Prediction of adipose tissue composition using Raman spectroscopy: average properties and individual fatty acids.

Abstract: Raman spectroscopy has been used for the first time to predict the FA composition of unextracted adipose tissue of pork, beef, lamb, and chicken. It was found that the bulk unsaturation parameters could be predicted successfully [R-2 = 0.97, root mean square error of prediction (RMSEP) = 4.6% of 4 sigma], with cis unsaturation, which accounted for the majority of the unsaturation, giving similar correlations. The combined abundance of all measured PUFA (>= 2 double bonds per chain) was also well predicted with R-2 = 0.97 and RMSEP = 4.0% of 4 sigma. Trans unsaturation was not as well modeled (R-2 = 0.52, RMSEP = 18% of 4 sigma); this reduced prediction ability can be attributed to the low levels of trans FA found in adipose tissue (0.035 times the cis unsaturation level). For the individual FA, the average partial least squares (PLS) regression coefficient of the 18 most abundant FA (relative abundances ranging from 0.1 to 38.6% of the total FA content) was R-2 = 0.73; the average RMSEP = 11.9% of 4 sigma. Regression coefficients and prediction errors for the five most abundant FA were all better than the average value (in some cases as low as RMSEP = 4.7% of 4 sigma). Cross-correlation between the abundances of the minor FA and more abundant acids could be determined by principal component analysis methods, and the resulting groups of correlated compounds were also well-predicted using PLS. The accuracy of the prediction of individual FA was at least as good as other spectroscopic methods, and the extremely straightforward sampling method meant that very rapid analysis of samples at ambient temperature was easily achieved. This work shows that Raman profiling of hundreds of samples per day is easily achievable with an automated sampling system.

Heritability of immune function in the caterpillar Spodoptera littoralis

Phenoloxidase (PO) is believed to be a key mediator of immune function in insects and has been implicated both in non-self recognition and in resistance to a variety of parasites and pathogens, including baculoviruses and parasitoids. Using larvae of the Egyptian cotton leafworm, Spodoptera littoralis, we found that despite its apparent importance, haemolymph PO activity varied markedly between individuals, even amongst insects reared under apparently identical conditions. Sib-analysis methods were used to determine whether individuals varied genetically in their PO activity, and hence in one aspect of immune function. The heritability estimate of haemolymph PO activity was high (h 2 = 0.690 +/- 0.069), and PO activity in the haemolymph was strongly correlated with PO activity in both the cuticle and midgut; the sites of entry for most parasites and pathogens. Haemolymph PO activity was also strongly correlated with the degree to which a synthetic parasite (a small piece of nylon monofilament) was encapsulated and melanized (r = 0.622 +/- 0.142), suggesting that the encapsulation response is also heritable. The mechanism maintaining this genetic variation has yet to be elucidated.

Genetic differentiation across the social transition in a socially polymorphic sweat bee, Halictus rubicundus

Eusociality is widely considered a major evolutionary transition. The socially polymorphic sweat bee Halictus rubicundus, solitary in cooler regions of its holarctic range and eusocial in warmer parts, is an excellent model organism to address this transition, and specifically the question of whether sociality is associated with a strong barrier to gene flow between phenotypically divergent populations. Mitochondrial DNA (COI) from specimens collected across the British Isles, where both solitary and social phenotypes are represented, displayed limited variation, but placed all specimens in the same European lineage; haplotype network analysis failed to differentiate solitary and social lineages. Microsatellite genetic variability was high and enabled us to quantify genetic differentiation among populations and social phenotypes across Great Britain and Ireland. Results from conceptually different analyses consistently showed greater genetic differentiation between geographically distant populations, independently of their social phenotype, suggesting that the two social forms are not reproductively isolated. A landscape genetic approach revealed significant isolation by distance (Mantel test r = 0.622, p

