4,887 research outputs found

    An Economic Analysis of the Luxury Car Tax in Australia

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    Luxury cars are a symbol of wealth, succe ss and prestige and are a commodity of a sophisticated monopolistically competitive market around the world. Considering luxury cars to be representative of s uperior goods, you would expect sales to be decreasing during an economic downturn. However, while sales of luxury cars in Europe and the US declined during the GFC, sales within Australia increased substantially. This paper presents a closer inspection of this market in Australia and particularly focuses on how the government has applied the Luxury Car Tax (LCT). It looks at the impact of the LCT on the Australian luxury car market from an economic perspectiv e, and attempts to explain the political rationale for maintaining such a tax

    Visualising a complex ritual landscape. Gaining a new perspective on the Late Period/Early Ptolemaic sacred landscape of North Saqqara through the application of digital technologies

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    The Late Period (747–332 BC)/Early Ptolemaic (332–30 BC) monuments at the necropolis of North Saqqara have historically been investigated either in isolation or within small spatially close groups. The monuments have rarely been compared within their wider landscape setting, or their relationship with the topography upon which they are imposed considered. This study seeks to redress the situation for the monuments associated with the sacred animal cults through the investigation of topographic associations, monument interconnectedness, and affordances and entanglements within the sacred landscape. To achieve this, a new and detailed GIS (Geographical Information System) of the North Saqqara and South Abusir archaeological areas was researched and compiled, as there was no other currently available. The GIS provided the foundation for the construction of an innovative multi-layered digital 3D representation of the ancient necropolis, which was used to examine the landscape from a terrestrial viewpoint. This was fundamental to developing an holistic understanding of a sacred landscape which is no longer wholly extant. By employing the creative power of digital reconstruction, the task of visualisation and the investigation of divergent viewpoints becomes achievable in ways that otherwise might not be possible. The employment of archaeological theory, not previously applied widely within the field of Egyptological studies, has permitted a nuanced interpretation of the funerary landscape visualised through the digital representation. Investigation of the landscape in this manner has offered new perspectives into the place of the monuments, and their topographic and interconnected relationships: a correlation between the sacred animal monuments, networks of movement, and specific milieus of terrain has been recognised; a mechanism of visual performance employed by the monument builders has been identified; and a new mixed-media narrative account of the landscape has been constructed

    CCL2 is transcriptionally controlled by the lysosomal protease cathepsin S in a CD74-dependent manner

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    Cathepsins S (CatS) has been implicated in numerous tumourigenic processes and here we document for the first time its involvement in CCL2 regulation within the tumour microenvironment. Analysis of syngeneic tumours highlighted reduced infiltrating macrophages in CatS depleted tumours. Interrogation of tumours and serum revealed genetic ablation of CatS leads to the depletion of several pro-inflammatory chemokines, most notably, CCL2. This observation was validated in vitro, where shRNA depletion of CatS resulted in reduced CCL2 expression. This regulation is transcriptionally mediated, as evident from RT-PCR analysis and CCL2 promoter studies. We revealed that CatS regulation of CCL2 is modulated through CD74 (also known as the invariant chain), a known substrate of CatS and a mediator of NFkB activity. Furthermore, CatS and CCL2 show a strong clinical correlation in brain, breast and colon tumours. In summary, these results highlight a novel mechanism by which CatS controls CCL2, which may present a useful pharmacodynamic marker for CatS inhibition

