Richard Rorty, innovation strategies & movie inspiration

Movie innovation is a conversation between screenwriters and producers in our mixed economy – a concept of innovation supported by Richard Rorty and Aristole's Poetics. During innovation conversations, inspired writers describe fresh movie actions to empathetic producers. Some inspired actions may confuse. Writers and producers use strategies to inquire about confusing actions. This Australian study redescribes 25 writer-producer strategies in the one place for the first time. It adds a new strategy. And, with more evidence than the current literature, it investigates writer inspiration, which drives film innovation. It reports inspiration in pioneering, verifiable detail.

48 Hour Game Making Challenge - In Progress [Four Episodes]

Statement: Jams, Jelly Beans and the Fruits of Passion Let us search, instead, for an epistemology of practice implicit in the artistic, intuitive processes which some practitioners do bring to situations of uncertainty, instability, uniqueness, and value conflict. (Schön 1983, p40) Game On was born out of the idea of creative community; finding, networking, supporting and inspiring the people behind the face of an industry, those in the mist of the machine and those intending to join. We understood this moment to be a pivotal opportunity to nurture a new emerging form of game making, in an era of change, where the old industry models were proving to be unsustainable. As soon as we started putting people into a room under pressure, to make something in 48hrs, a whole pile of evolutionary creative responses emerged. People refashioned their craft in a moment of intense creativity that demanded different ways of working, an adaptive approach to the craft of making games – small – fast – indie. An event like the 48hrs forces participants’ attention on the process as much as the outcome. As one game industry professional taking part in a challenge for the first time observed: there are three paths in the genesis from idea to finished work: the path that focuses on mechanics; the path that focuses on team structure and roles and the path that focuses on the idea, the spirit – and the more successful teams need to put the spirit of the work first and foremost. The spirit drives the adaptation, it becomes improvisation. As Schön says: “Improvisation consists on varying, combining and recombining a set of figures within the schema which bounds and gives coherence to the performance.” (1983, p55). This improvisational approach is all about those making the games: the people and the principles of their creative process. This documentation evidences the intensity of their passion, determination and the shit that they are prepared to put themselves through to achieve their goal – to win a cup full of jellybeans and make a working game in 48hrs. 48hr is a project where, on all levels, analogue meets digital. This concept was further explored through the documentation process. This set of four videos were created by Cameron Owen on the fly during the challenge using both the iphone video camera and editing software in order to be available with immediacy and allow the event audience to share the experience - and perhaps to give some insights into the creative process exposed by the 48 hour challenge. ____________________________ Schön, D. A. 1983, The Reflective Practitioner: How Professionals Think in Action, Basic Books, New York

What once was old is new again: reviving an early-modern form of interdisciplinarity for socio-legal studies

Socio-legal studies are an essentially interdisciplinary enterprise. However, there is currently only one form of interdisciplinarity that most socio-legal scholars (and criminologists) recognise and work with. This form is derived from the idea that 'society itself' - and by this most scholars mean 'civil society' - drives the law. However, another, rival understanding of society, which we term the authoritarian-liberal statist understanding that slipped from view in the late seventeenth century and remained obscure from then until now, may be used to generate another form of interdisciplinarity for sOcio-legal studies (and for criminology). However, this rival understanding of society does not simply allow us to reconfigure our notion of 'society'; it radically changes the role society plays in relation to the law. Two crucial points emerge from this rival account: first, society can no longer be understood as separable from (even though interacting with) the law; and second, society can no longer be understood as driving the law.

