988 resultados para anti-union
Resumo:
Zinc-rich ethyl silicate coatings are quite successful in protecting steel against corrosion under severe exposing conditions. In spite of providing excellent cathodic protection to steel structure after film curing, two-component zinc-rich ethyl silicate coatings have some limitations, one of which is inadequate shelf life as a result of in-can binder gelation. In this work, the preparation steps of ethyl silicate such as pre-hydrolysis, dehydration and organometallic reactions were surveyed and herein an approach towards understanding the cause and effect relationship of the use of ingredients is presented. The effects of water and catalytic acid dosages on gel time under accelerated conditions and the effect of alcoholic solvent order on the rate of the hydrolysis and dehydration reactions were studied via Karl-Fischer test determining the water content of hydrolysate. A thriving optimization in shelf life without any loss in physical–mechanical characteristics of the final film (e.g. hardness, adhesion, solvent and salt spray resistance) was obtained.
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Sortase A is a membrane enzyme responsible for the anchoring of surface-exposed proteins to the cell wall envelope of Gram-positive bacteria. As a well-studied member of the sortase subfamily catalysing the cell wall anchoring of important virulence factors to the surface of staphylococci, enterococci and streptococci, sortase A plays a critical role in Gram-positive bacterial pathogenesis. It is thus considered a promising target for the development of new anti-infective drugs that aim to interfere with important Gram-positive virulence mechanisms, such as adhesion to host tissues, evasion of host defences, and biofilm formation. The additional properties of sortase A as an enzyme that is not required for Gram-positive bacterial growth or viability and is conveniently located on the cell membrane making it more accessible to inhibitor targeting, constitute additional reasons reinforcing the view that sortase A is an ideal target for anti-virulence drug development. Many inhibitors of sortase A have been identified to date using high-throughput or in silico screening of compound libraries (synthetic or natural), and while many have proved useful tools for probing the action model of the enzyme, several are also promising candidates for the development into potent inhibitors. This review is focused on the most promising sortase A inhibitor compounds that are currently in development as leads towards a new class of anti-infective drugs that are urgently needed to help combat the alarming increase in antimicrobial resistance.
Resumo:
Periodontitis is an inflammatory disease that causes osteolysis and tooth loss. It is known that the nuclear factor kappa B (NF-κB) signalling pathway plays a key role in the progression of inflammation and osteoclastogenesis in periodontitis. Parthenolide (PTL), a sesquiterpene lactone extracted from the shoots of Tanacetum parthenium, has been shown to possess anti-inflammatory properties in various diseases. In the study reported herein, we investigated the effects of PTL on the inflammatory and osteoclastogenic response of human periodontal ligament-derived cells (hPDLCs) and revealed the signalling pathways in this process. Our results showed that PTL decreased NF-κB activation, I-κB degradation, and ERK activation in hPDLCs. PTL significantly reduced the expression of inflammatory (IL-1β, IL-6, and TNF-α) and osteoclastogenic (RANKL, OPG, and M-CSF) genes in LPS-stimulated hPDLCs. In addition, PTL attenuated hPDLC-induced osteoclastogenic differentiation of macrophages (RAW264.7 cells), as well as reducing gene expression of osteoclast-related markers in RAW264.7 cells in an hPDLC-macrophage coculture model. Taken together, these results demonstrate the anti-inflammatory and antiosteoclastogenic activities of PTL in hPDLCs in vitro. These data offer fundamental evidence supporting the potential use of PTL in periodontitis treatment.
Understanding the mechanisms of graft union formation in solanaceae plants using in vitro techniques
Resumo:
Interactions between the anti-carcinogens, bendamustine (BDM) and dexamethasone (DXM), with bovine serum albumin (BSA) were investigated with the use of fluorescence and UV–vis spectroscopies under pseudo-physiological conditions (Tris–HCl buffer, pH 7.4). The static mechanism was responsible for the fluorescence quenching during the interactions; the binding formation constant of the BSA–BDM complex and the binding number were 5.14 × 105 L mol−1 and 1.0, respectively. Spectroscopic studies for the formation of BDM–BSA complex were interpreted with the use of multivariate curve resolution – alternating least squares (MCR–ALS), which supported the complex formation. The BSA samples treated with site markers (warfarin – site I and ibuprofen – site II) were reacted separately with BDM and DXM; while both anti-carcinogens bound to site I, the binding constants suggested that DXM formed a more stable complex. Relative concentration profiles and the fluorescence spectra associated with BDM, DXM and BSA, were recovered simultaneously from the full fluorescence excitation–emission data with the use of the parallel factor analysis (PARAFAC) method. The results confirmed that on addition of DXM to the BDM–BSA complex, the BDM was replaced and the DXM–BSA complex formed; free BDM was released. This finding may have consequences for the transport of these drugs during any anti-cancer treatment.
