Multiple human single-stranded DNA binding proteins function in genome maintenance : structural, biochemical and functional analysis

DNA exists predominantly in a duplex form that is preserved via specific base pairing. This base pairing affords a considerable degree of protection against chemical or physical damage and preserves coding potential. However, there are many situations, e.g. during DNA damage and programmed cellular processes such as DNA replication and transcription, in which the DNA duplex is separated into two singlestranded DNA (ssDNA) strands. This ssDNA is vulnerable to attack by nucleases, binding by inappropriate proteins and chemical attack. It is very important to control the generation of ssDNA and protect it when it forms, and for this reason all cellular organisms and many viruses encode a ssDNA binding protein (SSB). All known SSBs use an oligosaccharide/oligonucleotide binding (OB)-fold domain for DNA binding. SSBs have multiple roles in binding and sequestering ssDNA, detecting DNA damage, stimulating strand-exchange proteins and helicases, and mediation of protein–protein interactions. Recently two additional human SSBs have been identified that are more closely related to bacterial and archaeal SSBs. Prior to this it was believed that replication protein A, RPA, was the only human equivalent of bacterial SSB. RPA is thought to be required for most aspects of DNA metabolism including DNA replication, recombination and repair. This review will discuss in further detail the biological pathways in which human SSBs function.

A framework for reasoning about inherent parallelism in modern object-oriented languages

With the emergence of multi-core processors into the mainstream, parallel programming is no longer the specialized domain it once was. There is a growing need for systems to allow programmers to more easily reason about data dependencies and inherent parallelism in general purpose programs. Many of these programs are written in popular imperative programming languages like Java and C]. In this thesis I present a system for reasoning about side-effects of evaluation in an abstract and composable manner that is suitable for use by both programmers and automated tools such as compilers. The goal of developing such a system is to both facilitate the automatic exploitation of the inherent parallelism present in imperative programs and to allow programmers to reason about dependencies which may be limiting the parallelism available for exploitation in their applications. Previous work on languages and type systems for parallel computing has tended to focus on providing the programmer with tools to facilitate the manual parallelization of programs; programmers must decide when and where it is safe to employ parallelism without the assistance of the compiler or other automated tools. None of the existing systems combine abstraction and composition with parallelization and correctness checking to produce a framework which helps both programmers and automated tools to reason about inherent parallelism. In this work I present a system for abstractly reasoning about side-effects and data dependencies in modern, imperative, object-oriented languages using a type and effect system based on ideas from Ownership Types. I have developed sufficient conditions for the safe, automated detection and exploitation of a number task, data and loop parallelism patterns in terms of ownership relationships. To validate my work, I have applied my ideas to the C] version 3.0 language to produce a language extension called Zal. I have implemented a compiler for the Zal language as an extension of the GPC] research compiler as a proof of concept of my system. I have used it to parallelize a number of real-world applications to demonstrate the feasibility of my proposed approach. In addition to this empirical validation, I present an argument for the correctness of the type system and language semantics I have proposed as well as sketches of proofs for the correctness of the sufficient conditions for parallelization proposed.

Sustainable fashion textiles design : value adding through technological enhancement

A key concern in the field of contemporary fashion/textiles design is the emergence of ‘fast fashion’: best explained as "buy it Friday, wear it Saturday and throw it away on Sunday" (O'Loughlin, 2007). In this contemporary retail atmosphere of “pile it high: sell it cheap” and “quick to market”, even designer goods have achieved a throwaway status. This modern culture of consumerism is the antithesis of sustainability and is proving a dilemma surrounding sustainable practice for designers and producers in the disciplines (de Blas, 2010). Design researchers including those in textiles/fashion have begun to explore what is a key question in the 21st century in order to create a vision and reason for their disciplines: Can products be designed to have added value to the consumer and hence contribute to a more sustainable industry? Fashion Textiles Design has much to answer for in contributing to the problems of unsustainable practices on a global scale in design, production and waste. However, designers within this field also have great potential to contribute to practical ‘real world’ solutions. ----- ----- This paper provides an overview of some of the design and technological developments from the fashion/textiles industry, endorsing a model where designers and technicians use their transferrable skills for wellbeing rather than desire. Smart materials in the form of responsive and adaptive fibres and fabrics combined with electro active devices, and ICT are increasingly shaping many aspects of society particularly in the leisure industry and interactive consumer products are ever more visible in healthcare. Combinations of biocompatible delivery devices with bio sensing elements can create analyse, sense and actuate early warning and monitoring systems which can be linked to data logging and patient records via intelligent networks. Patient sympathetic, ‘smart’ fashion/textiles applications based on interdisciplinary expertise utilising textiles design and technology is emerging. An analysis of a series of case studies demonstrates the potential of fashion textiles design practitioners to exploit the concept of value adding through technological garment and textiles applications and enhancement for health and wellbeing and in doing so contribute to a more sustainable future fashion/textiles design industry.

