58,243 research outputs found
Diffusive author(s), cohesive author: Analysis of S/N (1994)
No full textThis study indicates the ways in which various aspects of the author(s) are brought forth in Dumb type’s performance art, the S/N production. Previous research has suggested a non-hierarchical organization of Dumb type and the absence of a “privileged author” in Dumb type’s collaborative work, S/N. However, the results that I have investigated from member’s interviews on the creative process of S/N along with my analysis of the recorded images of S/N, indicate a different aspect of the author(s). First, S/N was created through, so to speak, the collective ideas of the members of Dumb type. Further, S/N has at least nine quotations from previous performances, installations, and printed writings, besides the work-in-progress technique. Explicating one of the “author functions” as given by Michel Foucault, each text has plural subjects of the author. However, it has been revealed from members’ interviews that Teiji Furuhashi had a decision-making role in selecting the members’ ideas within the performance. Since then, S/N has had plural subjects of creation; however, Furuhashi is one of the subjects of creation along with the “privileged author.” S/N has plural authors (diffusive authors) yet at the same time, it has a “privileged author,” Teiji Furuhashi (cohesive author)
The vanishing author in computer-generated works: a critical analysis of recent Australian case law
No full textAbstract
The use of software is ubiquitous in the creation of many copyright works, yet the requirement in copyright law that every work have a human author who engages in independent intellectual effort means that its use may prevent copyright subsistence. Several recent Australian cases have refocused attention on authorship as an essential criterion of copyright subsistence, and these cases suggest that much computer-produced output may be authorless and thus lack copyright protection. This article, the first in a two-part series, analyses how each case deals with the question of authorship of computer-produced works and why the use of software diminishes copyright protection for a significant number of computer-generated works. The article critiques the application of conventional notions of human authorship developed in the pre-computer age to modern productions and suggests alternative approaches to authorship that satisfy both the major objectives of copyright policy and the need to adapt to the computer age. The article argues that, without a broader judicial approach to authorship of computer-generated works, Parliament must remedy the lacuna in protection for these ‘authorless’ works. Possible solutions for reform are suggested. In a forthcoming article, the author comprehensively examines those reform proposals
Curtailing Endothelial TGF-beta Signaling Is Sufficient to Reduce Endothelial-Mesenchymal Transition and Fibrosis in CKD
No full textExcessive TGF-beta signaling in epithelial cells, pericytes, or fibroblasts has been implicated in CKD. This list has recently been joined by endothelial cells (ECs) undergoing mesenchymal transition. Although several studies focused on the effects of ablating epithelial or fibroblast TGF-beta signaling on development of fibrosis, there is a lack of information on ablating TGF-beta signaling in the endothelium because this ablation causes embryonic lethality. We generated endothelium-specific heterozygous TGF-beta receptor knockout (T beta R parallel to(endo+/-)) mice to explore whether curtailed TGF-beta signaling significantly modifies nephrosclerosis. These mice developed normally, but showed enhanced angiogenic potential compared with T beta R parallel to(endo+/+) mice under basal conditions. After induction of folic acid nephropathy or unilateral ureteral obstruction, T beta R parallel to(endo+/-) mice exhibited less tubulointerstitial fibrosis, enhanced preservation of renal microvasculature, improvement in renal blood flow, and less tissue hypoxia than T beta R parallel to(endo+/+) counterparts. In addition, partial deletion of T beta R parallel to in the endothelium reduced endothelial-to-mesenchymal transition (EndoMT). TGF-beta-induced canonical Smad2 signaling was reduced in T beta R parallel to(endo+/-) ECs; however, activin receptor-like kinase 1 (ALK1)-mediated Smad1/5 phosphorylation in T beta R parallel to(+/-) ECs remained unaffected. Furthermore, the S-endoglin/L-endoglin mRNA expression ratio was significantly lower in T beta R parallel to(+/-) ECs compared with T beta R parallel to(endo+/+) ECs. These observations support the hypothesis that EndoMT contributes to renal fibrosis and curtailing endothelial TGF-beta signals favors Snnad1/5 proangiogenic programs and dictates increased angiogenic responses. Our data implicate endothelial TGF-beta signaling and EndoMT in regulating angiogenic and fibrotic responses to injury
