25,691 research outputs found
The construction of Karen Karnak: The multi-author-function
No full textThis thesis is situated within the comparatively recent developments of Web 2.0 and the emergence of interactive WikiMedia, and explores the mode of authorship within a Read/Write culture compared to that of a Read/Only tradition. The hypothesis of this study is that the role of the audience has become merged with the author, and as such, represents new functions and attributes, distinct from a more conventional concept of authorship, in which the roles of audience and author are more separate. Read/Write and participatory culture, as defined by this study, is focused on collaboration, and includes the influences of D.I.Y. culture, Open-Source practices and the production of text by multiple authors. Multi-authorship presents a re-thinking of several concepts which support the notion of the individual author, since the focus of multi-authorship is not on attribution and ownership of a finished text, but on the continued malleability of a text. Modes of multi-authorship, demonstrated in the use of the pseudonyms Alan Smithee and Karen Eliot, represent declarative authors whose names signify multiple origins, whilst concurrently indicating a distinct body of work. The function of these names form an important context to this study, since primary research involves the construction of an experimental mode of multi-authorship utilising WikiMedia technology and the interaction of thirty nine participants, who are invited to create a body of work under the collective pseudonym Karen Karnak. The data generated by this experiment is analysed using aspects of Michel Foucault's author-function to identify and determine power structures inherent in the WikiMedia context. The interplay of power structures, including concepts such as identity, ownership and the body of work, affect the resulting mode of authorship and contribute to the construction of Karen Karnak, suggesting further areas of research into the emerging multi-author
Receptor Proteins for Nongenomic Actions of Thyroid Hormone.
No full textGenomic actions of thyroid hormone require the intranuclear binding by nuclear thyroid hormone receptors (TRs) of 3,5,3’-triiodo-L-thyronine (T3). Nongenomic actions of the hormone have been described that are initiated at the plasma membrane, in cytoplasm or in the mitochondrion. These are complex processes associated with maintenance of the cytoskeleton, control of cell respiration, cell proliferation—including tumor cell proliferation and angiogenesis—and nervous system function. We briefly review here the nature of the proteins which are now appreciated to initiate nongenomic actions of the hormone when they bind T3 or L-thyroxine (T4). These receptor proteins for nongenomic effects include truncated isoforms of TRalpha, cytoplasmic intact TRbeta, certain cytoplasmic enzymes and a structural protein of the plasma membrane, integrin alphaVbeta3
Thyroid Hormone and P- Glycoprotein in tumor cells.
No full textP-glycoprotein (P-gp; multidrug resistance pump 1, MDR1; ABCB1) is a plasma membrane efflux pump that when activated in
cancer cells exports chemotherapeutic agents. Transcription of the P-gp gene (MDR1) and activity of the P-gp protein are known to
be affected by thyroid hormone. A cell surface receptor for thyroid hormone on integrin v3 also binds tetraiodothyroacetic
acid (tetrac), a derivative of L-thyroxine (T4) that blocks nongenomic actions of T4 and of 3,5,3-triiodo-L-thyronine (T3) at
v3. Covalently bound to a nanoparticle, tetrac as nanotetrac acts at the integrin to increase intracellular residence time of
chemotherapeutic agents such as doxorubicin and etoposide that are substrates of P-gp. This action chemosensitizes cancer cells.
In this review, we examine possible molecular mechanisms for the inhibitory effect of nanotetrac on P-gp activity.Mechanisms for
consideration include cancer cell acidification via action of tetrac/nanotetrac on the Na+/H+ exchanger (NHE1) and hormone
analogue effects on calmodulin-dependent processes and on interactions of P-gp with epidermal growth factor (EGF) and
osteopontin (OPN), apparently via v3. Intracellular acidification and decreasedH+ efflux induced by tetrac/nanotetrac viaNHE1
is the most attractive explanation for the actions on P-gp and consequent increase in cancer cell retention of chemotherapeutic
agent-ligands of MDR1 protein
Language Change and SA-OT: The case of sentential negation
