Increased diversity of libraries from libraries: chemoinformatic analysis of bis-diazacyclic libraries

Combinatorial libraries continue to play a key role in drug discovery. To increase structural diversity, several experimental methods have been developed. However, limited efforts have been performed so far to quantify the diversity of the broadly used diversity-oriented synthetic (DOS) libraries. Herein we report a comprehensive characterization of 15 bis-diazacyclic combinatorial libraries obtained through libraries from libraries, which is a DOS approach. Using MACCS keys, radial and different pharmacophoric fingerprints as well as six molecular properties, it was demonstrated the increased structural and property diversity of the libraries from libraries over the individual libraries. Comparison of the libraries to existing drugs, NCI Diversity and the Molecular Libraries Small Molecule Repository revealed the structural uniqueness of the combinatorial libraries (mean similarity < 0.5 for any fingerprint representation). In particular, bis-cyclic thiourea libraries were the most structurally dissimilar to drugs retaining drug-like character in property space. This study represents the first comprehensive quantification of the diversity of libraries from libraries providing a solid quantitative approach to compare and contrast the diversity of DOS libraries with existing drugs or any other compound collection.

Improved time response for polymer fibre Bragg grating based humidity sensors

In this work we experimentally investigate the response time of humidity sensors based on polymer optical fibre (POF) Bragg gratings. By the use of etching with acetone we can control the diameter of POF based on poly (methyl methacrylate) in order to reduce the diffusion time of water into the polymer and hence speed up the relative wavelength change caused by humidity variations. A much improved response time of 11 minutes has been achieved by using a POF FBG with a reduced diameter of 135 microns.

All-fibre twist sensor system based on 45 and 81 tilted fibre gratings

We experimentally demonstrated a highly sensitive twist sensor system based on a 45° and an 81° tilted fibre grating (TFG). The 81°-TFG has a set of dual-peaks that are due to the birefringence induced by its extremely tilted structure. When the 81°-TFG subjected to twist, the coupling to the two peaks would interchange from each other, providing a mechanism to measure and monitor the twist. We have investigated the performance of the sensor system by three interrogation methods (spectral, power-measurement and voltage-measurement). The experimental results clearly show that the 81°-TFG and the 45°-TFG could be combined forming a full fibre twist sensor system capable of not just measuring the magnitude but also recognising the direction of the applied twist.

Numerical modelling of complex femtosecond laser inscribed fiber gratings - comparison wih experiment

We present experimental studies and numerical modeling based on a combination of the Bidirectional Beam Propagation Method and Finite Element Modeling that completely describes the wavelength spectra of point by point femtosecond laser inscribed fiber Bragg gratings, showing excellent agreement with experiment. We have investigated the dependence of different spectral parameters such as insertion loss, all dominant cladding and ghost modes and their shape relative to the position of the fiber Bragg grating in the core of the fiber. Our model is validated by comparing model predictions with experimental data and allows for predictive modeling of the gratings. We expand our analysis to more complicated structures, where we introduce symmetry breaking; this highlights the importance of centered gratings and how maintaining symmetry contributes to the overall spectral quality of the inscribed Bragg gratings. Finally, the numerical modeling is applied to superstructure gratings and a comparison with experimental results reveals a capability for dealing with complex grating structures that can be designed with particular wavelength characteristics.

Femtosecond laser inscribed superstructure fibre gratings

We demonstrate the development of femtosecond laser inscribed superstructure fiber gratings (fsSFG) in silica optical fibre. We utilise a single step process, to inscribe low loss and polarisation independent, sampled gratings in optical fibres using the point by point femtosecond laser inscription method. Our approach results in a controlled modulated index change with complete suppression of any overlapping LPG structure leading to highly symmetric superstructure spectra, with the grating reflection well within the Fourier design limit. We also solve Maxwell's equations and calculate the back reflection spectrum using the bidirectional beam propagation method (BiBPM). Experimental results validate our numerical analysis and the estimation of inscription parameters such as ac index modulation, wavelength and the relative peak strength. We also explore how changes in the grating's period influence the reflection spectrum.