The 'nurdle to leg' and other ways of winning cricket matches

The emergence of Twenty20 cricket at the elite level has been marketed on the excitement of the big hitter, where it seems that winning is a result of the muscular batter hitting boundaries at will. This version of the game has captured the imagination of many young players who all want to score runs with “big hits”. However, in junior cricket, boundary hitting is often more difficult due to size limitations of children and games played on outfields where the ball does not travel quickly. As a result, winning is often achieved via a less spectacular route – by scoring more singles than your opponents. However, most standard coaching texts only describe how to play boundary scoring shots (e.g. the drives, pulls, cuts and sweeps) and defensive shots to protect the wicket. Learning to bat appears to have been reduced to extremes of force production, i.e. maximal force production to hit boundaries or minimal force production to stop the ball from hitting the wicket. Initially, this is not a problem because the typical innings of a young player (<12 years) would be based on the concept of “block” or “bash” – they “block” the good balls and “bash” the short balls. This approach works because there are many opportunities to hit boundaries off the numerous inaccurate deliveries of novice bowlers. Most runs are scored behind the wicket by using the pace of the bowler’s delivery to re-direct the ball, because the intrinsic dynamics (i.e. lack of strength) of most children means that they can only create sufficient power by playing shots where the whole body can contribute to force production. This method works well until the novice player comes up against more accurate bowling when they find they have no way of scoring runs. Once batters begin to face “good” bowlers, batters have to learn to score runs via singles. In cricket coaching manuals (e.g. ECB, n.d), running between the wickets is treated as a separate task to batting, and the “basics” of running, such as how to “back- up”, carry the bat, calling and turning and sliding the bat into the crease are “drilled” into players. This task decomposition strategy focussing on techniques is a common approach to skill acquisition in many highly traditional sports, typified in cricket by activities where players hit balls off tees and receive “throw-downs” from coaches. However, the relative usefulness of these approaches in the acquisition of sporting skills is increasingly being questioned (Pinder, Renshaw & Davids, 2009). We will discuss why this is the case in the next section.

Intrinsically photosensitive melanopsin retinal ganglion cell contributions to the post-illumination pupil response and circadian rhythm

Intrinsically photosensitive retinal ganglion cells (ipRGCs) in the eye transmit the environmental light level, projecting to the suprachiasmatic nucleus (SCN) (Berson, Dunn & Takao, 2002; Hattar, Liao, Takao, Berson & Yau, 2002), the location of the circadian biological clock, and the olivary pretectal nucleus (OPN) of the pretectum, the start of the pupil reflex pathway (Hattar, Liao, Takao, Berson & Yau, 2002; Dacey, Liao, Peterson, Robinson, Smith, Pokorny, Yau & Gamlin, 2005). The SCN synchronizes the circadian rhythm, a cycle of biological processes coordinated to the solar day, and drives the sleep/wake cycle by controlling the release of melatonin from the pineal gland (Claustrat, Brun & Chazot, 2005). Encoded photic input from ipRGCs to the OPN also contributes to the pupil light reflex (PLR), the constriction and recovery of the pupil in response to light. IpRGCs control the post-illumination component of the PLR, the partial pupil constriction maintained for > 30 sec after a stimulus offset (Gamlin, McDougal, Pokorny, Smith, Yau & Dacey, 2007; Kankipati, Girkin & Gamlin, 2010; Markwell, Feigl & Zele, 2010). It is unknown if intrinsic ipRGC and cone-mediated inputs to ipRGCs show circadian variation in their photon-counting activity under constant illumination. If ipRGCs demonstrate circadian variation of the pupil response under constant illumination in vivo, when in vitro ipRGC activity does not (Weng, Wong & Berson, 2009), this would support central control of the ipRGC circadian activity. A preliminary experiment was conducted to determine the spectral sensitivity of the ipRGC post-illumination pupil response under the experimental conditions, confirming the successful isolation of the ipRGC response (Gamlin, et al., 2007) for the circadian experiment. In this main experiment, we demonstrate that ipRGC photon-counting activity has a circadian rhythm under constant experimental conditions, while direct rod and cone contributions to the PLR do not. Intrinsic ipRGC contributions to the post-illumination pupil response decreased 2:46 h prior to melatonin onset for our group model, with the peak ipRGC attenuation occurring 1:25 h after melatonin onset. Our results suggest a centrally controlled evening decrease in ipRGC activity, independent of environmental light, which is temporally synchronized (demonstrates a temporal phase-advanced relationship) to the SCN mediated release of melatonin. In the future the ipRGC post-illumination pupil response could be developed as a fast, non-invasive measure of circadian rhythm. This study establishes a basis for future investigation of cortical feedback mechanisms that modulate ipRGC activity.

