Ticagrelor, a platelet aggregation inhibitor for the potential prevention and treatment of arterial thrombosis and acute coronary syndromes

Ticagrelor is an orally active ADP P2Y12 receptor antagonist in development by AstraZeneca plc for the reduction of recurrent ischemic events in patients with acute coronary syndromes (ACS). Prior to the development of ticagrelor, thienopyridine compounds, such as clopidogrel, were the focus of research into therapies for ACS. Although the thienopyridines are effective platelet aggregation inhibitors, they are prodrugs and, consequently, exert a slow onset of action. In addition, the variability in inter-individual metabolism of thienopyridine prodrugs has been associated with reduced efficacy in some patients. Ticagrelor is not a prodrug and exhibits a more rapid onset of action than the thienopyridine prodrugs. In clinical trials conducted to date, ticagrelor was a potent inhibitor of ADP-induced platelet aggregation and demonstrated effects that were comparable to clopidogrel. In a phase II, short-term trial, the bleeding profile of participants treated with ticagrelor was similar to that obtained with clopidogrel; however, an increased incidence of dyspnea was observed - an effect that has not been reported with the thienopyridines. Considering the occurrence of dyspnea, and the apparent non-superiority of ticagrelor to clopidogrel, it is difficult to justify a clear benefit to the continued development of ticagrelor. Outcomes from an ongoing phase III trial comparing ticagrelor with clopidogrel in 18,000 patients with ACS are likely to impact on the future development of ticagrelor.

Tag based collaborative filtering for recommender systems

Collaborative tagging can help users organize, share and retrieve information in an easy and quick way. For the collaborative tagging information implies user’s important personal preference information, it can be used to recommend personalized items to users. This paper proposes a novel tag-based collaborative filtering approach for recommending personalized items to users of online communities that are equipped with tagging facilities. Based on the distinctive three dimensional relationships among users, tags and items, a new similarity measure method is proposed to generate the neighborhood of users with similar tagging behavior instead of similar implicit ratings. The promising experiment result shows that by using the tagging information the proposed approach outperforms the standard user and item based collaborative filtering approaches.

Collaborative Filtering Recommender Systems based on Popular Tags

The social tags in web 2.0 are becoming another important information source to profile users' interests and preferences for making personalized recommendations. However, the uncontrolled vocabulary causes a lot of problems to profile users accurately, such as ambiguity, synonyms, misspelling, low information sharing etc. To solve these problems, this paper proposes to use popular tags to represent the actual topics of tags, the content of items, and also the topic interests of users. A novel user profiling approach is proposed in this paper that first identifies popular tags, then represents users’ original tags using the popular tags, finally generates users’ topic interests based on the popular tags. A collaborative filtering based recommender system has been developed that builds the user profile using the proposed approach. The user profile generated using the proposed approach can represent user interests more accurately and the information sharing among users in the profile is also increased. Consequently the neighborhood of a user, which plays a crucial role in collaborative filtering based recommenders, can be much more accurately determined. The experimental results based on real world data obtained from Amazon.com show that the proposed approach outperforms other approaches.

Collaborative filtering recommender systems using tag information

Recommender Systems is one of the effective tools to deal with information overload issue. Similar with the explicit rating and other implicit rating behaviours such as purchase behaviour, click streams, and browsing history etc., the tagging information implies user’s important personal interests and preferences information, which can be used to recommend personalized items to users. This paper is to explore how to utilize tagging information to do personalized recommendations. Based on the distinctive three dimensional relationships among users, tags and items, a new user profiling and similarity measure method is proposed. The experiments suggest that the proposed approach is better than the traditional collaborative filtering recommender systems using only rating data.

