Interleukin-1beta induces human proximal tubule cell injury, alpha-smooth muscle actin expression and fibronectin production

BACKGROUND Tubulointerstitial lesions, characterized by tubular injury, interstitial fibrosis and the appearance of myofibroblasts, are the strongest predictors of the degree and progression of chronic renal failure. These lesions are typically preceded by macrophage infiltration of the tubulointerstitium, raising the possibility that these inflammatory cells promote progressive renal disease through fibrogenic actions on resident tubulointerstitial cells. The aim of the present study, therefore, was to investigate the potentially fibrogenic mechanisms of interleukin-1beta (IL-1beta), a macrophage-derived pro-inflammatory cytokine, on human proximal tubule cells (PTC). METHODS Confluent, quiescent, passage 2 PTC were established in primary culture from histologically normal segments of human renal cortex (N = 11) and then incubated in serum- and hormone-free media supplemented with either IL-1beta (0 to 4 ng/mL) or vehicle (control). RESULTS IL-1beta significantly enhanced fibronectin secretion by up to fourfold in a time- and concentration-dependent fashion. This was accompanied by significant (2.5- to 6-fold) increases in alpha-smooth muscle actin (alpha-SMA) expression, transforming growth factor beta (TGF-beta1) secretion, nitric oxide (NO) production, NO synthase 2 (NOS2) mRNA and lactate dehydrogenase (LDH) release. Cell proliferation was dose-dependently suppressed by IL-1beta. NG-methyl-l-arginine (L-NMMA; 1 mmol/L), a specific inhibitor of NOS, blocked NO production but did not alter basal or IL-1beta-stimulated fibronectin secretion. In contrast, a pan-specific TGF-beta neutralizing antibody significantly blocked the effects of IL-1beta on PTC fibronectin secretion (IL-1beta, 268.1 +/- 30.6 vs. IL-1beta+alphaTGF-beta 157.9 +/- 14.4%, of control values, P < 0.001) and DNA synthesis (IL-1beta 81.0 +/- 6.7% vs. IL-1beta+alphaTGF-beta 93.4 +/- 2.1%, of control values, P < 0.01). CONCLUSION IL-1beta acts on human PTC to suppress cell proliferation, enhance fibronectin production and promote alpha-smooth muscle actin expression. These actions appear to be mediated by a TGF-beta1 dependent mechanism and are independent of nitric oxide release.

Fundamental Tax Legislation [22nd Edition]

This edition includes a revised Year in Review section, which summarises the legislative developments in taxation over the previous 12 months, a listing of the passage of tax-related legislation during the last year and the inclusion of reference statistics (such as CPI quarterly figures and individual tax rates for residents and non-residents). A Tax Rates and Tables section which contains an accessible summary of the main tax rates and tables that students will need to refer to for their tax studies

A living sacrifice

"When Susannah Birch was two years old her mother cut her throat, in a ritual sacrifice, Susannah was very lucky to survive. This was the first of her mother’s psychotic episodes as she enacted a passage from The Old Testament...In this moving documentary Susannah and her father describe their memories of this shocking event and how it has affected them."--publisher website

Structural and material characterisation of insulated rail joints

Insulated rail joints are designed in a similar way to butt jointed steel structural systems, the difference being a purpose made gap between the main rail members to maintain electrical insulation for the proper functioning of the track circuitry at all times of train operation. When loaded wheels pass the gap, they induce an impact loading with the corresponding strains in the railhead edges exceeding the plastic limit significantly, which lead to metal flow across the gap thereby increasing the risk of short circuiting and impeding the proper functioning of the signalling and broken rail identification circuitries, of which the joints are a critical part. The performance of insulated rail joints under the passage of the wheel loading is complex due to the presence of a number of interacting components and hence is not well understood. This paper presents a dynamic wheel-rail contact-impact modelling method for the determination of the impact loading; a brief description of a field experiment to capture strain signatures for validating the predicted impact loading is also presented. The process and the results of the characterisation of the materials from virgin, in-service and damaged insulated rail joints using neutron diffraction method are also discussed.

Vertical dynamic interaction of trains and rail steel bridges

Rail steel bridges are vulnerable to high impact forces due to the passage of trains; unfortunately the determination of these transient impact forces is not straightforward as these are affected by a large number of parameters, including the wagon design, the wheel-rail contact and the design parameters of the bridge deck and track, as well as the operational parameters – wheel load and speed. To determine these impact forces, a detailed rail train-track/bridge dynamic interaction model has been developed, which includes a comprehensive train model using multi-body dynamics approach and a flexible track/bridge model using Euler– Bernoulli beam theory. Single and multi-span bridges have been modelled to examine their dynamic characteristics. From the single span bridge, the train critical speed is determined; the minimum distance of two peak loadings is found to affect the train critical speed. The impact factor and the dynamic characteristics are discussed.

