In vitro and in vivo studies on protease-activated receptor-2

Protease-activated receptor-2 (PAR2) is a G protein coupled receptor (GPCR) that is activated by proteolytic cleavage of its amino terminal domain by trypsin-like serine proteases. Cleavage of this receptor exposes a neoepitope, termed the tethered ligand (TL), which binds intramolecularly within the receptor to stimulate signal transduction via coupled G proteins. PAR2-mediated signal transduction is also experimentally stimulated by hexapeptides (agonist peptides; APs) that are homologous to the TL sequence. Due to the irreversible nature of PAR2 proteolysis, downstream signal transduction is tightly regulated. Following activation, PAR2 is rapidly uncoupled from downstream signalling by the post-translational modifications phosphorylation and ubiquination which facilitate interactions with ��- arrestin. This scaffolding protein couples PAR2 to the internalisation machinery initiating its desensitisation and trafficking through the early and late endosomes followed by receptor degradation. PAR2 is widely expressed in mammalian tissues with key roles for this receptor in cardiovascular, respiratory, nervous and musculoskeletal systems. This receptor has also been linked to pathological states with aberrant expression and signalling noted in several cancers. In prostate cancer, PAR2 signalling induces migration and proliferation of tumour derived cell lines, while elevated receptor expression has been noted in malignant tissues. Importantly, a role for this receptor has also been suggested in prostate cancer bone metastasis as coexpression of PAR2 and a proteolytic activator has been demonstrated by immunohistochemical analysis. Based on these data, the primary focus of this project has been on two aspects of PAR2 biology. The first is characterisation of cellular mechanisms that regulate PAR2 signalling and trafficking. The second aspect is the role of this receptor in prostate cancer bone metastasis. In addition, to permit these studies, it was first necessary to evaluate the specificity of the commercially available anti-PAR2 antibodies SAM11, C17, N19 and H99. The evaluation of the four commercially available antibodies was assessed using four techniques: immunoprecipitation; Western blot analysis; immunofluorescence; and flow cytometry. These approaches demonstrated that three of the antibodies efficiently detect ectopically expressed PAR2 by each of these techniques. A significant finding from this study was that N19 was the only antibody able to specifically detect N-glycosylated endogenous PAR2 by Western blot analysis. This analysis was performed on lysates from prostate cancer derived cell lines and tissue derived from wildtype and PAR2 knockout mice. Importantly, further evaluation demonstrated that this antibody also efficiently detects endogenous PAR2 at the cell surface by flow cytometry. The anti-PAR2 antibody N19 was used to explore the in vitro role of palmitoylation, the post-translational addition of palmitate, in PAR2 signalling, trafficking, cell surface expression and desensitization. Significantly, use of the palmitoylation inhibitor 2-bromopalmitate indicated that palmitate addition is important in trafficking of PAR2 endogenously expressed by prostate cancer cell lines. This was supported by palmitate labelling experiments using two approaches which showed that PAR2 stably expressed by CHO cells is palmitoylated and that palmitoylation occurs on cysteine 361. Another key finding from this study is that palmitoylation is required for optimal PAR2 signalling as Ca2+ flux assays indicated that in response to trypsin agonism, palmitoylation deficient PAR2 is ~9 fold less potent than wildtype receptor with a reduction of about 33% in the maximum signal induced via the mutant receptor. Confocal microscopy, flow cytometry and cell surface biotinylation analyses demonstrated that palmitoylation is required for efficient cell surface expression of PAR2. Importantly, this study also identified that palmitoylation of this receptor within the Golgi apparatus is required for efficient agonist-induced rab11amediated trafficking of PAR2 to the cell surface. Interestingly, palmitoylation is also required for receptor desensitization, as agonist-induced ��-arrestin recruitment and receptor degradation were markedly reduced in CHO-PAR2-C361A cells compared with CHO-PAR2 cells. Collectively, these data provide new insights on the life cycle of PAR2 and demonstrate that palmitoylation is critical for efficient signalling, trafficking, cell surface localization and degradation of this receptor. This project also evaluated PAR2 residues involved in ligand docking. Although the extracellular loop (ECL)2 of PAR2 is known to be required for agonist-induced signal transduction, the binding pocket for receptor agonists remains to be determined. In silico homology modelling, based on a crystal structure for the prototypical GPCR rhodopsin, and ligand docking were performed to identify PAR2 transmembrane (TM) amino acids potentially involved in agonist binding. These methods identified 12 candidate residues that were mutated to examine the binding site of the PAR2 TL, revealed by trypsin cleavage, as well as of the soluble ligands 2f-LIGRLO-NH2 and GB110, which are both structurally based on the AP SLIGRLNH2. Ligand binding was evaluated from the impact of the mutated residues on PAR2-mediated calcium mobilisation. An important finding from these experiments was that mutation of residues Y156 and Y326 significantly reduced 2f-LIGRLO-NH2 and GB110 agonist activity. L307 was also important for GB110 activity. Intriguingly, mutation of PAR2 residues did not alter trypsin-induced signalling to the same extent as for the soluble agonists. The reason for this difference remains to be further examined by in silico and in vitro experimentation and, potentially, crystal structure studies. However, these findings identified the importance of TM domains in PAR2 ligand docking and will enhance the design of both PAR2 agonists and potentially agents to inhibit signalling (antagonists). The potential importance of PAR2 in prostate cancer bone metastasis was examined using a mouse model. In patients, prostate cancer bone metastases cause bone growth by disrupting bone homeostasis. In an attempt to mimic prostate cancer growth in bone, PAR2 responsive 22Rv1 prostate cancer cells, which form mixed osteoblastic and osteolytic lesions, were injected into the proximal aspect of mouse tibiae. A role for PAR2 was assessed by treating these mice with the recently developed PAR2 antagonist GB88. As controls, animals bearing intra-tibial tumours were also treated with vehicle (olive oil) or the prostate cancer chemotherapeutic docetaxel. The effect of these treatments on bone was examined radiographically and by micro-CT. Consistent with previous studies, 22Rv1 tumours caused osteoblastic periosteal spicule formation and concurrent osteolytic bone loss. Significantly, blockade of PAR2 signalling reduced the osteoblastic and osteolytic phenotype of 22Rv1 tumours in bone. No bone defects were detected in mice treated with docetaxel. These qualitative data will be followed in the future by quantitative micro-CT analysis as well as histology and histomorphometry analysis of already collected tissues. Nonetheless, these preliminary experiments highlight a potential role for PAR2 in prostate cancer growth in bone. In summary, in vitro studies have defined mechanisms regulating PAR2 activation, downstream signalling and trafficking and in vivo studies point to a potential role for this receptor in prostate cancer bone metastasis. The outcomes of this project are that a greater understanding of the biology of PAR2 may lead to the development of strategies to modulate the function of this receptor in disease.

