mCOPA: analysis of heterogeneous features in cancer expression data

Background Cancer outlier profile analysis (COPA) has proven to be an effective approach to analyzing cancer expression data, leading to the discovery of the TMPRSS2 and ETS family gene fusion events in prostate cancer. However, the original COPA algorithm did not identify down-regulated outliers, and the currently available R package implementing the method is similarly restricted to the analysis of over-expressed outliers. Here we present a modified outlier detection method, mCOPA, which contains refinements to the outlier-detection algorithm, identifies both over- and under-expressed outliers, is freely available, and can be applied to any expression dataset. Results We compare our method to other feature-selection approaches, and demonstrate that mCOPA frequently selects more-informative features than do differential expression or variance-based feature selection approaches, and is able to recover observed clinical subtypes more consistently. We demonstrate the application of mCOPA to prostate cancer expression data, and explore the use of outliers in clustering, pathway analysis, and the identification of tumour suppressors. We analyse the under-expressed outliers to identify known and novel prostate cancer tumour suppressor genes, validating these against data in Oncomine and the Cancer Gene Index. We also demonstrate how a combination of outlier analysis and pathway analysis can identify molecular mechanisms disrupted in individual tumours. Conclusions We demonstrate that mCOPA offers advantages, compared to differential expression or variance, in selecting outlier features, and that the features so selected are better able to assign samples to clinically annotated subtypes. Further, we show that the biology explored by outlier analysis differs from that uncovered in differential expression or variance analysis. mCOPA is an important new tool for the exploration of cancer datasets and the discovery of new cancer subtypes, and can be combined with pathway and functional analysis approaches to discover mechanisms underpinning heterogeneity in cancers

Impact fees and new housing cost: A comparative analysis of the empirical models

Developers and policy makers are consistently at odds over the debate as to whether impact fees increase house prices. This debate continues despite the extensive body of theoretical and empirical international literature that discusses the passing on to home buyers of impact fees, and the corresponding increase to housing prices. In attempting to quantify this impact, over a dozen empirical studies have been carried out in the US and Canada since the 1980’s. However the methodologies used vary greatly, as do the results. Despite similar infrastructure funding policies in numerous developed countries, no such empirical works exist outside of the US/Canada. The purpose of this research is to analyse the existing econometric models in order to identify, compare and contrast the theoretical bases, methodologies, key assumptions and findings of each. This research will assist in identifying if further model development is required and/or whether any of these models have external validity and are readily transferable outside of the US. The findings conclude that there is very little explicit rationale behind the various model selections and that significant model deficiencies appear still to exist.

Model development and dynamic load-sharing analysis of longitudinal-connected air suspensions

The objective of this research was to investigate the effect of suspension parameters on dynamic load-sharing of longitudinal-connected air suspensions of a tri-axle semi-trailer. A novel nonlinear model of a multi-axle semi-trailer with longitudinal-connected air suspension was formulated based on fluid mechanics and thermodynamics and was validated through test results. The effects of suspension parameters on dynamic load-sharing and road-friendliness of the semi-trailer were analyzed. Simulation results indicate that the road-friendliness metric DLC (Dynamic Load Coefficient), is generally in accordance with the load-sharing metric - DLSC (Dynamic Load Sharing Coefficient). When the static height or static pressure increases, the DLSC optimization ratio declines monotonically. The effect of employing larger air lines and connectors on the DLSC optimization ratio gives varying results as road roughness increases and as driving speed increases. The results also indicate that if the air line diameter is always assumed to be larger than the connector diameter, the influence of air line diameter on load-sharing is more significant than that of the connector.

