704 resultados para Pad Pyrmont


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Now in its ninth edition, Australian Tax Analysis: Cases, Commentary, Commercial Applications and Questions has a proven track record as a high-level work for students of taxation law written by a team of authors with many years experience. Taking into account the fact that the volume of material needed to be processed by today’s taxation student can be overwhelming, the well-chosen extracts and thought-provoking commentary in Australian Tax Analysis, 9th edition, provide readers with the depth of knowledge, and reasoning and analytical skills which will be required of them as practitioners. In addition to the carefully selected case extracts and the helpful commentary, each chapter is supplemented by engaging practice questions involving problem solving, commercial decision-making, legal analysis and quantitative application. All these elements combined make Australian Tax Analysis an invaluable aid to the understanding of a subject which can be both technical and complex.

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Poets have a licence to couch great truths in succinct, emotionally powerful, and perhaps slightly mysterious and ambiguous ways. On the other hand, it is the task of academics to explore such truths intellectually, in depth and detail, identifying the key constructs and their underlying relations and structures, hopefully without impairing the essential truth. So it could be said that in January 2013, around 60 academics gathered at the University of Texas, Austin under the benign and encouraging eye of their own muse, Professor Rod Hart, to play their role in exploring and explaining the underlying truth of Yan Zhen’s words. The goals of this chapter are quite broad. Rod was explicit and yet also somewhat Delphic in his expectations and aspirations for the chapter. Even though DICTION was a key analytic tool in most chapters, this chapter was not to be about DICTION per se, or simply a critique of the individual chapters forming this section of the book. Rather DICTION and these studies, as well as some others that got our attention, were to be more a launching pad for observations on what they revealed about the current state of understanding and research into the language of institutions, as well as some ‘adventurous’, but not too outlandish reflections on future challenges and opportunities.

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In the last fifteen years digital storytelling has come to stand for considerably more than a specific form of collaborative media production. It is also an international network of new media artists, creative practitioners, curators, scholars, and facilitating community media organisations. In May this year the movement will converge on Ankara, Turkey for its Fifth International Conference and Exhibition. The event will draw together key adopters, adapters and innovators in community-based methods of collaborative media production from around the world. Researchers from the Queensland University of Technology will lead a delegation that will include key players in the Australian digital storytelling movement.

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"Taxation law can be an incredibly complex subject to absorb, particularly when time is limited. Written specifically for students, Principles of Taxation Law 2014 brings much needed clarity to this area of law. Utilising many methods to make this often daunting subject achievable, particular features of the 2014 edition include: seven parts: overview and structure, principles of income, deductions and offsets, timing issues, investment and business entities, tax avoidance and administration, and indirect taxes; clearly structured chapters within those parts grouped under helpful headings;flowcharts, diagrams and tables, end of chapter practice questions, and case summaries; an appendix containing all of the up to date and relevant rates; and the online self-testing component mentor, which provides questions for students of both business and law. Every major aspect of the Australian tax system is covered, with chapters on topics such as goods and services tax, superannuation, offsets, partnerships, capital gains tax, trusts, company tax and tax administration.All chapters have been thoroughly revised"-- Publishers website

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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

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Breast cancer metastasis to the bone occurs frequently, causing numerous complications including severe pain, fracture, hypercalcemia, and paralysis. Despite its prevalence and severity, few effective therapies exist. To address this, we examined whether the heat shock protein 90 (Hsp90) inhibitor, 17-allylamino-17-demethoxygeldanamycin (17-AAG), would be efficacious in inhibiting breast cancer metastasis to bone. Utilizing the human breast cancer subline, MDA-MB-231SA, previously in vivo selected for its enhanced ability to generate osteolytic bone lesions, we determined that 17-AAG potently inhibited its in vitro proliferation and migration. Moreover, 17-AAG significantly reduced MDA-MB-231SA tumor growth in the mammary-fat pad of nude mice. Despite these findings, 17-AAG enhanced the incidence of bone metastasis and osteolytic lesions following intracardiac inoculation in the nude mouse. Consistent with these findings, 17-AAG enhanced osteoclast formation 2- to 4-fold in mouse bone marrow/osteoblast cocultures, receptor activator of nuclear factor κB ligand (BANKL)-stimulated bone marrow, and RAW264.7 cell models of in vitro osteoclastogenesis. Moreover, the drug enhanced osteoclastogenesis in human cord blood progenitor cells, demonstrating that its effects were not limited to mouse models. In addition to 17-AAG, other Hsp90 inhibitors, such as radicicol and herbimycin A, also enhanced osteoclastogenesis. A pro-osteolytic action of 17-AAG independent of tumor presence was also determined in vivo, in which 17-AAG-treated tumor-naive mice had reduced trabecular bone volume with an associated increase in osteoclast number. Thus, HSP90 inhibitors can stimulate osteoclast formation, which may underlie the increased incidence of osteolysis and skeletal tumor incidence causedby 17-AAG in vivo. These data suggest an important contraindication to the Hsp90 targeted cancer therapy currently undergoing clinical trial.

