Mastering the canonical loop of serine protease inhibitors : enhancing potency by optimising the internal hydrogen bond network

Background Canonical serine protease inhibitors commonly bind to their targets through a rigid loop stabilised by an internal hydrogen bond network and disulfide bond(s). The smallest of these is sunflower trypsin inhibitor (SFTI-1), a potent and broad-range protease inhibitor. Recently, we re-engineered the contact β-sheet of SFTI-1 to produce a selective inhibitor of kallikrein-related peptidase 4 (KLK4), a protease associated with prostate cancer progression. However, modifications in the binding loop to achieve specificity may compromise structural rigidity and prevent re-engineered inhibitors from reaching optimal binding affinity. Methodology/Principal Findings In this study, the effect of amino acid substitutions on the internal hydrogen bonding network of SFTI were investigated using an in silico screen of inhibitor variants in complex with KLK4 or trypsin. Substitutions favouring internal hydrogen bond formation directly correlated with increased potency of inhibition in vitro. This produced a second generation inhibitor (SFTI-FCQR Asn14) which displayed both a 125-fold increased capacity to inhibit KLK4 (Ki = 0.0386±0.0060 nM) and enhanced selectivity over off-target serine proteases. Further, SFTI-FCQR Asn14 was stable in cell culture and bioavailable in mice when administered by intraperitoneal perfusion. Conclusion/Significance These findings highlight the importance of conserving structural rigidity of the binding loop in addition to optimising protease/inhibitor contacts when re-engineering canonical serine protease inhibitors.

Mastering medical terminology : Australia and New Zealand

Mastering Medical Terminology: Australia and New Zealand is medical terminology book of relevance to an audience in Australia and New Zealand. Australian terminology, perspectives, examples and spelling have been included and Australian pronunciation specified. The textbook is accompanied by a self-help workbook, an online workbook and a Smartphone app. Throughout Mastering Medical Terminology, review of medical terminology as it is used in clinical practice is highlighted. Features of the textbook, workbook and electronic product include: • Simple, non-technical explanations of medical terms • Workbook format with ample spaces to write answers • Explanations of clinical procedures, laboratory tests and abbreviations used in Australian clinical practice, as they apply to each body system and speciality area • Pronunciation of terms and spaces to write meanings of terms • Practical applications sections • Exercises that test understanding of terminology as students work through the text chapter by chapter • Review activities that pull together terminology to help students study • Comprehensive glossary and appendices for reference • Links to other useful references, such as websites and textbooks.

Mastering medical terminology : Australia and New Zealand Workbook

Mastering Medical Terminology: Australia and New Zealand Workbook is the indispensable companion to Mastering Medical Terminology Textbook. Packed with a range of exercises and activities to accompany the main text, the Workbook provides an ideal resource for self-testing and revision in a fun, practical and accessible format, and forms a key part of the Mastering Medical Terminology suite of products which are all available for separate purchase enabling you to pick and choose the right package for your learning requirements. Featuring a variety of question types including crossword puzzles, anagrams, multiple-choice questions and label-the-diagram exercises, the Workbook uses entirely Australian spelling and aligns to the chapters of the main text. When used in combination with the main text and MedWords app, Mastering Medical Terminology: Australia and New Zealand Workbook will make the scholarship of medical terminology not only manageable, but fun!

Mastering medical terminology online workbook

Key Features: "Aligns to Mastering Medical Terminology: Australia and New Zealand. Self-test to practise and revise combining forms, word roots, prefixes and suffixes. Crossword puzzles, anagrams and label-the-diagram exercises Also available iOS/Android app featuring audio glossary, flashcards and MCQs."--publisher website

Mastering your destiny

Dance psychologist Gene Moyle explains how your attitude can help your career.

Review article : ecological approach in studying the relation of perception-action : review of the theoretical and empirical data

In daily activities people are using a number of available means for the achievement of balance, such as the use of hands and the co-ordination of balance. One of the approaches that explains this relationship between perception and action is the ecological theory that is based on the work of a) Bernstein (1967), who imposed the problem of ‘the degrees of freedom’, b) Gibson (1979), who referred to the theory of perception and the way which the information is received from the environment in order for a certain movement to be achieved, c) Newell (1986), who proposed that movement can derive from the interaction of the constraints that imposed from the environment and the organism and d) Kugler, Kelso and Turvey (1982), who showed the way which “the degrees of freedom” are connected and interact. According to the above mentioned theories, the development of movement co-ordination can result from the different constraints that imposed into the organism-environment system. The close relation between the environmental and organismic constraints, as well as their interaction is responsible for the movement system that will be activated. These constraints apart from shaping the co-ordination of specific movements can be a rate limiting factor, to a certain degree, in the acquisition and mastering of a new skill. This frame of work can be an essential tool for the study of catching an object (e.g., a ball). The importance of this study becomes obvious due to the fact that movements that involved in catching an object are representative of every day actions and characteristic of the interaction between perception and action.

