Safety-critical medical device development using the UPP2SF model translation tool

Software-based control of life-critical embedded systems has become increasingly complex, and to a large extent has come to determine the safety of the human being. For example, implantable cardiac pacemakers have over 80,000 lines of code which are responsible for maintaining the heart within safe operating limits. As firmware-related recalls accounted for over 41% of the 600,000 devices recalled in the last decade, there is a need for rigorous model-driven design tools to generate verified code from verified software models. To this effect, we have developed the UPP2SF model-translation tool, which facilitates automatic conversion of verified models (in UPPAAL) to models that may be simulated and tested (in Simulink/Stateflow). We describe the translation rules that ensure correct model conversion, applicable to a large class of models. We demonstrate how UPP2SF is used in themodel-driven design of a pacemaker whosemodel is (a) designed and verified in UPPAAL (using timed automata), (b) automatically translated to Stateflow for simulation-based testing, and then (c) automatically generated into modular code for hardware-level integration testing of timing-related errors. In addition, we show how UPP2SF may be used for worst-case execution time estimation early in the design stage. Using UPP2SF, we demonstrate the value of integrated end-to-end modeling, verification, code-generation and testing process for complex software-controlled embedded systems. © 2014 ACM.

Actionable Nuggets: Knowledge Translation Tool for the Needs of Patients with Spinal Cord Injury

OBJECTIVE: To present the results of a pilot study of an innovative methodology for translating best evidence about spinal cord injury (SCI) for family practice.

MS2SV: Tradução de modelos em Simulink para VHDL-AMS

This paper presents a methodology and a tool for projects involving analogue and digital signals. A sub-systems group was developed to translation a Matlab/Simulink model in the correspondent structural model described in VHDL-AMS. The developed translation tool, named of MS(2)SV, can reads a file containing a Simulink model translating it in the correspondent VHDL-AMS structural code. The tool also creates the directories structure and necessary files to simulate the model translated in System Vision environment. Three models of D/A converters available commercially that use R-2R ladder network were studied. This work considers some of challenges set by the electronic industry for the further development of simulation methodologies and tools in the field of mixed-signal technology. Although the objective of the studies has been the D/A converter, the developed methodology has potentiality to be extended to consider control systems and mechatronic systems.

LOGO2VHDL: modelos descritos em VHDL a partir da linguagem do LOGO!Soft Comfort da Siemens

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

ART: An ontology based tool for the translation of papers into Semantic Web format

To be presented at SIG/ISMB07 ontology workshop: http://bio-ontologies.org.uk/index.php To be published in BMC Bioinformatics. Sponsorship: JISC

Columnar translation: an ancient interpretive tool that the Romans gave the Greeks

Among the more peculiar literary papyri uncovered in the past century are numerous bilingual texts of Virgil and Cicero, with the Latin original and a Greek translation arranged in distinctive narrow columns. These materials, variously classified as texts with translations or as glossaries, were evidently used by Greek-speaking students when they first started to read Latin literature. They thus provide a unique window into the experience of the first of many groups of non-native Latin speakers to struggle with reading the classics of Latin literature.

Saccharomyces Cerevisiae as a biotechnological tool for ageing research:studies on translation and metabolism