Creating fashion professionals for the 21st century : a tale of pedagogical tensions and emerging challenges

The ���Fashion Tales��� Conference identifies three fashion discourses: that of making, that of media, and that of scholarship. We propose a fourth, which provides a foundational base for the others: the discourse of fashion pedagogy. We begin with the argument that to thrive in any of these discourses, all fashion graduates require the ability to navigate the complexities of the 21st century fashion industry. Fashion graduates emerge into a professional world which demands a range of high level capabilities above and beyond those traditionally acknowledged by the discipline. Professional education in fashion must transform itself to accommodate these imperatives. In this paper, we document a tale of fashion learning, teaching and scholarship ��� the tale of a highly successful future-orientated boutique university-based undergraduate fashion course in Queensland, Australia. The Discipline consistently maintains the highest student satisfaction and lowest attrition of any course in the university, achieves extremely competitive student satisfaction scores when compared with other courses nationally and internationally, and reports outstanding graduate employment outcomes. The core of the article addresses how the course effectively balances five key pedagogical tensions identified from the findings of in-depth focus groups with graduating students, and interviews with teaching staff. The pedagogical tensions are: high concept/ authenticity; high disciplinarity/ interdisciplinarity; high rigour/ play; high autonomy/ scaffolding; and high individuality/ community, where community can be further divided into high challenge and high support. We discuss each of these tensions and how they are characterised within the course, using rich descriptions given by the students. We also draw upon the wider andragogical and learning futures literatures to link the tensions with what is already known about excellence in 21st century higher and further education curriculum and pedagogic practice. We ask: as the fashion industry becomes truly globalised, virtualised, and diversified, and as initial professional training for the industry becomes increasingly massified and performatised, what are the best teaching approaches to produce autonomous, professionally capable, enterprising and responsible graduates into the future? Can the pedagogical balances described in this case study be maintained in the light of these powerful external forces, and if so, how?