Primary students' group metacognitive processes in a computer supported collaborative learning environment

The current understanding of students’ group metacognition is limited. The research on metacognition has focused mainly on the individual student. The aim of this study was to address the void by developing a conceptual model to inform the use of scaffolds to facilitate group metacognition during mathematical problem solving in computer supported collaborative learning (CSCL) environments. An initial conceptual framework based on the literature from metacognition, cooperative learning, cooperative group metacognition, and computer supported collaborative learning was used to inform the study. In order to achieve the study aim, a design research methodology incorporating two cycles was used. The first cycle focused on the within-group metacognition for sixteen groups of primary school students working together around the computer; the second cycle included between-group metacognition for six groups of primary school students working together on the Knowledge Forum® CSCL environment. The study found that providing groups with group metacognitive scaffolds resulted in groups planning, monitoring, and evaluating the task and team aspects of their group work. The metacognitive scaffolds allowed students to focus on how their group was completing the problem-solving task and working together as a team. From these findings, a revised conceptual model to inform the use of scaffolds to facilitate group metacognition during mathematical problem solving in computer supported collaborative learning (CSCL) environments was generated.

The importance of a new kind of learning in collaborative networks

There is wide agreement that in order to manage the increasingly complex and uncertain tasks of business, government and community, organizations can no longer operate in supreme isolation, but must develop a more networked approach. Networks are not ‘business as usual’. Of particular note is what has been referred to as collaborative networks. Collaborative networks now constitute a significant part of our institutional infrastructure. A key driver for the proliferation of these multiorganizational arrangements is their ability to facilitate the learning and knowledge necessary to survive or to respond to increasingly complex social issues In this regard the emphasis is on the importance of learning in networks. Learning applies to networks in two different ways. These refer to the kinds of learning that occur as part of the interactive processes of networks. This paper looks at the importance of these two kinds of learning in collaborative networks. The first kind of learning relates to networks as learning networks or communities of practice. In learning networks people exchange ideas with each other and bring back this new knowledge for use in their own organizations. The second type of learning is referred to as network learning. Network learning refers to how people in collaborative networks learn new ways of communicating and behaving with each other. Network learning has been described as transformational in terms of leading to major systems changes and innovation. In order to be effective, all networks need to be involved as learning networks; however, collaborative networks must also be involved in network learning to be effective. In addition to these two kinds of learning in collaborative networks this paper also focuses on the importance of how we learn about collaborative networks. Maximizing the benefits of working through collaborative networks is dependent on understanding their unique characteristics and how this impacts on their operation. This requires a new look at how we specifically teach about collaborative networks and how this is similar to and/or different from how we currently teach about interorgnizational relations.

Providing youth with skills, training and employment opportunities through ICT Initiatives