Fibre optic sensors for high speed hypervelocity impact studies and low velocity drop tests

The initial aim of this project was to develop a non-contact fibre optic based displacement sensor to operate in the harsh environment of a 'Light Gas Gun' (LGG), which can 'fire' small particles at velocities ranging from 1-8.4 km/s. The LGG is used extensively for research in aerospace to analyze the effects of high speed impacts on materials. Ideally the measurement should be made close to the centre of the impact to minimise corruption of the data from edge effects and survive the impact. A further requirement is that it should operate at a stand-off distance of ~ 8cm. For these reasons we chose to develop a pseudo con-focal intensity sensor, which demonstrated resolution comparable with conventional PVDF sensors combined with high survivability and low cost. A second sensor was developed based on 'Fibre Bragg Gratings' (FBG) which although requiring contact with the target the low weight and very small contact area had minimal effect on the dynamics of the target. The FBG was mounted either on the surface of the target or tangentially between a fixed location. The output signals from the FBG were interrogated in time by a new method. Measurements were made on composite and aluminium plates in the LGG and on low speed drop tests. The particle momentum for the drop tests was chosen to be similar to that of the particles used in the LGG.

Une étude générique du metteur en scène au théâtre:son émergence et son rôle moderne et contemporain

The theatre director (metteur en scene in French) is a relatively new figure in theatre practice. It was not until the I820s that the term 'mise en scene' gained currency. The term 'director' was not in general use until the I880s. The emergence and the role of the director has been considered from a variety of perspectives, either through the history of theatre (Allevy, Jomaron, Sarrazac, Viala, Biet and Triau); the history of directing (Chinoy and Cole, Boll, Veinstein, Roubine); semiotic approaches to directing (Whitmore, Miller, Pavis); the semiotics of performance (De Marinis); generic approaches to the mise en scene (Thomasseau, Banu); post-dramatic approaches to theatre (Lehmann); approaches to performance process and the specifics of rehearsal methodology (Bradby and Williams, Giannachi and Luckhurst, Picon-Vallin, Styan). What the scholarly literature has not done so far is to map the parameters necessarily involved in the directing process, and to incorporate an analysis of the emergence of the theatre director during the modem period and consider its impact on contemporary performance practice. Directing relates primarily to the making of the performance guided by a director, a single figure charged with the authority to make binding artistic decisions. Each director may have her/his own personal approaches to the process of preparation prior to a show. This is exemplified, for example, by the variety of terms now used to describe the role and function of directing, from producer, to facilitator or outside eye. However, it is essential at the outset to make two observations, each of which contributes to a justification for a generic analysis (as opposed to a genetic approach). Firstly, a director does not work alone, and cooperation with others is involved at all stages of the process. Secondly, beyond individual variation, the role of the director remains twofold. The first is to guide the actors (meneur de jeu, directeur d'acteurs, coach); the second is to make a visual representation in the performance space (set designer, stage designer, costume designer, lighting designer, scenographe). The increasing place of scenography has brought contemporary theatre directors such as Wilson, Castellucci, Fabre to produce performances where the performance space becomes a semiotic dimension that displaces the primacy of the text. The play is not, therefore, the sole artistic vehicle for directing. This definition of directing obviously calls for a definition of what the making of the performance might be. The thesis defines the making of the performance as the activity of bringing a social event, by at least one performer, providing visual and/or textual meaning in a performance space. This definition enables us to evaluate four consistent parameters throughout theatre history: first, the social aspect associated to the performance event; second, the devising process which may be based on visual and/or textual elements; third, the presence of at least one performer in the show; fourth, the performance space (which is not simply related to the theatre stage). Although the thesis focuses primarily on theatre practice, such definition blurs the boundaries between theatre and other collaborative artistic disciplines (cinema, opera, music and dance). These parameters illustrate the possibility to undertake a generic analysis of directing, and resonate with the historical, political and artistic dimensions considered. Such a generic perspective on the role of the director addresses three significant questions: an historical question: how/why has the director emerged?; a sociopolitical question: how/why was the director a catalyst for the politicisation of theatre, and subsequently contributed to the rise of State-funded theatre policy?; and an artistic one: how/why the director has changed theatre practice and theory in the twentieth-century? Directing for the theatre as an artistic activity is a historically situated phenomenon. It would seem only natural from a contemporary perspective to associate the activity of directing to the function of the director. This is relativised, however, by the question of how the performance was produced before the modern period. The thesis demonstrates that the rise of the director is a progressive and historical phenomenon (Dort) rather than a mere invention (Viala, Sarrazac). A chronological analysis of the making of the performance throughout theatre history is the most useful way to open the study. In order to understand the emergence of the director, the research methodology assesses the interconnection of the four parameters above throughout four main periods of theatre history: the beginning of the Renaissance (meneur de jeu), the classical age (actor-manager and stage designer-manager), the modern period (director) and the contemporary period (director-facilitator, performer). This allows us properly to appraise the progressive emergence of the director, as well as to make an analysis of her/his modern and contemporary role. The first chapter argues that the physical separation between the performance space and its audience, which appeared in the early fifteenth-century, has been a crucial feature in the scenographic, aesthetic, political and social organisation of the performance. At the end of the Middle