Surviving an avalanche of data

Open the sports or business section of your daily newspaper, and you are immediately bombarded with an array of graphs, tables, diagrams, and statistical reports that require interpretation. Across all walks of life, the need to understand statistics is fundamental. Given that our youngsters��� future world will be increasingly data laden, scaffolding their statistical understanding and reasoning is imperative, from the early grades on. The National Council of Teachers of Mathematics (NCTM) continues to emphasize the importance of early statistical learning; data analysis and probability was the Council���s professional development ���Focus of the Year��� for 2007���2008. We need such a focus, especially given the results of the statistics items from the 2003 NAEP. As Shaughnessy (2007) noted, students��� performance was weak on more complex items involving interpretation or application of items of information in graphs and tables. Furthermore, little or no gains were made between the 2000 NAEP and the 2003 NAEP studies. One approach I have taken to promote young children���s statistical reasoning is through data modeling. Having implemented in grades 3 ���9 a number of model-eliciting activities involving working with data (e.g., English 2010), I observed how competently children could create their own mathematical ideas and representations���before being instructed how to do so. I thus wished to introduce data-modeling activities to younger children, confi dent that they would likewise generate their own mathematics. I recently implemented data-modeling activities in a cohort of three first-grade classrooms of six year- olds. I report on some of the children���s responses and discuss the components of data modeling the children engaged in.

Adaptive teachers embracing new ways of learning with robotics in Chinese schools

In July 2010, China announced the ���National Plan for Medium and Long-term Education Reform and Development(2010-2020)��� (PRC 2010). The Plan calls for an education system that: ��� promotes an integrated development which harnesses everyone���s talent; ��� combines learning and thinking; unifies knowledge and practice; ��� allows teachers to teach according to individuals��� needs; and ��� reforms education quality evaluation and personnel evaluation systems focusing on performance including character, knowledge, ability and other factors. This paper discusses the design and implementation of a Professional Learning Program (PLP) undertaken by 432 primary, middle and high school teachers in China. The aim of this initiative was to develop adaptive expertise in using technology that facilitated innovative science and technology teaching and learning as envisaged by the Chinese Ministry of Education���s (2010-2020) education reforms. Key principles derived from literature about professional learning and scaffolding of learning informed the design of the PLP. The analysis of data revealed that the participants had made substantial progress towards the development of adaptive expertise. This was manifested not only by advances in the participants��� repertoires of Subject Matter Knowledge and Pedagogical Content Knowledge but also in changes to their levels of confidence and identities as teachers. It was found that through time the participants had coalesced into a professional learning community that readily engaged in the sharing, peer review, reuse and adaption, and collaborative design of innovative science and technology learning and assessment activities.

Negotiating teacher identities : dialogic reflections on classroom interaction in a transnational context

