Synthesis and biological evaluation of nonpeptide mimetics of co-conotoxin GVIA

A benzothiazole-derived compound (4a) designed to mimic the C-alpha-C-beta bond vectors and terminal functionalities of Lys2, TyrI3 and Arg17 in omega-conotoxin GVIA was synthesised, together with analogues (4b-d), which had each side-chain mimic systematically truncated or eliminated. The affinity of these compounds for rat brain N-type and P/Q-type voltage gated calcium channels (VGCCs) was determined. In terms of N-type channel affinity and selectivity, two of these compounds (4a and 4d) were found to be highly promising, first generation mimetics of omega-conotoxin. The fully functionalised mimetic (4a) showed low PM binding affinity to N-type VGCCs (IC50 = 1.9 muM) and greater than 20-fold selectivity for this channel sub-type over P/Q-type VGCCs, whereas the mimetic in which the guanidine-type side chain was truncated back to an amine (4d, IC50 = 4.1 muM) showed a greater than 25-fold selectivity for the N-type channel. (C) 2004 Elsevier Ltd. All rights reserved.

Intelligent agent supported personalization for virtual learning environments

Virtual learning environments (VLEs) are computer-based online learning environments, which provide opportunities for online learners to learn at the time and location of their choosing, whilst allowing interactions and encounters with other online learners, as well as affording access to a wide range of resources. They have the capability of reaching learners in remote areas around the country or across country boundaries at very low cost. Personalized VLEs are those VLEs that provide a set of personalization functionalities, such as personalizing learning plans, learning materials, tests, and are capable of initializing the interaction with learners by providing advice, necessary instant messages, etc., to online learners. One of the major challenges involved in developing personalized VLEs is to achieve effective personalization functionalities, such as personalized content management, learner model, learner plan and adaptive instant interaction. Autonomous intelligent agents provide an important technology for accomplishing personalization in VLEs. A number of agents work collaboratively to enable personalization by recognizing an individual's eLeaming pace and reacting correspondingly. In this research, a personalization model has been developed that demonstrates dynamic eLearning processes; secondly, this study proposes an architecture for PVLE by using intelligent decision-making agents' autonomous, pre-active and proactive behaviors. A prototype system has been developed to demonstrate the implementation of this architecture. Furthemore, a field experiment has been conducted to investigate the performance of the prototype by comparing PVLE eLearning effectiveness with a non-personalized VLE. Data regarding participants' final exam scores were collected and analyzed. The results indicate that intelligent agent technology can be employed to achieve personalization in VLEs, and as a consequence to improve eLeaming effectiveness dramatically.

A web recommendation technique based on probabilistic latent semantic analysis

Web transaction data between Web visitors and Web functionalities usually convey user task-oriented behavior pattern. Mining such type of click-stream data will lead to capture usage pattern information. Nowadays Web usage mining technique has become one of most widely used methods for Web recommendation, which customizes Web content to user-preferred style. Traditional techniques of Web usage mining, such as Web user session or Web page clustering, association rule and frequent navigational path mining can only discover usage pattern explicitly. They, however, cannot reveal the underlying navigational activities and identify the latent relationships that are associated with the patterns among Web users as well as Web pages. In this work, we propose a Web recommendation framework incorporating Web usage mining technique based on Probabilistic Latent Semantic Analysis (PLSA) model. The main advantages of this method are, not only to discover usage-based access pattern, but also to reveal the underlying latent factor as well. With the discovered user access pattern, we then present user more interested content via collaborative recommendation. To validate the effectiveness of proposed approach, we conduct experiments on real world datasets and make comparisons with some existing traditional techniques. The preliminary experimental results demonstrate the usability of the proposed approach.

An incremental tri-partite approach to ontology learning

In this paper we present a new approach to ontology learning. Its basis lies in a dynamic and iterative view of knowledge acquisition for ontologies. The Abraxas approach is founded on three resources, a set of texts, a set of learning patterns and a set of ontological triples, each of which must remain in equilibrium. As events occur which disturb this equilibrium various actions are triggered to re-establish a balance between the resources. Such events include acquisition of a further text from external resources such as the Web or the addition of ontological triples to the ontology. We develop the concept of a knowledge gap between the coverage of an ontology and the corpus of texts as a measure triggering actions. We present an overview of the algorithm and its functionalities.

