Common Marmosets: A Potential Translational Animal Model of Juvenile Depression

Directory of Open Access Journals (Sweden)

Nicole Leite Galvão-Coelho

2017-09-01

Full Text Available Major depression is a psychiatric disorder with high prevalence in the general population, with increasing expression in adolescence, about 14% in young people. Frequently, it presents as a chronic condition, showing no remission even after several pharmacological treatments and persisting in adult life. Therefore, distinct protocols and animal models have been developed to increase the understanding of this disease or search for new therapies. To this end, this study investigated the effects of chronic social isolation and the potential antidepressant action of nortriptyline in juvenile Callithrix jacchus males and females by monitoring fecal cortisol, body weight, and behavioral parameters and searching for biomarkers and a protocol for inducing depression. The purpose was to validate this species and protocol as a translational model of juvenile depression, addressing all domain criteria of validation: etiologic, face, functional, predictive, inter-relational, evolutionary, and population. In both sexes and both protocols (IDS and DPT, we observed a significant reduction in cortisol levels in the last phase of social isolation, concomitant with increases in autogrooming, stereotyped and anxiety behaviors, and the presence of anhedonia. The alterations induced by chronic social isolation are characteristic of the depressive state in non-human primates and/or in humans, and were reversed in large part by treatment with an antidepressant drug (nortriptyline. Therefore, these results indicate C. jacchus as a potential translational model of juvenile depression by addressing all criteria of validation.

Pharmacologic therapy for acute pancreatitis

Science.gov (United States)

Kambhampati, Swetha; Park, Walter; Habtezion, Aida

2014-01-01

While conservative management such as fluid, bowel rest, and antibiotics is the mainstay of current acute pancreatitis management, there is a lot of promise in pharmacologic therapies that target various aspects of the pathogenesis of pancreatitis. Extensive review of preclinical studies, which include assessment of therapies such as anti-secretory agents, protease inhibitors, anti-inflammatory agents, and anti-oxidants are discussed. Many of these studies have shown therapeutic benefit and improved survival in experimental models. Based on available preclinical studies, we discuss potential novel targeted pharmacologic approaches that may offer promise in the treatment of acute pancreatitis. To date a variety of clinical studies have assessed the translational potential of animal model effective experimental therapies and have shown either failure or mixed results in human studies. Despite these discouraging clinical studies, there is a great clinical need and there exist several preclinical effective therapies that await investigation in patients. Better understanding of acute pancreatitis pathophysiology and lessons learned from past clinical studies are likely to offer a great foundation upon which to expand future therapies in acute pancreatitis. PMID:25493000

Methodologies for Quantitative Systems Pharmacology (QSP) Models: Design and Estimation.

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Ribba, B; Grimm, H P; Agoram, B; Davies, M R; Gadkar, K; Niederer, S; van Riel, N; Timmis, J; van der Graaf, P H

2017-08-01

With the increased interest in the application of quantitative systems pharmacology (QSP) models within medicine research and development, there is an increasing need to formalize model development and verification aspects. In February 2016, a workshop was held at Roche Pharma Research and Early Development to focus discussions on two critical methodological aspects of QSP model development: optimal structural granularity and parameter estimation. We here report in a perspective article a summary of presentations and discussions. © 2017 The Authors CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

A Flexible Statechart-to-Model-Checker Translator

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Rouquette, Nicolas; Dunphy, Julia; Feather, Martin S.

2000-01-01

Many current-day software design tools offer some variant of statechart notation for system specification. We, like others, have built an automatic translator from (a subset of) statecharts to a model checker, for use to validate behavioral requirements. Our translator is designed to be flexible. This allows us to quickly adjust the translator to variants of statechart semantics, including problem-specific notational conventions that designers employ. Our system demonstration will be of interest to the following two communities: (1) Potential end-users: Our demonstration will show translation from statecharts created in a commercial UML tool (Rational Rose) to Promela, the input language of Holzmann's model checker SPIN. The translation is accomplished automatically. To accommodate the major variants of statechart semantics, our tool offers user-selectable choices among semantic alternatives. Options for customized semantic variants are also made available. The net result is an easy-to-use tool that operates on a wide range of statechart diagrams to automate the pathway to model-checking input. (2) Other researchers: Our translator embodies, in one tool, ideas and approaches drawn from several sources. Solutions to the major challenges of statechart-to-model-checker translation (e.g., determining which transition(s) will fire, handling of concurrent activities) are retired in a uniform, fully mechanized, setting. The way in which the underlying architecture of the translator itself facilitates flexible and customizable translation will also be evident.

Harnessing Big Data for Systems Pharmacology.

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Xie, Lei; Draizen, Eli J; Bourne, Philip E

2017-01-06

Systems pharmacology aims to holistically understand mechanisms of drug actions to support drug discovery and clinical practice. Systems pharmacology modeling (SPM) is data driven. It integrates an exponentially growing amount of data at multiple scales (genetic, molecular, cellular, organismal, and environmental). The goal of SPM is to develop mechanistic or predictive multiscale models that are interpretable and actionable. The current explosions in genomics and other omics data, as well as the tremendous advances in big data technologies, have already enabled biologists to generate novel hypotheses and gain new knowledge through computational models of genome-wide, heterogeneous, and dynamic data sets. More work is needed to interpret and predict a drug response phenotype, which is dependent on many known and unknown factors. To gain a comprehensive understanding of drug actions, SPM requires close collaborations between domain experts from diverse fields and integration of heterogeneous models from biophysics, mathematics, statistics, machine learning, and semantic webs. This creates challenges in model management, model integration, model translation, and knowledge integration. In this review, we discuss several emergent issues in SPM and potential solutions using big data technology and analytics. The concurrent development of high-throughput techniques, cloud computing, data science, and the semantic web will likely allow SPM to be findable, accessible, interoperable, reusable, reliable, interpretable, and actionable.

Bilateral Cavernous Nerve Crush Injury in the Rat Model: A Comparative Review of Pharmacologic Interventions.

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Haney, Nora M; Nguyen, Hoang M T; Honda, Matthew; Abdel-Mageed, Asim B; Hellstrom, Wayne J G

2018-04-01

It is common for men to develop erectile dysfunction after radical prostatectomy. The anatomy of the rat allows the cavernous nerve (CN) to be identified, dissected, and injured in a controlled fashion. Therefore, bilateral CN injury (BCNI) in the rat model is routinely used to study post-prostatectomy erectile dysfunction. To compare and contrast the available literature on pharmacologic intervention after BCNI in the rat. A literature search was performed on PubMed for cavernous nerve and injury and erectile dysfunction and rat. Only articles with BCNI and pharmacologic intervention that could be grouped into categories of immune modulation, growth factor therapy, receptor kinase inhibition, phosphodiesterase type 5 inhibition, and anti-inflammatory and antifibrotic interventions were included. To assess outcomes of pharmaceutical intervention on erectile function recovery after BCNI in the rat model. The ratio of maximum intracavernous pressure to mean arterial pressure was the main outcome measure chosen for this analysis. All interventions improved erectile function recovery after BCNI based on the ratio of maximum intracavernous pressure to mean arterial pressure results. Additional end-point analysis examined the corpus cavernosa and/or the major pelvic ganglion and CN. There was extreme heterogeneity within the literature, making accurate comparisons between crush injury and therapeutic interventions difficult. BCNI in the rat is the accepted animal model used to study nerve-sparing post-prostatectomy erectile dysfunction. However, an important limitation is extreme variability. Efforts should be made to decrease this variability and increase the translational utility toward clinical trials in humans. Haney NM, Nguyen HMT, Honda M, et al. Bilateral Cavernous Nerve Crush Injury in the Rat Model: A Comparative Review of Pharmacologic Interventions. Sex Med Rev 2018;6:234-241. Copyright © 2017 International Society for Sexual Medicine. Published by Elsevier

Livestock models in translational medicine.

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Roth, James A; Tuggle, Christopher K

2015-01-01

This issue of the ILAR Journal focuses on livestock models in translational medicine. Livestock models of selected human diseases present important advantages as compared with rodent models for translating fundamental breakthroughs in biology to useful preventatives and therapeutics for humans. Livestock reflect the complexity of applying medical advances in an outbred species. In many cases, the pathogenesis of infectious, metabolic, genetic, and neoplastic diseases in livestock species more closely resembles that in humans than does the pathogenesis of rodent models. Livestock models also provide the advantage of similar organ size and function and the ability to serially sample an animal throughout the study period. Research using livestock models for human disease often benefits not only human health but animal health and food production as well. This issue of the ILAR Journal presents information on translational research using livestock models in two broad areas: microbiology and infectious disease (transmissible spongiform encephalopathies, mycobacterial infections, influenza A virus infection, vaccine development and testing, the human microbiota) and metabolic, neoplastic, and genetic disorders (stem cell therapy, male germ line cell biology, pulmonary adenocarcinoma, muscular dystrophy, wound healing). In addition, there is a manuscript devoted to Institutional Animal Care and Use Committees' responsibilities for reviewing research using livestock models. Conducting translational research using livestock models requires special facilities and researchers with expertise in livestock. There are many institutions in the world with experienced researchers and facilities designed for livestock research; primarily associated with colleges of agriculture and veterinary medicine or government laboratories. © The Author 2015. Published by Oxford University Press on behalf of the Institute for Laboratory Animal Research. All rights reserved. For permissions

Translating building information modeling to building energy modeling using model view definition.

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Jeong, WoonSeong; Kim, Jong Bum; Clayton, Mark J; Haberl, Jeff S; Yan, Wei

2014-01-01

This paper presents a new approach to translate between Building Information Modeling (BIM) and Building Energy Modeling (BEM) that uses Modelica, an object-oriented declarative, equation-based simulation environment. The approach (BIM2BEM) has been developed using a data modeling method to enable seamless model translations of building geometry, materials, and topology. Using data modeling, we created a Model View Definition (MVD) consisting of a process model and a class diagram. The process model demonstrates object-mapping between BIM and Modelica-based BEM (ModelicaBEM) and facilitates the definition of required information during model translations. The class diagram represents the information and object relationships to produce a class package intermediate between the BIM and BEM. The implementation of the intermediate class package enables system interface (Revit2Modelica) development for automatic BIM data translation into ModelicaBEM. In order to demonstrate and validate our approach, simulation result comparisons have been conducted via three test cases using (1) the BIM-based Modelica models generated from Revit2Modelica and (2) BEM models manually created using LBNL Modelica Buildings library. Our implementation shows that BIM2BEM (1) enables BIM models to be translated into ModelicaBEM models, (2) enables system interface development based on the MVD for thermal simulation, and (3) facilitates the reuse of original BIM data into building energy simulation without an import/export process.

Translating Building Information Modeling to Building Energy Modeling Using Model View Definition

Directory of Open Access Journals (Sweden)

WoonSeong Jeong

2014-01-01

Full Text Available This paper presents a new approach to translate between Building Information Modeling (BIM and Building Energy Modeling (BEM that uses Modelica, an object-oriented declarative, equation-based simulation environment. The approach (BIM2BEM has been developed using a data modeling method to enable seamless model translations of building geometry, materials, and topology. Using data modeling, we created a Model View Definition (MVD consisting of a process model and a class diagram. The process model demonstrates object-mapping between BIM and Modelica-based BEM (ModelicaBEM and facilitates the definition of required information during model translations. The class diagram represents the information and object relationships to produce a class package intermediate between the BIM and BEM. The implementation of the intermediate class package enables system interface (Revit2Modelica development for automatic BIM data translation into ModelicaBEM. In order to demonstrate and validate our approach, simulation result comparisons have been conducted via three test cases using (1 the BIM-based Modelica models generated from Revit2Modelica and (2 BEM models manually created using LBNL Modelica Buildings library. Our implementation shows that BIM2BEM (1 enables BIM models to be translated into ModelicaBEM models, (2 enables system interface development based on the MVD for thermal simulation, and (3 facilitates the reuse of original BIM data into building energy simulation without an import/export process.

Pharmacological Effects of Biotin in Animals.

Science.gov (United States)

Riveron-Negrete, Leticia; Fernandez-Mejia, Cristina

2017-01-01

In recent decades, it was found that vitamins affect biological functions in ways other than their long-known functions; niacin is the best example of a water-soluble vitamin known to possess multiple actions. Biotin, also known as vitamin B7 or vitamin H, is a water-soluble B-complex vitamin that serves as a covalently-bound coenzyme of carboxylases. It is now well documented that biotin has actions other than participating in classical enzyme catalysis reactions. Several lines of evidence have demonstrated that pharmacological concentrations of biotin affect glucose and lipid metabolism, hypertension, reproduction, development, and immunity. The effect of biotin on these functions is related to its actions at the transcriptional, translational, and post-translational levels. The bestsupported mechanism involved in the genetic effects of biotin is the soluble guanylate cyclase/protein kinase G (PKG) signaling cascade. Although there are commercially-available products containing pharmacological concentrations of biotin, the toxic effects of biotin have been poorly studied. This review summarizes the known actions and molecular mechanisms of pharmacological doses of biotin in animals and current information regarding biotin toxicity. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Pharmacological profile of brain-derived neurotrophic factor (BDNF) splice variant translation using a novel drug screening assay: a "quantitative code".

Science.gov (United States)

Vaghi, Valentina; Polacchini, Alessio; Baj, Gabriele; Pinheiro, Vera L M; Vicario, Annalisa; Tongiorgi, Enrico

2014-10-03

The neurotrophin brain-derived neurotrophic factor (BDNF) is a key regulator of neuronal development and plasticity. BDNF is a major pharmaceutical target in neurodevelopmental and psychiatric disorders. However, pharmacological modulation of this neurotrophin is challenging because BDNF is generated by multiple, alternatively spliced transcripts with different 5'- and 3'UTRs. Each BDNF mRNA variant is transcribed independently, but translation regulation is unknown. To evaluate the translatability of BDNF transcripts, we developed an in vitro luciferase assay in human neuroblastoma cells. In unstimulated cells, each BDNF 5'- and 3'UTR determined a different basal translation level of the luciferase reporter gene. However, constructs with either a 5'UTR or a 3'UTR alone showed poor translation modulation by BDNF, KCl, dihydroxyphenylglycine, AMPA, NMDA, dopamine, acetylcholine, norepinephrine, or serotonin. Constructs consisting of the luciferase reporter gene flanked by the 5'UTR of one of the most abundant BDNF transcripts in the brain (exons 1, 2c, 4, and 6) and the long 3'UTR responded selectively to stimulation with the different receptor agonists, and only transcripts 2c and 6 were increased by the antidepressants desipramine and mirtazapine. We propose that BDNF mRNA variants represent "a quantitative code" for regulated expression of the protein. Thus, to discriminate the efficacy of drugs in stimulating BDNF synthesis, it is appropriate to use variant-specific in vitro screening tests. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Model of cap-dependent translation initiation in sea urchin: a step towards the eukaryotic translation regulation network.

Science.gov (United States)

Bellé, Robert; Prigent, Sylvain; Siegel, Anne; Cormier, Patrick

2010-03-01

The large and rapid increase in the rate of protein synthesis following fertilization of the sea urchin egg has long been a paradigm of translational control, an important component of the regulation of gene expression in cells. This translational up-regulation is linked to physiological changes that occur upon fertilization and is necessary for entry into first cell division cycle. Accumulated knowledge on cap-dependent initiation of translation makes it suited and timely to start integrating the data into a system view of biological functions. Using a programming environment for system biology coupled with model validation (named Biocham), we have built an integrative model for cap-dependent initiation of translation. The model is described by abstract rules. It contains 51 reactions involved in 74 molecular complexes. The model proved to be coherent with existing knowledge by using queries based on computational tree logic (CTL) as well as Boolean simulations. The model could simulate the change in translation occurring at fertilization in the sea urchin model. It could also be coupled with an existing model designed for cell-cycle control. Therefore, the cap-dependent translation initiation model can be considered a first step towards the eukaryotic translation regulation network.

Getting Innovative Therapies Faster to Patients at the Right Dose: Impact of Quantitative Pharmacology Towards First Registration and Expanding Therapeutic Use.

Science.gov (United States)

Nayak, Satyaprakash; Sander, Oliver; Al-Huniti, Nidal; de Alwis, Dinesh; Chain, Anne; Chenel, Marylore; Sunkaraneni, Soujanya; Agrawal, Shruti; Gupta, Neeraj; Visser, Sandra A G

2018-03-01

Quantitative pharmacology (QP) applications in translational medicine, drug-development, and therapeutic use were crowd-sourced by the ASCPT Impact and Influence initiative. Highlighted QP case studies demonstrated faster access to innovative therapies for patients through 1) rational dose selection for pivotal trials; 2) reduced trial-burden for vulnerable populations; or 3) simplified posology. Critical success factors were proactive stakeholder engagement, alignment on the value of model-informed approaches, and utilizing foundational clinical pharmacology understanding of the therapy. © 2018 The Authors Clinical Pharmacology & Therapeutics published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

Sleep and its disorders in translational medicine.

Science.gov (United States)

Paterson, Louise M; Nutt, David J; Wilson, Sue J

2011-09-01

The study of sleep is a useful approach to studying the brain in psychiatric disorders and in investigating the effects of psychotropic drugs. Sleep physiology lends itself well to pharmacological and physiological manipulation, as it has the advantage of a functional output, the electroencephalograph, which is common to all mammals, and can be measured in freely moving (or naturally sleeping) animals under controlled laboratory conditions or in a naturalistic home environment. The complexity of sleep architecture varies between species but all share features which are comparable. In addition, sleep architecture is sensitive to changes in brain neurotransmitters such as serotonin, so cross-species sleep measurement can be combined with pharmacological manipulation to investigate the receptor mechanisms controlling sleep-wake regulation and sleep architecture in response to known and novel agents. Translational approaches such as these have improved our understanding of sleep circuitry and facilitated the development of new treatments for sleep disorders, particularly insomnia. This review provides examples of how research findings within the sleep field have been translated between animal models, healthy volunteers and patient populations with particular focus on the serotonergic system.

Recent developments in the behavioural and pharmacological enhancement of extinction of drug seeking.

Science.gov (United States)

Chesworth, Rose; Corbit, Laura H

2017-01-01

One of the principal barriers to overcoming addiction is the propensity to relapse, even after months or years of abstinence. Relapse can be precipitated by cues and contexts associated with drug use; thus, decreasing the conditioned properties of these cues and contexts may assist in preventing relapse. The predictive power of drug cues and contexts can be reduced by repeatedly presenting them in the absence of the drug reinforcer, a process known as extinction. The potential of extinction to limit relapse has generated considerable interest and research over the past few decades. While pre-clinical animal models suggest extinction learning assists relapse prevention, treatment efficacy is often lacking when extinction learning principles are translated into clinical trials. Conklin and Tiffany (Addiction, 2002) suggest the lack of efficacy in clinical practice may be due to limited translation of procedures demonstrated through animal research and propose several methodological improvements to enhance extinction learning for drug addiction. This review will examine recent advances in the behavioural and pharmacological manipulation of extinction learning, based on research from pre-clinical models. In addition, the translation of pre-clinical findings-both those suggested by Conklin and Tiffany () and novel demonstrations from the past 13 years-into clinical trials and the efficacy of these methods in reducing craving and relapse, where available, will be discussed. Finally, we highlight areas where promising pre-clinical models have not yet been integrated into current clinical practice but, if applied, could improve upon existing behavioural and pharmacological methods. © 2015 Society for the Study of Addiction.

Reverse and Forward Translational Neuropharmacology in Psychiatric Drug Discovery.

Science.gov (United States)

Shaffer, Christopher L

2018-02-01

The probability of achieving marketing approval of a novel therapeutic for psychiatric indications is extremely low due largely to the inability to demonstrate durable and reproducible efficacy in phase II trials and beyond. These failures are often attributed to the lack of translation of the underlying neuropharmacology from animal model(s) to the disease population. However, how assured is such a conclusion considering the clinical efficacy path rarely meticulously parallels the preclinical experiment(s) that underwrote it? © 2017 American Society for Clinical Pharmacology and Therapeutics.

MODEL OF TEACHING PROFESSION SPECIFIC BILATERAL TRANSLATION

Directory of Open Access Journals (Sweden)

Yana Fabrychna

2017-03-01

Full Text Available The article deals with the author’s interpretation of the process of teaching profession specific bilateral translation to student teacher of English in the Master’s program. The goal of the model of teaching profession specific bilateral translation development is to determine the logical sequence of educational activities of the teacher as the organizer of the educational process and students as its members. English and Ukrainian texts on methods of foreign languages and cultures teaching are defined as the object of study. Learning activities aimed at the development of student teachers of English profession specific competence in bilateral translation and Translation Proficiency Language Portfolio for Student Teachers of English are suggested as teaching tools. The realization of the model of teaching profession specific bilateral translation to student teachers of English in the Master’s program is suggested within the module topics of the academic discipline «Practice of English as the first foreign language»: Globalization; Localization; Education; Work; The role of new communication technologies in personal and professional development. We believe that the amount of time needed for efficient functioning of the model is 48 academic hours, which was determined by calculating the total number of academic hours allotted for the academic discipline «Practice of English as the first foreign language» in Ukrainian universities. Peculiarities of the model realization as well as learning goals and content of class activities and home self-study work of students are outlined.

Amphetamine, past and present--a pharmacological and clinical perspective.

Science.gov (United States)

Heal, David J; Smith, Sharon L; Gosden, Jane; Nutt, David J

2013-06-01

Amphetamine was discovered over 100 years ago. Since then, it has transformed from a drug that was freely available without prescription as a panacea for a broad range of disorders into a highly restricted Controlled Drug with therapeutic applications restricted to attention deficit hyperactivity disorder (ADHD) and narcolepsy. This review describes the relationship between chemical structure and pharmacology of amphetamine and its congeners. Amphetamine's diverse pharmacological actions translate not only into therapeutic efficacy, but also into the production of adverse events and liability for recreational abuse. Accordingly, the balance of benefit/risk is the key challenge for its clinical use. The review charts advances in pharmaceutical development from the introduction of once-daily formulations of amphetamine through to lisdexamfetamine, which is the first d-amphetamine prodrug approved for the management of ADHD in children, adolescents and adults. The unusual metabolic route for lisdexamfetamine to deliver d-amphetamine makes an important contribution to its pharmacology. How lisdexamfetamine's distinctive pharmacokinetic/pharmacodynamic profile translates into sustained efficacy as a treatment for ADHD and its reduced potential for recreational abuse is also discussed.

From Translational Research to Translational Effectiveness: The “Patient-Centered Dental Home” Model

Directory of Open Access Journals (Sweden)

Francesco Chiappelli

2011-06-01

Full Text Available Toward revitalizing the Nation’s primary medical care system, the Agency for Health Research & Quality (AHRQ stated that new foundational measures must be crafted for achieving high-quality, accessible, efficient health care for all Americans. The efficiency of medical care is viewed along two dimensions: first, we must continue to pursue translational research; and second, we must translate research to optimize effectiveness in specific clinical settings. It is increasingly evident that the efficiency of both translational processes is critical to the revitalization of health care, and that it rests on the practical functionality of the nexus among three cardinal entities: the researcher, the clinician, and the patient. A novel model has evolved that encapsulates this notion, and that proposes the advanced pri-mary care “medical home”, more commonly referred to as the “patient-centered medical home” (PCMH. It is a promising model for transforming the organization and delivery of primary medical care, because it is not simply a place per se, but it is a function-ing unit that delivers medical care along the fundamental principles of being patient-centered, comprehensive, coordinated, and accessible. It is energized by translational research, and its principal aim and ultimate goal is translational effectiveness. The PCMH is a model that works well within the priorities set by the American Recovery and Reinvestment Act of 2009, and the Health Care Reform Act of 2010. However, while dentistry has a clearly defined place in both Acts, the PCMH is designed for medical and nursing care. A parallel model of the “patient-centered dental home” (PCDH must be realized.

Pharmacological characterisation of murine α4β1δ GABAA receptors expressed in Xenopus oocytes

DEFF Research Database (Denmark)

Villumsen, Inge S; Wellendorph, Petrine; Smart, Trevor G

2015-01-01

BACKGROUND: GABAA receptor subunit composition has a profound effect on the receptor's physiological and pharmacological properties. The receptor β subunit is widely recognised for its importance in receptor assembly, trafficking and post-translational modifications, but its influence on extrasyn......BACKGROUND: GABAA receptor subunit composition has a profound effect on the receptor's physiological and pharmacological properties. The receptor β subunit is widely recognised for its importance in receptor assembly, trafficking and post-translational modifications, but its influence...

Modeling and prediction of human word search behavior in interactive machine translation

Science.gov (United States)

Ji, Duo; Yu, Bai; Ma, Bin; Ye, Na

2017-12-01

As a kind of computer aided translation method, Interactive Machine Translation technology reduced manual translation repetitive and mechanical operation through a variety of methods, so as to get the translation efficiency, and played an important role in the practical application of the translation work. In this paper, we regarded the behavior of users' frequently searching for words in the translation process as the research object, and transformed the behavior to the translation selection problem under the current translation. The paper presented a prediction model, which is a comprehensive utilization of alignment model, translation model and language model of the searching words behavior. It achieved a highly accurate prediction of searching words behavior, and reduced the switching of mouse and keyboard operations in the users' translation process.

The pharmacology of neurokinin receptors in addiction: prospects for therapy

Directory of Open Access Journals (Sweden)

Sandweiss AJ

2015-09-01

Full Text Available Alexander J Sandweiss, Todd W VanderahDepartment of Pharmacology, College of Medicine, University of Arizona, Tucson, AZ, USAAbstract: Addiction is a chronic disorder in which consumption of a substance or a habitual behavior becomes compulsive and often recurrent, despite adverse consequences. Substance p (SP is an undecapeptide and was the first neuropeptide of the neurokinin family to be discovered. The subsequent decades of research after its discovery implicated SP and its neurokinin relatives as neurotransmitters involved in the modulation of the reward pathway. Here, we review the neurokinin literature, giving a brief historical perspective of neurokinin pharmacology, localization in various brain regions involved in addictive behaviors, and the functional aspects of neurokinin pharmacology in relation to reward in preclinical models of addiction that have shaped the rational drug design of neurokinin antagonists that could translate into human research. Finally, we will cover the clinical investigations using neurokinin antagonists and discuss their potential as a therapy for drug abuse.Keywords: reward, substance p, alcohol, morphine, cocaine, dopamine

Latent domain models for statistical machine translation

NARCIS (Netherlands)

Hoàng, C.

2017-01-01

A data-driven approach to model translation suffers from the data mismatch problem and demands domain adaptation techniques. Given parallel training data originating from a specific domain, training an MT system on the data would result in a rather suboptimal translation for other domains. But does

A cognitive-pragmatic model for translation-shift analysis in ...

African Journals Online (AJOL)

A cognitive-pragmatic model for translation-shift analysis in descriptive case ... This model responds to the tendency of descriptive studies to analyse all translation shifts under the same rubric of neutrality. ... AJOL African Journals Online.

National Science and Technology Institute for Translational Medicine (INCT-TM): advancing the field of translational medicine and mental health.

Science.gov (United States)

Hallak, Jaime E C; Crippa, José Alexandre S; Quevedo, João; Roesler, Rafael; Schröder, Nadja; Nardi, Antonio Egidio; Kapczinski, Flávio

2010-03-01

Translational medicine has been described as the integrated application of innovative pharmacology tools, biomarkers, clinical methods, clinical technologies and study designs to improve the understanding of medical disorders. In medicine, translational research offers an opportunity for applying the findings obtained from basic research to every-day clinical applications. The National Science and Technology Institute for Translational Medicine is comprised of six member institutions (Universidade Federal do Rio Grande do Sul, Universidade de São Paulo-Ribeirão Preto, Universidade Federal do Rio de Janeiro, Pontifícia Universidade Católica do Rio Grande do Sul, Universidade Estadual de Santa Catarina and a core facility that serves all centers). The objectives of the project are divided into four areas: Institutional, Research, Human Resources and Technology for the Community and Productive Sector. In this manuscript, we describe some of the approaches used to attain the main objectives of the National Science and Technology Institute for Translational Medicine, which include the development of 1) animal models for bipolar disorder; 2) strategies to investigate neurobehavioral function and cognitive dysfunction associated with brain disorders; 3) experimental models of brain function and behavior, neuropsychiatric disorders, cell proliferation, and cancer; 4) Simulated Public Speaking and 5) Virtual reality simulation for inducing panic disorder and agoraphobia. The main focus of the National Science and Technology Institute for Translational Medicine is the development of more useful methods that allow for a better application of basic research-based knowledge to the medical field.

Evaluating Translational Research: A Process Marker Model

Science.gov (United States)

Trochim, William; Kane, Cathleen; Graham, Mark J.; Pincus, Harold A.

2011-01-01

Abstract Objective: We examine the concept of translational research from the perspective of evaluators charged with assessing translational efforts. One of the major tasks for evaluators involved in translational research is to help assess efforts that aim to reduce the time it takes to move research to practice and health impacts. Another is to assess efforts that are intended to increase the rate and volume of translation. Methods: We offer an alternative to the dominant contemporary tendency to define translational research in terms of a series of discrete “phases.”Results: We contend that this phased approach has been confusing and that it is insufficient as a basis for evaluation. Instead, we argue for the identification of key operational and measurable markers along a generalized process pathway from research to practice. Conclusions: This model provides a foundation for the evaluation of interventions designed to improve translational research and the integration of these findings into a field of translational studies. Clin Trans Sci 2011; Volume 4: 153–162 PMID:21707944

Amphetamine, past and present – a pharmacological and clinical perspective

Science.gov (United States)

Smith, Sharon L; Gosden, Jane; Nutt, David J

2013-01-01

Amphetamine was discovered over 100 years ago. Since then, it has transformed from a drug that was freely available without prescription as a panacea for a broad range of disorders into a highly restricted Controlled Drug with therapeutic applications restricted to attention deficit hyperactivity disorder (ADHD) and narcolepsy. This review describes the relationship between chemical structure and pharmacology of amphetamine and its congeners. Amphetamine’s diverse pharmacological actions translate not only into therapeutic efficacy, but also into the production of adverse events and liability for recreational abuse. Accordingly, the balance of benefit/risk is the key challenge for its clinical use. The review charts advances in pharmaceutical development from the introduction of once-daily formulations of amphetamine through to lisdexamfetamine, which is the first d-amphetamine prodrug approved for the management of ADHD in children, adolescents and adults. The unusual metabolic route for lisdexamfetamine to deliver d-amphetamine makes an important contribution to its pharmacology. How lisdexamfetamine’s distinctive pharmacokinetic/pharmacodynamic profile translates into sustained efficacy as a treatment for ADHD and its reduced potential for recreational abuse is also discussed. PMID:23539642

Translating Alcohol Research

Science.gov (United States)

Batman, Angela M.; Miles, Michael F.

2015-01-01

Alcohol use disorder (AUD) and its sequelae impose a major burden on the public health of the United States, and adequate long-term control of this disorder has not been achieved. Molecular and behavioral basic science research findings are providing the groundwork for understanding the mechanisms underlying AUD and have identified multiple candidate targets for ongoing clinical trials. However, the translation of basic research or clinical findings into improved therapeutic approaches for AUD must become more efficient. Translational research is a multistage process of streamlining the movement of basic biomedical research findings into clinical research and then to the clinical target populations. This process demands efficient bidirectional communication across basic, applied, and clinical science as well as with clinical practitioners. Ongoing work suggests rapid progress is being made with an evolving translational framework within the alcohol research field. This is helped by multiple interdisciplinary collaborative research structures that have been developed to advance translational work on AUD. Moreover, the integration of systems biology approaches with collaborative clinical studies may yield novel insights for future translational success. Finally, appreciation of genetic variation in pharmacological or behavioral treatment responses and optimal communication from bench to bedside and back may strengthen the success of translational research applications to AUD. PMID:26259085

Translational neuropharmacology and the appropriate and effective use of animal models.

Science.gov (United States)

Green, A R; Gabrielsson, J; Fone, K C F

2011-10-01

This issue of the British Journal of Pharmacology is dedicated to reviews of the major animal models used in neuropharmacology to examine drugs for both neurological and psychiatric conditions. Almost all major conditions are reviewed. In general, regulatory authorities require evidence for the efficacy of novel compounds in appropriate animal models. However, the failure of many compounds in clinical trials following clear demonstration of efficacy in animal models has called into question both the value of the models and the discovery process in general. These matters are expertly reviewed in this issue and proposals for better models outlined. In this editorial, we further suggest that more attention be made to incorporate pharmacokinetic knowledge into the studies (quantitative pharmacology). We also suggest that more attention be made to ensure that full methodological details are published and recommend that journals should be more amenable to publishing negative data. Finally, we propose that new approaches must be used in drug discovery so that preclinical studies become more reflective of the clinical situation, and studies using animal models mimic the anticipated design of studies to be performed in humans, as closely as possible. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

Create a translational medicine knowledge repository--research downsizing, mergers and increased outsourcing have reduced the depth of in-house translational medicine expertise and institutional memory at many pharmaceutical and biotech companies: how will they avoid relearning old lessons?

Science.gov (United States)

Littman, Bruce H; Marincola, Francesco M

2011-05-10

Pharmaceutical industry consolidation and overall research downsizing threatens the ability of companies to benefit from their previous investments in translational research as key leaders with the most knowledge of the successful use of biomarkers and translational pharmacology models are laid off or accept their severance packages. Two recently published books may help to preserve this type of knowledge but much of this type of information is not in the public domain. Here we propose the creation of a translational medicine knowledge repository where companies can submit their translational research data and access similar data from other companies in a precompetitive environment. This searchable repository would become an invaluable resource for translational scientists and drug developers that could speed and reduce the cost of new drug development.

Systems pharmacology - Towards the modeling of network interactions.

Science.gov (United States)

Danhof, Meindert

2016-10-30

Mechanism-based pharmacokinetic and pharmacodynamics (PKPD) and disease system (DS) models have been introduced in drug discovery and development research, to predict in a quantitative manner the effect of drug treatment in vivo in health and disease. This requires consideration of several fundamental properties of biological systems behavior including: hysteresis, non-linearity, variability, interdependency, convergence, resilience, and multi-stationarity. Classical physiology-based PKPD models consider linear transduction pathways, connecting processes on the causal path between drug administration and effect, as the basis of drug action. Depending on the drug and its biological target, such models may contain expressions to characterize i) the disposition and the target site distribution kinetics of the drug under investigation, ii) the kinetics of target binding and activation and iii) the kinetics of transduction. When connected to physiology-based DS models, PKPD models can characterize the effect on disease progression in a mechanistic manner. These models have been found useful to characterize hysteresis and non-linearity, yet they fail to explain the effects of the other fundamental properties of biological systems behavior. Recently systems pharmacology has been introduced as novel approach to predict in vivo drug effects, in which biological networks rather than single transduction pathways are considered as the basis of drug action and disease progression. These models contain expressions to characterize the functional interactions within a biological network. Such interactions are relevant when drugs act at multiple targets in the network or when homeostatic feedback mechanisms are operative. As a result systems pharmacology models are particularly useful to describe complex patterns of drug action (i.e. synergy, oscillatory behavior) and disease progression (i.e. episodic disorders). In this contribution it is shown how physiology-based PKPD and

Methodologies for quantitative systems pharmacology (QSP) models : Design and Estimation

NARCIS (Netherlands)

Ribba, B.; Grimm, Hp; Agoram, B.; Davies, M.R.; Gadkar, K.; Niederer, S.; van Riel, N.; Timmis, J.; van der Graaf, Ph.

2017-01-01

With the increased interest in the application of quantitative systems pharmacology (QSP) models within medicine research and development, there is an increasing need to formalize model development and verification aspects. In February 2016, a workshop was held at Roche Pharma Research and Early

Methodologies for Quantitative Systems Pharmacology (QSP) Models: Design and Estimation

NARCIS (Netherlands)

Ribba, B.; Grimm, H. P.; Agoram, B.; Davies, M. R.; Gadkar, K.; Niederer, S.; van Riel, N.; Timmis, J.; van der Graaf, P. H.

2017-01-01

With the increased interest in the application of quantitative systems pharmacology (QSP) models within medicine research and development, there is an increasing need to formalize model development and verification aspects. In February 2016, a workshop was held at Roche Pharma Research and Early

Dysregulated Translational Control: From Brain Disorders to Psychoactive Drugs

Directory of Open Access Journals (Sweden)

Emanuela eSantini

2011-11-01

Full Text Available In the last decade, a plethora of studies utilizing pharmacological, biochemical, and genetic approaches have shown that precise translational control is required for long-lasting synaptic plasticity and the formation of long-term memory. Moreover, more recent studies indicate that alterations in translational control are a common pathophysiological feature of human neurological disorders, including developmental disorders, neuropsychiatric disorders, and neurodegenerative diseases. Finally, translational control mechanisms are susceptible to modification by psychoactive drugs. Taken together, these findings point to a central role for translational control in the regulation of synaptic function and behavior.

