Modelling Cued-Target Recall using Quantum Inspired Models of Target Activation

This article presents and evaluates Quantum Inspired models of Target Activation using Cued-Target Recall Memory Modelling over multiple sources of Free Association data. Two components were evaluated: Whether Quantum Inspired models of Target Activation would provide a better framework than their classical psychological counterparts and how robust these models are across the different sources of Free Association data. In previous work, a formal model of cued-target recall did not exist and as such Target Activation was unable to be assessed directly. Further to that, the data source used was suspected of suffering from temporal and geographical bias. As a consequence, Target Activation was measured against cued-target recall data as an approximation of performance. Since then, a formal model of cued-target recall (PIER3) has been developed [10] with alternative sources of data also becoming available. This allowed us to directly model target activation in cued-target recall with human cued-target recall pairs and use multiply sources of Free Association Data. Featural Characteristics known to be important to Target Activation were measured for each of the data sources to identify any major differences that may explain variations in performance for each of the models. Each of the activation models were used in the PIER3 memory model for each of the data sources and was benchmarked against cued-target recall pairs provided by the University of South Florida (USF). Two methods where used to evaluate performance. The first involved measuring the divergence between the sets of results using the Kullback Leibler (KL) divergence with the second utilizing a previous statistical analysis of the errors [9]. Of the three sources of data, two were sourced from human subjects being the USF Free Association Norms and the University of Leuven (UL) Free Association Networks. The third was sourced from a new method put forward by Galea and Bruza, 2015 in which pseudo Free Association Networks (Corpus Based Association Networks - CANs) are built using co-occurrence statistics on large text corpus. It was found that the Quantum Inspired Models of Target Activation not only outperformed the classical psychological model but was more robust across a variety of data sources.

Kallikrein-related peptidase 4 activation of protease-activated receptor family members and association with prostate cancer

