Scleral matrix metalloproteinases, serine proteinase activity and hydrational capacity are increased in myopia induced by retinal image degradation

In the avian model of myopia, retinal image degradation quickly leads to ocular enlargement. We now give evidence that regionally specific changes in ocular size are correlated with both biomechanical indices of scleral remodeling, e.g. hydration capacity and with biochemical changes in proteinase activities. The latter include a 72 kDa matrix metalloproteinase (putatively MMP-2), other gelatin-binding MMPs, an acid pH MMP and a serine protease. Specifically, we have found that increases in scleral hydrational capacity parallel increases in collagen degrading activities. Gelatin zymography reveals that eyes with 7 days of retinal image degradation have elevated levels (1.4-fold) of gelatinolytic activities at 72 and 67 kDa M(r) in equatorial and posterior pole regions of the sclera while, after 14 days of treatment, increases are no longer apparent. Lower M(r) zymographic activities at 50, 46 and 37 kDa M(r) are collectively increased in eyes treated for both 7 and 14 days (1.4- and 2.4-fold respectively) in the equator and posterior pole areas of enlarging eyes. Western blot analyses of scleral extracts with an antibody to human MMP-2 reveals immunoreactive bands at 65, 30 and 25 kDa. Zymograms incubated under slightly acidic conditions reveal that, in enlarging eyes, MMP activities at 25 and 28 kDa M(r) are increased in scleral equator and posterior pole (1.6- and 4.5-fold respectively). A TIMP-like protein is also identified in sclera and cornea by Western blot analysis. Finally, retinal-image degradation also increases (~2.6-fold) the activity of a 23.5 kDa serine proteinase in limbus, equator and posterior pole sclera that is inhibited by aprotinin and soybean trypsin inhibitor. Taken together, these results indicate that eye growth induced by retinal-image degradation involves increases in the activities of multiple scleral proteinases that could modify the biomechanical properties of scleral structural components and contribute to tissue remodeling and growth.

Binding and degradation of hyaluronan by human breast cancer cell lines expressing different forms of CD44 : correlation with invasive potential

In the present study, we examined a panel of human breast cancer cell lines with regard to their expression of CD44 and ability to bind and degrade hyaluronan. The cell lines expressed varying amounts of different molecular weight forms of CD44 (85-200 kDa) and, in general, those that expressed the greatest amounts of CD44 were the most invasive as judged by in vitro assays. In addition, the ability to bind and degrade hyaluronan was restricted to the cell lines expressing high levels of CD44, and both these functions were blocked by an antibody to CD44 (Hermes-1). Moreover, the rate of [3H]hyaluronan degradation was highly correlated with the amount of CD44 (r = 0.951, P < 0.0001), as well as with the invasive potential of the cells. Scatchard analysis of the [3H]hyaluronan binding of these cells revealed the existence of significant differences in both their binding capacity and their dissociation constant. To determine the source of this deviation, the different molecular weight forms of CD44 were partially separated by gel filtration chromatography. In all cell lines, the 85 kDa form was able to bind hyaluronan, although with different affinities. In contrast, not all of the high molecular weight forms of CD44 had this ability. These results illustrate the diversity of CD44 molecules in invasive tumor cells, and suggest that one of their major functions is to degrade hyaluronan.

Integration of science and monitoring of river ecosystem health to guide investments in catchment protection and rehabilitation

1. Stream ecosystem health monitoring and reporting need to be developed in the context of an adaptive process that is clearly linked to identified values and objectives, is informed by rigorous science, guides management actions and is responsive to changing perceptions and values of stakeholders. To be effective, monitoring programmes also need to be underpinned by an understanding of the probable causal factors that influence the condition or health of important environmental assets and values. This is often difficult in stream and river ecosystems where multiple stressors, acting at different spatial and temporal scales, interact to affect water quality, biodiversity and ecosystem processes. 2. In this article, we describe the development of a freshwater monitoring programme in South East Queensland, Australia, and how this has been used to report on ecosystem health at a regional scale and to guide investments in catchment protection and rehabilitation. We also discuss some of the emerging science needs to identify the appropriate scale and spatial arrangement of rehabilitation to maximise river ecosystem health outcomes and, at the same time, derive other benefits downstream. 3. An objective process was used to identify potential indicators of stream ecosystem health and then test these across a known catchment land-use disturbance gradient. From the 75 indicators initially tested, 22 from five indicator groups (water quality, ecosystem metabolism, nutrient cycling, invertebrates and fish) responded strongly to the disturbance gradient, and 16 were subsequently recommended for inclusion in the monitoring programme. The freshwater monitoring programme was implemented in 2002, funded by local and State government authorities, and currently involves the assessment of over 120 sites, twice per year. This information, together with data from a similar programme on the region's estuarine and coastal marine waters, forms the basis of an annual report card that is presented in a public ceremony to local politicians and the broader community. 4. Several key lessons from the SEQ Healthy Waterways Programme are likely to be transferable to other regional programmes aimed at improving aquatic ecosystem health, including the importance of a shared common vision, the involvement of committed individuals, a cooperative approach, the need for defensible science and effective communication. 5. Thematic implications: this study highlights the use of conceptual models and objective testing of potential indicators against a known disturbance gradient to develop a freshwater ecosystem health monitoring programme that can diagnose the probable causes of degradation from multiple stressors and identify the appropriate spatial scale for rehabilitation or protection. This approach can lead to more targeted management investments in catchment protection and rehabilitation, greater public confidence that limited funds are being well spent and better outcomes for stream and river ecosystem health.