Ages, French farces which raised socio-political issues (see Bakhtin) made a clear division on a single outdoor stage (treteau) between the actors and the spectators, while religious plays (drame fiturgique, mystere) were mostly performed on various outdoor and opened multispaces. As long as the performance was liturgical or religious, and therefore confined within an acceptable framework, it was allowed. At the time, the French ecclesiastical and civil authorities tried, on several occasions, to prohibit staged performances. As a result, practitioners developed non-official indoor spaces, the Theatre de fa Trinite (1398) being the first French indoor theatre recognized by scholars. This self-exclusion from the open public space involved breaking the accepted rules by practitioners (e.g. Les Confreres de fa Passion), in terms of themes but also through individual input into a secular performance rather than the repetition of commonly known religious canvases. These developments heralded the authorised theatres that began to emerge from the mid-sixteenth century, which in some cases were subsidised in their construction. The construction of authorised indoor theatres associated with the development of printing led to a considerable increase in the production of dramatic texts for the stage. Profoundly affecting the reception of the dramatic text by the audience, the distance between the stage and the auditorium accompanied the changing relationship between practitioners and spectators. This distance gave rise to a major development of the role of the actor and of the stage designer. The second chapter looks at the significance of both the actor and set designer in the devising process of the performance from the sixteenth-century to the end of the nineteenth-century. The actor underwent an important shift in function in this period from the delivery of an unwritten text that is learned in the medieval oral tradition to a structured improvisation produced by the commedia dell 'arte. In this new form of theatre, a chef de troupe or an experienced actor shaped the story, but the text existed only through the improvisation of the actors. The preparation of those performances was, moreover, centred on acting technique and the individual skills of the actor. From this point, there is clear evidence that acting began to be the subject of a number of studies in the mid-sixteenth-century, and more significantly in the seventeenth-century, in Italy and France. This is revealed through the implementation of a system of notes written by the playwright to the actors (stage directions) in a range of plays (Gerard de Vivier, Comedie de la Fidelite Nuptiale, 1577). The thesis also focuses on Leoni de' Sommi (Quatro dialoghi, 1556 or 1565) who wrote about actors' techniques and introduced the meneur de jeu in Italy. The actor-manager (meneur de jeu), a professional actor, who scholars have compared to the director (see Strihan), trained the actors. Nothing, however, indicates that the actor-manager was directing the visual representation of the text in the performance space. From the end of the sixteenth-century, the dramatic text began to dominate the process of the performance and led to an expansion of acting techniques, such as the declamation. Stage designers carne from outside the theatre tradition and played a decisive role in the staging of religious celebrations (e.g. Actes des Apotres, 1536). In the sixteenth-century, both the proscenium arch and the borders, incorporated in the architecture of the new indoor theatres (theatre a l'italienne), contributed to create all kinds of illusions on the stage, principally the revival of perspective. This chapter shows ongoing audience demands for more elaborate visual effects on the stage. This led, throughout the classical age, and even more so during the eighteenth-century, to grant the stage design practitioner a major role in the making of the performance (see Ciceri). The second chapter demonstrates that the guidance of the actors and the scenographic conception, which are the artistic components of the role of the director, appear to have developed independently from one another until the nineteenth-century. The third chapter investigates the emergence of the director per se. The causes for this have been considered by a number of scholars, who have mainly identified two: the influence of Naturalism (illustrated by the Meiningen Company, Antoine, and Stanislavski) and the invention of electric lighting. The influence of the Naturalist movement on the emergence of the modem director in the late nineteenth-century is often considered as a radical factor in the history of theatre practice. Naturalism undoubtedly contributed to changes in staging, costume and lighting design, and to a more rigorous commitment to the harmonisation and visualisation of the overall production of the play. Although the art of theatre was dependent on the dramatic text, scholars (Osborne) demonstrate that the Naturalist directors did not strictly follow the playwright's indications written in the play in the late nineteenth-century. On the other hand, the main characteristic of directing in Naturalism at that time depended on a comprehensive understanding of the scenography, which had to respond to the requirements of verisimilitude. Electric lighting contributed to this by allowing for the construction of a visual narrative on stage. However, it was a master technician, rather than an emergent director, who was responsible for key operational decisions over how to use this emerging technology in venues such as the new Bayreuth theatre in 1876. Electric lighting reflects a normal technological evolution and cannot be considered as one of the main causes of the emergence of the director. Two further causes of the emergence of the director, not considered in previous studies, are the invention of cinema and the Symbolist movement (Lugne-Poe, Meyerhold). Cinema had an important technological influence on the practitioners of the Naturalist movement. In order to achieve a photographic truth on the stage (tableau, image), Naturalist directors strove to decorate the stage with the detailed elements that would be expected to be found if the situation were happening in reality. Film production had an influence on the work of actors (Walter). The filmmaker took over a primary role in the making of the film, as the source of the script, the filming process and the editing of the film. This role influenced the conception that theatre directors had of their own work. It is this concept of the director which influenced the development of the theatre director. As for the Symbolist movement, the director's approach was to dematerialise the text of the playwright, trying to expose the spirit, movement, colour and rhythm of the text. Therefore, the Symbolists disengaged themselves from