Youth population is increasing explosively particularly in developing countries as a result of rapid urbanization. This increase is bringing large number of social and economic problems. For instance the impacts of job and training availability, and the physical, social and cultural quality of urban environment on young people are enormous, and affect their health, lifestyles, and well-being (Gleeson and Sipe 2006). Besides this, globalization and technological developments are affecting youth in urban areas in all parts of the world, both positively and negatively (Robertson 1995). The rapidly advancing information and communications technologies (ICTs) helps in addressing social and economic problems caused by the rapid growth of urban youth populations in developing countries. ICTs offer opportunities to young people for learning, skill development and employment. But there are downsides: young people in many developing countries lack of having broad access to these new technologies, they are vulnerable to global market changes, and ICTs link them into global cultures which promote consumer goods, potentially eroding local cultures and community values (Manacorda and Petrongolo 1999). However we believe that the positives outweigh such negatives. At the beginning of the twenty-first century, the world’s young population number more than they ever have. There are over a billion young people between the ages of 15 and 24, which 85 per cent of them live in developing countries and mainly in urban environments. Many of these young people are in the process of making, or have already made, the transition from school to work. During the last two decades all around the world, these young people, as new workers, have faced a number of challenges associated with globalization and technological advances on labour markets (United Nations 2004). The continuous decrease in the manufacturing employment is made many of the young people facing three options: getting jobs in the informal economy with insecurity and poor wages and working conditions, or getting jobs in the low-tier service industries, or developing their vocational skills to benefit from new opportunities in the professional and advanced technical/knowledge sectors. Moreover in developing countries a large portion of young people are not even lucky enough to choose among any of these options, and consequently facing long-term unemployment, which makes them highly vulnerable. The United Nations’ World Youth Employment report (2004) indicates that in almost all countries, females tend to be far more vulnerable than males in terms of long-term unemployment, and young people who have advanced qualifications are far less likely to experience long-term unemployment than others. In the limited opportunities of the formal labour market, those with limited vocational skills resort to forced entrepreneurship and selfemployment in the informal economy, often working for low pay under hazardous conditions, with only few prospects for the future (United Nations 2005a). The International Labour Organization’s research (2004) revealed that the labour force participation rates for young people decreased by almost four per cent (which is equivalent of 88 million young people) between 1993 and 2003. This is largely as a result of the increased number of young people attending school, high overall unemployment rates, and the fact that some young people gave up any hope of finding work and dropped out of the labour market. At the regional level, youth unemployment was highest in Middle East and North Africa (MENA) (25.6%) and sub-Saharan Africa (21%) and lowest in East Asia (7%) and the industrialized economies(13.4%) (International Labour Organization 2004). The youth in economically disadvantaged regions (e.g. the MENA region) face many challenges in education and training that delivers them the right set of skills and knowledge demanded by the labour market. As a consequence, the transition from school to work is mostly unsuccessful and young population end up either unemployed or underemployed in the informal sectors (United Nations 2005b). Unemployment and lack of economic prospects of the urban youth are pushing many of them into criminal acts, excessive alcohol use, substance addiction, and also in many cases resulting in processes of social or political violence (Fernandez-Maldonado 2004; United Nations 2005a). Long-term unemployment leads young people in a process of marginalisation and social exclusion (United Nations 2004). The sustained high rates of long-term youth unemployment have a number of negative effects on societies. First, it results in countries failing to take advantage of the human resources to increase their productive potential, at a time of transition to a globalized world that inexorably demands such leaps in productive capacity. Second, it reinforces the intergenerational transmission of poverty. Third, owing to the discrepancy between more education and exposure to the mass media and fewer employment opportunities, it may encourage the spread of disruptive behaviours, recourse to illegal alternatives for generating income and the loss of basic societal values, all of which erode public safety and social capital. Fourth, it may trigger violent and intractable political conflicts. And lastly, it may exacerbate intergenerational conflicts when young people perceive a lack of opportunity and meritocracy in a system that favours adults who have less formal education and training but more wealth, power and job stability (Hopenhayn 2002). To assist in addressing youth’s skill training and employment problems this paper scrutinises useful international practices, policies, initiatives and programs targeting youth skill training, particularly in ICTs. The MENA national governments and local authorities could consider implementing similar initiative and strategies to address some of the youth employment issues. The broader aim of this paper is to investigate the successful practice and strategies for the information and communication related income generation opportunities for young people to: promote youth entrepreneurship; promote public-private partnerships; target vulnerable groups of young people; narrow digital divide; and put young people in charge. The rest of this paper is organised in five parts. First, the paper provides an overview of the literature on the knowledge economy, skill, education and training issues. Secondly, it reviews the role of ICTs for vocational skill development and employability. Thirdly, it discusses the issues surrounding the development of the digital divide. Fourthly, the paper underlines types and the importance of developing ICT initiatives targeting young people, and reviews some of the successful policy implementations on ICT-based initiatives from both developed and developing countries that offer opportunities to young people for learning, skill development and employment. Then the paper concludes by providing useful generalised recommendations for the MENA region countries and cities in: advocating possible opportunities for ICT generated employment for young people; and discussing how ICT policies could be modified and adopted to meet young people’s needs.

Enabling authentic collaborative education in an online environment : the QUT Virtual Law Placement

This paper explores an innovative model for work-integrated learning using a virtual paradigm – The Virtual Law Placement Unit at Queensland University of Technology (QUT) Australia. It builds upon the conceptual model previously explored at WACE 2007 and provides an account of the lessons learned from the pilot offering of the unit which was conducted and evaluated in 2008. ----- The Virtual Placement Unit offers students the opportunity to complete an authentic workplace task under the guidance of a real-life workplace supervisor, where student-student communication and student-supervisor communication is all conducted virtually (and potentially asynchronously) to create an engaging but flexible learning environment using a combination of Blackboard and SharePoint technologies. This virtual experience is pioneering in the sense that it enables law students to access an unprecedented range of law graduate destination workplaces and projects, including international and social justice placements, absent the constraints traditionally associated with arranging physical placements. ----- All aspects of this unit have been designed in conjunction with community partners with a view to balancing student learning objectives with community needs through co-operative education. This paper will also explore how the implementation of the project is serving to strengthen those partnerships with the wider community, simultaneously addressing the community engagement agenda of the University and enabling students to engage meaningfully with local, national and international community partners in the real world of work.