Two areas of particular importance in prostate cancer progression are primary tumour development and metastasis. These processes involve a number of physiological events, the mediators of which are still being discovered and characterised. Serine proteases have been shown to play a major role in cancer invasion and metastasis. The recently discovered phenomenon of their activation of a receptor family known as the protease activated receptors (PARs) has extended their physiological role to that of signaling molecule. Several serine proteases are expressed by malignant prostate cancer cells, including members of the kallikreinrelated peptidase (KLK) serine protease family, and increasingly these are being shown to be associated with prostate cancer progression. KLK4 is highly expressed in the prostate and expression levels increase during prostate cancer progression. Critically, recent studies have implicated KLK4 in processes associated with cancer. For example, the ectopic over-expression of KLK4 in prostate cancer cell lines results in an increased ability of these cells to form colonies, proliferate and migrate. In addition, it has been demonstrated that KLK4 is a potential mediator of cellular interactions between prostate cancer cells and osteoblasts (bone forming cells). The ability of KLK4 to influence cellular behaviour is believed to be through the selective cleavage of specific substrates. Identification of relevant in vivo substrates of KLK4 is critical to understanding the pathophysiological roles of this enzyme. Significantly, recent reports have demonstrated that several members of the KLK family are able to activate PARs. The PARs are relatively new members of the seven transmembrane domain containing G protein coupled receptor (GPCR) family. PARs are activated through proteolytic cleavage of their N-terminus by serine proteases, the resulting nascent N-terminal binds intramolecularly to initiate receptor activation. PARs are involved in a number of patho-physiological processes, including vascular repair and inflammation, and a growing body of evidence suggests roles in cancer. While expression of PAR family members has been documented in several types of cancers, including prostate, the role of these GPCRs in prostate cancer development and progression is yet to be examined. Interestingly, several studies have suggested potential roles in cellular invasion through the induction of cytoskeletal reorganisation and expression of basement membrane-degrading enzymes. Accordingly, this program of research focussed on the activation of the PARs by the prostate cancer associated enzyme KLK4, cellular processing of activated PARs and the expression pattern of receptor and agonist in prostate cancer. For these studies KLK4 was purified from the conditioned media of stably transfected Sf9 insect cells expressing a construct containing the complete human KLK4 coding sequence in frame with a V5 epitope and poly-histidine encoding sequences. The first aspect of this study was the further characterisation of this recombinant zymogen form of KLK4. The recombinant KLK4 zymogen was demonstrated to be activatable by the metalloendopeptidase thermolysin and amino terminal sequencing indicated that thermolysin activated KLK4 had the predicted N-terminus of mature active KLK4 (31IINED). Critically, removal of the pro-region successfully generated a catalytically active enzyme, with comparable activity to a previously published recombinant KLK4 produced from S2 insect cells. The second aspect of this study was the activation of the PARs by KLK4 and the initiation of signal transduction. This study demonstrated that KLK4 can activate PAR-1 and PAR-2 to mobilise intracellular Ca2+, but failed to activate PAR-4. Further, KLK4 activated PAR-1 and PAR-2 over distinct concentration ranges, with KLK4 activation and mobilisation of Ca2+ demonstrating higher efficacy through PAR-2. Thus, the remainder of this study focussed on PAR-2. KLK4 was demonstrated to directly cleave a synthetic peptide that mimicked the PAR-2 Nterminal activation sequence. Further, KLK4 mediated Ca2+ mobilisation through PAR-2 was accompanied by the initiation of the extra-cellular regulated kinase (ERK) cascade. The specificity of intracellular signaling mediated through PAR-2 by KLK4 activation was demonstrated by siRNA mediated protein depletion, with a reduction in PAR-2 protein levels correlating to a reduction in KLK4 mediated Ca2+mobilisation and ERK phosphorylation. The third aspect of this study examined cellular processing of KLK4 activated PAR- 2 in a prostate cancer cell line. PAR-2 was demonstrated to be expressed by five prostate derived cell lines including the prostate cancer cell line PC-3. It was also demonstrated by flow cytometry and confocal microscopy analyses that activation of PC-3 cell surface PAR-2 by KLK4 leads to internalisation of this receptor in a time dependent manner. Critically, in vivo relevance of the interaction between KLK4 and PAR-2 was established by the observation of the co-expression of receptor and agonist in primary prostate cancer and prostate cancer bone lesion samples by immunohistochemical analysis. Based on the results of this study a number of exciting future studies have been proposed, including, delineating differences in KLK4 cellular signaling via PAR-1 and PAR-2 and the role of PAR-1 and PAR-2 activation by KLK4 in prostate cancer cells and bone cells in prostate cancer progression.

Power of QTL detection using association tests with family controls

The power of testing for a population-wide association between a biallelic quantitative trait locus and a linked biallelic marker locus is predicted both empirically and deterministically for several tests. The tests were based on the analysis of variance (ANOVA) and on a number of transmission disequilibrium tests (TDT). Deterministic power predictions made use of family information, and were functions of population parameters including linkage disequilibrium, allele frequencies, and recombination rate. Deterministic power predictions were very close to the empirical power from simulations in all scenarios considered in this study. The different TDTs had very similar power, intermediate between one-way and nested ANOVAs. One-way ANOVA was the only test that was not robust against spurious disequilibrium. Our general framework for predicting power deterministically can be used to predict power in other association tests. Deterministic power calculations are a powerful tool for researchers to plan and evaluate experiments and obviate the need for elaborate simulation studies.