the material aspect of the production, and contributed to give greater artistic autonomy to the role of the director. Although the emergence of the director finds its roots amongst the Naturalist practitioners (through a rigorous attempt to provide a strict visual interpretation of the text on stage), the Symbolist director heralded the modem perspective of the making of performance. The emergence of the director significantly changed theatre practice and theory. For instance, the rehearsal period became a clear work in progress, a platform for both developing practitioners' techniques and staging the show. This chapter explores and contrasts several practitioners' methods based on the two aspects proposed for the definition of the director (guidance of the actors and materialisation of a visual space). The fourth chapter argues that the role of the director became stronger, more prominent, and more hierarchical, through a more political and didactic approach to theatre as exemplified by the cases of France and Germany at the end of the nineteenth-century and through the First World War. This didactic perspective to theatre defines the notion of political theatre. Political theatre is often approached by the literature (Esslin, Willett) through a Marxist interpretation of the great German directors' productions (Reinhardt, Piscator, Brecht). These directors certainly had a great influence on many directors after the Second World War, such as Jean Vilar, Judith Molina, Jean-Louis Barrault, Roger Planchon, Augusto Boal, and others. This chapter demonstrates, moreover, that the director was confirmed through both ontological and educational approaches to the process of making the performance, and consequently became a central and paternal figure in the organisational and structural processes practiced within her/his theatre company. In this way, the stance taken by the director influenced the State authorities in establishing theatrical policy. This is an entirely novel scholarly contribution to the study of the director. The German and French States were not indifferent to the development of political theatre. A network of public theatres was thus developed in the inter-war period, and more significantly after the Second World War. The fifth chapter shows how State theatre policies establish its sources in the development of political theatre, and more specifically in the German theatre trade union movement (Volksbiihne) and the great directors at the end of the nineteenth-century. French political theatre was more influenced by playwrights and actors (Romain Rolland, Louise Michel, Louis Lumet, Emile Berny). French theatre policy was based primarily on theatre directors who decentralised their activities in France during both the inter-war period and the German occupation. After the Second World War, the government established, through directors, a strong network of public theatres. Directors became both the artistic director and the executive director of those institutionalised theatres. The institution was, however, seriously shaken by the social and political upheaval of 1968. It is the link between the State and the institution in which established directors were entangled that was challenged by the young emerging directors who rejected institutionalised responsibility in favour of the autonomy of the artist in the 1960s. This process is elucidated in chapter five. The final chapter defines the contemporary role of the director in contrasting thework of a number of significant young theatre practitioners in the 1960s such as Peter Brook, Ariane Mnouchkine, The Living Theater, Jerzy Grotowski, Augusto Boal, Eugenio Barba, all of whom decided early on to detach their companies from any form of public funding. This chapter also demonstrates how they promoted new forms of performance such as the performance of the self. First, these practitioners explored new performance spaces outside the traditional theatre building. Producing performances in a non-dedicated theatre place (warehouse, street, etc.) was a more frequent practice in the 1960s than before. However, the recent development of cybertheatre questions both the separation of the audience and the practitioners and the place of the director's role since the 1990s. Secondly, the role of the director has been multifaceted since the 1960s. On the one hand, those directors, despite all their different working methods, explored western and non-western acting techniques based on both personal input and collective creation. They challenged theatrical conventions of both the character and the process of making the performance. On the other hand, recent observations and studies distinguish the two main functions of the director, the acting coach and the scenographe, both having found new developments in cinema, television, and in various others events. Thirdly, the contemporary director challenges the performance of the text. In this sense, Antonin Artaud was a visionary. His theatre illustrates the need for the consideration of the totality of the text, as well as that of theatrical production. By contrasting the theories of Artaud, based on a non-dramatic form of theatre, with one of his plays (Le Jet de Sang), this chapter demonstrates how Artaud examined the process of making the performance as a performance. Live art and autobiographical performance, both taken as directing the se(f, reinforce this suggestion. Finally, since the 1990s, autobiographical performance or the performance of the self is a growing practical and theoretical perspective in both performance studies and psychology-related studies. This relates to the premise that each individual is making a representation (through memory, interpretation, etc.) of her/his own life (performativity). This last section explores the links between the place of the director in contemporary theatre and performers in autobiographical practices. The role of the traditional actor is challenged through non-identification of the character in the play, while performers (such as Chris Burden, Ron Athey, Orlan, Franko B, Sterlac) have, likewise, explored their own story/life as a performance. The thesis demonstrates the validity of the four parameters (performer, performance space, devising process, social event) defining a generic approach to the director. A generic perspective on the role of the director would encompass: a historical dimension relative to the reasons for and stages of the 'emergence' of the director; a socio-political analysis concerning the relationship between the director, her/his institutionalisation, and the political realm; and the relationship between performance theory, practice and the contemporary role of the director. Such a generic approach is a new departure in theatre research and might resonate in the study of other collaborative artistic practices.

