School of Mathematics and Statistics - Research Publications
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ItemNo Preview AvailableHBO1 (KAT7) Does Not Have an Essential Role in Cell Proliferation, DNA Replication, or Histone 4 Acetylation in Human Cells(American Society for Microbiology, 2020-02-01)HBO1 (MYST2/KAT7) is essential for histone 3 lysine 14 acetylation (H3K14ac) but is dispensable for H4 acetylation and DNA replication in mouse tissues. In contrast, previous studies using small interfering RNA (siRNA) knockdown in human cell lines have suggested that HBO1 is essential for DNA replication. To determine if HBO1 has distinctly different roles in immortalized human cell lines and normal mouse cells, we performed siRNA knockdown of HBO1. In addition, we used CRISPR/Cas9 to generate 293T, MCF7, and HeLa cell lines lacking HBO1. Using both techniques, we show that HBO1 is essential for all H3K14ac in human cells and is unlikely to have a direct effect on H4 acetylation and only has minor effects on cell proliferation. Surprisingly, the loss of HBO1 and H3K14ac in HeLa cells led to the secondary loss of almost all H4 acetylation after 4 weeks. Thus, HBO1 is dispensable for DNA replication and cell proliferation in immortalized human cells. However, while cell proliferation proceeded without HBO1 and H3K14ac, HBO1 gene deletion led to profound changes in cell adhesion, particularly in 293T cells. Consistent with this phenotype, the loss of HBO1 in both 293T and HeLa principally affected genes mediating cell adhesion, with comparatively minor effects on other cellular processes.
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ItemNo Preview AvailableGata-3 Negatively Regulates the Tumor-Initiating Capacity of Mammary Luminal Progenitor Cells and Targets the Putative Tumor Suppressor Caspase-14(AMER SOC MICROBIOLOGY, 2011-11)The transcription factor Gata-3 is a definitive marker of luminal breast cancers and a key regulator of mammary morphogenesis. Here we have explored a role for Gata-3 in tumor initiation and the underlying cellular mechanisms using a mouse model of "luminal-like" cancer. Loss of a single Gata-3 allele markedly accelerated tumor progression in mice carrying the mouse mammary tumor virus promoter-driven polyomavirus middle T antigen (MMTV-PyMT mice), while overexpression of Gata-3 curtailed tumorigenesis. Through the identification of two distinct luminal progenitor cells in the mammary gland, we demonstrate that Gata-3 haplo-insufficiency increases the tumor-initiating capacity of these progenitors but not the stem cell-enriched population. Overexpression of a conditional Gata-3 transgene in the PyMT model promoted cellular differentiation and led to reduced tumor-initiating capacity as well as diminished angiogenesis. Transcript profiling studies identified caspase-14 as a novel downstream target of Gata-3, in keeping with its roles in differentiation and tumorigenesis. A strong association was evident between GATA-3 and caspase-14 expression in preinvasive ductal carcinoma in situ samples, where GATA-3 also displayed prognostic significance. Overall, these studies identify GATA-3 as an important regulator of tumor initiation through its ability to promote the differentiation of committed luminal progenitor cells.
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ItemEvaluation of blood parameters by linear discriminant models for the detection of testosterone administration(WILEY, 2021-07)The steroidal module of the Athlete Biological Passport (ABP) has been used since 2014 for the longitudinal monitoring of urinary testosterone and its metabolites to identify samples suspicious for the use of synthetic forms of Endogenous Anabolic Androgenic Steroids (EAAS). Multiple recent studies have suggested that monitoring of blood parameters may provide enhanced detectability of exogenous testosterone administration. Transdermal and intramuscular testosterone administration studies were carried out in 15 subjects, and the effect on blood steroidal levels, hematological parameters, and gonadotropins was evaluated. Serum testosterone and dihydrotestosterone levels increased while gonadotropin levels were suppressed after administration. A modest increase in reticulocytes was also observed. The blood parameters that were responsive to the administrations were combined into several linear discriminant models targeting both administration (on) and washout (off) phases. The models were effective in detecting the large dose intramuscular administration but were less successful in the detection of the lower dose transdermal application. The blood profiling models may provide complementary value but do not appear to be substantially more advantageous than longitudinal urinary profiling.