Mesoporous bioglass/silk composite scaffolds for bone tissue engineering

In the past 20 years, mesoporous materials have been attracted great attention due to their significant feature of large surface area, ordered mesoporous structure, tunable pore size and volume, and well-defined surface property. They have many potential applications, such as catalysis, adsorption/separation, biomedicine, etc. [1]. Recently, the studies of the applications of mesoporous materials have been expanded into the field of biomaterials science. A new class of bioactive glass, referred to as mesoporous bioactive glass (MBG), was first developed in 2004. This material has a highly ordered mesopore channel structure with a pore size ranging from 5–20 nm [1]. Compared to non-mesopore bioactive glass (BG), MBG possesses a more optimal surface area, pore volume and improved in vitro apatite mineralization in simulated body fluids [1,2]. Vallet-Regí et al. has systematically investigated the in vitro apatite formation of different types of mesoporous materials, and they demonstrated that an apatite-like layer can be formed on the surfaces of Mobil Composition of Matters (MCM)-48, hexagonal mesoporous silica (SBA-15), phosphorous-doped MCM-41, bioglass-containing MCM-41 and ordered mesoporous MBG, allowing their use in biomedical engineering for tissue regeneration [2-4]. Chang et al. has found that MBG particles can be used for a bioactive drug-delivery system [5,6]. Our study has shown that MBG powders, when incorporated into a poly (lactide-co-glycolide) (PLGA) film, significantly enhance the apatite-mineralization ability and cell response of PLGA films. compared to BG [7]. These studies suggest that MBG is a very promising bioactive material with respect to bone regeneration. It is known that for bone defect repair, tissue engineering represents an optional method by creating three-dimensional (3D) porous scaffolds which will have more advantages than powders or granules as 3D scaffolds will provide an interconnected macroporous network to allow cell migration, nutrient delivery, bone ingrowth, and eventually vascularization [8]. For this reason, we try to apply MBG for bone tissue engineering by developing MBG scaffolds. However, one of the main disadvantages of MBG scaffolds is their low mechanical strength and high brittleness; the other issue is that they have very quick degradation, which leads to an unstable surface for bone cell growth limiting their applications. Silk fibroin, as a new family of native biomaterials, has been widely studied for bone and cartilage repair applications in the form of pure silk or its composite scaffolds [9-14]. Compared to traditional synthetic polymer materials, such as PLGA and poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV), the chief advantage of silk fibroin is its water-soluble nature, which eliminates the need for organic solvents, that tend to be highly cytotoxic in the process of scaffold preparation [15]. Other advantages of silk scaffolds are their excellent mechanical properties, controllable biodegradability and cytocompatibility [15-17]. However, for the purposes of bone tissue engineering, the osteoconductivity of pure silk scaffolds is suboptimal. It is expected that combining MBG with silk to produce MBG/silk composite scaffolds would greatly improve their physiochemical and osteogenic properties for bone tissue engineering application. Therefore, in this chapter, we will introduce the research development of MBG/silk scaffolds for bone tissue engineering.

Access control : allocating resources to selfish agents

The ultimate goal of an authorisation system is to allocate each user the level of access they need to complete their job - no more and no less. This proves to be challenging in an organisational setting because on one hand employees need enough access to perform their tasks, while on the other hand more access will bring about an increasing risk of misuse - either intentionally, where an employee uses the access for personal benefit, or unintentionally through carelessness, losing the information or being socially engineered to give access to an adversary. With the goal of developing a more dynamic authorisation model, we have adopted a game theoretic framework to reason about the factors that may affect users’ likelihood to misuse a permission at the time of an access decision. Game theory provides a useful but previously ignored perspective in authorisation theory: the notion of the user as a self-interested player who selects among a range of possible actions depending on their pay-offs.

Unpacking Japan's 21st century "National Conversation" : images of the future beyond the iron cage of the "Catch Up" model