Generating rules with predicates, terms and variables from the pruned neural networks

Artificial neural networks (ANN) have demonstrated good predictive performance in a wide range of applications. They are, however, not considered sufficient for knowledge representation because of their inability to represent the reasoning process succinctly. This paper proposes a novel methodology Gyan that represents the knowledge of a trained network in the form of restricted first-order predicate rules. The empirical results demonstrate that an equivalent symbolic interpretation in the form of rules with predicates, terms and variables can be derived describing the overall behaviour of the trained ANN with improved comprehensibility while maintaining the accuracy and fidelity of the propositional rules.

Generating Flash files of Your Lectures: Good Practice Strategies Helping Students Engage with Their Learning

Our students come from diverse backgrounds. They need flexibility in their learning. First year students tend to worry when they miss lectures or part of lectures. Having the lecture as an on line resource allows students to miss a lecture without stressing about it and to be more relaxed in the lecture, knowing that anything they may miss will be available later. The resource: The Windows based program from Blueberry Software (not Blackberry!) - BB Flashback - allows the simultaneous recording of the computer screen together with the audio, as well as Webcam recording. Editing capabilities include adding pause buttons, graphics and text to the file before exporting it in a flash file. Any diagrams drawn on the board or shown via visualiser can be photographed and easily incorporated. The audio from the file can be extracted if required to be posted as podcast. Exporting modes other than Flash are also available, allowing vodcasting if you wish. What you will need: - the recording software: it can be installed on the lecture hall computer just prior to lecture if needed - a computer: either the ones in lecture halls, especially if fitted with audio recording, or a laptop (I have used audio recording via Bluetooth for mobility). Feedback from students has been positive and will be presented on the poster.

Recommending best answer in a collaborative question answering system

The World Wide Web has become a medium for people to share information. People use Web-based collaborative tools such as question answering (QA) portals, blogs/forums, email and instant messaging to acquire information and to form online-based communities. In an online QA portal, a user asks a question and other users can provide answers based on their knowledge, with the question usually being answered by many users. It can become overwhelming and/or time/resource consuming for a user to read all of the answers provided for a given question. Thus, there exists a need for a mechanism to rank the provided answers so users can focus on only reading good quality answers. The majority of online QA systems use user feedback to rank users’ answers and the user who asked the question can decide on the best answer. Other users who didn’t participate in answering the question can also vote to determine the best answer. However, ranking the best answer via this collaborative method is time consuming and requires an ongoing continuous involvement of users to provide the needed feedback. The objective of this research is to discover a way to recommend the best answer as part of a ranked list of answers for a posted question automatically, without the need for user feedback. The proposed approach combines both a non-content-based reputation method and a content-based method to solve the problem of recommending the best answer to the user who posted the question. The non-content method assigns a score to each user which reflects the users’ reputation level in using the QA portal system. Each user is assigned two types of non-content-based reputations cores: a local reputation score and a global reputation score. The local reputation score plays an important role in deciding the reputation level of a user for the category in which the question is asked. The global reputation score indicates the prestige of a user across all of the categories in the QA system. Due to the possibility of user cheating, such as awarding the best answer to a friend regardless of the answer quality, a content-based method for determining the quality of a given answer is proposed, alongside the non-content-based reputation method. Answers for a question from different users are compared with an ideal (or expert) answer using traditional Information Retrieval and Natural Language Processing techniques. Each answer provided for a question is assigned a content score according to how well it matched the ideal answer. To evaluate the performance of the proposed methods, each recommended best answer is compared with the best answer determined by one of the most popular link analysis methods, Hyperlink-Induced Topic Search (HITS). The proposed methods are able to yield high accuracy, as shown by correlation scores: Kendall correlation and Spearman correlation. The reputation method outperforms the HITS method in terms of recommending the best answer. The inclusion of the reputation score with the content score improves the overall performance, which is measured through the use of Top-n match scores.