No full textSimulated Annealing for Optimality Theory (SA-OT) updates Optimality Theory by adding a model of performance to a theory of linguistic competence. Our aim is to show that SA-OT can contribute to language change simulations. Performance "errors" are considered to be one of the causes of variation and change. We have chosen to model the evolution of sentential negation (SN). The descriptive background adopts Jespersen's Cycle, according to which the evolution of sentential negation follows three main stages (1. pre-verbal, 2. discontinuous, and 3. post-verbal). Therefore, we advance a novel model for SN, based on SA-OT. It reproduces the three pure and the two observed mixed stages, whereas it correctly predicts the lack of an intermediate stage between 3 and 1. The success of the approach corroborates the computational, performance-based approach to the data. Finally, we employ the iterated learning paradigm to reproduce historical changes in a "simulated corpus study". This enterprise turns out to be more difficult than one would naively believe.Appeared open access as: Computational Linguistics in the Netherlands Journal (CLIN), vol. 1 (2011), pp. 21-40, and is available at http://www.clinjournal.org/sites/default/files/Lopopolo.pdfA. Lopopolo and Biró, T., “Language Change and SA-OT. The case of sentential negation”, Computational Linguistics in the Netherlands Journal, vol. 1, pp. 21-40, 2011.Peer Reviewe
Comparative effectiveness of aflibercept for the treatment of patients with neovascular age-related macular degeneration
No full textMichael Thomas,1 Shaymaa S Mousa,2 Shaker A Mousa1 1Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Albany, NY, USA; 2The Johns Hopkins University, Baltimore, MD, USA Abstract: Wet age-related macular degeneration (AMD) is the most common reason for vision loss in the United States. Many treatments, such as laser therapy and photodynamic therapies, have been used but their efficacy is limited. Emerging anti-vascular endothelial growth factor (VEGF) therapies are now considered the standard of care. Anti-VEGF agents inhibit angiogenesis in the eye by suppressing abnormal blood vessel growth, leading to vision improvement. Ranibizumab and bevacizumab are two examples of anti-VEGF drugs that have been approved; both showed promise based on the visual acuity scale. Aflibercept, another new therapy known to trap VEGF and inhibit multiple growth factors, is promising not only because it can be taken bimonthly based on year 1 of the VIEW trials, but it can also be extended, as demonstrated in year 2 of the VIEW trials. Based on a cost–effect analysis, aflibercept is comparable to other leading therapies. This is a review of relevant clinical trials that have proven the non-inferiority and safety of aflibercept compared to the standard of care and its unique role in the current management of wet AMD. Keywords: aflibercept, VEGF, anti-VEGF, pegatanib, bevacizumab, ranibizumab, VIEW trial
Nongenomic regulation by thyroid hormone of plasma membrane ion and small molecule pumps
No full textThe sodium/proton (Na/H) exchanger, Na,K-ATPase, and Ca2+-ATPase are membrane ion pumps whose basal activities may be regulated by local nongenomic actions of thyroid hormone and hormone analogues via a hormone receptor on plasma membrane integrin αvβ3. System A amino acid transport and the activity of P-glycoprotein (P-gp; ABCB1), a multidrug efflux pump, are also modulated by thyroid hormone and αvβ3. Where signal transduction has been studied, the presence of the hormone at the receptor is transduced by mitogen-activated protein kinase (MAPK) isoforms (ERK1/2; p38) or phosphatidylinositol 3-kinase into local actions. The existence of the cell surface receptor offers opportunities to pharmacologically modify actions of these important transport functions with nanoparticulate formulations of T4 and T3 that do not enter the cell. Such formulations may reverse complex intracellular accumulations of H+, Na+, and Ca2+ that occur in clinical settings such as ischemia. In addition, nanoparticulate tetraiodothyroacetic acid (tetrac), a thyroid hormone analogue that inhibits binding of T4 and T3 to integrin αvβ3 as well as certain other functions of the integrin, may reverse P-gp-dependent resistance to anti-cancer drugs in tumor cells
Molecular mechanisms of actions of formulations of the thyroid hormone analogue, tetrac, on the inflammatory response.
No full textBACKGROUND: Tetraiodothyroacetic acid (tetrac) and its nanoparticulate formulation (Nanotetrac) act at a cell surface receptor to block angiogenesis and tumor cell proliferation.
OBJECTIVE: The complex anti-angiogenic properties of tetrac and Nanotetrac caused us to search in the literature and in certain of our unpublished mRNA experiments for evidence that these agents affect the early inflammatory response, perhaps through actions on specific cytokines and chemokines.