Advancing tuberculosis drug regimen development through innovative quantitative translational pharmacology methods and approaches.

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Hanna, Debra; Romero, Klaus; Schito, Marco

2017-03-01

The development of novel tuberculosis (TB) multi-drug regimens that are more efficacious and of shorter duration requires a robust drug development pipeline. Advances in quantitative modeling and simulation can be used to maximize the utility of patient-level data from prior and contemporary clinical trials, thus optimizing study design for anti-TB regimens. This perspective article highlights the work of seven project teams developing first-in-class translational and quantitative methodologies that aim to inform drug development decision-making, dose selection, trial design, and safety assessments, in order to achieve shorter and safer therapies for patients in need. These tools offer the opportunity to evaluate multiple hypotheses and provide a means to identify, quantify, and understand relevant sources of variability, to optimize translation and clinical trial design. When incorporated into the broader regulatory sciences framework, these efforts have the potential to transform the development paradigm for TB combination development, as well as other areas of global health. Copyright © 2016. Published by Elsevier Ltd.

Topical Review: Translating Translational Research in Behavioral Science.

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Hommel, Kevin A; Modi, Avani C; Piazza-Waggoner, Carrie; Myers, James D

2015-01-01

To present a model of translational research for behavioral science that communicates the role of behavioral research at each phase of translation. A task force identified gaps in knowledge regarding behavioral translational research processes and made recommendations regarding advancement of knowledge. A comprehensive model of translational behavioral research was developed. This model represents T1, T2, and T3 research activities, as well as Phase 1, 2, 3, and 4 clinical trials. Clinical illustrations of translational processes are also offered as support for the model. Behavioral science has struggled with defining a translational research model that effectively articulates each stage of translation and complements biomedical research. Our model defines key activities at each phase of translation from basic discovery to dissemination/implementation. This should be a starting point for communicating the role of behavioral science in translational research and a catalyst for better integration of biomedical and behavioral research. © The Author 2015. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Drug repurposing: translational pharmacology, chemistry, computers and the clinic.

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Issa, Naiem T; Byers, Stephen W; Dakshanamurthy, Sivanesan

2013-01-01

The process of discovering a pharmacological compound that elicits a desired clinical effect with minimal side effects is a challenge. Prior to the advent of high-performance computing and large-scale screening technologies, drug discovery was largely a serendipitous endeavor, as in the case of thalidomide for erythema nodosum leprosum or cancer drugs in general derived from flora located in far-reaching geographic locations. More recently, de novo drug discovery has become a more rationalized process where drug-target-effect hypotheses are formulated on the basis of already known compounds/protein targets and their structures. Although this approach is hypothesis-driven, the actual success has been very low, contributing to the soaring costs of research and development as well as the diminished pharmaceutical pipeline in the United States. In this review, we discuss the evolution in computational pharmacology as the next generation of successful drug discovery and implementation in the clinic where high-performance computing (HPC) is used to generate and validate drug-target-effect hypotheses completely in silico. The use of HPC would decrease development time and errors while increasing productivity prior to in vitro, animal and human testing. We highlight approaches in chemoinformatics, bioinformatics as well as network biopharmacology to illustrate potential avenues from which to design clinically efficacious drugs. We further discuss the implications of combining these approaches into an integrative methodology for high-accuracy computational predictions within the context of drug repositioning for the efficient streamlining of currently approved drugs back into clinical trials for possible new indications.

Create a translational medicine knowledge repository - Research downsizing, mergers and increased outsourcing have reduced the depth of in-house translational medicine expertise and institutional memory at many pharmaceutical and biotech companies: how will they avoid relearning old lessons?

Directory of Open Access Journals (Sweden)

Marincola Francesco M

2011-05-01

Full Text Available Abstract Pharmaceutical industry consolidation and overall research downsizing threatens the ability of companies to benefit from their previous investments in translational research as key leaders with the most knowledge of the successful use of biomarkers and translational pharmacology models are laid off or accept their severance packages. Two recently published books may help to preserve this type of knowledge but much of this type of information is not in the public domain. Here we propose the creation of a translational medicine knowledge repository where companies can submit their translational research data and access similar data from other companies in a precompetitive environment. This searchable repository would become an invaluable resource for translational scientists and drug developers that could speed and reduce the cost of new drug development.

Label-free integrative pharmacology on-target of drugs at the β2-adrenergic receptor

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Ferrie, Ann M.; Sun, Haiyan; Fang, Ye

2011-07-01

We describe a label-free integrative pharmacology on-target (iPOT) method to assess the pharmacology of drugs at the β2-adrenergic receptor. This method combines dynamic mass redistribution (DMR) assays using an array of probe molecule-hijacked cells with similarity analysis. The whole cell DMR assays track cell system-based, ligand-directed, and kinetics-dependent biased activities of the drugs, and translates their on-target pharmacology into numerical descriptors which are subject to similarity analysis. We demonstrate that the approach establishes an effective link between the label-free pharmacology and in vivo therapeutic indications of drugs.

Nursing students learning the pharmacology of diabetes mellitus with complexity-based computerized models: A quasi-experimental study.

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Dubovi, Ilana; Dagan, Efrat; Sader Mazbar, Ola; Nassar, Laila; Levy, Sharona T

2018-02-01

Pharmacology is a crucial component of medications administration in nursing, yet nursing students generally find it difficult and self-rate their pharmacology skills as low. To evaluate nursing students learning pharmacology with the Pharmacology Inter-Leaved Learning-Cells environment, a novel approach to modeling biochemical interactions using a multiscale, computer-based model with a complexity perspective based on a small set of entities and simple rules. This environment represents molecules, organelles and cells to enhance the understanding of cellular processes, and combines these cells at a higher scale to obtain whole-body interactions. Sophomore nursing students who learned the pharmacology of diabetes mellitus with the Pharmacology Inter-Leaved Learning-Cells environment (experimental group; n=94) or via a lecture-based curriculum (comparison group; n=54). A quasi-experimental pre- and post-test design was conducted. The Pharmacology-Diabetes-Mellitus questionnaire and the course's final exam were used to evaluate students' knowledge of the pharmacology of diabetes mellitus. Conceptual learning was significantly higher for the experimental than for the comparison group for the course final exam scores (unpaired t=-3.8, pLearning with complexity-based computerized models is highly effective and enhances the understanding of moving between micro and macro levels of the biochemical phenomena, this is then related to better understanding of medication actions. Moreover, the Pharmacology Inter-Leaved Learning-Cells approach provides a more general reasoning scheme for biochemical processes, which enhances pharmacology learning beyond the specific topic learned. The present study implies that deeper understanding of pharmacology will support nursing students' clinical decisions and empower their proficiency in medications administration. Copyright © 2017 Elsevier Ltd. All rights reserved.

Sketch of a Noisy Channel Model for the Translation Process

DEFF Research Database (Denmark)

Carl, Michael

default rendering" procedure, later conscious processes are triggered by a monitor who interferes when something goes wrong. An attempt is made to explain monitor activities with relevance theoretic concepts according to which a translator needs to ensure the similarity of explicatures and implicatures......The paper develops a Noisy Channel Model for the translation process that is based on actual user activity data. It builds on the monitor model and makes a distinction between early, automatic and late, conscious translation processes: while early priming processes are at the basis of a "literal...... of the source and the target texts. It is suggested that events and parameters in the model need be measurable and quantifiable in the user activity data so as to trace back monitoring activities in the translation process data. Michael Carl is a Professor with special responsibilities at the Department...

Non-clinical models: validation, study design and statistical consideration in safety pharmacology.

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Pugsley, M K; Towart, R; Authier, S; Gallacher, D J; Curtis, M J

2010-01-01

The current issue of the Journal of Pharmacological and Toxicological Methods (JPTM) focuses exclusively on safety pharmacology methods. This is the 7th year the Journal has published on this topic. Methods and models that specifically relate to methods relating to the assessment of the safety profile of a new chemical entity (NCE) prior to first in human (FIH) studies are described. Since the Journal started publishing on this topic there has been a major effort by safety pharmacologists, toxicologists and regulatory scientists within Industry (both large and small Pharma as well as Biotechnology companies) and also from Contract Research Organizations (CRO) to publish the surgical details of the non-clinical methods utilized but also provide important details related to standard and non-standard (or integrated) study models and designs. These details from core battery and secondary (or ancillary) drug safety assessment methods used in drug development programs have been the focus of these special issues and have been an attempt to provide validation of methods. Similarly, the safety pharmacology issues of the Journal provide the most relevant forum for scientists to present novel and modified methods with direct applicability to determination of drug safety-directly to the safety pharmacology scientific community. The content of the manuscripts in this issue includes the introduction of additional important surgical methods, novel data capture and data analysis methods, improved study design and effects of positive control compounds with known activity in the model. Copyright 2010 Elsevier Inc. All rights reserved.

From theoretical model to practical use: an example of knowledge translation.

Science.gov (United States)

Bjørk, Ida Torunn; Lomborg, Kirsten; Nielsen, Carsten Munch; Brynildsen, Grethe; Frederiksen, Anne-Marie Skovsgaard; Larsen, Karin; Reierson, Inger Åse; Sommer, Irene; Stenholt, Britta

2013-10-01

To present a case of knowledge translation in nursing education and practice and discusses mechanisms relevant to bringing knowledge into action. The process of knowledge translation aspires to close the gap between theory and practice. Knowledge translation is a cyclic process involving both the creation and application of knowledge in several phases. The case presented in this paper is the translation of the Model of Practical Skill Performance into education and practice. Advantages and problems with the use of this model and its adaptation and tailoring to local contexts illustrate the cyclic and iterative process of knowledge translation. The cultivation of a three-sided relationship between researchers, educators, and clinical nurses was a major asset in driving the process of knowledge translation. The knowledge translation process gained momentum by replacing passive diffusion strategies with interaction and teamwork between stakeholders. The use of knowledge creates feedback that might have consequences for the refinement and tailoring of that same knowledge itself. With end-users in mind, several heuristics were used by the research group to increase clarity of the model and to tailor the implementation of knowledge to the users. This article illustrates the need for enduring collaboration between stakeholders to promote the process of knowledge translation. Translation of research knowledge into practice is a time-consuming process that is enhanced when appropriate support is given by leaders in the involved facilities. Knowledge translation is a time-consuming and collaborative endeavour. On the basis of our experience we advocate the implementation and use of a conceptual framework for the entire process of knowledge translation. More descriptions of knowledge translation in the nursing discipline are needed to inspire and advise in this process. © 2013 Blackwell Publishing Ltd.

Targeting poly(ADP-ribose)polymerase1 in neurological diseases: A promising trove for new pharmacological interventions to enter clinical translation.

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Sriram, Chandra Shekhar; Jangra, Ashok; Kasala, Eshvendar Reddy; Bodduluru, Lakshmi Narendra; Bezbaruah, Babul Kumar

2014-10-01

The highly conserved abundant nuclear protein poly(ADP-ribose)polymerase1 (PARP1) functions at the center of cellular stress response and is mainly implied in DNA damage repair mechanism. Apart from its involvement in DNA damage repair, it does sway multiple vital cellular processes such as cell death pathways, cell aging, insulator function, chromatin modification, transcription and mitotic apparatus function. Since brain is the principal organ vulnerable to oxidative stress and inflammatory responses, upon stress encounters robust DNA damage can occur and intense PARP1 activation may result that will lead to various CNS diseases. In the context of soaring interest towards PARP1 as a therapeutic target for newer pharmacological interventions, here in the present review, we are attempting to give a silhouette of the role of PARP1 in the neurological diseases and the potential of its inhibitors to enter clinical translation, along with its structural and functional aspects. Copyright © 2014 Elsevier Ltd. All rights reserved.

Proposal for a telehealth concept in the translational research model.

Science.gov (United States)

Silva, Angélica Baptista; Morel, Carlos Médicis; Moraes, Ilara Hämmerli Sozzi de

2014-04-01

To review the conceptual relationship between telehealth and translational research. Bibliographical search on telehealth was conducted in the Scopus, Cochrane BVS, LILACS and MEDLINE databases to find experiences of telehealth in conjunction with discussion of translational research in health. The search retrieved eight studies based on analysis of models of the five stages of translational research and the multiple strands of public health policy in the context of telehealth in Brazil. The models were applied to telehealth activities concerning the Network of Human Milk Banks, in the Telemedicine University Network. The translational research cycle of human milk collected, stored and distributed presents several integrated telehealth initiatives, such as video conferencing, and software and portals for synthesizing knowledge, composing elements of an information ecosystem, mediated by information and communication technologies in the health system. Telehealth should be composed of a set of activities in a computer mediated network promoting the translation of knowledge between research and health services.

Efficient Embedded Decoding of Neural Network Language Models in a Machine Translation System.

Science.gov (United States)

Zamora-Martinez, Francisco; Castro-Bleda, Maria Jose

2018-02-22

Neural Network Language Models (NNLMs) are a successful approach to Natural Language Processing tasks, such as Machine Translation. We introduce in this work a Statistical Machine Translation (SMT) system which fully integrates NNLMs in the decoding stage, breaking the traditional approach based on [Formula: see text]-best list rescoring. The neural net models (both language models (LMs) and translation models) are fully coupled in the decoding stage, allowing to more strongly influence the translation quality. Computational issues were solved by using a novel idea based on memorization and smoothing of the softmax constants to avoid their computation, which introduces a trade-off between LM quality and computational cost. These ideas were studied in a machine translation task with different combinations of neural networks used both as translation models and as target LMs, comparing phrase-based and [Formula: see text]-gram-based systems, showing that the integrated approach seems more promising for [Formula: see text]-gram-based systems, even with nonfull-quality NNLMs.

Scopolamine provocation-based pharmacological MRI model for testing procognitive agents.

Science.gov (United States)

Hegedűs, Nikolett; Laszy, Judit; Gyertyán, István; Kocsis, Pál; Gajári, Dávid; Dávid, Szabolcs; Deli, Levente; Pozsgay, Zsófia; Tihanyi, Károly

2015-04-01

There is a huge unmet need to understand and treat pathological cognitive impairment. The development of disease modifying cognitive enhancers is hindered by the lack of correct pathomechanism and suitable animal models. Most animal models to study cognition and pathology do not fulfil either the predictive validity, face validity or construct validity criteria, and also outcome measures greatly differ from those of human trials. Fortunately, some pharmacological agents such as scopolamine evoke similar effects on cognition and cerebral circulation in rodents and humans and functional MRI enables us to compare cognitive agents directly in different species. In this paper we report the validation of a scopolamine based rodent pharmacological MRI provocation model. The effects of deemed procognitive agents (donepezil, vinpocetine, piracetam, alpha 7 selective cholinergic compounds EVP-6124, PNU-120596) were compared on the blood-oxygen-level dependent responses and also linked to rodent cognitive models. These drugs revealed significant effect on scopolamine induced blood-oxygen-level dependent change except for piracetam. In the water labyrinth test only PNU-120596 did not show a significant effect. This provocational model is suitable for testing procognitive compounds. These functional MR imaging experiments can be paralleled with human studies, which may help reduce the number of false cognitive clinical trials. © The Author(s) 2015.

Translation of a High-Level Temporal Model into Lower Level Models: Impact of Modelling at Different Description Levels

DEFF Research Database (Denmark)

Kraft, Peter; Sørensen, Jens Otto

2001-01-01

given types of properties, and examine how descriptions on higher levels translate into descriptions on lower levels. Our example looks at temporal properties where the information is concerned with the existence in time. In a high level temporal model with information kept in a three-dimensional space...... the existences in time can be mapped precisely and consistently securing a consistent handling of the temporal properties. We translate the high level temporal model into an entity-relationship model, with the information in a two-dimensional graph, and finally we look at the translations into relational...... and other textual models. We also consider the aptness of models that include procedural mechanisms such as active and object databases...

Exploration of Disease Markers under Translational Medicine Model

Directory of Open Access Journals (Sweden)

Rajagopal Krishnamoorthy

2015-06-01

Full Text Available Disease markers are defined as the biomarkers with specific characteristics during the general physical, pathological or therapeutic process, the detection of which can inform the progression of present biological process of organisms. However, the exploration of disease markers is complicated and difficult, and only a few markers can be used in clinical practice and there is no significant difference in the mortality of cancers before and after biomarker exploration. Translational medicine focuses on breaking the blockage between basic medicine and clinical practice. In addition, it also establishes an effective association between researchers engaged on basic scientific discovery and clinical physicians well informed of patients' requirements, and gives particular attentions on how to translate the basic molecular biological research to the most effective and appropriate methods for the diagnosis, treatment and prevention of diseases, hoping to translate basic research into the new therapeutic methods in clinic. Therefore, this study mainly summarized the exploration of disease markers under translational medicine model so as to provide a basis for the translation of basic research results into clinical application.

NADPH–Cytochrome P450 Oxidoreductase: Roles in Physiology, Pharmacology, and Toxicology

Science.gov (United States)

Ding, Xinxin; Wolf, C. Roland; Porter, Todd D.; Pandey, Amit V.; Zhang, Qing-Yu; Gu, Jun; Finn, Robert D.; Ronseaux, Sebastien; McLaughlin, Lesley A.; Henderson, Colin J.; Zou, Ling; Flück, Christa E.

2013-01-01

This is a report on a symposium sponsored by the American Society for Pharmacology and Experimental Therapeutics and held at the Experimental Biology 2012 meeting in San Diego, California, on April 25, 2012. The symposium speakers summarized and critically evaluated our current understanding of the physiologic, pharmacological, and toxicological roles of NADPH–cytochrome P450 oxidoreductase (POR), a flavoprotein involved in electron transfer to microsomal cytochromes P450 (P450), cytochrome b5, squalene mono-oxygenase, and heme oxygenase. Considerable insight has been derived from the development and characterization of mouse models with conditional Por deletion in particular tissues or partial suppression of POR expression in all tissues. Additional mouse models with global or conditional hepatic deletion of cytochrome b5 are helping to clarify the P450 isoform- and substrate-specific influences of cytochrome b5 on P450 electron transfer and catalytic function. This symposium also considered studies using siRNA to suppress POR expression in a hepatoma cell–culture model to explore the basis of the hepatic lipidosis phenotype observed in mice with conditional deletion of Por in liver. The symposium concluded with a strong translational perspective, relating the basic science of human POR structure and function to the impacts of POR genetic variation on human drug and steroid metabolism. PMID:23086197

Stem cell therapy for cardiovascular disease: the demise of alchemy and rise of pharmacology.

Science.gov (United States)

Jadczyk, T; Faulkner, A; Madeddu, P

2013-05-01

Regenerative medicine holds great promise as a way of addressing the limitations of current treatments of ischaemic disease. In preclinical models, transplantation of different types of stem cells or progenitor cells results in improved recovery from ischaemia. Furthermore, experimental studies indicate that cell therapy influences a spectrum of processes, including neovascularization and cardiomyogenesis as well as inflammation, apoptosis and interstitial fibrosis. Thus, distinct strategies might be required for specific regenerative needs. Nonetheless, clinical studies have so far investigated a relatively small number of options, focusing mainly on the use of bone marrow-derived cells. Rapid clinical translation resulted in a number of small clinical trials that do not have sufficient power to address the therapeutic potential of the new approach. Moreover, full exploitation has been hindered so far by the absence of a solid theoretical framework and inadequate development plans. This article reviews the current knowledge on cell therapy and proposes a model theory for interpretation of experimental and clinical outcomes from a pharmacological perspective. Eventually, with an increased association between cell therapy and traditional pharmacotherapy, we will soon need to adopt a unified theory for understanding how the two practices additively interact for a patient's benefit. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.

[The translation and its meanings of Materia Medica Part. I in the Jejungwon].

Science.gov (United States)

Park, Junhyoung; Park, Hyoungwoo

2011-12-31

For more systematic medical education, Dr. O. R. Avison translated medical textbooks into Korean since he took charge of Jejungwon in 1893. The first book he chose was Anatomy of the Human Body. He, however, failed to see it published after losing its manuscript twice. Instead, Materia Medica Part. I was brought into the world first in 1905, for which he translated Materia Medica and Therapeutics written by John Mitchell Bruce from the U. K. At that time, this book was in widespread use in the English-speaking world as a textbook for pharmacology. It is also assumed that Avison used it as a textbook for his classes in Canada before coming to Korea. For the publication of Materia Medica Part. I, Avison did not translate Bruce's original text in full, but translated only the selected passages. He followed a principle of using Korean alphabets (Hangeul) only, but in combination with Chinese characters, if necessary. He put pharmacological terms into existing Korean equivalents or newly coined words, but also borrowed many from Japanese terms. That's because Japan moved faster to introduce Western medicine than Korea did, so that many pharmacological terms could be defined and arranged more systematically in Japanese. Moreover, Japan took such a favorable stance in the state of international affairs that many of Japanese-style terms could be introduced into Korea in most fields including medicine. By translating Materia Medica Part. I in cooperation with his disciple KIM Pilsoon after Gray's Anatomy of the Human Body, Avison tried to lay groundwork for providing medical education in Korea based on the British-American medicine. It is assumed that he took an independent stance in selecting and translating Western medical textbooks on his own rather than simply accepting the existing Chinese translation of Western medical textbooks. Despite all his efforts, he might find it difficult to translate all the Western medical terms into Korean within a short period of time

Using Caenorhabditis elegans as a Model for Obesity Pharmacology Development.

Science.gov (United States)

Zheng, Jolene; Vasselli, Joseph R; King, Jason F; King, Michael L; We, Wenqian; Fitzpatrick, Zachary; Johnson, William D; Finley, John W; Martin, Roy J; Keenan, Michael J; Enright, Frederic M; Greenway, Frank L

The Caenorhabditis elegans model is a rapid and inexpensive method to address pharmacologic questions. We describe the use of C. elegans to explore 2 pharmacologic questions concerning candidate antiobesity drugs and illustrate its potential usefulness in pharmacologic research: (1) to determine a ratio of betahistine-olanzapine that blocks the olanzapine-induced intestinal fat deposition (IFD) as detected by Nile red staining and (2) to identify the mechanism of action of a pharmaceutical candidate AB-101 that reduces IFD. Olanzapine (53 μg/mL) increased the IFD (12.1 ± 0.1%, P < 0.02), which was blocked by betahistine (763 μg/mL, 39.3 ± 0.01%, P < 0.05) in wild-type C. elegans (N2). AB-101 (1.0%) reduced the IFD in N2 (P < 0.05), increased the pharyngeal pumping rate (P < 0.05), and reversed the elevated IFD induced by protease inhibitors atazanavir and ritonavir (P < 0.05). AB-101 did not affect IFD in a ACS null mutant strain acs-4(ok2872) III/hT2[bli-4(e937) let-?(q782) qIs48](I;III) suggesting an involvement of the lipid oxidation pathway and an upregulation of CPT-1. Our studies suggest that C. elegans may be used as a resource in pharmacologic research. This article is intended to stimulate a greater appreciation of its value in the development of new pharmaceutical interventions.

Genome-Scale Analysis of Translation Elongation with a Ribosome Flow Model

Science.gov (United States)

Meilijson, Isaac; Kupiec, Martin; Ruppin, Eytan

2011-01-01

We describe the first large scale analysis of gene translation that is based on a model that takes into account the physical and dynamical nature of this process. The Ribosomal Flow Model (RFM) predicts fundamental features of the translation process, including translation rates, protein abundance levels, ribosomal densities and the relation between all these variables, better than alternative (‘non-physical’) approaches. In addition, we show that the RFM can be used for accurate inference of various other quantities including genes' initiation rates and translation costs. These quantities could not be inferred by previous predictors. We find that increasing the number of available ribosomes (or equivalently the initiation rate) increases the genomic translation rate and the mean ribosome density only up to a certain point, beyond which both saturate. Strikingly, assuming that the translation system is tuned to work at the pre-saturation point maximizes the predictive power of the model with respect to experimental data. This result suggests that in all organisms that were analyzed (from bacteria to Human), the global initiation rate is optimized to attain the pre-saturation point. The fact that similar results were not observed for heterologous genes indicates that this feature is under selection. Remarkably, the gap between the performance of the RFM and alternative predictors is strikingly large in the case of heterologous genes, testifying to the model's promising biotechnological value in predicting the abundance of heterologous proteins before expressing them in the desired host. PMID:21909250

Key Questions for Translation of FFA Receptors: From Pharmacology to Medicines.

Science.gov (United States)

Suckow, Arthur T; Briscoe, Celia P

2017-01-01

The identification of fatty acids as ligands for the G-protein coupled free fatty acid (FFA) receptor family over 10 years ago led to intensive chemistry efforts to find small-molecule ligands for this class of receptors. Identification of potent, selective modulators of the FFA receptors and their utility in medicine has proven challenging, in part due to their complex pharmacology. Nevertheless, ligands have been identified that are sufficient for exploring the therapeutic potential of this class of receptors in rodents and, in the case of FFA1, FFA2, FFA4, and GPR84, also in humans. Expression profiling, the phenotyping of FFA receptor knockout mice, and the results of studies exploring the effects of these ligands in rodents have uncovered a number of indications where engagement of one or a combination of FFA receptors might provide some clinical benefit in areas including diabetes, inflammatory bowel syndrome, Alzheimer's, pain, and cancer. In this chapter, we will review the clinical potential of modulating FFA receptors based on preclinical and in some cases clinical studies with synthetic ligands. In particular, key aspects and challenges associated with small-molecule ligand identification and FFA receptor pharmacology will be addressed with a view of the hurdles that need to be overcome to fully understand the potential of the receptors as therapeutic targets.

Translational gastrointestinal pharmacology in the 21st century: 'the lesogaberan story'

NARCIS (Netherlands)

Boeckxstaens, Guy E.; Denison, Hans; Jensen, Jörgen M.; Lehmann, Anders; Ruth, Magnus

2011-01-01

The development of the novel γ-aminobutyric acid type-B receptor (GABAB) agonist lesogaberan is presented as an example of a partly successful translational strategy in the field of gastroenterology. Data on transient lower esophageal sphincter relaxations (TLESRs) and gastroesophageal reflux

Genetics and pharmacology of longevity: the road to therapeutics for healthy aging.

Science.gov (United States)

Castillo-Quan, Jorge Iván; Kinghorn, Kerri J; Bjedov, Ivana

2015-01-01

Aging can be defined as the progressive decline in tissue and organismal function and the ability to respond to stress that occurs in association with homeostatic failure and the accumulation of molecular damage. Aging is the biggest risk factor for human disease and results in a wide range of aging pathologies. Although we do not completely understand the underlying molecular basis that drives the aging process, we have gained exceptional insights into the plasticity of life span and healthspan from the use of model organisms such as the worm Caenorhabditis elegans and the fruit fly Drosophila melanogaster. Single-gene mutations in key cellular pathways that regulate environmental sensing, and the response to stress, have been identified that prolong life span across evolution from yeast to mammals. These genetic manipulations also correlate with a delay in the onset of tissue and organismal dysfunction. While the molecular genetics of aging will remain a prosperous and attractive area of research in biogerontology, we are moving towards an era defined by the search for therapeutic drugs that promote healthy aging. Translational biogerontology will require incorporation of both therapeutic and pharmacological concepts. The use of model organisms will remain central to the quest for drug discovery, but as we uncover molecular processes regulated by repurposed drugs and polypharmacy, studies of pharmacodynamics and pharmacokinetics, drug-drug interactions, drug toxicity, and therapeutic index will slowly become more prevalent in aging research. As we move from genetics to pharmacology and therapeutics, studies will not only require demonstration of life span extension and an underlying molecular mechanism, but also the translational relevance for human health and disease prevention. Copyright © 2015 Elsevier Inc. All rights reserved.

Translating Alcohol Research: Opportunities and Challenges.

Science.gov (United States)

Batman, Angela M; Miles, Michael F

2015-01-01

Alcohol use disorder (AUD) and its sequelae impose a major burden on the public health of the United States, and adequate long-term control of this disorder has not been achieved. Molecular and behavioral basic science research findings are providing the groundwork for understanding the mechanisms underlying AUD and have identified multiple candidate targets for ongoing clinical trials. However, the translation of basic research or clinical findings into improved therapeutic approaches for AUD must become more efficient. Translational research is a multistage process of stream-lining the movement of basic biomedical research findings into clinical research and then to the clinical target populations. This process demands efficient bidirectional communication across basic, applied, and clinical science as well as with clinical practitioners. Ongoing work suggests rapid progress is being made with an evolving translational framework within the alcohol research field. This is helped by multiple interdisciplinary collaborative research structures that have been developed to advance translational work on AUD. Moreover, the integration of systems biology approaches with collaborative clinical studies may yield novel insights for future translational success. Finally, appreciation of genetic variation in pharmacological or behavioral treatment responses and optimal communication from bench to bedside and back may strengthen the success of translational research applications to AUD.

Integrating Automatic Speech Recognition and Machine Translation for Better Translation Outputs

DEFF Research Database (Denmark)

Liyanapathirana, Jeevanthi

translations, combining machine translation with computer assisted translation has drawn attention in current research. This combines two prospects: the opportunity of ensuring high quality translation along with a significant performance gain. Automatic Speech Recognition (ASR) is another important area......, which caters important functionalities in language processing and natural language understanding tasks. In this work we integrate automatic speech recognition and machine translation in parallel. We aim to avoid manual typing of possible translations as dictating the translation would take less time...... to the n-best list rescoring, we also use word graphs with the expectation of arriving at a tighter integration of ASR and MT models. Integration methods include constraining ASR models using language and translation models of MT, and vice versa. We currently develop and experiment different methods...

Translational Models of Gambling-Related Decision-Making.

Science.gov (United States)

Winstanley, Catharine A; Clark, Luke

Gambling is a harmless, recreational pastime that is ubiquitous across cultures. However, for some, gambling becomes a maladaptive and compulsive, and this syndrome is conceptualized as a behavioural addiction. Laboratory models that capture the key cognitive processes involved in gambling behaviour, and that can be translated across species, have the potential to make an important contribution to both decision neuroscience and the study of addictive disorders. The Iowa gambling task has been widely used to assess human decision-making under uncertainty, and this paradigm can be successfully modelled in rodents. Similar neurobiological processes underpin choice behaviour in humans and rats, and thus, a preference for the disadvantageous "high-risk, high-reward" options may reflect meaningful vulnerability for mental health problems. However, the choice behaviour operationalized by these tasks does not necessarily approximate the vulnerability to gambling disorder (GD) per se. We consider a number of psychological challenges that apply to modelling gambling in a translational way, and evaluate the success of the existing models. Heterogeneity in the structure of gambling games, as well as in the motivations of individuals with GD, is highlighted. The potential issues with extrapolating too directly from established animal models of drug dependency are discussed, as are the inherent difficulties in validating animal models of GD in the absence of any approved treatments for GD. Further advances in modelling the cognitive biases endemic in human decision-making, which appear to be exacerbated in GD, may be a promising line of research.

Translation and development of the BNWL-geosphere model

International Nuclear Information System (INIS)

Grundfelt, B.

1977-02-01

The report deals with the rate of radioactivity discharge from a repository for radioactive waste in a geologic formation to the biosphere. A BASIC language computer program called GETOUT has been developed in USA. It was obtained by the Swedish project Nuclear Fuel Safety and has thereafter been translated into FORTRAN. The main extension of the code, that was made during the translation, is a model for averaging the hydrodynamic and geochemical parameters for the case of non-uniform packing of the column (e.g. considering a repository in cracked rock with crack width, crack spacing etc. in different zones). The program has been outtested on an IBM model 360/75 computer. The migration is governed by three parameters i.e. the ground water velocity, the dispersion coefficient and the nuclide retentivities. (L.B.)

PCI: A PATRAN-NASTRAN model translator

Science.gov (United States)

Sheerer, T. J.

1990-01-01

The amount of programming required to develop a PATRAN-NASTRAN translator was surprisingly small. The approach taken produced a highly flexible translator comparable with the PATNAS translator and superior to the PATCOS translator. The coding required varied from around ten lines for a shell element to around thirty for a bar element, and the time required to add a feature to the program is typically less than an hour. The use of a lookup table for element names makes the translator also applicable to other versions of NASTRAN. The saving in time as a result of using PDA's Gateway utilities was considerable. During the writing of the program it became apparent that, with a somewhat more complex structure, it would be possible to extend the element data file to contain all data required to define the translation from PATRAN to NASTRAN by mapping of data between formats. Similar data files on property, material and grid formats would produce a completely universal translator from PATRAN to any FEA program, or indeed any CAE system.

Animal to human translational paradigms relevant for approach avoidance conflict decision making.

Science.gov (United States)

Kirlic, Namik; Young, Jared; Aupperle, Robin L

2017-09-01

Avoidance behavior in clinical anxiety disorders is often a decision made in response to approach-avoidance conflict, resulting in a sacrifice of potential rewards to avoid potential negative affective consequences. Animal research has a long history of relying on paradigms related to approach-avoidance conflict to model anxiety-relevant behavior. This approach includes punishment-based conflict, exploratory, and social interaction tasks. There has been a recent surge of interest in the translation of paradigms from animal to human, in efforts to increase generalization of findings and support the development of more effective mental health treatments. This article briefly reviews animal tests related to approach-avoidance conflict and results from lesion and pharmacologic studies utilizing these tests. We then provide a description of translational human paradigms that have been developed to tap into related constructs, summarizing behavioral and neuroimaging findings. Similarities and differences in findings from analogous animal and human paradigms are discussed. Lastly, we highlight opportunities for future research and paradigm development that will support the clinical utility of this translational work. Copyright © 2017 Elsevier Ltd. All rights reserved.

Measuring Difficulty in English-Chinese Translation: Towards a General Model of Translation Difficulty

Science.gov (United States)

Sun, Sanjun

2012-01-01

Accurate assessment of a text's level of translation difficulty is critical for translator training and accreditation, translation research, and the language industry as well. Traditionally, people rely on their general impression to gauge a text's translation difficulty level. If the evaluation process is to be more effective and the…

Neural Machine Translation with Recurrent Attention Modeling

OpenAIRE

Yang, Zichao; Hu, Zhiting; Deng, Yuntian; Dyer, Chris; Smola, Alex

2016-01-01

Knowing which words have been attended to in previous time steps while generating a translation is a rich source of information for predicting what words will be attended to in the future. We improve upon the attention model of Bahdanau et al. (2014) by explicitly modeling the relationship between previous and subsequent attention levels for each word using one recurrent network per input word. This architecture easily captures informative features, such as fertility and regularities in relat...

Efficient accurate syntactic direct translation models: one tree at a time

NARCIS (Netherlands)

Hassan, H.; Sima'an, K.; Way, A.

2011-01-01

A challenging aspect of Statistical Machine Translation from Arabic to English lies in bringing the Arabic source morpho-syntax to bear on the lexical as well as word-order choices of the English target string. In this article, we extend the feature-rich discriminative Direct Translation Model 2

Fuzzy pharmacology: theory and applications.

Science.gov (United States)

Sproule, Beth A; Naranjo, Claudio A; Türksen, I Burhan

2002-09-01

Fuzzy pharmacology is a term coined to represent the application of fuzzy logic and fuzzy set theory to pharmacological problems. Fuzzy logic is the science of reasoning, thinking and inference that recognizes and uses the real world phenomenon that everything is a matter of degree. It is an extension of binary logic that is able to deal with complex systems because it does not require crisp definitions and distinctions for the system components. In pharmacology, fuzzy modeling has been used for the mechanical control of drug delivery in surgical settings, and work has begun evaluating its use in other pharmacokinetic and pharmacodynamic applications. Fuzzy pharmacology is an emerging field that, based on these initial explorations, warrants further investigation.

Modeling workflow to design machine translation applications for public health practice.

Science.gov (United States)

Turner, Anne M; Brownstein, Megumu K; Cole, Kate; Karasz, Hilary; Kirchhoff, Katrin

2015-02-01

Provide a detailed understanding of the information workflow processes related to translating health promotion materials for limited English proficiency individuals in order to inform the design of context-driven machine translation (MT) tools for public health (PH). We applied a cognitive work analysis framework to investigate the translation information workflow processes of two large health departments in Washington State. Researchers conducted interviews, performed a task analysis, and validated results with PH professionals to model translation workflow and identify functional requirements for a translation system for PH. The study resulted in a detailed description of work related to translation of PH materials, an information workflow diagram, and a description of attitudes towards MT technology. We identified a number of themes that hold design implications for incorporating MT in PH translation practice. A PH translation tool prototype was designed based on these findings. This study underscores the importance of understanding the work context and information workflow for which systems will be designed. Based on themes and translation information workflow processes, we identified key design guidelines for incorporating MT into PH translation work. Primary amongst these is that MT should be followed by human review for translations to be of high quality and for the technology to be adopted into practice. The time and costs of creating multilingual health promotion materials are barriers to translation. PH personnel were interested in MT's potential to improve access to low-cost translated PH materials, but expressed concerns about ensuring quality. We outline design considerations and a potential machine translation tool to best fit MT systems into PH practice. Copyright © 2014 Elsevier Inc. All rights reserved.

