Design and synthesis of potential antimicrobial agents

Chorismate mutase is one of the essential enzymes in the shikimate pathway and is key to the survival of the organism Mycobacterium tuberculosis. The x-ray crystal structure of this enzyme from Mycobacterium tuberculosis was manipulated to prepare an initial set of in silico protein models of the active site. Known inhibitors of the enzyme were docked into the active site using the flexible ligand / flexible active site side chains approach implemented in CAChe Worksystem (Fujitsu Ltd). The resulting complexes were refined by molecular dynamics studies in explicit water using Amber 9. This yielded a further set of protein models that were used for additional rounds of ligand docking. A binding hypothesis was established for the enzyme and this was used to screen a database of commercially available drug-like compounds. From these results new potential ligands were designed that fitted appropriately into the active site and matched the functional groups and binding motifs founds therein. Some of these compounds and close analogues were then synthesized and submitted for biological evaluation. As a separate part of this thesis, analogues of very active anti-tuberculosis pyridylcarboxamidrazone were also prepared. This was carried out by the addition and the deletion of the substitutions from the lead compound thereby preparing heteroaryl carboxamidrazone derivatives and related compounds. All these compounds were initially evaluated for biological activity against various gram positive organisms and then sent to the TAACF (USA) for screening against Mycobacterium tuberculosis. Some of the new compounds proved to be at least as potent as the original lead compound but less toxic.

H264 data partitioned video streaming

Motivated by the increasing demand and challenges of video streaming in this thesis, we investigate methods by which the quality of the video can be improved. We utilise overlay networks that have been created by implemented relay nodes to produce path diversity, and show through analytical and simulation models for which environments path diversity can improve the packet loss probability. We take the simulation and analytical models further by implementing a real overlay network on top of Planetlab, and show that when the network conditions remain constant the video quality received by the client can be improved. In addition, we show that in the environments where path diversity improves the video quality forward error correction can be used to further enhance the quality. We then investigate the effect of IEEE 802.11e Wireless LAN standard with quality of service enabled on the video quality received by a wireless client. We find that assigning all the video to a single class outperforms a cross class assignment scheme proposed by other researchers. The issue of virtual contention at the access point is also examined. We increase the intelligence of our relay nodes and enable them to cache video, in order to maximise the usefulness of these caches. For this purpose, we introduce a measure, called the PSNR profit, and present an optimal caching method for achieving the maximum PSNR profit at the relay nodes where partitioned video contents are stored and provide an enhanced quality for the client. We also show that the optimised cache the degradation in the video quality received by the client becomes more graceful than the non-optimised system when the network experiences packet loss or is congested.

Implications of query caching for JXTA peers

This dissertation studies the caching of queries and how to cache in an efficient way, so that retrieving previously accessed data does not need any intermediary nodes between the data-source peer and the querying peer in super-peer P2P network. A precise algorithm was devised that demonstrated how queries can be deconstructed to provide greater flexibility for reusing their constituent elements. It showed how subsequent queries can make use of more than one previous query and any part of those queries to reconstruct direct data communication with one or more source peers that have supplied data previously. In effect, a new query can search and exploit the entire cached list of queries to construct the list of the data locations it requires that might match any locations previously accessed. The new method increases the likelihood of repeat queries being able to reuse earlier queries and provides a viable way of by-passing shared data indexes in structured networks. It could also increase the efficiency of unstructured networks by reducing traffic and the propensity for network flooding. In addition, performance evaluation for predicting query routing performance by using a UML sequence diagram is introduced. This new method of performance evaluation provides designers with information about when it is most beneficial to use caching and how the peer connections can optimize its exploitation.