A quest for helpful feedback to programming coursework

The 2011 National Student Survey (NSS) revealed that 40% of full-time students in England did not think that the feedback on their work has been helpful, even though 66% of these students agreed that the feedback was detailed and 62% of them agreed that the feedback has been prompt. Detailed feedback that is not considered helpful by students means a waste of tutors' time while students continue to struggle with their learning. What do students consider as helpful feedback? What are the qualities of helpful feedback? What are the preferred forms of feedback? How should tutors write feedback so that students will find it helpful? Can ICT help to improve the quality of feedback? In our ongoing search for answers to the above questions, we have trialled the use of a novel Internet application, called eCAF, to assess programming coursework from Engineering, Mathematics and Computing students and have collected their views on the feedback received through a survey. The survey reveals that most students prefer electronic feedback as given through eCAF, with verbal feedback ranked second and hand-written feedback ranked even lower. The survey also indicates that the feedback from some tutors is considered more helpful than others. We report on the detailed findings of the survey. By comparing the kinds of feedback given by each tutor who took part in the trial, we explore ways to improve the helpfulness of feedback on programming coursework in a bid to promote learning amongst engineering students.

"No one said girls could do engineering":a fresh look at an old problem

Previous work has drawn attention to what, in many respects, appears to be an insurmountable problem, the lack of women and girls in engineering. The debate about why young women are not attracted to engineering mostly focuses around issues of gender, with the profession stereotypically perceived as being more suitable for men. In seeking to investigate why this should be the case a participatory research approach was adopted in which two 17 year old female High School students were employed to interview their peers about their perceptions of engineering as a career. This paper presents some of the emergent findings of this research. In total twenty teenage girls from two city centre Schools were interviewed. The two teenage researchers developed the questions themselves, focusing on issues they identified as being important factors informing girls’ views of engineering. This approach provided a ‘new’ perspective – looking at the topic through the eyes of the target sample group. By drawing attention to some of the issues around gender and engineering, this paper contributes to current debates in this area – in doing so it provides a fresh look at an old problem and offers some workable solutions for ‘how to get more girls into engineering’.

