Multivariate Statistical Analysis Applied to an IL6 Signal Transduction Model in Hepatocytes

This paper introduces the application of linear multivariate statistical techniques, including partial least squares (PLS), canonical correlation analysis (CCA) and reduced rank regression (RRR), into the area of Systems Biology. This new approach aims to extract the important proteins embedded in complex signal transduction pathway models.The analysis is performed on a model of intracellular signalling along the janus-associated kinases/signal transducers and transcription factors (JAK/STAT) and mitogen activated protein kinases (MAPK) signal transduction pathways in interleukin-6 (IL6) stimulated hepatocytes, which produce signal transducer and activator of transcription factor 3 (STAT3).A region of redundancy within the MAPK pathway that does not affect the STAT3 transcription was identified using CCA. This is the core finding of this analysis and cannot be obtained by inspecting the model by eye. In addition, RRR was found to isolate terms that do not significantly contribute to changes in protein concentrations, while the application of PLS does not provide such a detailed picture by virtue of its construction.This analysis has a similar objective to conventional model reduction techniques with the advantage of maintaining the meaning of the states prior to and after the reduction process. A significant model reduction is performed, with a marginal loss in accuracy, offering a more concise model while maintaining the main influencing factors on the STAT3 transcription.The findings offer a deeper understanding of the reaction terms involved, confirm the relevance of several proteins to the production of Acute Phase Proteins and complement existing findings regarding cross-talk between the two signalling pathways.

A time-domain approach to the analysis and modeling of on-body propagation characteristics using synchronized measurements at 2.45 GHz

Modeling of on-body propagation channels is of paramount importance to those wishing to evaluate radio channel performance for wearable devices in body area networks (BANs). Difficulties in modeling arise due to the highly variable channel conditions related to changes in the user's state and local environment. This study characterizes these influences by using time-series analysis to examine and model signal characteristics for on-body radio channels in user stationary and mobile scenarios in four different locations: anechoic chamber, open office area, hallway, and outdoor environment. Autocorrelation and cross-correlation functions are reported and shown to be dependent on body state and surroundings. Autoregressive (AR) transfer functions are used to perform time-series analysis and develop models for fading in various on-body links. Due to the non-Gaussian nature of the logarithmically transformed observed signal envelope in the majority of mobile user states, a simple method for reproducing the failing based on lognormal and Nakagami statistics is proposed. The validity of the AR models is evaluated using hypothesis testing, which is based on the Ljung-Box statistic, and the estimated distributional parameters of the simulator output compared with those from experimental results.

Beyond Compliance – Below Expectations? Cross-Border CSR, Development and the UN Global Compact.

In this paper, the results of an empirical analysis of a set of 416 descriptive case studies published by corporate members of the UN Global Compact are presented. Although these cases cannot be viewed as representative of the Compact itself or of corporate social responsibility (CSR) and development in general, they can illustrate which kinds of projects are deemed appropriate as best practice examples among Compact members, and therefore indicate the direction, in which predominantly voluntary and business-led CSR might at best be evolving. To help contextualize the analysis, the paper starts with a brief overview of recent academic work on the strengths and limitations of CSR in the light of international development, followed by the empirical analysis of Compact case studies. The results raise doubts regarding the general suitability of contemporary CSR initiatives to tackle some of the most pressing developmental challenges. Instead, only certain topics are commonly addressed, while a number of issues such as anti-corruption measures or labour rights are underrepresented in the case study sample. Regarding the target regions of the best practice examples, the majority is reported on activities based in OECD countries and a small number of emerging markets such as South Africa, India or China, while neglecting other regions such as sub-Saharan Africa (excluding South Africa). From a European Union policy perspective, these results indicate that there is a role to play for the state in order to create a better fit between CSR agendas and the actual developmental needs in the South.

Distance between home and work: A multilevel analysis of individual workers, neighbourhoods, and employment sites in Northern Ireland

Abstract. We explore the distances between home and work for employees at twenty-eight different employment sites across Northern Ireland. Substantively, this is important for better understanding the geography of labour catchments. Methodologically, with data on the distances between place of residence (566 wards) and place of work for some 15 000 workers, and the use of multilevel modelling (MLM), the analysis adds to the evidence derived from other census-based and survey-based studies. Descriptive analysis is supplemented with MLM that simultaneously explores individual, neighbourhood, and site variations in travel-to-work patterns using hierarchical and cross-classified model specifications, including individual and ecological predictor variables (and their cross-level interactions). In doing so we apportion variability to different levels and spatial contexts, and also outline the factors that shape spatial mobility. We find, as expected, that factors such as gender and occupation influence the distance between home and work, and also confirm the importance of neighbourhood characteristics (such as population density observed in ecological analyses at ward level) in shaping individual outcomes, with major differences found between urban and rural locations. Beyond this, the analysis of variability also points to the relative significance of residential location, with less individual variability in travel-to-work distance between workers within wards than within employment sites. We conclude by suggesting that, whilst some general ‘rules’ about the factors that shape labour catchments are possible (eg workers in rural areas and in higher occupations travel further than others), the complex variability between places highlighted by the MLM analysis illustrates the salience of place-specific uniqueness.