Mouse Models Applied to the Research of Pharmacological Treatments in Asthma.

Science.gov (United States)

Marqués-García, Fernando; Marcos-Vadillo, Elena

2016-01-01

Models developed for the study of asthma mechanisms can be used to investigate new compounds with pharmacological activity against this disease. The increasing number of compounds requires a preclinical evaluation before starting the application in humans. Preclinical evaluation in animal models reduces the number of clinical trials positively impacting in the cost and in safety. In this chapter, three protocols for the study of drugs are shown: a model to investigate corticoids as a classical treatment of asthma; a protocol to test the effects of retinoic acid (RA) on asthma; and a mouse model to test new therapies in asthma as monoclonal antibodies.

Translational invariance in bag model

International Nuclear Information System (INIS)

Megahed, F.

1981-10-01

In this thesis, the effect of restoring the translational invariance to an approximation to the MIT bag model on the calculation of deep inelastic structure functions is investigated. In chapter one, the model and its major problems are reviewed and Dirac's method of quantisation is outlined. This method is used in chapter two to quantise a two-dimensional complex scalar bag and formal expressions for the form factor and the structure functions are obtained. In chapter three, the expression for the structure function away from the Bjorken limit is studied. The corrections to the L 0 - approximation to the structure function is calculated in chapter four and it is shown to be large. Finally, in chapter five, a bag-like model for kinematic corrections to structure functions is introduced and agreement with data between 2 and 6 (GeV/C) 2 is obtained. (author)

Mapping Translation Technology Research in Translation Studies

DEFF Research Database (Denmark)

Schjoldager, Anne; Christensen, Tina Paulsen; Flanagan, Marian

2017-01-01

/Schjoldager 2010, 2011; Christensen 2011). Unfortunately, the increasing professional use of translation technology has not been mirrored within translation studies (TS) by a similar increase in research projects on translation technology (Munday 2009: 15; O’Hagan 2013; Doherty 2016: 952). The current thematic...... section aims to improve this situation by presenting new and innovative research papers that reflect on recent technological advances and their impact on the translation profession and translators from a diversity of perspectives and using a variety of methods. In Section 2, we present translation...... technology research as a subdiscipline of TS, and we define and discuss some basic concepts and models of the field that we use in the rest of the paper. Based on a small-scale study of papers published in TS journals between 2006 and 2016, Section 3 attempts to map relevant developments of translation...

Virtual Systems Pharmacology (ViSP software for mechanistic system-level model simulations

Directory of Open Access Journals (Sweden)

Sergey eErmakov

2014-10-01

Full Text Available Multiple software programs are available for designing and running large scale system-level pharmacology models used in the drug development process. Depending on the problem, scientists may be forced to use several modeling tools that could increase model development time, IT costs and so on. Therefore it is desirable to have a single platform that allows setting up and running large-scale simulations for the models that have been developed with different modeling tools. We developed a workflow and a software platform in which a model file is compiled into a self-contained executable that is no longer dependent on the software that was used to create the model. At the same time the full model specifics is preserved by presenting all model parameters as input parameters for the executable. This platform was implemented as a model agnostic, therapeutic area agnostic and web-based application with a database back-end that can be used to configure, manage and execute large-scale simulations for multiple models by multiple users. The user interface is designed to be easily configurable to reflect the specifics of the model and the user’s particular needs and the back-end database has been implemented to store and manage all aspects of the systems, such as Models, Virtual Patients, User Interface Settings, and Results. The platform can be adapted and deployed on an existing cluster or cloud computing environment. Its use was demonstrated with a metabolic disease systems pharmacology model that simulates the effects of two antidiabetic drugs, metformin and fasiglifam, in type 2 diabetes mellitus patients.

A pharma perspective on the systems medicine and pharmacology of inflammation.

Science.gov (United States)

Lahoz-Beneytez, Julio; Schnizler, Katrin; Eissing, Thomas

2015-02-01

Biological systems are complex and comprehend multiple scales of organisation. Hence, holistic approaches are necessary to capture the behaviour of these entities from the molecular and cellular to the whole organism level. This also applies to the understanding and treatment of different diseases. Traditional systems biology has been successful in describing different biological phenomena at the cellular level, but it still lacks of a holistic description of the multi-scale interactions within the body. The importance of the physiological context is of particular interest in inflammation. Regulatory agencies have urged the scientific community to increase the translational power of bio-medical research and it has been recognised that modelling and simulation could be a path to follow. Interestingly, in pharma R&D, modelling and simulation has been employed since a long time ago. Systems pharmacology, and particularly physiologically based pharmacokinetic/pharmacodynamic models, serve as a suitable framework to integrate the available and emerging knowledge at different levels of the drug development process. Systems medicine and pharmacology of inflammation will potentially benefit from this framework in order to better understand inflammatory diseases and to help to transfer the vast knowledge on the molecular and cellular level into a more physiological context. Ultimately, this may lead to reliable predictions of clinical outcomes such as disease progression or treatment efficacy, contributing thereby to a better care of patients. Copyright © 2014 Elsevier Inc. All rights reserved.

Parameter trajectory analysis to identify treatment effects of pharmacological interventions.

Directory of Open Access Journals (Sweden)

Christian A Tiemann

Full Text Available The field of medical systems biology aims to advance understanding of molecular mechanisms that drive disease progression and to translate this knowledge into therapies to effectively treat diseases. A challenging task is the investigation of long-term effects of a (pharmacological treatment, to establish its applicability and to identify potential side effects. We present a new modeling approach, called Analysis of Dynamic Adaptations in Parameter Trajectories (ADAPT, to analyze the long-term effects of a pharmacological intervention. A concept of time-dependent evolution of model parameters is introduced to study the dynamics of molecular adaptations. The progression of these adaptations is predicted by identifying necessary dynamic changes in the model parameters to describe the transition between experimental data obtained during different stages of the treatment. The trajectories provide insight in the affected underlying biological systems and identify the molecular events that should be studied in more detail to unravel the mechanistic basis of treatment outcome. Modulating effects caused by interactions with the proteome and transcriptome levels, which are often less well understood, can be captured by the time-dependent descriptions of the parameters. ADAPT was employed to identify metabolic adaptations induced upon pharmacological activation of the liver X receptor (LXR, a potential drug target to treat or prevent atherosclerosis. The trajectories were investigated to study the cascade of adaptations. This provided a counter-intuitive insight concerning the function of scavenger receptor class B1 (SR-B1, a receptor that facilitates the hepatic uptake of cholesterol. Although activation of LXR promotes cholesterol efflux and -excretion, our computational analysis showed that the hepatic capacity to clear cholesterol was reduced upon prolonged treatment. This prediction was confirmed experimentally by immunoblotting measurements of SR-B1

Metabotropic and ionotropic glutamate receptors as neurobiological targets in anxiety and stress-related disorders: focus on pharmacology and preclinical translational models

OpenAIRE

Harvey, Brian H.; Shahid, Mohammed

2012-01-01

Anxiety disorders are amongst the most common and disabling of psychiatric illnesses and have severe health and socio-economic implications. Despite the availability of a number of treatment options there is still a strong medical need for novel and improved pharmacological approaches in treating these disorders. New developments at the forefront of preclinical research have begun to identify the therapeutic potential of molecular entities integral to the biological response to ad...

Evaluating pharmacological models of high and low anxiety in sheep

Directory of Open Access Journals (Sweden)

Rebecca E. Doyle

2015-12-01

Full Text Available New tests of animal affect and welfare require validation in subjects experiencing putatively different states. Pharmacological manipulations of affective state are advantageous because they can be administered in a standardised fashion, and the duration of their action can be established and tailored to suit the length of a particular test. To this end, the current study aimed to evaluate a pharmacological model of high and low anxiety in an important agricultural and laboratory species, the sheep. Thirty-five 8-month-old female sheep received either an intramuscular injection of the putatively anxiogenic drug 1-(m-chlorophenylpiperazine (mCPP; 1 mg/kg; n = 12, an intravenous injection of the putatively anxiolytic drug diazepam (0.1 mg/kg; n = 12, or acted as a control (saline intramuscular injection n = 11. Thirty minutes after the treatments, sheep were individually exposed to a variety of tests assessing their general movement, performance in a ‘runway task’ (moving down a raceway for a food reward, response to startle, and behaviour in isolation. A test to assess feeding motivation was performed 2 days later following administration of the drugs to the same animals in the same manner. The mCPP sheep had poorer performance in the two runway tasks (6.8 and 7.7 × slower respectively than control group; p < 0.001, a greater startle response (1.4 vs. 0.6; p = 0.02, a higher level of movement during isolation (9.1 steps vs. 5.4; p < 0.001, and a lower feeding motivation (1.8 × slower; p < 0.001 than the control group, all of which act as indicators of anxiety. These results show that mCPP is an effective pharmacological model of high anxiety in sheep. Comparatively, the sheep treated with diazepam did not display any differences compared to the control sheep. Thus we suggest that mCPP is an effective treatment to validate future tests aimed at assessing anxiety in sheep, and that future studies should include other subtle indicators of

Pharmacological characterization of social isolation-induced hyperactivity

DEFF Research Database (Denmark)

Fabricius, Katrine; Helboe, Lone; Fink-Jensen, Anders

2011-01-01

Social isolation (SI) of rats directly after weaning is a non-pharmacological, non-lesion animal model based on the neurodevelopmental hypothesis of schizophrenia. The model causes several neurobiological and behavioral alterations consistent with observations in schizophrenia.......Social isolation (SI) of rats directly after weaning is a non-pharmacological, non-lesion animal model based on the neurodevelopmental hypothesis of schizophrenia. The model causes several neurobiological and behavioral alterations consistent with observations in schizophrenia....

Models of kulture in Nabokov's memoirs and translation memoirs in Serbian and Croatian language

Directory of Open Access Journals (Sweden)

Razdobudko-Čović Larisa I.

2012-01-01

Full Text Available The paper presents an analysis of two Serbian translations of V. Nabokov's memoirs, that is the translation of the novel 'Drugie berega' ('The Other Shores' published in Russian as an authorized translation from the original English version 'Conclusive Evidence', and the translation of Nabokov's authorized translation from Russian to English entitled 'Speak, Memory'. Creolization of three models of culture in translation from the two originals - Russian and English - Is presented. Specific features of the two Serbian translations are analyzed, and a survey of characteristic mistakes caused by some specific characteristics of the source language is given. Also, Nabokov's very original approach to translation which is quite interpretative is highlighted.

QEFSM model and Markov Algorithm for translating Quran reciting rules into Braille code

Directory of Open Access Journals (Sweden)

Abdallah M. Abualkishik

2015-07-01

Full Text Available The Holy Quran is the central religious verbal text of Islam. Muslims are expected to read, understand, and apply the teachings of the Holy Quran. The Holy Quran was translated to Braille code as a normal Arabic text without having its reciting rules included. It is obvious that the users of this transliteration will not be able to recite the Quran the right way. Through this work, Quran Braille Translator (QBT presents a specific translator to translate Quran verses and their reciting rules into the Braille code. Quran Extended Finite State Machine (QEFSM model is proposed through this study as it is able to detect the Quran reciting rules (QRR from the Quran text. Basis path testing was used to evaluate the inner work for the model by checking all the test cases for the model. Markov Algorithm (MA was used for translating the detected QRR and Quran text into the matched Braille code. The data entries for QBT are Arabic letters and diacritics. The outputs of this study are seen in the double lines of Braille symbols; the first line is the proposed Quran reciting rules and the second line is for the Quran scripts.

Multi-dimensional knowledge translation: enabling health informatics capacity audits using patient journey models.

Science.gov (United States)

Catley, Christina; McGregor, Carolyn; Percival, Jennifer; Curry, Joanne; James, Andrew

2008-01-01

This paper presents a multi-dimensional approach to knowledge translation, enabling results obtained from a survey evaluating the uptake of Information Technology within Neonatal Intensive Care Units to be translated into knowledge, in the form of health informatics capacity audits. Survey data, having multiple roles, patient care scenarios, levels, and hospitals, is translated using a structured data modeling approach, into patient journey models. The data model is defined such that users can develop queries to generate patient journey models based on a pre-defined Patient Journey Model architecture (PaJMa). PaJMa models are then analyzed to build capacity audits. Capacity audits offer a sophisticated view of health informatics usage, providing not only details of what IT solutions a hospital utilizes, but also answering the questions: when, how and why, by determining when the IT solutions are integrated into the patient journey, how they support the patient information flow, and why they improve the patient journey.

Dynamical modeling of microRNA action on the protein translation process.

Science.gov (United States)

Zinovyev, Andrei; Morozova, Nadya; Nonne, Nora; Barillot, Emmanuel; Harel-Bellan, Annick; Gorban, Alexander N

2010-02-24

Protein translation is a multistep process which can be represented as a cascade of biochemical reactions (initiation, ribosome assembly, elongation, etc.), the rate of which can be regulated by small non-coding microRNAs through multiple mechanisms. It remains unclear what mechanisms of microRNA action are the most dominant: moreover, many experimental reports deliver controversial messages on what is the concrete mechanism actually observed in the experiment. Nissan and Parker have recently demonstrated that it might be impossible to distinguish alternative biological hypotheses using the steady state data on the rate of protein synthesis. For their analysis they used two simple kinetic models of protein translation. In contrary to the study by Nissan and Parker, we show that dynamical data allow discriminating some of the mechanisms of microRNA action. We demonstrate this using the same models as developed by Nissan and Parker for the sake of comparison but the methods developed (asymptotology of biochemical networks) can be used for other models. We formulate a hypothesis that the effect of microRNA action is measurable and observable only if it affects the dominant system (generalization of the limiting step notion for complex networks) of the protein translation machinery. The dominant system can vary in different experimental conditions that can partially explain the existing controversy of some of the experimental data. Our analysis of the transient protein translation dynamics shows that it gives enough information to verify or reject a hypothesis about a particular molecular mechanism of microRNA action on protein translation. For multiscale systems only that action of microRNA is distinguishable which affects the parameters of dominant system (critical parameters), or changes the dominant system itself. Dominant systems generalize and further develop the old and very popular idea of limiting step. Algorithms for identifying dominant systems in multiscale

Dynamical modeling of microRNA action on the protein translation process

Directory of Open Access Journals (Sweden)

Barillot Emmanuel

2010-02-01

Full Text Available Abstract Background Protein translation is a multistep process which can be represented as a cascade of biochemical reactions (initiation, ribosome assembly, elongation, etc., the rate of which can be regulated by small non-coding microRNAs through multiple mechanisms. It remains unclear what mechanisms of microRNA action are the most dominant: moreover, many experimental reports deliver controversial messages on what is the concrete mechanism actually observed in the experiment. Nissan and Parker have recently demonstrated that it might be impossible to distinguish alternative biological hypotheses using the steady state data on the rate of protein synthesis. For their analysis they used two simple kinetic models of protein translation. Results In contrary to the study by Nissan and Parker, we show that dynamical data allow discriminating some of the mechanisms of microRNA action. We demonstrate this using the same models as developed by Nissan and Parker for the sake of comparison but the methods developed (asymptotology of biochemical networks can be used for other models. We formulate a hypothesis that the effect of microRNA action is measurable and observable only if it affects the dominant system (generalization of the limiting step notion for complex networks of the protein translation machinery. The dominant system can vary in different experimental conditions that can partially explain the existing controversy of some of the experimental data. Conclusions Our analysis of the transient protein translation dynamics shows that it gives enough information to verify or reject a hypothesis about a particular molecular mechanism of microRNA action on protein translation. For multiscale systems only that action of microRNA is distinguishable which affects the parameters of dominant system (critical parameters, or changes the dominant system itself. Dominant systems generalize and further develop the old and very popular idea of limiting step

Behavioral, Pharmacological, and Immunological Abnormalities after Streptococcal Exposure: A Novel Rat Model of Sydenham Chorea and Related Neuropsychiatric Disorders

Science.gov (United States)

Brimberg, Lior; Benhar, Itai; Mascaro-Blanco, Adita; Alvarez, Kathy; Lotan, Dafna; Winter, Christine; Klein, Julia; Moses, Allon E; Somnier, Finn E; Leckman, James F; Swedo, Susan E; Cunningham, Madeleine W; Joel, Daphna

2012-01-01

Group A streptococcal (GAS) infections and autoimmunity are associated with the onset of a spectrum of neuropsychiatric disorders in children, with the prototypical disorder being Sydenham chorea (SC). Our aim was to develop an animal model that resembled the behavioral, pharmacological, and immunological abnormalities of SC and other streptococcal-related neuropsychiatric disorders. Male Lewis rats exposed to GAS antigen exhibited motor symptoms (impaired food manipulation and beam walking) and compulsive behavior (increased induced-grooming). These symptoms were alleviated by the D2 blocker haloperidol and the selective serotonin reuptake inhibitor paroxetine, respectively, drugs that are used to treat motor symptoms and compulsions in streptococcal-related neuropsychiatric disorders. Streptococcal exposure resulted in antibody deposition in the striatum, thalamus, and frontal cortex, and concomitant alterations in dopamine and glutamate levels in cortex and basal ganglia, consistent with the known pathophysiology of SC and related neuropsychiatric disorders. Autoantibodies (IgG) of GAS rats reacted with tubulin and caused elevated calcium/calmodulin-dependent protein kinase II signaling in SK-N-SH neuronal cells, as previously found with sera from SC and related neuropsychiatric disorders. Our new animal model translates directly to human disease and led us to discover autoantibodies targeted against dopamine D1 and D2 receptors in the rat model as well as in SC and other streptococcal-related neuropsychiatric disorders. PMID:22534626

Syntactic discriminative language model rerankers for statistical machine translation

NARCIS (Netherlands)

Carter, S.; Monz, C.

2011-01-01

This article describes a method that successfully exploits syntactic features for n-best translation candidate reranking using perceptrons. We motivate the utility of syntax by demonstrating the superior performance of parsers over n-gram language models in differentiating between Statistical

Making sense of the Sense Model: translation priming with Japanese-English bilinguals

OpenAIRE

Allen, David; Conklin, Kathy; Van Heuven, Walter J.B.

2015-01-01

Many studies have reported that first language (L1) translation primes speed responses to second language (L2) targets, whereas L2 translation primes generally do not speed up responses to L1 targets in lexical decision. According to the Sense Model (Finkbeiner, Forster, Nicol & Nakamura, 2004) this asymmetry is due to the proportion of senses activated by the prime. Because L2 primes activate only a subset of the L1 translations senses, priming is not observed. In this study we test the pred...

Spectral and scattering theory for translation invariant models in quantum field theory

DEFF Research Database (Denmark)

Rasmussen, Morten Grud

This thesis is concerned with a large class of massive translation invariant models in quantum field theory, including the Nelson model and the Fröhlich polaron. The models in the class describe a matter particle, e.g. a nucleon or an electron, linearly coupled to a second quantised massive scalar...... by the physically relevant choices. The translation invariance implies that the Hamiltonian may be decomposed into a direct integral over the space of total momentum where the fixed momentum fiber Hamiltonians are given by , where denotes total momentum and is the Segal field operator. The fiber Hamiltonians...

A HUMANIZED CLINICALLY CALIBRATED QUANTITATIVE SYSTEMS PHARMACOLOGY MODEL FOR HYPOKINETIC MOTOR SYMPTOMS IN PARKINSON’S DISEASE

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Hugo eGeerts

2016-02-01

Full Text Available The current treatment of Parkinson’s disease with dopamine-centric approaches such as L-DOPA and dopamine agonists, although very succesfull, is in need of alternative treatment strategies, both in terms of disease modification and symptom management. Various non-dopaminergic treatment approaches did not result in a clear clinical benefit, despite showing a clear effect in preclinical animal models. In addition, polypharmacy is common, sometimes leading to unintended effects on non-motor symptoms such as in cognitive and psychiatric domains. To explore novel targets for symptomatic treatment and possible synergistic pharmacodynamic effects between different drugs, we developed a Quantitative Systems Pharmacology (QSP platform of the closed cortico-striatal-thalamic-cortical basal ganglia loop of the dorsal motor circuit. This mechanism-based simulation platform is based on the known neuro-anatomy and neurophysiology of the basal ganglia and explicitly incorporates domain expertise in a formalized way. The calculated beta/gamma power ratio of the local field potential in the subthalamic nucleus correlates well (R2=0.71 with clinically observed extra-pyramidal symptoms triggered by antipsychotics during schizophrenia treatment (43 drug-dose combinations. When incorporating Parkinsonian (PD pathology and reported compensatory changes, the computer model suggests a major increase in b/g ratio (corresponding to bradykinesia and rigidity from a dopamine depletion of 70% onwards. The correlation between the outcome of the QSP model and the reported changes in UPDRS III Motor Part for 22 placebo-normalized drug-dose combinations is R2=0.84. The model also correctly recapitulates the lack of clinical benefit for perampanel, MK-0567 and flupirtine and offers a hypothesis for the translational disconnect. Finally, using human PET imaging studies with placebo response, the computer model predicts well the placebo response for chronic treatment, but not

PIK3CA mutations enable targeting of a breast tumor dependency through mTOR-mediated MCL-1 translation

OpenAIRE

Anderson, Grace R.; Wardell, Suzanne E.; Cakir, Merve; Crawford, Lorin; Leeds, Jim C.; Nussbaum, Daniel P.; Shankar, Pallavi S.; Soderquist, Ryan S.; Stein, Elizabeth M.; Tingley, Jennifer P.; Winter, Peter S.; Zieser-Misenheimer, Elizabeth K.; Alley, Holly M.; Yllanes, Alexander; Haney, Victoria

2016-01-01

Therapies that efficiently induce apoptosis are likely to be required for durable clinical responses in patients with solid tumors. Using a pharmacological screening approach, we discovered that the combined inhibition of BCL-XL and the mTOR/4E-BP axis results in selective and synergistic induction of apoptosis in cellular and animal models of PIK3CA mutant breast cancers, including triple negative tumors. Mechanistically, inhibition of mTOR/4E-BP suppresses MCL-1 protein translation only in ...

Rho GTPases, their post-translational modifications, disease-associated mutations and pharmacological inhibitors.

Science.gov (United States)

Olson, Michael F

2018-05-04

The 20 members of the Rho GTPase family are key regulators of a wide-variety of biological activities. In response to activation, they signal via downstream effector proteins to induce dynamic alterations in the organization of the actomyosin cytoskeleton. In this review, post-translational modifications, mechanisms of dysregulation identified in human pathological conditions, and the ways that Rho GTPases might be targeted for chemotherapy will be discussed.

Probing for Neuroadaptations to Unpredictable Stressors in Addiction: Translational Methods and Emerging Evidence.

Science.gov (United States)

Kaye, Jesse T; Bradford, Daniel E; Magruder, Katherine P; Curtin, John J

2017-05-01

Stressors clearly contribute to addiction etiology and relapse in humans, but our understanding of specific mechanisms remains limited. Rodent models of addiction offer the power, flexibility, and precision necessary to delineate the causal role and specific mechanisms through which stressors influence alcohol and other drug use. This review describes a program of research using startle potentiation to unpredictable stressors that is well positioned to translate between animal models and clinical research with humans on stress neuroadaptations in addiction. This research rests on a solid foundation provided by three separate pillars of evidence from (a) rodent behavioral neuroscience on stress neuroadaptations in addiction, (b) rodent affective neuroscience on startle potentiation, and (c) human addiction and affective science with startle potentiation. Rodent stress neuroadaptation models implicate adaptations in corticotropin-releasing factor and norepinephrine circuits within the central extended amygdala following chronic alcohol and other drug use that mediate anxious behaviors and stress-induced reinstatement among drug-dependent rodents. Basic affective neuroscience indicates that these same neural mechanisms are involved in startle potentiation to unpredictable stressors in particular (vs. predictable stressors). We believe that synthesis of these evidence bases should focus us on the role of unpredictable stressors in addiction etiology and relapse. Startle potentiation in unpredictable stressor tasks is proposed to provide an attractive and flexible test bed to encourage tight translation and reverse translation between animal models and human clinical research on stress neuroadaptations. Experimental therapeutics approaches focused on unpredictable stressors hold high promise to identify, repurpose, or refine pharmacological and psychosocial interventions for addiction.

Probing for Neuroadaptations to Unpredictable Stressors in Addiction: Translational Methods and Emerging Evidence

Science.gov (United States)

Kaye, Jesse T.; Bradford, Daniel E.; Magruder, Katherine P.; Curtin, John J.

2017-01-01

Stressors clearly contribute to addiction etiology and relapse in humans, but our understanding of specific mechanisms remains limited. Rodent models of addiction offer the power, flexibility, and precision necessary to delineate the causal role and specific mechanisms through which stressors influence alcohol and other drug use. This review describes a program of research using startle potentiation to unpredictable stressors that is well positioned to translate between animal models and clinical research with humans on stress neuroadaptations in addiction. This research rests on a solid foundation provided by three separate pillars of evidence from (a) rodent behavioral neuroscience on stress neuroadaptations in addiction, (b) rodent affective neuroscience on startle potentiation, and (c) human addiction and affective science with startle potentiation. Rodent stress neuroadaptation models implicate adaptations in corticotropin-releasing factor and norepinephrine circuits within the central extended amygdala following chronic alcohol and other drug use that mediate anxious behaviors and stress-induced reinstatement among drug-dependent rodents. Basic affective neuroscience indicates that these same neural mechanisms are involved in startle potentiation to unpredictable stressors in particular (vs. predictable stressors). We believe that synthesis of these evidence bases should focus us on the role of unpredictable stressors in addiction etiology and relapse. Startle potentiation in unpredictable stressor tasks is proposed to provide an attractive and flexible test bed to encourage tight translation and reverse translation between animal models and human clinical research on stress neuroadaptations. Experimental therapeutics approaches focused on unpredictable stressors hold high promise to identify, repurpose, or refine pharmacological and psychosocial interventions for addiction. PMID:28499100

Assessing the effects of pharmacological agents on respiratory dynamics using time-series modeling.

Science.gov (United States)

Wong, Kin Foon Kevin; Gong, Jen J; Cotten, Joseph F; Solt, Ken; Brown, Emery N

2013-04-01

Developing quantitative descriptions of how stimulant and depressant drugs affect the respiratory system is an important focus in medical research. Respiratory variables-respiratory rate, tidal volume, and end tidal carbon dioxide-have prominent temporal dynamics that make it inappropriate to use standard hypothesis-testing methods that assume independent observations to assess the effects of these pharmacological agents. We present a polynomial signal plus autoregressive noise model for analysis of continuously recorded respiratory variables. We use a cyclic descent algorithm to maximize the conditional log likelihood of the parameters and the corrected Akaike's information criterion to choose simultaneously the orders of the polynomial and the autoregressive models. In an analysis of respiratory rates recorded from anesthetized rats before and after administration of the respiratory stimulant methylphenidate, we use the model to construct within-animal z-tests of the drug effect that take account of the time-varying nature of the mean respiratory rate and the serial dependence in rate measurements. We correct for the effect of model lack-of-fit on our inferences by also computing bootstrap confidence intervals for the average difference in respiratory rate pre- and postmethylphenidate treatment. Our time-series modeling quantifies within each animal the substantial increase in mean respiratory rate and respiratory dynamics following methylphenidate administration. This paradigm can be readily adapted to analyze the dynamics of other respiratory variables before and after pharmacologic treatments.

Comparison of Methods for Modeling a Hydraulic Loader Crane With Flexible Translational Links

DEFF Research Database (Denmark)

Pedersen, Henrik Clemmensen; Andersen, Torben O.; Nielsen, Brian K.

2015-01-01

not hold for translational links. Hence, special care has to be taken when including flexible translational links. In the current paper, different methods for modeling a hydraulic loader crane with a telescopic arm are investigated and compared using both the finite segment (FS) and AMs method...

A Minimal Cognitive Model for Translating and Post-editing

DEFF Research Database (Denmark)

Schaeffer, Moritz; Carl, Michael

2017-01-01

This study investigates the coordination of reading (input) and writing (output) activities in from-scratch translation and post-editing. We segment logged eye movements and keylogging data into minimal units of reading and writing activity and model the process of post-editing and from-scratch t...

Effects of different per translational kinetics on the dynamics of a core circadian clock model.

Science.gov (United States)

Nieto, Paula S; Revelli, Jorge A; Garbarino-Pico, Eduardo; Condat, Carlos A; Guido, Mario E; Tamarit, Francisco A

2015-01-01

Living beings display self-sustained daily rhythms in multiple biological processes, which persist in the absence of external cues since they are generated by endogenous circadian clocks. The period (per) gene is a central player within the core molecular mechanism for keeping circadian time in most animals. Recently, the modulation PER translation has been reported, both in mammals and flies, suggesting that translational regulation of clock components is important for the proper clock gene expression and molecular clock performance. Because translational regulation ultimately implies changes in the kinetics of translation and, therefore, in the circadian clock dynamics, we sought to study how and to what extent the molecular clock dynamics is affected by the kinetics of PER translation. With this objective, we used a minimal mathematical model of the molecular circadian clock to qualitatively characterize the dynamical changes derived from kinetically different PER translational mechanisms. We found that the emergence of self-sustained oscillations with characteristic period, amplitude, and phase lag (time delays) between per mRNA and protein expression depends on the kinetic parameters related to PER translation. Interestingly, under certain conditions, a PER translation mechanism with saturable kinetics introduces longer time delays than a mechanism ruled by a first-order kinetics. In addition, the kinetic laws of PER translation significantly changed the sensitivity of our model to parameters related to the synthesis and degradation of per mRNA and PER degradation. Lastly, we found a set of parameters, with realistic values, for which our model reproduces some experimental results reported recently for Drosophila melanogaster and we present some predictions derived from our analysis.

Pharmacologic Management of Duchenne Muscular Dystrophy: Target Identification and Preclinical Trials

Science.gov (United States)

Kornegay, Joe N.; Spurney, Christopher F.; Nghiem, Peter P.; Brinkmeyer-Langford, Candice L.; Hoffman, Eric P.; Nagaraju, Kanneboyina

2014-01-01

Duchenne muscular dystrophy (DMD) is an X-linked human disorder in which absence of the protein dystrophin causes degeneration of skeletal and cardiac muscle. For the sake of treatment development, over and above definitive genetic and cell-based therapies, there is considerable interest in drugs that target downstream disease mechanisms. Drug candidates have typically been chosen based on the nature of pathologic lesions and presumed underlying mechanisms and then tested in animal models. Mammalian dystrophinopathies have been characterized in mice (mdx mouse) and dogs (golden retriever muscular dystrophy [GRMD]). Despite promising results in the mdx mouse, some therapies have not shown efficacy in DMD. Although the GRMD model offers a higher hurdle for translation, dogs have primarily been used to test genetic and cellular therapies where there is greater risk. Failed translation of animal studies to DMD raises questions about the propriety of methods and models used to identify drug targets and test efficacy of pharmacologic intervention. The mdx mouse and GRMD dog are genetically homologous to DMD but not necessarily analogous. Subcellular species differences are undoubtedly magnified at the whole-body level in clinical trials. This problem is compounded by disparate cultures in clinical trials and preclinical studies, pointing to a need for greater rigor and transparency in animal experiments. Molecular assays such as mRNA arrays and genome-wide association studies allow identification of genetic drug targets more closely tied to disease pathogenesis. Genes in which polymorphisms have been directly linked to DMD disease progression, as with osteopontin, are particularly attractive targets. PMID:24936034

Russian translations for Cochrane.

Science.gov (United States)

Yudina, E V; Ziganshina, L E

2015-01-01

Cochrane collaboration has made a huge contribution to the development of evidence-based medicine; Cochrane work is the international gold standard of independent, credible and reliable high-quality information in medicine. Over the past 20 years the Cochrane Collaboration helped transforming decision-making in health and reforming it significantly, saving lives and contributing to longevity [1]. Until recently, Cochrane evidence were available only in English, which represents a significant barrier to their wider use in non-English speaking countries. To provide access to evidence, obtained from Cochrane Reviews, for health professionals and general public (from non-English-speaking countries), bypassing language barriers, Cochrane collaboration in 2014 initiated an international project of translating Plain language summaries of Cochrane Reviews into other languages [2, 3]. Russian translations of Plain language summaries were started in May 2014 by the team from Kazan Federal University (Department of Basic and Clinical Pharmacology; 2014-2015 as an Affiliated Centre in Tatarstan of the Nordic Cochrane Centre, since August 2015 as Cochrane Russia, a Russian branch of Cochrane Nordic, Head - Liliya Eugenevna Ziganshina) on a voluntary basis. To assess the quality of Russian translations of Cochrane Plain Language Summaries (PLS) and their potential impact on the Russian speaking community through user feedback with the overarching aim of furthering the translations project. We conducted the continuous online survey via Google Docs. We invited respondents through the electronic Russian language discussion forum on Essential Medicines (E-lek), links to survey on the Russian Cochrane.org website, invitations to Cochrane contributors registered in Archie from potential Russian-speaking countries. We set up the survey in Russian and English. The respondents were asked to respond to the questionnaire regarding the relevance and potential impact of the Cochrane Russian

Language Model Adaptation Using Machine-Translated Text for Resource-Deficient Languages

Directory of Open Access Journals (Sweden)

Sadaoki Furui

2009-01-01

Full Text Available Text corpus size is an important issue when building a language model (LM. This is a particularly important issue for languages where little data is available. This paper introduces an LM adaptation technique to improve an LM built using a small amount of task-dependent text with the help of a machine-translated text corpus. Icelandic speech recognition experiments were performed using data, machine translated (MT from English to Icelandic on a word-by-word and sentence-by-sentence basis. LM interpolation using the baseline LM and an LM built from either word-by-word or sentence-by-sentence translated text reduced the word error rate significantly when manually obtained utterances used as a baseline were very sparse.

A phased translation function

International Nuclear Information System (INIS)

Read, R.J.; Schierbeek, A.J.

1988-01-01

A phased translation function, which takes advantage of prior phase information to determine the position of an oriented mulecular replacement model, is examined. The function is the coefficient of correlation between the electron density computed with the prior phases and the electron density of the translated model, evaluated in reciprocal space as a Fourier transform. The correlation coefficient used in this work is closely related to an overlap function devised by Colman, Fehlhammer and Bartels. Tests with two protein structures, one of which was solved with the help of the phased translation function, show that little phase information is required to resolve the translation problem, and that the function is relatively insensitive to misorientation of the model. (orig.)

A generic method for automatic translation between input models for different versions of simulation codes

International Nuclear Information System (INIS)

Serfontein, Dawid E.; Mulder, Eben J.; Reitsma, Frederik

2014-01-01

A computer code was developed for the semi-automatic translation of input models for the VSOP-A diffusion neutronics simulation code to the format of the newer VSOP 99/05 code. In this paper, this algorithm is presented as a generic method for producing codes for the automatic translation of input models from the format of one code version to another, or even to that of a completely different code. Normally, such translations are done manually. However, input model files, such as for the VSOP codes, often are very large and may consist of many thousands of numeric entries that make no particular sense to the human eye. Therefore the task, of for instance nuclear regulators, to verify the accuracy of such translated files can be very difficult and cumbersome. This may cause translation errors not to be picked up, which may have disastrous consequences later on when a reactor with such a faulty design is built. Therefore a generic algorithm for producing such automatic translation codes may ease the translation and verification process to a great extent. It will also remove human error from the process, which may significantly enhance the accuracy and reliability of the process. The developed algorithm also automatically creates a verification log file which permanently record the names and values of each variable used, as well as the list of meanings of all the possible values. This should greatly facilitate reactor licensing applications

A generic method for automatic translation between input models for different versions of simulation codes

Energy Technology Data Exchange (ETDEWEB)

Serfontein, Dawid E., E-mail: Dawid.Serfontein@nwu.ac.za [School of Mechanical and Nuclear Engineering, North West University (PUK-Campus), PRIVATE BAG X6001 (Internal Post Box 360), Potchefstroom 2520 (South Africa); Mulder, Eben J. [School of Mechanical and Nuclear Engineering, North West University (South Africa); Reitsma, Frederik [Calvera Consultants (South Africa)

2014-05-01

A computer code was developed for the semi-automatic translation of input models for the VSOP-A diffusion neutronics simulation code to the format of the newer VSOP 99/05 code. In this paper, this algorithm is presented as a generic method for producing codes for the automatic translation of input models from the format of one code version to another, or even to that of a completely different code. Normally, such translations are done manually. However, input model files, such as for the VSOP codes, often are very large and may consist of many thousands of numeric entries that make no particular sense to the human eye. Therefore the task, of for instance nuclear regulators, to verify the accuracy of such translated files can be very difficult and cumbersome. This may cause translation errors not to be picked up, which may have disastrous consequences later on when a reactor with such a faulty design is built. Therefore a generic algorithm for producing such automatic translation codes may ease the translation and verification process to a great extent. It will also remove human error from the process, which may significantly enhance the accuracy and reliability of the process. The developed algorithm also automatically creates a verification log file which permanently record the names and values of each variable used, as well as the list of meanings of all the possible values. This should greatly facilitate reactor licensing applications.