Engineering education for the 21st century:scholarship, synergy and student success

Starting with the question “How can University level Engineering Education be developed in such a way so as to enhance the quality of the student learning experience?”, this discussion paper proposes an approach to engineering education developed by a senior engineering educator working alongside a pedagogical researcher in an attempt to engage colleagues in contemporary debates about the issues currently faced across the Sector. Such issues include difficulties with recruiting students onto programmes as well as high levels of student attrition and failure. Underpinned by three distinctive concepts: Synergy, Variety & Relationships (S+V+R), the approach brings together pedagogic and engineering epistemologies in an empirically grounded framework in such a way so as to provide an accessible and relevant learning approach that, if followed, engenders student success [S2]. Specifically developed with the intention of increasing retention and positively impacting student success [S2], the S+V+R=S2 approach provides a scholarly and Synergetic (S) approach to engineering education that is both innovative and exciting. Building on the argument that Variety (V) in education is pivotal to promoting originality and creativity in learning and teaching, this paper shows how, by purposefully developing a range of learning and teaching approaches, student engagement and thus success can be increased. It also considers the importance of Relationships (R) in higher education, arguing that belonging and relationships are crucial factors impacting student experiences. When taken together (Synergy, Variety and Relationships) and applied within an Engineering Education context, students are provided with a unique learning environment – one that both promotes individual success and improves organisational effectiveness. The uniqueness of the approach is in the synthesis of these three concepts within an Engineering Education epistemology.

LRD : Latent Relation Discovery for vector space expansion and information retrieval

In this paper, we propose a text mining method called LRD (latent relation discovery), which extends the traditional vector space model of document representation in order to improve information retrieval (IR) on documents and document clustering. Our LRD method extracts terms and entities, such as person, organization, or project names, and discovers relationships between them by taking into account their co-occurrence in textual corpora. Given a target entity, LRD discovers other entities closely related to the target effectively and efficiently. With respect to such relatedness, a measure of relation strength between entities is defined. LRD uses relation strength to enhance the vector space model, and uses the enhanced vector space model for query based IR on documents and clustering documents in order to discover complex relationships among terms and entities. Our experiments on a standard dataset for query based IR shows that our LRD method performed significantly better than traditional vector space model and other five standard statistical methods for vector expansion.

A paradigm shift for mobile interaction:a decade later

In the proceedings of CASCON'2003 we published an article entitled "A Paradigm Shift: Alternative Interaction Techniques for Use with Mobile & Wearable Devices" and were honoured to receive the Best Paper Award for that year's conference. A decade on, we are equally honoured to have the same paper recognised as the Most Influential Paper of the 2003 conference. To this end, we have been asked to provide a brief overview of our intervening research in relation to that original publication, and so that is the purpose of this extended abstract.

The integration of ProxiMAX randomisation with CIS display for the high-throughput production of novel peptides

Saturation mutagenesis is a powerful tool in modern protein engineering. This can allow the analysis of potential new properties thus allowing key residues within a protein to be targeted and randomised. However, the creation of large libraries using conventional saturation mutagenesis with degenerate codons (NNN or NNK) has inherent redundancy and disparities in residue representation. In this we describe the combination of ProxiMAX randomisation and CIS display for the use of generating novel peptides. Unlike other methods ProxiMAX randomisation does not require any intricate chemistry but simply utilises synthetic DNA and molecular biology techniques. Designed ‘MAX’ oligonucleotides were ligated, amplified and digested in an iterative cycle. Results show that randomised ‘MAX’ codons can be added sequentially to the base sequence creating a series of randomised non-degenerate codons that can subsequently be inserted into a gene. CIS display (Isogencia, UK) is an in vitro DNA based screening method that creates a genotype to phenotype link between a peptide and the nucleic acid that encodes it. The use of straight forward in vitro transcription/translation and other molecular biology techniques permits ease of use along with flexibility making it a potent screening technique. Using ProxiMAX randomisation in combination with CIS display, the aim is to produce randomised anti-nerve growth factor (NGF) and calcitonin gene-related (CGRP) peptides to demonstrate the high-throughput nature of this combination.