Peptide-functionalized polymeric nanoparticles for active targeting of damaged tissue in animals with experimental autoimmune encephalomyelitis

Increased permeability of blood vessels is an indicator for various injuries and diseases, including multiple sclerosis (MS), of the central nervous system. Nanoparticles have the potential to deliver drugs locally to sites of tissue damage, reducing the drug administered and limiting associated side effects, but efficient accumulation still remains a challenge. We developed peptide-functionalized polymeric nanoparticles to target blood clots and the extracellular matrix molecule nidogen, which are associated with areas of tissue damage. Using the induction of experimental autoimmune encephalomyelitis in rats to provide a model of MS associated with tissue damage and blood vessel lesions, all targeted nanoparticles were delivered systemically. In vivo data demonstrates enhanced accumulation of peptide functionalized nanoparticles at the injury site compared to scrambled and naive controls, particularly for nanoparticles functionalized to target fibrin clots. This suggests that further investigations with drug laden, peptide functionalized nanoparticles might be of particular interest in the development of treatment strategies for MS.

Active learning: A step towards automating medical concept extraction

Objective This paper presents an automatic active learning-based system for the extraction of medical concepts from clinical free-text reports. Specifically, (1) the contribution of active learning in reducing the annotation effort, and (2) the robustness of incremental active learning framework across different selection criteria and datasets is determined. Materials and methods The comparative performance of an active learning framework and a fully supervised approach were investigated to study how active learning reduces the annotation effort while achieving the same effectiveness as a supervised approach. Conditional Random Fields as the supervised method, and least confidence and information density as two selection criteria for active learning framework were used. The effect of incremental learning vs. standard learning on the robustness of the models within the active learning framework with different selection criteria was also investigated. Two clinical datasets were used for evaluation: the i2b2/VA 2010 NLP challenge and the ShARe/CLEF 2013 eHealth Evaluation Lab. Results The annotation effort saved by active learning to achieve the same effectiveness as supervised learning is up to 77%, 57%, and 46% of the total number of sequences, tokens, and concepts, respectively. Compared to the Random sampling baseline, the saving is at least doubled. Discussion Incremental active learning guarantees robustness across all selection criteria and datasets. The reduction of annotation effort is always above random sampling and longest sequence baselines. Conclusion Incremental active learning is a promising approach for building effective and robust medical concept extraction models, while significantly reducing the burden of manual annotation.

External knowledge and query strategies in active learning: A study in clinical information extraction

This paper presents a new active learning query strategy for information extraction, called Domain Knowledge Informativeness (DKI). Active learning is often used to reduce the amount of annotation effort required to obtain training data for machine learning algorithms. A key component of an active learning approach is the query strategy, which is used to iteratively select samples for annotation. Knowledge resources have been used in information extraction as a means to derive additional features for sample representation. DKI is, however, the first query strategy that exploits such resources to inform sample selection. To evaluate the merits of DKI, in particular with respect to the reduction in annotation effort that the new query strategy allows to achieve, we conduct a comprehensive empirical comparison of active learning query strategies for information extraction within the clinical domain. The clinical domain was chosen for this work because of the availability of extensive structured knowledge resources which have often been exploited for feature generation. In addition, the clinical domain offers a compelling use case for active learning because of the necessary high costs and hurdles associated with obtaining annotations in this domain. Our experimental findings demonstrated that 1) amongst existing query strategies, the ones based on the classification model’s confidence are a better choice for clinical data as they perform equally well with a much lighter computational load, and 2) significant reductions in annotation effort are achievable by exploiting knowledge resources within active learning query strategies, with up to 14% less tokens and concepts to manually annotate than with state-of-the-art query strategies.