This study investigates the development of teacher identity in a transnational context through an analysis of the voices of sixteen preservice teachers from Hong Kong who engage in interaction with primary students in an Australian classroom. The context for this research is the school-based experience undertaken by these preservice English as a second language teachers as part of their short language immersion (SLIM) program in Brisbane, Australia. Such SLIM programs are a genre of study abroad programs which have been gaining in popularity within teacher education in Australia, attended by preservice and inservice teachers from China, Hong Kong, Korea, and other Asian countries. This research is conducted at a time when the imperative to globalise higher education provision is a strategic factor in the educational policies of both Australia and Hong Kong. In Australia, international educational services now constitute the country���s third largest export with more than 400,000 students coming to Australia to study annually. In order to maintain Australia���s current global position as the third most popular Englishspeaking study destination, the government is now focusing on sustainability and the quality of the study experience being offered to international students (Bradley Review, 2008). In Hong Kong, the government sponsors both preservice and inservice English as a second language (ESL) teachers to undertake SLIM programs in Australia and other English-speaking countries, as part of their policy of promoting high levels of English proficiency in Hong Kong classrooms. Transnational teacher education is an important issue to which this study contributes insights into the affordances and constraints of a school-based experience in the transnational context. Second language teacher education has been defined as interventions designed to develop participants��� professional knowledge. In this study, it is argued that participation in a different community of practice helps to foreground tacit theories of second language pedagogy, making them visible and open to review. Questions of pedagogy are also seen as questions of teacher identity, constituting the way that one is in the classroom. I take up a sociocultural and poststructural framework, drawing on the work of James Gee and Mikhail Bakhtin, to theorise the construction of teacher identity as emerging through dialogic relations and socially situated discursive practices. From this perspective, this study investigates whether these teachers engage with different ways of representing themselves through appropriating, adapting or rejecting Discourses prevailing in the Australian classroom. Research suggests that reflecting on dilemmas encountered as lived experiences can extend professional understandings. In this study, the participants engage in a process of dialogic reflection on their intercultural classroom interactions, examining with their peers and their lecturer/researcher selected moments of dissonance that they have faced in the unfamiliar context of an Australian primary classroom. It is argued that the recursive and multivoiced nature of this process of reflection on practice allows participants opportunities to negotiate new understandings of second language teacher identity. Dialogic learning, based on the theories of Bakhtin and Vygotsky, provides the theoretic framing not only for the process of reflection instantiated in this study, but also features in the analysis of the participants��� second language classroom practices. The research design uses a combined discourse analytic and ethnographic approach as a logic-of-inquiry to explore the dialogic relationships which these second language teachers negotiate with their students and their peers in the transnational context. In this way, through discourse analysis of their classroom talk and reflective dialogues, assisted by the analytic tools of speech genres and discourse formats, I explore the participants��� ways of doing and being second language teachers. Thus, this analysis traces the process of ideological becoming of these beginner teachers as shifts in their understandings of teacher and student identities. This study also demonstrates the potential for a nontraditional stimulated recall interview to provide dialogic scaffolding for beginner teachers to reflect productively on their practice.

An innovative method to obtain porous PLLA scaffolds with highly spherical and interconnected pores

Scaffolding is an essential issue in tissue engineering and scaffolds should answer certain essential criteria: biocompatibility, high porosity, and important pore interconnectivity to facilitate cell migration and fluid diffusion. In this work, a modified solvent castingparticulate leaching out method is presented to produce scaffolds with spherical and interconnected pores. Sugar particles (200���300 lm and 300���500 lm) were poured through a horizontal Meker burner flame and collected below the flame. While crossing the high temperature zone, the particles melted and adopted a spherical shape. Spherical particles were compressed in plastic mold. Then, poly-L-lactic acid solution was cast in the sugar assembly. After solvent evaporation, the sugar was removed by immersing the structure into distilled water for 3 days. The obtained scaffolds presented highly spherical interconnected pores, with interconnection pathways from 10 to 100 lm. Pore interconnection was obtained without any additional step. Compression tests were carried out to evaluate the scaffold mechanical performances. Moreover, rabbit bone marrow mesenchymal stem cells were found to adhere and to proliferate in vitro in the scaffold over 21 days. This technique produced scaffold with highly spherical and interconnected pores without the use of additional organic solvents to leach out the porogen.

Zeta-potential and morphology of electrospun nano- and microfibers from biopolymers and their blends used as scaffolds in tissue engineering

Electrostatic spinning or electrospinning is a fiber spinning technique driven by a high-voltage electric field that produces fibers with diameters in a submicrometer to nanometer range.1 Nanofibers are typical one-dimensional colloidal objects with an increased tensile strength, whose length can achieve a few kilometers and the specific surface area can be 100 m2 g���1 or higher.2 Nano- and microfibers from biocompatible polymers and biopolymers have received much attention in medical applications3 including biomedical structural elements (scaffolding used in tissue engineering,2,4���6 wound dressing,7 artificial organs and vascular grafts8), drug and vaccine delivery,9���11 protective shields in speciality fabrics, multifunctional membranes, etc. Other applications concern superhydrophobic coatings,12 encapsulation of solid materials,13 filter media for submicron particles in separation industry, composite reinforcement and structures for nano-electronic machines.

