Expression of complement components and regulators by different subtypes of bone marrow-derived macrophages

Under inflammatory conditions, macrophages can differentiate into different functional subtypes. We show that bone marrow-derived macrophages constitutively express different levels of various complement-related genes. The relative expression levels are C1qb > Crry > CFH > C3 > C1r > CFB > DAF1 > CD59a > C2 > C1INH > C1s > C4. Upon activation, the expression of C1r, C1s, C3, C2, CFB, and C1INH was up-regulated, and CFH, CD59a, and DAF1, down-regulated in M1 (induced by interferon-? + lipopolysaccharides (LPS)) and M2b (induced by immune complex + LPS) macrophages. The expression of C4 and CFH was slightly up-regulated in interleukin (IL)-10-induced M2c macrophages. Complement gene expression in IL-4-induced M2a macrophages was weakly down-regulated as compared to resting M0 macrophages. Higher levels of C3, C1INH, and CFB but lower levels of CFH expression in M1 and M2b macrophage suggests that they may be involved in the alternative pathway of complement activation during inflammation.

Range expansion in an invasive small mammal: influence of life-history and habitat quality.

Invasive species pose a major threat to biodiversity but provide an opportunity to describe the processes that lead to changes in a species’ range. The bank vole (Myodes glareolus) is an invasive rodent that was introduced to Ireland in the early twentieth century. Given its continuing range expansion, the substantial empirical data on its spread thus far, and the absence of any eradication program, the bank vole in Ireland represents a unique model system for studying the mechanisms influencing the rate of range expansion in invasive small mammals. We described the invasion using a reaction–diffusion model informed by empirical data on life history traits and demographic parameters. We subsequently modelled the processes involved in its range expansion using a rule-based spatially explicit simulation. Habitat suitability interacted with density-dependent parameters to influence dispersal, most notably the density at which local populations started to donate emigrating individuals, the number of dispersing individuals and the direction of dispersal. Whilst local habitat variability influenced the rate of spread, on a larger scale the invasion resembled a simple reaction–diffusion process. Our results suggest a Type 1 range expansion where the rate of expansion is generally constant over time, but with some evidence for a lag period following introduction. We demonstrate that a two-parameter empirical model and a rule-based spatially explicit simulation are sufficient to accurately describe the invasion history of a species that exhibits a complex, density-dependent pattern of dispersal.

Management of long-term sickness absence: a systematic realist review

Purpose
The increasing impact and costs of long term sickness absence have been well documented. However, the diversity and complexity of interventions and of the contexts in which these take place makes a traditional review problematic. Therefore, we undertook a systematic realist review to identify the dominant programme theories underlying best practice, to assess the evidence for these theories, and to throw light on important enabling or disabling contextual factors.

Method
A search of the scholarly literature from 1950 to 2011 identified 5,576 articles, of which 269 formed the basis of the review.

Results
We found that the dominant programme theories in relation to effective management related to: early intervention or referral by employers; having proactive organisational procedures; good communication and cooperation between stakeholders; and workplace-based occupational rehabilitation. Significant contextual factors were identified as the level of support for interventions from top management, the size and structure of the organisation, the level of financial and organisational investment in the management of long-term sickness absence, and the quality of relationships between managers and staff.

Conclusions
Consequently, those with responsibility for managing absence should bear in mind the contextual factors that are likely to have an impact on interventions, and do what they can to ensure stakeholders have at least a mutual understanding (if not a common purpose) in relation to their perceptions of interventions, goals, culture and practice in the management of long term sickness absence.

Towards an understanding of the causes and effects of software requirements change: two case studies

Changes to software requirements not only pose a risk to the successful delivery of software applications but also provide opportunity for improved usability and value. Increased understanding of the causes and consequences of change can support requirements management and also make progress towards the goal of change anticipation. This paper presents the results of two case studies that address objectives arising from that ultimate goal. The first case study evaluated the potential of a change source taxonomy containing the elements ‘market’, ‘organisation’, ‘vision’, ‘specification’, and ‘solution’ to provide a meaningful basis for change classification and measurement. The second case study investigated whether the requirements attributes of novelty, complexity, and dependency correlated with requirements volatility. While insufficiency of data in the first case study precluded an investigation of changes arising due to the change source of ‘market’, for the remainder of the change sources, results indicate a significant difference in cost, value to the customer and management considerations. Findings show that higher cost and value changes arose more often from ‘organisation’ and ‘vision’ sources; these changes also generally involved the co-operation of more stakeholder groups and were considered to be less controllable than changes arising from the ‘specification’ or ‘solution’ sources. Results from the second case study indicate that only ‘requirements dependency’ is consistently correlated with volatility and that changes coming from each change source affect different groups of requirements. We conclude that the taxonomy can provide a meaningful means of change classification, but that a single requirement attribute is insufficient for change prediction. A theoretical causal account of requirements change is drawn from the implications of the combined results of the two case studies.