Experimental investigation into the effect of substrate clamping on the piezoelectric behaviour of thick-film PZT elements
No full textThis paper details an experimental investigation of the clamping effect associated with thick-film piezoelectric elements printed on a substrate. The clamping effect reduces the measured piezoelectric coefficient, d33, of the film. This reduction is due to the influence of the d31 component in the film when a deformation of the structure occurs, by either the direct or indirect piezoelectric effect. Theoretical analysis shows a reduction in the measured d33 of 62%, i.e. a standard bulk lead zirconate titanate (PZT)-5H sample with a manufacturer specified d33 of 593pC/N would fall to 227.8pC/N. To confirm this effect, the d33 coefficients of five thin bulk PZT-5H samples of 220µm thickness were measured before and after their attachment to a metallized 96% alumina substrate. The experimental results show a reduction in d33 of 74% from 529pC/N to 139pC/N. The theoretical analysis was then applied to existing University of Southampton thick-film devices. It is estimated that the measured d33 value of 131pC/N of the thick-film devices is the equivalent of an unconstrained d33 of 345pC/N
A molecular dynamics study of N-A-S-H gel with various Si/Al ratios
No full textThe understanding of sodium aluminosilicate hydrate (N-A-S-H) gel is still limited due to its complex and amorphous structure. Recently, molecular dynamics simulation has provided a unique opportunity to better understand the structure of N-A-S-H gel from nanoscale. In this work, the N-A-S-H gel structure was obtained by simulating the polymerization of Si and Al monomers by molecular dynamics. The simulated polymerization process is in good agreement with the experimental results especially in terms of the reaction rate of Si and Al species. The atomic structural features of the N-A-S-H gel were analyzed in terms of bond length and bond angle information, simulated X-ray diffraction (XRD) and Qn distribution. A significant finding is the existence of pentacoordinate Al in all simulated N-A-S-H structures, indicating that pentacoordinate Al in geopolymer does not only come from raw material. Besides, the results show that a smaller Si/Al ratio led to a more crosslinked and compacted structure of N-A-S-H gel
Receptor Guanylyl Cyclase C Cross-talk With Tyrosine Kinases And The Adaptor Protein, Crk
No full textSignal transduction is a crucial event that enables cells to sense and respond to cues from their immediate environment. Guanylyl cyclase C (GC-C) is a member of the family of receptor guanylyl cyclases. GC-C is a single transmembrane protein that responds to its ligands by the production of the second messenger cGMP. The guanylin family of peptides, (including the bacterially produced heat-stable enterotoxin ST) is the ligand for GC-C, elevates intracellular cGMP levels and activates downstream pathways. GC-C regulates the cystic fibrosis transmembrane conductance regulator (CFTR) by inducing phosphorylation by protein kinase G, resulting in chloride ion and fluid efflux. GC-C also regulates cell cycle progression through cGMP-gated Ca2+ channels. These functions are seen in the intestinal epithelium, the primary site for GC-C expression.
GC-C as a molecule has been studied in detail, but its functioning in the context of other signaling pathways remains unknown. The aim of the present investigation was to understand the regulation of signal transduction by GC-C and its cross-talk with other signaling pathways operating in the cell. Molecular events that commonly connect components in a signaling pathway are protein phosphorylation and protein-protein interaction. These two aspects are explored in this thesis.
