CTCombine : rotating and combining CT data with an accurate detector model, to simulate radiotherapy portal imaging at non-zero beam angles

Established Monte Carlo user codes BEAMnrc and DOSXYZnrc permit the accurate and straightforward simulation of radiotherapy experiments and treatments delivered from multiple beam angles. However, when an electronic portal imaging detector (EPID) is included in these simulations, treatment delivery from non-zero beam angles becomes problematic. This study introduces CTCombine, a purpose-built code for rotating selected CT data volumes, converting CT numbers to mass densities, combining the results with model EPIDs and writing output in a form which can easily be read and used by the dose calculation code DOSXYZnrc. The geometric and dosimetric accuracy of CTCombine’s output has been assessed by simulating simple and complex treatments applied to a rotated planar phantom and a rotated humanoid phantom and comparing the resulting virtual EPID images with the images acquired using experimental measurements and independent simulations of equivalent phantoms. It is expected that CTCombine will be useful for Monte Carlo studies of EPID dosimetry as well as other EPID imaging applications.

Kallikrein-related peptidase 4 activation of protease-activated receptor family members and association with prostate cancer

Two areas of particular importance in prostate cancer progression are primary tumour development and metastasis. These processes involve a number of physiological events, the mediators of which are still being discovered and characterised. Serine proteases have been shown to play a major role in cancer invasion and metastasis. The recently discovered phenomenon of their activation of a receptor family known as the protease activated receptors (PARs) has extended their physiological role to that of signaling molecule. Several serine proteases are expressed by malignant prostate cancer cells, including members of the kallikreinrelated peptidase (KLK) serine protease family, and increasingly these are being shown to be associated with prostate cancer progression. KLK4 is highly expressed in the prostate and expression levels increase during prostate cancer progression. Critically, recent studies have implicated KLK4 in processes associated with cancer. For example, the ectopic over-expression of KLK4 in prostate cancer cell lines results in an increased ability of these cells to form colonies, proliferate and migrate. In addition, it has been demonstrated that KLK4 is a potential mediator of cellular interactions between prostate cancer cells and osteoblasts (bone forming cells). The ability of KLK4 to influence cellular behaviour is believed to be through the selective cleavage of specific substrates. Identification of relevant in vivo substrates of KLK4 is critical to understanding the pathophysiological roles of this enzyme. Significantly, recent reports have demonstrated that several members of the KLK family are able to activate PARs. The PARs are relatively new members of the seven transmembrane domain containing G protein coupled receptor (GPCR) family. PARs are activated through proteolytic cleavage of their N-terminus by serine proteases, the resulting nascent N-terminal binds intramolecularly to initiate receptor activation. PARs are involved in a number of patho-physiological processes, including vascular repair and inflammation, and a growing body of evidence suggests roles in cancer. While expression of PAR family members has been documented in several types of cancers, including prostate, the role of these GPCRs in prostate cancer development and progression is yet to be examined. Interestingly, several studies have suggested potential roles in cellular invasion through the induction of cytoskeletal reorganisation and expression of basement membrane-degrading enzymes. Accordingly, this program of research focussed on the activation of the PARs by the prostate cancer associated enzyme KLK4, cellular processing of activated PARs and the expression pattern of receptor and agonist in prostate cancer. For these studies KLK4 was purified from the conditioned media of stably transfected Sf9 insect cells expressing a construct containing the complete human KLK4 coding sequence in frame with a V5 epitope and poly-histidine encoding sequences. The first aspect of this study was the further characterisation of this recombinant zymogen form of KLK4. The recombinant KLK4 zymogen was demonstrated to be activatable by the metalloendopeptidase thermolysin and amino terminal sequencing indicated that thermolysin activated KLK4 had the predicted N-terminus of mature active KLK4 (31IINED). Critically, removal of the pro-region successfully generated a catalytically active enzyme, with comparable activity to a previously published recombinant KLK4 produced from S2 insect cells. The second aspect of this study was the activation of the PARs by KLK4 and the initiation of signal transduction. This study demonstrated that KLK4 can activate PAR-1 and PAR-2 to mobilise intracellular Ca2+, but failed to activate PAR-4. Further, KLK4 activated PAR-1 and PAR-2 over distinct concentration ranges, with KLK4 activation and mobilisation of Ca2+ demonstrating higher efficacy through PAR-2. Thus, the remainder of this study focussed on PAR-2. KLK4 was demonstrated to directly cleave a synthetic peptide that mimicked the PAR-2 Nterminal activation sequence. Further, KLK4 mediated Ca2+ mobilisation through PAR-2 was accompanied by the initiation of the extra-cellular regulated kinase (ERK) cascade. The specificity of intracellular signaling mediated through PAR-2 by KLK4 activation was demonstrated by siRNA mediated protein depletion, with a reduction in PAR-2 protein levels correlating to a reduction in KLK4 mediated Ca2+mobilisation and ERK phosphorylation. The third aspect of this study examined cellular processing of KLK4 activated PAR- 2 in a prostate cancer cell line. PAR-2 was demonstrated to be expressed by five prostate derived cell lines including the prostate cancer cell line PC-3. It was also demonstrated by flow cytometry and confocal microscopy analyses that activation of PC-3 cell surface PAR-2 by KLK4 leads to internalisation of this receptor in a time dependent manner. Critically, in vivo relevance of the interaction between KLK4 and PAR-2 was established by the observation of the co-expression of receptor and agonist in primary prostate cancer and prostate cancer bone lesion samples by immunohistochemical analysis. Based on the results of this study a number of exciting future studies have been proposed, including, delineating differences in KLK4 cellular signaling via PAR-1 and PAR-2 and the role of PAR-1 and PAR-2 activation by KLK4 in prostate cancer cells and bone cells in prostate cancer progression.

