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Australia has played an important role in the development of potable reuse internationally. Most significantly, Australia was the first country to develop national water quality guidelines specifically for this purpose. This has recently been followed-up with the development of detailed protocols for the validation of treatment performance for a number of key advanced water treatment processes. Nonetheless, the successes of potable reuse projects, which have been proposed for development in Australia, have been variable. An important groundwater replenishment project is now operational in Perth, Western Australia. However, what was to be a similarly important reservoir-augmentation project in South East Queensland is currently idle. A smaller scheme in Sydney, New South Wales, produces highly treated reclaimed water for river-flow augmentation upstream of a drinking water offtake. Each of these projects has contributed to technical skills and provided important research opportunities. Key research topics and outcomes are described here. Finally, prospects for the future role of potable reuse in Australia are considered.

We measure the conductivity of neutral fermions in a cubic optical lattice. Using in-situ fluorescence microscopy, we observe the alternating current resultant from a single-frequency uniform force applied by displacement of a weak harmonic trapping potential. In the linear response regime, a neutral-particle analogue of Ohm's law gives the conductivity as the ratio of total current to force. For various lattice depths, temperatures, interaction strengths, and fillings, we measure both real and imaginary conductivity, up to a frequency sufficient to capture the transport dynamics within the lowest band. The spectral width of the real conductivity reveals the current dissipation rate in the lattice, and the integrated spectral weight is related to thermodynamic properties of the system through a sum rule. The global conductivity decreases with increased band-averaged effective mass, which at high temperatures approaches a T-linear regime. Relaxation of current is observed to require a finite lattice depth, which breaks Galilean invariance and enables damping through collisions between fermions.

Ageing is the biggest risk factor for cardiovascular health and is associated with increased incidence of cardiovascular disease. Cellular senescence, a process driven in part by telomere shortening, has been implicated in age-related tissue dysfunction. Here, we address the question of how senescence is induced in rarely dividing/post-mitotic cardiomyocytes and investigate if clearance of senescent cells attenuates age related cardiac dysfunction. During ageing, human and murine cardiomyocytes acquire a senescent-like phenotype characterised by persistent DNA damage at telomere regions that can be driven by mitochondrial dysfunction, and crucially can occur independently of cell-division and telomere length. Length-independent telomere damage in cardiomyocytes activates the classical senescence-inducing pathways, p21CIPand p16INK4aand results in a non-canonical senescence-associated secretory phenotype. Pharmacological or genetic clearance of senescent cells in mice alleviates myocardial hypertrophy and fibrosis, detrimental features of cardiac ageing, and promotes cardiomyocyte regeneration. Our data describes a mechanism by which senescence can occur and contribute to ageing in post-mitotic tissues.

Ageing is the biggest risk factor for impaired cardiovascular health, cardiovascular disease being the leading cause of death in 40% of individuals over 65 years old. Ageing is associated not only with an increased prevalence of cardiovascular disease but also with a poorer prognosis, including increased mortality or incidence of heart failure after myocardial infarction (MI). We have demonstrated that aged (23 month old) mice have an accumulation of cardiomyocyte senescence, reduced regenerative potential and display increased mortality as well as impaired recovery following MI. Cellular senescence is defined not only by the irreversible loss of division potential but also by the production of a senescence-associated secretory phenotype (SASP). This cocktail of pro-inflammatory cytokines, chemokines, matrix proteases and growth factors can impact on tissue function, inducing fibrosis, extracellular matrix degeneration and driving inflammation. We have therefore begun to test if clearance of senescent cardiomyocytes, using the senolytic compound Navitoclax, has the potential to improve cardiac health and post MI outcomes in aged animals. Following treatment with Navitoclax, but prior to MI, aged mice demonstrated a reduction in senescent cardiomyocytes which was associated increased cardiomyocyte generation, a decline in myocardial hypertrophy and a decrease in fibrosis. Following MI, Navitoclax treated mice displayed a tendency towards improved survival and had a significant improvement in cardiac function when compared to vehicle controls. We conclude that clearance of senescent cells is a potential therapeutic strategy for the treatment of age related cardiac dysfunction.

Inhibiting MAPK14 (p38α) diminishes cardiac damage in myocardial ischemia. During myocardial ischemia, p38α interacts with TAB1, a scaffold protein, which promotes p38α autoactivation; active p38α (pp38α) then transphosphorylates TAB1. Previously, we solved the X-ray structure of the p38α-TAB1 (residues 384-412) complex. Here, we further characterize the interaction by solving the structure of the pp38α-TAB1 (residues 1-438) complex in the active state. Based on this information, we created a global knock-in (KI) mouse with substitution of 4 residues on TAB1 that we show are required for docking onto p38α. Whereas ablating p38α or TAB1 resulted in early embryonal lethality, the TAB1-KI mice were viable and had no appreciable alteration in their lymphocyte repertoire or myocardial transcriptional profile; nonetheless, following in vivo regional myocardial ischemia, infarction volume was significantly reduced and the transphosphorylation of TAB1 was disabled. Unexpectedly, the activation of myocardial p38α during ischemia was only mildly attenuated in TAB1-KI hearts. We also identified a group of fragments able to disrupt the interaction between p38α and TAB1. We conclude that the interaction between the 2 proteins can be targeted with small molecules. The data reveal that it is possible to selectively inhibit signaling downstream of p38α to attenuate ischemic injury.