Resumo:
Host and donor dendritic cells (DC) stimulate alloreactive donor T lymphocytes, and initiate GVHD. We have shown that polyclonal antibody to the DC surface activation marker human CD83 (anti hCD83), which depletes activated DC, can prevent human DC and T cell induced lethal xenogeneic GVHD in SCID mice without impairing T cell mediated anti-leukaemic and anti-viral (CMV and influenza) immunity (J Exp Med 2009; 206: 387). Therefore, we made and tested a polyclonal anti mouse CD83 (RAM83) antibody in murine HSCT models and developed a human mAb against hCD83 as a potential new therapeutic immunosuppressive agent.
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Estimating the prevalence of drink driving is a difficult task. Self‐reported drink driving indicates that drink driving is far more common than official statistics suggest. In order to promote a responsible attitude towards alcohol consumption and drink driving within the Queensland community, the Queensland Police Service, Queensland Health and Queensland Transport developed the ‘Drink Rite’ program (Queensland Police Service information sheet, 2009). However, the feasibility of the program is now in doubt as the National Health and Medical Research Council’s guidelines for alcohol consumption changed in 2009 to state “For healthy men and women, drinking no more than four standard drinks on a single occasion reduces the risk of alcohol‐related injury arising from that occasion” (NHMRC Publication, 2009, p. 51). As such, adhering to the NHMRC guidelines places restrictions on how the existing Drink Rite program can be operated (i.e. by reducing the number of standard drinks provided to participants from eight to four). It is arguable that a reduction in the number of alcoholic drinks provided to participants in the program will result in a large reduction in observed BAC readings. This, in turn, will lead to a potential loss of message content when discussing the variation in the effects of alcohol.
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In this issue of Cancer Discovery, Hagel and colleagues report the design and the in vitro and in vivo activity of a novel, irreversible, paralog-specific kinase inhibitor of FGFR4, BLU9931. This compound binds covalently to a cysteine residue in the hinge region of FGFR4 but not in FGFR1-3. BLU9931 induces tumor shrinkage in hepatocellular carcinoma models that express a functioning ligand/receptor complex consisting of FGF19/FGFR4/KLB and adds to a growing list of anti-FGFR4 agents.
Resumo:
EphB4 is a membrane-bound receptor tyrosine kinase (RTK) commonly over-produced by many epithelial cancers but with low to no expression in most normal adult tissues. EphB4 over-production promotes ligand-independent signaling pathways that increase cancer cell viability and stimulate migration and invasion. Several studies have shown that normal ligand-dependent signaling is tumour suppressive and therefore novel therapeutics which block the tumour promoting ligand-independent signaling and/or stimulate tumour suppressive ligand-dependent signaling will find application in the treatment of cancer. An EphB4-specific polyclonal antibody, targeting a region of 200 amino acids in the extracellular portion of EphB4, showed potent in vitro anti-cancer effects measured by an increase in apoptosis and a decrease in anchorage independent growth. Peptide exclusion was used to identify the epitope targeted by this antibody within the cysteine-rich region of the EphB4 protein, a sequence defined as a potential ligand interacting interface. Addition of antibody to cancer cells resulted in phosphorylation and subsequent degradation of the EphB4 protein, suggesting a mechanism that is ligand mimetic and tumour suppressive. A monoclonal antibody which specifically targets this identified extracellular epitope of EphB4 significantly reduced breast cancer xenograft growth in vivo confirming that EphB4 is a useful target for ligand-mimicking antibody-based anti-cancer therapies.