Degradation modeling and monitoring of machines using operation-specific hidden Markov models

In this paper, a novel data-driven approach to monitoring of systems operating under variable operating conditions is described. The method is based on characterizing the degradation process via a set of operation-specific hidden Markov models (HMMs), whose hidden states represent the unobservable degradation states of the monitored system while its observable symbols represent the sensor readings. Using the HMM framework, modeling, identification and monitoring methods are detailed that allow one to identify a HMM of degradation for each operation from mixed-operation data and perform operation-specific monitoring of the system. Using a large data set provided by a major manufacturer, the new methods are applied to a semiconductor manufacturing process running multiple operations in a production environment.

Climate variability, climate change and land degradation

Effective response by government and individuals to the risk of land degradation requires an understanding of regional climate variations and the impacts of climate and management on condition and productivity of land and vegetation resources. Analysis of past land degradation and climate variability provides some understanding of vulnerability to current and future climate changes and the information needs for more sustainable management. We describe experience in providing climate risk assessment information for managing for the risk of land degradation in north-eastern Australian arid and semi-arid regions used for extensive grazing. However, we note that information based on historical climate variability, which has been relied on in the past, will now also have to factor in the influence of human-induced climate change. Examples illustrate trends in climate for Australia over the past decade and the impacts on indicators of resource condition. The analysis highlights the benefits of insights into past trends and variability in rainfall and other climate variables based on extended historic databases. This understanding in turn supports more reliable regional climate projections and decision support information for governments and land managers to better manage the risk of land degradation now and in the future.

Pasture Degradation and Recovery in Australia's Rangelands : Learning from History

"The extended drought periods in each degradation episode have provided a test of the capacity of grazing systems (i.e. land, plants, animals, humans and social structure) to handle stress. Evidence that degradation was already occurring was identified prior to the extended drought sequences. The sequence of dry years, ranging from two to eight years, exposed and/or amplified the degradation processes. The unequivocal evidence was provided by: (a) the physical 'horror' of bare landscapes, erosion scalds and gullies and dust storms; (b) the biological devastation of woody weeds and animal suffering/deaths or forced sales, and; (c) the financial and emotional plight of graziers and their families due to reduced production in some cases leading to abandonment of properties or, sadly, deaths (e.g. McDonald 1991, Ker Conway 1989)."--Publisher website

Speckle-type POZ protein mutations interrupt tumor suppressor function of speckle-type POZ protein in prostate cancer by affecting androgen receptor degradation

Large scale exome sequencing studies have revealed regions of the genome, which contribute to the castrate resistant prostate cancer (CRPC) phenotype. [1],[2],[3] Such studies have identified mutations in genes, which may have diagnostic/prognostic potential, or which may be targeted therapeutically. Two of these genes include the androgen receptor (AR) and speckle-type POZ protein (SPOP) genes. However, the findings from these exome sequencing studies can only be translated therapeutically once the functional consequences of these mutations have been determined. Here, we highlight the recent study by An et al. [4] which investigated the functional effects of mutations in the SPOP gene that were identified in the aforementioned exome sequencing studies, particularly in the context of SPOP-mediated degradation of the AR.

