: homozygous deletions of Apoe and Clu; hemizygous deletions of Bin1 and Cd2ap; and a transgenic APOEε4. Similar data from a transgenic APP/PS1 model was included for comparison to early-onset variant effects. Weighted gene co-expression network analysis (WGCNA) was used to identify modules of correlated genes and each module was tested for differential expression by strain. We then compared mouse modules with human postmortem brain modules from the Accelerating Medicine\u27s Partnership for AD (AMP-AD) to determine the LOAD-related processes affected by each genetic risk factor. RESULTS: Mouse modules were significantly enriched in multiple AD-related processes, including immune response, inflammation, lipid processing, endocytosis, and synaptic cell function. WGCNA modules were significantly associated with Apoe CONCLUSIONS: This study of genetic mouse models provides a basis to dissect the role of AD risk genes in relevant AD pathologies. We determined that different genetic perturbations affect different molecular mechanisms comprising AD, and mapped specific effects to each risk gene. Our approach provides a platform for further exploration into the causes and progression of AD by assessing animal models at different ages and/or with different combinations of LOAD risk variants

Late Devensian to Holocene environmental change, Loch Lomond, UK: a seismic sedimentary record of deglaciation, paraglacial and postglacial landscape evolution

We present an interpretation of two-dimensional sub-bottom profiling data from Loch Lomond, Scotland, UK. Sediments deposited during and following the last glacier advance have been investigated for decades around the shores of Loch Lomond. For the first time, this study presents an interpretation of the subsurface providing a window into the late Quaternary and Holocene history of Loch Lomond and its surrounding. The seismic stratigraphy records the infill of the loch during the final stages of the Loch Lomond Stadial (LLS, 12.9–11.7 ka BP), through the Holocene and into the present day. Results reveal the presence of distinct seismic facies (SF) identifying four principal seismic horizons; SF-I, SF-II, SF-III, and SF-IV. The SF-I horizon represents the glaciated surface, interpreted as subglacial till (locally forming drumlins), glacial moraines or bedrock. Ice retreat was accompanied by glaciolacustrine sedimentation in a proglacial lake setting, depositing up to 44 m of laminated sediments and ice marginal fans (SF-IIa, b). A period of landscape instability followed with extensive deposition of mass transport deposits (SF-III). These deposits, characterised by chaotic seismic facies with an erosional basal surface, are up to 43 m thick and may represent up to 50 % of the sediment fill. SF-IV comprises finely laminated sediments deposited during the Holocene and highlights slower sedimentation rates in comparison to earlier phases of sedimentation. This study reveals new insights into the deglaciation of Loch Lomond, including previously unrecognised extensive mass transport deposits buried in the subsurface, associated with a period of paraglacial adjustment