Multiproxy evidence for terrestrial and aquatic ecosystem responses during the 8.2 ka cold event as recorded at Hojby So, Denmark

A sediment succession from Hojby So, a lake in eastern Denmark, covering the time period 9400-7400 cal yr BP was studied using high-resolution geochemistry, magnetic susceptibility, pollen, macrofossil, diatom, and algal pigment analysis to investigate responses of the terrestrial and aquatic ecosystems to the 8.2 ka cold event. A reduced pollen production by thermophilous deciduous tree taxa in the period c. 8250-8000 cal yr BP reveal that the forest ecosystem was affected by low temperatures during the summer and winter/early-spring seasons. This finding is consistent with the timing of the 8.2 ka cold event as registered in the Greenland ice cores. At Hojby So, the climate anomaly appears to have started 200-250 yr earlier than the 8.2 ka cold event as the lake proxy data provide strong evidence for a precipitation-induced distinct increase in catchment soil erosion beginning around 8500 cal yr BP. Alteration of the terrestrial environment then resulted in a major aquatic ecosystem change with nutrient enrichment of the lake and enhanced productivity, which lasted until c. 7900 cal yr BP. (C) 2009 University of Washington. Published by Elsevier Inc. All rights reserved.

Meta analysis of the effects of lithium usage on serum creatinine levels

There is conflicting evidence concerning lithium’s effect on renal function. The aim is to clarify whether lithium affects kidney function and at what stage of treatment any effect may occur. Systematic review identified 23 studies split into three groups on which meta-analysis was performed to identify the following: A) lithium’s effect on renal function in cross-sectional case-control studies, B) studies of renal function before and after commencement on lithium, C) studies of longer term effect in those already established on lithium therapy. Group A showed a statistically significant increase of 5.7 µmol/L in creatinine in the study population compared with controls. Group B showed a non-statistically significant rise in creatinine (2.9 µmol/L) after a mean follow-up of 86 months. Group C showed a statistically significant increase in creatinine of 7.0 µmol/L over a mean duration of 64 months. An increase in creatinine of an average of 1.6 µmol/L/year on lithium was also identified in this group. Any lithium-associated increase in serum creatinine is quantitatively small and of questionable clinical significance. However, routine renal function monitoring of patients on lithium is essential.

China's Enterprise Bankruptcy Law (EBL 2006): Cross-Border Perspectives

With China's new Enterprise Bankruptcy Law (‘EBL 2006’) having come into effect on 1 June 2007, a critical issue arises as to the extent to which Article 5, as a cross-border provision, will strengthen creditors' rights across jurisdictions. In this paper attention will be paid in particular to how the Chinese People's Court is likely to exercise its discretion to grant recognition to a foreign court ruling, and vice versa. The paper will start with a brief introduction to the circumstances under which Article 5 came into being. The evolution of China's cross-border insolvency practices will be examined through an analysis of an inbound case of B&T (2002) as well as an outbound one of GITIC (2005). In spite of the fact that China has not adopted the UNCITRAL Model Law, essential factors deemed necessary to be considered by China's court and its counterparts in US and UK are to be highlighted throughout the paper. Although the effect of Article 5 remains to be seen, it will be critically analysed focusing on some controversial issues.

Immunobiosensor detection of domoic acid as a screening test in bivalve molluscs: Comparison with liquid chromatography-based analysis

A rapid and sensitive immuno-based screening method was developed to detect domoic acid (DA) present in extracts of shellfish species using a surface plasmon resonance-based optical biosensor. A rabbit polyclonal antibody raised against DA was mixed with standard or sample extracts and allowed to interact with DA immobilized onto a sensor chip surface. The characterization of the antibody strongly suggested high cross-reactivity with DA and important isomers of the toxin. The binding of this antibody to the sensor chip surface was inhibited in the presence of DA in either standard solutions or sample extracts. The DA chip surface proved to be highly stable, achieving approximately 800 analyses per chip without any loss of surface activity. A single analytical cycle (sample injection, chip regeneration, and system wash) took 10 min to complete. Sample analysis (scallops, mussels, cockles, oysters) was achieved by simple extraction with methanol. These extracts were then filtered and diluted before analysis. Detection limits in the ng/g range were achieved by the assay; however, the assay parameters chosen allowed the test to be performed most accurately at the European Union's official action limit for DA of 20 mu g/g. At this concentration, intra- and interassay variations were measured for a range of shellfish species and ranged from 4.5 to 7.4% and 2.3 to 9.7%, respectively.