SoundCipher

The SoundCipher software library provides an easy way to create music in the Processing development environment. With the SoundCipher library added to Processing you can write software programs that make music to go along with your graphics and you can add sounds to enhance your Processing animations or games. SoundCipher provides an easy interface for playing 'notes' on the JavaSound synthesizer, for playback of audio files, and comunicating via MIDI. It provides accurate scheduling and allows events to be organised in musical time; using beats and tempo. It uses a 'score' metaphor that allows the construction of simple or complex musical arrangements. SoundCipher is designed to facilitate the basics of algorithmic music and interactive sound design as well as providing a platform for sophisticated computational music, it allows integration with the Minim library when more sophisticated audio and synthesis functionality is required and integration with the oscP5 library for communicating via open sound control.

Generative Music editorial

An issue on generative music in Contemporary Music Review allows space to explore many of these controversies, and to explore the rich algorithmic scene in contemporary practice, as well as the diverse origins and manifestations of such a culture. A roster of interesting exponents from both academic and arts practice backgrounds are involved, matching the broad spectrum of current work. Contributed articles range from generative algorithms in live systems, from live coding to interactive music systems to computer games, through algorithmic modelling of longer-term form, evolutionary algorithms, to interfaces between modalities and mediums, in algorithmic choreography. A retrospective on the intensive experimentation into algorithmic music and sound synthesis at the Institute of Sonology in the 1960s and 70s creates a complementary strand, as well as an open paper on the issues raised by open source, as opposed to proprietary, software and operating systems, with consequences in the creation and archiving of algorithmic work.

Towards a definition of the performing AudioVisualist

The evolution of the laptop computer as a musical instrument in the 1990s provided a tool for empowering the solo musician and divergent approaches to the application of this technology in performance remain consistently debated.  The increasing ubiquity of digital media combined with the power of current generation notebook technology has provided the perfect platform to realise integrated audio-visual toolsets that respond to musical controllers and provide mixed-media results.  Despite emerging practitioners increasingly availing themselves to the musical affordances of this technology, theoretical discussion in the field ignores the various approaches a solo musician might take in developing integrated media works for performance.   In an increasingly crowded niche there is a clear compulsion to consider expanded modes of performance, yet lacking any formal framework these integrations can easily alienate an audience, distract from performance and lead to criticisms of novelty for novelty's sake. 

Performing with grid music systems

Grid music systems provide discrete geometric methods for simplified music-making by providing spatialised input to construct patterned music on a 2D matrix layout. While they are conceptually simple, grid systems may be layered to enable complex and satisfying musical results. Grid music systems have been applied to a range of systems from small portable devices up to larger systems. In this paper we will discuss the use of grid music systems in general and present an overview of the HarmonyGrid system we have developed as a new interactive performance system. We discuss a range of issues related to the design and use of larger-scale grid- based interactive performance systems such as the HarmonyGrid.

