Zugl.: Göttingen, Universiẗat, Diss., 2007.

Thesis (Ph.D.)--University of Tasmania, 1996.

Thesis (Ph. D.)--Open University. BLDSC no. DX211789.

Thèse--Université de Paris. / Title and author's name also in Chinese on t.p. Includes index. "Bibliographie": p. [21]-33.

Thèse--Université de Paris. / Title and author's name also in Chinese on t.p. Includes index. "Bibliographie": p. [21]-33.

Thesis (M.S)--Rochester Institute of Technology, 2005. / Typescript. Includes bibliographical references (leaves 79-83).

Texte remanié de: Diss. Ph. D.--San Diego (Calif.)--University of California, 1986. Titre de soutenance : Parameter setting ; evidence from use, acquisition and breakdown in American sign language. / Bibliogr. p. 218-234. Index.

The central argument of this project is that meaningful and intelligible experience is conditioned by the determinate relationship between realms of reality, and that our humanity is grounded on the semiotic process of symbolic references, which is manifest in Charles S. Peirce’s and Robert C. Neville’s theories of determination. However they are contained by the past such processes of determination can be extended to the future through transformative effort. My investigation ranges over multiple paths that lead toward determinate processes, by suggesting that the problem of interpretation and of the intelligibility of experience can be solved only in reference to the full purview of determinate features of experience. In his theory of determination, Peirce considered two processes of determination, the semiotic process and epistemology. The semiotic process is an extensional process from object to interpretant that consists of an infinite chain of references that can be spatially reversible. The epistemological process of determination is temporal and irreversible, where the idea grows into the individual mind, as the universe is unfolded by the agency of mind. Peirce’s study of the logic of individuals of Duns Scotus is to find answers for the problem of individuality. For Peirce, God is individualized in the course of determination and at the same time determines all possible determinations. Due to his adopting the Scotian sense of necessity, Neville also adopts Duns Scotus’s logic of individuals to his theory of determination and valuation. As revealed in his theory of determination, in the ontological act of creation God becomes individual as a creator, an individual as the determiner of all possible determinations. In his theory of determination, Neville proposes modes of determination at the ontological level, as well as a collection of cosmological determinations. Neville works “inter-cosmologically” in order to account for the fundamental conditions of our knowing that brings ontological and cosmological determinations together. In their theory of interpretation, Peirce and Neville suggest a triadic system of semiotic network. Among other things, Neville provides a more sophisticated version of theory of interpretation, which involves realms of intelligibility. Both Peirce and Neville symbolism allows for the pragmatic semiotics based upon a brokenness of signs, which opens for further interpretation.

Complement system includes a conglomeration of a set of soluble factors and membrane anchored receptors, which has been designed to recognise and clear non self (pathogens) and altered self (apoptotic cells, necrotic cells and transformed cells). In a general theme, the recognition subcomponents bind to target, which is followed by limited proteolytic cleavage of downstream complement components. Three pathways namely classical, alternative and lectin converge on the generation of C3 convertase. The alternative pathway is activated by spontaneous cleavage of C3, generating C3a, an anaphylatoxin, and C3b, which binds to the surface of pathogens. A C3 convertase is formed, which has a half-life of about 90 seconds, is stabilised by properdin, and in an amplification loop a C5 convertase is formed leading to lytic pathway and cell lysis. This puts properdin at the heart of up regulator of alternative pathway. Properdin is structurally organised into seven thrombospondin repeats (TSR), whose functions have been delineated via deletion mutagenesis studies. In the chapter 3, we have expressed TSR4 and TSR5 in tandem in E. coli and shown that the two-module recombinant protein binds to C3b, sulfatides, and glycosaminoglycans similarly to native properdin. The recombinant module also seems to be an efficient inhibitor of properdin’s ability to stabilise C3bBb complex, thus offering a therapeutic possibility to dampen alternative pathway. Although properdin’s definite role in perpetuating the alternative pathway is well established, its structural organisation also appears to suggest its potential as an independent innate immune soluble factor that would not require engagement with complement system. In chapter 4, we report the ability of properdin to interact with mycobacterium (BCG) via TSR4+5 module, down regulate the microbial uptake by macrophages, and up regulate pro-inflammatory cytokine response via enhancing anti-mycobacterial TNF-α production. In chapter 5, we demonstrate that properdin as well as TSR4+5 interacts directly with a range of influenza A virus strains leading to inhibition of infection and dampening of pro-inflammatory response. The ability of properdin to interact with non-self is further reaffirmed by its ability to interact with nanoparticles and modulate subsequent immune cell response as presented under discussion chapter. Thus, this thesis reports a set of novel observations highlighting non-complement properties of properdin, which may be crucial in host pathogen interaction.

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