Translational Cellular Research on the International Space Station

Science.gov (United States)

Love, John; Cooley, Vic

2016-01-01

The emerging field of Translational Research aims to coalesce interdisciplinary findings from basic science for biomedical applications. To complement spaceflight research using human subjects, translational studies can be designed to address aspects of space-related human health risks and help develop countermeasures to prevent or mitigate them, with therapeutical benefits for analogous conditions experienced on Earth. Translational research with cells and model organisms is being conducted onboard the International Space Station (ISS) in connection with various human systems impacted by spaceflight, such as the cardiovascular, musculoskeletal, and immune systems. Examples of recent cell-based translational investigations on the ISS include the following. The JAXA investigation Cell Mechanosensing seeks to identify gravity sensors in skeletal muscle cells to develop muscle atrophy countermeasures by analyzing tension fluctuations in the plasma membrane, which changes the expression of key proteins and genes. Earth applications of this study include therapeutic approaches for some forms of muscular dystrophy, which appear to parallel aspects of muscle wasting in space. Spheroids is an ESA investigation examining the system of endothelial cells lining the inner surface of all blood vessels in terms of vessel formation, cellular proliferation, and programmed cell death, because injury to the endothelium has been implicated as underpinning various cardiovascular and musculoskeletal problems arising during spaceflight. Since endothelial cells are involved in the functional integrity of the vascular wall, this research has applications to Earth diseases such as atherosclerosis, diabetes, and hypertension. The goal of the T-Cell Activation in Aging NASA investigation is to understand human immune system depression in microgravity by identifying gene expression patterns of candidate molecular regulators, which will provide further insight into factors that may play a

SVM Based Descriptor Selection and Classification of Neurodegenerative Disease Drugs for Pharmacological Modeling.

Science.gov (United States)

Shahid, Mohammad; Shahzad Cheema, Muhammad; Klenner, Alexander; Younesi, Erfan; Hofmann-Apitius, Martin

2013-03-01

Systems pharmacological modeling of drug mode of action for the next generation of multitarget drugs may open new routes for drug design and discovery. Computational methods are widely used in this context amongst which support vector machines (SVM) have proven successful in addressing the challenge of classifying drugs with similar features. We have applied a variety of such SVM-based approaches, namely SVM-based recursive feature elimination (SVM-RFE). We use the approach to predict the pharmacological properties of drugs widely used against complex neurodegenerative disorders (NDD) and to build an in-silico computational model for the binary classification of NDD drugs from other drugs. Application of an SVM-RFE model to a set of drugs successfully classified NDD drugs from non-NDD drugs and resulted in overall accuracy of ∼80 % with 10 fold cross validation using 40 top ranked molecular descriptors selected out of total 314 descriptors. Moreover, SVM-RFE method outperformed linear discriminant analysis (LDA) based feature selection and classification. The model reduced the multidimensional descriptors space of drugs dramatically and predicted NDD drugs with high accuracy, while avoiding over fitting. Based on these results, NDD-specific focused libraries of drug-like compounds can be designed and existing NDD-specific drugs can be characterized by a well-characterized set of molecular descriptors. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A conceptual model for translating omic data into clinical action

Directory of Open Access Journals (Sweden)

Timothy M Herr

2015-01-01

Full Text Available Genomic, proteomic, epigenomic, and other "omic" data have the potential to enable precision medicine, also commonly referred to as personalized medicine. The volume and complexity of omic data are rapidly overwhelming human cognitive capacity, requiring innovative approaches to translate such data into patient care. Here, we outline a conceptual model for the application of omic data in the clinical context, called "the omic funnel." This model parallels the classic "Data, Information, Knowledge, Wisdom pyramid" and adds context for how to move between each successive layer. Its goal is to allow informaticians, researchers, and clinicians to approach the problem of translating omic data from bench to bedside, by using discrete steps with clearly defined needs. Such an approach can facilitate the development of modular and interoperable software that can bring precision medicine into widespread practice.

Assessing the Quality of Persian Translation of Kite Runner based on House’s (2014 Functional Pragmatic Model

Directory of Open Access Journals (Sweden)

Fateme Kargarzadeh

2017-03-01

Full Text Available Translation quality assessment is at the heart of any theory of translation. It is used in the academic or teaching contexts to judge translations, to discuss their merits and demerits and to suggest solutions. However, literary translations needs more consideration in terms of quality and clarity as it is widely read form of translation. In this respect, Persian literary translation of Kite Runner was taken for investigation based on House’s (2014 functional pragmatic model of translation quality assessment. To this end, around 100 pages from the beginning of both English and Persian versions of the novel were selected and compared. Using House’s model, the profile of the source text register was created and the genre was recognized. The source text profile was compared to the translation text profile. The results were minute mismatches in field, tenor, and mode which accounted for as overt erroneous expressions and leading matches which were accounted for as covert translation. The mismatches were some mistranslations of tenses and selection of inappropriate meanings for the lexicon. Since the informal and culture specific terms were transferred thoroughly, the culture filter was not applied. Besides, as the translation was a covert one. The findings of the study have implications for translators, researchers and translator trainers.

Translation Training in the Jordanian Context: Curriculum Evaluation in Translator Education

Science.gov (United States)

Mahasneh, Anjad

2013-01-01

This study aims at drawing a clear picture of translator training in Jordan through the evaluation of translation programs at the Master's level. The framework of the Context, Input, Process, and Product components of the CIPP evaluation model developed by Daniel Stufflebeam in 1971 was used to evaluate the three translation Master's programs at…

Animal Models for Tuberculosis in Translational and Precision Medicine

Directory of Open Access Journals (Sweden)

Lingjun Zhan

2017-05-01

Full Text Available Tuberculosis (TB is a health threat to the global population. Anti-TB drugs and vaccines are key approaches for TB prevention and control. TB animal models are basic tools for developing biomarkers of diagnosis, drugs for therapy, vaccines for prevention and researching pathogenic mechanisms for identification of targets; thus, they serve as the cornerstone of comparative medicine, translational medicine, and precision medicine. In this review, we discuss the current use of TB animal models and their problems, as well as offering perspectives on the future of these models.

Anatomy and bronchoscopy of the porcine lung. A model for translational respiratory medicine.

LENUS (Irish Health Repository)

Judge, Eoin P

2014-09-01

The porcine model has contributed significantly to biomedical research over many decades. The similar size and anatomy of pig and human organs make this model particularly beneficial for translational research in areas such as medical device development, therapeutics and xenotransplantation. In recent years, a major limitation with the porcine model was overcome with the successful generation of gene-targeted pigs and the publication of the pig genome. As a result, the role of this model is likely to become even more important. For the respiratory medicine field, the similarities between pig and human lungs give the porcine model particular potential for advancing translational medicine. An increasing number of lung conditions are being studied and modeled in the pig. Genetically modified porcine models of cystic fibrosis have been generated that, unlike mouse models, develop lung disease similar to human cystic fibrosis. However, the scientific literature relating specifically to porcine lung anatomy and airway histology is limited and is largely restricted to veterinary literature and textbooks. Furthermore, methods for in vivo lung procedures in the pig are rarely described. The aims of this review are to collate the disparate literature on porcine lung anatomy, histology, and microbiology; to provide a comparison with the human lung; and to describe appropriate bronchoscopy procedures for the pig lungs to aid clinical researchers working in the area of translational respiratory medicine using the porcine model.

Incorporation of post-translational modified amino acids as an approach to increase both chemical and biological diversity of conotoxins and conopeptides.

Science.gov (United States)

Espiritu, Michael J; Cabalteja, Chino C; Sugai, Christopher K; Bingham, Jon-Paul

2014-01-01

Bioactive peptides from Conus venom contain a natural abundance of post-translational modifications that affect their chemical diversity, structural stability, and neuroactive properties. These modifications have continually presented hurdles in their identification and characterization. Early endeavors in their analysis relied on classical biochemical techniques that have led to the progressive development and use of novel proteomic-based approaches. The critical importance of these post-translationally modified amino acids and their specific assignment cannot be understated, having impact on their folding, pharmacological selectivity, and potency. Such modifications at an amino acid level may also provide additional insight into the advancement of conopeptide drugs in the quest for precise pharmacological targeting. To achieve this end, a concerted effort between the classical and novel approaches is needed to completely elucidate the role of post-translational modifications in conopeptide structure and dynamics. This paper provides a reflection in the advancements observed in dealing with numerous and multiple post-translationally modified amino acids within conotoxins and conopeptides and provides a summary of the current techniques used in their identification.

Selected translated abstracts of Russian-language climate-change publications. 4: General circulation models

Energy Technology Data Exchange (ETDEWEB)

Burtis, M.D. [comp.] [Oak Ridge National Lab., TN (United States). Carbon Dioxide Information Analysis Center; Razuvaev, V.N.; Sivachok, S.G. [All-Russian Research Inst. of Hydrometeorological Information--World Data Center, Obninsk (Russian Federation)

1996-10-01

This report presents English-translated abstracts of important Russian-language literature concerning general circulation models as they relate to climate change. Into addition to the bibliographic citations and abstracts translated into English, this report presents the original citations and abstracts in Russian. Author and title indexes are included to assist the reader in locating abstracts of particular interest.

Drug-disease modeling in the pharmaceutical industry - where mechanistic systems pharmacology and statistical pharmacometrics meet.

Science.gov (United States)

Helmlinger, Gabriel; Al-Huniti, Nidal; Aksenov, Sergey; Peskov, Kirill; Hallow, Karen M; Chu, Lulu; Boulton, David; Eriksson, Ulf; Hamrén, Bengt; Lambert, Craig; Masson, Eric; Tomkinson, Helen; Stanski, Donald

2017-11-15

Modeling & simulation (M&S) methodologies are established quantitative tools, which have proven to be useful in supporting the research, development (R&D), regulatory approval, and marketing of novel therapeutics. Applications of M&S help design efficient studies and interpret their results in context of all available data and knowledge to enable effective decision-making during the R&D process. In this mini-review, we focus on two sets of modeling approaches: population-based models, which are well-established within the pharmaceutical industry today, and fall under the discipline of clinical pharmacometrics (PMX); and systems dynamics models, which encompass a range of models of (patho-)physiology amenable to pharmacological intervention, of signaling pathways in biology, and of substance distribution in the body (today known as physiologically-based pharmacokinetic models) - which today may be collectively referred to as quantitative systems pharmacology models (QSP). We next describe the convergence - or rather selected integration - of PMX and QSP approaches into 'middle-out' drug-disease models, which retain selected mechanistic aspects, while remaining parsimonious, fit-for-purpose, and able to address variability and the testing of covariates. We further propose development opportunities for drug-disease systems models, to increase their utility and applicability throughout the preclinical and clinical spectrum of pharmaceutical R&D. Copyright © 2017 Elsevier B.V. All rights reserved.

Drosophila melanogaster "a potential model organism" for identification of pharmacological properties of plants/plant-derived components.

Science.gov (United States)

Panchal, Komal; Tiwari, Anand K

2017-05-01

Plants/plant-derived components have been used from ancient times to treat/cure several human diseases. Plants and their parts possess several chemical components that play the vital role in the improvement of human health and their life expectancy. Allopathic medicines have been playing a key role in the treatment of several diseases. Though allopathic medicines provide fast relief, long time consumption cause serious health concerns such as hyperallergic reactions, liver damage, etc. So, the study of medicinal plants which rarely cause any side effect is very important to mankind. Plants contain many health benefit properties like antioxidant, anti-aging, neuroprotective, anti-genotoxic, anti-mutagenic and bioinsecticidal activity. Thus, identification of pharmacological properties of plants/plant-derived components are of utmost importance to be explored. Several model organisms have been used to identify the pharmacological properties of the different plants or active components therein and Drosophila is one of them. Drosophila melanogaster "fruit fly" is a well understood, high-throughput model organism being used more than 110 years to study the different biological aspects related to the development and diseases. Most of the developmental and cell signaling pathways and ∼75% human disease-related genes are conserved between human and Drosophila. Using Drosophila, one can easily analyze the pharmacological properties of plants/plant-derived components by performing several assays available with flies such as survivorship, locomotor, antioxidant, cell death, etc. The current review focuses on the potential of Drosophila melanogaster for the identification of medicinal/pharmacological properties associated with plants/plant-derived components. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Lost in Translation (LiT): IUPHAR Review 6.

Science.gov (United States)

Dollery, Colin T

2014-05-01

Translational medicine is a roller coaster with occasional brilliant successes and a large majority of failures. Lost in Translation 1 ('LiT1'), beginning in the 1950s, was a golden era built upon earlier advances in experimental physiology, biochemistry and pharmacology, with a dash of serendipity, that led to the discovery of many new drugs for serious illnesses. LiT2 saw the large-scale industrialization of drug discovery using high-throughput screens and assays based on affinity for the target molecule. The links between drug development and university sciences and medicine weakened, but there were still some brilliant successes. In LiT3, the coverage of translational medicine expanded from molecular biology to drug budgets, with much greater emphasis on safety and official regulation. Compared with R&D expenditure, the number of breakthrough discoveries in LiT3 was disappointing, but monoclonal antibodies for immunity and inflammation brought in a new golden era and kinase inhibitors such as imatinib were breakthroughs in cancer. The pharmaceutical industry is trying to revive the LiT1 approach by using phenotypic assays and closer links with academia. LiT4 faces a data explosion generated by the genome project, GWAS, ENCODE and the 'omics' that is in danger of leaving LiT4 in a computerized cloud. Industrial laboratories are filled with masses of automated machinery while the scientists sit in a separate room viewing the results on their computers. Big Data will need Big Thinking in LiT4 but with so many unmet medical needs and so many new opportunities being revealed there are high hopes that the roller coaster will ride high again. © 2014 The British Pharmacological Society.

Pearls and pitfalls in human pharmacological models of migraine

DEFF Research Database (Denmark)

Ashina, Messoud; Hansen, Jakob Møller; Olesen, Jes

2013-01-01

In vitro studies have contributed to the characterization of receptors in cranial blood vessels and the identification of new possible anti-migraine agents. In vivo animal models enable the study of vascular responses, neurogenic inflammation, peptide release and genetic predisposition and thus......- or migraine-provoking property of naturally occurring signaling molecules can be tested in a human model. If such an endogenous substance can provoke migraine in human patients, then it is likely, although not certain, that blocking its effect will be effective in the treatment of acute migraine attacks...... an important role in translational migraine research leading to the identification of three new principally different targets in the treatment of acute migraine attacks and has been used to examine other endogenous signaling molecules as well as genetic susceptibility factors. New additions to the model...

Translational control of auditory imprinting and structural plasticity by eIF2α

Science.gov (United States)

Batista, Gervasio; Johnson, Jennifer Leigh; Dominguez, Elena; Costa-Mattioli, Mauro; Pena, Jose L

2016-01-01

The formation of imprinted memories during a critical period is crucial for vital behaviors, including filial attachment. Yet, little is known about the underlying molecular mechanisms. Using a combination of behavior, pharmacology, in vivo surface sensing of translation (SUnSET) and DiOlistic labeling we found that, translational control by the eukaryotic translation initiation factor 2 alpha (eIF2α) bidirectionally regulates auditory but not visual imprinting and related changes in structural plasticity in chickens. Increasing phosphorylation of eIF2α (p-eIF2α) reduces translation rates and spine plasticity, and selectively impairs auditory imprinting. By contrast, inhibition of an eIF2α kinase or blocking the translational program controlled by p-eIF2α enhances auditory imprinting. Importantly, these manipulations are able to reopen the critical period. Thus, we have identified a translational control mechanism that selectively underlies auditory imprinting. Restoring translational control of eIF2α holds the promise to rejuvenate adult brain plasticity and restore learning and memory in a variety of cognitive disorders. DOI: http://dx.doi.org/10.7554/eLife.17197.001 PMID:28009255

Potentials and Challenges for Arterial Spin Labeling in Pharmacological Magnetic Resonance Imaging

OpenAIRE

Wang, Danny J. J.; Chen, Yufen; Fernández-Seara, María A.; Detre, John A.

2011-01-01

Pharmacological magnetic resonance imaging (phMRI) is increasingly being used in drug discovery and development to speed the translation from the laboratory to the clinic. The two primary methods in phMRI include blood-oxygen-level-dependent (BOLD) contrast and arterial spin-labeled (ASL) perfusion MRI. BOLD contrast has been widely applied in existing phMRI studies. However, because of the lack of absolute quantification and poor reproducibility over time scales longer than hours or across s...

The Modelling of Axially Translating Flexible Beams

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Theodore, R. J.; Arakeri, J. H.; Ghosal, A.

1996-04-01

The axially translating flexible beam with a prismatic joint can be modelled by using the Euler-Bernoulli beam equation together with the convective terms. In general, the method of separation of variables cannot be applied to solve this partial differential equation. In this paper, a non-dimensional form of the Euler Bernoulli beam equation is presented, obtained by using the concept of group velocity, and also the conditions under which separation of variables and assumed modes method can be used. The use of clamped-mass boundary conditions leads to a time-dependent frequency equation for the translating flexible beam. A novel method is presented for solving this time dependent frequency equation by using a differential form of the frequency equation. The assume mode/Lagrangian formulation of dynamics is employed to derive closed form equations of motion. It is shown by using Lyapunov's first method that the dynamic responses of flexural modal variables become unstable during retraction of the flexible beam, which the dynamic response during extension of the beam is stable. Numerical simulation results are presented for the uniform axial motion induced transverse vibration for a typical flexible beam.

Modulation of early stress-induced neurobiological changes: a review of behavioural and pharmacological interventions in animal models.

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Harrison, E L; Baune, B T

2014-05-13

Childhood adversity alters the predisposition to psychiatric disorders later in life. Those with psychiatric conditions and a history of early adversity exhibit a higher incidence of treatment resistance compared with individuals with no such history. Modulation of the influence early stress exerts over neurobiology may help to prevent the development of psychiatric disorders in some cases, while attenuating the extent of treatment resistance in those with established psychiatric disorders. This review aims to critically evaluate the ability of behavioural, environmental and pharmacologic interventions to modulate neurobiological changes induced by early stress in animal models. Databases were systematically searched to locate literature relevant to this review. Early adversity was defined as stress that resulted from manipulation of the mother-infant relationship. Analysis was restricted to animal models to enable characterisation of how a given intervention altered specific neurobiological changes induced by early stress. A wide variety of changes in neurobiology due to early stress are amenable to intervention. Behavioural interventions in childhood, exercise in adolescence and administration of epigenetic-modifying drugs throughout life appear to best modulate cellar and behavioural alterations induced by childhood adversity. Other pharmacotherapies, such as endocannabinoid system modulators, anti-inflammatories and antidepressants can also influence these neurobiological and behavioural changes that result from early stress, although findings are less consistent at present and require further investigation. Further work is required to examine the influence that behavioural interventions, exercise and epigenetic-modifying drugs exert over alterations that occur following childhood stress in human studies, before possible translational into clinical practice is possible.

Using physiologically based models for clinical translation: predictive modelling, data interpretation or something in-between?

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Niederer, Steven A; Smith, Nic P

2016-12-01

Heart disease continues to be a significant clinical problem in Western society. Predictive models and simulations that integrate physiological understanding with patient information derived from clinical data have huge potential to contribute to improving our understanding of both the progression and treatment of heart disease. In particular they provide the potential to improve patient selection and optimisation of cardiovascular interventions across a range of pathologies. Currently a significant proportion of this potential is still to be realised. In this paper we discuss the opportunities and challenges associated with this realisation. Reviewing the successful elements of model translation for biophysically based models and the emerging supporting technologies, we propose three distinct modes of clinical translation. Finally we outline the challenges ahead that will be fundamental to overcome if the ultimate goal of fully personalised clinical cardiac care is to be achieved. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

An Emerging Translational Model to Screen Potential Medicinal Plants for Nephrolithiasis, an Independent Risk Factor for Chronic Kidney Disease

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San-Yuan Wu

2014-01-01

Full Text Available Pharmacological therapy for urolithiasis using medicinal plants has been increasingly adopted for the prevention of its recurrence. A Drosophila melanogaster model developed for translational research of urolithiasis was applied to evaluate agents with potential antilithic effects and calcium oxalate (CaOx formation. Potential antilithic herbs were prepared in a mixture of food in a diluted concentration of 5,000 from the original extract with 0.5% ethylene glycol (EG as the lithogenic agent. The control group was fed with food only. After 3 weeks, flies (n≥150 for each group were killed using CO2 narcotization, and the Malpighian tubules were dissected, removed, and processed for polarized light microscopy examination of the crystals. The crystal formation rate in the EG group was 100.0%. In the study, 16 tested herbal drugs reached the crystal formation rate of 0.0%, including Salviae miltiorrhizae, Paeonia lactiflora, and Carthami flos. Scutellaria baicalensis enhanced CaOx crystal formation. Two herbal drugs Commiphora molmol and Natrii sulfas caused the death of all flies. Our rapid screening methods provided evidence that some medicinal plants have potential antilithic effects. These useful medicinal plants can be further studied using other animal or human models to verify their effects.

Eye-movements During Translation

DEFF Research Database (Denmark)

Balling, Laura Winther

2013-01-01

texts as well as both eye-tracking and keylogging data. Based on this database, I present a large-scale analysis of gaze on the source text based on 91 translators' translations of six different texts from English into four different target languages. I use mixed-effects modelling to compare from......, and variables indexing the alignment between the source and target texts. The results are related to current models of translation processes and reading and compared to a parallel analysis of production time....

Respiratory nanoparticle-based vaccines and challenges associated with animal models and translation.

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Renukaradhya, Gourapura J; Narasimhan, Balaji; Mallapragada, Surya K

2015-12-10

Vaccine development has had a huge impact on human health. However, there is a significant need to develop efficacious vaccines for several existing as well as emerging respiratory infectious diseases. Several challenges need to be overcome to develop efficacious vaccines with translational potential. This review focuses on two aspects to overcome some barriers - 1) the development of nanoparticle-based vaccines, and 2) the choice of suitable animal models for respiratory infectious diseases that will allow for translation. Nanoparticle-based vaccines, including subunit vaccines involving synthetic and/or natural polymeric adjuvants and carriers, as well as those based on virus-like particles offer several key advantages to help overcome the barriers to effective vaccine development. These include the ability to deliver combinations of antigens, target the vaccine formulation to specific immune cells, enable cross-protection against divergent strains, act as adjuvants or immunomodulators, allow for sustained release of antigen, enable single dose delivery, and potentially obviate the cold chain. While mouse models have provided several important insights into the mechanisms of infectious diseases, they are often a limiting step in translation of new vaccines to the clinic. An overview of different animal models involved in vaccine research for respiratory infections, with advantages and disadvantages of each model, is discussed. Taken together, advances in nanotechnology, combined with the right animal models for evaluating vaccine efficacy, has the potential to revolutionize vaccine development for respiratory infections. Copyright © 2015 Elsevier B.V. All rights reserved.

Predictive biophysical modeling and understanding of the dynamics of mRNA translation and its evolution

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Zur, Hadas; Tuller, Tamir

2016-01-01

mRNA translation is the fundamental process of decoding the information encoded in mRNA molecules by the ribosome for the synthesis of proteins. The centrality of this process in various biomedical disciplines such as cell biology, evolution and biotechnology, encouraged the development of dozens of mathematical and computational models of translation in recent years. These models aimed at capturing various biophysical aspects of the process. The objective of this review is to survey these models, focusing on those based and/or validated on real large-scale genomic data. We consider aspects such as the complexity of the models, the biophysical aspects they regard and the predictions they may provide. Furthermore, we survey the central systems biology discoveries reported on their basis. This review demonstrates the fundamental advantages of employing computational biophysical translation models in general, and discusses the relative advantages of the different approaches and the challenges in the field. PMID:27591251

Jungmann's translation of Paradise Lost

OpenAIRE

Janů, Karel

2014-01-01

This thesis examines Josef Jungmann's translation of John Milton's Paradise Lost. Josef Jungmann was one of the leading figures of the Czech National Revival and translated Milton 's poem between the years 1800 and 1804. The thesis covers Jungmann's theoretical model of translation and presents Jungmann's motives for translation of Milton's epic poem. The paper also describes the aims Jungmann had with his translation and whether he has achieved them. The reception Jungmann's translation rece...

Efficient Generation and Selection of Virtual Populations in Quantitative Systems Pharmacology Models.

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Allen, R J; Rieger, T R; Musante, C J

2016-03-01

Quantitative systems pharmacology models mechanistically describe a biological system and the effect of drug treatment on system behavior. Because these models rarely are identifiable from the available data, the uncertainty in physiological parameters may be sampled to create alternative parameterizations of the model, sometimes termed "virtual patients." In order to reproduce the statistics of a clinical population, virtual patients are often weighted to form a virtual population that reflects the baseline characteristics of the clinical cohort. Here we introduce a novel technique to efficiently generate virtual patients and, from this ensemble, demonstrate how to select a virtual population that matches the observed data without the need for weighting. This approach improves confidence in model predictions by mitigating the risk that spurious virtual patients become overrepresented in virtual populations.

Model for bridging the translational "valleys of death" in spinal cord injury research

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Barrable B

2014-04-01

Full Text Available Bill Barrable,1 Nancy Thorogood,1 Vanessa Noonan,1,2 Jocelyn Tomkinson,1 Phalgun Joshi,1 Ken Stephenson,1 John Barclay,1 Katharina Kovacs Burns3 1Rick Hansen Institute, 2Division of Spine, Department of Orthopaedics, University of British Columbia, Vancouver, BC, 3Health Sciences Council, University of Alberta, Edmonton, AB, Canada Abstract: To improve health care outcomes with cost-effective treatments and prevention initiatives, basic health research must be translated into clinical application and studied during implementation, a process commonly referred to as translational research. It is estimated that only 14% of health-related scientific discoveries enter into medical practice and that it takes an average of 17 years for them to do so. The transition from basic research to clinical knowledge and from clinical knowledge to practice or implementation is so fraught with obstacles that these transitions are often referred to as “valleys of death”. The Rick Hansen Institute has developed a unique praxis model for translational research in the field of spinal cord injury (SCI. The praxis model involves three components. The first is a coordinated program strategy of cure, care, consumer engagement, and commercialization. The second is a knowledge cycle that consists of four phases, ie, environmental scanning, knowledge generation and synthesis, knowledge validation, and implementation. The third is the provision of relevant resources and infrastructure to overcome obstacles in the “valleys of death”, ie, funding, clinical research operations, informatics, clinical research and best practice implementation, consumer engagement, collaborative networks, and strategic partnerships. This model, which is to be independently evaluated in 2018 to determine its strengths and limitations, has been used to advance treatments for pressure ulcers in SCI. The Rick Hansen Institute has developed an innovative solution to move knowledge into action by

Translating the foundational model of anatomy into french using knowledge-based and lexical methods

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Merabti Tayeb

2011-10-01

Full Text Available Abstract Background The Foundational Model of Anatomy (FMA is the reference ontology regarding human anatomy. FMA vocabulary was integrated into the Health Multi Terminological Portal (HMTP developed by CISMeF based on the CISMeF Information System which also includes 26 other terminologies and controlled vocabularies, mainly in French. However, FMA is primarily in English. In this context, the translation of FMA English terms into French could also be useful for searching and indexing French anatomy resources. Various studies have investigated automatic methods to assist the translation of medical terminologies or create multilingual medical vocabularies. The goal of this study was to facilitate the translation of FMA vocabulary into French. Methods We compare two types of approaches to translate the FMA terms into French. The first one is UMLS-based on the conceptual information of the UMLS metathesaurus. The second method is lexically-based on several Natural Language Processing (NLP tools. Results The UMLS-based approach produced a translation of 3,661 FMA terms into French whereas the lexical approach produced a translation of 3,129 FMA terms into French. A qualitative evaluation was made on 100 FMA terms translated by each method. For the UMLS-based approach, among the 100 translations, 52% were manually rated as "very good" and only 7% translations as "bad". For the lexical approach, among the 100 translations, 47% were rated as "very good" and 20% translations as "bad". Conclusions Overall, a low rate of translations were demonstrated by the two methods. The two approaches permitted us to semi-automatically translate 3,776 FMA terms from English into French, this was to added to the existing 10,844 French FMA terms in the HMTP (4,436 FMA French terms and 6,408 FMA terms manually translated.

A Model of Translator's Competence from an Educational Perspective

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Eser, Oktay

2015-01-01

Translation as a business is a service. The concept of translation competence is a term covering the various skills and knowledge that a translator needs to have in order to translate functionally. The term which is often studied as a multi-componential concept in literature may not cover the necessary skills if it is taken from an organizational…

National Center for Advancing Translational Sciences

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... Models Core Technologies Clinical Innovation Clinical and Translational Science Awards Program Rare Diseases Clinical Research Network Patient ... to our monthly e-newsletter. About Translation Translational Science Spectrum Explore the full spectrum of translational science, ...

Pharmacological manipulations in animal models of anorexia and binge eating in relation to humans.

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van Gestel, M A; Kostrzewa, E; Adan, R A H; Janhunen, S K

2014-10-01

Eating disorders, such as anorexia nervosa (AN), bulimia nervosa (BN) and binge eating disorders (BED), are described as abnormal eating habits that usually involve insufficient or excessive food intake. Animal models have been developed that provide insight into certain aspects of eating disorders. Several drugs have been found efficacious in these animal models and some of them have eventually proven useful in the treatment of eating disorders. This review will cover the role of monoaminergic neurotransmitters in eating disorders and their pharmacological manipulations in animal models and humans. Dopamine, 5-HT (serotonin) and noradrenaline in hypothalamic and striatal regions regulate food intake by affecting hunger and satiety and by affecting rewarding and motivational aspects of feeding. Reduced neurotransmission by dopamine, 5-HT and noradrenaline and compensatory changes, at least in dopamine D2 and 5-HT(2C/2A) receptors, have been related to the pathophysiology of AN in humans and animal models. Also, in disorders and animal models of BN and BED, monoaminergic neurotransmission is down-regulated but receptor level changes are different from those seen in AN. A hypofunctional dopamine system or overactive α2-adrenoceptors may contribute to an attenuated response to (palatable) food and result in hedonic binge eating. Evidence for the efficacy of monoaminergic treatments for AN is limited, while more support exists for the treatment of BN or BED with monoaminergic drugs. © 2014 The British Pharmacological Society.

Glutamate and GABA in autism spectrum disorder-a translational magnetic resonance spectroscopy study in man and rodent models.

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Horder, Jamie; Petrinovic, Marija M; Mendez, Maria A; Bruns, Andreas; Takumi, Toru; Spooren, Will; Barker, Gareth J; Künnecke, Basil; Murphy, Declan G

2018-05-25

Autism spectrum disorder (ASD) is a pervasive neurodevelopmental syndrome with a high human and economic burden. The pathophysiology of ASD is largely unclear, thus hampering development of pharmacological treatments for the core symptoms of the disorder. Abnormalities in glutamate and GABA signaling have been hypothesized to underlie ASD symptoms, and may form a therapeutic target, but it is not known whether these abnormalities are recapitulated in humans with ASD, as well as in rodent models of the disorder. We used translational proton magnetic resonance spectroscopy ([1H]MRS) to compare glutamate and GABA levels in adult humans with ASD and in a panel of six diverse rodent ASD models, encompassing genetic and environmental etiologies. [1H]MRS was performed in the striatum and the medial prefrontal cortex, of the humans, mice, and rats in order to allow for direct cross-species comparisons in specific cortical and subcortical brain regions implicated in ASD. In humans with ASD, glutamate concentration was reduced in the striatum and this was correlated with the severity of social symptoms. GABA levels were not altered in either brain region. The reduction in striatal glutamate was recapitulated in mice prenatally exposed to valproate, and in mice and rats carrying Nlgn3 mutations, but not in rodent ASD models with other etiologies. Our findings suggest that glutamate/GABA abnormalities in the corticostriatal circuitry may be a key pathological mechanism in ASD; and may be linked to alterations in the neuroligin-neurexin signaling complex.

Semiotics of Umberto Eco in a Literary Translation Class: The Model Reader as the Competent Translator

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Ozturk Kasar, Sündüz; Can, Alize

2017-01-01

Classroom environment can be thought as an absolute place to practice and improve translation skills of students. They have the possibility to brainstorm and discuss problematic points they face with each other during a translation activity. It can be estimated in the same way in a literary translation class. Students who are supposed to become…

An Evaluation of Output Quality of Machine Translation (Padideh Software vs. Google Translate)

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Azer, Haniyeh Sadeghi; Aghayi, Mohammad Bagher

2015-01-01

This study aims to evaluate the translation quality of two machine translation systems in translating six different text-types, from English to Persian. The evaluation was based on criteria proposed by Van Slype (1979). The proposed model for evaluation is a black-box type, comparative and adequacy-oriented evaluation. To conduct the evaluation, a…

Screening of effective pharmacological treatments for MELAS syndrome using yeasts, fibroblasts and cybrid models of the disease.

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Garrido-Maraver, Juan; Cordero, Mario D; Moñino, Irene Domínguez; Pereira-Arenas, Sheila; Lechuga-Vieco, Ana V; Cotán, David; De la Mata, Mario; Oropesa-Ávila, Manuel; De Miguel, Manuel; Bautista Lorite, Juan; Rivas Infante, Eloy; Alvarez-Dolado, Manuel; Navas, Plácido; Jackson, Sandra; Francisci, Silvia; Sánchez-Alcázar, José A

2012-11-01

MELAS (mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes) is a mitochondrial disease most usually caused by point mutations in tRNA genes encoded by mitochondrial DNA (mtDNA). Approximately 80% of cases of MELAS syndrome are associated with a m.3243A > G mutation in the MT-TL1 gene, which encodes the mitochondrial tRNALeu (UUR). Currently, no effective treatments are available for this chronic progressive disorder. Treatment strategies in MELAS and other mitochondrial diseases consist of several drugs that diminish the deleterious effects of the abnormal respiratory chain function, reduce the presence of toxic agents or correct deficiencies in essential cofactors. We evaluated the effectiveness of some common pharmacological agents that have been utilized in the treatment of MELAS, in yeast, fibroblast and cybrid models of the disease. The yeast model harbouring the A14G mutation in the mitochondrial tRNALeu(UUR) gene, which is equivalent to the A3243G mutation in humans, was used in the initial screening. Next, the most effective drugs that were able to rescue the respiratory deficiency in MELAS yeast mutants were tested in fibroblasts and cybrid models of MELAS disease. According to our results, supplementation with riboflavin or coenzyme Q(10) effectively reversed the respiratory defect in MELAS yeast and improved the pathologic alterations in MELAS fibroblast and cybrid cell models. Our results indicate that cell models have great potential for screening and validating the effects of novel drug candidates for MELAS treatment and presumably also for other diseases with mitochondrial impairment. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.

The Translation and the Translator of the Peshitta of Hosea

Science.gov (United States)

Tully, Eric J.

2012-01-01

This comprehensive examination of the Syriac Peshitta of Hosea (P-Hosea) is the first study of the Peshitta conducted via insights and methods from the discipline of Translation Studies. It uses in particular Andrew Chesterman's Causal Model and Gideon Toury's descriptive approach. Every translator leaves residue of his or her…

Translational PK-PD modelling of molecular target modulation for the AMPA receptor positive allosteric modulator Org 26576.

Science.gov (United States)

Bursi, Roberta; Erdemli, Gul; Campbell, Robert; Hutmacher, Matthew M; Kerbusch, Thomas; Spanswick, David; Jeggo, Ross; Nations, Kari R; Dogterom, Peter; Schipper, Jacques; Shahid, Mohammed

2011-12-01

The α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor potentiator Org 26576 represents an interesting pharmacological tool to evaluate the utility of glutamatergic enhancement towards the treatment of psychiatric disorders. In this study, a rat-human translational pharmacokinetic-pharmacodynamic (PK-PD) model of AMPA receptor modulation was used to predict human target engagement and inform dose selection in efficacy clinical trials. Modelling and simulation was applied to rat plasma and cerebrospinal fluid (CSF) pharmacokinetic and pharmacodynamic measurements to identify a target concentration (EC(80)) for AMPA receptor modulation. Human plasma pharmacokinetics was determined from 33 healthy volunteers and eight major depressive disorder patients. From four out of these eight patients, CSF PK was also determined. Simulations of human CSF levels were performed for several doses of Org 26576. Org 26576 (0.1-10 mg/kg, i.v.) potentiated rat hippocampal AMPA receptor responses in an exposure-dependant manner. The rat plasma and CSF PK data were fitted by one-compartment model each. The rat CSF PK-PD model yielded an EC(80) value of 593 ng/ml (90% confidence interval 406.8, 1,264.1). The human plasma and CSF PK data were simultaneously well described by a two-compartment model. Simulations showed that in humans at 100 mg QD, CSF levels of Org 26576 would exceed the EC(80) target concentration for about 2 h and that 400 mg BID would engage AMPA receptors for 24 h. The modelling approach provided useful insight on the likely human dose-molecular target engagement relationship for Org 26576. Based on the current analysis, 100 and 400 mg BID would be suitable to provide 'phasic' and 'continuous' AMPA receptor engagement, respectively.