RESULTS AND DISCUSSION: Tetrac and Nanotetrac inhibit expression in tumor cells of cytokine genes, e.g., specific interleukins, and chemokine genes, such as fractalkine (CX3CL1), and chemokine receptor genes (CX3CR1) that have been identified as high priority targets in the development of inflammation-suppressant drugs. The possibility is also examined that tetrac formulations have an effect on the function of inflammatory cells
Cancer cell gene expression modulated from plasma membrane integrin αvβ3 by thyroid hormone and nanoparticulate tetrac
No full textIntegrin αvβ3 is generously expressed by cancer cells and rapidly dividing endothelial cells. The principal ligands of the integrin are extracellular matrix proteins, but we have described a cell surface small molecule receptor on αvβ3 that specifically binds thyroid hormone and thyroid hormone analogues. From this receptor, thyroid hormone (L-thyroxine, T4; 3,5,3’-triiodo-L-thyronine, T3) and tetraiodothyroacetic acid (tetrac) regulate expression of specific genes by a mechanism that is initiated nongenomically. At the integrin, T4 and T3 at physiological concentrations are pro-angiogenic by multiple mechanisms that include gene expression, and T4 supports tumor cell proliferation. Tetrac blocks the transcriptional activities directed by T4 and T3 at αvβ3, but, independently of T4 and T3, tetrac modulates transcription of cancer cell genes that are important to cell survival pathways, control of the cell cycle, angiogenesis, apoptosis, cell export of chemotherapeutic agents and repair of double-strand DNA breaks. We have covalently bound tetrac to a 200 nm biodegradable nanoparticle that prohibits cell entry of tetrac and limits its action to the hormone receptor on the extracellular domain of plasma membrane αvβ3. This reformulation has greater potency than unmodified tetrac at the integrin and affects a broader range of cancer-relevant genes. In addition to these actions on intracellular kinase-mediated regulation of gene expression, hormone analogues at αvβ3 have additional effects on intracellular protein-trafficking (cytosol compartment to nucleus), nucleoprotein phosphorylation and generation of nuclear coactivator complexes that are relevant to traditional genomic actions of T3. Thus, previously unrecognized cell surface-initiated actions of thyroid hormone and tetrac formulations at αvβ3 offer opportunities to regulate angiogenesis and multiple aspects of cancer cell behavior
Stakeholder research CoVE Water SA: CoVE Water SA the umbrella for all stakeholders
No full textThe water and sanitation sector faces well-documented issues that are challenging to address, leading to the establishment of the Platform of Vocational Excellence (PoVE) Water. This platform brings together five regional Centers of Vocational Excellence (CoVE) Water in Europe and South Africa to ensure high-quality skills and competencies in the water sector. These CoVEs facilitate collaboration among stakeholders, enabling the development of vocational education and training programs to increase awareness, responsiveness to industry needs, and address sector challenges. A few months ago, CoVE Water SA was established in South Africa to achieve the previously mentioned goals. Therefore, it is important that the following research question is answered in this initial set-up phase: What actions need to be taken to enhance the effectiveness of the CoVE Water SA? To answer this research question, several important stakeholders were interviewed. Subsequently, the interviews were analysed thematically in order to extract the most important themes and quotes, PI grids were created to assess power and interest dynamics among stakeholders, and a Social Network Analysis was conducted to understand the CoVE Water SA network and potential clusters.The research findings have unveiled key aspects for enhancing the effectiveness of CoVE Water SA. The current network in the water sector has a low density, implying that many collaborations are lacking. This leads to a high degree of interdependence within the network, resulting in a non dynamic system. The lack of collaborations, such as connections with TVET colleges, schools, farmers and local communities, results in a lack of knowledge, funding and connection to the labour market. Governmental stakeholders, like DWS, EWSeta, and BGCMA, have been identified as influential players with extensive networks and important resources, Local Authorities and Research Organizations also play important roles. Universities exhibit substantial international links, making them crucial contributors. These stakeholders have the potential to provide knowledge, collaboration, and power. These are valuable insights for CoVE Water SA, fostering network growth and effectiveness in the water sector. Furthermore, six key themes have been derived from the conducted interviews, addressing the needs of stakeholders and where CoVE can make a valuable contribution. These themes include raising awareness, reducing the skills gap in the water sector, fostering international collaborations, mitigating the labour shortage in the water sector, improving education material and establishing desired collaborations. For each theme, the interviewed stakeholders have presented their views and numerous suggestions on how CoVE Water SA can assist in addressing these issues. Additionally, stakeholders have also mentioned possible failures of CoVE Water SA, which can aid in preventing any shortcomings of the platform. Furthermore, stakeholders mentioned ongoing initiatives related to the six themes, through which they can contribute to the platform. From the Thematic Analysis, PI Grids and the SNA, a set of actions have emerged that are essential for enhancing the effectiveness of CoVE Water SA. These actions revolve around expanding and enhancing the network, organising activities and contributing to educational improvement. In terms of broadening and strengthening the network, the platform should focus on enhancing the collaborations among educational groups, building stronger relations with international institutions in Europe and Africa, involving TVETs and schools within the water network, improving stakeholder involvement and encouraging the involvement of Local Communities to increase awareness and knowledge about water issues. Furthermore, CoVE Water SA should play a role in organising activities to raise awareness of Water Resource Management. Additionally, it should assist in improving curricula, supporting students’ preparation for the workforce and making the education more practical instead of only theoretical. CoVE Water SA should also provide training and learning resources as well as comprehensive courses.However, this study recognizes several limitations that should be considered in future research and when implementing recommendations for CoVE Water SA. These limitations encompass factors like a limited scope due to resource and time constraints, minimal varied interviewee responses, and potential biases in responses. Addressing these limitations will be crucial in guiding future research and actions for CoVE Water SA.CEGM3000Civil Engineerin
Interview with Erica Jolly - teacher, author and founding member of SA Social Studies Teachers Association
No full textErica is a teacher and author who was a founding member of the SA Social Studies Teachers Association (contributing to its text books) and the SA History Teachers Association. She took her Masters in English Literature at Flinders University and taught in Girls and Boys Technical Colleges for 40 years. Erica's published works include a history of vocational education in South Australia from 1897 - 2001, We Came to Marion 1955 - 1995 (1995), A Broader Vision: Voices of Vocational Education in SA (2001), Challenging the Divide: Approaches to Science and Poetry (2010), and Making a Stand (2015)
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