Innovative use of Blackboard® to assess laboratory skills

A novel application of the popular web instruction architecture Blackboard Academic Suite® is described. The method was applied to a large number of students to assess quantitatively the accuracy of each student’s laboratory skills. The method provided immediate feedback to students on their personal skill level, replaced labour-intensive scrutiny of laboratory skills by teaching staff and identified immediately those students requiring further individual assistance in mastering the skill under evaluation. The method can be used for both formative and summative assessment. When used formatively, the assessment can be repeated by the student without penalty until the skill is mastered. When used for summative assessment, the method can save the teacher much time and effort in assessing laboratory skills of vital importance to students in the real world.

Alternatives to the behavioural technicist approaches to study skills

The content and approach of study skills courses are critiqued and alternatives are suggested. It is proposed that an approach providing students with knowledge about the cognitive processes involved in mastering complex material would make the study skills teacher an agent of social change aiming for the enlightenment and emancipation of students and lecturers.

Challenges and opportunities in the journey of the design-led innovation champions

The purpose of this study is to deepen our knowledge and understanding of the challenges faced by design champions in proposing and applying design methods and insights in existing firms. This study investigates the early stages of the journey of the design champions as they incorporate design into operational and strategic conversations and practices, and their progress in mastering these challenges as opportunities in a firm context. Little research on this topic has been reported, yet it is of growing interest as more firms turn to design-led innovation to shape their strategies and practices. Interviews with design champions were used to investigate first hand the experience and reflections the many challenges provide. Findings from the study provide some early insights that can be extended through further research.

Playing with Grammar in the Early Years : Learning about Language in the Australian Curriculum : English

As teacher/researchers interested in the pursuit of socially-just outcomes in early childhood education, the form and function of language occupies a special position in our work. We believe that mastering a range of literacy competences includes not only the technical skills for learning, but also the resources for viewing and constructing the world (Freire and Macdeo, 1987). Rather than seeing knowledge about language as the accumulation of technical skills alone, the viewpoint to which we subscribe treats knowledge about language as a dialectic that evolves from, is situated in, and contributes to a social arena (Halliday, 1978). We do not shy away from this position just because children are in the early years of schooling. In ‘Playing with Grammar’, we focus on the Foundation to Year 2 grouping, in line with the Australian Curriculum, Assessment and Reporting Authority’s (hereafter ACARA) advice on the ‘nature of learners’ (ACARA, 2013). With our focus on the early years of schooling comes our acknowledgement of the importance and complexity of play. At a time where accountability in education has moved many teachers to a sense of urgency to prove language and literacy achievement (Genishi and Dyson, 2009), we encourage space to revisit what we know about literature choices and learning experiences and bring these together to facilitate language learning. We can neither ignore, nor overemphasise, the importance of play for the development of language through: the opportunities presented for creative use and practice; social interactions for real purposes; and, identifying and solving problems in the lives of young children (Marsh and Hallet, 2008). We argue that by engaging young children in opportunities to play with language we are ultimately empowering them to be active in their language learning and in the process fostering a love of language and the intricacies it holds. Our goal in this publication is to provide a range of highly practical strategies for scaffolding young children through some of the Content Descriptions from the Australian Curriculum English Version 5.0, hereafter AC:E V5.0 (ACARA, 2013). This recently released curriculum offers a new theoretical approach to building children’s knowledge about language. The AC:E V5.0 uses selected traditional terms through an approach developed in systemic functional linguistics (see Halliday and Matthiessen, 2004) to highlight the dynamic forms and functions of multimodal language in texts. For example, the following statement, taken from the ‘Language: Knowing about the English language’ strand states: English uses standard grammatical terminology within a contextual framework, in which language choices are seen to vary according to the topics at hand, the nature and proximity of the relationships between the language users, and the modalities or channels of communication available (ACARA, 2013). Put simply, traditional grammar terms are used within a functional framework made up of field, tenor, and mode. An understanding of genre is noted with the reference to a ‘contextual framework’. The ‘topics at hand’ concern the field or subject matter of the text. The ‘relationships between the language users’ is a description of tenor. There is reference to ‘modalities’, such as spoken, written or visual text. We posit that this innovative approach is necessary for working with contemporary multimodal and cross-cultural texts (see Exley and Mills, 2012). We believe there is enormous power in using literature to expose children to the richness of language and in turn develop language and literacy skills. Taking time to look at language patterns within actual literature is a pathway to ‘…capture interest, stir the imagination and absorb the [child]’ into the world of language and literacy (Saxby, 1993, p. 55). In the following three sections, we have tried to remain faithful to our interpretation of the AC:E V5.0 Content Descriptions without giving an exhaustive explanation of the grammatical terms. Other excellent tomes, such as Derewianka (2011), Humphrey, Droga and Feez (2012), and Rossbridge and Rushton (2011) provide these more comprehensive explanations as does the AC:E V5.0 Glossary. We’ve reproduced some of the AC:E V5.0 glossary at the end of this publication. Our focus is on the structure and unfolding of the learning experiences. We outline strategies for working with children in Foundation, Year 1 and Year 2 by providing some demonstration learning experiences based on texts we’ve selected, but maintain that the affordances of these strategies will only be realised when teaching and learning is purposively tied to authentic projects in local contexts. We strongly encourage you not to use only the resource texts we’ve selected, but to capitalise upon your skill for identifying the language features in the texts you and the children are studying and adapt some of the strategies we have outlined. Each learning experience is connected to one of the Content Descriptions from the AC:E V5.0 and contains an experience specific purpose, a suggested resource text and a sequence for the experience that always commences with an orientation to text followed by an examination of a particular grammatical resource. We expect that each of these learning experiences will take a couple if not a few teaching episodes to work through, especially if children are meeting a concept for the first time. We hope you use as much, or as little, of each experience as is needed. Our plans allow for focused discussion, shared exploration and opportunities to revisit the same text for the purpose of enhancing meaning making. We do not want the teaching of grammar to slip into a crisis of irrelevance or to be seen as a series of worksheet drills with finite answers. Strategies for effective practice, however, have much portability. We are both very keen to hear from teachers who are adopting and adapting these learning experiences in their classrooms. Please email us on b.exley@qut.edu.au or lkervin@uow.edu.au. We’d love to continue the conversation with you over time.