A social marketing approach to value creation in a Well-Women’s health service

Understanding consumer value is imperative in health care as the receipt of value drives the demand for health care services. While there is increasing research into health-care that adopts an economic approach to value, this paper investigates a non-financial exchange context and uses an experiential approach to value, guided by a social marketing approach to behaviour change. An experiential approach is deemed more appropriate for government health-care services that are free and for preventative rather than treatment purposes. Thus instead of using an illness-paradigm to view health services outcomes, we adopt a wellness paradigm. Using qualitative data gathered during 25 depth interviews the authors demonstrate how social marketing thinking has guided the identification of six themes that represent four dimensions of value (functional, emotional, social and altruistic) evident during the health care consumption process of a free government service.

Visceral hedonic rhetoric

Emotional responses can incite and entice consumers to select a particular product from a row of similar items and thus have a considerable impact on purchase decisions. Consequently, more and more companies are challenging designers to address the emotional impact of their work and to design for emotion and consumerproduct relationships. Furthermore, the creation of emotional attachment to one’s possessions is one way of approaching a sustainable consumer-product relationship. The aim of this research is to gain a deeper understanding of the instantaneous emotional attachment that consumers form with products and its subsequent implications for product development. The foci of the study are visceral design, consumer hedonics and product rhetoric. Studied in a conglomerate they become an area of new investigation: visceral hedonic rhetoric. In this context, the term “visceral hedonic rhetoric” is defined as the properties of a product that persuasively elicit the pursuit of pleasure at an instinctual level of cognition. This study explores visceral hedonic rhetoric evident in the design of interactive products and resides within the context of emotional design research. It employs an empirical approach to understand how consumers respond hedonically on a visceral level to rhetoric in products. Specifically, it examines visceral hedonic responses given by thirty participants to the stimuli of six mobile telephones, six Mp3 players and six USB memory flash drives. The study findings demonstrate a hierarchy of visceral hedonic rhetoric evident in interactive products. This hierarchy of visceral hedonic attributes include: colour, size, shape, intrigue, material, perceived usability, portability, perceived function, novelty, analogy, brand, quality, texture and gender. However, it is the interrelationships between these visceral hedonic attributes that are the most significant findings of this research. Certain associations were revealed between product attribute combinations and consumer perception. The most predominant of these were: gender bias associated with colour selection; the creation of intrigue through a vibrant attention-grabbing colour; perceived ease of use and function; product confidence as a result of brand familiarity and perceived usability; analogous association through familiarity with similar objects and shapes; and the association of longevity with quality, novelty or recent technology. A significant outcome of the research is the distillation of visceral hedonic rhetoric design principles, and a tool to assist designers in harnessing the full potential of visceral hedonic rhetoric. This study contributes to the identification of the emerging research field of visceral hedonic rhetoric. Application of this study’s findings has the potential to provide a hedonic consumer-product relationship that is more meaningful, less disposable and more sustainable. This theory of visceral hedonic rhetoric is not only a significant contribution to design knowledge but is also generally transferable to other research domains, as later suggested in future research avenues.

