Loss-of-function fibroblast growth factor receptor-2 mutations in melanoma

We report that 10% of melanoma tumors and cell lines harbor mutations in the fibroblast growth factor receptor 2 (FGFR2) gene. These novel mutations include three truncating mutations and 20 missense mutations occurring at evolutionary conserved residues in FGFR2 as well as among all four FGFRs. The mutation spectrum is characteristic of those induced by UV radiation. Mapping of these mutations onto the known crystal structures of FGFR2 followed by in vitro and in vivo studies show that these mutations result in receptor loss of function through several distinct mechanisms, including loss of ligand binding affinity, impaired receptor dimerization, destabilization of the extracellular domains, and reduced kinase activity. To our knowledge, this is the first demonstration of loss-of-function mutations in a class IV receptor tyrosine kinase in cancer. Taken into account with our recent discovery of activating FGFR2 mutations in endometrial cancer, we suggest that FGFR2 may join the list of genes that play context-dependent opposing roles in cancer.

Assessment of retinal structure and visual function in association with diabetic peripheral neuropathy

Diabetes is an increasingly prevalent disease worldwide. Providing early management of the complications can prevent morbidity and mortality in this population. Peripheral neuropathy, a significant complication of diabetes, is the major cause of foot ulceration and amputation in diabetes. Delay in attending to complication of the disease contributes to significant medical expenses for diabetic patients and the community. Early structural changes to the neural components of the retina have been demonstrated to occur prior to the clinically visible retinal vasculature complication of diabetic retinopathy. Additionally visual functionloss has been shown to exist before the ophthalmoscopic manifestations of vasculature damage. The purpose of this thesis was to evaluate the relationship between diabetic peripheral neuropathy and both retinal structure and visual function. The key question was whether diabetic peripheral neuropathy is the potential underlying factor responsible for retinal anatomical change and visual functional loss in people with diabetes. This study was conducted on a cohort with type 2 diabetes. Retinal nerve fibre layer thickness was assessed by means of Optical Coherence Tomography (OCT). Visual function was assessed using two different methods; Standard Automated Perimetry (SAP) and flicker perimetry were performed within the central 30 degrees of fixation. The level of diabetic peripheral neuropathy (DPN) was assessed using two techniques - Quantitative Sensory Testing and Neuropathy Disability Score (NDS). These techniques are known to be capable of detecting DPN at very early stages. NDS has also been shown as a gold standard for detecting 'risk of foot ulceration'. Findings reported in this thesis showed that RNFL thickness, particularly in the inferior quadrant, has a significant association with severity of DPN when the condition has been assessed using NDS. More specifically it was observed that inferior RNFL thickness has the ability to differentiate individuals who are at higher risk of foot ulceration from those who are at lower risk, indicating that RNFL thickness can predict late-staged DPN. Investigating the association between RNFL and QST did not show any meaningful interaction, which indicates that RNFL thickness for this cohort was not as predictive of neuropathy status as NDS. In both of these studies, control participants did not have different results from the type 2 cohort who did not DPN suggesting that RNFL thickness is not a marker for diagnosing DPN at early stages. The latter finding also indicated that diabetes per se, is unlikely to affect the RNFL thickness. Visual function as measured by SAP and flicker perimetry was found to be associated with severity of peripheral neuropathy as measured by NDS. These findings were also capable of differentiating individuals at higher risk of foot ulceration; however, visual function also proved not to be a maker for early diagnosis of DPN. It was found that neither SAP, nor flicker sensitivity have meaningful associations with DPN when neuropathy status was measured using QST. Importantly diabetic retinopathy did not explain any of the findings in these experiments. The work described here is valuable as no other research to date has investigated the association between diabetic peripheral neuropathy and either retinal structure or visual function.