Unintended consequences : satellite policy and Indigenous television

This article examines two instances of media policy involving satellite transmission and Indigenous television: the introduction of the Viewer Access Satellite Television (VAST) platform in 2010 and the introduction of AUSSAT in the mid-1980s. The government’s failure to provide community and Indigenous broadcasters with an access regime at the time of AUSSAT resulted in Australia’s first and only Indigenous commercial television licensee, Imparja. Over a quarter of a century later, Imparja now forms part of the joint-venture company that runs VAST, a key component of Australia’s digital switchover planning. During the passage of the legislative amendments required to establish VAST, the issue of access resurfaced – this time in relation to Australia’s national and community Indigenous television channels. The article recounts the events leading up to the 2010 Bill, and examines the intended and unintended consequences of satellite policy in relation to Indigenous media, including equalisation and transparency of government funding programs.

Construction of interstellar cumulenes and heterocumulenes : Mass spectrometric studies

The last few years have brought an increasing interest in the chemistry of rite interstellar and circumstellar environs. Many of the molecular species discovered in remote galactic regions have been dubbed 'non-terrestrial' because of their unique structures (Thaddeus et al, 1993). These findings have provided a challenge to chemists in many differing fields to attempt to generate these unusual species in the laboratory of particular recent interest have been the unsaturated hydrocarbon families, CnH and CnH2, which have been pursued by a number of diverse methodologies. A wine range of heterocumulenes, including CnO, HCnO, CnN, HCnN, CnS, HCnS, CnSi and HCnSi have also provided intriguing targets for laboratory experiments. Strictly the term cumulene refers to a class of compounds that possess a series of adjacent double bonds, with allene representing the simplest example (H2C=C=CH2). However for many of the non-terrestrial molecules presented here, the carbon chain cannot be described in terms of a single simple valence structure, and so we use the terms cumulene and heterocumulene in a more general sense: to describe molecular species that contain an unsaturated polycarbon chain. Mass spectrometry has proved an invaluable tool in the quest for interstellar cumulenes and heterocumulenes in the laboratory it has the ability in its many forms, to (i) generate charged analogs of these species in the gas phase, (ii) probe their connectivity, ion chemistry, and thermochemistry, and (iii) in some cases, elucidate the neutrals themselves. Here, we will discuss the progress of these studies to this time. (C) 1999 John Wiley & Sons, Inc.

Overview of the INEX 2008 Ad Hoc Track

This paper gives an overview of the INEX 2008 Ad Hoc Track. The main goals of the Ad Hoc Track were two-fold. The first goal was to investigate the value of the internal document structure (as provided by the XML mark-up) for retrieving relevant information. This is a continuation of INEX 2007 and, for this reason, the retrieval results are liberalized to arbitrary passages and measures were chosen to fairly compare systems retrieving elements, ranges of elements, and arbitrary passages. The second goal was to compare focused retrieval to article retrieval more directly than in earlier years. For this reason, standard document retrieval rankings have been derived from all runs, and evaluated with standard measures. In addition, a set of queries targeting Wikipedia have been derived from a proxy log, and the runs are also evaluated against the clicked Wikipedia pages. The INEX 2008 Ad Hoc Track featured three tasks: For the Focused Task a ranked-list of nonoverlapping results (elements or passages) was needed. For the Relevant in Context Task non-overlapping results (elements or passages) were returned grouped by the article from which they came. For the Best in Context Task a single starting point (element start tag or passage start) for each article was needed. We discuss the results for the three tasks, and examine the relative effectiveness of element and passage retrieval. This is examined in the context of content only (CO, or Keyword) search as well as content and structure (CAS, or structured) search. Finally, we look at the ability of focused retrieval techniques to rank articles, using standard document retrieval techniques, both against the judged topics as well as against queries and clicks from a proxy log.

Effect of vertical misalignment of adjacent sleepers on the increase in dynamic loads around rail joints

In spite of the extensive usage of continuous welded rails, a number of rail joints still exist in the track. Although a number of them exist as part of turnouts in the yards where the speed is not of concern, the Insultated Rail Joints (IRJs) that exist in ballasted tracks remain a source of significant impact loading. A portion of the dynamic load generated at the rail joints due to wheel passage is transmitted to the support system which leads to permanent settlements of the ballast layer with subsequent vertical misalignment of the sleepers around the rail joints. The vertical misalignment of the adjacent sleepers forms a source of high frequency dynamic load raisers causing significant maintenance work including localised grinding of railhead around the joint, re-alignment of the sleepers and/or ballast tamping or track component renewals/repairs. These localised maintenance activities often require manual inspections and disruptions to the train traffic loading to significant costs to the rail industry. Whilst a number of studies have modelled the effect of joints as dips, none have specifically attended to the effect of vertical misalignment of the sleepers on the dynamic response of rail joints. This paper presents a coupled finite element track model and rigid body track-vehicle interaction model through which the effects of vertical of sleepers on the increase in dynamic loads around the IRJ are studied. The finite element track model is employed to determine the generated dip from elastic deformations as well as the vertical displacement of sleepers around the joint. These data (dip and vertical misalignments) are then imported into the rigid body vehicle-track interaction model to calculate the dynamic loads.

