Natural and engineered plasmin inhibitors : applications and design strategies

Plasmin is the primary enzyme responsible for dissolution of fibrin in the circulatory system. Plasminogen, the zymogen of plasmin is expressed ubiquitously in the human body [1], with the predominant source being the liver [2, 3]. Plasminogen is produced as an 810 amino acid protein with a 19 amino acid leader peptide, which is cleaved during secretion to produce the mature 791 amino acid one-chain zymogen. This is converted to plasmin by cleavage of the Arg561 - Val562 scissile bond [4], resulting in an active protease consisting of two disulfide linked chains. The amino-terminal heavy chain (residues Glu1-Arg561) is comprised of a plasminogen/apple/nematode (PAN) domain [5] and five kringle domains of approximately equal size [6] while the light chain (residues Val562-Asn791) contains a serine protease domain homologous to trypsin with a catalytic triad comprising His603, Asp646 and Ser741 [7]. Both plasmin and plasminogen occur in two forms, full length and a Lys77-Lys78 activated variant produced through self catalysis (Figure 1). The former exists in a tight conformation through binding of Lys50 and/or Lys62 to kringle domain 5 [8, 9] while Lys78-plasminogen assumes a more relaxed conformation rendering it more susceptible to plasmin conversion [10, 11].

Early challenges of shifting an Australian manufacturer’s utilisation of design

This paper presents the findings from the initial exploration phase of an 11 month project, identifying the early challenges that a design innovation catalyst faces while initiating a shift in the way a medium sized manufacturing firm utilises design. Ultimately, the overarching aims of the project are to transform the utilisation of design within the participating company from a styling tool to a strategic process through the implementation of a design led approach to innovation. Insights were found through qualitative interviews with company staff and reflective journal entries as part of an Action Research methodology. Challenges identified include managing expectations, conveying the potential of a design innovation catalyst and a design led approach to innovation, and a siloed and risk averse culture. Findings presented in this paper will assist in identifying and understanding the preliminary challenges encountered by a design innovation catalyst when embarking on a design led transformation. Future innovation catalysts can prepare for possible barriers by highlighting considerations, opportunities and challenges when embarking on a design led transformation. Implications of this research are provided as possible approaches to overcoming these challenges.

From production to purpose : using design led innovation to Build Strategic Potential in a Family-Owned SME

There is an evident need to develop the strategic capabilities of companies from within, to ensure competitive competence in a time where strategy is a necessity. This paper is based on the first 4 months of a longitudinal embedded case study of a family-owned Australian small to medium enterprise, in their journey towards design integration. The first author was embedded as a ‘Design Innovation Catalyst’ to collaborate on overcoming early barriers of strategic development, using design led innovation. Action research methodology, semi-structured interviews with seven out of eight employees and a reflective journal revealed the absence of a shared vision, conflicting drivers and a focus on operational efficiency rather than strategy. Through the Catalyst’s facilitation, a company vision, general awareness, practice and knowledge in strategic development have emerged as the first steps to generating strategic design competence within the firm.

The challenges of adopting design-led innovative strategies in not for profits : the role of consumers, culture and employees

Major changes to regulations, funding and consumer demand in the Australian aged care industry are driving not for profits in this sector to reshape and rethink the services they offer and the ways in which they deliver their services to consumers. Many not for profit organisations facing these new challenges are also facing organisational cultural barriers in the development and implementation of innovative strategies. This paper presents a case study where one organisation, using design led innovation, explored consumer insights and employee values to find new ways to facilitate change.

Design led innovation : shifting from smart follower to digital strategy leader in the Australian airport sector

This paper presents and discusses organisational barriers and opportunities arising from the dissemination of design led innovation within a leading Australian airport corporation. This research is part of a greater action research program which aims to integrate design as a strategic capability through design led innovation within Australian businesses. Findings reveal that there is an opportunity to employ the theoretical framework and tools of design led innovation in practice to build collaborative idea generation by involving customers and stakeholders within the proposal of new to world propositions. The iterative gathering of deep customer insights also provided an opportunity to leverage a greater understanding of stakeholders and customers in strengthening continuing business partnerships through co-design. Challenges to the design led approach include resistance to the exploratory nature of gathering deep customer insights, the testing of long held assumptions and market data, and the disruption of an organisational mindset geared toward risk aversion instilled within the aviation industry. The implication from these findings is that design led innovation can provide the critical platform to allow for a business to grow and sustain internal design capabilities necessary to challenge prevailing assumptions about how its business model operates to deliver value to customers and stakeholders alike. The platform of design led innovation also provides an avenue to support a cultural transformation towards anticipating future needs necessary for establishing a position of leadership within the broader economic environment.

