Estimating outflow facility through pressure dependent pathways of the human eye

We develop and test a new theory for pressure dependent outflow from the eye. The theory comprises three main parameters: (i) a constant hydraulic conductivity, (ii) an exponential decay constant and (iii) a no-flow intraocular pressure, from which the total pressure dependent outflow, average outflow facilities and local outflow facilities for the whole eye may be evaluated. We use a new notation to specify precisely the meaning of model parameters and so model outputs. Drawing on a range of published data, we apply the theory to animal eyes, enucleated eyes and in vivo human eyes, and demonstrate how to evaluate model parameters. It is shown that the theory can fit high quality experimental data remarkably well. The new theory predicts that outflow facilities and total pressure dependent outflow for the whole eye are more than twice as large as estimates based on the Goldman equation and fluorometric analysis of anterior aqueous outflow. It appears likely that this discrepancy can be largely explained by pseudofacility and aqueous flow through the retinal pigmented epithelium, while any residual discrepancy may be due to pathological processes in aged eyes. The model predicts that if the hydraulic conductivity is too small, or the exponential decay constant is too large, then intraocular eye pressure may become unstable when subjected to normal circadian changes in aqueous production. The model also predicts relationships between variables that may be helpful when planning future experiments, and the model generates many novel testable hypotheses. With additional research, the analysis described here may find application in the differential diagnosis, prognosis and monitoring of glaucoma

Bone balance within a cortical BMU: Local controls of bone resorption and formation

Maintaining bone volume during bone turnover by a BMU is known as bone balance. Balance is required to maintain structural integrity of the bone and is often dysregulated in disease. Consequently, understanding how a BMU controls bone balance is of considerable interest. This paper develops a methodology for identifying potential balance controls within a single cortical BMU. The theoretical framework developed offers the possibility of a directed search for biological processes compatible with the constraints of balance control. We first derive general control constraint equations and then introduce constitutive equations to identify potential control processes that link key variables that describe the state of the BMU. The paper describes specific local bone volume balance controls that may be associated with bone resorption and bone formation. Because bone resorption and formation both involve averaging over time, short-term fluctuations in the environment are removed, leaving the control systems to manage deviations in longer-term trends back towards their desired values. The length of time for averaging is much greater for bone formation than for bone resorption, which enables more filtering of variability in the bone formation environment. Remarkably, the duration for averaging of bone formation may also grow to control deviations in long-term trends of bone formation. Providing there is sufficient bone formation capacity by osteoblasts, this leads to an extraordinarily robust control mechanism that is independent of either osteoblast number or the cellular osteoid formation rate. A complex picture begins to emerge for the control of bone volume. Different control relationships may achieve the same objective, and the ‘integration of information’ occurring within a BMU may be interpreted as different sets of BMU control systems coming to the fore as different information is supplied to the BMU, which in turn leads to different observable BMU behaviors

Petrography and Geochemistry of Metals in Almahata Sitta Ureilites

Ureilites are ultramafic achondrites, predominantly composed of olivine and pyroxenes with accessory carbon, metal and sulfide. The majority of ureilites are believed to represent the mantle of the ureilite parent body (UPB) [1]. Although ureilites have lost much of their original metal [2], the metal that remains retains a record of the formative processes. Almahata Sitta is predominantly composed of unbrecciated ureilites with a wide range of silicate compositions [3,4]. As a fall it presents a rare opportunity to examine fresh ureilite metal in-situ, and analyzing their highly siderophile element (HSE) ratios gives clues to their formation. Bulk siderophile element analyses of Almahata Sitta fall within the range observed in other ureilites [5]. We have examined the metals in seven ureilitic samples of Almahata Sitta (AS) and one associated chondrite fragment (AS#25)

Estimating outflow facility parameters for the human eye using hypotensive pressure-time data

We have previously developed a new theory for pressure dependent outflow from the human eye, and tested the model using experimental data at intraocular pressures above normal eye pressures. In this paper, we use our model to analyze a hypotensive pressure-time dataset obtained following application of a Honan balloon. Here we show that the hypotensive pressure-time data can be successfully analyzed using our proposed pressure dependent outflow model. When the most uncertain initial data point is removed from the dataset, then parameter estimates are close to our previous parameter estimates, but clearly parameter estimates are very sensitive to assumptions. We further show that (i) for a measured intraocular pressure-time curve, the estimated model parameter for whole eye surface hydraulic conductivity is primarily a function of the ocular rigidity, and (ii) the estimated model parameter that controls the rate of decrease of outflow with increasing pressure is primarily a function of the convexity of the monotonic pressure-time curve. Reducing parameter uncertainty could be accomplished using new technologies to obtain higher quality datasets, and by gathering additional data to better define model parameter ranges for the normal eye. With additional research, we expect the pressure dependent outflow analysis described herein may find applications in the differential diagnosis, prognosis and monitoring of the glaucomatous eye