MedWords : Australia and New Zealand

MedWords is the essential accompaniment to the Mastering Medical Terminology suite of learning tools.Learn correct pronunciation by listening to expert Australian voice recordings of over 2,000 medical terms. Practice by recording your own voice

Ten principles of good business process management

Purpose The purpose of this paper is to foster a common understanding of business process management (BPM) by proposing a set of ten principles that characterize BPM as a research domain and guide its successful use in organizational practice. Design/methodology/approach The identification and discussion of the principles reflects our viewpoint, which was informed by extant literature and focus groups, including 20 BPM experts from academia and practice. Findings We identify ten principles which represent a set of capabilities essential for mastering contemporary and future challenges in BPM. Their antonyms signify potential roadblocks and bad practices in BPM. We also identify a set of open research questions that can guide future BPM research. Research limitation/implication Our findings suggest several areas of research regarding each of the identified principles of good BPM. Also, the principles themselves should be systematically and empirically examined in future studies. Practical implications – Our findings allow practitioners to comprehensively scope their BPM initiatives and provide a general guidance for BPM implementation. Moreover, the principles may also serve to tackle contemporary issues in other management areas. Originality/value This is the first paper that distills principles of BPM in the sense of both good and bad practice recommendations. The value of the principles lies in providing normative advice to practitioners as well as in identifying open research areas for academia, thereby extending the reach and richness of BPM beyond its traditional frontiers.

Self-reflection as an intervention to influence achievement goal orientations and intrinsic motivation

In the context of physical activity, intrinsic motivation refers to the inherent satisfaction associated with participation in the activity. Interest-enjoyment, perceived competence, and effort have been identified as three underlying components of intrinsic motivation. Achievement goal theory stipulates that achievement goals guide our beliefs and behavior. The two main achievement goal orientations identified in the sport and physical activity literature are task and ego orientations. A person with a strong task orientation defines success in self-referenced terms, as improving one’s own performance or mastering new skills. Someone with a strong ego orientation defines success normatively, as being better than others. The majority of research suggests that having a strong task orientation is a good thing, whether with regard to motivationally adaptive responses, sources of sport confidence, students’ satisfaction with learning, or the use of cognitive and self-regulatory strategies. Although the literature supporting the potential benefits of having a strong task orientation is vast, considerably less research has tested interventions designed to strengthen task orientations and intrinsic motivation. A climate that emphasises individual mastery has resulted in increased interest-enjoyment and perceived competence, whereas an emphasis on competition and comparison with others has resulted in a decrease in interest-enjoyment and an increase in tension-pressure. One possible intervention is the use of structured self-reflection. Using self-reflection sheets that cause respondents to focus on specific elements of technique or skills, and rate one’s own performance, should theoretically promote a task focus. Hanrahan suggested that engaging in self-reflection may enhance intrinsic motivation. Perceived competence could be positively affected, as self-analysis and self-monitoring have been found to positively influence the acquisition of physical skills. The purpose of this study was to determine if the use of structured self-reflection in community dance classes would influence achievement goal orientations or levels of intrinsic motivation.