A language and toolkit for the specification, execution and monitoring of dependable distributed applications

PhD ThesisThis thesis addresses the problem of specifying the composition of distributed applications out of existing applications, possibly legacy ones. With the automation of business processes on the increase, more and more applications of this kind are being constructed. The resulting applications can be quite complex, usually long-lived and are executed in a heterogeneous environment. In a distributed environment, long-lived activities need support for fault tolerance and dynamic reconfiguration. Indeed, it is likely that the environment where they are run will change (nodes may fail, services may be moved elsewhere or withdrawn) during their execution and the specification will have to be modified. There is also a need for modularity, scalability and openness. However, most of the existing systems only consider part of these requirements. A new area of research, called workflow management has been trying to address these issues. This work first looks at what needs to be addressed to support the specification and execution of these new applications in a heterogeneous, distributed environment. A co- ordination language (scripting language) is developed that fulfils the requirements of specifying the composition and inter-dependencies of distributed applications with the properties of dynamic reconfiguration, fault tolerance, modularity, scalability and openness. The architecture of the overall workflow system and its implementation are then presented. The system has been implemented as a set of CORBA services and the execution environment is built using a transactional workflow management system. Next, the thesis describes the design of a toolkit to specify, execute and monitor distributed applications. The design of the co-ordination language and the toolkit represents the main contribution of the thesis.UK Engineering and Physical Sciences Research Council, CaberNet, Northern Telecom (Nortel)

Industrial-scale proteomics: from liters of plasma to chemically synthesized proteins

Human blood plasma is a useful source of proteins associated with both health and disease. Analysis of human blood plasma is a challenge due to the large number of peptides and proteins present and the very wide range of concentrations. In order to identify as many proteins as possible for subsequent comparative studies, we developed an industrial-scale (2.5 liter) approach involving sample pooling for the analysis of smaller proteins (M(r) generally < ca. 40 000 and some fragments of very large proteins). Plasma from healthy males was depleted of abundant proteins (albumin and IgG), then smaller proteins and polypeptides were separated into 12 960 fractions by chromatographic techniques. Analysis of proteins and polypeptides was performed by mass spectrometry prior to and after enzymatic digestion. Thousands of peptide identifications were made, permitting the identification of 502 different proteins and polypeptides from a single pool, 405 of which are listed here. The numbers refer to chromatographically separable polypeptide entities present prior to digestion. Combining results from studies with other plasma pools we have identified over 700 different proteins and polypeptides in plasma. Relatively low abundance proteins such as leptin and ghrelin and peptides such as bradykinin, all invisible to two-dimensional gel technology, were clearly identified. Proteins of interest were synthesized by chemical methods for bioassays. We believe that this is the first time that the small proteins in human blood plasma have been separated and analyzed so extensively