The yeast Saccharomyces cerevisiae is an important model organism for the study of cell biology. The similarity between yeast and human genes and the conservation of fundamental pathways means it can be used to investigate characteristics of healthy and diseased cells throughout the lifespan. Yeast is an equally important biotechnological tool that has long been the organism of choice for the production of alcoholic beverages, bread and a large variety of industrial products. For example, yeast is used to manufacture biofuels, lubricants, detergents, industrial enzymes, food additives and pharmaceuticals such as anti-parasitics, anti-cancer compounds, hormones (including insulin), vaccines and nutraceuticals. Its function as a cell factory is possible because of the speed with which it can be grown to high cell yields, the knowledge that it is generally recognized as safe (GRAS) and the ease with which metabolism and cellular pathways, such as translation can be manipulated. In this thesis, these two pathways are explored in the context of their biotechnological application to ageing research: (i) understanding translational processes during the high-yielding production of membrane protein drug targets and (ii) the manipulation of yeast metabolism to study the molecule, L-carnosine, which has been proposed to have anti-ageing properties. In the first of these themes, the yeast strains, spt3?, srb5?, gcn5? and yTHCBMS1, were examined since they have been previously demonstrated to dramatically increase the yields of a target membrane protein (the aquaporin, Fps1) compared to wild-type cells. The mechanisms underlying this discovery were therefore investigated. All high yielding strains were shown to have an altered translational state (mostly characterised by an initiation block) and constitutive phosphorylation of the translational initiation factor, eIF2a. The relevance of the initiation block was further supported by the finding that other strains, with known initiation blocks, are also high yielding for Fps1. A correlation in all strains between increased Fps1 yields and increased production of the transcriptional activator protein, Gcn4, suggested that yields are subject to translational control. Analysis of the 5´ untranslated region (UTR) of FPS1 revealed two upstream open reading frames (uORFs). Mutagenesis data suggest that high yielding strains may circumvent these control elements through either a leaky scanning or a re-initiation mechanism. In the second theme, the dipeptide L-carnosine (ß-alanyl-L-histidine) was investigated: it has previously been shown to inhibit the growth of cancer cells but delay senescence in cultured human fibroblasts and extend the lifespan of male fruit flies. To understand these apparently contradictory properties, the effects of L-carnosine on yeast were studied. S. cerevisiae can respire aerobically when grown on a non-fermentable carbon source as a substrate but has a respiro-fermentative metabolism when grown on a fermentable carbon source; these metabolisms mimic normal cell and cancerous cell metabolisms, respectively. When yeast were grown on fermentable carbon sources, in the presence of L-carnosine, a reduction in cell growth and viability was observed, which was not apparent for cells grown on a non-fermentable carbon source. The metabolism-dependent mechanism was confirmed in the respiratory yeast species Pichia pastoris. Further analysis of S. cerevisiae yeast strains with deletions in their nutrient-sensing pathway, which result in an increase in respiratory metabolism, confirmed the metabolism-dependent effects of L-carnosine.

Translation of addictions science into practice : update and future directions.

Recent advances in the understanding of the genetic, neurochemical, behavioral and cultural underpinnings of addiction have led to rapid advances in the understanding of addiction as a disease. In fact, advances in basic science and the development of new pharmacological and behavioral therapies associated with them are appearing faster than can be assimilated not only by clinical researchers but practitioners and policy makers as well. Translation of science-based addictions knowledge into improved prevention, assessment and treatment, and communication of these changes to researchers and practitioners are significant challenges to the field. The general aim of this book is to summarize current and potential linkages between advances in addiction science and innovations in clinical practice. Whilst this book is primarily focused on translation, it also encompasses some scientific advances that are relevant to dissemination, and the book is itself a tool for disseminating innovative thinking. The goal is to generate interest in application opportunities from both recent research and theoretical advances.

Translation of addictions science into practice

Recent advances in the understanding of the genetic, neurochemical, behavioral and cultural underpinnings of addiction have led to rapid advances in the understanding of addiction as a disease. In fact, advances in basic science and the development of new pharmacological and behavioral therapies associated with them are appearing faster than can be assimilated not only by clinical researchers but practitioners and policy makers as well. Translation of science-based addictions knowledge into improved prevention, assessment and treatment, and communication of these changes to researchers and practitioners are significant challenges to the field. The general aim of this book is to summarize current and potential linkages between advances in addiction science and innovations in clinical practice. Whilst this book is primarily focused on translation, it also encompasses some scientific advances that are relevant to dissemination, and the book is itself a tool for disseminating innovative thinking. The goal is to generate interest in application opportunities from both recent research and theoretical advances.

The ethnographer as community manager : language translation and user negotiation

This article investigates the ethnographic methodological question of how the researcher observes objectively while being part of the problem they are observing. It uses a case study of ABC Pool to argue a cooperative approach that combines the roles of the ethnographer with that of a community manager who assists in constructing a true representation of the researched environment. By using reflexivity as a research tool, the ethnographer engages in a process to self-check their personal presumptions and prejudices, and to strengthen the constructed representation of the researched environment. This article also suggests combining management and expertise research from the social sciences with ethnography, to understand and engage with the research field participants more intimately - which, ultimately, assists in gathering and analysing richer qualitative data.

The development and piloting of the ISPCAN child abuse screening tool-parent version (ICAST-P)