NON-GAUSSIAN STATISTICS OF OIL PRICING TIME-SERIES: A CASE STUDY

The stochastic nature of oil price fluctuations is investigated over a twelve-year period, borrowing feedback from an existing database (USA Energy Information Administration database, available online). We evaluate the scaling exponents of the fluctuations by employing different statistical analysis methods, namely rescaled range analysis (R/S), scale windowed variance analysis (SWV) and the generalized Hurst exponent (GH) method. Relying on the scaling exponents obtained, we apply a rescaling procedure to investigate the complex characteristics of the probability density functions (PDFs) dominating oil price fluctuations. It is found that PDFs exhibit scale invariance, and in fact collapse onto a single curve when increments are measured over microscales (typically less than 30 days). The time evolution of the distributions is well fitted by a Levy-type stable distribution. The relevance of a Levy distribution is made plausible by a simple model of nonlinear transfer. Our results also exhibit a degree of multifractality as the PDFs change and converge toward to a Gaussian distribution at the macroscales.

Activated oncogenic pathways and therapeutic targets in extranodal nasal-type NK/T cell lymphoma revealed by gene expression profiling

We performed comprehensive genome-wide gene expression profiling (GEP) of extranodal nasal-type natural killer/T-cell lymphoma (NKTL) using formalin-fixed, paraffin-embedded tissue (n = 9) and NK cell lines (n = 5) in comparison with normal NK cells, with the objective of understanding the oncogenic pathways involved in the pathogenesis of NKTL and to identify potential therapeutic targets. Pathway and network analysis of genes differentially expressed between NKTL and normal NK cells revealed significant enrichment for cell cycle-related genes and pathways, such as PLK1, CDK1, and Aurora-A. Furthermore, our results demonstrated a pro-proliferative and anti-apoptotic phenotype in NKTL characterized by activation of Myc and nuclear factor kappa B (NF-kappa B), and deregulation of p53. In corroboration with GEP findings, a significant percentage of NKTLs (n = 33) overexpressed c-Myc (45.4%), p53 (87.9%), and NF-kappa B p50 (67.7%) on immunohistochemistry using a tissue microarray containing 33 NKTL samples. Notably, overexpression of survivin was observed in 97% of cases. Based on our findings, we propose a model of NKTL pathogenesis where deregulation of p53 together with activation of Myc and NF-kappa B, possibly driven by EBV LMP-1, results in the cumulative up-regulation of survivin. Down-regulation of survivin with Terameprocol (EM-1421, a survivin inhibitor) results in reduced cell viability and increased apoptosis in tumour cells, suggesting that targeting survivin may be a potential novel therapeutic strategy in NKTL. Copyright (C) 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Rapid construction of arch bridges using the innovative FlexiArch

Masonry arches are strong, durable, aesthetically pleasing and largely maintenance free, yet since 1900 there has been a dramatic decline in their use. However, designers, contractors and clients now have access to a new method of constructing arches incorporating precast concrete voussoirs interconnected via polymeric reinforcement and a concrete screed. No centring is necessary, as the FlexiArch, when it is lifted, transforms under the forces of gravity into the desired arch shape. After discussing general aspects of innovation, the basic concept of the arch bridge system is presented along with technological advances since it was patented. Experiences gained from building over 40 FlexiArch bridges in the UK and Ireland and from model and full-scale tests carried out to validate the system during installation and in service are described. Thus under load the system behaves like a traditional masonry arch and existing analysis methods can be used for design and assessment.

Relative quantification of the proteomeic changes associated with the mycotoxin zearalenone in the H295R steroidogenesis model

Zearalenone (ZEN) is a mycotoxin with endocrine disrupting effects having vast economic implications in e.g. pig farming. Structurally, ZEN resembles 17b-estradiol, and thus is able to bind to estrogen receptors (ER) in target cells. Because of this, it is also classified as a non-steroidal estrogen, a phytoestrogen, a mycoestrogen, and a growth promoter. Quantitative proteomic analysis was undertaken using stable-isotope labeling by amino acids in cell culture (SILAC) upon exposure of the steroidogenesis cell model H295R with ZEN to elucidate its effect on protein regulation. ZEN significantly regulated 21 proteins, including proteins with known endocrine disrupting effects and several oncogenes. In addition, network analysis using Ingenuity Pathway Analysis showed that ZEN affected the oxidative phosphorylation pathway and the mitochondrial dysfunction pathway, both previously reported to be involved in endocrine dysfunction.