Interactive processes link the multiple symptoms of fatigue in sport competition

Muscle physiologists often describe fatigue simply as a decline of muscle force and infer this causes an athlete to slow down. In contrast, exercise scientists describe fatigue during sport competition more holistically as an exercise-induced impairment of performance. The aim of this review is to reconcile the different views by evaluating the many performance symptoms/measures and mechanisms of fatigue. We describe how fatigue is assessed with muscle, exercise or competition performance measures. Muscle performance (single muscle test measures) declines due to peripheral fatigue (reduced muscle cell force) and/or central fatigue (reduced motor drive from the CNS). Peak muscle force seldom falls by >30% during sport but is often exacerbated during electrical stimulation and laboratory exercise tasks. Exercise performance (whole-body exercise test measures) reveals impaired physical/technical abilities and subjective fatigue sensations. Exercise intensity is initially sustained by recruitment of new motor units and help from synergistic muscles before it declines. Technique/motor skill execution deviates as exercise proceeds to maintain outcomes before they deteriorate, e.g. reduced accuracy or velocity. The sensation of fatigue incorporates an elevated rating of perceived exertion (RPE) during submaximal tasks, due to a combination of peripheral and higher CNS inputs. Competition performance (sport symptoms) is affected more by decision-making and psychological aspects, since there are opponents and a greater importance on the result. Laboratory based decision making is generally faster or unimpaired. Motivation, self-efficacy and anxiety can change during exercise to modify RPE and, hence, alter physical performance. Symptoms of fatigue during racing, team-game or racquet sports are largely anecdotal, but sometimes assessed with time-motion analysis. Fatigue during brief all-out racing is described biomechanically as a decline of peak velocity, along with altered kinematic components. Longer sport events involve pacing strategies, central and peripheral fatigue contributions and elevated RPE. During match play, the work rate can decline late in a match (or tournament) and/or transiently after intense exercise bursts. Repeated sprint ability, agility and leg strength become slightly impaired. Technique outcomes, such as velocity and accuracy for throwing, passing, hitting and kicking, can deteriorate. Physical and subjective changes are both less severe in real rather than simulated sport activities. Little objective evidence exists to support exercise-induced mental lapses during sport. A model depicting mind-body interactions during sport competition shows that the RPE centre-motor cortex-working muscle sequence drives overall performance levels and, hence, fatigue symptoms. The sporting outputs from this sequence can be modulated by interactions with muscle afferent and circulatory feedback, psychological and decision-making inputs. Importantly, compensatory processes exist at many levels to protect against performance decrements. Small changes of putative fatigue factors can also be protective. We show that individual fatigue factors including diminished carbohydrate availability, elevated serotonin, hypoxia, acidosis, hyperkalaemia, hyperthermia, dehydration and reactive oxygen species, each contribute to several fatigue symptoms. Thus, multiple symptoms of fatigue can occur simultaneously and the underlying mechanisms overlap and interact. Based on this understanding, we reinforce the proposal that fatigue is best described globally as an exercise-induced decline of performance as this is inclusive of all viewpoints.

Jams, jelly beans and the fruits of passion - art book (26 Pages)

Statement: Jams, Jelly Beans and the Fruits of Passion Let us search, instead, for an epistemology of practice implicit in the artistic, intuitive processes which some practitioners do bring to situations of uncertainty, instability, uniqueness, and value conflict. (Schön 1983, p40) Game On was born out of the idea of creative community; finding, networking, supporting and inspiring the people behind the face of an industry, those in the mist of the machine and those intending to join. We understood this moment to be a pivotal opportunity to nurture a new emerging form of game making, in an era of change, where the old industry models were proving to be unsustainable. As soon as we started putting people into a room under pressure, to make something in 48hrs, a whole pile of evolutionary creative responses emerged. People refashioned their craft in a moment of intense creativity that demanded different ways of working, an adaptive approach to the craft of making games – small – fast – indie. An event like the 48hrs forces participants’ attention onto the process as much as the outcome. As one game industry professional taking part in a challenge for the first time observed: there are three paths in the genesis from idea to finished work: the path that focuses on mechanics; the path that focuses on team structure and roles, and the path that focuses on the idea, the spirit – and the more successful teams put the spirit of the work first and foremost. The spirit drives the adaptation, it becomes improvisation. As Schön says: “Improvisation consists on varying, combining and recombining a set of figures within the schema which bounds and gives coherence to the performance.” (1983, p55). This improvisational approach is all about those making the games: the people and the principles of their creative process. This documentation evidences the intensity of their passion, determination and the shit that they are prepared to put themselves through to achieve their goal – to win a cup full of jellybeans and make a working game in 48hrs. 48hr is a project where, on all levels, analogue meets digital. This concept was further explored through the documentation process. All of these pictures were taken with a 1945 Leica III camera. The use of this classic, film-based camera, gives the images a granularity and depth, this older slower technology exposes the very human moments of digital creativity. ____________________________ Schön, D. A. 1983, The Reflective Practitioner: How Professionals Think in Action, Basic Books, New York