The Effect of Triptolide in Rheumatoid Arthritis: From Basic Research towards Clinical Translation

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Danping Fan

2018-01-01

Full Text Available Triptolide (TP, a major extract of the herb Tripterygium wilfordii Hook F (TWHF, has been shown to exert potent pharmacological effects, especially an immunosuppressive effect in the treatment of rheumatoid arthritis (RA. However, its multiorgan toxicity prevents it from being widely used in clinical practice. Recently, several attempts are being performed to reduce TP toxicity. In this review, recent progress in the use of TP for RA, including its pharmacological effects and toxicity, is summarized. Meanwhile, strategies relying on chemical structural modifications, innovative delivery systems, and drug combinations to alleviate the disadvantages of TP are also reviewed. Furthermore, we also discuss the challenges and perspectives in their clinical translation.

Interdisciplinarity in translation teaching: competence-based education, translation task-based approach, context-based text typology

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Edelweiss Vitol Gysel

2017-05-01

Full Text Available In the context of competence-based teaching, this paper draws upon the model of Translation Competence (TC put forward by the PACTE group (2003 to establish a dialogue between cognitive-constructivist paradigms for translation teaching and the model of the Context-based Text Typology (MATTHIESSEN et al., 2007. In this theoretical environment, it proposes a model for the design of a Teaching Unit (TU for the development of the bilingual competence in would-be-translators.To this end, it explores translation as a cognitive, communicative and textual activity (HURTADO ALBIR, 2011 and considers its teaching from the translation task-based approach (HURTADO ALBIR, 1999. This approach is illustrated through the practical example of the design of a TU elaborated for the subject ‘Introduction to Specialized Translation’,part of the curricular grid of the program ‘Secretariado Executivo’ at Universidade Federal de Santa Catarina. Aspects such as the establishment of learning objectives and their alignment with the translation tasks composing the TU are addressed for this specific pedagogical situation. We argue for the development of textual competences by means of the acquisition of strategies derived from the Context-based Text Typology to solve problems arising from the translation of different text types and contextual configurations.

Early-life stress origins of gastrointestinal disease: animal models, intestinal pathophysiology, and translational implications

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Pohl, Calvin S.; Medland, Julia E.

2015-01-01

Early-life stress and adversity are major risk factors in the onset and severity of gastrointestinal (GI) disease in humans later in life. The mechanisms by which early-life stress leads to increased GI disease susceptibility in adult life remain poorly understood. Animal models of early-life stress have provided a foundation from which to gain a more fundamental understanding of this important GI disease paradigm. This review focuses on animal models of early-life stress-induced GI disease, with a specific emphasis on translational aspects of each model to specific human GI disease states. Early postnatal development of major GI systems and the consequences of stress on their development are discussed in detail. Relevant translational differences between species and models are highlighted. PMID:26451004

The Impact of Machine Translation and Computer-aided Translation on Translators

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Peng, Hao

2018-03-01

Under the context of globalization, communications between countries and cultures are becoming increasingly frequent, which make it imperative to use some techniques to help translate. This paper is to explore the influence of computer-aided translation on translators, which is derived from the field of the computer-aided translation (CAT) and machine translation (MT). Followed by an introduction to the development of machine and computer-aided translation, it then depicts the technologies practicable to translators, which are trying to analyze the demand of designing the computer-aided translation so far in translation practice, and optimize the designation of computer-aided translation techniques, and analyze its operability in translation. The findings underline the advantages and disadvantages of MT and CAT tools, and the serviceability and future development of MT and CAT technologies. Finally, this thesis probes into the impact of these new technologies on translators in hope that more translators and translation researchers can learn to use such tools to improve their productivity.

Pharmacological Evaluation of Chrozophora tinctoria as Wound Healing Potential in Diabetic Rat’s Model

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Harikesh Maurya

2016-01-01

Full Text Available Objective. The study was designed to evaluate pharmacological potential of hydroalcoholic leaves extract of Chrozophora tinctoria intended for wound healing in diabetic rats’ model. Methods. The method used to evaluate the pharmacological potential of hydroalcoholic leave extract was physical incision rat model. In this model, cutting of the skin and/or other tissues with a sharp blade has been made and the rapid disruption of tissue integrity with minimal collateral damage was observed shortly. Animals used in the study were divided into four groups that consist of six animals in each group. Group I serves as normal control, Group II serves as disease control, Group III was used as standard treatment (Povidone iodine 50 mg/kg b.w., and Group IV was used for test drug (C. tinctoria 50 mg/kg b.w.. Result. The hydroalcoholic leave extract of Chrozophora tinctoria has been significantly observed to heal the wound (98% in diabetic rats within 21 days, while standard drug (Povidone iodine healed the wound about 95% in the same condition. The oral dose (50 mg/kg b.w. of Chrozophora tinctoria was also found to improve the elevated blood glucose level in comparison to disease control group, which increased after the oral administration of Streptozotocin. Conclusion. The Chrozophora tinctoria has significant wound healing potential in the animal having physically damaged tissue in diabetic condition.

Determinants of translation ambiguity

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Degani, Tamar; Prior, Anat; Eddington, Chelsea M.; Arêas da Luz Fontes, Ana B.; Tokowicz, Natasha

2016-01-01

Ambiguity in translation is highly prevalent, and has consequences for second-language learning and for bilingual lexical processing. To better understand this phenomenon, the current study compared the determinants of translation ambiguity across four sets of translation norms from English to Spanish, Dutch, German and Hebrew. The number of translations an English word received was correlated across these different languages, and was also correlated with the number of senses the word has in English, demonstrating that translation ambiguity is partially determined by within-language semantic ambiguity. For semantically-ambiguous English words, the probability of the different translations in Spanish and Hebrew was predicted by the meaning-dominance structure in English, beyond the influence of other lexical and semantic factors, for bilinguals translating from their L1, and translating from their L2. These findings are consistent with models postulating direct access to meaning from L2 words for moderately-proficient bilinguals. PMID:27882188

Typologically robust statistical machine translation : Understanding and exploiting differences and similarities between languages in machine translation

NARCIS (Netherlands)

Daiber, J.

2018-01-01

Machine translation systems often incorporate modeling assumptions motivated by properties of the language pairs they initially target. When such systems are applied to language families with considerably different properties, translation quality can deteriorate. Phrase-based machine translation

Resetting translational homeostasis restores myelination in Charcot-Marie-Tooth disease type 1B mice.

Science.gov (United States)

D'Antonio, Maurizio; Musner, Nicolò; Scapin, Cristina; Ungaro, Daniela; Del Carro, Ubaldo; Ron, David; Feltri, M Laura; Wrabetz, Lawrence

2013-04-08

P0 glycoprotein is an abundant product of terminal differentiation in myelinating Schwann cells. The mutant P0S63del causes Charcot-Marie-Tooth 1B neuropathy in humans, and a very similar demyelinating neuropathy in transgenic mice. P0S63del is retained in the endoplasmic reticulum of Schwann cells, where it promotes unfolded protein stress and elicits an unfolded protein response (UPR) associated with translational attenuation. Ablation of Chop, a UPR mediator, from S63del mice completely rescues their motor deficit and reduces active demyelination by half. Here, we show that Gadd34 is a detrimental effector of CHOP that reactivates translation too aggressively in myelinating Schwann cells. Genetic or pharmacological limitation of Gadd34 function moderates translational reactivation, improves myelination in S63del nerves, and reduces accumulation of P0S63del in the ER. Resetting translational homeostasis may provide a therapeutic strategy in tissues impaired by misfolded proteins that are synthesized during terminal differentiation.

Exaggerated Cap-Dependent Translation as a Mechanism for Corticostriatal Dysfunction in Fragile X Syndrome Model Mice

Science.gov (United States)

2017-11-01

AWARD NUMBER: W81XWH-15-1-0361 TITLE: “Exaggerated Cap-Dependent Translation as a Mechanism for Corticostriatal Dysfunction in Fragile X...Annual 3. DATES COVERED 19Oct2016 - 18Oct2017 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER “Exaggerated Cap-Dependent Translation as a Mechanism for... translation inhibitors. Our specific tasks are centered on a proteomic study of FXS striatal synapses by using a transgenic mouse model that allows to

Translation Theory 'Translated'

DEFF Research Database (Denmark)

Wæraas, Arild; Nielsen, Jeppe

2016-01-01

Translation theory has proved to be a versatile analytical lens used by scholars working from different traditions. On the basis of a systematic literature review, this study adds to our understanding of the ‘translations’ of translation theory by identifying the distinguishing features of the most...... common theoretical approaches to translation within the organization and management discipline: actor-network theory, knowledge-based theory, and Scandinavian institutionalism. Although each of these approaches already has borne much fruit in research, the literature is diverse and somewhat fragmented......, but also overlapping. We discuss the ways in which the three versions of translation theory may be combined and enrich each other so as to inform future research, thereby offering a more complete understanding of translation in and across organizational settings....

Binary translation using peephole translation rules

Science.gov (United States)

Bansal, Sorav; Aiken, Alex

2010-05-04

An efficient binary translator uses peephole translation rules to directly translate executable code from one instruction set to another. In a preferred embodiment, the translation rules are generated using superoptimization techniques that enable the translator to automatically learn translation rules for translating code from the source to target instruction set architecture.

Early-life stress origins of gastrointestinal disease: animal models, intestinal pathophysiology, and translational implications.

Science.gov (United States)

Pohl, Calvin S; Medland, Julia E; Moeser, Adam J

2015-12-15

Early-life stress and adversity are major risk factors in the onset and severity of gastrointestinal (GI) disease in humans later in life. The mechanisms by which early-life stress leads to increased GI disease susceptibility in adult life remain poorly understood. Animal models of early-life stress have provided a foundation from which to gain a more fundamental understanding of this important GI disease paradigm. This review focuses on animal models of early-life stress-induced GI disease, with a specific emphasis on translational aspects of each model to specific human GI disease states. Early postnatal development of major GI systems and the consequences of stress on their development are discussed in detail. Relevant translational differences between species and models are highlighted. Copyright © 2015 the American Physiological Society.

Pharmacological effects of two cytolysins isolated from the sea ...

Indian Academy of Sciences (India)

Sticholysins I and II (St I/II) are cytolysins purified from the sea anemone Stichodactyla helianthus. In this study, we show their pharmacological action on guinea-pig and snail models in native and pH-denatured conditions in order to correlate the pharmacological findings with the pore-forming activity of both isoforms.

[New approaches in pharmacology: numerical modelling and simulation].

Science.gov (United States)

Boissel, Jean-Pierre; Cucherat, Michel; Nony, Patrice; Dronne, Marie-Aimée; Kassaï, Behrouz; Chabaud, Sylvie

2005-01-01

The complexity of pathophysiological mechanisms is beyond the capabilities of traditional approaches. Many of the decision-making problems in public health, such as initiating mass screening, are complex. Progress in genomics and proteomics, and the resulting extraordinary increase in knowledge with regard to interactions between gene expression, the environment and behaviour, the customisation of risk factors and the need to combine therapies that individually have minimal though well documented efficacy, has led doctors to raise new questions: how to optimise choice and the application of therapeutic strategies at the individual rather than the group level, while taking into account all the available evidence? This is essentially a problem of complexity with dimensions similar to the previous ones: multiple parameters with nonlinear relationships between them, varying time scales that cannot be ignored etc. Numerical modelling and simulation (in silico investigations) have the potential to meet these challenges. Such approaches are considered in drug innovation and development. They require a multidisciplinary approach, and this will involve modification of the way research in pharmacology is conducted.

Quality management of pharmacology and safety pharmacology studies

DEFF Research Database (Denmark)

Spindler, Per; Seiler, Jürg P

2002-01-01

to safety pharmacology studies, and, when indicated, to secondary pharmacodynamic studies, does not influence the scientific standards of studies. However, applying formal GLP standards will ensure the quality, reliability and integrity of studies, which reflect sound study management. It is important...... to encourage a positive attitude among researchers and academics towards these lines, whenever possible. GLP principles applied to the management of non-clinical safety studies are appropriate quality standards when studies are used in the context of protecting public health, and these quality standards...... of pharmacology studies (ICH S7A): primary pharmacodynamic, secondary pharmacodynamic and safety pharmacology studies, and guidance on the quality standards (expectations for GLP conformity) for these study types have been provided. Primary pharmacodynamic studies are the only study types that are fully exempt...

Untranslated regions of diverse plant viral RNAs vary greatly in translation enhancement efficiency

Directory of Open Access Journals (Sweden)

Fan Qiuling

2012-05-01

Full Text Available Abstract Background Whole plants or plant cell cultures can serve as low cost bioreactors to produce massive amounts of a specific protein for pharmacological or industrial use. To maximize protein expression, translation of mRNA must be optimized. Many plant viral RNAs harbor extremely efficient translation enhancers. However, few of these different translation elements have been compared side-by-side. Thus, it is unclear which are the most efficient translation enhancers. Here, we compare the effects of untranslated regions (UTRs containing translation elements from six plant viruses on translation in wheat germ extract and in monocotyledenous and dicotyledenous plant cells. Results The highest expressing uncapped mRNAs contained viral UTRs harboring Barley yellow dwarf virus (BYDV-like cap-independent translation elements (BTEs. The BYDV BTE conferred the most efficient translation of a luciferase reporter in wheat germ extract and oat protoplasts, while uncapped mRNA containing the BTE from Tobacco necrosis virus-D translated most efficiently in tobacco cells. Capped mRNA containing the Tobacco mosaic virus omega sequence was the most efficient mRNA in tobacco cells. UTRs from Satellite tobacco necrosis virus, Tomato bushy stunt virus, and Crucifer-infecting tobamovirus (crTMV did not stimulate translation efficiently. mRNA with the crTMV 5′ UTR was unstable in tobacco protoplasts. Conclusions BTEs confer the highest levels of translation of uncapped mRNAs in vitro and in vivo, while the capped omega sequence is most efficient in tobacco cells. These results provide a basis for understanding mechanisms of translation enhancement, and for maximizing protein synthesis in cell-free systems, transgenic plants, or in viral expression vectors.

Morphological Analysis for Statistical Machine Translation

National Research Council Canada - National Science Library

Lee, Young-Suk

2004-01-01

.... The technique improves Arabic-to-English translation qualities significantly when applied to IBM Model 1 and Phrase Translation Models trained on the training corpus size ranging from 3,500 to 3.3 million sentence pairs.

Modeling timelines for translational science in cancer; the impact of technological maturation.

Directory of Open Access Journals (Sweden)

Laura M McNamee

Full Text Available This work examines translational science in cancer based on theories of innovation that posit a relationship between the maturation of technologies and their capacity to generate successful products. We examined the growth of technologies associated with 138 anticancer drugs using an analytical model that identifies the point of initiation of exponential growth and the point at which growth slows as the technology becomes established. Approval of targeted and biological products corresponded with technological maturation, with first approval averaging 14 years after the established point and 44 years after initiation of associated technologies. The lag in cancer drug approvals after the increases in cancer funding and dramatic scientific advances of the 1970s thus reflects predictable timelines of technology maturation. Analytical models of technological maturation may be used for technological forecasting to guide more efficient translation of scientific discoveries into cures.

PKPD modelling of PR and QRS intervals in conscious dogs using standard safety pharmacology data.

Science.gov (United States)

Bergenholm, Linnéa; Collins, Teresa; Evans, Neil D; Chappell, Michael J; Parkinson, Joanna

2016-01-01

Pharmacokinetic-pharmacodynamic (PKPD) modelling can improve safety assessment, but few PKPD models describing drug-induced QRS and PR prolongations have been published. This investigation aims to develop and evaluate PKPD models for describing QRS and PR effects in routine safety studies. Exposure and telemetry data from safety pharmacology studies in conscious beagle dogs were acquired. Mixed effects baseline and PK-QRS/PR models were developed for the anti-arrhythmic compounds AZD1305, flecainide, quinidine and verapamil and the anti-muscarinic compounds AZD8683 and AZD9164. RR interval correction and circadian rhythms were investigated for predicting baseline variability. Individual PK predictions were used to drive the pharmacological effects evaluating linear and non-linear direct and effect compartment models. Conduction slowing induced by the tested anti-arrhythmics was direct and proportional at low exposures, whilst time delays and non-linear effects were evident for the tested anti-muscarinics. AZD1305, flecainide and quinidine induced QRS widening with 4.2, 10 and 5.6% μM(-1) unbound drug. AZD1305 and flecainide also prolonged PR with 13.5 and 11.5% μM(-1). PR prolongations induced by the anti-muscarinics and verapamil were best described by Emax models with maximal effects ranging from 55 to 95%. RR interval correction and circadian rhythm improved PR but not QRS modelling. However, circadian rhythm had minor impact on estimated drug effects. Baseline and drug-induced effects on QRS and PR intervals can be effectively described with PKPD models using routine data, providing quantitative safety information to support drug discovery and development. Copyright © 2016 Elsevier Inc. All rights reserved.

Pharmacological Classification and Activity Evaluation of Furan and Thiophene Amide Derivatives Applying Semi-Empirical ab initio Molecular Modeling Methods

Directory of Open Access Journals (Sweden)

Leszek Bober

2012-05-01

Full Text Available Pharmacological and physicochemical classification of the furan and thiophene amide derivatives by multiple regression analysis and partial least square (PLS based on semi-empirical ab initio molecular modeling studies and high-performance liquid chromatography (HPLC retention data is proposed. Structural parameters obtained from the PCM (Polarizable Continuum Model method and the literature values of biological activity (antiproliferative for the A431 cells expressed as LD₅₀ of the examined furan and thiophene derivatives was used to search for relationships. It was tested how variable molecular modeling conditions considered together, with or without HPLC retention data, allow evaluation of the structural recognition of furan and thiophene derivatives with respect to their pharmacological properties.

Machine Translation and Other Translation Technologies.

Science.gov (United States)

Melby, Alan

1996-01-01

Examines the application of linguistic theory to machine translation and translator tools, discusses the use of machine translation and translator tools in the real world of translation, and addresses the impact of translation technology on conceptions of language and other issues. Findings indicate that the human mind is flexible and linguistic…

Sobol Sensitivity Analysis: A Tool to Guide the Development and Evaluation of Systems Pharmacology Models

Science.gov (United States)

Trame, MN; Lesko, LJ

2015-01-01

A systems pharmacology model typically integrates pharmacokinetic, biochemical network, and systems biology concepts into a unifying approach. It typically consists of a large number of parameters and reaction species that are interlinked based upon the underlying (patho)physiology and the mechanism of drug action. The more complex these models are, the greater the challenge of reliably identifying and estimating respective model parameters. Global sensitivity analysis provides an innovative tool that can meet this challenge. CPT Pharmacometrics Syst. Pharmacol. (2015) 4, 69–79; doi:10.1002/psp4.6; published online 25 February 2015 PMID:27548289

Double pharmacological challenge on repolarization opens new avenues for drug safety research

DEFF Research Database (Denmark)

Thomsen, Morten Bækgaard

2007-01-01

pointes (TdP) arrhythmia. Both the pharmaceutical industry and the regulatory bodies are neglecting the available proarrhythmia models. In vitro studies have suggested that combined pharmacological hits on repolarization will produce a superior substrate for in vivo proarrhythmia, compared to the single......-drug assessment. By using consecutive pharmacological challenges, a simple model is proposed, in which combinatorial pharmacology is employed to provoke TdP in the conscious dog. The pharmaceutical industry interested in evaluating the proarrhythmic potential of their present and future drugs now has a simple...

Trends in safety pharmacology: posters presented at the annual meetings of the Safety Pharmacology Society 2001-2010.

Science.gov (United States)

Redfern, William S; Valentin, Jean-Pierre

2011-01-01

The inaugural meeting of the Safety Pharmacology Society (SPS) was in 2001, soon after ICH S7A had been adopted. The 10th anniversary is an appropriate milestone at which to analyse trends in the science and themes of safety pharmacology, as reflected in posters presented at the annual meetings. The source information was the poster abstract booklets from each of the first ten annual meetings. The number of posters rose steadily from 34 in 2001 to 201 in 2010. The proportion of posters containing in vitro data has remained constant throughout the decade at ~30%. In terms of organ functions, themes relating to the cardiovascular system (CVS) have always generated the majority of posters, remaining above 60% of the total for the last 9years. The dominant theme has been around 'QT liability'. This peaked in 2003 at 68% of all posters presented, around the time of the ICHS7B discussions, and has remained above 30% thereafter. Apart from 2003 (dipping to 4%), CNS-related posters have remained steady at 11-17% throughout the decade. Respiratory-related posters have remained at 5-8% over the last 5years. Gastrointestinal (GI)-related posters have contributed 2-6% throughout the decade, and renal-related posters 1-3%. Posters on combined organ assessments have appeared in recent years. The relative emphasis on the different organ functions is broadly proportional to the causes of candidate drug attrition preclinically, whereas both CNS and GI are under-represented when considering their contribution to significant adverse effects during clinical development. Trends are either regulatory-driven (e.g. increase in posters on abuse-dependence liability since EMEA/CHMP/SWP/94227/2004), technology-driven (e.g. automated hERG assay; left ventricular function; non-invasive CVS measurements; stem cells, etc.), or relate to the predictive ability of safety pharmacology data (e.g. clinical translation initiatives; concordance between in vitro and in vivo preclinical data; integrated

Delirium in the elderly: A systematic review of pharmacological and non-pharmacological treatments

Directory of Open Access Journals (Sweden)

Cecília Carboni Tardelli Cerveira

Full Text Available ABSTRACT Delirium is a common disorder associated with poor prognosis, especially in the elderly. The impact of different treatment approaches for delirium on morbimortality and long-term welfare is not completely understood. OBJECTIVE: To determine the efficacy of pharmacological and non-pharmacological treatments in elderly patients with delirium. METHODS: This systematic review compared pharmacological and non-pharmacological treatments in patients over 60 years old with delirium. Databases used were: MEDLINE (PubMed, EMBASE, Cochrane CENTRAL and LILACS from inception to January 6th, 2016. RESULTS: A total of ten articles were selected. The six non-pharmacological intervention studies showed no impact on duration of delirium, mortality or institutionalization, but a decrease in severity of delirium and improvement in medium-term cognitive function were observed. The most commonly used interventions were temporal-spatial orientation, orientation to self and others, early mobilization and sleep hygiene. The four studies with pharmacological interventions found that rivastigmine reduced the duration of delirium, improved cognitive function and reduced caregiver burden; olanzapine and haloperidol decreased the severity of delirium; droperidol reduced length of hospitalization and improved delirium remission rate. CONCLUSION: Although the pharmacological approach has been used in the treatment of delirium among elderly, there have been few studies assessing its efficacy, involving a small number of patients. However, the improvements in delirium duration and severity suggest these drugs are effective in treating the condition. Once delirium has developed, non-pharmacological treatment seems less effective in controlling symptoms, and there is a lack of studies describing different non-pharmacological interventions.

Pharmacology Portal: An Open Database for Clinical Pharmacologic Laboratory Services.

Science.gov (United States)

Karlsen Bjånes, Tormod; Mjåset Hjertø, Espen; Lønne, Lars; Aronsen, Lena; Andsnes Berg, Jon; Bergan, Stein; Otto Berg-Hansen, Grim; Bernard, Jean-Paul; Larsen Burns, Margrete; Toralf Fosen, Jan; Frost, Joachim; Hilberg, Thor; Krabseth, Hege-Merete; Kvan, Elena; Narum, Sigrid; Austgulen Westin, Andreas

2016-01-01

More than 50 Norwegian public and private laboratories provide one or more analyses for therapeutic drug monitoring or testing for drugs of abuse. Practices differ among laboratories, and analytical repertoires can change rapidly as new substances become available for analysis. The Pharmacology Portal was developed to provide an overview of these activities and to standardize the practices and terminology among laboratories. The Pharmacology Portal is a modern dynamic web database comprising all available analyses within therapeutic drug monitoring and testing for drugs of abuse in Norway. Content can be retrieved by using the search engine or by scrolling through substance lists. The core content is a substance registry updated by a national editorial board of experts within the field of clinical pharmacology. This ensures quality and consistency regarding substance terminologies and classification. All laboratories publish their own repertoires in a user-friendly workflow, adding laboratory-specific details to the core information in the substance registry. The user management system ensures that laboratories are restricted from editing content in the database core or in repertoires within other laboratory subpages. The portal is for nonprofit use, and has been fully funded by the Norwegian Medical Association, the Norwegian Society of Clinical Pharmacology, and the 8 largest pharmacologic institutions in Norway. The database server runs an open-source content management system that ensures flexibility with respect to further development projects, including the potential expansion of the Pharmacology Portal to other countries. Copyright © 2016 Elsevier HS Journals, Inc. All rights reserved.

Pharmacometrics and systems pharmacology of immune checkpoint inhibitor nivolumab in cancer translational medicine

Directory of Open Access Journals (Sweden)

Sujit Nair

2016-02-01

Full Text Available Nivolumab, a fully human immunoglobulin G4 (IgG4 monoclonal antibody (mAb that targets the programmed cell death-1 (PD-1 inhibitory receptor expressed on lymphocytes and dendritic cells, has been approved for metastatic melanoma, advanced squamous non-small cell lung cancer (NSCLC and metastatic renal cell carcinoma. In this review, pharmacology and pharmacometrics systems of this immunopharmaceutical are discussed. Mechanistic actions of T-cell biology with respect to both “priming phase” (anti-cytotoxic T-lymphocyte associated antigen 4 (anti-CTLA-4 mAb; ipilimumab and “effector phase” (anti-PD-1 mAb; nivolumab was discussed, respectively. Key pharmacometric variables in anticancer efficacy of nivolumab such as target engagement, metabolism, pharmacology systems and clearance are elucidated with an emphasis on current knowledge from pre-clinical as well as phase 1, 2 and 3 clinical trials information, including the data presented at the American Society of Clinical Oncology (ASCO 2015 and European Cancer Congress 2015. Nivolumab biomarkers, safety, and synergistic combination immunotherapies are delineated. Nivolumab, administered via intravenous infusion, has an acceptable safety profile and good efficacy. Indeed, the way forward to leverage maximum benefits for the cancer patient may be to synergize anti-PD-1 blockade with complementary targets in immune checkpoint pathways or other oncogenic signal transduction pathways. The encouraging results with nivolumab lend credence to the promise of immune checkpoint blockade as a therapeutic strategy that has been come-of-age in clinical oncology. Of necessity, the burden of “financial toxicity” on cancer patients and families must be factored in considering nivolumab therapy. The problem of ligand PD-L1 being a weak biomarker in clinical practice was discussed. Appropriate patient selection methods including immunopharmacogenomics may be used to identify those patients who are most

DG TO FT - AUTOMATIC TRANSLATION OF DIGRAPH TO FAULT TREE MODELS

Science.gov (United States)

Iverson, D. L.

1994-01-01

Fault tree and digraph models are frequently used for system failure analysis. Both types of models represent a failure space view of the system using AND and OR nodes in a directed graph structure. Each model has its advantages. While digraphs can be derived in a fairly straightforward manner from system schematics and knowledge about component failure modes and system design, fault tree structure allows for fast processing using efficient techniques developed for tree data structures. The similarities between digraphs and fault trees permits the information encoded in the digraph to be translated into a logically equivalent fault tree. The DG TO FT translation tool will automatically translate digraph models, including those with loops or cycles, into fault tree models that have the same minimum cut set solutions as the input digraph. This tool could be useful, for example, if some parts of a system have been modeled using digraphs and others using fault trees. The digraphs could be translated and incorporated into the fault trees, allowing them to be analyzed using a number of powerful fault tree processing codes, such as cut set and quantitative solution codes. A cut set for a given node is a group of failure events that will cause the failure of the node. A minimum cut set for a node is any cut set that, if any of the failures in the set were to be removed, the occurrence of the other failures in the set will not cause the failure of the event represented by the node. Cut sets calculations can be used to find dependencies, weak links, and vital system components whose failures would cause serious systems failure. The DG TO FT translation system reads in a digraph with each node listed as a separate object in the input file. The user specifies a terminal node for the digraph that will be used as the top node of the resulting fault tree. A fault tree basic event node representing the failure of that digraph node is created and becomes a child of the terminal

Programming peptidomimetic syntheses by translating genetic codes designed de novo.

Science.gov (United States)

Forster, Anthony C; Tan, Zhongping; Nalam, Madhavi N L; Lin, Hening; Qu, Hui; Cornish, Virginia W; Blacklow, Stephen C

2003-05-27

Although the universal genetic code exhibits only minor variations in nature, Francis Crick proposed in 1955 that "the adaptor hypothesis allows one to construct, in theory, codes of bewildering variety." The existing code has been expanded to enable incorporation of a variety of unnatural amino acids at one or two nonadjacent sites within a protein by using nonsense or frameshift suppressor aminoacyl-tRNAs (aa-tRNAs) as adaptors. However, the suppressor strategy is inherently limited by compatibility with only a small subset of codons, by the ways such codons can be combined, and by variation in the efficiency of incorporation. Here, by preventing competing reactions with aa-tRNA synthetases, aa-tRNAs, and release factors during translation and by using nonsuppressor aa-tRNA substrates, we realize a potentially generalizable approach for template-encoded polymer synthesis that unmasks the substantially broader versatility of the core translation apparatus as a catalyst. We show that several adjacent, arbitrarily chosen sense codons can be completely reassigned to various unnatural amino acids according to de novo genetic codes by translating mRNAs into specific peptide analog polymers (peptidomimetics). Unnatural aa-tRNA substrates do not uniformly function as well as natural substrates, revealing important recognition elements for the translation apparatus. Genetic programming of peptidomimetic synthesis should facilitate mechanistic studies of translation and may ultimately enable the directed evolution of small molecules with desirable catalytic or pharmacological properties.

Translational plant proteomics: a perspective.

Science.gov (United States)

Agrawal, Ganesh Kumar; Pedreschi, Romina; Barkla, Bronwyn J; Bindschedler, Laurence Veronique; Cramer, Rainer; Sarkar, Abhijit; Renaut, Jenny; Job, Dominique; Rakwal, Randeep

2012-08-03

Translational proteomics is an emerging sub-discipline of the proteomics field in the biological sciences. Translational plant proteomics aims to integrate knowledge from basic sciences to translate it into field applications to solve issues related but not limited to the recreational and economic values of plants, food security and safety, and energy sustainability. In this review, we highlight the substantial progress reached in plant proteomics during the past decade which has paved the way for translational plant proteomics. Increasing proteomics knowledge in plants is not limited to model and non-model plants, proteogenomics, crop improvement, and food analysis, safety, and nutrition but to many more potential applications. Given the wealth of information generated and to some extent applied, there is the need for more efficient and broader channels to freely disseminate the information to the scientific community. This article is part of a Special Issue entitled: Translational Proteomics. Copyright © 2012 Elsevier B.V. All rights reserved.

Noise analysis of genome-scale protein synthesis using a discrete computational model of translation

Energy Technology Data Exchange (ETDEWEB)

Racle, Julien; Hatzimanikatis, Vassily, E-mail: vassily.hatzimanikatis@epfl.ch [Laboratory of Computational Systems Biotechnology, Ecole Polytechnique Fédérale de Lausanne (EPFL), CH-1015 Lausanne (Switzerland); Swiss Institute of Bioinformatics (SIB), CH-1015 Lausanne (Switzerland); Stefaniuk, Adam Jan [Laboratory of Computational Systems Biotechnology, Ecole Polytechnique Fédérale de Lausanne (EPFL), CH-1015 Lausanne (Switzerland)

2015-07-28

Noise in genetic networks has been the subject of extensive experimental and computational studies. However, very few of these studies have considered noise properties using mechanistic models that account for the discrete movement of ribosomes and RNA polymerases along their corresponding templates (messenger RNA (mRNA) and DNA). The large size of these systems, which scales with the number of genes, mRNA copies, codons per mRNA, and ribosomes, is responsible for some of the challenges. Additionally, one should be able to describe the dynamics of ribosome exchange between the free ribosome pool and those bound to mRNAs, as well as how mRNA species compete for ribosomes. We developed an efficient algorithm for stochastic simulations that addresses these issues and used it to study the contribution and trade-offs of noise to translation properties (rates, time delays, and rate-limiting steps). The algorithm scales linearly with the number of mRNA copies, which allowed us to study the importance of genome-scale competition between mRNAs for the same ribosomes. We determined that noise is minimized under conditions maximizing the specific synthesis rate. Moreover, sensitivity analysis of the stochastic system revealed the importance of the elongation rate in the resultant noise, whereas the translation initiation rate constant was more closely related to the average protein synthesis rate. We observed significant differences between our results and the noise properties of the most commonly used translation models. Overall, our studies demonstrate that the use of full mechanistic models is essential for the study of noise in translation and transcription.

Learning by Translating: A Contrastive Methodology for ESP Learning and Translation

Directory of Open Access Journals (Sweden)

Sara Laviosa

2015-11-01

Full Text Available Over the last few years applied linguists have explored the possibility of integrating the insights of second language acquisition theories, contrastive analysis, foreign language teaching methodologies, and translation studies with a view to enhancing current communicative models and techniques for L2 teaching and translator training (see for example Sewell and Higgins 1996; Laviosa-Braithwaite 1997; Campbell 1998; Malmkjær 1998; Laviosa 2000; Colina 2002. We intend to make a contribution to this interdisciplinary orientation by putting forward a translation-based methodology for learning ESP vocabulary and grammar through real life mediating communicative activities. With particular reference to the translation task itself, we endeavour to provide teachers of English for special purposes and translator trainers with a methodology for guiding their students in producing, to the best of their abilities, a target text which meets the quality criteria of terminological accuracy and stylistic fluency, and is also effective in terms of the communicative situation it is intended for. After outlining the rationale and main theoretical approaches underpinning our work, we will illustrate our methodology for learning ESP vocabulary and translation skills from a contrastive perspective, as in our book Learning by Translating (Laviosa and Cleverton 2003.

Recent Advances in Translational Magnetic Resonance Imaging in Animal Models of Stress and Depression.

Science.gov (United States)

McIntosh, Allison L; Gormley, Shane; Tozzi, Leonardo; Frodl, Thomas; Harkin, Andrew

2017-01-01

Magnetic resonance imaging (MRI) is a valuable translational tool that can be used to investigate alterations in brain structure and function in both patients and animal models of disease. Regional changes in brain structure, functional connectivity, and metabolite concentrations have been reported in depressed patients, giving insight into the networks and brain regions involved, however preclinical models are less well characterized. The development of more effective treatments depends upon animal models that best translate to the human condition and animal models may be exploited to assess the molecular and cellular alterations that accompany neuroimaging changes. Recent advances in preclinical imaging have facilitated significant developments within the field, particularly relating to high resolution structural imaging and resting-state functional imaging which are emerging techniques in clinical research. This review aims to bring together the current literature on preclinical neuroimaging in animal models of stress and depression, highlighting promising avenues of research toward understanding the pathological basis of this hugely prevalent disorder.

Recent Advances in Translational Magnetic Resonance Imaging in Animal Models of Stress and Depression

Directory of Open Access Journals (Sweden)

Allison L. McIntosh

2017-05-01

Full Text Available Magnetic resonance imaging (MRI is a valuable translational tool that can be used to investigate alterations in brain structure and function in both patients and animal models of disease. Regional changes in brain structure, functional connectivity, and metabolite concentrations have been reported in depressed patients, giving insight into the networks and brain regions involved, however preclinical models are less well characterized. The development of more effective treatments depends upon animal models that best translate to the human condition and animal models may be exploited to assess the molecular and cellular alterations that accompany neuroimaging changes. Recent advances in preclinical imaging have facilitated significant developments within the field, particularly relating to high resolution structural imaging and resting-state functional imaging which are emerging techniques in clinical research. This review aims to bring together the current literature on preclinical neuroimaging in animal models of stress and depression, highlighting promising avenues of research toward understanding the pathological basis of this hugely prevalent disorder.