How does the image of the future operate upon history, and upon national and individual identities? To what extent are possible futures colonized by the image? What are the un-said futurecratic discourses that underlie the image of the future? Such questions inspired the examination of Japan’s futures images in this thesis. The theoretical point of departure for this examination is Polak’s (1973) seminal research into the theory of the ‘image of the future’ and seven contemporary Japanese texts which offer various alternative images for Japan’s futures, selected as representative of a ‘national conversation’ about the futures of that nation. These seven images of the future are: 1. Report of the Prime Minister’s Commission on Japan’s Goals in the 21st Century—The Frontier Within: Individual Empowerment and Better Governance in the New Millennium, compiled by a committee headed by Japan’s preeminent Jungian psychologist Kawai Hayao (1928-2007); 2. Slow Is Beautiful—a publication by Tsuji Shinichi, in which he re-images Japan as a culture represented by the metaphor of the sloth, concerned with slow and quality-oriented livingry as a preferred image of the future to Japan’s current post-bubble cult of speed and economic efficiency; 3. MuRatopia is an image of the future in the form of a microcosmic prototype community and on-going project based on the historically significant island of Awaji, and established by Japanese economist and futures thinker Yamaguchi Kaoru; 4. F.U.C.K, I Love Japan, by author Tanja Yujiro provides this seven text image of the future line-up with a youth oriented sub-culture perspective on that nation’s futures; 5. IMAGINATION / CREATION—a compilation of round table discussions about Japan’s futures seen from the point of view of Japan’s creative vanguard; 6. Visionary People in a Visionless Country: 21 Earth Connecting Human Stories is a collection of twenty one essays compiled by Denmark born Tokyo resident Peter David Pedersen; and, 7. EXODUS to the Land of Hope, authored by Murakami Ryu, one of Japan’s most prolific and influential writers, this novel suggests a future scenario portraying a massive exodus of Japan’s youth, who, literate with state-of-the-art information and communication technologies (ICTs) move en masse to Japan’s northern island of Hokkaido to launch a cyber-revolution from the peripheries. The thesis employs a Futures Triangle Analysis (FTA) as the macro organizing framework and as such examines both pushes of the present and weights from the past before moving to focus on the pulls to the future represented by the seven texts mentioned above. Inayatullah’s (1999) Causal Layered Analysis (CLA) is the analytical framework used in examining the texts. Poststructuralist concepts derived primarily from the work of Michel Foucault are a particular (but not exclusive) reference point for the analytical approach it encompasses. The research questions which reflect the triangulated analytic matrix are: 1. What are the pushes—in terms of current trends—that are affecting Japan’s futures? 2. What are the historical and cultural weights that influence Japan’s futures? 3. What are the emerging transformative Japanese images of the future discourses, as embodied in actual texts, and what potential do they offer for transformative change in Japan? Research questions one and two are discussed in Chapter five and research question three is discussed in Chapter six. The first two research questions should be considered preliminary. The weights outlined in Chapter five indicate that the forces working against change in Japan are formidable, structurally deep-rooted, wide-spread, and under-recognized as change-adverse. Findings and analyses of the push dimension reveal strong forces towards a potentially very different type of Japan. However it is the seven contemporary Japanese images of the future, from which there is hope for transformative potential, which form the analytical heart of the thesis. In analyzing these texts the thesis establishes the richness of Japan’s images of the future and, as such, demonstrates the robustness of Japan’s stance vis-à-vis the problem of a perceived map-less and model-less future for Japan. Frontier is a useful image of the future, whose hybrid textuality, consisting of government, business, academia, and creative minority perspectives, demonstrates the earnestness of Japan’s leaders in favour of the creation of innovative futures for that nation. Slow is powerful in its aim to reconceptualize Japan’s philosophies of temporality, and build a new kind of nation founded on the principles of a human-oriented and expanded vision of economy based around the core metaphor of slowness culture. However its viability in Japan, with its post-Meiji historical pushes to an increasingly speed-obsessed social construction of reality, could render it impotent. MuRatopia is compelling in its creative hybridity indicative of an advanced IT society, set in a modern day utopian space based upon principles of a high communicative social paradigm, and sustainability. IMAGINATION / CREATION is less the plan than the platform for a new discussion on Japan’s transformation from an econo-centric social framework to a new Creative Age. It accords with emerging discourses from the Creative Industries, which would re-conceive of Japan as a leading maker of meaning, rather than as the so-called guzu, a term referred to in the book meaning ‘laggard’. In total, Love Japan is still the most idiosyncratic of all the images of the future discussed. Its communication style, which appeals to Japan’s youth cohort, establishes it as a potentially formidable change agent in a competitive market of futures images. Visionary People is a compelling image for its revolutionary and subversive stance against Japan’s vision-less political leadership, showing that it is the people, not the futures-making elite or aristocracy who must take the lead and create a new vanguard for the nation. Finally, Murakami’s Exodus cannot be ruled out as a compelling image of the future. Sharing the appeal of Tanja’s Love Japan to an increasingly disenfranchised youth, Exodus portrays a near-term future that is achievable in the here and now, by Japan’s teenagers, using information and communications technologies (ICTs) to subvert leadership, and create utopianist communities based on alternative social principles. The principal contribution from this investigation in terms of theory belongs to that of developing the Japanese image of the future. In this respect, the literature reviews represent a significant compilation, specifically about Japanese futures thinking, the Japanese image of the future, and the Japanese utopia. Though not exhaustive, this compilation will hopefully serve as a useful starting point for future research, not only for the Japanese image of the future, but also for all image of the future research. Many of the sources are in Japanese and their English summations are an added reason to respect this achievement. Secondly, the seven images of the future analysed in Chapter six represent the first time that Japanese image of the future texts have been systematically organized and analysed. Their translation from Japanese to English can be claimed as a significant secondary contribution. What is more, they have been analysed according to current futures methodologies that reveal a layeredness, depth, and overall richness existing in Japanese futures images. Revealing this image-richness has been one of the most significant findings of this investigation, suggesting that there is fertile research to be found from this still under-explored field, whose implications go beyond domestic Japanese concerns, and may offer fertile material for futures thinkers and researchers, Japanologists, social planners, and policy makers.