Adaptive cache aware multiprocessor scheduling framework

Computer resource allocation represents a significant challenge particularly for multiprocessor systems, which consist of shared computing resources to be allocated among co-runner processes and threads. While an efficient resource allocation would result in a highly efficient and stable overall multiprocessor system and individual thread performance, ineffective poor resource allocation causes significant performance bottlenecks even for the system with high computing resources. This thesis proposes a cache aware adaptive closed loop scheduling framework as an efficient resource allocation strategy for the highly dynamic resource management problem, which requires instant estimation of highly uncertain and unpredictable resource patterns. Many different approaches to this highly dynamic resource allocation problem have been developed but neither the dynamic nature nor the time-varying and uncertain characteristics of the resource allocation problem is well considered. These approaches facilitate either static and dynamic optimization methods or advanced scheduling algorithms such as the Proportional Fair (PFair) scheduling algorithm. Some of these approaches, which consider the dynamic nature of multiprocessor systems, apply only a basic closed loop system; hence, they fail to take the time-varying and uncertainty of the system into account. Therefore, further research into the multiprocessor resource allocation is required. Our closed loop cache aware adaptive scheduling framework takes the resource availability and the resource usage patterns into account by measuring time-varying factors such as cache miss counts, stalls and instruction counts. More specifically, the cache usage pattern of the thread is identified using QR recursive least square algorithm (RLS) and cache miss count time series statistics. For the identified cache resource dynamics, our closed loop cache aware adaptive scheduling framework enforces instruction fairness for the threads. Fairness in the context of our research project is defined as a resource allocation equity, which reduces corunner thread dependence in a shared resource environment. In this way, instruction count degradation due to shared cache resource conflicts is overcome. In this respect, our closed loop cache aware adaptive scheduling framework contributes to the research field in two major and three minor aspects. The two major contributions lead to the cache aware scheduling system. The first major contribution is the development of the execution fairness algorithm, which degrades the co-runner cache impact on the thread performance. The second contribution is the development of relevant mathematical models, such as thread execution pattern and cache access pattern models, which in fact formulate the execution fairness algorithm in terms of mathematical quantities. Following the development of the cache aware scheduling system, our adaptive self-tuning control framework is constructed to add an adaptive closed loop aspect to the cache aware scheduling system. This control framework in fact consists of two main components: the parameter estimator, and the controller design module. The first minor contribution is the development of the parameter estimators; the QR Recursive Least Square(RLS) algorithm is applied into our closed loop cache aware adaptive scheduling framework to estimate highly uncertain and time-varying cache resource patterns of threads. The second minor contribution is the designing of a controller design module; the algebraic controller design algorithm, Pole Placement, is utilized to design the relevant controller, which is able to provide desired timevarying control action. The adaptive self-tuning control framework and cache aware scheduling system in fact constitute our final framework, closed loop cache aware adaptive scheduling framework. The third minor contribution is to validate this cache aware adaptive closed loop scheduling framework efficiency in overwhelming the co-runner cache dependency. The timeseries statistical counters are developed for M-Sim Multi-Core Simulator; and the theoretical findings and mathematical formulations are applied as MATLAB m-file software codes. In this way, the overall framework is tested and experiment outcomes are analyzed. According to our experiment outcomes, it is concluded that our closed loop cache aware adaptive scheduling framework successfully drives co-runner cache dependent thread instruction count to co-runner independent instruction count with an error margin up to 25% in case cache is highly utilized. In addition, thread cache access pattern is also estimated with 75% accuracy.

