An Examination of Transformation Techniques to Investigate and Interpret Multivariate Geochemical Data Analysis: Tellus Case Study

This research aims to use the multivariate geochemical dataset, generated by the Tellus project, to investigate the appropriate use of transformation methods to maintain the integrity of geochemical data and inherent constrained behaviour in multivariate relationships. The widely used normal score transform is compared with the use of a stepwise conditional transform technique. The Tellus Project, managed by GSNI and funded by the Department of Enterprise Trade and Development and the EU’s Building Sustainable Prosperity Fund, involves the most comprehensive geological mapping project ever undertaken in Northern Ireland. Previous study has demonstrated spatial variability in the Tellus data but geostatistical analysis and interpretation of the datasets requires use of an appropriate methodology that reproduces the inherently complex multivariate relations. Previous investigation of the Tellus geochemical data has included use of Gaussian-based techniques. However, earth science variables are rarely Gaussian, hence transformation of data is integral to the approach. The multivariate geochemical dataset generated by the Tellus project provides an opportunity to investigate the appropriate use of transformation methods, as required for Gaussian-based geostatistical analysis. In particular, the stepwise conditional transform is investigated and developed for the geochemical datasets obtained as part of the Tellus project. The transform is applied to four variables in a bivariate nested fashion due to the limited availability of data. Simulation of these transformed variables is then carried out, along with a corresponding back transformation to original units. Results show that the stepwise transform is successful in reproducing both univariate statistics and the complex bivariate relations exhibited by the data. Greater fidelity to multivariate relationships will improve uncertainty models, which are required for consequent geological, environmental and economic inferences.

Molecular and clinicopathological markers of prognosis in breast cancer

A vast body of research in breast cancer prognostication has accumulated. Yet despite this, patients within current prognostic categories may have significantly different outcomes. There is a need to more accurately divide those cancer types associated with an excellent prognosis from those requiring more aggressive therapy. Gene expression array studies have revealed the numerous molecular breast cancer subtypes that are associated with differing outcomes. Furthermore, as next generation technologies evolve and further reveal the complexities of breast cancer, it is likely that existing prognostic approaches will become progressively refined. Future prognostication in breast cancer requires a morphomolecular, multifaceted approach involving the assessment of anatomical disease extent and levels of protein, DNA and RNA expression. One of the major challenges in prognostication will be the integration of potential assays into existing clinical systems and identification of appropriate patient subgroups for analysis.

Antioxidants and diabetic retinopathy

The biochemical perturbations in diabetes mellitus (DM) create the conditions for the production of free radicals, the consequence of which is increased oxidative stress. Evidence has accrued over the past 2 decades that suggests that oxidative stress is an important pathogenetic factor in the development of diabetic retinopathy (DR). Experimental data show that the use of strategies that ameliorate oxidative stress can prevent and retard the development of DR in the animal model. Clinical observations also suggest that reducing oxidative stress may help to reverse pathological manifestations of DR. The present article constitutes an examination of the role of antioxidants in the management of DR and the current state of clinically relevant knowledge. © 2013 Springer Science+Business Media New York.

Prognostic and therapeutic relevance of FLIP and procaspase-8 overexpression in non-small cell lung cancer

Non-small cell lung carcinoma remains by far the leading cause of cancer-related deaths worldwide. Overexpression of FLIP, which blocks the extrinsic apoptotic pathway by inhibiting caspase-8 activation, has been identified in various cancers. We investigated FLIP and procaspase-8 expression in NSCLC and the effect of HDAC inhibitors on FLIP expression, activation of caspase-8 and drug resistance in NSCLC and normal lung cell line models. Immunohistochemical analysis of cytoplasmic and nuclear FLIP and procaspase-8 protein expression was carried out using a novel digital pathology approach. Both FLIP and procaspase-8 were found to be significantly overexpressed in tumours, and importantly, high cytoplasmic expression of FLIP significantly correlated with shorter overall survival. Treatment with HDAC inhibitors targeting HDAC1-3 downregulated FLIP expression predominantly via post-transcriptional mechanisms, and this resulted in death receptor- and caspase-8-dependent apoptosis in NSCLC cells, but not normal lung cells. In addition, HDAC inhibitors synergized with TRAIL and cisplatin in NSCLC cells in a FLIP- and caspase-8-dependent manner. Thus, FLIP and procaspase-8 are overexpressed in NSCLC, and high cytoplasmic FLIP expression is indicative of poor prognosis. Targeting high FLIP expression using HDAC1-3 selective inhibitors such as entinostat to exploit high procaspase-8 expression in NSCLC has promising therapeutic potential, particularly when used in combination with TRAIL receptor-targeted agents.