Active fibers: Matching deformable tract templates to diffusion tensor images

Reliable quantitative analysis of white matter connectivity in the brain is an open problem in neuroimaging, with common solutions requiring tools for fiber tracking, tractography segmentation and estimation of intersubject correspondence. This paper proposes a novel, template matching approach to the problem. In the proposed method, a deformable fiber-bundle model is aligned directly with the subject tensor field, skipping the fiber tracking step. Furthermore, the use of a common template eliminates the need for tractography segmentation and defines intersubject shape correspondence. The method is validated using phantom DTI data and applications are presented, including automatic fiber-bundle reconstruction and tract-based morphometry. © 2009 Elsevier Inc. All rights reserved.

Generation of catalytically active materials from a liquid metal precursor

A facile route to prepare catalystically active materials from a galinstan liquid metal alloy is introduced. Sonicating liquid galinstan in alkaline solution or treating it in reducing media results in the creation of solid In/Sn rich microspheres that show catalytic activity toward both potassium ferricyanide and 4-nitrophenol reduction.

Effects of cold water immersion and active recovery on hemodynamics and recovery of muscle strength following resistance exercise

Cold water immersion (CWI) and active recovery (ACT) are frequently used as post-exercise recovery strategies. However, the physiological effects of CWI and ACT after resistance exercise are not well characterized. We examined the effects of CWI and ACT on cardiac output (Q), muscle oxygenation (SmO2) and blood volume (tHb), muscle temperature (Tmuscle ) and isometric strength after resistance exercise. On separate days, 10 men performed resistance exercise, followed by 10 min CWI at 10°C or 10 min ACT (low-intensity cycling). Q (7.9±2.7 l) and Tmuscle (2.2±0.8ºC) increased, whereas SmO2 (-21.5±8.8%) and tHb (-10.1±7.7 μM) decreased after exercise (p<0.05). During CWI, Q ̇(-1.1±0.7 l) and Tmuscle (-6.6±5.3ºC) decreased, while tHb (121±77 μM) increased (p<0.05). In the hour after CWI, Q ̇and Tmuscle remained low, while tHb also decreased (p<0.05). By contrast, during ACT, Q ̇(3.9±2.3 l), Tmuscle (2.2±0.5ºC), SmO2 (17.1±5.7%) and tHb (91±66 μM) all increased (p<0.05). In the hour after ACT, Tmuscle and tHb remained high (p<0.05). Peak isometric strength during 10 s maximum voluntary contractions (MVCs) did not change significantly after CWI, whereas it decreased after ACT (-30 to -45 Nm; p<0.05). Muscle deoxygenation time during MVCs increased after ACT (p<0.05), but not after CWI. Muscle reoxygenation time after MVCs tended to increase after CWI (p=0.052). These findings suggest firstly that hemodynamics and muscle temperature after resistance exercise are dependent on ambient temperature and metabolic demands with skeletal muscle, and secondly, that recovery of strength after resistance exercise is independent of changes in hemodynamics and muscle temperature.

Failure to launch: The self-regulating Md -MYB10R6 gene from apple is active in flowers but not leaves of Petunia

Coloured foliage due to anthocyanin pigments (bronze/red/black) is an attractive trait that is often lacking in many bedding, ornamental and horticultural plants. Apples (Malus × domestica) containing an allelic variant of the anthocyanin regulator, Md-MYB10R6, are highly pigmented throughout the plant, due to autoregulation by MYB10 upon its own promoter. We investigated whether Md-MYB10R6 from apple is capable of functioning within the heterologous host Petunia hybrida to generate plants with novel pigmentation patterns. The Md-MYB10R6 transgene (MYB10–R6pro:MYB10:MYB10term) activated anthocyanin synthesis when transiently expressed in Antirrhinumroseadorsea petals and petunia leaf discs. Stable transgenic petunias containing Md-MYB10R6 lacked foliar pigmentation but had coloured flowers, complementing the an2 phenotype of ‘Mitchell’ petunia. The absence of foliar pigmentation was due to the failure of the Md-MYB10R6 gene to self-activate in vegetative tissues, suggesting that additional protein partners are required for Md-MYB10 to activate target genes in this heterologous system. In petunia flowers, where endogenous components including MYB-bHLH-WDR (MBW) proteins were present, expression of the Md-MYB10R6 promoter was initiated, allowing auto-regulation to occur and activating anthocyanin production. Md-MYB10 is capable of operating within the petunia MBW gene regulation network that controls the expression of the anthocyanin biosynthesis genes, AN1 (bHLH) and MYBx (R3-MYB repressor) in petals.