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The ability to activate pro-matrix metalloproteinase (pro-MMP)-2 via membrane type-MMP is a hallmark of human breast cancer cell lines that show increased invasiveness, suggesting that MMP-2 contributes to human breast cancer progression. To investigate this, we have stably transfected pro-MMP-2 into the human breast cancer cell line MDA-MB-231, which lacks MMP-2 expression but does express its cell surface activator, membrane type 1-MMP. Multiple clones were derived and shown to produce pro-MMP-2 and to activate it in response to concanavalin A. In vitro analysis showed that the pro-MMP-2-transfected clones exhibited an increased invasive potential in Boyden chamber and Matrigel outgrowth assays, compared with the parental cells or those transfected with vector only. When inoculated into the mammary fat pad of nude mice, each of the MMP-2-tranfected clones grew faster than each of the vector controls tested. After intracardiac inoculation into nude mice, pro-MMP-2-transfected clones showed a significant increase in the incidence of metastasis to brain, liver, bone, and kidney compared with the vector control clones but not lung. Increased tumor burden was seen in the primary site and in lung metastases, and a trend toward increased burden was seen in bone, however, no change was seen in brain, liver, or kidney. This data supports a role for MMP-2 in breast cancer progression, both in the growth of primary tumors and in their spread to distant organs. MMP-2 may be a useful target for breast cancer therapy when refinement of MMP inhibitors provides for MMP-specific agents.

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We have previously isolated a series of MCF-7 human breast cancer cell variants which no longer require estrogen-supplementation for tumor growth in nude mice (Clarke et al. Proc Natl Acad Sci USA 86: 3649-3653, 1989). We now report that these hormone-independent and hormone-responsive variants (MIII, MCF7/LCC1) can invade locally from solid mammary fat pad tumors, and produce primary extensions on the surface of intraperitoneal structures including liver, pancreas, and diaphragm. Both lymphatic and hematogenous dissemination are observed, resulting in the establishing of pulmonary, bone, and renal metastases. The pattern of metastasis by MIII and MCF7/LCC1 cells closely resembles that frequently observed in breast cancer patients, and provides the first evidence of metastasis from MCF-7 cells growing in vivo without supplementary estrogen. The interexperimental incidence of metastases, and the time from cell inoculation to the appearance of metastatic disease are variable. The increased metastatic potential is not associated with an increase in either the level of laminin attachment, laminin receptor mRNA expression, or secreted type IV collagenolytic activity. We also did not detect a significant decrease in the steady-state mRNA levels of the metastasis inhibitor nm23 gene. However, when growing without estrogen in vitro, MCF7/LCC1 cells produce elevated levels of the estrogen-inducible cathepsin D enzyme.

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We have investigated the role of bone sialoprotein (BSP), a secreted glycoprotein normally found in bone, in breast cancer progression. To explore functions for BSP in human breast cancer invasion and metastasis, the full-length BSP cDNA was transfected into the MDA-MB-231-BAG human breast cancer cell line under the control of the CMV promoter. Clones expressing BSP and vector control clones were isolated. BSP producing clones showed increased monolayer wound healing, a faster rate of stellate outgrowth in Matrigel and increased rate of invasion into a collagen matrix when compared to control clones. Clones were also examined in models of breast cancer growth and metastasis in vivo. BSP transfected clones showed an increased rate of primary tumor growth following mammary fat pad injection of nude mice. BSP transfected clones and vector control clones metastasized to soft organs and bone at a similar rate after intra-cardiac injection as determined by real-time PCR and X-ray analysis. Although these organs were targets for both BSP transfected and non-transfected cells, the size of the metastatic lesion was shown to be significantly larger for BSP expressing clones. This was determined by real-time PCR analysis for soft organs and by X-ray analysis of bone lesions. For bone this was confirmed by intra-tibial injections of cells in nude mice. We conclude that BSP acts to drive primary and secondary tumor growth of breast cancers in vivo.