Influencing the experience of people in urban public places through mobile mediated interactions

This paper introduces our research on influencing the experience of people in urban public places through mobile mediated interactions. Information and communication technology (ICT) devices are sometimes used to create personal space while in public. ICT devices could also be utilised to digitally augment the urban space with non-privacy sensitive data enabling mobile mediated interactions in an anonymous way between collocated strangers. We present what motivates the research on digital augmentations and mobile mediated interactions between unknown urban dwellers, define the research problem that drives this study and why it is significant research in the field of pervasive social networking. The paper illustrates three design interventions enabling social pervasive content sharing and employing pervasive presence, awareness and anonymous social user interaction in urban public places. The paper concludes with an outlook and summarises the research effort.

Rational design of serine protease inhibitors

Proteases regulate a spectrum of diverse physiological processes, and dysregulation of proteolytic activity drives a plethora of pathological conditions. Understanding protease function is essential to appreciating many aspects of normal physiology and progression of disease. Consequently, development of potent and specific inhibitors of proteolytic enzymes is vital to provide tools for the dissection of protease function in biological systems and for the treatment of diseases linked to aberrant proteolytic activity. The studies in this thesis describe the rational design of potent inhibitors of three proteases that are implicated in disease development. Additionally, key features of the interaction of proteases and their cognate inhibitors or substrates are analysed and a series of rational inhibitor design principles are expounded and tested. Rational design of protease inhibitors relies on a comprehensive understanding of protease structure and biochemistry. Analysis of known protease cleavage sites in proteins and peptides is a commonly used source of such information. However, model peptide substrate and protein sequences have widely differing levels of backbone constraint and hence can adopt highly divergent structures when binding to a protease’s active site. This may result in identical sequences in peptides and proteins having different conformations and diverse spatial distribution of amino acid functionalities. Regardless of this, protein and peptide cleavage sites are often regarded as being equivalent. One of the key findings in the following studies is a definitive demonstration of the lack of equivalence between these two classes of substrate and invalidation of the common practice of using the sequences of model peptide substrates to predict cleavage of proteins in vivo. Another important feature for protease substrate recognition is subsite cooperativity. This type of cooperativity is commonly referred to as protease or substrate binding subsite cooperativity and is distinct from allosteric cooperativity, where binding of a molecule distant from the protease active site affects the binding affinity of a substrate. Subsite cooperativity may be intramolecular where neighbouring residues in substrates are interacting, affecting the scissile bond’s susceptibility to protease cleavage. Subsite cooperativity can also be intermolecular where a particular residue’s contribution to binding affinity changes depending on the identity of neighbouring amino acids. Although numerous studies have identified subsite cooperativity effects, these findings are frequently ignored in investigations probing subsite selectivity by screening against diverse combinatorial libraries of peptides (positional scanning synthetic combinatorial library; PS-SCL). This strategy for determining cleavage specificity relies on the averaged rates of hydrolysis for an uncharacterised ensemble of peptide sequences, as opposed to the defined rate of hydrolysis of a known specific substrate. Further, since PS-SCL screens probe the preference of the various protease subsites independently, this method is inherently unable to detect subsite cooperativity. However, mean hydrolysis rates from PS-SCL screens are often interpreted as being comparable to those produced by single peptide cleavages. Before this study no large systematic evaluation had been made to determine the level of correlation between protease selectivity as predicted by screening against a library of combinatorial peptides and cleavage of individual peptides. This subject is specifically explored in the studies described here. In order to establish whether PS-SCL screens could accurately determine the substrate preferences of proteases, a systematic comparison of data from PS-SCLs with libraries containing individually synthesised peptides (sparse matrix library; SML) was carried out. These SML libraries were designed to include all possible sequence combinations of the residues that were suggested to be preferred by a protease using the PS-SCL method. SML screening against the three serine proteases kallikrein 4 (KLK4), kallikrein 14 (KLK14) and plasmin revealed highly preferred peptide substrates that could not have been deduced by PS-SCL screening alone. Comparing