Power allocation strategies across N orthogonal channels for single-relay networks at both source and relay

We consider a wireless relay network with one source, one relay and one destination, where communications between nodes are preformed over N orthogonal channels. This, for example, is the case when orthogonal frequency division multiplexing is employed for data communications. Since the power available at the source and relay is limited, we study optimal power allocation strategies at the source and relay in order to maximize the overall source-destination capacity. Depending on the availability of the channel state information at both the source and relay or only at the relay, power allocation is performed at both the source and relay or only at the relay. Considering different setups for the problem, various optimization problems are formulated and solved. Some properties of the optimal solution are also proved.

FPGA Prototyping of Emerging Manycore Architectures for Parallel Programming Research using Formic Boards

Performance evaluation of parallel software and architectural exploration of innovative hardware support face a common challenge with emerging manycore platforms: they are limited by the slow running time and the low accuracy of software simulators. Manycore FPGA prototypes are difficult to build, but they offer great rewards. Software running on such prototypes runs orders of magnitude faster than current simulators. Moreover, researchers gain significant architectural insight during the modeling process. We use the Formic FPGA prototyping board [1], which specifically targets scalable and cost-efficient multi-board prototyping, to build and test a 64-board model of a 512-core, MicroBlaze-based, non-coherent hardware prototype with a full network-on-chip in a 3D-mesh topology. We expand the hardware architecture to include the ARM Versatile Express platforms and build a 520-core heterogeneous prototype of 8 Cortex-A9 cores and 512 MicroBlaze cores. We then develop an MPI library for the prototype and evaluate it extensively using several bare-metal and MPI benchmarks. We find that our processor prototype is highly scalable, models faithfully single-chip multicore architectures, and is a very efficient platform for parallel programming research, being 50,000 times faster than software simulation.

Applied physics: Trawling for complements

A method has been invented for determining nanoscale variations in the distribution of electric charge on surfaces. It has so far been used to examine specific inorganic materials, but could find widespread applications in imaging.

Using mesh-geometry relationships to transfer analysis models between CAE tools

Integrating analysis and design models is a complex task due to differences between the models and the architectures of the toolsets used to create them. This complexity is increased with the use of many different tools for specific tasks using an analysis process. In this work various design and analysis models are linked throughout the design lifecycle, allowing them to be moved between packages in a way not currently available. Three technologies named Cellular Modeling, Virtual Topology and Equivalencing are combined to demonstrate how different finite element meshes generated on abstract analysis geometries can be linked to their original geometry. Cellular models allow interfaces between adjacent cells to be extracted and exploited to transfer analysis attributes such as mesh associativity or boundary conditions between equivalent model representations. Virtual Topology descriptions used for geometry clean-up operations are explicitly stored so they can be reused by downstream applications. Establishing the equivalence relationships between models enables analysts to utilize multiple packages for specialist tasks without worrying about compatibility issues or substantial rework.

Brca1 and brca2:Role in the DNA damage response, cancer formation and treatment

BRCA1 and BRCA2 are highly penetrant breast and ovarian cancer susceptibility genes that are mutated in a significant proportion of familial breast and ovarian cancer syndromes. Both of these genes are tumour suppressors, the products of which play vital roles in the cellular response to DNA damage. These proteins function in a number of cellular pathways in order to maintain genomic stability including DNA damage signaling, DNA repair, cell cycle regulation, protein ubiquitination, chromatin remodeling, transcriptional regulation and apoptosis. This chapter will discuss the functions of these proteins and how they relate to tumour development, and therapy. © 2009 Springer Science+Business Media B.V.

Biosensor based toxicity dissection of tannery and associated environmental samples

Kenyan tannery and associated environmental samples were selected for ecotoxicological assessment. A tool-kit of techniques was developed, including whole-cell biosensor and chemical assays. A luminescence based bacterial biosensor (Escherichia coli HB101 pUCD607) (via a multi-copy plasmid) was used for toxicity assessment. Samples were manipulated prior to biosensor interrogation to identify the nature of the toxic contaminants. Untreated samples (before any manipulations) showed a strong toxic effect at the discharge point in comparison to other sampling points. Sparging was used to identify toxicity associated with volatile organics. The toxicity of contaminants, removed by treatment with activated charcoal was identified for all the sampling points except for those upstream of effluent discharges. Filtration identified toxicity associated with suspended solids. Changes in availability of toxic contaminants due to pH adjustment of most samples from the tannery effluent treatment pits were also associated with the extreme pH values (4.0 and 8.0). The approach used has highlighted the complexicity of toxic pollutants in effluent from the tanning industry and the dissection of toxicity points to possible remediation strategies for effluents from the tanning industry.

Cognition, metacognition and patient safety

This article explores the factors that contribute to patient safety incidents. It highlights the importance of human factors in influencing the clinician's performance. Rather than focusing on clinical skills, the article explores the range of non-technical skills which are seen to each contribute to patient safety, including: communication, teamworking, leadership, active followership, situational awareness, decision-making, assertiveness, and workload management. It asks how cognitive processes can influence safe decision-making.