Factors regulating basement membrane invasion by tumor cells

Basement membranes serve as significant barriers to the passage of tumor cells but ones which metastatic cells can pass. This involves the production of a cascade of proteases leading to the activation of a specific collagenase that degrades the unique collagen network in basement membrane. Breast cancer cells, when estrogen dependent, show a requirement for estrogen for invasive activity. However, when these cells progress to an estrogen independent state and increased malignancy, they express an invasive phenotype constitutively. Studies with various anti-estrogens suggest that these responses are mediated via the estrogen receptor. Anti-estrogens lacking agonist activity suppress invasiveness as well as growth of the breast cancer cells.

Assessment of angiogenic potential--the use of AIDS-KS cell supernatants as an in vitro model

Metastasis, the passage of primary tumour cells throughout the body via the vascular system and their subsequent proliferation into secondary lesions in distant organs, represents a poor prognosis and therefore an understandably feared event for cancer patients. Despite considerable advances in cancer diagnosis and treatment, most deaths are the result of metastases resistant to conventional treatment [1]. Rather than being a random process, metastasis involves a series of organised steps leading to the growth of a secondary tumour. Malignant tumours stimulate the production of new vessels by the host, and this process is a prerequisite for the increase in size of a new tumour [2]. Angiogenesis, not only permits tumour expansion but also allows the entry of tumour cells into the circulation and is probably the most vital event for the metastatic process [3]. Metastasis and angiogenesis [4] have received much attention in recent years. A biological understanding of both phenomena seems to be an urgent priority towards the search for an effective prevention and treatment of tumour progression. Studies in vitro and in vivo have shown that one of the most important barriers to the passage of malignant cells is the basement membrane. The crossing of such barriers is a vital step in the formation of a metastasis [5].

Failure of discontinuous railhead edges due to plastic strain accumulation

Railhead is perhaps the highest stressed civil infrastructure due to the passage of heavily loaded wheels through a very small contact patch. The stresses at the contact patch cause yielding of the railhead material and wear. Many theories exist for the prediction of these mechanisms of continuous rails; this process in the discontinuous rails is relatively sparingly researched. Discontinuous railhead edges fail due to accumulating excessive plastic strains. Significant safety concern is widely reported as these edges form part of Insulated Rail Joints (IRJs) in the signalling track circuitry. Since Hertzian contact is not valid at a discontinuous edge, 3D finite element (3DFE) models of wheel contact at a railhead edge have been used in this research. Elastic–plastic material properties of the head hardened rail steel have been experimentally determined through uniaxial monotonic tension tests and incorporated into a FE model of a cylindrical specimen subject to cyclic tension load- ing. The parameters required for the Chaboche kinematic hardening model have been determined from the stabilised hysteresis loops of the cyclic load simulation and imple- mented into the 3DFE model. The 3DFE predictions of the plastic strain accumulation in the vicinity of the wheel contact at discontinuous railhead edges are shown to be affected by the contact due to passage of wheels rather than the magnitude of the loads the wheels carry. Therefore to eliminate this failure mechanism, modification to the contact patch is essential; reduction in wheel load cannot solve this problem.

Particle number emissions from a large fleet of diesel and CNG buses

Exhaust emissions were monitored in real-time at the kerb of a busy busway used by a mix of diesel and CNG-powered transport buses. Particle number concentration in the size range 3 nm to 3 µm was measured with a TSI condensation particle counter (CPC 3025). Particle mass (PM2.5) was measured with a TSI Dustrak 8520. The CO2 emissions were measured with a fast response CO2 analyser (Sable CA-10A). All emission concentrations were recorded in real time at 1 sec resolution, together with the precise passage times of buses. The instantaneous ratio of particle number (or mass) to CO2 concentration, denoted Z, was used as a measure of the particle number (or mass) emission factor of each passing bus.

Computational fluid dynamics simulation and turbomachinery code validation of a high pressure ratio radial-inflow turbine

The present study explores reproducing the closest geometry of a high pressure ratio single stage radial-inflow turbine applied in the Sundstrans Power Systems T-100 Multipurpose Small Power Unit. The commercial software ANSYS-Vista RTD along with a built in module, BladeGen, is used to conduct a meanline design and create 3D geometry of one flow passage. Carefully examining the proposed design against the geometrical and experimental data, ANSYS-TurboGrid is applied to generate computational mesh. CFD simulations are performed with ANSYS-CFX in which three-dimensional Reynolds-Averaged Navier-Stokes equations are solved subject to appropriate boundary conditions. Results are compared with numerical and experimental data published in the literature in order to generate the exact geometry of the existing turbine and validate the numerical results against the experimental ones.

Rough Seas

Favel Parrett’s second novel, When the Night Comes, opens with its teenage protagonist Isla lying awake in her bunk on a night ferry to Tasmania in the mid-1980s, ‘waiting for the rough seas’. Her younger brother sleeps beside her, and her distracted, emotionally distant mother – the kind of woman who is ‘always sitting places by herself in the night’ – is smoking on deck. Together, the three are weathering the roiling overnight passage in order to escape a violent past and make a new life in Hobart. The rough seas the novel goes on to navigate are, as one might expect, both literal and metaphorical...