No evidence for association of ataxia-telangiectasia mutated gene T2119C and C3161G amino acid substitution variants with risk of breast cancer

Background There is evidence that certain mutations in the double-strand break repair pathway ataxia-telangiectasia mutated gene act in a dominant-negative manner to increase the risk of breast cancer. There are also some reports to suggest that the amino acid substitution variants T2119C Ser707Pro and C3161G Pro1054Arg may be associated with breast cancer risk. We investigate the breast cancer risk associated with these two nonconservative amino acid substitution variants using a large Australian population-based case–control study. Methods The polymorphisms were genotyped in more than 1300 cases and 600 controls using 5' exonuclease assays. Case–control analyses and genotype distributions were compared by logistic regression. Results The 2119C variant was rare, occurring at frequencies of 1.4 and 1.3% in cases and controls, respectively (P = 0.8). There was no difference in genotype distribution between cases and controls (P = 0.8), and the TC genotype was not associated with increased risk of breast cancer (adjusted odds ratio = 1.08, 95% confidence interval = 0.59–1.97, P = 0.8). Similarly, the 3161G variant was no more common in cases than in controls (2.9% versus 2.2%, P = 0.2), there was no difference in genotype distribution between cases and controls (P = 0.1), and the CG genotype was not associated with an increased risk of breast cancer (adjusted odds ratio = 1.30, 95% confidence interval = 0.85–1.98, P = 0.2). This lack of evidence for an association persisted within groups defined by the family history of breast cancer or by age. Conclusion The 2119C and 3161G amino acid substitution variants are not associated with moderate or high risks of breast cancer in Australian women.

Creating and enabling opportunities for increased student participation in experience based learning in professional practice

This paper explores models for enabling increased participation in experience based learning in legal professional practice. Legal placements as part of “for-credit” units offer students the opportunity to develop their professional skills in practice, reflect on their learning and job performance and take responsibility for their career development and planning. In short, work integrated learning (WIL) in law supports students in making the transition from university to practice. Despite its importance, WIL has traditionally taken place in practical legal training courses (after graduation) rather than during undergraduate law courses. Undergraduate WIL in Australian law schools has generally been limited to legal clinics which require intensive academic supervision, partnerships with community legal organisations and government funding. This paper will propose two models of WIL for undergraduate law which may overcome many of the challenges to engaging in WIL in law (which are consistent with those identified generally by the WIL Report). The first is a virtual law placement in which students use technology to complete a real world project in a virtual workplace under the guidance of a workplace supervisor. The second enables students to complete placements in private legal firms, government legal offices, or community legal centres under the supervision of a legal practitioner. The units complement each other by a) creating and enabling placement opportunities for students who may not otherwise have been able to participate in work placement by reason of family responsibilities, financial constraints, visa restrictions, distance etc; and b) enabling students to capitalise on existing work experience. This paper will report on the pilot offering of the units in 2008, the evaluation of the models and changes implemented in 2009. It will conclude that this multi-pronged approach can be successful in creating opportunities for, and overcoming barriers to participation in experiential learning in legal professional practice.

Augmenting RatSLAM using FAB-MAP-based visual data association

This paper investigates the use of the FAB-MAP appearance-only SLAM algorithm as a method for performing visual data association for RatSLAM, a semi-metric full SLAM system. While both systems have shown the ability to map large (60-70km) outdoor locations of approximately the same scale, for either larger areas or across longer time periods both algorithms encounter difficulties with false positive matches. By combining these algorithms using a mapping between appearance and pose space, both false positives and false negatives generated by FAB-MAP are significantly reduced during outdoor mapping using a forward-facing camera. The hybrid FAB-MAP-RatSLAM system developed demonstrates the potential for successful SLAM over large periods of time.

A new family of Marx generator based on resonant converter

This paper presents a novel topology to generate high voltage with utilization of slow and fast power switches. New concepts used in this topology include numbers of diode-capacitor units in parallel with resonant circuits which are connected to a positive buck-boost converter. The resonant circuit reverses the voltage polarity of the capacitors. This configuration has capability of generating a flexible high voltage with certain number of capacitors. The advantage of this topology is to use slow switches, less number of diodes and capacitors compare to Marx generator. Simulations have been performed to verify the proposed topology.

