A gene expression signature for insulin resistance

Insulin resistance is a heterogeneous disorder caused by a range of genetic and environmental factors, and we hypothesize that its aetiology varies considerably between individuals. This heterogeneity provides significant challenges to the development of effective therapeutic regimes for long-term management of type 2 diabetes. We describe a novel strategy, using large-scale gene expression profiling, to develop a Gene Expression Signature (GES) that reflects the overall state of insulin resistance in cells and patients. The GES was developed from 3T3-L1 adipocytes that were made ‘insulin resistant’ by treatment with tumour necrosis factor-alpha (TNFα) and then reversed with aspirin and troglitazone (‘re-sensitized’). The GES consisted of five genes whose expression levels best discriminated between the insulin resistant and insulin re-sensitized states. We then used this GES to screen a compound library for agents that affected the GES genes in 3T3- L1 adipocytes in a way that most closely resembled the changes seen when insulin resistance was successfully reversed using aspirin and troglitazone. This screen identified both known and new insulin sensitizing compounds including non-steroidal anti inflammatory agents, β-adrenergic antagonists, beta-lactams and sodium channel blockers. We tested the biological relevance of this GES in participants in the San Antonio Family Heart Study (n = 1,240) and showed that patients with the lowest GES scores were more insulin resistant (according to HOMA_IR and fasting plasma insulin levels, P < 0.001). These findings show that GES technology can be used for both the discovery of insulin sensitizing compounds and the characterization of patients into subtypes of insulin resistance according to GES scores, opening the possibility of developing a personalized medicine approach to type 2 diabetes.

An automatic application signature construction system for unknown traffic

Identifying applications and classifying network traffic flows according to their source applications are critical for a broad range of network activities. Such a decision can be based on packet header fields, packet payload content, statistical characteristics of traffic and communication patterns of network hosts. However, most present techniques rely on some sort of apriori knowledge, which means they require labor-intensive preprocessing before running and cannot deal with previously unknown applications. In this paper, we propose a traffic classification system based on application signatures, with a novel approach to fully automate the process of deriving signatures from unidentified traffic. The key idea is to integrate statistics-based flow clustering with payload-based signature matching method, so as to eliminate the requirement of pre-labeled training data sets. We evaluate the efficiency of our approach using real-world traffic trace, and the results indicate that signature classifiers built from clustered data and pre-labeled data are able to achieve similar high accuracy better than 99%.

Professional training in applied psychology : towards a signature pedagogy for forensic psychology training

Forensic Psychology is a recognised and important sub-specialty of the Psychology discipline. However, after an expansion in the number of training places that were offered when programmes were first developed, recent years have seen these diminish in response to changes in university policies, resulting from reformulated Federal government funding models. In this article, we argue that it is important for the future of specialist areas of professional psychology to not only articulate the core skills and competencies that are associated with specialist practice but also to develop unique and distinctive approaches to teaching and learning signature pedagogies. Based on the premise that forensic psychological practice is, indeed, a distinctive activity that requires different skills and, importantly, different ways of thinking about the work from other areas of professional psychology, it is suggested that professional training in this area should aim to develop a signature pedagogy which combines methods of teaching and learning that have been developed in legal training programmes with principles of problem-based learning.

Parallel matrix inversion techniques

In this paper, we present techniques for inverting sparse, symmetric and positive definite matrices on parallel and distributed computers. We propose two algorithms, one for SIMD implementation and the other for MIMD implementation. These algorithms are modified versions of Gaussian elimination and they take into account the sparseness of the matrix. Our algorithms perform better than the general parallel Gaussian elimination algorithm. In order to demonstrate the usefulness of our technique, we implemented the snake problem using our sparse matrix algorithm. Our studies reveal that the proposed sparse matrix inversion algorithm significantly reduces the time taken for obtaining the solution of the snake problem. In this paper, we present the results of our experimental work.

A representation-intensive signature pedagogy for school science?

In this paper we examine Shulman’s notion of signature pedagogies for its usefulness extended to school science. We argue that school science is in an important sense an apprenticeship, and that calls for reform in school science are compatible with Shulman’s practice-based vision of professional learning. Two case studies of teaching and learning will be presented based on research in primary and secondary schools that involved working closely with teachers to develop and validate involving a representation-intensive pedagogy that lays claim to bringing school science closer to the knowledge building practices of science. Video images of classrooms, interviews with students and teachers, and documentation of students’ work, were used to construct insights into the teaching and learning process. It is argued that Shulman’s notion of professional practice as involving apprenticeships of knowledge, practice and identity provides a useful lens through which to view this innovation. Shulman’s characterisation of signature pedagogy is used to identify key features of the approach.

Fault detection and diagnosis of induction motors using motor current signature analysis and a hybrid FMM-CART model

In this paper, a novel approach to detect and classify comprehensive fault conditions of induction motors using a hybrid fuzzy min-max (FMM) neural network and classification and regression tree (CART) is proposed. The hybrid model, known as FMM-CART, exploits the advantages of both FMM and CART for undertaking data classification and rule extraction problems. A series of real experiments is conducted, whereby the motor current signature analysis method is applied to form a database comprising stator current signatures under different motor conditions. The signal harmonics from the power spectral density are extracted as discriminative input features for fault detection and classification with FMM-CART. A comprehensive list of induction motor fault conditions, viz., broken rotor bars, unbalanced voltages, stator winding faults, and eccentricity problems, has been successfully classified using FMM-CART with good accuracy rates. The results are comparable, if not better, than those reported in the literature. Useful explanatory rules in the form of a decision tree are also elicited from FMM-CART to analyze and understand different fault conditions of induction motors.