Modeling the impact of potential vaccines on epidemics of sexually transmitted chlamydia trachomatis infection

Background. We investigated the likely impact of vaccines on the prevalence of and morbidity due to Chlamydia trachomatis (chlamydia) infections in heterosexual populations. Methods.An individual‐based mathematical model of chlamydia transmission was developed and linked to the infection course in chlamydia‐infected individuals. The model describes the impact of a vaccine through its effect on the chlamydial load required to infect susceptible individuals (the “critical load”), the load in infected individuals, and their subsequent infectiousness. The model was calibrated using behavioral, biological, and clinical data. Results.A fully protective chlamydia vaccine administered before sexual debut can theoretically eliminate chlamydia epidemics within 20 years. Partially effective vaccines can still greatly reduce the incidence of chlamydia infection. Vaccines should aim primarily to increase the critical load in susceptible individuals and secondarily to decrease the peak load and/or the duration of infection in vaccinated individuals who become infected. Vaccinating both sexes has a beneficial impact on chlamydia‐related morbidity, but targeting women is more effective than targeting men. Conclusions.Our findings can be used in laboratory settings to evaluate vaccine candidates in animal models, by regulatory bodies in the promotion of candidates for clinical trials, and by public health authorities in deciding on optimal intervention strategies.

Recombinant protein production using a Tobacco yellow dwarf virus-based episomal expression vector : control of Rep activity