Adaptive music techniques

There are many interactive media systems, including computer games and media art works, in which it is desirable for music to vary in response to changes in the environment. In this paper we will outline a range of algorithmic techniques that enable music to adapt to such changes, taking into account the need for the music to vary in its expressiveness or mood while remaining coherent and recognisable. We will discuss the approaches which we have arrived at after experience in a range of adaptive music systems over recent years, and draw upon these experiences to inform discussion of relevant considerations and to illustrate the techniques and their effect.

Do androids dream of electric chimera?

This paper describes the use of the Chimera Architecture as the basis for a generative rhythmic improvisation system that is intended for use in ensemble contexts. This interactive soft- ware system learns in real time based on an audio input from live performers. The paper describes the components of the Chimera Architecture including a novel analysis engine that uses prediction to robustly assess the rhythmic salience of the input stream. Analytical results are stored in a hierarchical structure that includes multiple scenarios which allow ab- stracted and alternate interpretations of the current metrical context. The system draws upon this Chimera Architecture when generating a musical response. The generated rhythms are intended to have a particular ambiguity in relation to the music performance by other members of the ensemble. Ambi- guity is controlled through alternate interpretations of the Chimera. We describe an implementation of the Chimera Ar- chitecture that focuses on rhythmic material, and present and discuss initial experimental results of the software system playing along with recordings of a live performance.

Generation in context : an exploratory method for musical enquiry

This paper discusses a method, Generation in Context, for interrogating theories of music analysis and music perception. Given an analytic theory, the method consists of creating a generative process that implements the theory in reverse. Instead of using the theory to create analyses from scores, the theory is used to generate scores from analyses. Subjective evaluation of the quality of the musical output provides a mechanism for testing the theory in a contextually robust fashion. The method is exploratory, meaning that in addition to testing extant theories it provides a general mechanism for generating new theoretical insights. We outline our initial explorations in the use of generative processes for music research, and we discuss how generative processes provide evidence as to the veracity of theories about how music is experienced, with insights into how these theories may be improved and, concurrently, provide new techniques for music creation. We conclude that Generation in Context will help reveal new perspectives on our understanding of music.

Soundcipher : a music and sound library for processing

SoundCipher is a software library written in the Java language that adds important music and sound features to the Processing environment that is widely used by media artists and otherwise has an orientation toward computational graphics. This article introduces the SoundCipher library and its features, describes its influences and design intentions, and positions it within the field of computer music programming tools. SoundCipher enables the rich history of algorithmic music techniques to be accessible within one of today’s most popular media art platforms. It also provides an accessible means for learning to create algorithmic music and sound programs.

Eco-structure data forms : classification of data analysis using perceived design affordances for musical outcomes

This paper explores a method of comparative analysis and classification of data through perceived design affordances. Included is discussion about the musical potential of data forms that are derived through eco-structural analysis of musical features inherent in audio recordings of natural sounds. A system of classification of these forms is proposed based on their structural contours. The classifications include four primitive types; steady, iterative, unstable and impulse. The classification extends previous taxonomies used to describe the gestural morphology of sound. The methods presented are used to provide compositional support for eco-structuralism.

TraSe algorithm : automatic evolutionary morphing of electronic dance music

The TraSe (Transform-Select) algorithm has been developed to investigate the morphing of electronic music through automatically applying a series of deterministic compositional transformations to the source, guided towards a target by similarity metrics. This is in contrast to other morphing techniques such as interpolation or parameters or probabilistic variation. TraSe allows control over stylistic elements of the music through user-defined weighting of numerous compositional transformations. The formal evaluation of TraSe was mostly qualitative and occurred through nine participants completing an online questionnaire. The music generated by TraSe was generally felt to be less coherent than a human composed benchmark but in some cases judged as more creative.

Evolving interactions : agile design for networked media performance

Network Jamming systems provide real-time collaborative performance experiences for novice or inexperienced users. In this paper we will outline the interaction design considerations that have emerged during through evolutionary development cycles of the jam2jam Network Jamming software that employs generative techniques that require particular attention to the human computer relationship. In particular we describe the co-evolution of features and uses, explore the role of agile development methods in supporting this evolution, and show how the provision of a clear core capability can be matched with options for enhanced features support multi-levelled user experience and skill develop.