Analysis of Object-Specific Authorization Protocol (OSAP) using coloured Petri nets

The use of Trusted Platform Module (TPM) is be- coming increasingly popular in many security sys- tems. To access objects protected by TPM (such as cryptographic keys), several cryptographic proto- cols, such as the Object Specific Authorization Pro- tocol (OSAP), can be used. Given the sensitivity and the importance of those objects protected by TPM, the security of this protocol is vital. Formal meth- ods allow a precise and complete analysis of crypto- graphic protocols such that their security properties can be asserted with high assurance. Unfortunately, formal verification of these protocols are limited, de- spite the abundance of formal tools that one can use. In this paper, we demonstrate the use of Coloured Petri Nets (CPN) - a type of formal technique, to formally model the OSAP. Using this model, we then verify the authentication property of this protocol us- ing the state space analysis technique. The results of analysis demonstrates that as reported by Chen and Ryan the authentication property of OSAP can be violated.

Content analysis of international research in geographical and environmental education : eighteen years of academic publishing

This paper examines the history of the IRGEE Journal in terms of its sustainable future. The development of geographical and environmental education is evaluated, as reflected from the articles published in the Journal “International Research in Geographical and Environmental Education” (IRGEE). A content analysis of all papers and forum sections which have appeared in the journal since Volume 1 Number 1 was published in 1992 has been conducted, examining the content of as many as 526 articles. The method was a content analysis, and revealed themes which have experienced an increasing or declining interest over the 18 years of publication of IRGEE (1992-2009), while other themes have remained current during this period. The main findings of this analysis are: a) the total number of articles has increased more than threefold, b) articles related to geographical education (sensu stricto) outweighed those related to environmental education, c) the themes “syllabi, textbooks, curricula” and “values, attitudes” attract the attention of researchers with increasing strength and d) emerging subjects, such as GIS and sustainability have appeared dynamically in the last years.

Statistical and scientometric analysis of international research in geographical and environmental education

Certain statistic and scientometric features of articles published in the journal “International Research in Geographical and Environmental Education” are examined in this paper, for the period 1992-2009, by applying nonparametric statistics and Shannon’s entropy (diversity) formula. The main findings of this analysis are: a) after 2004 the research priorities of researchers in geographical and environmental education seem to have changed, b) “teacher education” has been the most recurrent theme throughout these 18 years, followed by “values & attitudes” and “inquiry & problem solving” c) the themes “GIS” and “Sustainability” were the most “stable” throughout the 18 years, meaning that they maintained their ranks as publication priorities more than other themes, d) citations of IRGEE increase annually, e) the average thematic diversity of articles published during the period 1992-2009 is 82.7% of the maximum thematic diversity (very high), meaning that the Journal has the capacity to attract a wide readership for the 10 themes it has successfully covered throughout the 18 years of its publication.

Empirical analysis of the effect of dimension reduction and word order on semantic vectors

The aim of this paper is to provide a comparison of various algorithms and parameters to build reduced semantic spaces. The effect of dimension reduction, the stability of the representation and the effect of word order are examined in the context of the five algorithms bearing on semantic vectors: Random projection (RP), singular value decom- position (SVD), non-negative matrix factorization (NMF), permutations and holographic reduced representations (HRR). The quality of semantic representation was tested by means of synonym finding task using the TOEFL test on the TASA corpus. Dimension reduction was found to improve the quality of semantic representation but it is hard to find the optimal parameter settings. Even though dimension reduction by RP was found to be more generally applicable than SVD, the semantic vectors produced by RP are somewhat unstable. The effect of encoding word order into the semantic vector representation via HRR did not lead to any increase in scores over vectors constructed from word co-occurrence in context information. In this regard, very small context windows resulted in better semantic vectors for the TOEFL test.