Engineering education and sustainable development: Rapid curriculum renewal

The issue of engineering education and how it can systemically embed sustainable development knowledge and skills is now a major consideration for engineering educators globally. In this plenary presentation Ms Desha will begin by highlighting the rapidly changing market and regulatory environment and the time lag dilemma facing higher education with regard to delivering professionals who can address societal needs. She will then briefly present a series of elements of curriculum renewal to support engineering educators who are grappling with how programs of study can be rapidly renewed to address such emerging 21st Century challenges. The presentation will conclude with a discussion of the need for astrategic approach by higher education institutions, to ensure that the latest research and opportunities are communicated, while being sufficiently pragmatic and realistic with regard to the scale of the challenges, and existing inertia within the higher education system.

Audience as performer: The changing role of theatre audiences in the twenty-first century

'Actors always talk about what the audience does. I don’t understand, we are just sitting here.' Audience as Performer proposes that in the theatre, there are two troupes of performers: the actors and the audience. Although academics have scrutinised how audiences respond, make meaning and co-create while watching a performance, little research has considered the behaviour of the theatre audience as a performance in and of itself. This insightful book describes how an audience performs through its myriad gestural, vocal and paralingual actions, and considers the following questions: •If the audience are performers, who are their audiences? •How have audiences’ roles changed throughout history? •How do talkbacks and technology influence the audience’s role as critics? •What influence does the audience have on the creation of community in theatre? •How can the audience function as both consumer and co-creator? Drawing from over 140 interviews with audience members, actors and ushers in the UK, USA and Australia, Heim reveals the lived experience of audience members at the theatrical event. It is a fresh reading of mainstream audiences’ activities, bringing their voices to the fore and exploring their emerging new roles in the theatre of the Twenty-First Century.

Info-active and info-passive: The new type of consumer classification

Social media platforms, that foster user generated content, have altered the ways consumers search for product related information. Conducting online searches, reading product reviews, and comparing products ratings, is becoming a more common information seeking pathway. This research demonstrates that info-active consumers are becoming less reliant on information provided by retailers or manufacturers, hence marketing generated online content may have a reduced impact on their purchasing behaviour. The results of this study indicate that beyond traditional methods of segmenting consumers, in the online context, new classifications such as info-active and info-passive would be beneficial in digital marketing. This cross-sectional, mixed-methods study is based on 43 in-depth interviews and an online survey with 500 consumers from 30 countries.

Senior entrepreneurship in Australia: Active ageing and extending working lives

As populations live longer, healthier lives in countries like Australia the growing population of older people is increasing the strains on social security and pension systems. Yet many seniors are healthy and want to remain active during the later years in life. Whilst there is significant research on seniors, ageing and the employment of mature-aged people there is scant research on seniors creating jobs as opposed to seeking jobs as employees. This is the first empirical research specifically on senior entrepreneurship in Australia. Seniors often have the skills, financial resources and time available to contribute to economic activity, which leads to the growing prevalence of senior entrepreneurship. Senior entrepreneurship is the process whereby people aged 50+ participate in business start-ups; however, despite representing the fastest growing segment of entrepreneurship little is known about this phenomenon. This research seeks to answer the following questions: What is the scope of senior entrepreneurship in Australia? What are the impacts of senior entrepreneurship in Australia? What perceptions do seniors hold about entrepreneurship as a career option? What policy implications and recommendations can be derived to enhance active ageing, and extend working lives through senior entrepreneurship?

