Dietary supplementation with vitamin C but not vitamin E reduces constitutive expression of ICAM-1 in peripheral blood monocytes of normal subjects with low plasma vitamin C levels

Monocytes play a central role in inflammatory responses through systemic antigen presentation and cytokine secretion. Regulation of monocyte adhesion molecule and inflammatory gene expression is via redox sensitive transcription factors. Therefore we have investigated the hypothesis that dietary antioxidant supplementation with vitamins C (250mg/d) or E (400iU/d) for six weeks can modulate monocyte ICAM-1 expression in healthy male subjects with low plasma vitamin C at baseline. In a randomised, double-blind, crossover study, ICAM-1 mRNA and protein was analysed using quantitative RTPCR with ELISA measurement of PCR products and by flow cytometry and ELISA respectively. Monocyte numbers were unaltered by supplementation. Subjects with low plasma vitamin C (<50uM) prior to supplementation expressed higher levels of monocyte ICAM-1 mRNA, and showed a significant (50%) reduction in ICAM-1 mRNA expression after 6 weeks of 250mg/d vitamin C supplementation compared to subjects with normal plasma vitamin C. This was paralleled by a reduction in plasma sICAM-1. Vitamin E supplementation had no effect on ICAM-1 expression. For the first time, these results show that dietary vitamin C can modulate monocyte ICAM-1 gene expression in vivo, where regulation of gene expression represents a novel mechanism for benefit from dietary antioxidants.

Typical kernel size and number of sparse random matrices over Galois fields: a statistical physics approach

Using methods of statistical physics, we study the average number and kernel size of general sparse random matrices over GF(q), with a given connectivity profile, in the thermodynamical limit of large matrices. We introduce a mapping of GF(q) matrices onto spin systems using the representation of the cyclic group of order q as the q-th complex roots of unity. This representation facilitates the derivation of the average kernel size of random matrices using the replica approach, under the replica symmetric ansatz, resulting in saddle point equations for general connectivity distributions. Numerical solutions are then obtained for particular cases by population dynamics. Similar techniques also allow us to obtain an expression for the exact and average number of random matrices for any general connectivity profile. We present numerical results for particular distributions.

Properties of sparse random matrices over finite fields

Typical properties of sparse random matrices over finite (Galois) fields are studied, in the limit of large matrices, using techniques from the physics of disordered systems. For the case of a finite field GF(q) with prime order q, we present results for the average kernel dimension, average dimension of the eigenvector spaces and the distribution of the eigenvalues. The number of matrices for a given distribution of entries is also calculated for the general case. The significance of these results to error-correcting codes and random graphs is also discussed.

The ratio of diffuse to mature beta/A4 deposits in Alzheimer's disease varies in cases with and without pronounced congophilic angiopathy

The density of diffuse, primitive, classic and compact beta/A4 deposits was estimated in the cortex and hippocampus in Alzheimer's disease (AD) cases with and without pronounced congophilic angiopathy (CA). The total density of beta/A4 deposits in a given brain region was similar in cases with and without CA. Significantly fewer diffuse deposits and more primitive/classic deposits were found in the cases with CA. The densities of the primitive, classic and compact deposits were positively correlated in the cases without CA. However, no correlations were observed between the density of the mature subtypes and the diffuse deposits in these cases. In the cases with CA, the density of the primitive deposits was positively correlated with the diffuse but not with the classic deposits. The data suggest that the mature beta/A4 deposits are derived from the diffuse deposits and that the presence of pronounced CA enhances their formation.

Web based expert elicitation of uncertainties in environmental model inputs

When constructing and using environmental models, it is typical that many of the inputs to the models will not be known perfectly. In some cases, it will be possible to make observations, or occasionally physics-based uncertainty propagation, to ascertain the uncertainty on these inputs. However, such observations are often either not available or even possible, and another approach to characterising the uncertainty on the inputs must be sought. Even when observations are available, if the analysis is being carried out within a Bayesian framework then prior distributions will have to be specified. One option for gathering or at least estimating this information is to employ expert elicitation. Expert elicitation is well studied within statistics and psychology and involves the assessment of the beliefs of a group of experts about an uncertain quantity, (for example an input / parameter within a model), typically in terms of obtaining a probability distribution. One of the challenges in expert elicitation is to minimise the biases that might enter into the judgements made by the individual experts, and then to come to a consensus decision within the group of experts. Effort is made in the elicitation exercise to prevent biases clouding the judgements through well-devised questioning schemes. It is also important that, when reaching a consensus, the experts are exposed to the knowledge of the others in the group. Within the FP7 UncertWeb project (http://www.uncertweb.org/), there is a requirement to build a Webbased tool for expert elicitation. In this paper, we discuss some of the issues of building a Web-based elicitation system - both the technological aspects and the statistical and scientific issues. In particular, we demonstrate two tools: a Web-based system for the elicitation of continuous random variables and a system designed to elicit uncertainty about categorical random variables in the setting of landcover classification uncertainty. The first of these examples is a generic tool developed to elicit uncertainty about univariate continuous random variables. It is designed to be used within an application context and extends the existing SHELF method, adding a web interface and access to metadata. The tool is developed so that it can be readily integrated with environmental models exposed as web services. The second example was developed for the TREES-3 initiative which monitors tropical landcover change through ground-truthing at confluence points. It allows experts to validate the accuracy of automated landcover classifications using site-specific imagery and local knowledge. Experts may provide uncertainty information at various levels: from a general rating of their confidence in a site validation to a numerical ranking of the possible landcover types within a segment. A key challenge in the web based setting is the design of the user interface and the method of interacting between the problem owner and the problem experts. We show the workflow of the elicitation tool, and show how we can represent the final elicited distributions and confusion matrices using UncertML, ready for integration into uncertainty enabled workflows.We also show how the metadata associated with the elicitation exercise is captured and can be referenced from the elicited result, providing crucial lineage information and thus traceability in the decision making process.