Adapting wheat sowing dates to projected climate change in the Australian subtropics: analysis of crop water use and yield

Projected increases in atmospheric carbon dioxide concentration ([CO2]) and air temperature associated with future climate change are expected to affect crop development, crop yield, and, consequently, global food supplies. They are also likely to change agricultural production practices, especially those related to agricultural water management and sowing date. The magnitude of these changes and their implications to local production systems are mostly unknown. The objectives of this study were to: (i) simulate the effect of projected climate change on spring wheat (Triticum aestivum L. cv. Lang) yield and water use for the subtropical environment of the Darling Downs, Queensland, Australia; and (ii) investigate the impact of changing sowing date, as an adaptation strategy to future climate change scenarios, on wheat yield and water use. The multimodel climate projections from the IPCC Coupled Model Intercomparison Project (CMIP3) for the period 2030–2070 were used in this study. Climate scenarios included combinations of four changes in air temperature (08C, 18C, 28C, and 38C), three [CO2] levels (380 ppm, 500 ppm, and 600 ppm), and three changes in rainfall (–30%, 0%, and +20%), which were superimposed on observed station data. Crop management scenarios included a combination of six sowing dates (1 May, 10 May, 20 May, 1 June, 10 June, and 20 June) and three irrigation regimes (no irrigation (NI), deficit irrigation (DI), and full irrigation (FI)). Simulations were performed with the model DSSAT4.5, using 50 years of daily weather data.Wefound that: (1) grain yield and water-use efficiency (yield/evapotranspiration) increased linearly with [CO2]; (2) increases in [CO2] had minimal impact on evapotranspiration; (3) yield increased with increasing temperature for the irrigated scenarios (DI and FI), but decreased for the NI scenario; (4) yield increased with earlier sowing dates; and (5) changes in rainfall had a small impact on yield for DI and FI, but a high impact for the NI scenario.

On the diversity analysis of the sequential slotted amplify-decode-and-forward protocol

In this paper, we review the sequential slotted amplify-decode-and-forward (SADF) protocol with half-duplex single-antenna and evaluate its performance in terms of pairwise error probability (PEP). We obtain the PEP upper bound of the protocol and find out that the achievable diversity order of the protocol is two with arbitrary number of relay terminals. To achieve the maximum achievable diversity order, we propose a simple precoder that is easy to implement with any number of relay terminals and transmission slots. Simulation results show that the proposed precoder achieves the maximum achievable diversity order and has similar BER performance compared to some of the existing precoders.

Life impact of ankle fractures : qualitative analysis of patient and clinician experiences

Background: Ankle fractures are one of the more commonly occurring forms of trauma managed by orthopaedic teams worldwide. The impacts of these injuries are not restricted to pain and disability caused at the time of the incident, but may also result in long term physical, psychological, and social consequences. There are currently no ankle fracture specific patient-reported outcome measures with a robust content foundation. This investigation aimed to develop a thematic conceptual framework of life impacts following ankle fracture from the experiences of people who have suffered ankle fractures as well as the health professionals who treat them. Methods: A qualitative investigation was undertaken using in-depth semi-structured interviews with people (n=12) who had previously sustained an ankle fracture (patients) and health professionals (n=6) that treat people with ankle fractures. Interviews were audio-recorded and transcribed. Each phrase was individually coded and grouped in categories and aligned under emerging themes by two independent researchers. Results: Saturation occurred after 10 in-depth patient interviews. Time since injury for patients ranged from 6 weeks to more than 2 years. Experience of health professionals ranged from 1 year to 16 years working with people with ankle fractures. Health professionals included an Orthopaedic surgeon (1), physiotherapists (3), a podiatrist (1) and an occupational therapist (1). The emerging framework derived from patient data included eight themes (Physical, Psychological, Daily Living, Social, Occupational and Domestic, Financial, Aesthetic and Medication Taking). Health professional responses did not reveal any additional themes, but tended to focus on physical and occupational themes. Conclusions: The nature of life impact following ankle fractures can extend beyond short term pain and discomfort into many areas of life. The findings from this research have provided an empirically derived framework from which a condition-specific patient-reported outcome measure can be developed.

