Choosing an appropriate modelling framework for analysing multispecies co-culture cell biology experiments

In vitro cell biology assays play a crucial role in informing our understanding of the migratory, proliferative and invasive properties of many cell types in different biological contexts. While mono-culture assays involve the study of a population of cells composed of a single cell type, co-culture assays study a population of cells composed of multiple cell types (or subpopulations of cells). Such co-culture assays can provide more realistic insights into many biological processes including tissue repair, tissue regeneration and malignant spreading. Typically, system parameters, such as motility and proliferation rates, are estimated by calibrating a mathematical or computational model to the observed experimental data. However, parameter estimates can be highly sensitive to the choice of model and modelling framework. This observation motivates us to consider the fundamental question of how we can best choose a model to facilitate accurate parameter estimation for a particular assay. In this work we describe three mathematical models of mono-culture and co-culture assays that include different levels of spatial detail. We study various spatial summary statistics to explore if they can be used to distinguish between the suitability of each model over a range of parameter space. Our results for mono-culture experiments are promising, in that we suggest two spatial statistics that can be used to direct model choice. However, co-culture experiments are far more challenging: we show that these same spatial statistics which provide useful insight into mono-culture systems are insuffcient for co-culture systems. Therefore, we conclude that great care ought to be exercised when estimating the parameters of co-culture assays.

Indigenous Youth Justice Programs Evaluation

Diversion from the youth justice system is a critical goal for addressing the overrepresentation of Indigenous young people in the criminal justice system. In this report, four programs that were already being implemented by states and territories and identified by them under the National Indigenous Law & Justice Framework as promising practice in diversion are examined. The programs were evaluated, as part of a broader initiative, to determine whether and on what basis they represent good practice (ie are supported by evidence). State and territory governments nominated the programs for evaluation.

Language change in socially structured populations

Language contact is a significant external social factor that impacts on the change in natural languages over time. In some circumstances this corresponds to language competition, in which individuals in a population choose one language over another based on their social interactions. We investigated the dynamics of language change in two initially separate populations of agents that were then mixed with levels of influence determined by the social classes of the two populations, with 16 different combinations tested. As expected, the study found that how the communities interact with each other impacts on the communal language developed. However, it was also found that the acquisition of new words was substantial even with limited interaction between populations and low levels of influence, and that comprehension could be well established across language groups even when production of words from the other language group was low.

Enhancing Raman signal sufficiently for practical sensing applications

Techniques are presented for enhancing weak Raman scattering signals for rapid yet accurate substance detection. Novel surfaces that allow signal enhancement quantification are described as are eye-safe methodologies that maximize the stand-off Raman detection range.

Multi-agent systems for modeling high penetration photovoltaic system impacts in distribution networks

This paper reviews the use of multi-agent systems to model the impacts of high levels of photovoltaic (PV) system penetration in distribution networks and presents some preliminary data obtained from the Perth Solar City high penetration PV trial. The Perth Solar City trial consists of a low voltage distribution feeder supplying 75 customers where 29 consumers have roof top photovoltaic systems. Data is collected from smart meters at each consumer premises, from data loggers at the transformer low voltage (LV) side and from a nearby distribution network SCADA measurement point on the high voltage side (HV) side of the transformer. The data will be used to progressively develop MAS models.

Insurance and transport law : controlling insurance contract terms : Section 54 of the Insurance Contracts Act – compliance, recovery and accountability