Determining propeller induced erosion alongside quay walls in harbours using Artificial Neural Networks

In shallow waters, such as those found close to berth structures, the wash from a manoeuvring ship’s propeller can cause erosion of the seabed. This erosion can be increased if the wash intersects a berth structure. A number of researchers have undertaken model studies and used regression analysis to develop predictive relationships for the scouring action. This paper presents an experimental investigation with Artificial Neural Networks (ANN’s), used to analyse the results. The purpose of using ANN’s was to examine the prediction accuracy of the Networks in comparison with previous regression analysis methods. ANN’s were found to provide a more accurate method of predicting propeller wash scour than the equations presented by previous investigators.

Genome-wide profiling of methylation identifies novel targets with aberrant hyper-methylation and reduced expression in low-risk myelodysplastic syndromes

Gene expression profiling signatures may be used to classify the subtypes of Myelodysplastic syndrome (MDS) patients. However, there are few reports on the global methylation status in MDS. The integration of genome-wide epigenetic regulatory marks with gene expression levels would provide additional information regarding the biological differences between MDS and healthy controls. Gene expression and methylation status were measured using high-density microarrays. A total of 552 differentially methylated CpG loci were identified as being present in low-risk MDS; hypermethylated genes were more frequent than hypomethylated genes. In addition, mRNA expression profiling identified 1005 genes that significantly differed between low-risk MDS and the control group. Integrative analysis of the epigenetic and expression profiles revealed that 66.7% of the hypermethylated genes were underexpressed in low-risk MDS cases. Gene network analysis revealed molecular mechanisms associated with the low-risk MDS group, including altered apoptosis pathways. The two key apoptotic genes BCL2 and ETS1 were identified as silenced genes. In addition, the immune response and micro RNA biogenesis were affected by the hypermethylation and underexpression of IL27RA and DICER1. Our integrative analysis revealed that aberrant epigenetic regulation is a hallmark of low-risk MDS patients and could have a central role in these diseases.

Pharmacogenomic Profiling and Pathway Analyses Identify MAPK-Dependent Migration as an Acute Response to SN38 in p53 Null and p53-Mutant Colorectal Cancer Cells.

The topoisomerase I inhibitor irinotecan is used to treat advanced colorectal cancer and has been shown to have p53-independent anticancer activity. The aim of this study was to identify the p53-independent signaling mechanisms activated by irinotecan. Transcriptional profiling of isogenic HCT116 p53 wild-type and p53 null cells was carried out following treatment with the active metabolite of irinotecan, SN38. Unsupervised analysis methods showed that p53 status had a highly significant impact on gene expression changes in response to SN38. Pathway analysis indicated that pathways involved in cell motility [adherens junction, focal adhesion, mitogen-activated protein kinase (MAPK), and regulation of the actin cytoskeleton] were significantly activated in p53 null cells, but not p53 wild-type cells, following SN38 treatment. In functional assays, SN38 treatment increased the migratory potential of p53 null and p53-mutant colorectal cancer cell lines, but not p53 wild-type lines. Moreover, p53 null SN38-resistant cells were found to migrate at a faster rate than parental drug-sensitive p53 null cells, whereas p53 wild-type SN38-resistant cells failed to migrate. Notably, cotreatment with inhibitors of the MAPK pathway inhibited the increased migration observed following SN38 treatment in p53 null and p53-mutant cells. Thus, in the absence of wild-type p53, SN38 promotes migration of colorectal cancer cells, and inhibiting MAPK blocks this potentially prometastatic adaptive response to this anticancer drug.

Defending the Faith(s)?:Democracy and Hereditary Right in England

The persistence of traditional monarchies in modern societies, which are otherwise characterized by democratic and egalitarian values, remains a paradox in the social sciences. In part this is attributable to the lack of psychological investigation into the relationship between subject and sovereign, and in particular the ways in which the political and social values of the citizenry shape understandings of a hereditary monarch’s right to represent a national community. Adopting the qualitative analysis methods of discursive psychology and grounded theory, the current study examines vernacular accounts of nationhood and monarchy in England in both formalized conversational interviews (n = 60) and impromptu street interviews (n = 56). Focusing on accounts of Prince Charles’s recent proposal to change the role of the monarch, from “Defender of the (Christian) Faith” to “Defender of Faiths,” those in favor treated it as a positive step towards reflecting a diverse (religious) community, bringing the monarchy into line with current concerns of pluralism and upholding
values of personal choice and individual rights. Participants who rejected the proposed change in title construed it as antithetical to these values in terms of reflecting personal stake and interest, an abuse of power, or an imposition on other faiths. In all accounts, the prime concern was in safeguarding the political and social values of the citizenry. In conclusion it is argued that the study of subjects’ relationship to the monarch, its function and legitimacy, can provide an opportunity to examine how values can characterize a national community and facilitate national diversity.