Ultra-fast calorimetry study of Ge₂Sb₂Te₅ crystallization between dielectric layers

Phase changes in chalcogenides such as Ge2Sb2Te5 can be exploited in non-volatile random-access memory, with fast crystallization crucial for device operation. Ultra-fast differential scanning calorimetry, heating at rates up to 40,000K s-1, has been used to study the crystallization of amorphous Ge2Sb2Te5 with and without sandwich layers of ZnS-SiO2. At heating rates up to 1000K s-1, the sandwich layers retard crystallization, an effect attributed to crystallization-induced stress. At greater heating rates (>or = 5000K s-1), and consequently higher crystallization temperatures, the stress is relaxed, and sandwich layers catalyze crystallization. Implications for memory-device performance are discussed

Time evolution of deformation in a human cartilage under cyclic loading

Recent imaging has revealed that in vivo contact deformations of human knee cartilage under physiological loadings are surprisingly large—typically on the order of 10%, but up to 20 or 30% of tibiofemora cartilage thickness depending on loading conditions. In this paper we develop a biphasic, large deformation, non-linear poroelastic model of cartilage that can accurately represent the time dependence and magnitude of cyclic cartilage deformations in vivo. The model takes into account cartilage tension–compression nonlinearity and a new constitutive relation in which the compressive stiffness and hydraulic permeability of the cartilage adjusts in response to the strain-dependent aggrecan concentration. The model predictions are validated using experimental test results on osteochondral plugs obtained from human cadavers. We find that model parameters can be optimised to give an excellent fit to the experimental data. Using typical hydraulic conductivity and stiffness parameters for healthy cartilage, we find that the experimentally observed transient and steady state tissue deformations under cyclic loading and unloading can be reproduced by the model. Steady state tissue deformations are shown to cycle between 10% (exudation strain) and 20% (total strain) in response to the cyclic test loads. At steady-state cyclic loading, the pore fluid exuded from the tissue is exactly equal to the pore fluid imbibed by the tissue during each load cycle

Embracing conservation success of recovering humpback whale populations: Evaluating the case for downlisting their conservation status in Australia

Optimism and hope in conservation biology are supported by examples of endangered species recovery, such as the population growth observed in humpback whales in several of the world's oceans. In Australia, monitoring data suggest rapid recovery for both east and west coast populations, which are now larger than 50% of their pre-whaling abundance. The measured growth rates exceed known species trends worldwide and have no indication of diminishing. Under Australian Commonwealth legislation and regulations, these populations should be considered for downlisting, as they are not eligible for listing as a threatened species against all statutory criteria. A change in conservation status will produce new challenges for the conservation and management of a recovered species, especially with the Australian economic landscape experiencing large-scale growth and development in recent years. More importantly, a recovered humpback whale population may bring a positive shift in the research goals and objectives throughout Australia by ensuring other endangered species an equal chance of recovery while delivering hope, optimism, and an opportunity to celebrate a conservation success

Cell organisation in the colonic crypt: A theoretical comparison of the pedigree and niche concepts

The intestinal mucosa is a monolayer of rapidly self-renewing epithelial cells which is not only responsible for absorption of water and nutrients into the bloodstream but also acts as a protective barrier against harmful microbes entering the body. New functional epithelial cells are produced from stem cells, and their proliferating progeny. These stem cells are found within millions of crypts (tubular pits) spaced along the intestinal tract. The entire intestinal epithelium is replaced every 2–3 days in mice (3–5 days in humans) and hence cell production, differentiation, migration and turnover need to be tightly regulated. Malfunctions in this regulation are strongly linked to inflammatory bowel diseases and to the formation of adenomas and ultimately cancerous tumours. Despite a great deal of biological experimentation and observation, precisely how colonic crypts are regulated to produce mature colonocytes remains unclear. To assist in understanding how cell organisation in crypts is achieved, two very different conceptual models of cell behaviour are developed here, referred to as the ‘pedigree’ and the ‘niche’ models. The pedigree model proposes that crypt cells are largely preprogrammed and receive minimal prompting from the environment as they move through a routine of cell differentiation and proliferation to become mature colonocytes. The niche model proposes that crypt cells are primarily influenced by the local microenvironments along the crypt, and that predetermined cell behaviour plays a negligible role in their development. In this paper we present a computational model of colonic crypts in the mouse, which enables a comparison of the quality and controllability of mature coloncyte production by crypts operating under these two contrasting conceptual models of crypt regulation