Over the past decade, plants have been used as expression hosts for the production of pharmaceutically important and commercially valuable proteins. Plants offer many advantages over other expression systems such as lower production costs, rapid scale up of production, similar post-translational modification as animals and the low likelihood of contamination with animal pathogens, microbial toxins or oncogenic sequences. However, improving recombinant protein yield remains one of the greatest challenges to molecular farming. In-Plant Activation (InPAct) is a newly developed technology that offers activatable and high-level expression of heterologous proteins in plants. InPAct vectors contain the geminivirus cis elements essential for rolling circle replication (RCR) and are arranged such that the gene of interest is only expressed in the presence of the cognate viral replication-associated protein (Rep). The expression of Rep in planta may be controlled by a tissue-specific, developmentally regulated or chemically inducible promoter such that heterologous protein accumulation can be spatially and temporally controlled. One of the challenges for the successful exploitation of InPAct technology is the control of Rep expression as even very low levels of this protein can reduce transformation efficiency, cause abnormal phenotypes and premature activation of the InPAct vector in regenerated plants. Tight regulation over transgene expression is also essential if expressing cytotoxic products. Unfortunately, many tissue-specific and inducible promoters are unsuitable for controlling expression of Rep due to low basal activity in the absence of inducer or in tissues other than the target tissue. This PhD aimed to control Rep activity through the production of single chain variable fragments (scFvs) specific to the motif III of Tobacco yellow dwarf virus (TbYDV) Rep. Due to the important role played by the conserved motif III in the RCR, it was postulated that such scFvs can be used to neutralise the activity of the low amount of Rep expressed from a “leaky” inducible promoter, thus preventing activation of the TbYDV-based InPAct vector until intentional induction. Such scFvs could also offer the potential to confer partial or complete resistance to TbYDV, and possibly heterologous viruses as motif III is conserved between geminiviruses. Studies were first undertaken to determine the levels of TbYDV Rep and TbYDV replication-associated protein A (RepA) required for optimal transgene expression from a TbYDV-based InPAct vector. Transient assays in a non-regenerable Nicotiana tabacum (NT-1) cell line were undertaken using a TbYDV-based InPAct vector containing the uidA reporter gene (encoding GUS) in combination with TbYDV Rep and RepA under the control of promoters with high (CaMV 35S) or low (Banana bunchy top virus DNA-R, BT1) activity. The replication enhancer protein of Tomato leaf curl begomovirus (ToLCV), REn, was also used in some co-bombardment experiments to examine whether RepA could be substituted by a replication enhancer from another geminivirus genus. GUS expression was observed both quantitatively and qualitatively by fluorometric and histochemical assays, respectively. GUS expression from the TbYDV-based InPAct vector was found to be greater when Rep was expected to be expressed at low levels (BT1 promoter) rather than high levels (35S promoter). GUS expression was further enhanced when Rep and RepA were co-bombarded with a low ratio of Rep to RepA. Substituting TbYDV RepA with ToLCV REn also enhanced GUS expression but more importantly highest GUS expression was observed when cells were co-transformed with expression vectors directing low levels of Rep and high levels of RepA irrespective of the level of REn. In this case, GUS expression was approximately 74-fold higher than that from a non-replicating vector. The use of different terminators, namely CaMV 35S and Nos terminators, in InPAct vectors was found to influence GUS expression. In the presence of Rep, GUS expression was greater using pInPActGUS-Nos rather than pInPActGUS-35S. The only instance of GUS expression being greater from vectors containing the 35S terminator was when comparing expression from cells transformed with Rep, RepA and REnexpressing vectors and either non-replicating vectors, p35SGS-Nos or p35SGS-35S. This difference was most likely caused by an interaction of viral replication proteins with each other and the terminators. These results indicated that (i) the level of replication associated proteins is critical to high transgene expression, (ii) the choice of terminator within the InPAct vector may affect expression levels and (iii) very low levels of Rep can activate InPAct vectors hence controlling its activity is critical. Prior to generating recombinant scFvs, a recombinant TbYDV Rep was produced in E. coli to act as a control to enable the screening for Rep-specific antibodies. A bacterial expression vector was constructed to express recombinant TbYDV Rep with an Nterminal His-tag (N-His-Rep). Despite investigating several purification techniques including Ni-NTA, anion exchange, hydrophobic interaction and size exclusion chromatography, N-His-Rep could only be partially purified using a Ni-NTA column under native conditions. Although it was not certain that this recombinant N-His-Rep had the same conformation as the native TbYDV Rep and was functional, results from an electromobility shift assay (EMSA) showed that N-His-Rep was able to interact with the TbYDV LIR and was, therefore, possibly functional. Two hybridoma cell lines from mice, immunised with a synthetic peptide containing the TbYDV Rep motif III amino acid sequence, were generated by GenScript (USA). Monoclonal antibodies secreted by the two hybridoma cell lines were first screened against denatured N-His-Rep in Western analysis. After demonstrating their ability to bind N-His-Rep, two scFvs (scFv1 and scFv2) were generated using a PCR-based approach. Whereas the variable heavy chain (VH) from both cell lines could be amplified, only the variable light chain (VL) from cell line 2 was amplified. As a result, scFv1 contained VH and VL from cell line 1, whereas scFv2 contained VH from cell line 2 and VL from cell line 1. Both scFvs were first expressed in E. coli in order to evaluate their affinity to the recombinant TbYDV N-His-Rep. The preliminary results demonstrated that both scFvs were able to bind to the denatured N-His-Rep. However, EMSAs revealed that only scFv2 was able to bind to native N-His-Rep and prevent it from interacting with the TbYDV LIR. Each scFv was cloned into plant expression vectors and co-bombarded into NT-1 cells with the TbYDV-based InPAct GUS expression vector and pBT1-Rep to examine whether the scFvs could prevent Rep from mediating RCR. Although it was expected that the addition of the scFvs would result in decreased GUS expression, GUS expression was found to slightly increase. This increase was even more pronounced when the scFvs were targeted to the cell nucleus by the inclusion of the Simian virus 40 large T antigen (SV40) nuclear localisation signal (NLS). It was postulated that the scFvs were binding to a proportion of Rep, leaving a small amount available to mediate RCR. The outcomes of this project provide evidence that very high levels of recombinant protein can theoretically be expressed using InPAct vectors with judicious selection and control of viral replication proteins. However, the question of whether the scFvs generated in this project have sufficient affinity for TbYDV Rep to prevent its activity in a stably transformed plant remains unknown. It may be that other scFvs with different combinations of VH and VL may have greater affinity for TbYDV Rep. Such scFvs, when expressed at high levels in planta, might also confer resistance to TbYDV and possibly heterologous geminiviruses.