In situ preparation and protein delivery of silicate/alginate composite microspheres with core-shell structure

It is predicted that with increased life expectancy in the developed world, there will be a greater demand for synthetic materials to repair or regenerate lost, injured or diseased bone (Hench & Thompson 2010). There are still few synthetic materials having true bone inductivity, which limits their application for bone regeneration, especially in large-size bone defects. To solve this problem, growth factors, such as bone morphogenetic proteins (BMPs), have been incorporated into synthetic materials in order to stimulate de novo bone formation in the center of large-size bone defects. The greatest obstacle with this approach is that the rapid diffusion of the protein from the carrier material, leading to a precipitous loss of bioactivity; the result is often insufficient local induction or failure of bone regeneration (Wei et al. 2007). It is critical that the protein is loaded in the carrier material in conditions which maintains its bioactivity (van de Manakker et al. 2009). For this reason, the efficient loading and controlled release of a protein from a synthetic material has remained a significant challenge. The use of microspheres as protein/drug carriers has received considerable attention in recent years (Lee et al. 2010; Pareta & Edirisinghe 2006; Wu & Zreiqat 2010). Compared to macroporous block scaffolds, the chief advantage of microspheres is their superior protein-delivery properties and ability to fill bone defects with irregular and complex shapes and sizes. Upon implantation, the microspheres are easily conformed to the irregular implant site, and the interstices between the particles provide space for both tissue and vascular ingrowth, which are important for effective and functional bone regeneration (Hsu et al. 1999). Alginates are natural polysaccharides and their production does not have the implicit risk of contamination with allo or xeno-proteins or viruses (Xie et al. 2010). Because alginate is generally cytocompatible, it has been used extensively in medicine, including cell therapy and tissue engineering applications (Tampieri et al. 2005; Xie et al. 2010; Xu et al. 2007). Calcium cross-linked alginate hydrogel is considered a promising material as a delivery matrix for drugs and proteins, since its gel microspheres form readily in aqueous solutions at room temperature, eliminating the need for harsh organic solvents, thereby maintaining the bioactivity of proteins in the process of loading into the microspheres (Jay & Saltzman 2009; Kikuchi et al. 1999). In addition, calcium cross-linked alginate hydrogel is degradable under physiological conditions (Kibat PG et al. 1990; Park K et al. 1993), which makes alginate stand out as an attractive candidate material for the protein carrier and bone regeneration (Hosoya et al. 2004; Matsuno et al. 2008; Turco et al. 2009). However, the major disadvantages of alginate microspheres is their low loading efficiency and also rapid release of proteins due to the mesh-like networks of the gel (Halder et al. 2005). Previous studies have shown that a core-shell structure in drug/protein carriers can overcome the issues of limited loading efficiencies and rapid release of drug or protein (Chang et al. 2010; Molvinger et al. 2004; Soppimath et al. 2007). We therefore hypothesized that introducing a core-shell structure into the alginate microspheres could solve the shortcomings of the pure alginate. Calcium silicate (CS) has been tested as a biodegradable biomaterial for bone tissue regeneration. CS is capable of inducing bone-like apatite formation in simulated body fluid (SBF) and its apatite-formation rate in SBF is faster than that of Bioglass® and A-W glass-ceramics (De Aza et al. 2000; Siriphannon et al. 2002). Titanium alloys plasma-spray coated with CS have excellent in vivo bioactivity (Xue et al. 2005) and porous CS scaffolds have enhanced in vivo bone formation ability compared to porous β-tricalcium phosphate ceramics (Xu et al. 2008). In light of the many advantages of this material, we decided to prepare CS/alginate composite microspheres by combining a CS shell with an alginate core to improve their protein delivery and mineralization for potential protein delivery and bone repair applications