Analysis of interactions among variables of renewable energy projects:a case study on renewable energy project in India

This study highlights the variables associated with the implementation of renewable energy (RE) projects for sustainable development in India, by using an interpretive structural modeling (ISM) - based approach to model variables' interactions, which impact RE adoption. These variables have been categorized under enablers that help to enhance implementation of RE projects for sustainable development. A major finding is that public awareness regarding RE for sustainable development is a very significant enabler. For successful implementation of RE projects, it has been observed that top management should focus on improving highdriving power enablers (leadership, strategic planning, public awareness, management commitment, availability of finance, government support, and support from interest groups).

Statnote 9: The one-way analysis of variance (random effects model)

There is an alternative model of the 1-way ANOVA called the 'random effects' model or ‘nested’ design in which the objective is not to test specific effects but to estimate the degree of variation of a particular measurement and to compare different sources of variation that influence the measurement in space and/or time. The most important statistics from a random effects model are the components of variance which estimate the variance associated with each of the sources of variation influencing a measurement. The nested design is particularly useful in preliminary experiments designed to estimate different sources of variation and in the planning of appropriate sampling strategies.

The effect of inversion on the encoding of normal and “thatcherized” faces

In the "Thatcher illusion" a face, in which the eyes and mouth are inverted relative to the rest of the face, looks grotesque when shown upright but not when inverted. In four experiments we investigated the contribution of local and global processing to this illusion in normal observers. We examined inversion effects (i.e., better performance for upright than for inverted faces) in a task requiring discrimination of whether faces were or were not "thatcherized". Observers made same/different judgements to isolated face parts (Experiments 1-2) and to whole faces (Experiments 3-4). Face pairs had the same or different identity, allowing for different processing strategies using feature-based or configural information, respectively. In Experiment 1, feature-based matching of same-person face parts yielded only a small inversion effect for normal face parts. However, when feature-based matching was prevented by using the face parts of different people on all trials (Experiment 2) an inversion effect occurred for normal but not for thatcherized parts. In Experiments 3 and 4, inversion effects occurred with normal but not with thatcherized whole faces, on both same- and different-person matching tasks. This suggests that a common configural strategy was used with whole (normal) faces. Face context facilitated attention to misoriented parts in same-person but not in different-person matching. The results indicate that (1) face inversion disrupts local configural processing, but not the processing of image features, and (2) thatcherization disrupts local configural processing in upright faces.

Development of a multicellular co-culture model of normal and cystic fibrosis human airways in vitro

Cystic fibrosis (CF) is the most common lethal inherited disease among Caucasians and arises due to mutations in a chloride channel, called cystic fibrosis transmembrane conductance regulator. A hallmark of this disease is the chronic bacterial infection of the airways, which is usually, associated with pathogens such as Pseudomonas aeruginosa, S. aureus and recently becoming more prominent, B. cepacia. The excessive inflammatory response, which leads to irreversible lung damage, will in the long term lead to mortality of the patient at around the age of 40 years. Understanding the pathogenesis of CF currently relies on animal models, such as those employing genetically-modified mice, and on single cell culture models, which are grown either as polarised or non-polarised epithelium in vitro. Whilst these approaches partially enable the study of disease progression in CF, both types of models have inherent limitations. The overall aim of this thesis was to establish a multicellular co-culture model of normal and CF human airways in vitro, which helps to partially overcome these limitations and permits analysis of cell-to-cell communication in the airways. These models could then be used to examine the co-ordinated response of the airways to infection with relevant pathogens in order to validate this approach over animals/single cell models. Therefore epithelial cell lines of non-CF and CF background were employed in a co-culture model together with human pulmonary fibroblasts. Co-cultures were grown on collagen-coated permeable supports at air-liquid interface to promote epithelial cell differentiation. The models were characterised and essential features for investigating CF infections and inflammatory responses were investigated and analysed. A pseudostratified like epithelial cell layer was established at air liquid interface (ALI) of mono-and co-cultures and cell layer integrity was verified by tight junction (TJ) staining and transepithelial resistance measurements (TER). Mono- and co-cultures were also found to secrete the airway mucin MUC5AC. Influence of bacterial infections was found to be most challenging when intact S. aureus, B. cepacia and P. aeruginosa were used. CF mono- and co-cultures were found to mimic the hyperinflammatory state found in CF, which was confirmed by analysing IL-8 secretions of these models. These co-culture models will help to elucidate the role fibroblasts play in the inflammatory response to bacteria and will provide a useful testing platform to further investigate the dysregulated airway responses seen in CF.