Introduction: Mapping the Contours of East Asian Commercial Law for the Asian Century

The centre of economic gravity in the new century is shifting to the East. Since 200 1, according to the International Monetary Fund (IMF), Asia's contribution to world economic growth has matched that of the United States and Europe combined, and, since 2006, has even exceeded it (IMF, 20 I I; Neumann and Arora, 20 II ). This surge is easy to explain: China has emerged as a global super-power; Japan remains the third-largest world economy, despite only recently emerging from over twenty years of economic stagnation (The Age, 2013); South Korea and the ' tiger ' economies of Taiwan, Hong Kong and Singapore have achieved high-level economic development through capital investment and technological innovation; and Indonesia, Thailand, the Philippines and Malaysia have supplied riches in labour and resources to the regional economy (Macintyre and Naughton, 2005, p. 78). A growing middle class is lifting consumption. ‘Billions of Asians,' writes Mahbubani (2008, p. 3), 'are marching to modernity.’ This book examines scholarly interpretations for the role commercial law has played in East Asia's economic rise. At first blush, this might seem a daunting task. After all, as some theorists have argued, the East Asian experience is largely neglected in writings on Jaw generally and commercial law more broadly (Wolff, 20 12). This is because law, as a discipline, was largely forged in the prior European and American centuries; these 'Anglo-American moorings' ill-serve legal analysis in the new Asian Century (Cossman, 1997, p. 539).

Corporate Governance in the 21st Century: Japan's Gradual Transformation

The 'lost' decade of economic stagnation in Japan during the 1990s has become a 'found decade' for regulatory and institutional reform. With nearly all areas of the 'law in the books' reviewed, revised and rewritten, the Japanese legal system is no longer the system that foreign commentators felt they were finally starting to understand by the 1980s. Nowhere is this more evident than in corporate governance. Corporate and securities legislation has been comprehensively revamped over 1993-2007, creating a more flexible and transparent regime for shareholders and managers. Financial markets law and regulatory institutions have changed, too, creating a new context for Japan's 'main banks' as alternative or additional outside monitors of managerial performance in borrowing firms. Even the legislation surrounding labour regulations has been amended, reinforcing the lifelong security privileges for elite employee-stakeholders, yet also hastening the growth of other atypical employment relationships. But how do such legislative reforms affecting key players in Japanese firms, covering areas central to the design of Japanese capitlaism, play out in the 'law in action'? Overall, this book argues that a significant gradual transformation has occurred. Although this is evident also in other advanced industrialised democracies, such as Germany, Japan reveals especially complex interactions in the various fields that sometimes emphasise different ways of achieving such transformation.

Enrichment of circulating interleukin-17-secreting interleukin-23 receptor-positive γ/δ T cells in patients with active ankylosing spondylitis

Objective Ankylosing spondylitis (AS) is a common inflammatory arthritis affecting primarily the axial skeleton. IL23R is genetically associated with AS. This study was undertaken to investigate and characterize the role of interleukin-23 (IL-23) signaling in AS pathogenesis. Methods The study population consisted of patients with active AS (n = 17), patients with psoriatic arthritis (n = 8), patients with rheumatoid arthritis, (n = 9), and healthy subjects (n = 20). IL-23 receptor (IL-23R) expression in T cells was determined in each subject group, and expression levels were compared. Results The proportion of IL-23R-expressing T cells in the periphery was 2-fold higher in AS patients than in healthy controls, specifically driven by a 3-fold increase in IL-23R-positive γ/δ T cells in AS patients. The proportions of CD4+ and CD8+ cells that were positive for IL-17 were unchanged. This increased IL-23R expression on γ/δ T cells was also associated with enhanced IL-17 secretion, with no observable IL-17 production from IL-23R-negative γ/δ T cells in AS patients. Furthermore, γ/δ T cells from AS patients were heavily skewed toward IL-17 production in response to stimulation with IL-23 and/or anti-CD3/CD28. Conclusion Recently, mouse models have shown IL-17-secreting γ/δ T cells to be pathogenic in infection and autoimmunity. Our data provide the first description of a potentially pathogenic role of these cells in a human autoimmune disease. Since IL-23 is a maturation and growth factor for IL-17-producing cells, increased IL-23R expression may regulate the function of this putative pathogenic γ/δ T cell population.