Cellular senescence has been associated with the structural and functional decline observed during physiological lung aging and in chronic obstructive pulmonary disease (COPD). Airway epithelial cells are the first line of defense in the lungs and are important to COPD pathogenesis. However, the mechanisms underlying airway epithelial cell senescence, and particularly the role of telomere dysfunction in this process, are poorly understood. We aimed to investigate telomere dysfunction in airway epithelial cells from patients with COPD, in the aging murine lung and following cigarette smoke exposure. We evaluated colocalization of γ-histone protein 2A.X and telomeres and telomere length in small airway epithelial cells from patients with COPD, during murine lung aging, and following cigarette smoke exposure in vivo and in vitro. We found that telomere-associated DNA damage foci increase in small airway epithelial cells from patients with COPD, without significant telomere shortening detected. With age, telomere-associated foci increase in small airway epithelial cells of the murine lung, which is accelerated by cigarette smoke exposure. Moreover, telomere-associated foci predict age-dependent emphysema, and late-generation Terc null mice, which harbor dysfunctional telomeres, show early-onset emphysema. We found that cigarette smoke accelerates telomere dysfunction via reactive oxygen species in vitro and may be associated with ataxia telangiectasia mutated-dependent secretion of inflammatory cytokines interleukin-6 and -8. We propose that telomeres are highly sensitive to cigarette smoke-induced damage, and telomere dysfunction may underlie decline of lung function observed during aging and in COPD.

Simulation software for medical linear accelerators that can be used in a teaching environment was developed. The components of linear accelerators were modeled to first order accuracy using analytical expressions taken from the literature. The expressions used constants that were empirically set such that realistic response could be expected. These expressions were programmed in a MATLAB environment with a graphical user interface in order to produce an environment similar to that of linear accelerator service mode. The program was evaluated in a systematic fashion, where parameters affecting the clinical properties of medical linear accelerator beams were adjusted independently, and the effects on beam energy and dose rate recorded. These results confirmed that beam tuning adjustments could be simulated in a simple environment. Further, adjustment of service parameters over a large range was possible, and this allows the demonstration of linear accelerator physics in an environment accessible to both medical physicists and linear accelerator service engineers. In conclusion, a software tool, named SIMAC, was developed to improve the teaching of linear accelerator physics in a simulated environment. SIMAC performed in a similar manner to medical linear accelerators. The authors hope that this tool will be valuable as a teaching tool for medical physicists and linear accelerator service engineers. PACS number: 87.55Gh, 87.56bd

Cardiovascular disease (CVD) is the leading cause of death globally. Although the number one risk factor for CVD is age, the detrimental biological processes that occur in the heart during ageing remain elusive. It is therefore vitality important to understand the fundamental mechanisms driving heart ageing to enable the development of preventions and treatments targeting these processes. Cellular senescence has been described more than fifty years ago as the irreversible cell-cycle arrest which occurs in somatic cells. Emerging evidence suggests that cellular senescence plays a key role in heart ageing, however the cell-types involved and the underlying mechanisms are not yet elucidated. In this review we discuss the current understanding of how mechanisms known to contribute to senescence impact on heart ageing and CVD. Finally, we will review recent data suggesting that targeting senescent cells may be a viable therapy to counteract the ageing of the heart.

We demonstrate fluorescence microscopy of individual fermionic potassium atoms in a 527-nm-period optical lattice. Using electromagnetically induced transparency (EIT) cooling on the 770.1-nm D$_1$ transition of $^{40}$K, we find that atoms remain at individual sites of a 0.3-mK-deep lattice, with a $1/e$ pinning lifetime of $67(9)\,\rm{s}$, while scattering $\sim 10^3$ photons per second. The plane to be imaged is isolated using microwave spectroscopy in a magnetic field gradient, and can be chosen at any depth within the three-dimensional lattice. With a similar protocol, we also demonstrate patterned selection within a single lattice plane. High resolution images are acquired using a microscope objective with 0.8 numerical aperture, from which we determine the occupation of lattice sites in the imaging plane with 94(2)\% fidelity per atom. Imaging with single-atom sensitivity and addressing with single-site accuracy are key steps towards the search for unconventional superfluidity of fermions in optical lattices, the initialization and characterization of transport and non-equilibrium dynamics, and the observation of magnetic domains.

Telomeres are specialized nucleoprotein structures, which protect chromosome ends and have been implicated in the ageing process. Telomere shortening has been shown to contribute to a persistent DNA damage response (DDR) during replicative senescence, the irreversible loss of division potential of somatic cells. Similarly, persistent DDR foci can be found in stress-induced senescence, although their nature is not understood. Here we show, using immuno-fluorescent in situ hybridization and ChIP, that up to half of the DNA damage foci in stress-induced senescence are located at telomeres irrespective of telomerase activity. Moreover, live-cell imaging experiments reveal that all persistent foci are associated with telomeres. Finally, we report an age-dependent increase in frequencies of telomere-associated foci in gut and liver of mice, occurring irrespectively of telomere length. We conclude that telomeres are important targets for stress in vitro and in vivo and this has important consequences for the ageing process.