The possibility of tyrosine phosphorylation of GC-C has been explored earlier in our laboratory. In vitro studies indicated that the residue Tyr820 was a site for phosphorylation by the Src family of non-receptor tyrosine kinases and those studies also suggested that phosphorylated Tyr820 could bind to the SH2 domain of Src. We generated a nonphosphorylatable mutant of GC-C, GC-CY820F, and a phosphomimetic mutant GC-CY820E to study the effect of phosphorylation of Tyr820, on the functioning of GC-C. A stable cell line of HEK293:GC-CY820F cells was generated and compared with HEK293:GC-CWT. Dose response to ST in the two cell lines showed that cGMP accumulation by GC-CY820F was greater than that of GC-CWT, although the EC50 remained unchanged. The phosphomimetic GC-CY820E mutant receptor was non-responsive to ST. Further in HEK293 cells, phosphorylation of GC-CWT by constitutively active v-Src resulted in decreased ST stimulation and this effect of v-Src was reduced with GC-CY820F. Inhibition of ST stimulation brought about by v-Src required catalytically active Src, as the kinase inactive v-SrcK295R did not inhibit ST stimulation. These results were corroborated by in vitro studies by using the recombinant catalytic domain of GC-C expressed in insect cells and by phosphorylation using a purified kinase, Hck. Observations suggested that phosphorylation of Tyr820 in the catalytic domain of GC-C compromises the guanylyl cyclase activity of GC-C.
T84 and Caco-2 colon carcinoma cells endogenously express GC-C. The effect of tyrosine phosphorylation of GC-C was studied by using HgCl2, a known activator of Src kinases, and by the inhibition of protein tyrosine phosphatases using pervanadate, an irreversible inhibitor. Both these ways of achieving increased tyrosine phosphorylation resulted in decreased ST-stimulated cGMP production by GC-C, as suggested from v-Src transfection studies. This decrease was reversed by using a Src kinase specific inhibitor PP2, confirming the role of Src kinases in the inhibition of GC-C activity. Interestingly, in Caco-2 cells that differentiate in culture, the effect of pervanadate on the inhibition of ST-stimulated GC-C activation was dependent on the differentiation stage. Crypt-like cells showed higher inhibition with pervanadate. As they matured into villus-like cells, the effect of pervanadate on GC-C activation was gradually lost. This effect also correlated with a decrease in the expression of Lck, suggesting that in the context of the intestine there could be differential regulation of tyrosine phosphorylation of GC-C along the crypt-villus axis. Intestinal ligated loop assays in rats demonstrated that ST-induced fluid accumulation in the intestine was abrogated on pervanadate treatment. Reduction in this fluid accumulation by pervanadate was not observed with 8-Br-cGMP, a cell permeable analogue of cGMP. This indicated that tyrosine phosphorylation of proteins is important for ST-induced fluid accumulation, and perhaps pervanadate modulates this by phosphorylation of GC-C, thereby causing a reduction in fluid accumulation.
Earlier in vitro studies on Src-SH2 binding from the laboratory had suggested the possibility of activation of Src family kinases by GC-C. The activation status of Src kinases was monitored by using phosphorylation-state specific antibody, pSFK416. ST stimulation in T84 cells increased Tyr416 phosphorylation of Src kinases in a time dependent manner, indicating that Src kinases are activated downstream of GC-C. This activation of Src kinases was also seen with the endogenous ligand of GC-C, uroguanylin. Interestingly, 8-Br-cGMP a cell permeable analogue of cGMP that is known to mimic other cellular effects of GC-C, namely Cl-secretion and cell cycle progression, did not activate Src kinases, suggesting that the mechanism of Src kinase activation by GC-C could be independent of cGMP.
Binding affinities of Src, Lck, Fyn and Yes SH2 domains to Tyr820 phosphorylated GCC peptide were in the nM range, indicating a high affinity of interaction. In vitro GST-SH2 pull down experiments suggested that phosphorylation of Tyr820 in full length GC-C allows interaction of GC-C to the SH2 domain of Src. These studies suggest a dual cross-talk between Src kinases and GC-C; Src phosphorylation inhibits GC-C signaling and stimulation of GC-C by its ligands activates Src kinases.
Interaction of proteins containing SH2 and SH3 domains are commonly found in signaling molecules. In accordance with the observation that there are three PXXP motifs in GCC, many SH3 domains could interact with GC-C. GC-C appears to show a preference to bind the SH3 domains of Fyn, Hck, Abl tyrosine kinases, Grb2 and Crk adaptor proteins, the α-subunit of P85 PI3 kinase, PLC-γ and cortactin to various extents. The SH3 domains of spectrin and Nck did not show any detectable interaction with GC-C. In SH3 pull-down assays, the N-terminal SH3 domain of Crk, CrkSH3 (N), bound GC-C maximally, suggesting that Crk is a good candidate for interaction with GC-C.