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ItemOuter limits of subdifferentials for min–max type functions(Taylor and Francis Group, 2019-07-03)We generalise the outer subdifferential construction suggested by Cánovas, Henrion, L_opez and Parra for max type functions to pointwise minima of regular Lipschitz functions. We also answer an open question about the relation between the outer subdifferential of the support of a regular function and the end set of its subdifferential posed by Li, Meng and Yang.
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ItemNo Preview AvailableOn the Conjecture by Demyanov–Ryabova in Converting Finite Exhausters(Springer, 2017-09)The Demyanov–Ryabova conjecture is a geometric problem originating from duality relations between nonconvex objects. Given a finite collection of polytopes, one obtains its dual collection as convex hulls of the maximal facet of sets in the original collection, for each direction in the space (thus constructing upper convex representations of positively homogeneous functions from lower ones and, vice versa, via Minkowski duality). It is conjectured that an iterative application of this conversion procedure to finite families of polytopes results in a cycle of length at most two. We prove a special case of the conjecture assuming an affine independence condition on the vertices of polytopes in the collection. We also obtain a purely combinatorial reformulation of the conjecture.
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ItemSource-Based Jamming for Physical-Layer Security on Untrusted Full-Duplex Relay(IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC, 2019-05)We address the problem of secure wireless communications over an untrusted full-duplex (FD) relay based on the source jamming scheme. The optimal power allocation between the confidential signal and the jamming signal is derived to maximize the secrecy rate. Then, the corresponding secrecy outage probability (SOP) and the average secrecy rate (ASR) are analyzed. A tight approximation and an asymptotic result are further obtained for the single-antenna destination case both in simple forms. The large-antenna destination case is also analyzed rigorously. Further discussion reveals that transmit-power dependent self-interference has significant negative impact on the secrecy performance.
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ItemNo Preview AvailablePhysical-Layer Security in Full-Duplex Multi-Hop Multi-User Wireless Network With Relay Selection(IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC, 2019-02)This paper investigates the relay selection (RS) problem for multi-hop full-duplex relay networks where multiple source-destination (SD) pairs compete for the same pool of relays, under the attack of multiple eavesdroppers. To enhance the physical-layer security, within a given coherence time, our objective is to jointly assign the available relays at each hop to different SD pairs to maximize the minimum secrecy rate among all pairs. Two RS schemes, optimal RS and suboptimal RS (SRS), are proposed for two-hop networks based on global channel state information (CSI) and only SD pairs CSI, respectively. Since all users can communicate within the same coherence time, our joint RS schemes are important for the user-fairness and ultra-reliable low-latency communications. To evaluate the performance, the exact secrecy outage probability of the SRS scheme is derived under two residual self-interference models. The asymptotic analysis shows that the SRS scheme achieves full diversity. A relay-based jamming scheme is also proposed by using unassigned relays for user communications. Finally, the two-hop RS schemes and the analysis are extended to the general multi-hop network with multiple eavesdroppers. The numerical results reveal interesting fundamental trends where the proposed schemes can significantly enhance the secrecy performance.
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ItemPregnant women maintain body temperatures within safe limits during moderate-intensity aqua-aerobic classes conducted in pools heated up to 33 degrees Celsius: an observational study(AUSTRALIAN PHYSIOTHERAPY ASSOC, 2015-10)QUESTION: What is the body temperature response of healthy pregnant women exercising at moderate intensity in an aqua-aerobics class where the water temperature is in the range of 28 to 33 degrees Celsius, as typically found in community swimming pools? DESIGN: An observational study. PARTICIPANTS: One hundred and nine women in the second and third trimester of pregnancy who were enrolled in a standardised aqua-aerobics class. OUTCOME MEASURES: Tympanic temperature was measured at rest pre-immersion (T1), after 35minutes of moderate-intensity aqua-aerobic exercise (T2), after a further 10minutes of light exercise while still in the water (T3) and finally on departure from the facility (T4). The range of water temperatures in seven indoor community pools was 28.8 to 33.4 degrees Celsius. RESULTS: Body temperature increased by a mean of 0.16 degrees Celsius (SD 0.35, p<0.001) at T2, was maintained at this level at T3 and had returned to pre-immersion resting values at T4. Regression analysis demonstrated that the temperature response was not related to the water temperature (T2 r = -0.01, p = 0.9; T3 r = -0.02, p=0.9; T4 r=0.03, p=0.8). Analysis of variance demonstrated no difference in body temperature response between participants when grouped in the cooler, medium and warmer water temperatures (T2 F=0.94, p=0.40; T3 F=0.93, p=0.40; T4 F=0.70, p=0.50). CONCLUSIONS: Healthy pregnant women maintain body temperatures within safe limits during moderate-intensity aqua-aerobic exercise conducted in pools heated up to 33 degrees Celsius. The study provides evidence to inform guidelines for safe water temperatures for aqua-aerobic exercise during pregnancy.