Theoretical investigation of thermal tweezers for parallel manipulation of atoms and nanoparticles on surfaces

A major focus of research in nanotechnology is the development of novel, high throughput techniques for fabrication of arbitrarily shaped surface nanostructures of sub 100 nm to atomic scale. A related pursuit is the development of simple and efficient means for parallel manipulation and redistribution of adsorbed atoms, molecules and nanoparticles on surfaces – adparticle manipulation. These techniques will be used for the manufacture of nanoscale surface supported functional devices in nanotechnologies such as quantum computing, molecular electronics and lab-on-achip, as well as for modifying surfaces to obtain novel optical, electronic, chemical, or mechanical properties. A favourable approach to formation of surface nanostructures is self-assembly. In self-assembly, nanostructures are grown by aggregation of individual adparticles that diffuse by thermally activated processes on the surface. The passive nature of this process means it is generally not suited to formation of arbitrarily shaped structures. The self-assembly of nanostructures at arbitrary positions has been demonstrated, though these have typically required a pre-patterning treatment of the surface using sophisticated techniques such as electron beam lithography. On the other hand, a parallel adparticle manipulation technique would be suited for directing the selfassembly process to occur at arbitrary positions, without the need for pre-patterning the surface. There is at present a lack of techniques for parallel manipulation and redistribution of adparticles to arbitrary positions on the surface. This is an issue that needs to be addressed since these techniques can play an important role in nanotechnology. In this thesis, we propose such a technique – thermal tweezers. In thermal tweezers, adparticles are redistributed by localised heating of the surface. This locally enhances surface diffusion of adparticles so that they rapidly diffuse away from the heated regions. Using this technique, the redistribution of adparticles to form a desired pattern is achieved by heating the surface at specific regions. In this project, we have focussed on the holographic implementation of this approach, where the surface is heated by holographic patterns of interfering pulsed laser beams. This implementation is suitable for the formation of arbitrarily shaped structures; the only condition is that the shape can be produced by holographic means. In the simplest case, the laser pulses are linearly polarised and intersect to form an interference pattern that is a modulation of intensity along a single direction. Strong optical absorption at the intensity maxima of the interference pattern results in approximately a sinusoidal variation of the surface temperature along one direction. The main aim of this research project is to investigate the feasibility of the holographic implementation of thermal tweezers as an adparticle manipulation technique. Firstly, we investigate theoretically the surface diffusion of adparticles in the presence of sinusoidal modulation of the surface temperature. Very strong redistribution of adparticles is predicted when there is strong interaction between the adparticle and the surface, and the amplitude of the temperature modulation is ~100 K. We have proposed a thin metallic film deposited on a glass substrate heated by interfering laser beams (optical wavelengths) as a means of generating very large amplitude of surface temperature modulation. Indeed, we predict theoretically by numerical solution of the thermal conduction equation that amplitude of the temperature modulation on the metallic film can be much greater than 100 K when heated by nanosecond pulses with an energy ~1 mJ. The formation of surface nanostructures of less than 100 nm in width is predicted at optical wavelengths in this implementation of thermal tweezers. Furthermore, we propose a simple extension to this technique where spatial phase shift of the temperature modulation effectively doubles or triples the resolution. At the same time, increased resolution is predicted by reducing the wavelength of the laser pulses. In addition, we present two distinctly different, computationally efficient numerical approaches for theoretical investigation of surface diffusion of interacting adparticles – the Monte Carlo Interaction Method (MCIM) and the random potential well method (RPWM). Using each of these approaches we have investigated thermal tweezers for redistribution of both strongly and weakly interacting adparticles. We have predicted that strong interactions between adparticles can increase the effectiveness of thermal tweezers, by demonstrating practically complete adparticle redistribution into the low temperature regions of the surface. This is promising from the point of view of thermal tweezers applied to directed self-assembly of nanostructures. Finally, we present a new and more efficient numerical approach to theoretical investigation of thermal tweezers of non-interacting adparticles. In this approach, the local diffusion coefficient is determined from solution of the Fokker-Planck equation. The diffusion equation is then solved numerically using the finite volume method (FVM) to directly obtain the probability density of adparticle position. We compare predictions of this approach to those of the Ermak algorithm solution of the Langevin equation, and relatively good agreement is shown at intermediate and high friction. In the low friction regime, we predict and investigate the phenomenon of ‘optimal’ friction and describe its occurrence due to very long jumps of adparticles as they diffuse from the hot regions of the surface. Future research directions, both theoretical and experimental are also discussed.