Repeat participation in colorectal cancer screening utilizing fecal occult blood testing : a community-based project in a rural setting

Background and Aim: To investigate participation in a second round of colorectal cancer screening using a fecal occult blood test (FOBT) in an Australian rural community, and to assess the demographic characteristics and individual perspectives associated with repeat screening. ---------- Methods: Potential participants from round 1 (50–74 years of age) were sent an intervention package and asked to return a completed FOBT (n = 3406). Doctors of participants testing positive referred to colonoscopy as appropriate. Following screening, 119 participants completed qualitative telephone interviews. Multivariable logistic regression models evaluated the association between round-2 participation and other variables.---------- Results: Round-2 participation was 34.7%; the strongest predictor was participation in round 1. Repeat participants were more likely to be female; inconsistent screeners were more likely to be younger (aged 50–59 years). The proportion of positive FOBT was 12.7%, that of colonoscopy compliance was 98.6%, and the positive predictive value for cancer or adenoma of advanced pathology was 23.9%. Reasons for participation included testing as a precautionary measure or having family history/friends with colorectal cancer; reasons for non-participation included apathy or doctors’ advice against screening.---------- Conclusion: Participation was relatively low and consistent across rounds. Unless suitable strategies are identified to overcome behavioral trends and/or to screen out ineligible participants, little change in overall participation rates can be expected across rounds.

A new family of Marx generators based on commutation circuits

This paper presents a novel topology for the generation of high voltage pulses that uses both slow and fast solid-state power switches. This topology includes diode-capacitor units in parallel with commutation circuits connected to a positive buck-boost converter. This enables the generation of a range of high output voltages with a given number of capacitors. The advantages of this topology are the use of slow switches and a reduced number of diodes in comparison with conventional Marx generator. Simulations performed for single and repetitive pulse generation and experimental tests of a prototype hardware verify the proposed topology.

Perioperative mortality after hemiarthroplasty related to fixation method : a study based on the Australian Orthopaedic Association National Joint Replacement Registry

Background and purpose: The appropriate fixation method for hemiarthroplasty of the hip as it relates to implant survivorship and patient mortality is a matter of ongoing debate. We examined the influence of fixation method on revision rate and mortality.----- ----- Methods: We analyzed approximately 25,000 hemiarthroplasty cases from the AOA National Joint Replacement Registry. Deaths at 1 day, 1 week, 1 month, and 1 year were compared for all patients and among subgroups based on implant type.----- ----- Results: Patients treated with cemented monoblock hemiarthroplasty had a 1.7-times higher day-1 mortality compared to uncemented monoblock components (p < 0.001). This finding was reversed by 1 week, 1 month, and 1 year after surgery (p < 0.001). Modular hemiarthroplasties did not reveal a difference in mortality between fixation methods at any time point.----- ----- Interpretation: This study shows lower (or similar) overall mortality with cemented hemiarthroplasty of the hip.

Non-redundant sequential association rule mining based on closed sequential patterns

In many applications, e.g., bioinformatics, web access traces, system utilisation logs, etc., the data is naturally in the form of sequences. People have taken great interest in analysing the sequential data and finding the inherent characteristics or relationships within the data. Sequential association rule mining is one of the possible methods used to analyse this data. As conventional sequential association rule mining very often generates a huge number of association rules, of which many are redundant, it is desirable to find a solution to get rid of those unnecessary association rules. Because of the complexity and temporal ordered characteristics of sequential data, current research on sequential association rule mining is limited. Although several sequential association rule prediction models using either sequence constraints or temporal constraints have been proposed, none of them considered the redundancy problem in rule mining. The main contribution of this research is to propose a non-redundant association rule mining method based on closed frequent sequences and minimal sequential generators. We also give a definition for the non-redundant sequential rules, which are sequential rules with minimal antecedents but maximal consequents. A new algorithm called CSGM (closed sequential and generator mining) for generating closed sequences and minimal sequential generators is also introduced. A further experiment has been done to compare the performance of generating non-redundant sequential rules and full sequential rules, meanwhile, performance evaluation of our CSGM and other closed sequential pattern mining or generator mining algorithms has also been conducted. We also use generated non-redundant sequential rules for query expansion in order to improve recommendations for infrequently purchased products.