Computational learning of the conditional phase-type (C-Ph) distribution: Learning C-Ph distributions

This paper presents a new algorithm for learning the structure of a special type of Bayesian network. The conditional phase-type (C-Ph) distribution is a Bayesian network that models the probabilistic causal relationships between a skewed continuous variable, modelled by the Coxian phase-type distribution, a special type of Markov model, and a set of interacting discrete variables. The algorithm takes a dataset as input and produces the structure, parameters and graphical representations of the fit of the C-Ph distribution as output.The algorithm, which uses a greedy-search technique and has been implemented in MATLAB, is evaluated using a simulated data set consisting of 20,000 cases. The results show that the original C-Ph distribution is recaptured and the fit of the network to the data is discussed.

Low flow water quality in rivers; septic tank systems and high-resolution phosphorus signals

Rural point sources of phosphorus (P), including septic tank systems, provide a small part of the overall phosphorus budget to surface waters in agricultural catchments but can have a disproportionate impact on the low flow P concentration of receiving rivers. This has particular importance as the discharges are approximately constant into receiving waters and these have restricted dilution capacity during ecologically sensitive summer periods. In this study, a number of identified high impact septic systems were replaced with modern sequential batch reactors in three rural catchments during a monitoring period of 4 years. Sub-hourly P monitoring was conducted using bankside-analysers. Results show that strategic replacement of defective septic tank systems with modern systems and polishing filters decreased the low flow P concentration of one catchment stream by 0.032 mg TP L- 1 (0.018 mg TRP L- 1) over the 4 years. However two of the catchment mitigation efforts were offset by continued new-builds that increased the density of septic systems from 3.4 km- 2 to 4.6 km- 2 and 13.8 km- 2 to 17.2 km- 2 and subsequently increased low flow P concentrations. Future considerations for septic system mitigation should include catchment carrying capacity as well as technology changes.

Influence of aggregate and curing regime on the mechanical properties of ultra-high performance fibre reinforced concrete (UHPFRC)

A new generation of concrete, Ultra-high performance fibre reinforced concrete (UHPFRC) has been developed for its outstanding mechanical performance and shows a very promising future in construction applications. In this paper, several possibilities are examined for reducing the price of producing UHPFRC and for bringing UHPFRC away from solely precast applications and onto the construction site as an in situ material. Recycled glass cullet and two types of local natural sand were examined as replacement materials for the more expensive silica sand normally used to produce UHPFRC. In addition, curing of UHPFRC cubes and prisms at 20 degrees C and 90 degrees C has been investigated to determine differences in both mechanical and ductility.

The typology of Irish hard rock aquifers based on an integrated hydrogeological and geophysical approach

Groundwater flow in hard-rock aquifers is strongly controlled by the characteristics and distribution of structural heterogeneity. A methodology for catchment-scale characterisation is presented, based on the integration of complementary, multi-scale hydrogeological, geophysical and geological approaches. This was applied to three contrasting catchments underlain by metamorphic rocks in the northern parts of Ireland (Republic of Ireland and Northern Ireland, UK). Cross-validated surface and borehole geophysical investigations confirm the discontinuous overburden, lithological compartmentalisation of the bedrock and important spatial variations of the weathered bedrock profiles at macro-scale. Fracture analysis suggests that the recent (Alpine) tectonic fabric exerts strong control on the internal aquifer structure at meso-scale, which is likely to impact on the anisotropy of aquifer properties. The combination of the interpretation of depth-specific hydraulic-test data with the structural information provided by geophysical tests allows characterisation of the hydrodynamic properties of the identified aquifer units. Regionally, the distribution of hydraulic conductivities can be described by inverse power laws specific to the aquifer litho-type. Observed groundwater flow directions reflect this multi-scale structure. The proposed integrated approach applies widely available investigative tools to identify key dominant structures controlling groundwater flow, characterising the aquifer type for each catchment and resolving the spatial distribution of relevant aquifer units and associated hydrodynamic parameters.