Differential susceptibility to performance degradation across categories of facial emotion - a model confirmation

Patients with a number of psychiatric and neuropathological conditions demonstrate problems in recognising facial expressions of emotion. Research indicating that patients with schizophrenia perform more poorly in the recognition of negative valence facial stimuli than positive valence stimuli has been interpreted as evidence of a negative emotion specific deficit. An alternate explanation rests in the psychometric properties of the stimulus materials. This model suggests that the pattern of impairment observed in schizophrenia may reflect initial discrepancies in task difficulty between stimulus categories, which are not apparent in healthy subjects because of ceiling effects. This hypothesis is tested, by examining the performance of healthy subjects in a facial emotion categorisation task with three levels of stimulus resolution. Results confirm the predictions of the model, showing that performance degrades differentially across emotion categories, with the greatest deterioration to negative valence stimuli. In the light of these results, a possible methodology for detecting emotion specific deficits in clinical samples is discussed.

Degradation of hydroxycinnamic acid mixtures in aqueous sucrose solutions by the Fenton process

The degradation efficiencies and behaviors of caffeic acid (CaA), p-coumaric acid (pCoA) and ferulic acid (FeA) in aqueous sucrose solutions containing the mixture of these hydroxycinnamic acids (HCAs) mixtures were studied by the Fenton oxidation process. Central composite design and multi-response surface methodology were used to evaluate and optimize the interactive effects of process parameters. Four quadratic polynomial models were developed for the degradation of each individual acid in the mixture and the total HCAs degraded. Sucrose was the most influential parameter that significantly affected the total amount of HCA degraded. Under the conditions studied there was < 0.01% loss of sucrose in all reactions. The optimal values of the process parameters for a 200 mg/L HCA mixture in water (pH 4.73, 25.15 °C) and sucrose solution (13 mass%, pH 5.39, 35.98 °C) were 77% and 57% respectively. Regression analysis showed goodness of fit between the experimental results and the predicted values. The degradation behavior of CaA differed from those of pCoA and FeA, where further CaA degradation is observed at increasing sucrose and decreasing solution pH. The differences (established using UV/Vis and ATR-FTIR spectroscopy) were because, unlike the other acids, CaA formed a complex with Fe(III) or with Fe(III) hydrogen-bonded to sucrose, and coprecipitated with lepidocrocite, an iron oxyhydroxide.

Adaptive online gradient descent

We study the rates of growth of the regret in online convex optimization. First, we show that a simple extension of the algorithm of Hazan et al eliminates the need for a priori knowledge of the lower bound on the second derivatives of the observed functions. We then provide an algorithm, Adaptive Online Gradient Descent, which interpolates between the results of Zinkevich for linear functions and of Hazan et al for strongly convex functions, achieving intermediate rates between [square root T] and [log T]. Furthermore, we show strong optimality of the algorithm. Finally, we provide an extension of our results to general norms.

Child health and the income gradient : evidence from Australia

The positive relationship between household income and child health is well documented in the child health literature but the precise mechanisms via which income generates better health and whether the income gradient is increasing in child age are not well understood. This paper presents new Australian evidence on the child health–income gradient. We use data from the Longitudinal Study of Australian Children (LSAC), which involved two waves of data collection for children born between March 2003 and February 2004 (B-Cohort: 0–3 years), and between March 1999 and February 2000 (K-Cohort: 4–7 years). This data set allows us to test the robustness of some of the findings of the influential studies of Case et al. [Case, A., Lubotsky, D., Paxson, C., 2002. Economic status and health in childhood: the origins of the gradient. The American Economic Review 92 (5) 1308–1344] and Currie and Stabile [Currie, J., Stabile, M., 2003. Socioeconomic status and child health: why is the relationship stronger for older children. The American Economic Review 93 (5) 1813–1823], and a recent study by Currie et al. [Currie, A., Shields, M.A., Price, S.W., 2007. The child health/family income gradient: evidence from England. Journal of Health Economics 26 (2) 213–232]. The richness of the LSAC data set also allows us to conduct further exploration of the determinants of child health. Our results reveal an increasing income gradient by child age using similar covariates to Case et al. [Case, A., Lubotsky, D., Paxson, C., 2002. Economic status and health in childhood: the origins of the gradient. The American Economic Review 92 (5) 1308–1344]. However, the income gradient disappears if we include a rich set of controls. Our results indicate that parental health and, in particular, the mother's health plays a significant role, reducing the income coefficient to zero; suggesting an underlying mechanism that can explain the observed relationship between child health and family income. Overall, our results for Australian children are similar to those produced by Propper et al. [Propper, C., Rigg, J., Burgess, S., 2007. Child health: evidence on the roles of family income and maternal mental health from a UK birth cohort. Health Economics 16 (11) 1245–1269] on their British child cohort.