Resumo:
In response to scientific breakthroughs in biotechnology, the development of new technologies, and the demands of a hungry capitalist marketplace, patent law has expanded to accommodate a range of biological inventions. There has been much academic and public debate as to whether gene patents have a positive impact upon research and development, health-care, and the protection of the environment. In a satire of prevailing patenting practices, the English poet and part-time casino waitress, Donna MacLean, sought a patent application - GB0000180.0 - in respect of herself. She explained that she had satisfied the usual patent criteria - in that she was novel, inventive, and useful: It has taken 30 years of hard labor for me to discover and invent myself, and now I wish to protect my invention from unauthorized exploitation, genetic or otherwise. I am new: I have led a private existence and I have not made the invention of myself public. I am not obvious (2000: 18). MacLean said she had many industrial applications. ’For example, my genes can be used in medical research to extremely profitable ends - I therefore wish to have sole control of my own genetic material' (2000: 18). She observed in an interview: ’There's a kind of unpleasant, grasping, greedy atmosphere at the moment around the mapping of the human genome ... I wanted to see if a human being could protect their own genes in law' (Meek, 2000). This special issue of Law in Context charts a new era in the long-standing debate over biological inventions. In the wake of the expansion of patentable subject matter, there has been great strain placed upon patent criteria - such as ’novelty', ’inventive step', and ’utility'. Furthermore, there has been a new focus upon legal doctrines which facilitate access to patented inventions - like the defence of experimental use, the ’Bolar' exception, patent pooling, and compulsory licensing. There has been a concerted effort to renew patent law with an infusion of ethical principles dealing with informed consent and benefit sharing. There has also been a backlash against the commercialisation of biological inventions, and a call by some activists for the abolition of patents on genetic inventions. This collection considers a wide range of biological inventions - ranging from micro-organisms, plants and flowers and transgenic animals to genes, express sequence tags, and research tools, as well as genetic diagnostic tests and pharmaceutical drugs. It is thus an important corrective to much policy work, which has been limited in its purview to merely gene patents and biomedical research. This collection compares and contrasts the various approaches of a number of jurisdictions to the legal problems in respect of biological inventions. In particular, it looks at the complexities of the 1998 European Union Directive on the Legal Protection of Biotechnological Inventions, as well as decisions of member states, such as the Netherlands, and peripheral states, like Iceland. The edition considers US jurisprudence on patent law and policy, as well as recent developments in Canada. It also focuses upon recent developments in Australia - especially in the wake of parallel policy inquiries into gene patents and access to genetic resources.
Resumo:
In an exploration of intellectual property and fashion, this article examines the question of the intermediary liability of online auction-houses for counterfeiting. In the United States, the illustrious jewellery store, Tiffany & Co, brought a legal action against eBay Inc, alleging direct trademark infringement, contributory trademark infringement, false advertising, unfair competition and trademark dilution. The luxury store depicted the online auction-house as a pirate bazaar, a flea-market and a haven for counterfeiting. During epic litigation, eBay Inc successfully defended itself against these allegations in a United States District Court and the United States Court of Appeals for the Second Circuit. Tiffany & Co made a desperate, unsuccessful effort to appeal the matter to the Supreme Court of the United States. The matter featured a number of interventions from amicus curiae — Tiffany was supported by Coty, the Fashion Designer's Guild, and the International Anticounterfeiting Coalition, while eBay was defended by publicly-spirited civil society groups such as Electronic Frontier Foundation, Public Citizen, and Public Knowledge as well as Yahoo!, Google Inc, Amazon.com, and associations representing telecommunications carriers and internet service providers. The litigation in the United States can be counterpointed with the fusillade of legal action against eBay in the European Union. In contrast to Tiffany & Co, Louis Vuitton triumphed over eBay in the French courts — claiming its victory as vindication of the need to protect the commercial interests and cultural heritage of France. However, eBay has fared somewhat better in a dispute with L’Oréal in Great Britain and the European Court of Justice. It is argued that, in a time of flux and uncertainty, Australia should follow the position of the United States courts in Tiffany & Co v eBay Inc. The final part examines the ramifications of this litigation over online auction-houses for trade mark law reform and consumer rights; parallel disputes over intermediary liability and safe harbours in the field of copyright law and the Anti-Counterfeiting Trade Agreement 2010. The conclusion calls for a revision of trade mark law, animated by a respect for consumers’ rights and interests in the electronic marketplace.
Resumo:
I must admit that I approached the European Union-supported educational research 1995-2003: Briefing papers for policy makers with a sense of trepidation. As a researcher who defines himself as socially critical, I wondered about the dynamics of a policy document that was published by the bureaucracy that has, in some form, a vested interest in the structure and operation of education in its various guises. In turning my attention to this review, I decided to focus my attention on the third guiding question that argues education and training "are strongly interconnected with concerns that include citizenship and democratic participation, inequalities and social justice, cultural diversity and quality of life" (Millei, 2005). The Briefing Papers include recommendations on democracy and citizenship, social exclusion and equality, gender and dealing with mental illness in schools...