Parallel Peptidome and Transcriptome Analyses of Amphibian Skin Secretions Using Archived Frozen Acid-Solvated Samples

Amphibian skin secretions are unique sources of bioactive peptides and their donor species are currently rapidly disappearing from the biosphere. Here, we report that both peptides and polyadenylated mRNAs from skin granular glands remain amenable to study in samples of stimulated skin secretions following their storage in 0.1 % aqueous trifluoroacetic acid at -20 °C for many years. Frozen acidified solutions of toad (Bombina variegata) skin secretions, stored for 12 years, were thawed and samples removed for direct reverse phase HPLC fractionation. Additional samples were removed, snap frozen and lyophilised for construction of cDNA libraries following polyadenylated mRNA capture using magnetic oligo-dT beads and reverse transcription. Using the bombesin and bradykinin peptides found in bombinid toad skin as models, individual variant peptides of each type were located in reverse phase HPLC fractions and their corresponding biosynthetic precursor-encoding mRNA transcripts were cloned from the cDNA library using a RACE PCR strategy. This study illustrates unequivocally that both amphibian skin secretion peptides and their biosynthetic precursor-encoding polyadenylated mRNAs are stable in frozen acid-solvated skin secretion samples for considerable periods of time-a finding that may have fundamental implications in the study of archived materials but also in the wider field of molecular biology.

Use of NMR metabolomic plasma profiling methodologies to identify illicit growth-promoting administrations

Detection of growth-promoter use in animal production systems still proves to be an analytical challenge despite years of activity in the field. This study reports on the capability of NMR metabolomic profiling techniques to discriminate between plasma samples obtained from cattle treated with different groups of growth-promoting hormones (dexamethasone, prednisolone, oestradiol) based on recorded metabolite profiles. Two methods of NMR analysis were investigated—a Carr–Purcell–Meiboom–Gill (CPMG)-pulse sequence technique and a conventional 1H NMR method using pre-extracted plasma. Using the CPMG method, 17 distinct metabolites could be identified from the spectra. 1H NMR analysis of extracted plasma facilitated identification of 23 metabolites—six more than the alternative method and all within the aromatic region. Multivariate statistical analysis of acquired data from both forms of NMR analysis separated the plasma metabolite profiles into distinct sample cluster sets representative of the different animal study groups. Samples from both sets of corticosteroid-treated animals—dexamethasone and prednisolone—were found to be clustered relatively closely and had similar alterations to identified metabolite panels. Distinctive metabolite profiles, different from those observed within plasma from corticosteroid-treated animal plasma, were observed in oestradiol-treated animals and samples from these animals formed a cluster spatially isolated from control animal plasma samples. These findings suggest the potential use of NMR methodologies of plasma metabolite analysis as a high-throughput screening technique to aid detection of growth promoter use.

Ageing in changing community contexts: Cross-border perspectives from rural Ireland and Northern Ireland

Ongoing demographic, social, economic and cultural changes point to the dynamic and continually changing contexts of rural areas in Ireland and Northern Ireland. However, the influence of such changes on the lives of older people remains under-explored, particularly the question of how older people perceive, connect to and engage in their communities. Drawing on interviews and focus groups with indigenous and non-indigenous older people in three case-study sites in Ireland, Northern Ireland and a cross-border region, this article presents a comparative analysis of how changing community contexts have shaped the lives of rural-dwelling older people. The analysis focuses on four key areas: economic structure and service access; social relations and social cohesion; meanings and attachments; and community engagement. While the findings demonstrate that some dimensions of participants’ lives were affected by complex economic and social changes, others dimensions were connected in a more significant way to life course and residential history and the desire to maintain community capacity.

Design of composite asymmetric cellular beams and beams with large web openings

The design of composite asymmetric cellular beams is not fully covered by existing guidance but is an area of important practical application. Asymmetry in the shape of the cross-section of cellular beams causes development of additional bending moments in the web-posts between closely placed openings. Furthermore, the development of local composite action influences the distribution of forces in the web-flange Tees. The design method presented in this paper takes account of high degrees of asymmetry in the cross-section and also the influence of elongated or rectangular openings.

Autoclave Cure Simulation of Composite Structures Applying Implicit and Explicit FE

Simulation of the autoclave manufacturing technique of composites can yield a preliminary estimation of induced residual thermal stresses and deformations that affect component fatigue life, and required tolerances for assembly. In this paper, an approach is proposed to simulate the autoclave manufacturing technique for unidirectional composites. The proposed approach consists of three modules. The first module is a Thermo-chemical model to estimate the temperature and the degree of cure distributions in the composite part during the cure cycle. The second and third modules are a sequential stress analysis using FE-Implicit and FE-Explicit respectively. User-material subroutine is used to model the Viscoelastic properties of the material based on theory of micromechanics.