A grand challenge : reflecting on university science curriculum design, collaborative partnerships and integration of information literacy skills

In 2012, Queensland University of Technology (QUT) committed to the massive project of revitalizing its Bachelor of Science (ST01) degree. Like most universities in Australia, QUT has begun work to align all courses by 2015 to the requirements of the updated Australian Qualifications Framework (AQF) which is regulated by the Tertiary Education Quality and Standards Agency (TEQSA). From the very start of the redesigned degree program, students approach scientific study with an exciting mix of theory and highly topical real world examples through their chosen ���grand challenge.��� These challenges, Fukushima and nuclear energy for example, are the lenses used to explore science and lead to 21st century learning outcomes for students. For the teaching and learning support staff, our grand challenge is to expose all science students to multidisciplinary content with a strong emphasis on embedding information literacies into the curriculum. With ST01, QUT is taking the initiative to rethink not only content but how units are delivered and even how we work together between the faculty, the library and learning and teaching support. This was the desired outcome but as we move from design to implementation, has this goal been achieved? A main component of the new degree is to ensure scaffolding of information literacy skills throughout the entirety of the three year course. However, with the strong focus on problem-based learning and group work skills, many issues arise both for students and lecturers. A move away from a traditional lecture style is necessary but impacts on academics��� workload and comfort levels. Therefore, academics in collaboration with librarians and other learning support staff must draw on each others��� expertise to work together to ensure pedagogy, assessments and targeted classroom activities are mapped within and between units. This partnership can counteract the tendency of isolated, unsupported academics to concentrate on day-to-day teaching at the expense of consistency between units and big picture objectives. Support staff may have a more holistic view of a course or degree than coordinators of individual units, making communication and truly collaborative planning even more critical. As well, due to staffing time pressures, design and delivery of new curriculum is generally done quickly with no option for the designers to stop and reflect on the experience and outcomes. It is vital we take this unique opportunity to closely examine what QUT has and hasn���t achieved to be able to recommend a better way forward. This presentation will discuss these important issues and stumbling blocks, to provide a set of best practice guidelines for QUT and other institutions. The aim is to help improve collaboration within the university, as well as to maximize students��� ability to put information literacy skills into action. As our students embark on their own grand challenges, we must challenge ourselves to honestly assess our own work.

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.

Cultural Policy

The development of cultural policy during the twentieth century is underscored by three key developments. First, the formation of the Arts Council of Great Britain in 1946, first headed by the Cambridge economist Lord Keynes, saw the scaffolding developed for ongoing government support for the arts. In doing so, it established the principle of an ���arm���s length��� relationship between the government of the day and individual artists, through the development of independent arts boards engaged in the peer review of creative works. Second, the formation of the Fifth Republic in France in 1958 saw the creation of a Ministry of Culture, headed by the writer Andr�� Malraux. Malraux and his successors have seen three major tasks for a national cultural policy: government support for the creation of new artistic and cultural works; the promotion and maintenance of cultural heritage; and enabling equitable access to creative works and creative opportunities through all segments of society. Finally, at a global level, agencies such as UNESCO have sought to promote national cultural policies as an element of national sovereignty, particularly in the developing world, and this has involved addressing sources of structural inequality in the distribution of global cultural and communications resources...

Complexity and the science of implementation in health IT ��� knowledge gaps and future visions

Objectives The intent of this paper is in the examination of health IT implementation processes ��� the barriers to and facilitators of successful implementation, identification of a beginning set of implementation best practices, the identification of gaps in the health IT implementation body of knowledge, and recommendations for future study and application. Methods A literature review resulted in the identification of six health IT related implementation best practices which were subsequently debated and clarified by participants attending the NI2012 Research Post Conference held in Montreal in the summer of 2012. Using the framework for implementation research (CFIR) to guide their application, the six best practices were applied to two distinct health IT implementation studies to assess their applicability. Results Assessing the implementation processes from two markedly diverse settings illustrated both the challenges and potentials of using standardized implementation processes. In support of what was discovered in the review of the literature, ���one size fits all��� in health IT implementation is a fallacy, particularly when global diversity is added into the mix. At the same time, several frameworks show promise for use as ���scaffolding��� to begin to assess best practices, their distinct dimensions, and their applicability for use. Conclusions Health IT innovations, regardless of the implementation setting, requires a close assessment of many dimensions. While there is no ���one size fits all���, there are commonalities and best practices that can be blended, adapted, and utilized to improve the process of implementation. This paper examines health IT implementation processes and identifies a beginning set of implementation best practices, which could begin to address gaps in the health IT implementation body of knowledge.

