Interdisciplinary Legal Scholarship in Search of a Paradigm

A “mature” science, according to Thomas Kuhn, can afford to be uncritical. It has finally answered to its practitioners\u27 satisfaction the fundamental, foundational questions of their field. It finally rests (“for a time,” at least) on an established scientific achievement that epitomizes the accomplished, collective wisdom of an age and defines the terms, conditions, directions, and limits of further refining research. With this “paradigm” in place, researchers are spared the incessant and distracting reexamination of first principles, the extravagant costs of intellectual retooling; they can proceed with confidence, effectiveness, and efficiency to do what they do best: articulating and specifying the received paradigm in more depth and detail, extending and applying it to new areas of interest. Because a paradigm “provides rules that tell the practitioner of a mature specialty what both the world and his science are like,” the practitioner “can concentrate with assurance upon the esoteric problems that these rules and existing knowledge define for him.” Postmodern legal theory appropriates and assimilates Kuhn\u27s insights in ways and to an extent that have not, I think, yet been fully recognized. In describing the development of legal scholarship in Kuhnian terms, I am thus merely elaborating assumptions integral to contemporary intellectual discourse. In particular, interdisciplinary legal scholarship regularly proceeds on the assumption that it possesses a stable, accepted, and uncontroversial paradigm for further research-in other words, that it constitutes a “mature science.” But beneath the institutional trappings of interdisciplinary legal scholarship I detect not a scholarly tradition that has finally resolved to general acclaim all its basic, foundational, methodological problems, but rather one that has never really confronted them. As a result, the attempt to apply the supposed paradigm of interdisciplinary legal scholarship to its subject matter reveals significant “anomalies” in the application. In what follows I shall first analyze and discuss these anomalies and then consider in some detail a specific example of contemporary interdisciplinary legal scholarship

Augmenting Agent Platforms to Facilitate Conversation Reasoning

Within Multi Agent Systems, communication by means of Agent Communication Languages (ACLs) has a key role to play in the co-operation, co-ordination and knowledge-sharing between agents. Despite this, complex reasoning about agent messaging, and specifically about conversations between agents, tends not to have widespread support amongst general-purpose agent programming languages. ACRE (Agent Communication Reasoning Engine) aims to complement the existing logical reasoning capabilities of agent programming languages with the capability of reasoning about complex interaction protocols in order to facilitate conversations between agents. This paper outlines the aims of the ACRE project and gives details of the functioning of a prototype implementation within the Agent Factory multi agent framework

Induction of endothelial cell proliferation by recombinant and microparticle-tissue factor involves β1-integrin and extracellular signal regulated kinase activation

Objective: Increased levels of circulating tissue factor (TF) in the form of microparticles increase the risk of thrombosis. However, any direct influence of microparticle-associated TF on vascular endothelial cell proliferation is not known. In this study, the influence of recombinant and microparticle- associated TF on endothelial cell proliferation and mitogen-activated protein kinase signaling mechanisms was examined. Methods and Results: Incubation of human coronary artery endothelial cells with lipidated recombinant full-length TF, or TF-containing microparticles (50 to 200 pmol/L TF), increased the rate of cell proliferation and induced phosphorylation of extracellular signal regulated kinase 1 in a TF-dependent manner. Inhibition of extracellular signal regulated kinase 1/2 using PD98059 or extracellular signal regulated kinase 1/2 antisense oligonucleotides or inhibition of c-Jun N-terminal kinase reduced recombinant TF-mediated cell proliferation. PD98059 also reduced cell proliferation in response to TF-containing microparticles. Inclusion of FVIIa (5 nmol/L) and FXa (10 nmol/L) or preincubation of cells with an inhibitory anti-FVIIa antibody had no additional influence on TF-mediated cell proliferation. However, preincubation of exogenous TF with a β1-integrin peptide (amino acids 579 to 799) reduced TF-mediated proliferation. Conclusion: High concentrations of recombinant or microparticle-associated TF stimulate endothelial cell proliferation through activation of the extracellular signal regulated kinase 1/2 pathway, mediated through a novel mechanism requiring the interaction of exogenous TF with cell surface β1-integrin and independent of FVIIa. © 2010 American Heart Association, Inc

Filamin-A is required for the incorporation of tissue factor into cell-derived microvesicles