Spatial Allocation of Material Flow Analysis: A Geographic Information System Application of Material Flow Analysis in Ireland

This study concerns the spatial allocation of material flows, with emphasis on construction material in the Irish housing sector. It addresses some of the key issues concerning anthropogenic impact on the environment through spatial temporal visualisation of the flow of materials, wastes and emissions at different spatial levels. This is presented in the form of a spatial model, Spatial Allocation of Material Flow Analysis (SAMFA), which enables the simulation of construction material flows and associated energy use. SAMFA parallels the Island Limits project (EPA funded under 2004-SD-MS-22-M2), which aimed to create a material flow analysis of the Irish economy classified by industrial sector. SAMFA further develops this by attempting to establish the material flows at the subnational geographical scale that could be used in the development of local authority (LA) sustainability strategies and spatial planning frameworks by highlighting the cumulative environmental impacts of the development of the built environment. By drawing on the idea of planning support systems, SAMFA also aims to provide a cross-disciplinary, integrative medium for involving stakeholders in strategies for a sustainable built environment and, as such, would help illustrate the sustainability consequences of alternative The pilot run of the model in Kildare has shown that the model can be successfully calibrated and applied to develop alternative material flows and energy-use scenarios at the ED level. This has been demonstrated through the development of an integrated and a business-as-usual scenario, with the former integrating a range of potential material efficiency and energysaving policy options and the latter replicating conditions that best describe the current trend. Their comparison shows that the former is better than the latter in terms of both material and energy use. This report also identifies a number of potential areas of future research and areas of broader application. This includes improving the accuracy of the SAMFA model (e.g. by establishing actual life expectancy of buildings in the Irish context through field surveys) and the extension of the model to other Irish counties. This would establish SAMFA as a valuable predicting and monitoring tool that is capable of integrating national and local spatial planning objectives with actual environmental impacts. Furthermore, should the model prove successful at this level, it then has the potential to transfer the modelling approach to other areas of the built environment, such as commercial development and other key contributors of greenhouse emissions. The ultimate aim is to develop a meta-model for predicting the consequences of consumption patterns at the local scale. This therefore offers the possibility of creating critical links between socio technical systems with the most important challenge of all the limitations of the biophysical environment.

Generalized social trust across 22 European countries: A multi-level analysis of four competing models

Concern with what can explain variation in generalized social trust has led to an abundance of theoretical models. Defining generalized social trust as a belief in human benevolence, we focus on the emancipation theory and social capital theory as well as the ethnic diversity and economic development models of trust. We then determine which dimensions of individuals’ behavior and attitudes as well as of their national context are the most important predictors. Using data from 20 countries that participated in round one of the European Social Survey, we test these models at their respective level of analysis, individual and/or national. Our analysis revealed that individuals’ own trust in the political system as a moral and competent institution was the most important predictor of generalized social trust at the individual level, while a country’s level of affluence was the most important contextual predictor, indicating that different dimensions are significant at the two levels of analysis. This analysis also raised further questions as to the meaning of social capital at the two levels of analysis and the conceptual equivalence of its civic engagement dimension across cultures.

Flow cytometric analysis of within-strain variation in polysaccharide expression by Bacteroides fragilis by use of murine monoclonal antibodies.

The reactivity of four different monoclonal antibodies (MAbs) with populations of Bacteroides fragilis NCTC 9343, enriched by density gradient centrifugation for a large capsule, small capsule and electron-dense layer (EDL) only visible by electronmicroscopy, was examined. The MAbs reacted strongly with polysaccharides present in both the large capsule- and EDL-enriched populations but not in the small capsule-enriched populations. The pattern of labelling was determined by immunoblotting, immunofluorescence and immuno-electronmicroscopy, and flow cytometry. The MAbs labelled cell membrane-associated epitopes in the large capsule- and EDL-enriched populations and cell-free material in the EDL population. By immunoblotting, ladders of repeating polysaccharide subunits were evident in the EDL population but not in the large capsule population. The proportion of cells labelled within each population was determined by flow cytometry. The reactivity of another MAb with the small capsule population was confirmed by flow cytometry. A qualitative indication of epitope expression was obtained by examination of the flow cytometric profiles. Differential expression of the same saccharide epitope was observed both between and within structurally distinct B. fragilis populations. The MAbs were species-specific and cross-reacted with several recent clinical isolates. These polysaccharides may be relevant to the virulence of B. fragilis.