Symmetric operating point for increasing the extinction ratio of semiconductor based optical loop mirrors

Terahertz optical asymmetric demultiplexors (TOADs) use a semiconductor optical amplifier in an interferometer to create an all-optical switch and have potential uses in many optical networking applications. Here we demonstrate and compare experimentally a novel and simple method of dramatically increasing the extinction ratio of the device using a symmetrical configuration as compared to a ‘traditional’ configuration. The new configuration is designed to suppress the occurrence of self-switching in the device thus allowing signal pulses to be used at higher power levels. Using the proposed configuration an increase in extinction ratio of 10 dB has been measured on the transmitted port whilst benefiting from an improved input signal power handling capability.

The importance of optical coherence tomography examination of normal fellow eyes in neovascular age-related macular degeneration monitoring clinics

Purpose: To demonstrate the importance of OCT examination of fellow, normal eyes in unilateral nAMD follow up clinics. Methods: The authors present three cases of unilateral nAMD who were undergoing treatment with ranibizumab, in whom OCT evaluation of the previously unaffected, asymptomatic fellow eye allowed early diagnosis, treatment and preservation of vision. Fundus examination had previously failed to demonstrate abnormality. Results: Intravitreal anti-VEGF treatment for nAMD has caused a sharp increase in the number of subjects attending macular clinics, frequently overburdening the system. It may sometimes be tempting for hospitals to reduce the workload by for example, concentrating only on OCT examination of the affected eye in cases of unilateral nAMD. The three reported cases demonstrate that OCT scanning of the fellow, previously unaffected eye is essential in detecting asymptomatic nAMD, which gives a better chance of preservation of vision. Conclusions: Patients with unilateral neovascular AMD undergoing review in macular clinics should always undergo OCT scanning of normal, fellow eyes, as otherwise asymptomatic, “invisible” choroidal neovascular membranes may be missed.

Improper use of formative endogenous variables

Researchers often develop and test conceptual models containing formative variables. In many cases, these formative variables are specified as being endogenous. This article provides a clarification of formative variable theory, distinguishing between the formative latent variable and the formative composite variable. When an endogenous latent variable relies on formative indicators for measurement, empirical studies can say nothing about the relationship between exogenous variables and the endogenous formative latent variable: conclusions can only be drawn regarding the exogenous variables' relationships with a composite variable. The authors also show the dangers associated with developing theory about antecedents to endogenous formative variables at the (aggregate) formative latent variable level. Modeling relationships with endogenous formative variables at the (disaggregate) indicator level informs richer theory development, and encourages more precise empirical testing. When antecedents' relationships with endogenous formative variables are modeled at the formative latent variable level rather than the formative indicator level, theory construction can verge on the superficial, and empirical findings can be ambiguous in substantive meaning.

On the structural repertoire of pools of short, random RNA sequences

A detailed knowledge of the mapping between sequence and structure spaces in populations of RNA molecules is essential to better understand their present-day functional properties, to envisage a plausible early evolution of RNA in a prebiotic chemical environment and to improve the design of in vitro evolution experiments, among others. Analysis of natural RNAs, as well as in vitro and computational studies, show that certain RNA structural motifs are much more abundant than others, pointing out a complex relation between sequence and structure. Within this framework, we have investigated computationally the structural properties of a large pool (10 molecules) of single-stranded, 35 nt-long, random RNA sequences. The secondary structures obtained are ranked and classified into structure families. The number of structures in main families is analytically calculated and compared with the numerical results. This permits a quantification of the fraction of structure space covered by a large pool of sequences. We further show that the number of structural motifs and their frequency is highly unbalanced with respect to the nucleotide composition: simple structures such as stem-loops and hairpins arise from sequences depleted in G, while more complex structures require an enrichment of G. In general, we observe a strong correlation between subfamilies-characterized by a fixed number of paired nucleotides-and nucleotide composition. Our results are compared to the structural repertoire obtained in a second pool where isolated base pairs are prohibited. © 2008 Elsevier Ltd. All rights reserved.