Characterising secondary school teacher imperatives as subject (signature) pedagogies : a pedagogy of support in maths and a pedagogy of engagement in science

The ideas of Lee Shulman have played a major role in reconceptualising pedagogical description. In 2005, Shulman described a construct called “signature pedagogies” in order to describe recognisable and distinctive pedagogies used to prepare future practitioners for their profession. As a broader application of Shulman’s ideas, this paper asks, what is the efficacy of describing pedagogies that have become entrenched in secondary school subjects as signature pedagogies? Approached from a cultural perspective these questions are examined by comparing the subject cultures of junior school maths and science as experienced by, and represented in the classrooms of, a small number of teachers from two secondary schools in Victoria, Australia. In this research, subject culture is underpinned by shared basic assumptions that govern the dominance of certain “subject paradigms” (what should be taught) and “subject pedagogies” (how this should be taught) (Ball & Lacey, 1980). In this secondary school setting, the term signature pedagogies can be equated to the term subject pedagogies on the basis that both aim to characterise practice across the subject, or discipline, based on what was perceived as central to the task of teaching and learning. The paper draws on classroom observation and teacher interview data to show how six teachers positioned two aspects of their teaching in relation to what they believed was central in shaping their maths and science teaching: the effect of the arrangement of curriculum content on teachers’ conceptualisations of the teaching task; and a pedagogical imperative to engage students through activity-based learning experiences. The cultural expectations surrounding these two aspects of teaching appear to have a strong influence on practice, and in some senses teachers’ pedagogical responses were clear. These common responses are what I am calling “subject pedagogies” (see Ball & Lacey, 1980) because there was general agreement about what was central to the teaching task. Two subject pedagogies were seen to represent strong discourses occurring in both subjects: a “Pedagogy of Support” in maths, and “Pedagogy of Engagement” in science. Their established and shared character resembled Shulman’s posited “signature pedagogies” (Shulman, 2005). The data shows that by evaluating cultural practices that teachers have in common, and assumptions underpinning these, there is potential for highlighting imbalances, strengths and weaknesses, and connections and disconnections, associated with prevailing subject pedagogies.

A distinct DNA methylation signature defines pediatric pre-B cell acute lymphoblastic leukemia

Pre-B cell acute lymphoblastic leukemia (ALL) is the most prevalent childhood malignancy and remains one of the highest causes of childhood mortality. Despite this, the mechanisms leading to disease remain poorly understood. We asked if recurrent aberrant DNA methylation plays a role in childhood ALL and have defined a genome-scale DNA methylation profile associated with the ETV6-RUNX1 subtype of pediatric ALL. Archival bone marrow smears from 19 children collected at diagnosis and remission were used to derive a disease specific DNA methylation profile. The gene signature was confirmed in an independent cohort of 86 patients. A further 163 patients were analyzed for DNA methylation of a three gene signature. We found that the DNA methylation signature at diagnosis was unique from remission. Fifteen loci were sufficient to discriminate leukemia from disease-free samples and purified CD34+ cells. DNA methylation of these loci was recurrent irrespective of cytogenetic subtype of pre-B cell ALL. We show that recurrent aberrant genomic methylation is a common feature of pre-B ALL, suggesting a shared pathway for disease development. By revealing new DNA methylation markers associated with disease, this study has identified putative targets for development of novel epigenetic-based therapies.

High volume versus low volume balance training on postural sway in adults with previous ankle inversion injury

Balance training is commonly used in the rehabilitation process of ankle injuries; however, the exercise prescription guidelines for prescribing balance training are poorly understood. The aim of the present study was to determine if high or low volume balance training is more effective in improving postural sway after an 8 week balance training program utilising the same exercises. Seventeen subjects (14 male, 3 female) with a mean age of 24.06 ± 5.6 years were randomly allocated into a control group (CG), low volume training (LVT) or high volume training (HVT). All subjects had sustained at least two inversion ankle injuries within the last 18 months. Subjects completed 8 weeks of balance training of up to 30 mins duration, 3 times per week. LVT consisted of 40 repetitions for week 1, progressing to 90 repetitions by week 8. HVT consisted of 60 repetitions for week 1, progressing to 130 repetitions by week 8. The maximum centre of pressure (COP) excursion was obtained from the porce plate in the medial-lateral (ML) direction and subsequently used for pre-test and post-test analysis. After the 8 week training intervention, there was a significant (P<0.001) difference in postural sway between pre and post testing for both the LVT (pre = 88.69mm ± 25.08mm, post = 72.17mm ± 27.53mm) and HVT (pre = 77.47mm ±10.57mm, post = 58.54mm ± 7.01mm) groups. There was no significant (P>0.01) difference detected for improvements between the LVT and HVT, however reported effect sizes (ES) showed large effect size chances in the high volume training (ES = 1.7) whereas low volume training showed medium effect sizes changes (ES = 0.6). This preliminary study demonstrates the importance of training volume in the rehabilitation of ankle injuries, with the HVT being superior to LVT.