Theorizing why in e-learning ��� a frontier for cognitive engagement

Asking why is an important foundation of inquiry and fundamental to the development of reasoning skills and learning. Despite this, and despite the relentless and often disruptive nature of innovations in information and communications technology (ICT), sophisticated tools that directly support this basic act of learning appear to be undeveloped, not yet recognized, or in the very early stages of development. Why is this so? To this question, there is no single satisfactory answer; instead, numerous plausible explanations and related questions arise. After learning something, however, explaining why can be revealing of a person���s understanding (or lack of it). What then differentiates explanation from information; and, explanatory from descriptive content? What ICT scaffolding might support inquiry instigated by why-questioning? What is the role of reflective practice in inquiry-based learning? These and other questions have emerged from this investigation and underscore that why-questions often propagate further questions and are a catalyst for cognitive engagement and dialogue. This paper reports on a multi-disciplinary, theoretical investigation that informs the broad discourse on e-learning and points to a specific frontier for design and development of e-learning tools. Probing why reveals that versatile and ambiguous semantics present the core challenge ��� asking, learning, knowing, understanding, and explaining why.

Tandem B1 SINE retro-elements may provide a basis for natural antisense transcription in the Magi1 locus of the mouse (Mus musculus)

Transposable elements, which are DNA sequences that can move between different sites in genomes, comprise approximately 40% of the genome of mammals and are emerging as important contributors to biological diversity. Here we report a transcription unit lying within intron 1 of the murine Magi1 (membrane associated guanylate kinase inverted 1) gene that codes for a cell-cell junction scaffolding protein. The transcription unit, termed Magi1OS (Magi1 Opposite Strand), originates from a region with tandem B1 short interspersed nuclear elements (SINEs) and is an antisense gene to Magi1. Mag1OS transcription initiates in a proximal B1 element that shows only 4% divergence from the consensus sequence, indicating that it has been recently inserted into the mouse genome and could be replication competent. Moreover, a chimaeric transcript may result from intra-chromosomal interaction and trans-splicing of the Magi1 antisense transcript (Magi1OS) and Ghrl, which codes for the multifunctional peptide hormone ghrelin. These two genes are 20 megabases apart on chromosome 6 and are transcribed in opposite directions. We propose that the Magi1OS locus may serve as a useful model system to study exaptation and retrotransposition of B1 SINEs, as well as to examine the mechanisms of intra-chromosomal trans-splicing.

The why dimension - opening frontiers for digital learning

Digital learning has come a long way from the days of simple 'if-then' queries. It is now enabled by countless innovations that support knowledge sharing, openness, flexibility, and independent inquiry. Set against an evolutionary context this study investigated innovations that directly support human inquiry. Specifically, it identified five activities that together are defined as the 'why dimension' ��� asking, learning, understanding, knowing, and explaining why. Findings highlight deficiencies in mainstream search-based approaches to inquiry, which tend to privilege the retrieval of information as distinct from explanation. Instrumental to sense-making, the 'why dimension' provides a conceptual framework for development of 'sense-making technologies'.

Use of genetically modified muscle and fat grafts to repair defects in bone and cartilage

We report a novel technology for the rapid healing of large osseous and chondral defects, based upon the genetic modification of autologous skeletal muscle and fat grafts. These tissues were selected because they not only possess mesenchymal progenitor cells and scaffolding properties, but also can be biopsied, genetically modified and returned to the patient in a single operative session. First generation adenovirus vector carrying cDNA encoding human bone morphogenetic protein-2 (Ad.BMP-2) was used for gene transfer to biopsies of muscle and fat. To assess bone healing, the genetically modified (���gene activated���) tissues were implanted into 5mm-long critical size, mid-diaphyseal, stabilized defects in the femora of Fischer rats. Unlike control defects, those receiving gene-activated muscle underwent rapid healing, with evidence of radiologic bridging as early as 10 days after implantation and restoration of full mechanical strength by 8 weeks. Histologic analysis suggests that the grafts rapidly differentiated into cartilage, followed by efficient endochondral ossification. Fluorescence in situ hybridization detection of Y-chromosomes following the transfer of male donor muscle into female rats demonstrated that at least some of the osteoblasts of the healed bone were derived from donor muscle. Gene activated fat also healed critical sized defects, but less quickly than muscle and with more variability. Anti-adenovirus antibodies were not detected. Pilot studies in a rabbit osteochondral defect model demonstrated the promise of this technology for healing cartilage defects. Further development of these methods should provide ways to heal bone and cartilage more expeditiously, and at lower cost, than is presently possible.