冲突--翻译伦理模式理论再思考%Conflicts---Second Thought on Models of Translational Ethics

Institute of Scientific and Technical Information of China (English)

梅阳春; 汤金霞

2013-01-01

　　One of the major trends in the translating study in China is drawing inspiration from western trans-lational ethics and constructing Chinese translational ethics .Among the western schools of translational eth-ics ,theory of models of translation ethics constituted by translational ethics of representation ,of service ,of communication ,norm-based translational ethics and translational ethics of commitment gives such inspiration to the construction of Chinese translational ethics that there comes from the circle of translation in China the voice of formulating Chinese translation ethics on the basis of this theory .It is discovered that the first four models of translational ethics contradict each other in what interest group they should serve most ,in what sta-tus they should confer on each of the translation agents but the translator and in what status they should con -fer on the translator . Translational ethics of commitment ,with the purpose of integrating four preceding models of translational ethics can not solve the problem of incompatibility between the four translational eth-ics .Therefore ,theory of models of translational ethics ,though beneficial to the construction of Chinese trans-lational ethics ,can not act as the basis of this construction .%　　借鉴西方翻译伦理学研究成果构建中国翻译伦理学是当今中国翻译学的主要发展趋势之一。在西方翻译伦理学诸流派中，由翻译的再现伦理、服务伦理、交际伦理、规范伦理和承诺伦理构建的翻译伦理模式理论对中国翻译伦理学的发展影响最大，以至于国内翻译界出现了要以该理论为基础构建中国翻译伦理学的呼声。但该理论的前四种伦理在服务主体、主体定位和译者定位三个维度上的冲突导致它们互不兼容，旨在融合四种翻译伦理的承诺伦理也未能解决兼容性问题。因此，以翻译伦理模式为基础构建中国翻译伦理学的设想并不可行。

A Novel Genomic Signature with Translational Significance for Human Idiopathic Pulmonary Fibrosis

Science.gov (United States)

Tedrow, John; de Bernard, Simon; Birker-Robaczewska, Magdalena; Gibson, Kevin F.; Guardela, Brenda Juan; Hess, Patrick; Klenk, Axel; Lindell, Kathleen O.; Poirey, Sylvie; Renault, Bérengère; Rey, Markus; Weber, Edgar; Nayler, Oliver; Kaminski, Naftali

2015-01-01

The bleomycin-induced rodent lung fibrosis model is commonly used to study mechanisms of lung fibrosis and to test potential therapeutic interventions, despite the well recognized dissimilarities to human idiopathic pulmonary fibrosis (IPF). Therefore, in this study, we sought to identify genomic commonalities between the gene expression profiles from 100 IPF lungs and 108 control lungs that were obtained from the Lung Tissue Research Consortium, and rat lungs harvested at Days 3, 7, 14, 21, 28, 42, and 56 after bleomycin instillation. Surprisingly, the highest gene expression similarity between bleomycin-treated rat and IPF lungs was observed at Day 7. At this point of maximal rat–human commonality, we identified a novel set of 12 disease-relevant translational gene markers (C6, CTHRC1, CTSE, FHL2, GAL, GREM1, LCN2, MMP7, NELL1, PCSK1, PLA2G2A, and SLC2A5) that was able to separate almost all patients with IPF from control subjects in our cohort and in two additional IPF/control cohorts (GSE10667 and GSE24206). Furthermore, in combination with diffusing capacity of carbon monoxide measurements, four members of the translational gene marker set contributed to stratify patients with IPF according to disease severity. Significantly, pirfenidone attenuated the expression change of one (CTHRC1) translational gene marker in the bleomycin-induced lung fibrosis model, in transforming growth factor-β1–treated primary human lung fibroblasts and transforming growth factor-β1–treated human epithelial A549 cells. Our results suggest that a strategy focused on rodent model–human disease commonalities may identify genes that could be used to predict the pharmacological impact of therapeutic interventions, and thus facilitate the development of novel treatments for this devastating lung disease. PMID:25029475

Translation techniques for distributed-shared memory programming models

Energy Technology Data Exchange (ETDEWEB)

Fuller, Douglas James [Iowa State Univ., Ames, IA (United States)

2005-01-01

The high performance computing community has experienced an explosive improvement in distributed-shared memory hardware. Driven by increasing real-world problem complexity, this explosion has ushered in vast numbers of new systems. Each new system presents new challenges to programmers and application developers. Part of the challenge is adapting to new architectures with new performance characteristics. Different vendors release systems with widely varying architectures that perform differently in different situations. Furthermore, since vendors need only provide a single performance number (total MFLOPS, typically for a single benchmark), they only have strong incentive initially to optimize the API of their choice. Consequently, only a fraction of the available APIs are well optimized on most systems. This causes issues porting and writing maintainable software, let alone issues for programmers burdened with mastering each new API as it is released. Also, programmers wishing to use a certain machine must choose their API based on the underlying hardware instead of the application. This thesis argues that a flexible, extensible translator for distributed-shared memory APIs can help address some of these issues. For example, a translator might take as input code in one API and output an equivalent program in another. Such a translator could provide instant porting for applications to new systems that do not support the application's library or language natively. While open-source APIs are abundant, they do not perform optimally everywhere. A translator would also allow performance testing using a single base code translated to a number of different APIs. Most significantly, this type of translator frees programmers to select the most appropriate API for a given application based on the application (and developer) itself instead of the underlying hardware.

Slow dynamics in translation-invariant quantum lattice models

Science.gov (United States)

Michailidis, Alexios A.; Žnidarič, Marko; Medvedyeva, Mariya; Abanin, Dmitry A.; Prosen, Tomaž; Papić, Z.

2018-03-01

Many-body quantum systems typically display fast dynamics and ballistic spreading of information. Here we address the open problem of how slow the dynamics can be after a generic breaking of integrability by local interactions. We develop a method based on degenerate perturbation theory that reveals slow dynamical regimes and delocalization processes in general translation invariant models, along with accurate estimates of their delocalization time scales. Our results shed light on the fundamental questions of the robustness of quantum integrable systems and the possibility of many-body localization without disorder. As an example, we construct a large class of one-dimensional lattice models where, despite the absence of asymptotic localization, the transient dynamics is exceptionally slow, i.e., the dynamics is indistinguishable from that of many-body localized systems for the system sizes and time scales accessible in experiments and numerical simulations.

Translating VDM to Alloy

DEFF Research Database (Denmark)

Lausdahl, Kenneth

2013-01-01

specifications. However, to take advantage of the automated analysis of Alloy, the model-oriented VDM specifications must be translated into a constraint-based Alloy specifications. We describe how a sub- set of VDM can be translated into Alloy and how assertions can be expressed in VDM and checked by the Alloy...

A Translational Model of Research-Practice Integration

Science.gov (United States)

Vivian, Dina; Hershenberg, Rachel; Teachman, Bethany A.; Drabick, Deborah A. G.; Goldfried, Marvin R.; Wolfe, Barry

2013-01-01

We propose a four-level, recursive Research-Practice Integration framework as a heuristic to (a) integrate and reflect on the articles in this Special Section as contributing to a bidirectional bridge between research and practice, and (b) consider additional opportunities to address the research–practice gap. Level 1 addresses Treatment Validation studies and includes an article by Lochman and colleagues concerning the programmatic adaptation, implementation, and dissemination of the empirically supported Coping Power treatment program for youth aggression. Level 2 translation, Training in Evidence-Based Practice, includes a paper by Hershenberg, Drabick, and Vivian, which focuses on the critical role that predoctoral training plays in bridging the research–practice gap. Level 3 addresses the Assessment of Clinical Utility and Feedback to Research aspects of translation. The articles by Lambert and Youn, Kraus, and Castonguay illustrate the use of commercial outcome packages that enable psychotherapists to integrate ongoing client assessment, thus enhancing the effectiveness of treatment implementation and providing data that can be fed back to researchers. Lastly, Level 4 translation, the Cross-Level Integrative Research and Communication, concerns research efforts that integrate data from clinical practice and all other levels of translation, as well as communication efforts among all stakeholders, such as researchers, psychotherapists, and clients. Using a two-chair technique as a framework for his discussion, Wolfe's article depicts the struggle inherent in research–practice integration efforts and proposes a rapprochement that highlights advancements in the field. PMID:22642522

The relationship between impulsive choice and impulsive action: a cross-species translational study.

Directory of Open Access Journals (Sweden)

Nienke Broos

Full Text Available Maladaptive impulsivity is a core symptom in various psychiatric disorders. However, there is only limited evidence available on whether different measures of impulsivity represent largely unrelated aspects or a unitary construct. In a cross-species translational study, thirty rats were trained in impulsive choice (delayed reward task and impulsive action (five-choice serial reaction time task paradigms. The correlation between those measures was assessed during baseline performance and after pharmacological manipulations with the psychostimulant amphetamine and the norepinephrine reuptake inhibitor atomoxetine. In parallel, to validate the animal data, 101 human subjects performed analogous measures of impulsive choice (delay discounting task, DDT and impulsive action (immediate and delayed memory task, IMT/DMT. Moreover, all subjects completed the Stop Signal Task (SST, as an additional measure of impulsive action and filled out the Barratt impulsiveness scale (BIS-11. Correlations between DDT and IMT/DMT were determined and a principal component analysis was performed on all human measures of impulsivity. In both rats and humans measures of impulsive choice and impulsive action did not correlate. In rats the within-subject pharmacological effects of amphetamine and atomoxetine did not correlate between tasks, suggesting distinct underlying neural correlates. Furthermore, in humans, principal component analysis identified three independent factors: (1 self-reported impulsivity (BIS-11; (2 impulsive action (IMT/DMT and SST; (3 impulsive choice (DDT. This is the first study directly comparing aspects of impulsivity using a cross-species translational approach. The present data reveal the non-unitary nature of impulsivity on a behavioral and pharmacological level. Collectively, this warrants a stronger focus on the relative contribution of distinct forms of impulsivity in psychopathology.

A Course Evaluation Tool Based on SPICES Model, and its Application to Evaluation of Medical Pharmacology Course

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Tahereh Changiz

2009-02-01

Full Text Available Background and purpose: The SPICES model has been proposed to be used both as a framework for quality improvement in medical education and as a guide for evaluation of curricula. The six strategies of SPICES are representatives of innovative approaches to medical education, and each one has been considered as a continuum. The present study models a theory-based questionnaire, based on SPICES, to be used as a course evaluation tool, through developing a conceptual model for eachcontinuum of the six.Methods: At the first step, operational definition and questionnaire development was performed as an extensive literature review and consensus building in a focus groups of experts .The content andface validity of questionnaire was confirmed. In the second phase-as a pilot -, the questionnaire was used for evaluation of Medical Pharmacology course at Isfahan University of Medical Sciences.Results: The results showed that Medical Pharmacology course located in the traditional end of SPICES continua according to the most aspects of the course.Conclusion: The pilot study showed that the questionnaire scale should be changed. Also it may be more feasible and valid if an item bank is prepared based on the proposed matrix and appropriate items are selected according to the general situation of the curriculum.Keywords: SPICES MODEL, EVALUATION

PATRAN-STAGS translator (PATSTAGS)

Science.gov (United States)

Otte, Neil

1990-01-01

A a computer program used to translate PATRAN finite element model data into Structural Analysis of General Shells (STAGS) input data is presented. The program supports translation of nodal, nodal constraints, element, force, and pressure data. The subroutine UPRESS required for the readings of live pressure data into STAGS is also presented.

Translating Institutional Templates: A Historical Account of the Consequences of Importing Policing Models into Argentina

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Matías Dewey

2017-01-01

Full Text Available This article focuses on the translation of the French and English law enforcement models into Argentina and analyzes its consequences in terms of social order. Whereas in the former two models the judiciary and police institutions originated in large-scale processes of historical consolidation, in the latter these institutions were implanted without the antecedents present in their countries of origin. The empirical references are Argentine police institutions, particularly the police of the Buenos Aires Province, observed at two moments in which the institutional import was particularly intense: towards the end of the nineteenth and beginning of the twentieth centuries, and at the end of the twentieth century. By way of tracing these processes of police constitution and reform, we show how new models of law enforcement and policing interacted with indigenous political structures and cultural frames, as well as how this constellation produced a social order in which legality and illegality are closely interwoven. The article is an attempt to go beyond the common observations regarding how an imported model failed; instead, it dissects the effects the translation actually produced and how the translated models transform into resources that reshape the new social order. A crucial element, the article shows, is that these resources can be instrumentalized according to »idiosyncrasies«, interests, and quotas of power.

Mapping Translation Technology Research in Translation Studies

DEFF Research Database (Denmark)

Schjoldager, Anne; Christensen, Tina Paulsen; Flanagan, Marian

2017-01-01

section aims to improve this situation by presenting new and innovative research papers that reflect on recent technological advances and their impact on the translation profession and translators from a diversity of perspectives and using a variety of methods. In Section 2, we present translation......Due to the growing uptake of translation technology in the language industry and its documented impact on the translation profession, translation students and scholars need in-depth and empirically founded knowledge of the nature and influences of translation technology (e.g. Christensen....../Schjoldager 2010, 2011; Christensen 2011). Unfortunately, the increasing professional use of translation technology has not been mirrored within translation studies (TS) by a similar increase in research projects on translation technology (Munday 2009: 15; O’Hagan 2013; Doherty 2016: 952). The current thematic...

Process Pharmacology: A Pharmacological Data Science Approach to Drug Development and Therapy.

Science.gov (United States)

Lötsch, Jörn; Ultsch, Alfred

2016-04-01

A novel functional-genomics based concept of pharmacology that uses artificial intelligence techniques for mining and knowledge discovery in "big data" providing comprehensive information about the drugs' targets and their functional genomics is proposed. In "process pharmacology", drugs are associated with biological processes. This puts the disease, regarded as alterations in the activity in one or several cellular processes, in the focus of drug therapy. In this setting, the molecular drug targets are merely intermediates. The identification of drugs for therapeutic or repurposing is based on similarities in the high-dimensional space of the biological processes that a drug influences. Applying this principle to data associated with lymphoblastic leukemia identified a short list of candidate drugs, including one that was recently proposed as novel rescue medication for lymphocytic leukemia. The pharmacological data science approach provides successful selections of drug candidates within development and repurposing tasks. © 2016 The Authors CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

Translational Rodent Models for Research on Parasitic Protozoa-A Review of Confounders and Possibilities.

Science.gov (United States)

Ehret, Totta; Torelli, Francesca; Klotz, Christian; Pedersen, Amy B; Seeber, Frank

2017-01-01

Rodents, in particular Mus musculus , have a long and invaluable history as models for human diseases in biomedical research, although their translational value has been challenged in a number of cases. We provide some examples in which rodents have been suboptimal as models for human biology and discuss confounders which influence experiments and may explain some of the misleading results. Infections of rodents with protozoan parasites are no exception in requiring close consideration upon model choice. We focus on the significant differences between inbred, outbred and wild animals, and the importance of factors such as microbiota, which are gaining attention as crucial variables in infection experiments. Frequently, mouse or rat models are chosen for convenience, e.g., availability in the institution rather than on an unbiased evaluation of whether they provide the answer to a given question. Apart from a general discussion on translational success or failure, we provide examples where infections with single-celled parasites in a chosen lab rodent gave contradictory or misleading results, and when possible discuss the reason for this. We present emerging alternatives to traditional rodent models, such as humanized mice and organoid primary cell cultures. So-called recombinant inbred strains such as the Collaborative Cross collection are also a potential solution for certain challenges. In addition, we emphasize the advantages of using wild rodents for certain immunological, ecological, and/or behavioral questions. The experimental challenges (e.g., availability of species-specific reagents) that come with the use of such non-model systems are also discussed. Our intention is to foster critical judgment of both traditional and newly available translational rodent models for research on parasitic protozoa that can complement the existing mouse and rat models.

Translational Rodent Models for Research on Parasitic Protozoa—A Review of Confounders and Possibilities

Directory of Open Access Journals (Sweden)

Totta Ehret

2017-06-01

Full Text Available Rodents, in particular Mus musculus, have a long and invaluable history as models for human diseases in biomedical research, although their translational value has been challenged in a number of cases. We provide some examples in which rodents have been suboptimal as models for human biology and discuss confounders which influence experiments and may explain some of the misleading results. Infections of rodents with protozoan parasites are no exception in requiring close consideration upon model choice. We focus on the significant differences between inbred, outbred and wild animals, and the importance of factors such as microbiota, which are gaining attention as crucial variables in infection experiments. Frequently, mouse or rat models are chosen for convenience, e.g., availability in the institution rather than on an unbiased evaluation of whether they provide the answer to a given question. Apart from a general discussion on translational success or failure, we provide examples where infections with single-celled parasites in a chosen lab rodent gave contradictory or misleading results, and when possible discuss the reason for this. We present emerging alternatives to traditional rodent models, such as humanized mice and organoid primary cell cultures. So-called recombinant inbred strains such as the Collaborative Cross collection are also a potential solution for certain challenges. In addition, we emphasize the advantages of using wild rodents for certain immunological, ecological, and/or behavioral questions. The experimental challenges (e.g., availability of species-specific reagents that come with the use of such non-model systems are also discussed. Our intention is to foster critical judgment of both traditional and newly available translational rodent models for research on parasitic protozoa that can complement the existing mouse and rat models.

Rapid acquisition and model-based analysis of cell-free transcription–translation reactions from nonmodel bacteria

Science.gov (United States)

Wienecke, Sarah; Ishwarbhai, Alka; Tsipa, Argyro; Aw, Rochelle; Kylilis, Nicolas; Bell, David J.; McClymont, David W.; Jensen, Kirsten; Biedendieck, Rebekka

2018-01-01

Native cell-free transcription–translation systems offer a rapid route to characterize the regulatory elements (promoters, transcription factors) for gene expression from nonmodel microbial hosts, which can be difficult to assess through traditional in vivo approaches. One such host, Bacillus megaterium, is a giant Gram-positive bacterium with potential biotechnology applications, although many of its regulatory elements remain uncharacterized. Here, we have developed a rapid automated platform for measuring and modeling in vitro cell-free reactions and have applied this to B. megaterium to quantify a range of ribosome binding site variants and previously uncharacterized endogenous constitutive and inducible promoters. To provide quantitative models for cell-free systems, we have also applied a Bayesian approach to infer ordinary differential equation model parameters by simultaneously using time-course data from multiple experimental conditions. Using this modeling framework, we were able to infer previously unknown transcription factor binding affinities and quantify the sharing of cell-free transcription–translation resources (energy, ribosomes, RNA polymerases, nucleotides, and amino acids) using a promoter competition experiment. This allows insights into resource limiting-factors in batch cell-free synthesis mode. Our combined automated and modeling platform allows for the rapid acquisition and model-based analysis of cell-free transcription–translation data from uncharacterized microbial cell hosts, as well as resource competition within cell-free systems, which potentially can be applied to a range of cell-free synthetic biology and biotechnology applications. PMID:29666238

Modeling and control of lateral vibration of an axially translating flexible link

Energy Technology Data Exchange (ETDEWEB)

Shin, Heon Seop; Rhim, Sung Soo [Kyung Hee University, Yongin (Korea, Republic of)

2015-01-15

Manipulators used for the transportation of large panel-shape payloads often adopt long and slender links (or forks) with translational joins to carry the payloads. As the size of the payload increases, the length of the links also increases to hold the payload securely. The increased length of the link inevitably amplifies the effect of the flexure in the link. Intuitively, the translational motion of the link in its longitudinal direction should have no effect on the lateral vibration of the link because of the orthogonality between the direction of the translational motion and the lateral vibration. If, however, the link was flexible and translated horizontally (perpendicular to the gravitational field) the asymmetric deflection of the link caused by gravity would break the orthogonality between the two directions, and the longitudinal motion of the link would excite lateral motion in the link. In this paper, the lateral oscillatory motion of the flexible link in a large-scale solar cell panel handling robot is investigated where the links carry the panel in its longitudinal direction. The Newtonian approach in conjunction with the assumed modes method is used for derivation of the equation of motion for the flexible forks where non-zero control force is applied at the base of the link. The analysis illustrates the effect of longitudinal motion on the lateral vibration and dynamic stiffening effect (variation of the natural frequency) of the link due to the translational velocity. Lateral vibration behavior is simulated using the derived equations of the motion. A robust vibration control scheme, the input shaping filter technique, is implemented on the model and the effectiveness of the scheme is verified numerically.

Modeling and control of lateral vibration of an axially translating flexible link

International Nuclear Information System (INIS)

Shin, Heon Seop; Rhim, Sung Soo

2015-01-01

Manipulators used for the transportation of large panel-shape payloads often adopt long and slender links (or forks) with translational joins to carry the payloads. As the size of the payload increases, the length of the links also increases to hold the payload securely. The increased length of the link inevitably amplifies the effect of the flexure in the link. Intuitively, the translational motion of the link in its longitudinal direction should have no effect on the lateral vibration of the link because of the orthogonality between the direction of the translational motion and the lateral vibration. If, however, the link was flexible and translated horizontally (perpendicular to the gravitational field) the asymmetric deflection of the link caused by gravity would break the orthogonality between the two directions, and the longitudinal motion of the link would excite lateral motion in the link. In this paper, the lateral oscillatory motion of the flexible link in a large-scale solar cell panel handling robot is investigated where the links carry the panel in its longitudinal direction. The Newtonian approach in conjunction with the assumed modes method is used for derivation of the equation of motion for the flexible forks where non-zero control force is applied at the base of the link. The analysis illustrates the effect of longitudinal motion on the lateral vibration and dynamic stiffening effect (variation of the natural frequency) of the link due to the translational velocity. Lateral vibration behavior is simulated using the derived equations of the motion. A robust vibration control scheme, the input shaping filter technique, is implemented on the model and the effectiveness of the scheme is verified numerically.

Machine Translation as a Model for Overcoming Some Common Errors in English-into-Arabic Translation among EFL University Freshmen

Science.gov (United States)

El-Banna, Adel I.; Naeem, Marwa A.

2016-01-01

This research work aimed at making use of Machine Translation to help students avoid some syntactic, semantic and pragmatic common errors in translation from English into Arabic. Participants were a hundred and five freshmen who studied the "Translation Common Errors Remedial Program" prepared by the researchers. A testing kit that…

FRC translation into a compression coil

International Nuclear Information System (INIS)

Chrien, R.E.

1985-01-01

Several features of the problem of FRC translation into a compression coil are considered. First, the magnitude of the guide field is calculated and found to exceed that which would be applied to a flux conserver. Second, energy conservation is applied to FRC translation from a flux conserver into a compression coil. It is found that a significant temperature decrease is required for translation to be energetically possible. The temperature change depends on the external inductance in the compression circuit. An analogous case is that of a compression region composed of a compound magnet; in this case the temperature change depends on the ratio of inner and outer coil radii. Finally, the kinematics of intermediate translation states are calculated using an ''abrupt transition'' model. It is found, in this model, that the FRC must overcome a potential hill during translation, which requires a small initial velocity

FRC translation into a compression coil

International Nuclear Information System (INIS)

Chrien, R.E.

1986-01-01

The equilibrium and translational kinematics of Field-Reversed Configurations (FRCs) in a cylindrical coil which does not conserve flux are problems that arise in connection with adiabatic compressional heating. In this paper, they consider several features of the problem of FRC translation into a compression coil. First, the magnitude of the guide field is calculated and found to exceed that which would be applied to a flux conserver. Second, energy conservation is applied to FRC translation from a flux conserver into a compression coil. It is found that a significant temperature decrease is required for translation to be energetically possible. The temperature change depends on the external inductance in the compression circuit. An analogous case is that of a compression region composed of a compound magnet; in this case the temperature change depends on the ratio of inner and outer coil radii. Finally, the kinematics of intermediate translation states are calculated using an abrupt transition model. It is found, in this model, that the FRC must overcome a potential hill during translation, which requires a small initial velocity

Targeting RNA transcription and translation in ovarian cancer cells with pharmacological inhibitor CDKI-73.

Science.gov (United States)

Lam, Frankie; Abbas, Abdullahi Y; Shao, Hao; Teo, Theodosia; Adams, Julian; Li, Peng; Bradshaw, Tracey D; Fischer, Peter M; Walsby, Elisabeth; Pepper, Chris; Chen, Yi; Ding, Jian; Wang, Shudong

2014-09-15

Dysregulation of cellular transcription and translation is a fundamental hallmark of cancer. As CDK9 and Mnks play pivotal roles in the regulation of RNA transcription and protein synthesis, respectively, they are important targets for drug development. We herein report the cellular mechanism of a novel CDK9 inhibitor CDKI-73 in an ovarian cancer cell line (A2780). We also used shRNA-mediated CDK9 knockdown to investigate the importance of CDK9 in the maintenance of A2780 cells. This study revealed that CDKI-73 rapidly inhibited cellular CDK9 kinase activity and down-regulated the RNAPII phosphorylation. This subsequently caused a decrease in the eIF4E phosphorylation by blocking Mnk1 kinase activity. Consistently, CDK9 shRNA was also found to down-regulate the Mnk1 expression. Both CDKI-73 and CDK9 shRNA decreased anti-apoptotic proteins Mcl-1 and Bcl-2 and induced apoptosis. The study confirmed that CDK9 is required for cell survival and that ovarian cancer may be susceptible to CDK9 inhibition strategy. The data also implied a role of CDK9 in eIF4E-mediated translational control, suggesting that CDK9 may have important implication in the Mnk-eIF4E axis, the key determinants of PI3K/Akt/mTOR- and Ras/Raf/MAPK-mediated tumorigenic activity. As such, CDK9 inhibitor drug candidate CDKI-73 should have a major impact on these pathways in human cancers.

MSD Recombination Method in Statistical Machine Translation

Science.gov (United States)

Gros, Jerneja Žganec

2008-11-01

Freely available tools and language resources were used to build the VoiceTRAN statistical machine translation (SMT) system. Various configuration variations of the system are presented and evaluated. The VoiceTRAN SMT system outperformed the baseline conventional rule-based MT system in all English-Slovenian in-domain test setups. To further increase the generalization capability of the translation model for lower-coverage out-of-domain test sentences, an "MSD-recombination" approach was proposed. This approach not only allows a better exploitation of conventional translation models, but also performs well in the more demanding translation direction; that is, into a highly inflectional language. Using this approach in the out-of-domain setup of the English-Slovenian JRC-ACQUIS task, we have achieved significant improvements in translation quality.

A Novel Translational Model of Spinal Cord Injury in Nonhuman Primate.

Science.gov (United States)

Le Corre, Marine; Noristani, Harun N; Mestre-Frances, Nadine; Saint-Martin, Guillaume P; Coillot, Christophe; Goze-Bac, Christophe; Lonjon, Nicolas; Perrin, Florence E

2017-11-27

Spinal cord injuries (SCI) lead to major disabilities affecting > 2.5 million people worldwide. Major shortcomings in clinical translation result from multiple factors, including species differences, development of moderately predictive animal models, and differences in methodologies between preclinical and clinical studies. To overcome these obstacles, we first conducted a comparative neuroanatomical analysis of the spinal cord between mice, Microcebus murinus (a nonhuman primate), and humans. Next, we developed and characterized a new model of lateral spinal cord hemisection in M. murinus. Over a 3-month period after SCI, we carried out a detailed, longitudinal, behavioral follow-up associated with in vivo magnetic resonance imaging ( 1 H-MRI) monitoring. Then, we compared lesion extension and tissue alteration using 3 methods: in vivo 1 H-MRI, ex vivo 1 H-MRI, and classical histology. The general organization and glial cell distribution/morphology in the spinal cord of M. murinus closely resembles that of humans. Animals assessed at different stages following lateral hemisection of the spinal cord presented specific motor deficits and spinal cord tissue alterations. We also found a close correlation between 1 H-MRI signal and microglia reactivity and/or associated post-trauma phenomena. Spinal cord hemisection in M. murinus provides a reliable new nonhuman primate model that can be used to promote translational research on SCI and represents a novel and more affordable alternative to larger primates.

Advances in non-dopaminergic pharmacological treatments of Parkinson's disease

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Sandy eStayte

2014-05-01

Full Text Available Since the 1960’s treatments for Parkinson's disease (PD have traditionally been directed to effectively restore or replace dopamine, with L-Dopa the gold standard. However, chronic L-Dopa use is associated with debilitating dyskinesias, limiting its effectiveness. This has created a need to develop new therapies that work in ways other than restoring or replacing dopamine. We provide a comprehensive overview of the emerging non-dopaminergic pharmacological treatments including drugs targeting adenosine, glutamate, adrenergic, and serotonin receptors, as well as GLP-1 agonists, calcium channel blockers, iron chelators, anti-inflammatories, neurotrophic factors and gene therapy, with a detailed overview of their success in animal models and their translation to human clinical trials. We suggest that further developments in the identification of novel therapeutics, particularly those offering disease-modifying effects, will consistently be met with challenges until improvements in clinical trial design and advances in understanding the basic science of PD are made. We consider how developments in genetics, the possibility that PD may consist of multiple disease states, and potential etiology in non-dopaminergic regions will influence drug development. We conclude that despite the challenges ahead patients have much cause for optimism that novel therapeutics that offer better disease management and/or which slow disease progression are inevitable.

Systems Pharmacology Dissecting Holistic Medicine for Treatment of Complex Diseases: An Example Using Cardiocerebrovascular Diseases Treated by TCM.

Science.gov (United States)

Wang, Yonghua; Zheng, Chunli; Huang, Chao; Li, Yan; Chen, Xuetong; Wu, Ziyin; Wang, Zhenzhong; Xiao, Wei; Zhang, Boli

2015-01-01

Holistic medicine is an interdisciplinary field of study that integrates all types of biological information (protein, small molecules, tissues, organs, external environmental signals, etc.) to lead to predictive and actionable models for health care and disease treatment. Despite the global and integrative character of this discipline, a comprehensive picture of holistic medicine for the treatment of complex diseases is still lacking. In this study, we develop a novel systems pharmacology approach to dissect holistic medicine in treating cardiocerebrovascular diseases (CCDs) by TCM (traditional Chinese medicine). Firstly, by applying the TCM active ingredients screened out by a systems-ADME process, we explored and experimentalized the signed drug-target interactions for revealing the pharmacological actions of drugs at a molecule level. Then, at a/an tissue/organ level, the drug therapeutic mechanisms were further investigated by a target-organ location method. Finally, a translational integrating pathway approach was applied to extract the diseases-therapeutic modules for understanding the complex disease and its therapy at systems level. For the first time, the feature of the drug-target-pathway-organ-cooperations for treatment of multiple organ diseases in holistic medicine was revealed, facilitating the development of novel treatment paradigm for complex diseases in the future.

Translational neuropharmacology: the use of human isolated gastrointestinal tissues.

Science.gov (United States)

Sanger, G J; Broad, J; Kung, V; Knowles, C H

2013-01-01

Translational sciences increasingly emphasize the measurement of functions in native human tissues. However, such studies must confront variations in patient age, gender, genetic background and disease. Here, these are discussed with reference to neuromuscular and neurosecretory functions of the human gastrointestinal (GI) tract. Tissues are obtained after informed consent, in collaboration with surgeons (surgical techniques help minimize variables) and pathologists. Given the difficulties of directly recording from human myenteric neurones (embedded between muscle layers), enteric motor nerve functions are studied by measuring muscle contractions/relaxations evoked by electrical stimulation of intrinsic nerves; responses are regionally dependent, often involving cholinergic and nitrergic phenotypes. Enteric sensory functions can be studied by evoking the peristaltic reflex, involving enteric sensory and motor nerves, but this has rarely been achieved. As submucosal neurones are more accessible (after removing the mucosa), direct neuronal recordings are possible. Neurosecretory functions are studied by measuring changes in short-circuit current across the mucosa. For all experiments, basic questions must be addressed. Because tissues are from patients, what are the controls and the influence of disease? How long does it take before function fully recovers? What is the impact of age- and gender-related differences? What is the optimal sample size? Addressing these and other questions minimizes variability and raises the scientific credibility of human tissue research. Such studies also reduce animal use. Further, the many differences between animal and human GI functions also means that human tissue research must question the ethical validity of using strains of animals with unproved translational significance. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.

The Translator's Turn: in the Cultural Turn

Institute of Scientific and Technical Information of China (English)

徐玮玮

2003-01-01

@@ Introduction: Douglas Robinson rose to the defense of the " atheoretical" American literary translator in The Translator's Turn (1991). Here, I borrowed the title from him, but I will write my paper in the thought of the translator's role in translating. In his book, Robinson argued that the literary translator embodies an integration of feeling and thought, of intuition and systematization. In analyzing the " turn" that the translator take from the source text to the target text, Robinson offered a " dialogical" model, that is the translator's dialogical engagement with the source language and with the ethic of the target language. Robinson allows for the translator to intervene, subvert, divert, even entertain, emphasizing the creative aspect of literary translation. The translation linguists, scientists, and philosophers have had their chance at translation theory; now it is time, he argued, for the literary translators to have their " turn".

Gregory Rabassa’s Views on Translation

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Bolaños Cuéllar Sergio

2011-06-01

Full Text Available Gregory Rabassa is noted for his translations of famous Latin American authors (García Márquez, Vargas Llosa, Clarice Lispector, Jorge Amado, etc.. Less known are his views on translating. In this paper I aim at presenting and discussing his viewpoints as to the definition of translation (with a key discussion of the concept of equivalence, the role of the translator (a model speaker-listener of the target text, and some of the translation strategies he applies in his translational work (original's pre-eminence, problem solving, foreignizing, fictionalizing, and semantic networking. I argue that most of Rabassa's stances towards translating can be explained and are still valid within the framework of a modern translation approach. Examples from the English, French, German, Portuguese and Russian translations of García Márquez's Cien años de soledad are taken from a multilingual parallel corpus collected by the author of this paper.

Shared Representations and the Translation Process

DEFF Research Database (Denmark)

Schaeffer, Moritz; Carl, Michael

2015-01-01

The purpose of the present chapter is to investigate automated processing during translation. We provide evidence from a translation priming study which suggests that translation involves activation of shared lexico-semantic and syntactical representations, i.e., the activation of features of both...... source and target language items which share one single cognitive representation. We argue that activation of shared representations facilitates automated processing. The chapter revises the literal translation hypothesis and the monitor model (Ivir 1981; Toury 1995; Tirkkonen-Condit 2005), and re...

Shared Representations and the Translation Process

DEFF Research Database (Denmark)

Schaeffer, Moritz; Carl, Michael

2013-01-01

The purpose of the present paper is to investigate automated processing during translation. We provide evidence from a translation priming study which suggests that translation involves activation of shared lexico-semantic and syntactical representations, i.e., the activation of features of both...... source and target language items which share one single cognitive representation. We argue that activation of shared representations facilitates automated processing. The paper revises the literal translation hypothesis and the monitor model (Ivir 1981; Toury 1995; Tirkkonen-Condit 2005), and re...

Experimental psychopathology paradigms for alcohol use disorders: Applications for translational research.

Science.gov (United States)

Bujarski, Spencer; Ray, Lara A

2016-11-01

In spite of high prevalence and disease burden, scientific consensus on the etiology and treatment of Alcohol Use Disorder (AUD) has yet to be reached. The development and utilization of experimental psychopathology paradigms in the human laboratory represents a cornerstone of AUD research. In this review, we describe and critically evaluate the major experimental psychopathology paradigms developed for AUD, with an emphasis on their implications, strengths, weaknesses, and methodological considerations. Specifically we review alcohol administration, self-administration, cue-reactivity, and stress-reactivity paradigms. We also provide an introduction to the application of experimental psychopathology methods to translational research including genetics, neuroimaging, pharmacological and behavioral treatment development, and translational science. Through refining and manipulating key phenotypes of interest, these experimental paradigms have the potential to elucidate AUD etiological factors, improve the efficiency of treatment developments, and refine treatment targets thus advancing precision medicine. Copyright © 2016 Elsevier Ltd. All rights reserved.

Caenorhabditis elegans as Model System in Pharmacology and Toxicology: Effects of Flavonoids on Redox-Sensitive Signalling Pathways and Ageing

Directory of Open Access Journals (Sweden)

Karoline Koch

2014-01-01

Full Text Available Flavonoids are secondary plant compounds that mediate diverse biological activities, for example, by scavenging free radicals and modulating intracellular signalling pathways. It has been shown in various studies that distinct flavonoid compounds enhance stress resistance and even prolong the life span of organisms. In the last years the model organism C. elegans has gained increasing importance in pharmacological and toxicological sciences due to the availability of various genetically modified nematode strains, the simplicity of modulating genes by RNAi, and the relatively short life span. Several studies have been performed demonstrating that secondary plant compounds influence ageing, stress resistance, and distinct signalling pathways in the nematode. Here we present an overview of the modulating effects of different flavonoids on oxidative stress, redox-sensitive signalling pathways, and life span in C. elegans introducing the usability of this model system for pharmacological and toxicological research.

Caenorhabditis elegans as Model System in Pharmacology and Toxicology: Effects of Flavonoids on Redox-Sensitive Signalling Pathways and Ageing

Science.gov (United States)

Koch, Karoline; Havermann, Susannah; Büchter, Christian

2014-01-01

Flavonoids are secondary plant compounds that mediate diverse biological activities, for example, by scavenging free radicals and modulating intracellular signalling pathways. It has been shown in various studies that distinct flavonoid compounds enhance stress resistance and even prolong the life span of organisms. In the last years the model organism C. elegans has gained increasing importance in pharmacological and toxicological sciences due to the availability of various genetically modified nematode strains, the simplicity of modulating genes by RNAi, and the relatively short life span. Several studies have been performed demonstrating that secondary plant compounds influence ageing, stress resistance, and distinct signalling pathways in the nematode. Here we present an overview of the modulating effects of different flavonoids on oxidative stress, redox-sensitive signalling pathways, and life span in C. elegans introducing the usability of this model system for pharmacological and toxicological research. PMID:24895670

Understanding Translation

DEFF Research Database (Denmark)

Schjoldager, Anne Gram; Gottlieb, Henrik; Klitgård, Ida

Understanding Translation is designed as a textbook for courses on the theory and practice of translation in general and of particular types of translation - such as interpreting, screen translation and literary translation. The aim of the book is to help you gain an in-depth understanding...... of the phenomenon of translation and to provide you with a conceptual framework for the analysis of various aspects of professional translation. Intended readers are students of translation and languages, but the book will also be relevant for others who are interested in the theory and practice of translation...... - translators, language teachers, translation users and literary, TV and film critics, for instance. Discussions focus on translation between Danish and English....