Quantitative risk assessment of groundwater quality utilizing GIS technology and coupled groundwater models

The thesis presents a two-dimensional Risk Assessment Method (RAM) where the assessment of risk to the groundwater resources incorporates both the quantification of the probability of the occurrence of contaminant source terms, as well as the assessment of the resultant impacts. The approach emphasizes the need for a greater dependency on the potential pollution sources, rather than the traditional approach where assessment is based mainly on the intrinsic geo-hydrologic parameters. The risk is calculated using Monte Carlo simulation methods whereby random pollution events were generated to the same distribution as historically occurring events or a priori potential probability distribution. Integrated mathematical models then simulate contaminant concentrations at the predefined monitoring points within the aquifer. The spatial and temporal distributions of the concentrations were calculated from repeated realisations, and the number of times when a user defined concentration magnitude was exceeded is quantified as a risk. The method was setup by integrating MODFLOW-2000, MT3DMS and a FORTRAN coded risk model, and automated, using a DOS batch processing file. GIS software was employed in producing the input files and for the presentation of the results. The functionalities of the method, as well as its sensitivities to the model grid sizes, contaminant loading rates, length of stress periods, and the historical frequencies of occurrence of pollution events were evaluated using hypothetical scenarios and a case study. Chloride-related pollution sources were compiled and used as indicative potential contaminant sources for the case study. At any active model cell, if a random generated number is less than the probability of pollution occurrence, then the risk model will generate synthetic contaminant source term as an input into the transport model. The results of the applications of the method are presented in the form of tables, graphs and spatial maps. Varying the model grid sizes indicates no significant effects on the simulated groundwater head. The simulated frequency of daily occurrence of pollution incidents is also independent of the model dimensions. However, the simulated total contaminant mass generated within the aquifer, and the associated volumetric numerical error appear to increase with the increasing grid sizes. Also, the migration of contaminant plume advances faster with the coarse grid sizes as compared to the finer grid sizes. The number of daily contaminant source terms generated and consequently the total mass of contaminant within the aquifer increases in a non linear proportion to the increasing frequency of occurrence of pollution events. The risk of pollution from a number of sources all occurring by chance together was evaluated, and quantitatively presented as risk maps. This capability to combine the risk to a groundwater feature from numerous potential sources of pollution proved to be a great asset to the method, and a large benefit over the contemporary risk and vulnerability methods.

Spatially orthogonal chemical functionalization of a hierarchical pore network for catalytic cascade reactions

The chemical functionality within porous architectures dictates their performance as heterogeneous catalysts; however, synthetic routes to control the spatial distribution of individual functions within porous solids are limited. Here we report the fabrication of spatially orthogonal bifunctional porous catalysts, through the stepwise template removal and chemical functionalization of an interconnected silica framework. Selective removal of polystyrene nanosphere templates from a lyotropic liquid crystal-templated silica sol–gel matrix, followed by extraction of the liquid crystal template, affords a hierarchical macroporous–mesoporous architecture. Decoupling of the individual template extractions allows independent functionalization of macropore and mesopore networks on the basis of chemical and/or size specificity. Spatial compartmentalization of, and directed molecular transport between, chemical functionalities affords control over the reaction sequence in catalytic cascades; herein illustrated by the Pd/Pt-catalysed oxidation of cinnamyl alcohol to cinnamic acid. We anticipate that our methodology will prompt further design of multifunctional materials comprising spatially compartmentalized functions.

Intracellular protein determination using droplet-based immunoassays

This paper describes the implementation of a sensitive, on-chip immunoassay for the analysis of intracellular proteins, developed using microdroplet technology. The system offers a number of analytical functionalities, enabling the lysis of low cell numbers, as well as protein detection and quantification, integrated within a single process flow. Cells were introduced into the device in suspension and were electrically lysed in situ. The cell lysate was subsequently encapsulated together with antibody-functionalized beads into stable, water-in-oil droplets, which were stored on-chip. The binding of intracellular proteins to the beads was monitored fluorescently. By analyzing many individual droplets and quantifying the data obtained against standard additions, we measured the level of two intracellular proteins, namely, HRas-mCitrine, expressed within HEK-293 cells, and actin-EGFP, expressed within MCF-7 cells. We determined the concentrations of these proteins over 5 orders of magnitude, from ~50 pM to 1 µM. The results from this semiautomated method were compared to those for determinations made using Western blots, and were found not only to be faster, but required a smaller number of cells. © 2011 American Chemical Society.