Resumo:
The secretive 2011 Anti-Counterfeiting Trade Agreement – known in short by the catchy acronym ACTA – is a controversial trade pact designed to provide for stronger enforcement of intellectual property rights. The preamble to the treaty reads like pulp fiction – it raises moral panics about piracy, counterfeiting, organised crime, and border security. The agreement contains provisions on civil remedies and criminal offences; copyright law and trademark law; the regulation of the digital environment; and border measures. Memorably, Susan Sell called the international treaty a TRIPS Double-Plus Agreement, because its obligations far exceed those of the World Trade Organization's TRIPS Agreement 1994, and TRIPS-Plus Agreements, such as the Australia-United States Free Trade Agreement 2004. ACTA lacks the language of other international intellectual property agreements, which emphasise the need to balance the protection of intellectual property owners with the wider public interest in access to medicines, human development, and transfer of knowledge and technology. In Australia, there was much controversy both about the form and the substance of ACTA. While the Department of Foreign Affairs and Trade was a partisan supporter of the agreement, a wide range of stakeholders were openly critical. After holding hearings and taking note of the position of the European Parliament and the controversy in the United States, the Joint Standing Committee on Treaties in the Australian Parliament recommended the deferral of ratification of ACTA. This was striking as representatives of all the main parties agreed on the recommendation. The committee was concerned about the lack of transparency, due process, public participation, and substantive analysis of the treaty. There were also reservations about the ambiguity of the treaty text, and its potential implications for the digital economy, innovation and competition, plain packaging of tobacco products, and access to essential medicines. The treaty has provoked much soul-searching as to whether the Trick or Treaty reforms on the international treaty-making process in Australia have been compromised or undermined. Although ACTA stalled in the Australian Parliament, the debate over it is yet to conclude. There have been concerns in Australia and elsewhere that ACTA will be revived as a ‘zombie agreement’. Indeed, in March 2013, the Canadian government introduced a bill to ensure compliance with ACTA. Will it be also resurrected in Australia? Has it already been revived? There are three possibilities. First, the Australian government passed enhanced remedies with respect to piracy, counterfeiting and border measures in a separate piece of legislation – the Intellectual Property Laws Amendment (Raising the Bar) Act 2012 (Cth). Second, the Department of Foreign Affairs and Trade remains supportive of ACTA. It is possible, after further analysis, that the next Australian Parliament – to be elected in September 2013 – will ratify the treaty. Third, Australia is involved in the Trans-Pacific Partnership negotiations. The government has argued that ACTA should be a template for the Intellectual Property Chapter in the Trans-Pacific Partnership. The United States Trade Representative would prefer a regime even stronger than ACTA. This chapter provides a portrait of the Australian debate over ACTA. It is the account of an interested participant in the policy proceedings. This chapter will first consider the deliberations and recommendations of the Joint Standing Committee on Treaties on ACTA. Second, there was a concern that ACTA had failed to provide appropriate safeguards with respect to civil liberties, human rights, consumer protection and privacy laws. Third, there was a concern about the lack of balance in the treaty’s copyright measures; the definition of piracy is overbroad; the suite of civil remedies, criminal offences and border measures is excessive; and there is a lack of suitable protection for copyright exceptions, limitations and remedies. Fourth, there was a worry that the provisions on trademark law, intermediary liability and counterfeiting could have an adverse impact upon consumer interests, competition policy and innovation in the digital economy. Fifth, there was significant debate about the impact of ACTA on pharmaceutical drugs, access to essential medicines and health-care. Sixth, there was concern over the lobbying by tobacco industries for ACTA – particularly given Australia’s leadership on tobacco control and the plain packaging of tobacco products. Seventh, there were concerns about the operation of border measures in ACTA. Eighth, the Joint Standing Committee on Treaties was concerned about the jurisdiction of the ACTA Committee, and the treaty’s protean nature. Finally, the chapter raises fundamental issues about the relationship between the executive and the Australian Parliament with respect to treaty-making. There is a need to reconsider the efficacy of the Trick or Treaty reforms passed by the Australian Parliament in the 1990s.