Pharmacology profiling of chemicals and proteins

DEFF Research Database (Denmark)

Kringelum, Jens Vindahl

between pharmaceuticals and proteins in vivo potential leads to unwanted adverse effects, toxicity and reduced half-life, but can also lead to novel therapeutic effects of already approved pharmaceuticals. Hence identification of in vivo targets is of importance in discovery, development and repurposing....... This limitation complicates adverse effect assessment in the early drug-development phase, thus contributing to drugattrition. Prediction models offer the possibility to close these gaps and provide more complete pharmacology profiles, however improvements in performances are required for these tools to serve...... to its nonself origin, which potentially alters the pharmacology profile of the substance. The neutralization of biopharmaceuticals by antidrug antibodies (ADAs) is an important element in the immune response cascade, however studies of ADA binding site on biopharmaceuticals, referred to as B...

Only connect: the merger of BMC Pharmacology and BMC Clinical Pharmacology.

Science.gov (United States)

Moylan, Elizabeth C; Morrey, Christopher; Appleford-Cook, Joanne M

2012-08-13

This editorial celebrates the launch of BMC Pharmacology and Toxicology within the BMC series of journals published by BioMed Central. The scope of the journal is interdisciplinary encompassing toxicology, experimental and clinical pharmacology including clinical trials. In this editorial we discuss the origins of this new journal and the ethos and policies under which it will operate.

Combining patient journey modelling and visual multi-agent computer simulation: a framework to improving knowledge translation in a healthcare environment.

Science.gov (United States)

Curry, Joanne; Fitzgerald, Anneke; Prodan, Ante; Dadich, Ann; Sloan, Terry

2014-01-01

This article focuses on a framework that will investigate the integration of two disparate methodologies: patient journey modelling and visual multi-agent simulation, and its impact on the speed and quality of knowledge translation to healthcare stakeholders. Literature describes patient journey modelling and visual simulation as discrete activities. This paper suggests that their combination and their impact on translating knowledge to practitioners are greater than the sum of the two technologies. The test-bed is ambulatory care and the goal is to determine if this approach can improve health services delivery, workflow, and patient outcomes and satisfaction. The multidisciplinary research team is comprised of expertise in patient journey modelling, simulation, and knowledge translation.

Developing a Collection of Composable Data Translation Software Units to Improve Efficiency and Reproducibility in Ecohydrologic Modeling Workflows

Science.gov (United States)

Olschanowsky, C.; Flores, A. N.; FitzGerald, K.; Masarik, M. T.; Rudisill, W. J.; Aguayo, M.

2017-12-01

Dynamic models of the spatiotemporal evolution of water, energy, and nutrient cycling are important tools to assess impacts of climate and other environmental changes on ecohydrologic systems. These models require spatiotemporally varying environmental forcings like precipitation, temperature, humidity, windspeed, and solar radiation. These input data originate from a variety of sources, including global and regional weather and climate models, global and regional reanalysis products, and geostatistically interpolated surface observations. Data translation measures, often subsetting in space and/or time and transforming and converting variable units, represent a seemingly mundane, but critical step in the application workflows. Translation steps can introduce errors, misrepresentations of data, slow execution time, and interrupt data provenance. We leverage a workflow that subsets a large regional dataset derived from the Weather Research and Forecasting (WRF) model and prepares inputs to the Parflow integrated hydrologic model to demonstrate the impact translation tool software quality on scientific workflow results and performance. We propose that such workflows will benefit from a community approved collection of data transformation components. The components should be self-contained composable units of code. This design pattern enables automated parallelization and software verification, improving performance and reliability. Ensuring that individual translation components are self-contained and target minute tasks increases reliability. The small code size of each component enables effective unit and regression testing. The components can be automatically composed for efficient execution. An efficient data translation framework should be written to minimize data movement. Composing components within a single streaming process reduces data movement. Each component will typically have a low arithmetic intensity, meaning that it requires about the same number of

TREXMO: A Translation Tool to Support the Use of Regulatory Occupational Exposure Models.

Science.gov (United States)

Savic, Nenad; Racordon, Dimitri; Buchs, Didier; Gasic, Bojan; Vernez, David

2016-10-01

Occupational exposure models vary significantly in their complexity, purpose, and the level of expertise required from the user. Different parameters in the same model may lead to different exposure estimates for the same exposure situation. This paper presents a tool developed to deal with this concern-TREXMO or TRanslation of EXposure MOdels. TREXMO integrates six commonly used occupational exposure models, namely, ART v.1.5, STOFFENMANAGER(®) v.5.1, ECETOC TRA v.3, MEASE v.1.02.01, EMKG-EXPO-TOOL, and EASE v.2.0. By enabling a semi-automatic translation between the parameters of these six models, TREXMO facilitates their simultaneous use. For a given exposure situation, defined by a set of parameters in one of the models, TREXMO provides the user with the most appropriate parameters to use in the other exposure models. Results showed that, once an exposure situation and parameters were set in ART, TREXMO reduced the number of possible outcomes in the other models by 1-4 orders of magnitude. The tool should manage to reduce the uncertain entry or selection of parameters in the six models, improve between-user reliability, and reduce the time required for running several models for a given exposure situation. In addition to these advantages, registrants of chemicals and authorities should benefit from more reliable exposure estimates for the risk characterization of dangerous chemicals under Regulation, Evaluation, Authorisation and restriction of CHemicals (REACH). © The Author 2016. Published by Oxford University Press on behalf of the British Occupational Hygiene Society.

Machine Translation Using Constraint-Based Synchronous Grammar

Institute of Scientific and Technical Information of China (English)

WONG Fai; DONG Mingchui; HU Dongcheng

2006-01-01

A synchronous grammar based on the formalism of context-free grammar was developed by generalizing the first component of production that models the source text. Unlike other synchronous grammars,the grammar allows multiple target productions to be associated to a single production rule which can be used to guide a parser to infer different possible translational equivalences for a recognized input string according to the feature constraints of symbols in the pattern. An extended generalized LR algorithm was adapted to the parsing of the proposed formalism to analyze the syntactic structure of a language. The grammar was used as the basis for building a machine translation system for Portuguese to Chinese translation. The empirical results show that the grammar is more expressive when modeling the translational equivalences of parallel texts for machine translation and grammar rewriting applications.

Telemedicine as a special case of machine translation.

Science.gov (United States)

Wołk, Krzysztof; Marasek, Krzysztof; Glinkowski, Wojciech

2015-12-01

Machine translation is evolving quite rapidly in terms of quality. Nowadays, we have several machine translation systems available in the web, which provide reasonable translations. However, these systems are not perfect, and their quality may decrease in some specific domains. This paper examines the effects of different training methods when it comes to Polish-English Statistical Machine Translation system used for the medical data. Numerous elements of the EMEA parallel text corpora and not related OPUS Open Subtitles project were used as the ground for creation of phrase tables and different language models including the development, tuning and testing of these translation systems. The BLEU, NIST, METEOR, and TER metrics have been used in order to evaluate the results of various systems. Our experiments deal with the systems that include POS tagging, factored phrase models, hierarchical models, syntactic taggers, and other alignment methods. We also executed a deep analysis of Polish data as preparatory work before automatized data processing such as true casing or punctuation normalization phase. Normalized metrics was used to compare results. Scores lower than 15% mean that Machine Translation engine is unable to provide satisfying quality, scores greater than 30% mean that translations should be understandable without problems and scores over 50 reflect adequate translations. The average results of Polish to English translations scores for BLEU, NIST, METEOR, and TER were relatively high and ranged from 7058 to 8272. The lowest score was 6438. The average results ranges for English to Polish translations were little lower (6758-7897). The real-life implementations of presented high quality Machine Translation Systems are anticipated in general medical practice and telemedicine. Copyright © 2015. Published by Elsevier Ltd.

Physiological and Pharmacological Aspects of the Vas Deferens - an Update

Directory of Open Access Journals (Sweden)

David Stewart Koslov

2013-08-01

Full Text Available The vas deferens, a muscular conduit conveying spermatozoa from the epididymis to the urethra, has been used as a model tissue for smooth muscle pharmacological and physiological advancements. Many drugs, notably α-adrenergic antagonists, have effects on contractility and thus normal ejaculation, incurring significant side effects for patients that may interfere with compliance. A more thorough understanding of the innervation and neurotransmitter pharmacology of the vas has indicated that this is a highly complex structure and a model for co-transmission at the synapse. Recent models have shown clinical scenarios that alter the vas contraction. This review covers structure, receptors, neurotransmitters, smooth muscle physiology, and clinical implications of the vas deferens.

Experimental liver fibrosis research: update on animal models, legal issues and translational aspects

Science.gov (United States)

2013-01-01

Liver fibrosis is defined as excessive extracellular matrix deposition and is based on complex interactions between matrix-producing hepatic stellate cells and an abundance of liver-resident and infiltrating cells. Investigation of these processes requires in vitro and in vivo experimental work in animals. However, the use of animals in translational research will be increasingly challenged, at least in countries of the European Union, because of the adoption of new animal welfare rules in 2013. These rules will create an urgent need for optimized standard operating procedures regarding animal experimentation and improved international communication in the liver fibrosis community. This review gives an update on current animal models, techniques and underlying pathomechanisms with the aim of fostering a critical discussion of the limitations and potential of up-to-date animal experimentation. We discuss potential complications in experimental liver fibrosis and provide examples of how the findings of studies in which these models are used can be translated to human disease and therapy. In this review, we want to motivate the international community to design more standardized animal models which might help to address the legally requested replacement, refinement and reduction of animals in fibrosis research. PMID:24274743

Impact of Online Versus Hardcopy Dictionaries‟ Application on Translation Quality of Iranian M. A. Translation Students

Directory of Open Access Journals (Sweden)

Sheida Zarei

2017-12-01

Full Text Available The study aimed at investigating the impact of online versus hardcopy dictionaries‟ application on translation quality of senior M.A. students of translation based on Bleu model introduced by Papineni et al. (2002. To this end, using Oxford Proficiency test 50 (out of 70 female senior M.A. students of translation were selected and they were assigned to two groups: Online and hardcopy, using systematic sampling. Next, an English text was selected as the reference text. This reference text was given to three translators: 1 A male English translation expert with a Ph.D. degree in Computational Linguistics (Ref. 1; 2 A female English translation expert with an M.A. degree working at an English Translation Center and with more than 5 years of experience (Ref. 2, and 3 A male Ph.D. candidate in English translation (Ref. 3. These three versions were used as reference Persian standard translations to be entered into Bleu. Later, the English text was given to the hardcopy and online groups. Then, the translations of the participants were compared with the three reference Persian translations using Bleu. The time taken by each student to translate the text into Persian was also recorded. The results indicated that there was no statistically significant difference between the translations of the hardcopy and online groups from fluency/precision points of view. Comparison of the speed of translation in the two groups indicated that the online group was meaningfully faster. The possible beneficiaries of the findings of this research can be university professors, policy makers, and students in the realm of translation.

A note on the translation of conceptual data models into description logics: disjointness and covering assumptions

CSIR Research Space (South Africa)

Casini, G

2012-10-01

Full Text Available possibilities for conceptual data modeling. It also raises the question of how existing conceptual models using ER, UML or ORM could be translated into Description Logics (DLs), a family of logics that have proved to be particularly appropriate for formalizing...

TEACHING COMMUNICATIVE TRANSLATION: AN ACTIVE RECEPTION ANALYSIS BETWEEN THE TRANSLATION AND READER’S RECEPTION

Directory of Open Access Journals (Sweden)

Venny Eka Meidasari

2014-06-01

Full Text Available Literary theory sees reception theory from the reader response that emphasizes the reader’s reception of a literary text. It is generally called audience reception in the analysis of communications models. In literary studies, reception theory originated from the work of Hans-Robert Jauss in the late 1960s. Communication only means that the original message will be clearly sent in its equivalent context to the target receptor. Similarly, the main role of translators is to send the message across without any form of distortion or emphasis. It is delivering the genuine context of the message to the language that the active receptor understands. A single mistake in a context translation can result to offensive message that can eventually lead to misunderstandings between active receptors. This paper proposes on the role of translator as the mediator between a writer of the original text and the active target language receptors of translated version in the course of communication which definitely affects the process and result of translation practice. It also reveals the emphasis on the creation text of the translation theories originated from the strategic communication theories, which hopefully leads to a dream of the most equivalence between the text and the translated version.

BRIDG: a domain information model for translational and clinical protocol-driven research.

Science.gov (United States)

Becnel, Lauren B; Hastak, Smita; Ver Hoef, Wendy; Milius, Robert P; Slack, MaryAnn; Wold, Diane; Glickman, Michael L; Brodsky, Boris; Jaffe, Charles; Kush, Rebecca; Helton, Edward

2017-09-01

It is critical to integrate and analyze data from biological, translational, and clinical studies with data from health systems; however, electronic artifacts are stored in thousands of disparate systems that are often unable to readily exchange data. To facilitate meaningful data exchange, a model that presents a common understanding of biomedical research concepts and their relationships with health care semantics is required. The Biomedical Research Integrated Domain Group (BRIDG) domain information model fulfills this need. Software systems created from BRIDG have shared meaning "baked in," enabling interoperability among disparate systems. For nearly 10 years, the Clinical Data Standards Interchange Consortium, the National Cancer Institute, the US Food and Drug Administration, and Health Level 7 International have been key stakeholders in developing BRIDG. BRIDG is an open-source Unified Modeling Language-class model developed through use cases and harmonization with other models. With its 4+ releases, BRIDG includes clinical and now translational research concepts in its Common, Protocol Representation, Study Conduct, Adverse Events, Regulatory, Statistical Analysis, Experiment, Biospecimen, and Molecular Biology subdomains. The model is a Clinical Data Standards Interchange Consortium, Health Level 7 International, and International Standards Organization standard that has been utilized in national and international standards-based software development projects. It will continue to mature and evolve in the areas of clinical imaging, pathology, ontology, and vocabulary support. BRIDG 4.1.1 and prior releases are freely available at https://bridgmodel.nci.nih.gov . © The Author 2017. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Monovalent cations transfer through isolated human amnion: a new pharmacological model

Energy Technology Data Exchange (ETDEWEB)

Bara, M.; Guiet-Bara, A.; Durlach, J.

1985-04-01

Transfer of monovalent cations through the isolated human amnion consists of different factors: paracellular, coupling, ATPase dependent cellular transfer, leak cellular transfer. Understanding this transfer permits testing of the action of various substances. Physiological substances (Mg, taurine) increase ionic transfer and there is a vicarious effect between Mg and taurine. The tocolytic agents MgSO/sub 4/ and ethanol do not exhibit a good effect on the transfer: decrease with ethanol; equality between entry and exit fluxes with MgSO/sub 4/. On the other hand, amphotericin B increases mother-to-fetus transfer. Polluting metals (Pb, Cd, Hg, As) dramatically reduce exchanges and almost completely inhibit amnion permeability. Ingestion of ethanol also exhibits a dramatic effect on the exchange between mother and fetus through the amnion. Study of ionic transfer in vitro can be considered a pharmacological model to investigate the modifications of mother-fetus exchanges by various substances.

Providing data science support for systems pharmacology and its implications to drug discovery.

Science.gov (United States)

Hart, Thomas; Xie, Lei

2016-01-01

The conventional one-drug-one-target-one-disease drug discovery process has been less successful in tracking multi-genic, multi-faceted complex diseases. Systems pharmacology has emerged as a new discipline to tackle the current challenges in drug discovery. The goal of systems pharmacology is to transform huge, heterogeneous, and dynamic biological and clinical data into interpretable and actionable mechanistic models for decision making in drug discovery and patient treatment. Thus, big data technology and data science will play an essential role in systems pharmacology. This paper critically reviews the impact of three fundamental concepts of data science on systems pharmacology: similarity inference, overfitting avoidance, and disentangling causality from correlation. The authors then discuss recent advances and future directions in applying the three concepts of data science to drug discovery, with a focus on proteome-wide context-specific quantitative drug target deconvolution and personalized adverse drug reaction prediction. Data science will facilitate reducing the complexity of systems pharmacology modeling, detecting hidden correlations between complex data sets, and distinguishing causation from correlation. The power of data science can only be fully realized when integrated with mechanism-based multi-scale modeling that explicitly takes into account the hierarchical organization of biological systems from nucleic acid to proteins, to molecular interaction networks, to cells, to tissues, to patients, and to populations.

Left Dislocation and its translation in some Germanic languages ...

African Journals Online (AJOL)

In terms of the theoretical framework of an influential recent model of Bible translation, Left Dislocation (=LD) can be regarded as a “communicate clue” that translators must try to interpretively resemble in their target text translation. This exploratory study investigates how twenty translations (fifteen English, three Afrikaans, ...

L-leucine partially rescues translational and developmental defects associated with zebrafish models of Cornelia de Lange syndrome.

Science.gov (United States)

Xu, Baoshan; Sowa, Nenja; Cardenas, Maria E; Gerton, Jennifer L

2015-03-15

Cohesinopathies are human genetic disorders that include Cornelia de Lange syndrome (CdLS) and Roberts syndrome (RBS) and are characterized by defects in limb and craniofacial development as well as mental retardation. The developmental phenotypes of CdLS and other cohesinopathies suggest that mutations in the structure and regulation of the cohesin complex during embryogenesis interfere with gene regulation. In a previous project, we showed that RBS was associated with highly fragmented nucleoli and defects in both ribosome biogenesis and protein translation. l-leucine stimulation of the mTOR pathway partially rescued translation in human RBS cells and development in zebrafish models of RBS. In this study, we investigate protein translation in zebrafish models of CdLS. Our results show that phosphorylation of RPS6 as well as 4E-binding protein 1 (4EBP1) was reduced in nipbla/b, rad21 and smc3-morphant embryos, a pattern indicating reduced translation. Moreover, protein biosynthesis and rRNA production were decreased in the cohesin morphant embryo cells. l-leucine partly rescued protein synthesis and rRNA production in the cohesin morphants and partially restored phosphorylation of RPS6 and 4EBP1. Concomitantly, l-leucine treatment partially improved cohesinopathy embryo development including the formation of craniofacial cartilage. Interestingly, we observed that alpha-ketoisocaproate (α-KIC), which is a keto derivative of leucine, also partially rescued the development of rad21 and nipbla/b morphants by boosting mTOR-dependent translation. In summary, our results suggest that cohesinopathies are caused in part by defective protein synthesis, and stimulation of the mTOR pathway through l-leucine or its metabolite α-KIC can partially rescue development in zebrafish models for CdLS. © The Author 2014. Published by Oxford University Press.

[Study on the first translated obstetrics book Tai chan ju yao (Essentials in Obstetrics)].

Science.gov (United States)

Wu, M

2018-01-28

In 1893, Wan Tsun-mo translated and published Tai chan ju yao ( Essentials in Obstetrics ), the first monograph of western obstetrics in modern China, symbolizing the independence of obstetrics from such maternal and child books as Fu ying xin shuo and Fu ke jing yun tu shuo , which occupies an important position in the history of the development of modern Chinese obstetrics. The book introduced anatomy, physiology, pathology, embryology, diagnostics, surgery, pharmacology and other knowledge of obstetrics in a catechismal form, and had a detailed discussion of such advanced obstetrical technologies as antiseptic, anesthesia, forceps and cesarean section for the first time.Judging from the content and translation of Tai chan ju yao , this book has already possessed the basic knowledge system of modern obstetrics, though the translation appeared to be somewhat jerky and not elegant and the terminology needing to be further improved, it was not only used as an important medium for the introduction of obstetrical knowledge, but also of great clinical value.However, its influence was so weak that later researchers seldom mentioned this book.

Pharmacologic and non-pharmacologic treatments for chronic pain in individuals with HIV: a systematic review

Science.gov (United States)

Merlin, Jessica S.; Bulls, Hailey W.; Vucovich, Lee A.; Edelman, E. Jennifer; Starrels, Joanna L.

2016-01-01

Chronic pain occurs in as many as 85% of individuals with HIV and is associated with substantial functional impairment. Little guidance is available for HIV providers seeking to address their patients’ chronic pain. We conducted a systematic review to identify clinical trials and observational studies that examined the impact of pharmacologic or non-pharmacologic interventions on pain and/or functional outcomes among HIV-infected individuals with chronic pain in high-development countries. Eleven studies met inclusion criteria and were mostly low or very low quality. Seven examined pharmacologic interventions (gabapentin, pregabalin, capsaicin, analgesics including opioids) and four examined non-pharmacologic interventions (cognitive behavioral therapy, self-hypnosis, smoked cannabis). The only controlled studies with positive results were of capsaicin and cannabis, and had short-term follow-up (≤12 weeks). Among the seven studies of pharmacologic interventions, five had substantial pharmaceutical industry sponsorship. These findings highlight several important gaps in the HIV/chronic pain literature that require further research. PMID:27267445

COLLABORATING WITH THE COMMUNITY: THE EXTRA-TERRITORIAL TRANSLATIONAL RESEARCH TEAM.

Science.gov (United States)

Kotarba, Joseph A; Croisant, Sharon A; Elferink, Cornelis; Scott, Lauren E

2014-12-05

The purpose of the present study is to suggest a revision of the team science concept to the more inclusive extra-territorial research team (ETRT). Translational thinking is largely marked by the perception of the team as a thing-like structure at the center of the scientific activity. Collaboration accordingly involves bringing external others (e.g., scientists, community members, and clinicians) into the team through limited or dependent participation. We suggest that a promising and innovative way to see the team is as an idea : a schema for assembling and managing relationships among otherwise disparate individuals with vested interests in the problem at hand. Thus, the ETRT can be seen as a process as well as an object . We provide a case study derived from a qualitative analysis of the impact of the logic of translational science on a team assessment of environmental health following an off-coast oil disaster. The ETRT in question displayed the following principles of constructive relationship management: a high sense of adventure given the quick pace and timeliness given the relevance of the oil spill to all team members; regular meetings in the community to avoid the appearance of academic hegemony; open access by lay as well as institutional scientists; integration of emergency management coordinators into the group; and the languages of public health, environmental pharmacology/toxicology and coastal culture seamlessly interwoven in discussion. The ETRT model is an appropriate strategy for mobilizing and integrating the knowledge and skills needed for comprehensive science and service responses, especially during crisis.

Translational Creativity

DEFF Research Database (Denmark)

Nielsen, Sandro

2010-01-01

A long-established approach to legal translation focuses on terminological equivalence making translators strictly follow the words of source texts. Recent research suggests that there is room for some creativity allowing translators to deviate from the source texts. However, little attention...... is given to genre conventions in source texts and the ways in which they can best be translated. I propose that translators of statutes with an informative function in expert-to-expert communication may be allowed limited translational creativity when translating specific types of genre convention....... This creativity is a result of translators adopting either a source-language or a target-language oriented strategy and is limited by the pragmatic principle of co-operation. Examples of translation options are provided illustrating the different results in target texts. The use of a target-language oriented...

Dynamic Modeling of GAIT System Reveals Transcriptome Expansion and Translational Trickle Control Device

Science.gov (United States)

Yao, Peng; Potdar, Alka A.; Arif, Abul; Ray, Partho Sarothi; Mukhopadhyay, Rupak; Willard, Belinda; Xu, Yichi; Yan, Jun; Saidel, Gerald M.; Fox, Paul L.

2012-01-01

SUMMARY Post-transcriptional regulatory mechanisms superimpose “fine-tuning” control upon “on-off” switches characteristic of gene transcription. We have exploited computational modeling with experimental validation to resolve an anomalous relationship between mRNA expression and protein synthesis. Differential GAIT (Gamma-interferon Activated Inhibitor of Translation) complex activation repressed VEGF-A synthesis to a low, constant rate despite high, variable VEGFA mRNA expression. Dynamic model simulations indicated the presence of an unidentified, inhibitory GAIT element-interacting factor. We discovered a truncated form of glutamyl-prolyl tRNA synthetase (EPRS), the GAIT constituent that binds the 3’-UTR GAIT element in target transcripts. The truncated protein, EPRSN1, prevents binding of functional GAIT complex. EPRSN1 mRNA is generated by a remarkable polyadenylation-directed conversion of a Tyr codon in the EPRS coding sequence to a stop codon (PAY*). By low-level protection of GAIT element-bearing transcripts, EPRSN1 imposes a robust “translational trickle” of target protein expression. Genome-wide analysis shows PAY* generates multiple truncated transcripts thereby contributing to transcriptome expansion. PMID:22386318

Mapping research questions about translation to methods, measures, and models

NARCIS (Netherlands)

Berninger, V.; Rijlaarsdam, G.; Fayol, M.L.; Fayol, M.; Alamargot, D.; Berninger, V.W.

2012-01-01

About the book: Translation of cognitive representations into written language is one of the most important processes in writing. This volume provides a long-awaited updated overview of the field. The contributors discuss each of the commonly used research methods for studying translation; theorize

Recognition of Translator Expertise using Sequences of Fixations and Keystrokes

DEFF Research Database (Denmark)

Gómez, Pascual Martínez; Minocha, Akshay; Huang, Jin

2014-01-01

Professional human translation is necessary to meet high quality standards in industry and governmental agencies. Translators engage in multiple activities during their task, and there is a need to model their behavior, with the objective to understand and optimize the translation process....... In recent years, user interfaces enabled us to record user events such as eye-movements or keystrokes. Although there have been insightful descriptive analysis of the translation process, there are multiple advantages in enabling quantitative inference. We present methods to classify sequences of fixations...... and keystrokes into activities and model translation sessions with the objective to recognize translator expertise. We show significant error reductions in the task of recognizing certified translators and their years of experience, and analyze the characterizing patterns....

Finite translation surfaces with maximal number of translations

OpenAIRE

Schlage-Puchta, Jan-Christoph; Weitze-Schmithuesen, Gabriela

2013-01-01

The natural automorphism group of a translation surface is its group of translations. For finite translation surfaces of genus g > 1 the order of this group is naturally bounded in terms of g due to a Riemann-Hurwitz formula argument. In analogy with classical Hurwitz surfaces, we call surfaces which achieve the maximal bound Hurwitz translation surfaces. We study for which g there exist Hurwitz translation surfaces of genus g.

On the Universality of Theory Models of Translation Ethics:From the Perspective of the Exact Referent and Status of Each Translation Agent%翻译伦理模式理论普适性思考之翻译主体指涉与定位探究

Institute of Scientific and Technical Information of China (English)

汤金霞; 梅阳春

2014-01-01

由翻译的再现伦理、服务伦理、交际伦理、规范伦理和承诺伦理组成的翻译伦理模式理论对中西方翻译伦理学的发展贡献巨大，以致于国内翻译界出现了以该理论为基础构建普适性翻译伦理的建议。然而再现伦理、服务伦理、交际伦理和规范伦理没有明确翻译主体(译者除外)的具体指涉，对翻译主体(译者除外)的定位也不一致，旨在融合这4种翻译伦理的承诺伦理也没有解决这两个问题。因此，以翻译伦理模式理论为基础构建普世翻译伦理的设想不可行。%Theory of models of translation ethics constituted by translational ethics of representation, of service, of communication, of norm-based translational ethics and translation ethics of commitment contributes a lot to the development of translation ethics home and abroad. In the circle of translation of China, there comes the voice of formulating universal translation ethics on the basis of this theory. Therefore, this paper deals with the feasibility of the formulation of universal translation ethics on the basis of the theory models of translation ethics. In this paper, the exact referents of the translation agents ( mainly including the source, the target culture, the original writer, the client, the translator and the target readership) illustrated in translation ethics of representation, service, communication, norm-based translation ethics and the status of each translation agent conferred by each of the four translation ethics are compared and contrasted. It is discovered that, in the first four models of translation ethics, the referents of all the translation agents except the translator and the status conferred to each of the relevant translation agents except the target readership contradict each other. Translation ethics of commitment, with the purpose of integrating four preceding models of translation ethics does not solve the two problems either. Therefore

Integrated quantitative pharmacology for treatment optimization in oncology

NARCIS (Netherlands)

Hasselt, J.G.C. van

2014-01-01

This thesis describes the development and application of quantitative pharmacological models in oncology for treatment optimization and for the design and analysis of clinical trials with respect to pharmacokinetics, toxicity, efficacy and cost-effectiveness. A recurring theme throughout this

Machine Translation Tools - Tools of The Translator's Trade

DEFF Research Database (Denmark)

Kastberg, Peter

2012-01-01

In this article three of the more common types of translation tools are presented, discussed and critically evaluated. The types of translation tools dealt with in this article are: Fully Automated Machine Translation (or FAMT), Human Aided Machine Translation (or HAMT) and Machine Aided Human...... Translation (or MAHT). The strengths and weaknesses of the different types of tools are discussed and evaluated by means of a number of examples. The article aims at two things: at presenting a sort of state of the art of what is commonly referred to as “machine translation” as well as at providing the reader...... with a sound basis for considering what translation tool (if any) is the most appropriate in order to meet his or her specific translation needs....

Intercultural communication. Prerequisites for translation effectiveness

Directory of Open Access Journals (Sweden)

Titela Vîlceanu

2008-01-01

Full Text Available The paper is intended to raise awareness of some recurrent problems related to cultural and linguistic security in translation alongside strategies of achieving it. Globalisation means global thinking, individual accountability and the development of new sensitivities and capabilities. Different models of Intercultural Communicative Competence are scrutinised in an attempt to identify a common core of generalisable traits, which could be further applied to a wide range of translation situations. The (intercultural load is of paramount importance in translation being, more often than not, the cause of serious misunderstanding if the translator does not adequately equate the two cultures or bridge the cultural gap.

Translating Chicana Rap: Snow Tha Product

Directory of Open Access Journals (Sweden)

Adriana Onita

2017-06-01

Full Text Available This project examines rap lyrics, interviews, and music videos by Chicana artist Snow Tha Product to show how rap has been culturally translated, performed, and appropriated by females in order to “flip the script,” or subvert the dichotomous model of female sexuality that has been imposed upon them. Weaving insights from three academic fields (cultural translation, Chican@ studies, and hip-hop feminism, this paper also aims to creatively expand the definition of translation by positioning rap music as a performative language in its own right, capable of encoding and translating complex cultural issues related to race, gender, and sexuality.

Information Retrieval Diary of an Expert Technical Translator.

Science.gov (United States)

Cremmins, Edward T.

1984-01-01

Recommends use of entries from the information retrieval diary of Ted Crump, expert technical translator at the National Institute of Health, in the construction of computer models showing how expert translators solve problems of ambiguity in language. Expert and inexpert translation systems, eponyms, abbreviations, and alphabetic solutions are…

The translational metaphor in psychoanalysis.

Science.gov (United States)

Kirshner, Lewis

2015-02-01

The translational metaphor in psychoanalysis refers to the traditional method of interpreting or restating the meaning of verbal and behavioral acts of a patient in other, presumably more accurate terms that specify the forces and conflicts underlying symptoms. The analyst translates the clinical phenomenology to explain its true meaning and origin. This model of analytic process has been challenged from different vantage points by authors presenting alternative conceptions of therapeutic action. Although the temptation to find and make interpretations of clinical material is difficult to resist, behaving in this way places the analyst in the position of a teacher or diagnostician, seeking a specific etiology, which has not proven fruitful. Despite its historical appeal, I argue that the translational model is a misleading and anachronistic version of what actually occurs in psychoanalysis. I emphasize instead the capacity of analysis to promote the emergence of new forms of representation, or figuration, from the unconscious, using the work of Lacan, Laplanche, and Modell to exemplify this reformulation, and provide clinical illustrations of how it looks in practice. Copyright © 2014 Institute of Psychoanalysis.

Integrated quantitative pharmacology for treatment optimization in oncology

NARCIS (Netherlands)

van Hasselt, J.G.C.

2014-01-01

This thesis describes the development and application of quantitative pharmacological models in oncology for treatment optimization and for the design and analysis of clinical trials with respect to pharmacokinetics, toxicity, efficacy and cost-effectiveness. A recurring theme throughout this thesis

Neuroscience of behavioral and pharmacological treatments for addictions

Science.gov (United States)

Potenza, Marc N.; Sofuoglu, Mehmet; Carroll, Kathleen M.; Rounsaville, Bruce J.

2011-01-01

Summary Although substantial advances have been made in behavioral and pharmacological treatments for addictions, moving treatment development to the next stage may require novel ways of approaching addictions, particularly those derived from new findings regarding of the neurobiological underpinnings of addictions, while assimilating and incorporating relevant information from earlier approaches. In this review, we first briefly review theoretical and biological models of addiction and then describe existing behavioral and pharmacologic therapies for the addictions within this framework. We then propose new directions for treatment development and targets that are informed by recent evidence regarding the heterogeneity of addictions and the neurobiological contributions to these disorders. PMID:21338880

Modeling timelines for translational science in cancer; the impact of technological maturation

OpenAIRE

McNamee, Laura M.; Ledley, Fred D.

2017-01-01

This work examines translational science in cancer based on theories of innovation that posit a relationship between the maturation of technologies and their capacity to generate successful products. We examined the growth of technologies associated with 138 anticancer drugs using an analytical model that identifies the point of initiation of exponential growth and the point at which growth slows as the technology becomes established. Approval of targeted and biological products corresponded ...

Pharmacological Intervention through Dietary Nutraceuticals in Gastrointestinal Neoplasia.

Science.gov (United States)

Ullah, Mohammad F; Bhat, Showket H; Husain, Eram; Abu-Duhier, Faisel; Hadi, S M; Sarkar, Fazlul H; Ahmad, Aamir

2016-07-03

Neoplastic conditions associated with gastrointestinal (GI) tract are common worldwide with colorectal cancer alone accounting for the third leading rate of cancer incidence. Other GI malignancies such as esophageal carcinoma have shown an increasing trend in the last few years. The poor survival statistics of these fatal cancer diseases highlight the need for multiple alternative treatment options along with effective prophylactic strategies. Worldwide geographical variation in cancer incidence indicates a correlation between dietary habits and cancer risk. Epidemiological studies have suggested that populations with high intake of certain dietary agents in their regular meals have lower cancer rates. Thus, an impressive embodiment of evidence supports the concept that dietary factors are key modulators of cancer including those of GI origin. Preclinical studies on animal models of carcinogenesis have reflected the pharmacological significance of certain dietary agents called as nutraceuticals in the chemoprevention of GI neoplasia. These include stilbenes (from red grapes and red wine), isoflavones (from soy), carotenoids (from tomatoes), curcuminoids (from spice turmeric), catechins (from green tea), and various other small plant metabolites (from fruits, vegetables, and cereals). Pleiotropic action mechanisms have been reported for these diet-derived chemopreventive agents to retard, block, or reverse carcinogenesis. This review presents a prophylactic approach to primary prevention of GI cancers by highlighting the translational potential of plant-derived nutraceuticals from epidemiological, laboratory, and clinical studies, for the better management of these cancers through consumption of nutraceutical rich diets and their intervention in cancer therapeutics.

On Interactive Teaching Model of Translation Course Based on Wechat

Science.gov (United States)

Lin, Wang

2017-01-01

Constructivism is a theory related to knowledge and learning, focusing on learners' subjective initiative, based on which the interactive approach has been proved to play a crucial role in language learning. Accordingly, the interactive approach can also be applied to translation teaching since translation itself is a bilingual transformational…

Translation Techniques

OpenAIRE

Marcia Pinheiro

2015-01-01

In this paper, we discuss three translation techniques: literal, cultural, and artistic. Literal translation is a well-known technique, which means that it is quite easy to find sources on the topic. Cultural and artistic translation may be new terms. Whilst cultural translation focuses on matching contexts, artistic translation focuses on matching reactions. Because literal translation matches only words, it is not hard to find situations in which we should not use this technique.  Because a...

Proposed Model for Translational Research at a Teaching-Intensive College of Pharmacy.