Services for activities in group editing 'sage'

The project described in this thesis investigates the needs of a group of people working cooperatively in an OSI environment, and recommends tools and services to meet these needs. The project looks specifically at Services for Activities in Group Editing, and is identified as the `SAGE' project. The project uses case studies to identify user requirements and to determine common functionalities for a variety of group editing activities. A prototype is implemented in an X.400 environment to help refine user requirements, as a source of new ideas and to test the proposed functionalities. The conceptual modelling follows current CCITT proposals, but a new classification of group activities is proposed: Informative, Objective and Supportive application groups. It is proposed that each of these application groups have their own Service Agent. Use of this classification allows the possibility of developing three sets of tools which will cover a wide range of group activities, rather than developing tools for individual activities. Group editing is considered to be in the Supportive application group. A set of additional services and tools to support group editing are proposed in the context of the CCITT draft on group communication, X.gc. The proposed services and tools are mapped onto the X.400 series of recommendations, with the Abstract Service Definition of the operational objects defined, along with their associated component files, by extending the X.420 protocol functionality. It is proposed that each of the Informative, Objective and Supportive application groups should be implemented as a modified X.420 inter-personal messaging system.

Characterisation and surface-profiling techniques for composite particles produced by dry powder coating in pharmaceutical drug delivery

The production of composite particles using dry powder coating is a one-step, environmentally friendly, process for the fabrication of particles with targeted properties and favourable functionalities. Diverse functionalities, such flowability enhancement, content uniformity, and dissolution, can be developed from dry particle coating. In this review, we discuss the particle functionalities that can be tailored and the selection of characterisation techniques relevant to understanding their molecular basis. We address key features in the powder blend sampling process and explore the relevant characterisation techniques, focussing on the functionality delivered by dry coating and on surface profiling that explores the dynamics and surface characteristics of the composite blends. Dry particle coating is a solvent- and heat-free process that can be used to develop functionalised particles. However, assessment of the resultant functionality requires careful selection of sensitive analytical techniques that can distinguish particle surface changes within nano and/or micrometre ranges.

An evaluation of TCP over wired-to-wireless networks

To exploit the popularity of TCP as still the dominant sender and protocol of choice for transporting data reliably across the heterogeneous Internet, this thesis explores end-to-end performance issues and behaviours of TCP senders when transferring data to wireless end-users. The theme throughout is on end-users located specifically within 802.11 WLANs at the edges of the Internet, a largely untapped area of work. To exploit the interests of researchers wanting to study the performance of TCP accurately over heterogeneous conditions, this thesis proposes a flexible wired-to-wireless experimental testbed that better reflects conditions in the real-world. To exploit the transparent functionalities between TCP in the wired domain and the IEEE 802.11 WLAN protocols, this thesis proposes a more accurate methodology for gauging the transmission and error characteristics of real-world 802.11 WLANs. It also aims to correlate any findings with the functionality of fixed TCP senders. To exploit the popularity of Linux as a popular operating system for many of the Internet’s data servers, this thesis studies and evaluates various sender-side TCP congestion control implementations within the recent Linux v2.6. A selection of the implementations are put under systematic testing using real-world wired-to-wireless conditions in order to screen and present a viable candidate/s for further development and usage in the modern-day heterogeneous Internet. Overall, this thesis comprises a set of systematic evaluations of TCP senders over 802.11 WLANs, incorporating measurements in the form of simulations, emulations, and through the use of a real-world-like experimental testbed. The goal of the work is to ensure that all aspects concerned are comprehensively investigated in order to establish rules that can help to decide under which circumstances the deployment of TCP is optimal i.e. a set of paradigms for advancing the state-of-the-art in data transport across the Internet.