Non-invasive assessment of tear film surface quality

The tear film plays an important role preserving the health of the ocular surface and maintaining the optimal refractive power of the cornea. Moreover dry eye syndrome is one of the most commonly reported eye health problems. This syndrome is caused by abnormalities in the properties of the tear film. Current clinical tools to assess the tear film properties have shown certain limitations. The traditional invasive methods for the assessment of tear film quality, which are used by most clinicians, have been criticized for the lack of reliability and/or repeatability. A range of non-invasive methods of tear assessment have been investigated, but also present limitations. Hence no “gold standard” test is currently available to assess the tear film integrity. Therefore, improving techniques for the assessment of the tear film quality is of clinical significance and the main motivation for the work described in this thesis. In this study the tear film surface quality (TFSQ) changes were investigated by means of high-speed videokeratoscopy (HSV). In this technique, a set of concentric rings formed in an illuminated cone or a bowl is projected on the anterior cornea and their reflection from the ocular surface imaged on a charge-coupled device (CCD). The reflection of the light is produced in the outer most layer of the cornea, the tear film. Hence, when the tear film is smooth the reflected image presents a well structure pattern. In contrast, when the tear film surface presents irregularities, the pattern also becomes irregular due to the light scatter and deviation of the reflected light. The videokeratoscope provides an estimate of the corneal topography associated with each Placido disk image. Topographical estimates, which have been used in the past to quantify tear film changes, may not always be suitable for the evaluation of all the dynamic phases of the tear film. However the Placido disk image itself, which contains the reflected pattern, may be more appropriate to assess the tear film dynamics. A set of novel routines have been purposely developed to quantify the changes of the reflected pattern and to extract a time series estimate of the TFSQ from the video recording. The routine extracts from each frame of the video recording a maximized area of analysis. In this area a metric of the TFSQ is calculated. Initially two metrics based on the Gabor filter and Gaussian gradient-based techniques, were used to quantify the consistency of the pattern’s local orientation as a metric of TFSQ. These metrics have helped to demonstrate the applicability of HSV to assess the tear film, and the influence of contact lens wear on TFSQ. The results suggest that the dynamic-area analysis method of HSV was able to distinguish and quantify the subtle, but systematic degradation of tear film surface quality in the inter-blink interval in contact lens wear. It was also able to clearly show a difference between bare eye and contact lens wearing conditions. Thus, the HSV method appears to be a useful technique for quantitatively investigating the effects of contact lens wear on the TFSQ. Subsequently a larger clinical study was conducted to perform a comparison between HSV and two other non-invasive techniques, lateral shearing interferometry (LSI) and dynamic wavefront sensing (DWS). Of these non-invasive techniques, the HSV appeared to be the most precise method for measuring TFSQ, by virtue of its lower coefficient of variation. While the LSI appears to be the most sensitive method for analyzing the tear build-up time (TBUT). The capability of each of the non-invasive methods to discriminate dry eye from normal subjects was also investigated. The receiver operating characteristic (ROC) curves were calculated to assess the ability of each method to predict dry eye syndrome. The LSI technique gave the best results under both natural blinking conditions and in suppressed blinking conditions, which was closely followed by HSV. The DWS did not perform as well as LSI or HSV. The main limitation of the HSV technique, which was identified during the former clinical study, was the lack of the sensitivity to quantify the build-up/formation phase of the tear film cycle. For that reason an extra metric based on image transformation and block processing was proposed. In this metric, the area of analysis was transformed from Cartesian to Polar coordinates, converting the concentric circles pattern into a quasi-straight lines image in which a block statistics value was extracted. This metric has shown better sensitivity under low pattern disturbance as well as has improved the performance of the ROC curves. Additionally a theoretical study, based on ray-tracing techniques and topographical models of the tear film, was proposed to fully comprehend the HSV measurement and the instrument’s potential limitations. Of special interested was the assessment of the instrument’s sensitivity under subtle topographic changes. The theoretical simulations have helped to provide some understanding on the tear film dynamics, for instance the model extracted for the build-up phase has helped to provide some insight into the dynamics during this initial phase. Finally some aspects of the mathematical modeling of TFSQ time series have been reported in this thesis. Over the years, different functions have been used to model the time series as well as to extract the key clinical parameters (i.e., timing). Unfortunately those techniques to model the tear film time series do not simultaneously consider the underlying physiological mechanism and the parameter extraction methods. A set of guidelines are proposed to meet both criteria. Special attention was given to a commonly used fit, the polynomial function, and considerations to select the appropriate model order to ensure the true derivative of the signal is accurately represented. The work described in this thesis has shown the potential of using high-speed videokeratoscopy to assess tear film surface quality. A set of novel image and signal processing techniques have been proposed to quantify different aspects of the tear film assessment, analysis and modeling. The dynamic-area HSV has shown good performance in a broad range of conditions (i.e., contact lens, normal and dry eye subjects). As a result, this technique could be a useful clinical tool to assess tear film surface quality in the future.

Optimization of container process at seaport terminals

Seaport container terminals are an important part of the logistics systems in international trades. This paper investigates the relationship between quay cranes, yard machines and container storage locations in a multi-berth and multi-ship environment. The aims are to develop a model for improving the operation efficiency of the seaports and to develop an analytical tool for yard operation planning. Due to the fact that the container transfer times are sequence-dependent and with the large number of variables involve, the proposed model cannot be solved in a reasonable time interval for realistically sized problems. For this reason, List Scheduling and Tabu Search algorithms have been developed to solve this formidable and NP-hard scheduling problem. Numerical implementations have been analysed and promising results have been achieved.

A forensic investigation of single human hair fibres using FTIR-ATR spectroscopy and chemometrics