We previously reported that the incorporation of tissue factor (TF) into cell-derived microvesicles (MVs) is regulated by the phosphorylation of the cytoplasmic domain of TF. Since the cytoskeletal protein filamin-A is known to bind to the cytoplasmic domain of TF in a phosphorylation-dependent manner, the involvement of filamin-A in the incorporation of TF into MVs was examined. Endothelial cells were transfected to express TF, whereas MDA-MB-231 cells were used to examine endogenously expressed TF. MV release was induced by activating protease-activated receptor-2 (PAR2). Partial suppression of filamin-A expression using two different filamin-A siRNA sequences resulted in significant reductions in the incorporation of TF antigen into MVs as determined by TF-ELISA and western blot analysis, and was reflected in reduced thrombin-generation and FXa-generation capacities of these MVs. Deletion of the cytoplasmic domain of TF also resulted in reduced incorporation of TF into MVs, whereas the suppression of filamin-A expression had no additional effect on the incorporation of truncated TF into MVs. Partial suppression of filamin-A expression had no effect on the number and size distribution of the released MVs. However, >90 % suppression of filamin-A expression resulted in increased MV release, possibly as a result of increased instability of the plasma membrane and underlying cytoskeleton. In conclusion, the presence of filamin-A appears to be essential for the incorporation of TF into MVs following PAR2 activation, but is not required for the process of MV formation and release following PAR2 activation

A new substrate for sampling deep river macroinvertebrates

We compared macroinvertebrate communities colonising multiplate samplers constructed from perspex or tempered hardboard (wood) with an alternative artificial substrate constructed from folded coconut fibre matting (coir) enclosed in nylon netting. Substrates were incubated for 62 days over January to March 2007 at six sites over 240 km along the Waikato River. The three substrates supported similar numbers of invertebrate taxa (27 - 29 taxa), but coir samples contained 71% of total invertebrate numbers from all substrates combined, compared with <17% for each type of multiplate sampler. Coir faunas were heavily dominated by the hydrobiid snail Potamopyrgus (84 % of numbers), and this taxon along with the amphipod Paracalliope comprised 58 - 66 % of invertebrates on both types of multiplate samplers. Analysis of a Bray-Curtis matrix suggested statistically significant differences in percent community composition between coir samplers and each type of multiplate sampler over the late summer study period. Densities per cm3 of Oligochaeta, Mollusca, and "other worms" (Platyhelminthes, Rhabdocoela, Nemertea and Hirudinea combined) were significantly higher in coir samples than one or both of the multiplate samplers. Results suggest coir samplers may provide a useful supplement to multiplate samplers for deep river invertebrate studies by collecting a different range of taxa, including those favouring cover and characteristic of depositional environments

Accumulation of tissue factor in endothelial cells induces cell apoptosis, mediated through p38 and p53 activation

We previously reported that high levels of tissue factor (TF) can induce cellular apoptosis in endothelial. In this study, TF-mediated mechanisms of induction of apoptosis were explored. Endothelial cells were transfected to express wild-type TF. Additionally, cells were transfected to express Asp253-substituted, or Ala253-substitued TF to enhance or prevent TF release respectively. Alternatively, cells were pre-incubated with TF-rich and TF-poor microvesicles. Cell proliferation, apoptosis and the expression of cyclin D1, p53, bax and p21 were measured following activation of cells with PAR2-agonist peptide. Greatest levels of cell proliferation and cyclin D1 expression were observed in cells expressing wild-type or Asp253-substituted TF. In contrast, increased cellular apoptosis was observed in cells expressing Ala253-substituted TF, or cells pre-incubated with TF-rich microvesicles. The level of p53 protein, p53-phosphorylation at ser33, p53 nuclear localisation and transcriptional activity, but not p53 mRNA, were increased in cells expressing wild-type and Ala253-substituted TF, or in cells pre-incubated with TF-rich microvesicles. However, the expression of bax and p21 mRNA, and Bax protein were only increased in cells pre-incubated with TF-rich microvesicle and in cells expressing Ala253-substituted TF. Inhibition of the transcriptional activity of p53 using pifithrin-α suppressed the expression of Bax. Finally, siRNA–mediated suppression of p38α, or inhibition using SB202190 significantly reduced the p53 protein levels, p53 nuclear localisation and transcriptional activity, suppressed Bax expression and prevented cellular apoptosis. In conclusion, accumulation of TF within endothelial cell, or sequestered from the surrounding can induce cellular apoptosis through mechanisms mediated by p38, and involves the stabilisation of p53