Unpacking the opportunities for change within a family owned manufacturing sme : a design led innovation case study

This thesis explored how an Australian, family owned, manufacturing firm responded to a design led innovation approach as conducted by the action researcher. Specifically, it investigated the barriers and opportunities that arose within the firm when trying to affect change to drive innovation. In doing so, key opportunities were identified that could help the firm to integrate a design led approach and remain competitive within an increasingly accessible global marketplace.

Photovoltaic DC-DC module integrated converter for novel cascaded and bypass grid connection topologies - design and optimisation

Grid connected photovoltaic (PV) inverters fall into three broad categories - central, string and module integrated converters (MICs). MICs offer many advantages in performance and flexibility, but are at a cost disadvantage. Two alternative novel approaches proposed by the author - cascaded dc-dc MICs and bypass dc-dc MICs - integrate a simple non-isolated intelligent dc-dc converter with each PV module to provide the advantages of dc-ac MICs at a lower cost. A suitable universal 150 W 5 A dc-dc converter design is presented based on two interleaved MOSFET half bridges. Testing shows zero voltage switching (ZVS) keeps losses under 1 W for bi-directional power flows up to 15 W between two adjacent 12 V PV modules for the bypass application, and efficiencies over 94% for most of the operational power range for the cascaded converter application. Based on the experimental results, potential optimizations to further reduce losses are discussed.

Vehicle energy throughput analysis as a drivetrain motor design aid

There are many variables to consider in the design of an electric motor. However, meeting the performance requirements for an electric vehicle drive may cause a designer to loose focus on its typical operation and hence fail to optimise the motor in the region where it processes the most power. This paper investigates operating requirements of electric vehicle motor drives using the University concept vehicle as an example. The paper outlines a methodology for determining primary operating region of a vehicle drive. The methodology is applied to standard driving cycles that are commonly used in the design and testing of vehicles.

Design considerations in an indirectly coupled multilevel motor controller

Permanent magnet (PM) motors utilising ironless stator structures have been incorporated into a wide variety of applications where high efficiency and stringent torque control are required. With recent developments in magnetic materials, improved design strategies, and power outputs of up to 40kW, PM motors have become an attractive candidate for traction drives in electric and hybrid electric vehicles. However, due to their large air gaps and ironless stators these motors can have inductances as low as 2μH, imposing increased requirements on the converter to minimise current ripple. Multilevel converters with n cells can effectively increase the motor inductance by a factor of n2 and are an excellent approach to minimise the motor ripple current. Furthermore by indirectly coupling the outputs of each cell, improvements in converter input and cell ripple current can also be realised. This paper examines the issues in designing a high current indirectly coupled multilevel motor controller for an ironless BLDC traction drive and highlights the limitations of the common ladder core structure.

Two stage unity power factor rectifier design

This paper presents the design process utilised for producing a two stage isolated Unity Power Factor (UPF) rectifier. The important yet less intuitive aspects of the design process are highlighted to aid in the simplification of designing a power converter which meets future UPF standards. Two converter designs are presented, a 200W converter utilising a critical conduction controller and a 750W converter based around a continuous conduction controller. Both designs presented were based on the requirements of an audio power amplifier, but the processes apply equally to a range of applications.

A parametric analysis technique for design of fuel cell and hybrid-electric vehicles

This paper presents a new simplified parametric analysis technique for the design of fuel cell and hybrid-electric vehicles. The technique utilizes a comprehensive set of ∼30 parameters to fully characterize the vehicle platform, powertrain components, vehicle performance requirements and driving conditions. It is best applied to the sizing of powertrain components and prediction of energy consumption in a vehicle. This new parametric technique makes a good complement to existing vehicle simulation software packages and therefore represents a potentially valuable tool for the hybrid vehicle designer.

Design optimisation of ironless motors based on magnet selection

This paper considers the design of a radial flux permanent magnet iron less core brushless DC motor for use in an electric wheel drive with an integrated epicyclic gear reduction. The motor has been designed for a continuous output torque of 30 Nm and peak rating of 60 Nm with a maximum operating speed of 7000 RPM. In the design of brushless DC motors with a toothed iron stator the peak air-gap magnetic flux density is typically chosen to be close to that of the remanence value of the magnets used. This paper demonstrates that for an ironless motor the optimal peak air-gap flux density is closer to the maximum energy product of the magnets used. The use of a radial flux topology allows for high frequency operation and can be shown to give high specific power output while maintaining a relatively low magnet mass. Two-dimensional finite element analysis is used to predict the air-gap flux density. The motor design is based around commonly available NdFeB bar magnet size