Human hair fibres are ubiquitous in nature and are found frequently at crime scenes often as a result of exchange between the perpetrator, victim and/or the surroundings according to Locard's Principle. Therefore, hair fibre evidence can provide important information for crime investigation. For human hair evidence, the current forensic methods of analysis rely on comparisons of either hair morphology by microscopic examination or nuclear and mitochondrial DNA analyses. Unfortunately in some instances the utilisation of microscopy and DNA analyses are difficult and often not feasible. This dissertation is arguably the first comprehensive investigation aimed to compare, classify and identify the single human scalp hair fibres with the aid of FTIR-ATR spectroscopy in a forensic context. Spectra were collected from the hair of 66 subjects of Asian, Caucasian and African (i.e. African-type). The fibres ranged from untreated to variously mildly and heavily cosmetically treated hairs. The collected spectra reflected the physical and chemical nature of a hair from the near-surface particularly, the cuticle layer. In total, 550 spectra were acquired and processed to construct a relatively large database. To assist with the interpretation of the complex spectra from various types of human hair, Derivative Spectroscopy and Chemometric methods such as Principal Component Analysis (PCA), Fuzzy Clustering (FC) and Multi-Criteria Decision Making (MCDM) program; Preference Ranking Organisation Method for Enrichment Evaluation (PROMETHEE) and Geometrical Analysis for Interactive Aid (GAIA); were utilised. FTIR-ATR spectroscopy had two important advantages over to previous methods: (i) sample throughput and spectral collection were significantly improved (no physical flattening or microscope manipulations), and (ii) given the recent advances in FTIR-ATR instrument portability, there is real potential to transfer this work.s findings seamlessly to on-field applications. The "raw" spectra, spectral subtractions and second derivative spectra were compared to demonstrate the subtle differences in human hair. SEM images were used as corroborative evidence to demonstrate the surface topography of hair. It indicated that the condition of the cuticle surface could be of three types: untreated, mildly treated and treated hair. Extensive studies of potential spectral band regions responsible for matching and discrimination of various types of hair samples suggested the 1690-1500 cm^-1 IR spectral region was to be preferred in comparison with the commonly used 1750-800 cm^-1. The principal reason was the presence of the highly variable spectral profiles of cystine oxidation products (1200-1000 cm^-1), which contributed significantly to spectral scatter and hence, poor hair sample matching. In the preferred 1690-1500 cm^-1 region, conformational changes in the keratin protein attributed to the α-helical to β-sheet transitions in the Amide I and Amide II vibrations and played a significant role in matching and discrimination of the spectra and hence, the hair fibre samples. For gender comparison, the Amide II band is significant for differentiation. The results illustrated that the male hair spectra exhibit a more intense β-sheet vibration in the Amide II band at approximately 1511 cm^-1 whilst the female hair spectra displayed more intense α-helical vibration at 1520-1515cm^-1. In terms of chemical composition, female hair spectra exhibit greater intensity of the amino acid tryptophan (1554 cm^-1), aspartic and glutamic acid (1577 cm^-1). It was also observed that for the separation of samples based on racial differences, untreated Caucasian hair was discriminated from Asian hair as a result of having higher levels of the amino acid cystine and cysteic acid. However, when mildly or chemically treated, Asian and Caucasian hair fibres are similar, whereas African-type hair fibres are different. In terms of the investigation's novel contribution to the field of forensic science, it has allowed for the development of a novel, multifaceted, methodical protocol where previously none had existed. The protocol is a systematic method to rapidly investigate unknown or questioned single human hair FTIR-ATR spectra from different genders and racial origin, including fibres of different cosmetic treatments. Unknown or questioned spectra are first separated on the basis of chemical treatment i.e. untreated, mildly treated or chemically treated, genders, and racial origin i.e. Asian, Caucasian and African-type. The methodology has the potential to complement the current forensic analysis methods of fibre evidence (i.e. Microscopy and DNA), providing information on the morphological, genetic and structural levels.

'Which is the best Doctor Who story?' : a case study in value judgements outside the academy'

One of Cultural Studies' most important contributions to academic thinking about culture is the acceptance as axiomatic that we must not simply accept traditional value hierarchies in relation to cultural objects (see, for example, McGuigan, 1992: 157; Brunsdon, 1997: 5; Wark, 2001). Since Richard Hoggart and Raymond Williams took popular culture as a worthy object of study, Cultural Studies practitioners have accepted that the terms in which cultural debate had previously been conducted involved a category error. Opera is not 'better' than pop music, we believe in Cultural Studies - 'better for what?', we would ask. Similarly, Shakespeare is not 'better' than Mills and Boon, unless you can specify the purpose for which you want to use the texts. Shakespeare is indeed better than Mills and Boon for understanding seventeenth century ideas about social organisation; but Mills and Boon is unquestionably better than Shakespeare if you want slightly scandalous, but ultimately reassuring representations of sexual intercourse. The reason that we do not accept traditional hierarchies of cultural value is that we know that the culture that is commonly understood to be 'best' also happens to be that which is preferred by the most educated and most materially well-off people in any given culture (Bourdieu, 1984: 1- 2; Ross, 1989: 211). We can interpret this information in at least two ways. On the one hand, it can be read as proving that the poorer and less well-educated members of a society do indeed have tastes which are innately less worthwhile than those of the material and educational elite. On the other hand, this information can be interpreted as demonstrating that the cultural and material elite publicly represent their own tastes as being the only correct ones. In Cultural Studies, we tend to favour the latter interpretation. We reject the idea that cultural objects have innate value, in terms of beauty, truth, excellence, simply 'there' in the object. That is, we reject 'aesthetic' approaches to culture (Bourdieu, 1984: 6; 485; Hartley, 1994: 6)1. In this, Cultural Studies is similar to other postmodern institutions, where high and popular culture can be mixed in ways unfamiliar to modernist culture (Sim, 1992: 1; Jameson, 1998: 100). So far, so familiar.

