Theorizing accounting and other [calculative] practices in private equity:Experimenting with Schatzki’s ‘site’ ontology

This thesis contributes to social studies of finance and accounting (Vollmer, Mennicken, & Preda, 2009) and the practice theory literatures (Feldman & Orlikowski, 2011) by experimenting (Baxter & Chua, 2008) with concepts developed by Theodore Schatzki and demonstrating their relevance and usefulness in theorizing and explaining accounting and other organizational phenomena. Influenced by Schatzki, I have undertaken a sociological investigation of the practices, arrangements, and nexuses forming (part of) the social ‘site’ of private equity (PE). I have examined and explained the organization of practices within the PE industry. More specifically, I have sought to throw light on the practice organizations animating various PE practices. I have problematized a particular aspect of Schatzki’s practice organization framework: ‘general understanding’, which has so far been poorly understood and taken for granted in the accounting literature. I have tried to further explore the concept to clarify important definitional issues surrounding its empirical application. In investigating the forms of accounting and control practices in PE firms and how they link with other practices forming part of the ‘site’, I have sought to explain how the ‘situated functionality’ of accounting is ‘prefigured’ by its ‘dispersed’ nature. In doing so, this thesis addresses the recent calls for research on accounting and control practices within financial services firms. This thesis contributes to the social studies of finance and accounting literature also by opening the blackbox of investment [e]valuation practices prevalent in the PE industry. I theorize the due diligence of PE funds as a complex of linked calculative practices and bring to fore the important aspects of ‘practical intelligibility’ of the investment professionals undertaking investment evaluation. I also identify and differentiate the ‘causal’ and ‘prefigurational’ relations between investment evaluation practices and the material entities ‘constituting’ those practices. Moreover, I demonstrate the role of practice memory in those practices. Finally, the thesis also contributes to the practice theory literature by identifying and attempting to clarify and/or improve the poorly defined and/or underdeveloped concepts of Schatzki’s ‘site’ ontology framework.

Computational modelling approaches to vaccinology

Excepting the Peripheral and Central Nervous Systems, the Immune System is the most complex of somatic systems in higher animals. This complexity manifests itself at many levels from the molecular to that of the whole organism. Much insight into this confounding complexity can be gained through computational simulation. Such simulations range in application from epitope prediction through to the modelling of vaccination strategies. In this review, we evaluate selectively various key applications relevant to computational vaccinology: these include technique that operates at different scale that is, from molecular to organisms and even to population level.

The immune system as drug target

The immune system is perhaps the largest yet most diffuse and distributed somatic system in vertebrates. It plays vital roles in fighting infection and in the homeostatic control of chronic disease. As such, the immune system in both pathological and healthy states is a prime target for therapeutic interventions by drugs-both small-molecule and biologic. Comprising both the innate and adaptive immune systems, human immunity is awash with potential unexploited molecular targets. Key examples include the pattern recognition receptors of the innate immune system and the major histocompatibility complex of the adaptive immune system. Moreover, the immune system is also the source of many current and, hopefully, future drugs, of which the prime example is the monoclonal antibody, the most exciting and profitable type of present-day drug moiety. This brief review explores the identity and synergies of the hierarchy of drug targets represented by the human immune system, with particular emphasis on the emerging paradigm of systems pharmacology. © the authors, publisher and licensee Libertas Academica Limited.

Identifying key residues important for CGRP binding to its receptor

The calcitonin gene related peptide (CGRP) is a 37 amino acid neuropeptide. Its receptor is a heterodimeric complex of calcitonin receptor-like receptor (CLR) – a family B G-protein coupled receptor – and a single-pass transmembrane protein, receptoractivity modifying protein 1 (RAMP1). Here, we identify residues, within the N-terminal extracellular domain (ECD) of CLR, potentially involved in ligand binding.Certain residues presumed to be possible sites of contact for the CGRP were picked from the CLR/RAMP1 ECD crystal structure (PDB 3N7S). Residues were mutated to alanine (A) bysite-directed mutagenesis (QuikChangeTM, Stratagene). Mutants were analysed for their ability to stimulate cAMP and cell surface expression as previously described [1]. All mutants showed reduced potency, though to varying degrees as indicated by their pEC50 values. W69A and D70Ashowed significant reduction in cell surface expression.These findings suggest that these residues are important for the interaction of CGRP with its receptor. W69A and D70A, part of the WDG motif of family B GPCRs, are thought to rather play a role in receptor stability [2]. The data is consistent with CGRP binding in agroove between CLR and RAMP1. This project was supported byAston School of Life and Health Sciences.References1. Barwell J, Conner A & Poyner D (2011) Extracellular loops 1and 3 and their associated transmembrane regions of the calcitonin receptor-like receptor are needed for CGRP receptor function. Biochim Biophys Acta 1813, 1906–1916.2. Kumar S, Pioszak A, Zhang C et al. (2011) Crystal Structure of the PAC1R Extracellular Domain Unifies a Consensus Fold for Hormone Recognition by Class B G-Protein Cou-pled Receptors. PLoS One 6, e19682