Commonwealth legislation covering insurance contracts contains numerous provisions designed to control the operation and effect of terms in life and general insurance contracts. For example, the Life Insurance Act 1995 (Cth) contains provisions regulating the consequences attendant upon incorrect statements in proposals [1] and non-payment of premiums, [2] provides that an insurer may only exclude liability in the case of suicide if it has made express provision for such contingency in its policy, [3] and severely restricts the efficacy of conditions as to war risks. [4] The Insurance Contracts Act 1984 (Cth) is even more intrusive and has a major impact upon contractual provisions in the general insurance field. It is beyond the scope of this note to explore all of these provisions in any detail but examples of controls and constraints imposed upon the operation and effect of contractual provisions include the following. A party is precluded from relying upon a provision in a contract of insurance if such reliance would amount to a failure to act with the utmost good faith. [5] Similarly, a policy provision which requires differences or disputes arising out of the insurance to be submitted to arbitration is void, [6] unless the insurance is a genuine cover for excess of loss over and above another specified insurance. [7] Similarly clause such as conciliation clauses, [8] average clauses, [9] and unusual terms [10] are given qualified operation. [11] However the provision in the Insurance Contracts Act that has the greatest impact upon, and application to, a wide range of insurance clauses and claims is s 54. This section has already generated a significant volume of case law and is the focus of this note. In particular this note examines two recent cases. The first, Johnson v Triple C Furniture and Electrical Pty Ltd [2012] 2 Qd R 337, (hereafter the Triple C case), is a decision of the Queensland Court of Appeal; and the second, Matthew Maxwell v Highway Hauliers Pty Ltd [2013] WASCA 115, (hereafter the Highway Hauliers case), is a decision of the Court of Appeal in Western Australia. This latter decision is on appeal to the High Court of Australia. The note considers too the decision of the New South Wales Court of Appeal in Prepaid Services Pty Ltd v Atradius Credit Insurance NV [2013] NSWCA 252 (hereafter the Prepaid Services case).These cases serve to highlight the complex nature of s 54 and its application, as well as the difficulty in achieving a balance between an insurer and an insured's reasonable expectations.

An unrelated income tax for Australia?

The Australian tax regime for not for profit organisations is notable because of its tolerance of such organisations generating untaxed trading income, unlike the United States and United Kingdom tax regimes. In 2011, the Australian government announced new arrangements for untaxed trading income after a High Court case drew attention to it. This chapter identifies issues experienced on a practical level in the US and the UK, where unrelated business income is taxed, and offers directions for any future Australian attempt to tax this income.

The co-transcriptome of uropathogenic Escherichia coli-infected mouse macrophages reveals new insights into host-pathogen interactions

Urinary tract infections (UTI) are among the most common infections in humans. Uropathogenic Escherichia coli (UPEC) can invade and replicate within bladder epithelial cells, and some UPEC strains can also survive within macrophages. To understand the UPEC transcriptional program associated with intramacrophage survival, we performed host–pathogen co-transcriptome analyses using RNA sequencing. Mouse bone marrow-derived macrophages (BMMs) were challenged over a 24 h time course with two UPEC reference strains that possess contrasting intramacrophage phenotypes: UTI89, which survives in BMMs, and 83972, which is killed by BMMs. Neither of these strains caused significant BMM cell death at the low multiplicity of infection that was used in this study. We developed an effective computational framework that simultaneously separated, annotated, and quantified the mammalian and bacterial transcriptomes. BMMs responded to the two UPEC strains with a broadly similar gene expression program. In contrast, the transcriptional responses of the UPEC strains diverged markedly from each other. We identified UTI89 genes upregulated at 24 h post-infection, and hypothesized that some may contribute to intramacrophage survival. Indeed, we showed that deletion of one such gene (pspA) significantly reduced UTI89 survival within BMMs. Our study provides a technological framework for simultaneously capturing global changes at the transcriptional level in co-cultures, and has generated new insights into the mechanisms that UPEC use to persist within the intramacrophage environment.

Pre-processing for approximate Bayesian computation in image analysis

Most of the existing algorithms for approximate Bayesian computation (ABC) assume that it is feasible to simulate pseudo-data from the model at each iteration. However, the computational cost of these simulations can be prohibitive for high dimensional data. An important example is the Potts model, which is commonly used in image analysis. Images encountered in real world applications can have millions of pixels, therefore scalability is a major concern. We apply ABC with a synthetic likelihood to the hidden Potts model with additive Gaussian noise. Using a pre-processing step, we fit a binding function to model the relationship between the model parameters and the synthetic likelihood parameters. Our numerical experiments demonstrate that the precomputed binding function dramatically improves the scalability of ABC, reducing the average runtime required for model fitting from 71 hours to only 7 minutes. We also illustrate the method by estimating the smoothing parameter for remotely sensed satellite imagery. Without precomputation, Bayesian inference is impractical for datasets of that scale.