Body-site distribution of skin cancer, pre-malignant and common benign pigmented lesions excised in general practice

Background Concern about skin cancer is a common reason for people from predominantly fair-skinned populations to present to primary care doctors. Objectives To examine the frequency and body-site distribution of malignant, pre-malignant and benign pigmented skin lesions excised in primary care. Methods This prospective study conducted in Queensland, Australia, included 154 primary care doctors. For all excised or biopsied lesions, doctors recorded the patient's age and sex, body site, level of patient pressure to excise, and the clinical diagnosis. Histological confirmation was obtained through pathology laboratories. Results Of 9650 skin lesions, 57·7% were excised in males and 75·0% excised in patients ≥50years. The most common diagnoses were basal cell carcinoma (BCC) (35·1%) and squamous cell carcinoma (SCC) (19·7%). Compared with the whole body, the highest densities for SCC, BCC and actinic keratoses were observed on chronically sun-exposed areas of the body including the face in males and females, the scalp and ears in males, and the hands in females. The density of BCC was also high on intermittently or rarely exposed body sites. Females, younger patients and patients with melanocytic naevi were significantly more likely to exert moderate/high levels of pressure on the doctor to excise. Conclusions More than half the excised lesions were skin cancer, which mostly occurred on the more chronically sun-exposed areas of the body. Information on the type and body-site distribution of skin lesions can aid in the diagnosis and planned management of skin cancer and other skin lesions commonly presented in primary care.

Journalists at war

Journalism is an especially hazardous profession when it takes the reporter into zones of war and conflict. The Committee to Protect Journalists records that in 2010 44 journalists were killed while carrying out their duties. Some of these were reporting conflict in Afghanistan, Somalia, Iraq and elsewhere. Others were on assignments covering crime and corruption in Mexico, Russia, Venezuela*all places where telling truth to power can easily get you killed, beaten or banged up. In the last 20 years some 874 journalists have been killed on the job, and we salute them all. Journalists get criticised a lot by we scholars, and often for good reason. They can be villains, for sure, but they can also be heroes, when they lay down their lives in the pursuit of the truth. As this piece was being edited, photojournalists Tim Hetherington and Chris Hondros were killed in Libya.

The coming of post-reflexive society : a critique of the political economy of digital capitalism

Language is a unique aspect of human communication because it can be used to discuss itself in its own terms. For this reason, human societies potentially have superior capacities of co-ordination, reflexive self-correction, and innovation than other animal, physical or cybernetic systems. However, this analysis also reveals that language is interconnected with the economically and technologically mediated social sphere and hence is vulnerable to abstraction, objectification, reification, and therefore ideology – all of which are antithetical to its reflexive function, whilst paradoxically being a fundamental part of it. In particular, in capitalism, language is increasingly commodified within the social domains created and affected by ubiquitous communication technologies. The advent of the so-called ‘knowledge economy’ implicates exchangeable forms of thought (language) as the fundamental commodities of this emerging system. The historical point at which a ‘knowledge economy’ emerges, then, is the critical point at which thought itself becomes a commodified ‘thing’, and language becomes its “objective” means of exchange. However, the processes by which such commodification and objectification occurs obscures the unique social relations within which these language commodities are produced. The latest economic phase of capitalism – the knowledge economy – and the obfuscating trajectory which accompanies it, we argue, is destroying the reflexive capacity of language particularly through the process of commodification. This can be seen in that the language practices that have emerged in conjunction with digital technologies are increasingly non-reflexive and therefore less capable of self-critical, conscious change.

Influence of culture conditions on the molecular signature of mesenchymal stem cells