Optical grooming switch with regenerative functionality for transparent interconnection of networks

We demonstrate a regenerative optical grooming switch for buffer-less interconnection of metro/access and metro/core ring networks with switching functionality in time, space and wavelength domain. Key functionalities of the router are the traffic aggregation with time-slot interchanging (TSI) functionality, the WDM-to-ODTM multiplexing and the OTDM-to-WDM demultiplexing of high-speed channel into lower bit-rate tributaries as well as multi-wavelength all-optical 2R regeneration of several higher-speed signals. BER and Q-factor measurements of different switching scenarios show excellent performance with no error floor and Q-factors above 21 dB.

Gamma-shaped long-cavity normal-dispersion mode-locked Er-fiber laser for sub-nanosecond high-energy pulsed generation

We propose the design of a novel ?-shaped fiber laser resonator and apply it to build a long-cavity normaldispersion mode-locked Er-fiber laser which features enhanced functionalities for management and optimization of pulsed lasing regimes. We report the generation of sub-nanosecond pulses with the energy of ~0.5 µJ at a kilohertz-scale repetition rate in an all-fiber system based on the new laser design. A combination of special design solutions in the laser, such as polarization instability compensation in the ultra-long arm of the resonator, intra-cavity spectral selection of radiation with a broadband fiber Bragg grating, and polarization selection by means of a tilted refractive index grating, ensures low amplified spontaneous emission (ASE) noise and high stability of the laser system output parameters.

An all-optical grooming switch for interconnecting access and metro ring networks

A regenerative all-optical grooming switch for interconnecting 130 Gbit/s on-off keying (OOK) metro/core ring and 43 Gbit/s-OOK metro/access ring networks with switching functionality in time, space, and wavelength domains is demonstrated. Key functionalities of the switch are traffic aggregation with time-slot interchanging functionality, optical time division multiplexing (OTDM) to wavelength division multiplexing (WDM) demultiplexing, and multi-wavelength 2R regeneration. Laboratory and field demonstrations show the excellent performance of the new concept with error-free signal transmission and Q-factors above 20 dB.

Synthesis and characterization of dual-functionalized core-shell fluorescent microspheres for bioconjugation and cellular delivery

The efficient transport of micron-sized beads into cells, via a non-endocytosis mediated mechanism, has only recently been described. As such there is considerable scope for optimization and exploitation of this procedure to enable imaging and sensing applications to be realized. Herein, we report the design, synthesis and characterization of fluorescent microsphere-based cellular delivery agents that can also carry biological cargoes. These core-shell polymer microspheres possess two distinct chemical environments; the core is hydrophobic and can be labeled with fluorescent dye, to permit visual tracking of the microsphere during and after cellular delivery, whilst the outer shell renders the external surfaces of the microspheres hydrophilic, thus facilitating both bioconjugation and cellular compatibility. Cross-linked core particles were prepared in a dispersion polymerization reaction employing styrene, divinylbenzene and a thiol-functionalized co-monomer. These core particles were then shelled in a seeded emulsion polymerization reaction, employing styrene, divinylbenzene and methacrylic acid, to generate orthogonally functionalized core-shell microspheres which were internally labeled via the core thiol moieties through reaction with a thiol reactive dye (DY630-maleimide). Following internal labeling, bioconjugation of green fluorescent protein (GFP) to their carboxyl-functionalized surfaces was successfully accomplished using standard coupling protocols. The resultant dual-labeled microspheres were visualized by both of the fully resolvable fluorescence emissions of their cores (DY630) and shells (GFP). In vitro cellular uptake of these microspheres by HeLa cells was demonstrated conventionally by fluorescence-based flow cytometry, whilst MTT assays demonstrated that 92% of HeLa cells remained viable after uptake. Due to their size and surface functionalities, these far-red-labeled microspheres are ideal candidates for in vitro, cellular delivery of proteins, as described in the accompanying paper.

Enabling effective user interactions in content-based image retrieval

This paper presents an interactive content-based image retrieval framework—uInteract, for delivering a novel four-factor user interaction model visually. The four-factor user interaction model is an interactive relevance feedback mechanism that we proposed, aiming to improve the interaction between users and the CBIR system and in turn users overall search experience. In this paper, we present how the framework is developed to deliver the four-factor user interaction model, and how the visual interface is designed to support user interaction activities. From our preliminary user evaluation result on the ease of use and usefulness of the proposed framework, we have learnt what the users like about the framework and the aspects we could improve in future studies. Whilst the framework is developed for our research purposes, we believe the functionalities could be adapted to any content-based image search framework.