A non-linear dynamic analysis of heavy haul track line sleepers under wheel flat

Significant wheel-rail dynamic forces occur because of imperfections in the wheels and/or rail. One of the key responses to the transmission of these forces down through the track is impact force on the sleepers. Dynamic analysis of nonlinear systems is very complicated and does not lend itself easily to a classical solution of multiple equations. Trying to deduce the behaviour of track components from experimental data is very difficult because such data is hard to obtain and applies to only the particular conditions of the track being tested. The finite element method can be the best solution to this dilemma. This paper describes a finite element model using the software package ANSYS for various sized flat defects in the tread of a wheel rolling at a typical speed on heavy haul track. The paper explores the dynamic response of a prestressed concrete sleeper to these defects.

A dynamic wheel-rail impact analysis of railway track under wheel flat by Finite Element Analysis

Wheel–rail interaction is one of the most important research topics in railway engineering. It involves track impact response, track vibration and track safety. Track structure failures caused by wheel–rail impact forces can lead to significant economic loss for track owners through damage to rails and to the sleepers beneath. Wheel–rail impact forces occur because of imperfections in the wheels or rails such as wheel flats, irregular wheel profiles, rail corrugations and differences in the heights of rails connected at a welded joint. A wheel flat can cause a large dynamic impact force as well as a forced vibration with a high frequency, which can cause damage to the track structure. In the present work, a three-dimensional (3-D) finite element (FE) model for the impact analysis induced by the wheel flat is developed by use of the finite element analysis (FEA) software package ANSYS and validated by another validated simulation. The effect of wheel flats on impact forces is thoroughly investigated. It is found that the presence of a wheel flat will significantly increase the dynamic impact force on both rail and sleeper. The impact force will monotonically increase with the size of wheel flats. The relationships between the impact force and the wheel flat size are explored from this finite element analysis and they are important for track engineers to improve their understanding of the design and maintenance of the track system.

A meta-analysis of genome-wide association studies to identify prostate cancer susceptibility loci associated with aggressive and non-aggressive disease

Genome-wide association studies (GWAS) have identified multiple common genetic variants associated with an increased risk of prostate cancer (PrCa), but these explain less than one-third of the heritability. To identify further susceptibility alleles, we conducted a meta-analysis of four GWAS including 5953 cases of aggressive PrCa and 11 463 controls (men without PrCa). We computed association tests for approximately 2.6 million SNPs and followed up the most significant SNPs by genotyping 49 121 samples in 29 studies through the international PRACTICAL and BPC3 consortia. We not only confirmed the association of a PrCa susceptibility locus, rs11672691 on chromosome 19, but also showed an association with aggressive PrCa [odds ratio = 1.12 (95% confidence interval 1.03-1.21), P = 1.4 × 10(-8)]. This report describes a genetic variant which is associated with aggressive PrCa, which is a type of PrCa associated with a poorer prognosis.

A confirmatory factor analysis of the Observer Alexithymia Scale in treatment seeking alcohol-dependent patients

Confirmatory factor analyses evaluated the factorial validity of the Observer Alexithymia Scale (OAS) in an alcohol-dependent sample. Observation was conducted by clinical psychologists. All models examined were rejected, given their poor fit. Given the psychometric limitations of the OAS shown in this study, the OAS may not be the most appropriate measure to use early in treatment among alcohol-dependent individuals.

Analysis of heat transfer and fluid flow in a triangular enclosure in presence of an adiabatic fin

Natural convection thermal boundary layer adjacent to the heated inclined wall of a right angled triangle with an adiabatic fin attached to that surface is investigated by numerical simulations. The finite volume based unsteady numerical model is adopted for the simulation. It is revealed from the numerical results that the development of the boundary layer along the inclined surface is characterized by three distinct stages, i.e. a start-up stage, a transitional stage and a steady stage. These three stages can be clearly identified from the numerical simulations. Moreover, in presence of adiabatic fin, the thermal boundary layer adjacent to the inclined wall breaks initially. However, it is reattached with the downstream boundary layer next to the fin. More attention has been given to the boundary layer development near the fin area.