Towards a quantitative theory of epidermal calcium profile formation in unwounded skin

We propose and mathematically examine a theory of calcium profile formation in unwounded mammalian epidermis based on: changes in keratinocyte proliferation, fluid and calcium exchange with the extracellular fluid during these cells' passage through the epidermal sublayers, and the barrier functions of both the stratum corneum and tight junctions localised in the stratum granulosum. Using this theory, we develop a mathematical model that predicts epidermal sublayer transit times, partitioning of the epidermal calcium gradient between intracellular and extracellular domains, and the permeability of the tight junction barrier to calcium ions. Comparison of our model's predictions of epidermal transit times with experimental data indicates that keratinocytes lose at least 87% of their volume during their disintegration to become corneocytes. Intracellular calcium is suggested as the main contributor to the epidermal calcium gradient, with its distribution actively regulated by a phenotypic switch in calcium exchange between keratinocytes and extracellular fluid present at the boundary between the stratum spinosum and the stratum granulosum. Formation of the extracellular calcium distribution, which rises in concentration through the stratum granulosum towards the skin surface, is attributed to a tight junction barrier in this sublayer possessing permeability to calcium ions that is less than 15 nm/s in human epidermis and less than 37 nm/s in murine epidermis. Future experimental work may refine the presented theory and reduce the mathematical uncertainty present in the model predictions.

Primary and secondary neural networks of auditory prepulse inhibition: a functional magnetic resonance imaging study of sensorimotor gating of the human acoustic startle response

Feedforward inhibition deficits have been consistently demonstrated in a range of neuropsychiatric conditions using prepulse inhibition (PPI) of the acoustic startle eye-blink reflex when assessing sensorimotor gating. While PPI can be recorded in acutely decerebrated rats, behavioural, pharmacological and psychophysiological studies suggest the involvement of a complex neural network extending from brainstem nuclei to higher order cortical areas. The current functional magnetic resonance imaging study investigated the neural network underlying PPI and its association with electromyographically (EMG) recorded PPI of the acoustic startle eye-blink reflex in 16 healthy volunteers. A sparse imaging design was employed to model signal changes in blood oxygenation level-dependent (BOLD) responses to acoustic startle probes that were preceded by a prepulse at 120 ms or 480 ms stimulus onset asynchrony or without prepulse. Sensorimotor gating was EMG confirmed for the 120-ms prepulse condition, while startle responses in the 480-ms prepulse condition did not differ from startle alone. Multiple regression analysis of BOLD contrasts identified activation in pons, thalamus, caudate nuclei, left angular gyrus and bilaterally in anterior cingulate, associated with EMGrecorded sensorimotor gating. Planned contrasts confirmed increased pons activation for startle alone vs 120-ms prepulse condition, while increased anterior superior frontal gyrus activation was confirmed for the reverse contrast. Our findings are consistent with a primary pontine circuitry of sensorimotor gating that interconnects with inferior parietal, superior temporal, frontal and prefrontal cortices via thalamus and striatum. PPI processes in the prefrontal, frontal and superior temporal cortex were functionally distinct from sensorimotor gating.

Indicator Bats Program: A System for the Global Acoustic Monitoring of Bats

Bats are an important component of mammalian biodiversity and fill such a wide array of ecological niches that they may offer an important multisensory bioindicator role in assessing ecosystem health. There is a need to monitor population trends of bats for their own sake because many populations face numerous environmental threats related to climate change, habitat loss, fragmentation, hunting, and emerging diseases. To be able to establish bat ultrasonic biodiversity trends as a reliable indicator, it is important to standardize monitoring protocols, data management, and analyses. This chapter discusses the main issues to be considered in developing a bat ultrasonic indicator. It focuses on the results from indicator bats program (iBats), a system for the global acoustic monitoring of bats, in Eastern Europe. Finally, the chapter reviews the strengths and weaknesses of the Program and considers the opportunities and threats that it may face in the future.