    A bioavailable cathepsin S nitrile inhibitor abrogates tumor development

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    BACKGROUND: Cathepsin S has been implicated in a variety of malignancies with genetic ablation studies demonstrating a key role in tumor invasion and neo-angiogenesis. Thus, the application of cathepsin S inhibitors may have clinical utility in the treatment of cancer. In this investigation, we applied a cell-permeable dipeptidyl nitrile inhibitor of cathepsin S, originally developed to target cathepsin S in inflammatory diseases, in both in vitro and in vivo tumor models. METHODS: Validation of cathepsin S selectivity was carried out by assaying fluorogenic substrate turnover using recombinant cathepsin protease. Complete kinetic analysis was carried out and true K(i) values calculated. Abrogation of tumour invasion using murine MC38 and human MCF7 cell lines were carried out in vitro using a transwell migration assay. Effect on endothelial tube formation was evaluated using primary HUVEC cells. The effect of inhibitor in vivo on MC38 and MCF7 tumor progression was evaluated using cells propagated in C57BL/6 and BALB/c mice respectively. Subsequent immunohistochemical staining of proliferation (Ki67) and apoptosis (TUNEL) was carried out on MCF7 tumors. RESULTS: We confirmed that this inhibitor was able to selectively target cathepsin S over family members K, V, L and B. The inhibitor also significantly reduced MC38 and MCF7 cell invasion and furthermore, significantly reduced HUVEC endothelial tubule formation in vitro. In vivo analysis revealed that the compound could significantly reduce tumor volume in murine MC38 syngeneic and MCF7 xenograft models. Immunohistochemical analysis of MCF7 tumors revealed cathepsin S inhibitor treatment significantly reduced proliferation and increased apoptosis. CONCLUSIONS: In summary, these results highlight the characterisation of this nitrile cathepsin S inhibitor using in vitro and in vivo tumor models, presenting a compound which may be used to further dissect the role of cathepsin S in cancer progression and may hold therapeutic potential. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12943-016-0513-7) contains supplementary material, which is available to authorized users

    An optical coherence microscope for 3-dimensional imaging in developmental biology

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    An optical coherence microscope (OCM) has been designed and constructed to acquire 3-dimensional images of highly scattering biological tissue. Volume-rendering software is used to enhance 3-D visualization of the data sets. Lateral resolution of the OCM is 5 mm (FWHM), and the depth resolution is 10 mm (FWHM) in tissue. The design trade-offs for a 3-D OCM are discussed, and the fundamental photon noise limitation is measured and compared with theory. A rotating 3-D image of a frog embryo is presented to illustrate the capabilities of the instrument

    MASE: A New Data--Reduction Pipeline for the Magellan Echellette Spectrograph

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    We introduce a data reduction package written in Interactive Data Language (IDL) for the Magellan Echellete Spectrograph (MAGE). MAGE is a medium-resolution (R ~4100), cross-dispersed, optical spectrograph, with coverage from ~3000-10000 Angstroms. The MAGE Spectral Extractor (MASE) incorporates the entire image reduction and calibration process, including bias subtraction, flat fielding, wavelength calibration, sky subtraction, object extraction and flux calibration of point sources. We include examples of the user interface and reduced spectra. We show that the wavelength calibration is sufficient to achieve ~5 km/s RMS accuracy and relative flux calibrations better than 10%. A light-weight version of the full reduction pipeline has been included for real-time source extraction and signal-to-noise estimation at the telescope.Comment: 10 pages (ApJ format), accepted PAS

    Neural responses to facial and vocal expressions of fear and disgust

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    Neuropsychological studies report more impaired responses to facial expressions of fear than disgust in people with amygdala lesions, and vice versa in people with Huntington's disease. Experiments using functional magnetic resonance imaging (fMRI) have confirmed the role of the amygdala in the response to fearful faces and have implicated the anterior insula in the response to facial expressions of disgust. We used fMRI to extend these studies to the perception of fear and disgust from both facial and vocal expressions. Consistent with neuropsychological findings, both types of fearful stimuli activated the amygdala. Facial expressions of disgust activated the anterior insula and the caudate-putamen; vocal expressions of disgust did not significantly activate either of these regions. All four types of stimuli activated the superior temporal gyrus. Our findings therefore (i) support the differential localization of the neural substrates of fear and disgust; (ii) confirm the involvement of the amygdala in the emotion of fear, whether evoked by facial or vocal expressions; (iii) confirm the involvement of the anterior insula and the striatum in reactions to facial expressions of disgust; and (iv) suggest a possible general role for the perception of emotional expressions for the superior temporal gyrus
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