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ItemA Bayesian method for comparing and combining binary classifiers in the absence of a gold standard.(Springer Science and Business Media LLC, 2012-07-27)BACKGROUND: Many problems in bioinformatics involve classification based on features such as sequence, structure or morphology. Given multiple classifiers, two crucial questions arise: how does their performance compare, and how can they best be combined to produce a better classifier? A classifier can be evaluated in terms of sensitivity and specificity using benchmark, or gold standard, data, that is, data for which the true classification is known. However, a gold standard is not always available. Here we demonstrate that a Bayesian model for comparing medical diagnostics without a gold standard can be successfully applied in the bioinformatics domain, to genomic scale data sets. We present a new implementation, which unlike previous implementations is applicable to any number of classifiers. We apply this model, for the first time, to the problem of finding the globally optimal logical combination of classifiers. RESULTS: We compared three classifiers of protein subcellular localisation, and evaluated our estimates of sensitivity and specificity against estimates obtained using a gold standard. The method overestimated sensitivity and specificity with only a small discrepancy, and correctly ranked the classifiers. Diagnostic tests for swine flu were then compared on a small data set. Lastly, classifiers for a genome-wide association study of macular degeneration with 541094 SNPs were analysed. In all cases, run times were feasible, and results precise. The optimal logical combination of classifiers was also determined for all three data sets. Code and data are available from http://bioinformatics.monash.edu.au/downloads/. CONCLUSIONS: The examples demonstrate the methods are suitable for both small and large data sets, applicable to the wide range of bioinformatics classification problems, and robust to dependence between classifiers. In all three test cases, the globally optimal logical combination of the classifiers was found to be their union, according to three out of four ranking criteria. We propose as a general rule of thumb that the union of classifiers will be close to optimal.
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ItemPsychosocial Well-Being and Functional Outcomes in Youth With Type 1 Diabetes 12 years After Disease Onset(AMER DIABETES ASSOC, 2010-07)OBJECTIVE: Type 1 diabetes in youth and community controls were compared on functional outcomes. Relationships were examined between psychosocial variables at diagnosis and functional outcome 12 years later. RESEARCH DESIGN AND METHODS: Participants were subjects with type 1 diabetes (n = 110, mean age 20.7 years, SD 4.3) and control subjects (n = 76, mean age 20.8 years, SD 4.0). The measures used included the Youth Self-Report and Young Adult Self-Report and a semi-structured interview of functional outcomes. Type 1 diabetes participants also provided information about current diabetes care and metabolic control from diagnosis. RESULTS: Type 1 diabetes participants and control subjects reported similar levels of current well-being but for the youth with type 1 diabetes, the mental health referral rates over the previous 12 years were higher by 19% and school completion rates were lower by 17%. Over one-third of clinical participants were not currently receiving specialist care and this group had higher mental health service usage in the past (61 vs. 33%) and lower current psychosocial well- being. Within the type 1 diabetes group, behavior problems, high activity, and low family cohesion at diagnosis predicted lower current well-being, but were not associated with metabolic control history. Poorer metabolic control was associated with higher mental health service usage. CONCLUSIONS: Type 1 diabetes participants report similar levels of current psychosocial well-being compared with control subjects, but higher levels of psychiatric morbidity since diagnosis and lower school completion rates. Psychiatric morbidity was associated with poor metabolic control and failure to transition to tertiary adult diabetes care.