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We investigated the effects of the matrix metalloproteinase 13 (MMP13)-selective inhibitor, 5-(4-{4-[4-(4-fluorophenyl)-1,3-oxazol-2-yl]phenoxy}phenoxy)-5-(2-methoxyethyl) pyrimidine-2,4,6(1H,3H,5H)-trione (Cmpd-1), on the primary tumor growth and breast cancer-associated bone remodeling using xenograft and syngeneic mouse models. We used human breast cancer MDA-MB-231 cells inoculated into the mammary fat pad and left ventricle of BALB/c Nu/Nu mice, respectively, and spontaneously metastasizing 4T1.2-Luc mouse mammary cells inoculated into mammary fat pad of BALB/c mice. In a prevention setting, treatment with Cmpd-1 markedly delayed the growth of primary tumors in both models, and reduced the onset and severity of osteolytic lesions in the MDA-MB-231 intracardiac model. Intervention treatment with Cmpd-1 on established MDA-MB-231 primary tumors also significantly inhibited subsequent growth. In contrast, no effects of Cmpd-1 were observed on soft organ metastatic burden following intracardiac or mammary fat pad inoculations of MDA-MB-231 and 4T1.2-Luc cells respectively. MMP13 immunostaining of clinical primary breast tumors and experimental mice tumors revealed intra-tumoral and stromal expression in most tumors, and vasculature expression in all. MMP13 was also detected in osteoblasts in clinical samples of breast-to-bone metastases. The data suggest that MMP13-selective inhibitors, which lack musculoskeletal side effects, may have therapeutic potential both in primary breast cancer and cancer-induced bone osteolysis.

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In human breast cancer (HBC), as with many carcinoma systems, most matrix metalloproteinases (MMPs) are largely expressed by the stromal cells, whereas the tumour cells are relatively silent in MMP expression. To determine the tissue source of the most relevant MMPs, we xenografted HBC cell lines and HBC tissues into the mammary fat pad (MFP) or bone of immunocompromised mice and measured the expression of human and mouse MMP-2, -9, -11, -13, membrane-type-1 MMP (MT1-MMP), MT2-MMP and MT3-MMP by species-specific real-time quantitative RT-PCR. Our data confirm a stromal origin for most tumour-associated MMPs and indicate marked and consistent upregulation of stromal (mouse) MMP-13 and MT1-MMP in all xenografts studied, irrespective of implantation in the MFP or bone environments. In addition, we show increased expression of both human MMP-13 and human MT1-MMP by the MDA-MB-231 tumour cells grown in the MFP compared to in vitro production. MMP protein and activity data confirm the upregulation of MMP mRNA production and indicate an increase in the activated MMP-2 species as a result of tumour implantation. These data directly demonstrate tumour induction of MMP production by stromal cells in both the MFP and bone environments. These xenografts are a valuable means for examining in vivo production of MMPs and suggest that MMP-13 and MT1-MMP will be relevant targets for inhibiting breast cancer progression.

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Operators of hydroelectric power stations sometimes call upon engineers to modify existing hydroelectric turbines, usually several decades old, for improved maintainability and reliability. One common modification is the hybridisation of plain thrust pads to allow hydrostatic operation to reduce the risk of bearing wipe at low speed (virtually all new installations benefit from this feature). A modification such as this is not a difficult undertaking; however, there are numerous factors that need to be considered in order to maximize bearing performance. One factor that stands out above the others is whether the thrust bearing should be designed to lift the turbine immediately from the standing condition, which presents an interesting challenge: the recess has to have a sufficiently large area in order for the supply pressure to be able to overcome the dead weight of the turbine. If the combination of groove area and pressure is insufficient, then lifting is neither immediate nor guaranteed. This need not be a significant problem, as the bearings have exhibited adequate performance even in the absence of a hydrostatic lubricant supply. A case study is presented whereby relatively large hydrostatic recesses are added to the pads of thrust bearing. It is demonstrated with the aid of simple numerical modelling that the impact of the recess relative to the original pad is small under normal operating conditions. Most surprising, however, is that significant reductions in average oil film temperature and power dissipation are predicted.