protease subsite preference profiles from screens of the two types of peptide libraries showed that the most preferred substrates were not detected by PS SCL screening as a consequence of intermolecular cooperativity being negated by the very nature of PS SCL screening. Sequences that are highly favoured as result of intermolecular cooperativity achieve optimal protease subsite occupancy, and thereby interact with very specific determinants of the protease. Identifying these substrate sequences is important since they may be used to produce potent and selective inhibitors of protolytic enzymes. This study found that highly favoured substrate sequences that relied on intermolecular cooperativity allowed for the production of potent inhibitors of KLK4, KLK14 and plasmin. Peptide aldehydes based on preferred plasmin sequences produced high affinity transition state analogue inhibitors for this protease. The most potent of these maintained specificity over plasma kallikrein (known to have a very similar substrate preference to plasmin). Furthermore, the efficiency of this inhibitor in blocking fibrinolysis in vitro was comparable to aprotinin, which previously saw clinical use to reduce perioperative bleeding. One substrate sequence particularly favoured by KLK4 was substituted into the 14 amino acid, circular sunflower trypsin inhibitor (SFTI). This resulted in a highly potent and selective inhibitor (SFTI-FCQR) which attenuated protease activated receptor signalling by KLK4 in vitro. Moreover, SFTI-FCQR and paclitaxel synergistically reduced growth of ovarian cancer cells in vitro, making this inhibitor a lead compound for further therapeutic development. Similar incorporation of a preferred KLK14 amino acid sequence into the SFTI scaffold produced a potent inhibitor for this protease. However, the conformationally constrained SFTI backbone enforced a different intramolecular cooperativity, which masked a KLK14 specific determinant. As a consequence, the level of selectivity achievable was lower than that found for the KLK4 inhibitor. Standard mechanism inhibitors such as SFTI rely on a stable acyl-enzyme intermediate for high affinity binding. This is achieved by a conformationally constrained canonical binding loop that allows for reformation of the scissile peptide bond after cleavage. Amino acid substitutions within the inhibitor to target a particular protease may compromise structural determinants that support the rigidity of the binding loop and thereby prevent the engineered inhibitor reaching its full potential. An in silico analysis was carried out to examine the potential for further improvements to the potency and selectivity of the SFTI-based KLK4 and KLK14 inhibitors. Molecular dynamics simulations suggested that the substitutions within SFTI required to target KLK4 and KLK14 had compromised the intramolecular hydrogen bond network of the inhibitor and caused a concomitant loss of binding loop stability. Furthermore in silico amino acid substitution revealed a consistent correlation between a higher frequency of formation and the number of internal hydrogen bonds of SFTI-variants and lower inhibition constants. These predictions allowed for the production of second generation inhibitors with enhanced binding affinity toward both targets and highlight the importance of considering intramolecular cooperativity effects when engineering proteins or circular peptides to target proteases. The findings from this study show that although PS-SCLs are a useful tool for high throughput screening of approximate protease preference, later refinement by SML screening is needed to reveal optimal subsite occupancy due to cooperativity in substrate recognition. This investigation has also demonstrated the importance of maintaining structural determinants of backbone constraint and conformation when engineering standard mechanism inhibitors for new targets. Combined these results show that backbone conformation and amino acid cooperativity have more prominent roles than previously appreciated in determining substrate/inhibitor specificity and binding affinity. The three key inhibitors designed during this investigation are now being developed as lead compounds for cancer chemotherapy, control of fibrinolysis and cosmeceutical applications. These compounds form the basis of a portfolio of intellectual property which will be further developed in the coming years.

Is anybody there? Bootstrapping attendance with engagement

The report card for the introductory programming unit at our university has historically been unremarkable in terms of attendance rates, student success rates and student retention in both the unit and the degree course. After a course restructure recently involving a fresh approach to introducing programming, we reported a high retention in the unit, with consistently high attendance and a very low failure rate. Following those encouraging results, we collected student attendance data for several semesters and compared attendance rates to student results. We have found that interesting workshop material which directly relates to course-relevant assessment items and therefore drives the learning, in an engaging collaborative learning environment has improved attendance to an extraordinary extent, with student failure rates plummeting to the lowest in recorded history at our university.