Do hens have friends?

Recent interest in positive welfare has encouraged consideration of the formation of socio-positive relationships in farmed species which may provide a means by which to manage positive states. We investigated in detail the existence of dyadic preferential associations in small groups of domestic laying hens. Spatial and temporal associations were examined in two contexts (day activity and evening roosting), within 8 identical pens of 15 laying hens over 8 weeks. Little aggression was observed. Social network analysis was performed to investigate correlations in who associated with whom using weighted degree (number) and binary (presence or absence) data for shared resource areas and proximity to other individuals. No consistent evidence was found for hens actively preferring others in their choice of resource area, or in companion proximity. Perch-roosting positions chosen by the hens were compared with data generated from a random-choice model. Hens showed no position preferences. Most dyads were never observed roosting together and, although some apparently perched together frequently, the low number of nights perching and proportion of nights spent together indicates these findings should be interpreted with caution. Overall, we found no convincing evidence of dyadic preferential relationships expressed by close active and resting proximities. Further work is required to confirm whether these findings hold true in other experimental contexts, are affected by social experience and if they hold in common with the progenitor sub-species. © 2012 Elsevier B.V.

Resolution theory, and static and frequency-dependent cross-talk in piezoresponse force microscopy

Probing the functionality of materials locally by means of scanning probe microscopy (SPM) requires a reliable framework for identifying the target signal and separating it from the effects of surface morphology and instrument non-idealities, e.g. instrumental and topographical cross-talk. Here we develop a linear resolution theory framework in order to describe the cross-talk effects, and apply it for elucidation of frequency-dependent cross-talk mechanisms in piezoresponse force microscopy. The use of a band excitation method allows electromechanical/electrical and mechanical/topographic signals to be unambiguously separated. The applicability of a functional fit approach and multivariate statistical analysis methods for identification of data in band excitation SPM is explored.

Influence of the experimental design of gene expression studies on the inference of gene regulatory networks: environmental factors

The inference of gene regulatory networks gained within recent years a considerable interest in the biology and biomedical community. The purpose of this paper is to investigate the influence that environmental conditions can exhibit on the inference performance of network inference algorithms. Specifically, we study five network inference methods, Aracne, BC3NET, CLR, C3NET and MRNET, and compare the results for three different conditions: (I) observational gene expression data: normal environmental condition, (II) interventional gene expression data: growth in rich media, (III) interventional gene expression data: normal environmental condition interrupted by a positive spike-in stimulation. Overall, we find that different statistical inference methods lead to comparable, but condition-specific results. Further, our results suggest that non-steady-state data enhance the inferability of regulatory networks.

Integrating allowable design strains in composites with whole life value

Fibre-Reinforced Plastics (FRPs) have been used in civil aerospace vehicles for decades. The current state-of-the-art in airframe design and manufacture results in approximately half the airframe mass attributable to FRP materials. The continual increase in the use of FRP materials over metallic alloys is attributable to the material's superior specific strength and stiffness, fatigue performance and corrosion resistance. However, the full potential of these materials has yet to be exploited as analysis methods to predict physical failure with equal accuracy and robustness are not yet available. The result is a conservative approach to design, but one that can bring benefit via increased inspection intervals and reduced cost over the vehicle life. The challenge is that the methods used in practice are based on empirical tests and real relationships and drivers are difficult to see in this complex process and so the trade-off decision is challenging and uncertain. The aim of this feasibility study was to scope a viable process which could help develop some rules and relationships based on the fundamental mechanics of composite material and the economics of production and operation, which would enhance understanding of the role and impact of design allowables across the life of a composite structure.