Objective Child maltreatment is a problem that has longer recognition in the northern hemisphere and in high-income countries. Recent work has highlighted the nearly universal nature of the problem in other countries but demonstrated the lack of comparability of studies because of the variations in definitions and measures used. The International Society for the Prevention of Child Abuse and Neglect has developed instrumentation that may be used with cross-cultural and cross-national benchmarking by local investigators. Design and sampling The instrument design began with a team of expert in Brisbane in 2004. A large bank of questions were subjected to two rounds of Delphi review to develop the fielded version of the instrument. Convenience samples included approximately 120 parent respondents with children under the age of 18 in each of six countries (697 total). Results This paper presents an instrument that measures parental behaviors directed at children and reports data from pilot work in 6 countries and 7 languages. Patterns of response revealed few missing values and distributions of responses that generally were similar in the six countries. Subscales performed well in terms of internal consistency with Cronbach's alpha in very good range (0.77–0.88) with the exception of the neglect and sex abuse subscales. Results varied by child age and gender in expected directions but with large variations among the samples. About 15% of children were shaken, 24% hit on the buttocks with an object, and 37% were spanked. Reports of choking and smothering were made by 2% of parents. Conclusion These pilot data demonstrate that the instrument is well tolerated and captures variations in, and potentially harmful forms of child discipline. Practice implications The ISPCAN Child Abuse Screening Tool – Parent Version (ICAST-P) has been developed as a survey instrument to be administered to parents for the assessment of child maltreatment in a multi-national and multi-cultural context. It was developed with broad input from international experts and subjected to Dephi review, translation, and pilot testing in six countries. The results of the Delphi study and pilot testing are presented. This study demonstrates that a single instrument can be used in a broad range of cultures and languages with low rates of missing data and moderate to high internal consistency.

Circulating tumor cells: Isolation, expansion, characterization and translation to clinic

Circulating tumor cells (CTCs) are the seeds for cancer metastases development, which is responsible for >90% of cancer-related deaths. Accurate quantification of CTCs in human fluids could be an invaluable tool for understanding cancer prognosis, delivering personalized medicine to prevent metastasis and finding cancer therapy effectiveness. Although CTCs were first discovered more than 200 years ago, until now it has been a nightmare for clinical practitioners to capture and diagnose CTCs in clinical settings. Our society needs rapid, sensitive, and reliable assays to identify the CTCs from blood in order to help save millions of lives. Due to the phenotypic EMT transition, CTCs are undetected for more than one-third of metastatic breast cancer patients in clinics. To tackle the above challenges, the first volume in “Circulating Tumor Cells (CTCs): Detection Methods, Health Impact and Emerging Clinical Challenges discusses recent developments of different technologies, which have the capability to target and elucidate the phenotype heterogenity of CTCS. It contains seven chapters written by world leaders in this area, covering basic science to possible device design which can have beneficial applications in society. This book is unique in its design and content, providing an in-depth analysis to elucidate biological mechanisms of cancer disease progression, CTC detection challenges, possible health effects and the latest research on evolving technologies which have the capability to tackle the above challenges. It describes the broad range of coverage on understanding CTCs biology from early predictors of the metastatic spread of cancer, new promising technology for CTC separation and detection in clinical environment and monitoring therapy efficacy via finding the heterogeneous nature of CTCs. (Imprint: Nova Biomedical)

Professing translation: the acts-in-between

Drawing on scholarship in translation ethics (Berman 1992; Cronin 2003) and performance studies (Conquergood 2002; Jackson 2004), this article approaches translation in the theatre from the double perspective of theory and practice. Professing translation as a model for the resolution of entrenched binaries (scholar/artist; theoretician/practitioner), the author sees the practice of translating for performance not just as a method of discovery or a hermeneutic tool but also as a mode of reflection that brings together both “readerly” and “writerly” approaches to text (Barthes 1974). By drawing on the experience of writing translations of García Lorca for the Belgrade Theatre, Calderón for the Royal Shakespeare Company, and Lope de Vega for the Watermill Theatre and the Washington Shakespeare Theatre, the article attempts to characterise such translation as an act of physical imagination, of a holistic understanding of both language and performance, into which textuality is incorporated and by which it is superseded. © John Benjamins Publishing Company

mRNA metabolism: nonsense mediated mRNA decay as a tool for gene therapy and the role of human DIS3L2 in transcript degradation

Tese de mestrado em Biologia Humana e Ambiente, apresentada à Universidade de Lisboa, através da Faculdade de Ciências, 2015

Translation to success of surgical innovation.

Contemporary thoracic and cardiovascular surgery uses extensive equipment and devices to enable its performance. As the specialties develop and new frontiers are crossed, the technology needs to advance in a parallel fashion. Strokes of genius or problem-solving brain-storming may generate great ideas, but the metamorphosis of an idea into a physical functioning tool requires a lot more than just a thinking process. A modern surgical device is the end-point of a sophisticated, complicated and potentially treacherous route, which incorporates new skills and knowledge acquisition. Processes including technology transfer, commercialisation, corporate and product development, intellectual property and regulatory routes all play pivotal roles in this voyage. Many good ideas may fall by the wayside for a multitude of reasons as they may not be marketable or may be badly marketed. In this article, we attempt to illuminate the components required in the process of surgical innovation, which we believe must remain in the remit of the modern-day thoracic and cardiovascular surgeon.