By overlay analysis, the region of GC-C that binds CrkSH3 (N) was narrowed down to the catalytic domain of GC-C containing a ‘PGLP’ motif. Mutations were generated in GC-C at this site to generate GC-CP916Q and GC-CW918R. These mutations compromised the binding of full length receptor to CrkSH3 (N). In cells, CrkII and GC-C co-transfection inhibited the ST stimulation of GC-C. A CrkII mutant, that has compromised binding through its SH3 domain, did not inhibit the activity of GC-C. CrkII from T84 cells co-immunoprecipitated with GC-C and interestingly, the phosphorylated form of CrkII did not, indicating that GC-C - Crk interaction could be regulated by the phosphorylation of Crk.
In summary, this study places GC-C, in the context of tyrosine kinase signaling pathway and interaction with the adaptor protein Crk. These studies suggest that GC-C signal transduction can be altered by cross-talk with other signaling events in the cell. Reversible phosphorylation of tyrosine residues inhibits the activity of GC-C, and this is mediated by Src family kinases. Src kinases themselves are activated on stimulation of GC-C by its ligands, possibly because of SH2 domain interaction with GC-C. Association of Crk by its SH3 domain regulates GC-C functioning primarily by inhibiting ST-stimulated cGMP production. This opens up the possibility of GC-C signaling through a multimeric complex involving other binding partners of Crk, and these cross-talks involving GC-C with the two proto-oncogenes, Src and Crk, might have far reaching consequences in the regulation of cellular functions
Enhanced structural and electrical properties due to the effect of co-doping ceria electrolyte
No full textRatio of n-6/n-3 in the diets of beef cattle
No full textEffects of feeding heat-treated canola (C), soybean (S) and flax (F) or mixtures on growth and slaughter characteristics, taste and fatty acid (FA) composition of beef tissue were investigated using 128 crossbred steers to determine the potential of improving the nutritional quality of beef for humans. For Trial 1 (48 steers), dietary treatments were: roasted C, extruded C, roasted S, extruded S, roasted F and extruded F. For Trial 2 (80 steers), the dietary treatments were: S:F (1:1), S:C (1:1), C:F (1:1) and S:F:C (1:1:1), and the oilseeds were processed either by roasting or extruding before mixing. Soybean meal and soybean oil were used to give equivalent lipid and protein contents to each experimental diet. The basal diet consisted of grass silage, barley grain, vitamins and minerals. Steers were fed for a minimum of 100d then slaughtered at a uniform degree of finish. Growth and slaughter characteristics of the steers were only slightly affected by dietary treatment in that the soybean-fed steers consumed more feed and had a higher average daily gain than the canola or flax-fed animals in Trial 1. There was no difference in taste panel parameters for any of the treatments. Inclusion of flax in the diet increased the total n-3 content of meat. Similar results were found for canola and C18:1n-9 although this was not the case for soybean and the n-6 FA. For the n-6 FA in the PL and neutral lipid fractions of the meat samples, levels were correlated with high dietary levels of n-6 or n-9 with low levels of n-3 while for the n-3 FA, levels were correlated with high dietary n-3 levels and low n-6 levels. Oilseed processing method did not have an effect on any fatty acid levels. It is possible to modify the FA composition of beef meat toward a healthier profile by including heat-treated oilseeds in the diet to influence the degree of lipid metabolism in the rumen.ID: S0377840111004007; M3: Article; Accession Number: S0377840111004007; Author: M.A. McNiven (a, ⁎); Author: J.L. Duynisveld (b); Author: T. Turner (a); Author: A.W. Mitchell (a); Affiliation: Department of Health Management, Atlantic Veterinary College, University of PEI, Charlottetown, PEI, Canada C1A 4P3; Affiliation: Agriculture and Agri-Food Canada, Nappan, NS, Canada B0L 1C0; Keyword: Oilseeds; Keyword: Roasted; Keyword: Extruded; Keyword: Fatty acids; Keyword: Healthy fat; Number of Pages: 11; Language: English
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