3D ellipsoid fitting for multi-view gait recognition

Gait recognition approaches continue to struggle with challenges including view-invariance, low-resolution data, robustness to unconstrained environments, and fluctuating gait patterns due to subjects carrying goods or wearing different clothes. Although computationally expensive, model based techniques offer promise over appearance based techniques for these challenges as they gather gait features and interpret gait dynamics in skeleton form. In this paper, we propose a fast 3D ellipsoidal-based gait recognition algorithm using a 3D voxel model derived from multi-view silhouette images. This approach directly solves the limitations of view dependency and self-occlusion in existing ellipse fitting model-based approaches. Voxel models are segmented into four components (left and right legs, above and below the knee), and ellipsoids are fitted to each region using eigenvalue decomposition. Features derived from the ellipsoid parameters are modeled using a Fourier representation to retain the temporal dynamic pattern for classification. We demonstrate the proposed approach using the CMU MoBo database and show that an improvement of 15-20% can be achieved over a 2D ellipse fitting baseline.

Frequency response function based structural damage detection using artificial neural networks

Damage detection in structures has become increasingly important in recent years. While a number of damage detection and localization methods have been proposed, few attempts have been made to explore the structure damage with frequency response functions (FRFs). This paper illustrates the damage identification and condition assessment of a beam structure using a new frequency response functions (FRFs) based damage index and Artificial Neural Networks (ANNs). In practice, usage of all available FRF data as an input to artificial neural networks makes the training and convergence impossible. Therefore one of the data reduction techniques Principal Component Analysis (PCA) is introduced in the algorithm. In the proposed procedure, a large set of FRFs are divided into sub-sets in order to find the damage indices for different frequency points of different damage scenarios. The basic idea of this method is to establish features of damaged structure using FRFs from different measurement points of different sub-sets of intact structure. Then using these features, damage indices of different damage cases of the structure are identified after reconstructing of available FRF data using PCA. The obtained damage indices corresponding to different damage locations and severities are introduced as input variable to developed artificial neural networks. Finally, the effectiveness of the proposed method is illustrated and validated by using the finite element modal of a beam structure. The illustrated results show that the PCA based damage index is suitable and effective for structural damage detection and condition assessment of building structures.

Gait energy volumes and frontal gait recognition using depth images

Gait energy images (GEIs) and its variants form the basis of many recent appearance-based gait recognition systems. The GEI combines good recognition performance with a simple implementation, though it suffers problems inherent to appearance-based approaches, such as being highly view dependent. In this paper, we extend the concept of the GEI to 3D, to create what we call the gait energy volume, or GEV. A basic GEV implementation is tested on the CMU MoBo database, showing improvements over both the GEI baseline and a fused multi-view GEI approach. We also demonstrate the efficacy of this approach on partial volume reconstructions created from frontal depth images, which can be more practically acquired, for example, in biometric portals implemented with stereo cameras, or other depth acquisition systems. Experiments on frontal depth images are evaluated on an in-house developed database captured using the Microsoft Kinect, and demonstrate the validity of the proposed approach.

Compressive sensing for gait recognition

Compressive Sensing (CS) is a popular signal processing technique, that can exactly reconstruct a signal given a small number of random projections of the original signal, provided that the signal is sufficiently sparse. We demonstrate the applicability of CS in the field of gait recognition as a very effective dimensionality reduction technique, using the gait energy image (GEI) as the feature extraction process. We compare the CS based approach to the principal component analysis (PCA) and show that the proposed method outperforms this baseline, particularly under situations where there are appearance changes in the subject. Applying CS to the gait features also avoids the need to train the models, by using a generalised random projection.

An exploration of young students' ability to generalise function tasks

The Early Years Generalising Project involves Australian students, Years 1-4 (age 5-9), and explores how the students grasp and express generalisations. This paper focuses on the data collected from clinical interviews with Year 3 and 4 cohorts in an investigative study focusing on the identifications, prediction and justification of function rules. It reports on students' attempts to generalise from function machine contexts, describing the various ways students express generalisation and highlighting the different levels of justification given by students. Finally, we conjecture that there are a set of stages in the expression and justification of generalisations that assist students to reach generality within tasks.

Footwear modifies coronal plane forefoot and sagittal plane hallux kinematics during stance phase of walking gait

Footwear is designed to reduce injury, and enhance performance. However, the effect footwear has on foot and ankle kinematics currently remains unknown. Acknowledging the need for improved understanding, multi-segment models of the foot-shoe complex need to be established to both describe and quantify the effect footwear has on the foot and ankle during stance phase of gait. The purpose of this study was to quantify how footwear alters the kinematics of the foot inside the shoe during stance phase of walking gait.