Design optimisation of ironless motors based on magnet selection

This paper considers the design of a radial flux permanent magnet ironless core brushless DC motor for use in an electric wheel drive with an integrated epicyclic gear reduction. The motor has been designed for a continuous output torque of 30 Nm and peak rating of 60 Nm with a maximum operating speed of 7000 RPM. In the design of brushless DC motors with a toothed iron stator the peak air-gap magnetic flux density is typically chosen to be close to that of the remanence value of the magnets used. This paper demonstrates that for an ironless motor the optimal peak air-gap flux density is closer to the maximum energy product of the magnets used. The use of a radial flux topology allows for high frequency operation and can be shown to give high specific power output while maintaining a relatively low magnet mass. Two-dimensional finite element analysis is used to predict the airgap flux density. The motor design is based around commonly available NdFeB bar magnet size

Making sense of purpose, direction and innovation : an embedded design led innovation case study in the Australian mining industry

The mining equipment technology services sector is driven by a reactive and user-centered design approach, with a technological focus on incremental new product development. As Australia moves out of its sustained mining boom, companies need to rethink their strategic position, to become agile to stay relevant in an enigmatic market. This paper reports on the first five months on an embedded case study within an Australian, family-owned mining manufacturer. The first author is currently engaged in a longitudinal design led innovation project, as a catalyst to guide the company’s journey to design integration. The results find that design led innovation could act as a channel for highlighting and exploring company disconnections with the marketplace and offer a customer-centric catalyst for internal change. Data collected for this study is from 12 analysed semistructured interviews, a focus group and a reflective journal, over a five-month period. This paper explores limitations to design integration, and highlights opportunities to explore and leverage entrepreneurial characteristics to stay agile, broaden innovation and future-proof through the next commodity cycle in the mining industry.

Middle schooling and scientific literacy : bringing the students to science

This study is about young adolescents' engagement in learning science. The middle years of schooling are critical in the development of students' interest and engagement with learning. Successful school experiences enhance dispositions towards a career related to those experiences. Poor experiences lead to negative attitudes and rejection of certain career pathways. At a time when students are becoming more aware, more independent and focused on peer relationships and social status, the high school environment in some circumstances offers more a content-centred curriculum that is less personally relevant to their lives than the social melee surrounding them. Science education can further exacerbate the situation by presenting abstract concepts that have limited contextual relevance and a seemingly difficult vocabulary that further alienates adolescents from the curriculum. In an attempt to reverse a perceived growing disinterest by students to science (Goodrum, Druhan & Abbs, 2011), a study was initiated based on a student-centred unit designed to enhance and sustain adolescent engagement in science. The premise of the study was that adolescent students are more responsive toward learning if they are given an appropriate learning environment that helps connect their learning with life beyond the school. The purpose of this study was to examine the experiences of young adolescents with the aim of transforming school learning in science into meaningful experiences that connected with their lives. Two areas were specifically canvassed and subsumed within the study to strengthen the design base. One area that of the middle schooling ideology, offered specific pedagogical approaches and a philosophical framework that could provide opportunities for reform. The other area, the construct of scientific literacy (OECD, 2007) as defined by Holbrook and Rannikmae, (2009) appeared to provide a sense of purpose for students to aim toward and value for becoming active citizens. The study reported here is a self-reflection of a teacher/researcher exploring practice and challenging existing approaches to the teaching of science in the middle years of schooling. The case study approach (Yin, 2003) was adopted to guide the design of the study. Over a 6-month period, the researcher, an experienced secondary-science teacher, designed, implemented and documented a range of student-centred pedagogical practices with a Year-7 secondary science class. Data for this case study included video recordings, journals, interviews and surveys of students. Both quantitative and qualitative data sources were employed in a partially mixed methods research approach (Leech & Onwuegbuzie, 2009) dominated by qualitative data with the concurrent collection of quantitative data to corroborate interpretations as a means of analysing and developing a model of the dynamic learning environment. The findings from the case study identified five propositions that became the basis for a model of a student-centred learning environment that was able to sustain student participation and thus engagement in science. The study suggested that adolescent student engagement can be promoted and sustained by providing a classroom climate that encourages and strengthens social interaction. Engagement in science can be enhanced by presenting developmentally appropriate challenges that require rigorous exploration of contextually relevant learning environments; supporting students to develop connections with a curriculum that aligns with their own experiences. By setting an environment empathetic to adolescent needs and understandings, students were able to actively explore phenomena collaboratively through developmentally appropriate experiences. A significant outcome of this study was the transformative experiences of an insider, the teacher as researcher, whose reflections provide an authentic model for reforming pedagogy. The model and theory presented became an adjunct to my repertoire for science teaching in the middle years of schooling. The study was rewarding in that it helped address a void in my understanding of middle years of schooling by prompting me to re-think the notion of adolescence in the context of the science classroom. This study is timely given the report "The Status and Quality of Year 11 and 12 Science in Australian Schools" (Goodrum, Druhan & Abbs, 2011) and national curricular changes that are being proposed for science (ACARA, 2009).