Cell based therapies require cells capable of self renewal and differentiation, and a prerequisite is the ability to prepare an effective dose of ex vivo expanded cells for autologous transplants. The in vivo identification of a source of physiologically relevant cell types suitable for cell therapies is therefore an integral part of tissue engineering. Bone marrow is the most easily accessible source of mesenchymal stem cells (MSCs), and harbours two distinct populations of adult stem cells; namely hematopoietic stem cells (HSCs) and bone mesenchymal stem cells (BMSCs). Unlike HSCs, there are yet no rigorous criteria for characterizing BMSCs. Changing understanding about the pluripotency of BMSCs in recent studies has expanded their potential application; however, the underlying molecular pathways which impart the features distinctive to BMSCs remain elusive. Furthermore, the sparse in vivo distribution of these cells imposes a clear limitation to their in vitro study. Also, when BMSCs are cultured in vitro there is a loss of the in vivo microenvironment which results in a progressive decline in proliferation potential and multipotentiality. This is further exacerbated with increased passage number, characterized by the onset of senescence related changes. Accordingly, establishing protocols for generating large numbers of BMSCs without affecting their differentiation potential is necessary. The principal aims of this thesis were to identify potential molecular factors for characterizing BMSCs from osteoarthritic patients, and also to attempt to establish culture protocols favourable for generating large number of BMSCs, while at the same time retaining their proliferation and differentiation potential. Previously published studies concerning clonal cells have demonstrated that BMSCs are heterogeneous populations of cells at various stages of growth. Some cells are higher in the hierarchy and represent the progenitors, while other cells occupy a lower position in the hierarchy and are therefore more committed to a particular lineage. This feature of BMSCs was made evident by the work of Mareddy et al., which involved generating clonal populations of BMSCs from bone marrow of osteoarthritic patients, by a single cell clonal culture method. Proliferation potential and differentiation capabilities were used to group cells into fast growing and slow growing clones. The study presented here is a continuation of the work of Mareddy et al. and employed immunological and array based techniques to identify the primary molecular factors involved in regulating phenotypic characteristics exhibited by contrasting clonal populations. The subtractive immunization (SI) was used to generate novel antibodies against favourably expressed proteins in the fast growing clonal cell population. The difference between the clonal populations at the transcriptional level was determined using a Stem Cell RT2 Profiler TM PCR Array which focuses on stem cell pathway gene expression. Monoclonal antibodies (mAb) generated by SI were able to effectively highlight differentially expressed antigenic determinants, as was evident by Western blot analysis and confocal microscopy. Co-immunoprecipitation, followed by mass spectroscopy analysis, identified a favourably expressed protein as the cytoskeletal protein vimentin. The stem cell gene array highlighted genes that were highly upregulated in the fast growing clonal cell population. Based on their functions these genes were grouped into growth factors, cell fate determination and maintenance of embryonic and neural stem cell renewal. Furthermore, on a closer analysis it was established that the cytoskeletal protein vimentin and nine out of ten genes identified by gene array were associated with chondrogenesis or cartilage repair, consistent with the potential role played by BMSCs in defect repair and maintaining tissue homeostasis, by modulating the gene expression pattern to compensate for degenerated cartilage in osteoarthritic tissues. The gene array also presented transcripts for embryonic lineage markers such as FOXA2 and Sox2, both of which were significantly over expressed in fast growing clonal populations. A recent groundbreaking study by Yamanaka et al imparted embryonic stem cell (ESCs) -like characteristic to somatic cells in a process termed nuclear reprogramming, by the ectopic expression of the genes Sox2, cMyc and Oct4. The expression of embryonic lineage markers in adult stem cells may be a mechanism by which the favourable behaviour of fast growing clonal cells is determined and suggests a possible active phenomenon of spontaneous reprogramming in fast growing clonal cells. The expression pattern of these critical molecular markers could be indicative of the competence of BMSCs. For this reason, the expression pattern of Sox2, Oct4 and cMyc, at various passages in heterogeneous BMSCs population and tissue derived cells (osteoblasts and chondrocytes), was investigated by a real-time PCR and immunoflourescence staining. A strong nuclear staining was observed for Sox2, Oct4 and cMyc, which gradually weakened accompanied with cytoplasmic translocation after several passage. The mRNA and protein expression of Sox2, Oct4 and cMyc peaked at the third passage for osteoblasts, chondrocytes and third passage for BMSCs, and declined with each subsequent passage, indicating towards a possible mechanism of spontaneous reprogramming. This study proposes that the progressive decline in proliferation potential and multipotentiality associated with increased passaging of BMSCs in vitro might be a consequence of loss of these propluripotency factors. We therefore hypothesise that the expression of these master genes is not an intrinsic cell function, but rather an outcome of interaction of the cells with their microenvironment; this was evident by the fact that when removed from their in vivo microenvironment, BMSCs undergo a rapid loss of stemness after only a few passages. One of the most interesting aspects of this study was the integration of factors in the culture conditions, which to some extent, mimicked the in vivo microenvironmental niche of the BMSCs. A number of studies have successfully established that the cellular niche is not an inert tissue component but is of prime importance. The total sum of stimuli from the microenvironment underpins the complex interplay of regulatory mechanisms which control multiple functions in stem cells most importantly stem cell renewal. Therefore, well characterised factors which affect BMSCs characteristics, such as fibronectin (FN) coating, and morphogens such as FGF2 and BMP4, were incorporated into the cell culture conditions. The experimental set up was designed to provide insight into the expression pattern of the stem cell related transcription factors Sox2, cMyc and Oct4, in BMSCs with respect to passaging and changes in culture conditions. Induction of these pluripotency markers in somatic cells by retroviral transfection has been shown to confer pluripotency and an ESCs like state. Our study demonstrated that all treatments could transiently induce the expression of Sox2, cMyc and Oct4, and favourably affect the proliferation potential of BMSCs. The combined effect of these treatments was able to induce and retain the endogenous nuclear expression of stem cell transcription factors in BMSCs over an extended number of in vitro passages. Our results therefore suggest that the transient induction and manipulation of endogenous expression of transcription factors critical for stemness can be achieved by modulating the culture conditions; the benefit of which is to circumvent the need for genetic manipulations. In summary, this study has explored the role of BMSCs in the diseased state of osteoarthritis, by employing transcriptional profiling along with SI. In particular this study pioneered the use of primary cells for generating novel antibodies by SI. We established that somatic cells and BMSCs have a basal level of expression of pluripotency markers. Furthermore, our study indicates that intrinsic signalling mechanisms of BMSCs are intimately linked with extrinsic cues from the microenvironment and that these signals appear to be critical for retaining the expression of genes to maintain cell stemness in long term in vitro culture. This project provides a basis for developing an “artificial niche” required for reversion of commitment and maintenance of BMSC in their uncommitted homeostatic state.