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.

Job Strain and Alcohol Intake:A Collaborative Meta-Analysis of Individual-Participant Data from 140 000 Men and Women

BACKGROUND: The relationship between work-related stress and alcohol intake is uncertain. In order to add to the thus far inconsistent evidence from relatively small studies, we conducted individual-participant meta-analyses of the association between work-related stress (operationalised as self-reported job strain) and alcohol intake. METHODOLOGY AND PRINCIPAL FINDINGS: We analysed cross-sectional data from 12 European studies (n?=?142 140) and longitudinal data from four studies (n?=?48 646). Job strain and alcohol intake were self-reported. Job strain was analysed as a binary variable (strain vs. no strain). Alcohol intake was harmonised into the following categories: none, moderate (women: 1-14, men: 1-21 drinks/week), intermediate (women: 15-20, men: 22-27 drinks/week) and heavy (women: >20, men: >27 drinks/week). Cross-sectional associations were modelled using logistic regression and the results pooled in random effects meta-analyses. Longitudinal associations were examined using mixed effects logistic and modified Poisson regression. Compared to moderate drinkers, non-drinkers and (random effects odds ratio (OR): 1.10, 95% CI: 1.05, 1.14) and heavy drinkers (OR: 1.12, 95% CI: 1.00, 1.26) had higher odds of job strain. Intermediate drinkers, on the other hand, had lower odds of job strain (OR: 0.92, 95% CI: 0.86, 0.99). We found no clear evidence for longitudinal associations between job strain and alcohol intake. CONCLUSIONS: Our findings suggest that compared to moderate drinkers, non-drinkers and heavy drinkers are more likely and intermediate drinkers less likely to report work-related stress.

Job Strain and Tobacco Smoking:An Individual-Participant Data Meta-Analysis of 166 130 Adults in 15 European Studies

BACKGROUND: Tobacco smoking is a major contributor to the public health burden and healthcare costs worldwide, but the determinants of smoking behaviours are poorly understood. We conducted a large individual-participant meta-analysis to examine the extent to which work-related stress, operationalised as job strain, is associated with tobacco smoking in working adults. METHODOLOGY AND PRINCIPAL FINDINGS: We analysed cross-sectional data from 15 European studies comprising 166 130 participants. Longitudinal data from six studies were used. Job strain and smoking were self-reported. Smoking was harmonised into three categories never, ex- and current. We modelled the cross-sectional associations using logistic regression and the results pooled in random effects meta-analyses. Mixed effects logistic regression was used to examine longitudinal associations. Of the 166 130 participants, 17% reported job strain, 42% were never smokers, 33% ex-smokers and 25% current smokers. In the analyses of the cross-sectional data, current smokers had higher odds of job strain than never-smokers (age, sex and socioeconomic position-adjusted odds ratio: 1.11, 95% confidence interval: 1.03, 1.18). Current smokers with job strain smoked, on average, three cigarettes per week more than current smokers without job strain. In the analyses of longitudinal data (1 to 9 years of follow-up), there was no clear evidence for longitudinal associations between job strain and taking up or quitting smoking. CONCLUSIONS: Our findings show that smokers are slightly more likely than non-smokers to report work-related stress. In addition, smokers who reported work stress smoked, on average, slightly more cigarettes than stress-free smokers.

"The Heart of Irish-Language Proverbs": A Linguo-Stylistic Analysis of Explicit Metaphor

Metaphor has featured frequently in attempts to define the proverb (see Taylor 1931, Whiting 1932, Mieder 1985, 1996), and since the advent of modern paremiological scholarship, it has been identified as one of the most salient markers of ‘proverbiality’ (Arora 1984) across a broad spectrum of world languages. Significant language-specific analyses, such as Klimenko (1946), Silverman-Weinreich (1981), and Arora (1984) have provided valuable qualitative information on the form and function of metaphor in Russian, Yiddish, and Spanish proverbs respectively. Unfortunately, no academic scholarship has engaged with the subject of metaphor in Irish proverbs. This study builds on international paremiological research on metaphor and provides for the first time a comprehensive quantitative and qualitative analysis of the form, frequency, and nature of linguistic metaphors in Irish proverbs (1856-1952). Moreover, from the perspective of paremiology, it presents a methodological template and result-set that can be applied cross-linguistically to compare metaphor in the proverbs of other languages.