Science.gov (United States)

Ulrich, Erin; Grady, Sarah; Vonderhaar, Jacqueline; Ruplin, Andrew

2017-08-08

Many American colleges of pharmacy are small, private, teaching institutions. Faculty are required to maintain a research agenda, although the publication quota is less compared with their publicly funded college of pharmacy peers. Faculty at these smaller schools conduct research with very little internal or external funding. This tends to lead to smaller, less impactful research findings. Translational research is becoming popular for research faculty as it bridges theory to practice. The Knowledge-to-Action (KTA) framework presents the steps to conduct translational research. To apply and determine if the KTA framework would be able to produce practice-impactful research at an institution that does not depend on grant funding as part of faculty research agendas. An interdisciplinary team was formed with providers at the clinical faculty's practice site. As the team moved through the KTA steps, authors documented the roles of each team member. It was clear that many different types of teams were formed throughout the KTA process. These teams were then categorized according to the Interdisciplinary Teamwork System. The final result is a proposed model of types of teams and required member roles that are necessary within each KTA step for faculty to conduct practice-impactful research at a small, private, teaching institution without substantial grant funding awards. Applying the KTA framework, two impactful original research manuscripts were developed over two academic years. Furthermore, the practitioners at the clinical faculty member's site were very pleased with the ease of conducting research, as they were never required to take a lead role. In addition, both faculty members alternated lead and support role allowing for a decreased burden of workload while producing theory-driven research. The KTA framework can create a model for translational research and may be particularly beneficial to small teaching institutions to conduct impactful research. Copyright �

Pharmacological Inhibition of PKCθ Counteracts Muscle Disease in a Mouse Model of Duchenne Muscular Dystrophy.

Science.gov (United States)

Marrocco, V; Fiore, P; Benedetti, A; Pisu, S; Rizzuto, E; Musarò, A; Madaro, L; Lozanoska-Ochser, B; Bouché, M

2017-02-01

Inflammation plays a considerable role in the progression of Duchenne Muscular Dystrophy (DMD), a severe muscle disease caused by a mutation in the dystrophin gene. We previously showed that genetic ablation of Protein Kinase C θ (PKCθ) in mdx, the mouse model of DMD, improves muscle healing and regeneration, preventing massive inflammation. To establish whether pharmacological targeting of PKCθ in DMD can be proposed as a therapeutic option, in this study we treated young mdx mice with the PKCθ inhibitor Compound 20 (C20). We show that C20 treatment led to a significant reduction in muscle damage associated with reduced immune cells infiltration, reduced inflammatory pathways activation, and maintained muscle regeneration. Importantly, C20 treatment is efficient in recovering muscle performance in mdx mice, by preserving muscle integrity. Together, these results provide proof of principle that pharmacological inhibition of PKCθ in DMD can be considered an attractive strategy to modulate immune response and prevent the progression of the disease. Duchenne muscular dystrophy (DMD) is a severe muscle disease affecting 1:3500 male births. DMD is caused by a mutation in dystrophin gene, coding for a protein required for skeletal and cardiac muscle integrity. Lack of a functional dystrophin is primarily responsible for the muscle eccentric contraction-induced muscle damage, observed in dystrophic muscle. However, inflammation plays a considerable role in the progression of DMD. Glucocorticoids, which have anti-inflammatory properties, are being used to treat DMD with some success; however, long term treatment with these drugs induces muscle atrophy and wasting, outweighing their benefit. The identification of specific targets for anti-inflammatory therapies is one of the ongoing therapeutic options. Although blunting inflammation would not be a "cure" for the disease, the emerging clue is that multiple strategies, addressing different aspects of the pathology

Translational physiology: from molecules to public health.

Science.gov (United States)

Seals, Douglas R

2013-07-15

The term 'translational research' was coined 20 years ago and has become a guiding influence in biomedical research. It refers to a process by which the findings of basic research are extended to the clinical research setting (bench to bedside) and then to clinical practice and eventually health policy (bedside to community). It is a dynamic, multidisciplinary research approach. The concept of translational physiology applies the translational research model to the physiological sciences. It differs from the traditional areas of integrative and clinical physiology by its broad investigative scope of basic research to community health. Translational physiology offers exciting opportunities, but presently is under-developed and -utilized. A key challenge will be to expand physiological research by extending investigations to communities of patients and healthy (or at risk) individuals. This will allow bidirectional physiological investigation throughout the translational continuum: basic research observations can be studied up to the population level, and mechanisms can be assessed by 'reverse translation' in clinical research settings and preclinical models based on initial observations made in populations. Examples of translational physiology questions, experimental approaches, roadblocks and strategies for promotion are discussed. Translational physiology provides a novel framework for physiology programs and an investigational platform for physiologists to study function from molecular events to public health. It holds promise for enhancing the completeness and societal impact of our work, while further solidifying the critical role of physiology in the biomedical research enterprise.

Translation Ambiguity but Not Word Class Predicts Translation Performance

Science.gov (United States)

Prior, Anat; Kroll, Judith F.; Macwhinney, Brian

2013-01-01

We investigated the influence of word class and translation ambiguity on cross-linguistic representation and processing. Bilingual speakers of English and Spanish performed translation production and translation recognition tasks on nouns and verbs in both languages. Words either had a single translation or more than one translation. Translation…

Examining English-German Translation Ambiguity Using Primed Translation Recognition

Science.gov (United States)

Eddington, Chelsea M.; Tokowicz, Natasha

2013-01-01

Many words have more than one translation across languages. Such "translation-ambiguous" words are translated more slowly and less accurately than their unambiguous counterparts. We examine the extent to which word context and translation dominance influence the processing of translation-ambiguous words. We further examine how these factors…

A GRAMMATICAL ADJUSTMENT ANALYSIS OF STATISTICAL MACHINE TRANSLATION METHOD USED BY GOOGLE TRANSLATE COMPARED TO HUMAN TRANSLATION IN TRANSLATING ENGLISH TEXT TO INDONESIAN

Directory of Open Access Journals (Sweden)

Eko Pujianto

2017-04-01

Full Text Available Google translate is a program which provides fast, free and effortless translating service. This service uses a unique method to translate. The system is called ―Statistical Machine Translation‖, the newest method in automatic translation. Machine translation (MT is an area of many kinds of different subjects of study and technique from linguistics, computers science, artificial intelligent (AI, translation theory, and statistics. SMT works by using statistical methods and mathematics to process the training data. The training data is corpus-based. It is a compilation of sentences and words of the languages (SL and TL from translation done by human. By using this method, Google let their machine discovers the rules for themselves. They do this by analyzing millions of documents that have already been translated by human translators and then generate the result based on the corpus/training data. However, questions arise when the results of the automatic translation prove to be unreliable in some extent. This paper questions the dependability of Google translate in comparison with grammatical adjustment that naturally characterizes human translators' specific advantage. The attempt is manifested through the analysis of the TL of some texts translated by the SMT. It is expected that by using the sample of TL produced by SMT we can learn the potential flaws of the translation. If such exists, the partial of more substantial undependability of SMT may open more windows to the debates of whether this service may suffice the users‘ need.

Learning of medical pharmacology via innovation:a personal experience at McMaster and in Asia

Institute of Scientific and Technical Information of China (English)

Chiu-yin KWAN

2004-01-01

Pharmacology in the traditional medical curriculum has been treated as a discrete "preclinical" discipline identifying itself distinctly different from the other preclinical sciences or clinical subjects in knowledge base as well as learning/teaching instructions. It is usually run in series with other pre-clinical courses (eg, anatomy, biochemistry,physiology etc), but in parallel with other paraclinical courses such as pathology, microbiology and community medicine. Clinical pharmacology was only introduced relatively recently designed to overcome the perceived deficiency in "preclinical" pharmacology regarding its therapeutic relevance and application to medicine. In many universities, both preclinical and clinical pharmacology courses co-exist, usually independently offered by two separate, sometimes non-interacting Departments of Pharmacology and Clinical Pharmacology. In this model,pharmacology is generally taught in a teacher-centered, discipline-oriented, and knowledge-based curriculum.Furthermore, pharmacology courses are commonly taught by "expert" teachers, who usually engage in excessiveteaching, often adopt a knowledge-based approach in both instruction and assessment, and frequently evade or ignore clinical relevance. The clinical relevance of the pharmacological sciences is sometimes also taught in a didactic and problem-solving manner, although it is usually case-oriented. In recent years, problem-based medical curricula have emerged, in varying forms, as a platform in which pharmacology is viewed as an integrated component in a holistic approach to medical education. In this problem-based learning (PBL) model, pharmacology is learned in a student-centered environment, based on self-directed, clinically relevant and case-oriented approach,usually in a small-group tutorial format. In PBL, pharmacology is learned in concert with other subject issues relevant to the case-problem in question, such as anatomy, physiology, pathology, microbiology

Entrainment to periodic initiation and transition rates in a computational model for gene translation.

Directory of Open Access Journals (Sweden)

Michael Margaliot

Full Text Available Periodic oscillations play an important role in many biomedical systems. Proper functioning of biological systems that respond to periodic signals requires the ability to synchronize with the periodic excitation. For example, the sleep/wake cycle is a manifestation of an internal timing system that synchronizes to the solar day. In the terminology of systems theory, the biological system must entrain or phase-lock to the periodic excitation. Entrainment is also important in synthetic biology. For example, connecting several artificial biological systems that entrain to a common clock may lead to a well-functioning modular system. The cell-cycle is a periodic program that regulates DNA synthesis and cell division. Recent biological studies suggest that cell-cycle related genes entrain to this periodic program at the gene translation level, leading to periodically-varying protein levels of these genes. The ribosome flow model (RFM is a deterministic model obtained via a mean-field approximation of a stochastic model from statistical physics that has been used to model numerous processes including ribosome flow along the mRNA. Here we analyze the RFM under the assumption that the initiation and/or transition rates vary periodically with a common period T. We show that the ribosome distribution profile in the RFM entrains to this periodic excitation. In particular, the protein synthesis pattern converges to a unique periodic solution with period T. To the best of our knowledge, this is the first proof of entrainment in a mathematical model for translation that encapsulates aspects such as initiation and termination rates, ribosomal movement and interactions, and non-homogeneous elongation speeds along the mRNA. Our results support the conjecture that periodic oscillations in tRNA levels and other factors related to the translation process can induce periodic oscillations in protein levels, and may suggest a new approach for re-engineering genetic

Towards predictive cardiovascular safety : a systems pharmacology approach

NARCIS (Netherlands)

Snelder, Nelleke

2014-01-01

Cardiovascular safety issues related to changes in blood pressure, arise frequently in drug development. In the thesis “Towards predictive cardiovascular safety – a systems pharmacology approach”, a system-specific model is described to quantify drug effects on the interrelationship between mean

Translation-coupling systems

Science.gov (United States)

Pfleger, Brian; Mendez-Perez, Daniel

2013-11-05

Disclosed are systems and methods for coupling translation of a target gene to a detectable response gene. A version of the invention includes a translation-coupling cassette. The translation-coupling cassette includes a target gene, a response gene, a response-gene translation control element, and a secondary structure-forming sequence that reversibly forms a secondary structure masking the response-gene translation control element. Masking of the response-gene translation control element inhibits translation of the response gene. Full translation of the target gene results in unfolding of the secondary structure and consequent translation of the response gene. Translation of the target gene is determined by detecting presence of the response-gene protein product. The invention further includes RNA transcripts of the translation-coupling cassettes, vectors comprising the translation-coupling cassettes, hosts comprising the translation-coupling cassettes, methods of using the translation-coupling cassettes, and gene products produced with the translation-coupling cassettes.

The Role of Semantics in Translation Recognition: Effects of Number of Translations, Dominance of Translations and Semantic Relatedness of Multiple Translations

Science.gov (United States)

Laxen, Jannika; Lavaur, Jean-Marc

2010-01-01

This study aims to examine the influence of multiple translations of a word on bilingual processing in three translation recognition experiments during which French-English bilinguals had to decide whether two words were translations of each other or not. In the first experiment, words with only one translation were recognized as translations…

Anesthetic pharmacology

National Research Council Canada - National Science Library

Evers, Alex S; Maze, M; Kharasch, Evan D

2011-01-01

...: Section 1 introduces the principles of drug action, Section 2 presents the molecular, cellular and integrated physiology of the target organ/functional system and Section 3 reviews the pharmacology...

Working with corpora in the translation classroom

Directory of Open Access Journals (Sweden)

Ralph Krüger

2012-10-01

Full Text Available This article sets out to illustrate possible applications of electronic corpora in the translation classroom. Starting with a survey of corpus use within corpus-based translation studies, the didactic value of corpora in the translation classroom and their epistemic value in translation teaching and practice will be elaborated. A typology of translation practice-oriented corpora will be presented, and the use of corpora in translation will be positioned within two general models of translation competence. Special consideration will then be given to the design and application of so-called Do-it-yourself (DIY corpora, which are compiled ad hoc with the aim of completing a specific translation task. In this context, possible sources for retrieving corpus texts will be presented and evaluated and it will be argued that, owing to time and availability constraints in real-life translation, the Internet should be used as a major source of corpus data. After a brief discussion of possible Internet research techniques for targeted and quality-focused corpus compilation, the possible use of the Internet itself as a macro-corpus will be elaborated. The article concludes with a brief presentation of corpus use in translation teaching in the MA in Specialised Translation Programme offered at Cologne University of Applied Sciences, Germany.

Predicting Translation Initiation Rates for Designing Synthetic Biology

International Nuclear Information System (INIS)

Reeve, Benjamin; Hargest, Thomas; Gilbert, Charlie; Ellis, Tom

2014-01-01

In synthetic biology, precise control over protein expression is required in order to construct functional biological systems. A core principle of the synthetic biology approach is a model-guided design and based on the biological understanding of the process, models of prokaryotic protein production have been described. Translation initiation rate is a rate-limiting step in protein production from mRNA and is dependent on the sequence of the 5′-untranslated region and the start of the coding sequence. Translation rate calculators are programs that estimate protein translation rates based on the sequence of these regions of an mRNA, and as protein expression is proportional to the rate of translation initiation, such calculators have been shown to give good approximations of protein expression levels. In this review, three currently available translation rate calculators developed for synthetic biology are considered, with limitations and possible future progress discussed.

Translational Assays for Assessment of Cognition in Rodent Models of Alzheimer's Disease and Dementia.

Science.gov (United States)

Shepherd, A; Tyebji, S; Hannan, A J; Burrows, E L

2016-11-01

Cognitive dysfunction appears as a core feature of dementia, which includes its most prevalent form, Alzheimer's disease (AD), as well as vascular dementia, frontotemporal dementia, and other brain disorders. AD alone affects more than 45 million people worldwide, with growing prevalence in aging populations. There is no cure, and therapeutic options remain limited. Gene-edited and transgenic animal models, expressing disease-specific gene mutations, illuminate pathogenic mechanisms leading to cognitive decline in AD and other forms of dementia. To date, cognitive tests in AD mouse models have not been directly relevant to the clinical presentation of AD, providing challenges for translation of findings to the clinic. Touchscreen testing in mice has enabled the assessment of specific cognitive domains in mice that are directly relevant to impairments described in human AD patients. In this review, we provide context for how cognitive decline is measured in the clinic, describe traditional methods for assessing cognition in mice, and outline novel approaches, including the use of the touchscreen platform for cognitive testing. We highlight the limitations of traditional memory-testing paradigms in mice, particularly their capacity for direct translation into cognitive testing of patients. While it is not possible to expect direct translation in testing methodologies, we can aim to develop tests that engage similar neural substrates in both humans and mice. Ultimately, that would enable us to better predict efficacy across species and therefore improve the chances that a treatment that works in mice will also work in the clinic.

A Transparent Translation from Legacy System Model into Common Information Model: Preprint

Energy Technology Data Exchange (ETDEWEB)

Ding, Fei [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Simpson, Jeffrey [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Zhang, Yingchen [National Renewable Energy Laboratory (NREL), Golden, CO (United States)

2018-04-27

Advance in smart grid is forcing utilities towards better monitoring, control and analysis of distribution systems, and requires extensive cyber-based intelligent systems and applications to realize various functionalities. The ability of systems, or components within systems, to interact and exchange services or information with each other is the key to the success of smart grid technologies, and it requires efficient information exchanging and data sharing infrastructure. The Common Information Model (CIM) is a standard that allows different applications to exchange information about an electrical system, and it has become a widely accepted solution for information exchange among different platforms and applications. However, most existing legacy systems are not developed using CIM, but using their own languages. Integrating such legacy systems is a challenge for utilities, and the appropriate utilization of the integrated legacy systems is even more intricate. Thus, this paper has developed an approach and open-source tool in order to translate legacy system models into CIM format. The developed tool is tested for a commercial distribution management system and simulation results have proved its effectiveness.

Drosophila Melanogaster as an Emerging Translational Model of Human Nephrolithiasis

Science.gov (United States)

Miller, Joe; Chi, Thomas; Kapahi, Pankaj; Kahn, Arnold J.; Kim, Man Su; Hirata, Taku; Romero, Michael F.; Dow, Julian A.T.; Stoller, Marshall L.

2013-01-01

Purpose The limitations imposed by human clinical studies and mammalian models of nephrolithiasis have hampered the development of effective medical treatments and preventative measures for decades. The simple but elegant Drosophila melanogaster is emerging as a powerful translational model of human disease, including nephrolithiasis and may provide important information essential to our understanding of stone formation. We present the current state of research using D. melanogaster as a model of human nephrolithiasis. Materials and Methods A comprehensive review of the English language literature was performed using PUBMED. When necessary, authoritative texts on relevant subtopics were consulted. Results The genetic composition, anatomic structure and physiologic function of Drosophila Malpighian tubules are remarkably similar to those of the human nephron. The direct effects of dietary manipulation, environmental alteration, and genetic variation on stone formation can be observed and quantified in a matter of days. Several Drosophila models of human nephrolithiasis, including genetically linked and environmentally induced stones, have been developed. A model of calcium oxalate stone formation is among the most recent fly models of human nephrolithiasis. Conclusions The ability to readily manipulate and quantify stone formation in D. melanogaster models of human nephrolithiasis presents the urologic community with a unique opportunity to increase our understanding of this enigmatic disease. PMID:23500641

Parsing statistical machine translation output

NARCIS (Netherlands)

Carter, S.; Monz, C.; Vetulani, Z.

2009-01-01

Despite increasing research into the use of syntax during statistical machine translation, the incorporation of syntax into language models has seen limited success. We present a study of the discriminative abilities of generative syntax-based language models, over and above standard n-gram models,

Towards Vocational Translation in German Studies in Nigeria and Beyond: Lessons from Translation Teaching and Practice in Germany

OpenAIRE

Oyetoyan, Oludamilola Iyadunni

2016-01-01

The argument in this research work has been that Vocational Translation Teaching (VOTT) can serve as the bridge between Translation Studies and Foreign Language Studies, a study field from which several graduates may proceed to take up translation jobs. The use of the VOTT-model can also lead to benefits of motivation in terms of job prospects and increase the work skills of students. The declarative and procedural knowledge necessary for implementing VOTT in an FLL environment have been...

PATSTAGS: PATRAN-To-STAGSC-1 Translator

Science.gov (United States)

Otte, Neil

1993-01-01

PATSTAGS computer program translates data from PATRAN finite-element mathematical model into STAGS input records used for engineering analysis. Reads data from PATRAN neutral file and writes STAGS input records into STAGS input file and UPRESS data file. Supports translations of nodal constraints, and of nodal, element, force, and pressure data. Written in FORTRAN 77.

PERSONALITY TYPE AND TRANSLATION PERFORMANCE OF PERSIAN TRANSLATOR TRAINEES

Directory of Open Access Journals (Sweden)

Reza Shaki

2017-09-01

Full Text Available The study investigated the relationship between the personality typology of a sample of Iranian translation students and their translation quality in terms of expressive, appellative, and informative text types. The study also attempted to identify the personality types that can perform better in English to Persian translation of the three text types. For that purpose, the personality type and the translation quality of the participants was assessed using Myers-Briggs Type Indicator (MBTI personality test and translation quality assessment (TQA, respectively. The analysis of the data revealed that the personality type of the participants seemed relevant to the translation quality of all the text types. The translation quality of the participants with intuitive and thinking types was significantly better than the sensing type counterparts in translating expressive texts. The participants with intuitive and feeling types also performed better than their counterparts with sensing type in translation of the informative text. Moreover, the participants with intuitive, feeling, and thinking personality types performed more successfully than the participants with sensing type in translation of the appellative text. The findings of the study are discussed in light of the existing research literature.

NASA-IGES Translator and Viewer

Science.gov (United States)

Chou, Jin J.; Logan, Michael A.

1995-01-01

NASA-IGES Translator (NIGEStranslator) is a batch program that translates a general IGES (Initial Graphics Exchange Specification) file to a NASA-IGES-Nurbs-Only (NINO) file. IGES is the most popular geometry exchange standard among Computer Aided Geometric Design (CAD) systems. NINO format is a subset of IGES, implementing the simple and yet the most popular NURBS (Non-Uniform Rational B-Splines) representation. NIGEStranslator converts a complex IGES file to the simpler NINO file to simplify the tasks of CFD grid generation for models in CAD format. The NASA-IGES Viewer (NIGESview) is an Open-Inventor-based, highly interactive viewer/ editor for NINO files. Geometry in the IGES files can be viewed, copied, transformed, deleted, and inquired. Users can use NIGEStranslator to translate IGES files from CAD systems to NINO files. The geometry then can be examined with NIGESview. Extraneous geometries can be interactively removed, and the cleaned model can be written to an IGES file, ready to be used in grid generation.

Narrative review of frameworks for translating research evidence into policy and practice.

Science.gov (United States)

Milat, Andrew J; Li, Ben

2017-02-15

A significant challenge in research translation is that interested parties interpret and apply the associated terms and conceptual frameworks in different ways. The purpose of this review was to: a) examine different research translation frameworks; b) examine the similarities and differences between the frameworks; and c) identify key strengths and weaknesses of the models when they are applied in practice. The review involved a keyword search of PubMed. The search string was (translational research OR knowledge translation OR evidence to practice) AND (framework OR model OR theory) AND (public health OR health promotion OR medicine). Included studies were published in English between January 1990 and December 2014, and described frameworks, models or theories associated with research translation. The final review included 98 papers, and 41 different frameworks and models were identified. The most frequently applied knowledge translation framework in the literature was RE-AIM, followed by the knowledge translation continuum or 'T' models, the Knowledge to Action framework, the PARiHS framework, evidence based public health models, and the stages of research and evaluation model. The models identified in this review stem from different fields, including implementation science, basic and medical sciences, health services research and public health, and propose different but related pathways to closing the research-practice gap.

Physical Properties and Effect in a Battery of Safety Pharmacology Models for Three Structurally Distinct Enteric Polymers Employed as Spray-dried Dispersion Carriers

Directory of Open Access Journals (Sweden)

Ryan M Fryer

2016-10-01

Full Text Available Establishing a wide therapeutic index (TI for pre-clinical safety is important during lead optimization (LO in research, prior to clinical development, although is often limited by a molecules physiochemical characteristics. Recent advances in the application of the innovative vibrating mesh spray-drying technology to prepare amorphous solid dispersions may offer an opportunity to achieve high plasma concentrations of poorly soluble NCEs to enable testing and establishment of a wide TI in safety pharmacology studies. While some of the amorphous solid dispersion carriers are generally recognized as safe for clinical use, whether they are sufficiently benign to enable in vivo pharmacology studies has not been sufficiently demonstrated. Thus, the physical properties, and effect in a battery of in vivo safety pharmacology models, were assessed in three classes of polymers employed as spray-dried dispersion carriers. The polymers (HPMC-AS, Eudragit, PVAP displayed low affinity with acetone/methanol, suitable for solvent-based spray drying. The water sorption of the polymers was moderate, and the degree of hysteresis of HPMC-AS was smaller than Eudragit and PVAP indicating the intermolecular interaction of water-cellulose molecules is weaker than water-acrylate or water-polyvinyl molecules. The polymer particles were well-suspended without aggregation with a mean particle size less than 3 µm in an aqueous vehicle. When tested in conscious Wistar Han rats in safety pharmacology models (n=6-8/dose/polymer investigating effects on CNS, gastrointestinal, and cardiovascular function, no liabilities were identified at any dose tested (30-300 mg/kg PO, suspension. In brief, the polymers had no effect in a modified Irwin test that included observational and evoked endpoints related to stereotypies, excitation, sedation, pain/anesthesia, autonomic balance, reflexes, and others. No effect of the polymers on gastric emptying or intestinal transit was observed

[Note on the epistemology of clinical pharmacology: comparison with the approach of Karl Popper].

Science.gov (United States)

Boissel, J P

1999-01-01

Is clinical pharmacology a science or only an application of science? Karl Popper suggested a method to identify science and to sort it out from other logical activities such as metaphysics, whereby the falsification criterion he proposed can apply to the theory in such a way that the theory could be refuted. The clinical pharmacologist's approach requires the build-up of a therapeutic model on the basis of two other models: the physiopathologic and the pharmacological. The three-model construct is a theory. Is it scientific in the Popperian sense? From the therapeutic model, one can predict the efficacy of a drug, and the corresponding statement is tested by a clinical trial. Whatever the original statement, it is modified into a refutable one because of the use of the statistical approach in clinical trials. Furthermore, the predicate represents a hypothesis of the model validity, which will then be confronted with 'reality' through clinical experiment. As the therapeutic model is refutable, clinical pharmacology is a science in the Popperian sense.

Pharmacological ascorbate and ionizing radiation (IR increase labile iron in pancreatic cancer

Directory of Open Access Journals (Sweden)

Justin C. Moser

2014-01-01

Full Text Available Labile iron, i.e. iron that is weakly bound and is relatively unrestricted in its redox activity, has been implicated in both the pathogenesis as well as treatment of cancer. Two cancer treatments where labile iron may contribute to their mechanism of action are pharmacological ascorbate and ionizing radiation (IR. Pharmacological ascorbate has been shown to have tumor-specific toxic effects due to the formation of hydrogen peroxide. By catalyzing the oxidation of ascorbate, labile iron can enhance the rate of formation of hydrogen peroxide; labile iron can also react with hydrogen peroxide. Here we have investigated the magnitude of the labile iron pool in tumor and normal tissue. We also examined the ability of pharmacological ascorbate and IR to change the size of the labile iron pool. Although a significant amount of labile iron was seen in tumors (MIA PaCa-2 cells in athymic nude mice, higher levels were seen in murine tissues that were not susceptible to pharmacological ascorbate. Pharmacological ascorbate and irradiation were shown to increase the labile iron in tumor homogenates from this murine model of pancreatic cancer. As both IR and pharmacological ascorbate may rely on labile iron for their effects on tumor tissues, our data suggest that pharmacological ascorbate could be used as a radio-sensitizing agent for some radio-resistant tumors.

The feasibility of implementing recovery, psychosocial and pharmacological interventions for psychosis: comparison study.

Science.gov (United States)

van der Krieke, Lian; Bird, Victoria; Leamy, Mary; Bacon, Faye; Dunn, Rebecca; Pesola, Francesca; Janosik, Monika; Le Boutillier, Clair; Williams, Julie; Slade, Mike

2015-05-23

Clinical guidelines for the treatment of people experiencing psychosis have existed for over a decade, but implementation of recommended interventions is limited. Identifying influences on implementation may help to reduce this translational gap. The Structured Assessment of Feasibility (SAFE) measure is a standardised assessment of implementation blocks and enablers. The aim of this study was to characterise and compare the implementation blocks and enablers for recommended psychosis interventions. SAFE was used to evaluate and compare three groups of interventions recommended in the 2014 NICE psychosis guideline: pharmacological (43 trials testing 5 interventions), psychosocial (65 trials testing 5 interventions), and recovery (19 trials testing 5 interventions). The 127 trial reports rated with SAFE were supplemented by published intervention manuals, research protocols, trial registrations and design papers. Differences in the number of blocks and enablers across the three interventions were tested statistically, and feasibility profiles were generated. There was no difference between psychosocial and recovery interventions in the number of blocks or enablers to implementation. Pharmacological interventions (a) had fewer blocks than both psychosocial interventions (χ (2)(3) = 133.77, p Feasibility profiles show that pharmacological interventions are relatively easy to implement but can sometimes involve risks. Psychosocial and recovery interventions are relatively complex but tend to be more flexible and more often manualised. SAFE ratings can contribute to tackling the current implementation challenges in mental health services, by providing a reporting guideline structure for researchers to maximise the potential for implementation and by informing prioritisation decisions by clinical guideline developers and service managers.

Levelling the playing field: an investigation into the translation of ...

African Journals Online (AJOL)

A possible solution to the benchmarking problem was to translate the Afrikaans test into English. The translation framework, adopted for this study, was Nord's functionalist model. This paper will elaborate on the translation procedure, and the variance in students' performance on the translated version compared to previous ...

Gravito-Inertial Force Resolution in Perception of Synchronized Tilt and Translation

Science.gov (United States)

Wood, Scott J.; Holly, Jan; Zhang, Guen-Lu

2011-01-01

Natural movements in the sagittal plane involve pitch tilt relative to gravity combined with translation motion. The Gravito-Inertial Force (GIF) resolution hypothesis states that the resultant force on the body is perceptually resolved into tilt and translation consistently with the laws of physics. The purpose of this study was to test this hypothesis for human perception during combined tilt and translation motion. EXPERIMENTAL METHODS: Twelve subjects provided verbal reports during 0.3 Hz motion in the dark with 4 types of tilt and/or translation motion: 1) pitch tilt about an interaural axis at +/-10deg or +/-20deg, 2) fore-aft translation with acceleration equivalent to +/-10deg or +/-20deg, 3) combined "in phase" tilt and translation motion resulting in acceleration equivalent to +/-20deg, and 4) "out of phase" tilt and translation motion that maintained the resultant gravito-inertial force aligned with the longitudinal body axis. The amplitude of perceived pitch tilt and translation at the head were obtained during separate trials. MODELING METHODS: Three-dimensional mathematical modeling was performed to test the GIF-resolution hypothesis using a dynamical model. The model encoded GIF-resolution using the standard vector equation, and used an internal model of motion parameters, including gravity. Differential equations conveyed time-varying predictions. The six motion profiles were tested, resulting in predicted perceived amplitude of tilt and translation for each. RESULTS: The modeling results exhibited the same pattern as the experimental results. Most importantly, both modeling and experimental results showed greater perceived tilt during the "in phase" profile than the "out of phase" profile, and greater perceived tilt during combined "in phase" motion than during pure tilt of the same amplitude. However, the model did not predict as much perceived translation as reported by subjects during pure tilt. CONCLUSION: Human perception is consistent with

From translational research to open technology innovation systems.

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Savory, Clive; Fortune, Joyce

2015-01-01

The purpose of this paper is to question whether the emphasis placed within translational research on a linear model of innovation provides the most effective model for managing health technology innovation. Several alternative perspectives are presented that have potential to enhance the existing model of translational research. A case study is presented of innovation of a clinical decision support system. The paper concludes from the case study that an extending the triple helix model of technology transfer, to one based on a quadruple helix, present a basis for improving the performance translational research. A case study approach is used to help understand development of an innovative technology within a teaching hospital. The case is then used to develop and refine a model of the health technology innovation system. The paper concludes from the case study that existing models of translational research could be refined further through the development of a quadruple helix model of heath technology innovation that encompasses greater emphasis on user-led and open innovation perspectives. The paper presents several implications for future research based on the need to enhance the model of health technology innovation used to guide policy and practice. The quadruple helix model of innovation that is proposed can potentially guide alterations to the existing model of translational research in the healthcare sector. Several suggestions are made for how innovation activity can be better supported at both a policy and operational level. This paper presents a synthesis of the innovation literature applied to a theoretically important case of open innovation in the UK National Health Service. It draws in perspectives from other industrial sectors and applies them specifically to the management and organisation of innovation activities around health technology and the services in which they are embedded.

Advancing neurosurgery through translational research.

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Lacey, Claire; Sutherland, Garnette

2013-01-01

Every year, the number of published research articles increases significantly. However, many potentially useful ideas are lost in this flood of data. Translational research provides a framework through which investigators or laboratories can maximize the likelihood that the product of their research will be adopted in medical practice. There are 2 recognizable models of translation appropriate for the majority of research: investigator driven and industry enabled. Investigator-driven research has more range because it does not have to consider the profit margin of research, but it is a slow process. The industry-enabled model accelerates the translational research process through the power of industry funding but is interested primarily in products with potential for profit. Two cases are examined to illustrate different methods of partnering with industry. IMRIS is a company founded by investigators to distribute intraoperative magnetic resonance imaging technology based on a movable high-field magnet. It took 7 years for IMRIS to make its first sale, but it is now a successful company. With neuroArm, a surgical robot, investigators decided to sell the intellectual property to an established company to ensure successful global commercialization. Translational research advances medicine by creating and distributing effective solutions to contemporary problems.

Guidelines for the preclinical in vivo evaluation of pharmacological active drugs for ALS/MND: report on the 142nd ENMC international workshop.

Science.gov (United States)

Ludolph, Albert C; Bendotti, Caterina; Blaugrund, Eran; Hengerer, Bastian; Löffler, Jean-Philippe; Martin, Joanne; Meininger, Vincent; Meyer, Thomas; Moussaoui, Saliha; Robberecht, Wim; Scott, Sean; Silani, Vincenzo; Van Den Berg, Leonard H

2007-08-01

A transgenic animal model for anterior horn cell loss was established in 1994. This model is based on the insertion of a high copy number of disease-causing human Cu/Zn SOD mutations into the intact mouse genome. It serves to establish hypotheses for the pathogenesis of anterior horn cell death, but also to test potential pharmacological approaches to therapy in human ALS. Today, more than 100 -- published and unpublished -- compounds have been tested in this animal model, a large part of them being reported as successful. However, it proved to be difficult to translate these therapeutic successes in the animal model into human trials. Also, a number of disease-modifying strategies were difficult to reproduce, even by the same group. On the other hand, the step from mice to men means a huge investment for the sponsors of clinical trials and the scientific community. Therefore, establishment of standard methods for drug testing in ALS models is mandatory. In this workshop, clinical and preclinical researchers established in the field of ALS/MND met in Holland in March 2006 in order to establish guidelines for the community for drug testing in mouse models.

Rabbit models for the study of human atherosclerosis: from pathophysiological mechanisms to translational medicine.

Science.gov (United States)

Fan, Jianglin; Kitajima, Shuji; Watanabe, Teruo; Xu, Jie; Zhang, Jifeng; Liu, Enqi; Chen, Y Eugene

2015-02-01

Laboratory animal models play an important role in the study of human diseases. Using appropriate animals is critical not only for basic research but also for the development of therapeutics and diagnostic tools. Rabbits are widely used for the study of human atherosclerosis. Because rabbits have a unique feature of lipoprotein metabolism (like humans but unlike rodents) and are sensitive to a cholesterol diet, rabbit models have not only provided many insights into the pathogenesis and development of human atherosclerosis but also made a great contribution to translational research. In fact, rabbit was the first animal model used for studying human atherosclerosis, more than a century ago. Currently, three types of rabbit model are commonly used for the study of human atherosclerosis and lipid metabolism: (1) cholesterol-fed rabbits, (2) Watanabe heritable hyperlipidemic rabbits, analogous to human familial hypercholesterolemia due to genetic deficiency of LDL receptors, and (3) genetically modified (transgenic and knock-out) rabbits. Despite their importance, compared with the mouse, the most widely used laboratory animal model nowadays, the use of rabbit models is still limited. In this review, we focus on the features of rabbit lipoprotein metabolism and pathology of atherosclerotic lesions that make it the optimal model for human atherosclerotic disease, especially for the translational medicine. For the sake of clarity, the review is not an attempt to be completely inclusive, but instead attempts to summarize substantial information concisely and provide a guideline for experiments using rabbits. Copyright © 2014 Elsevier Inc. All rights reserved.

Neuropathic pain in people with cancer (part 2): pharmacological and non-pharmacological management.

Science.gov (United States)

Taverner, Tarnia

2015-08-01

The aim of this paper is to provide an overview of the management of neuropathic pain associated with cancer and to provide helpful clinical advice for nurses working with patients who may have neuropathic pain. While cancer pain is a mixed-mechanism pain, this article will focus only on neuropathic pain management. The impact of neuropathic pain on patients' quality of life is great and while many patients recover from their cancer, a significant number continue to suffer from a neuropathic pain syndrome. Management of neuropathic pain is significantly different from management of nociceptive pain with respect to pharmacological and non-pharmacological strategies. Neuropathic pain is complex, and as such requires complex management using pharmacological as well as non-pharmacological approaches. Specific drugs for neuropathic pain may be effective for some patients, but not all; therefore, ongoing and comprehensive assessment and management are required. Furthermore, these patients may require trials of several drugs before they find one that works for them. It is important for nurses to understand neuropathic pain, its manifestation, impact on quality of life and management when nursing patients with neuropathic pain associated with cancer.

From gene networks to drugs: systems pharmacology approaches for AUD.

Science.gov (United States)

Ferguson, Laura B; Harris, R Adron; Mayfield, Roy Dayne

2018-06-01

The alcohol research field has amassed an impressive number of gene expression datasets spanning key brain areas for addiction, species (humans as well as multiple animal models), and stages in the addiction cycle (binge/intoxication, withdrawal/negative effect, and preoccupation/anticipation). These data have improved our understanding of the molecular adaptations that eventually lead to dysregulation of brain function and the chronic, relapsing disorder of addiction. Identification of new medications to treat alcohol use disorder (AUD) will likely benefit from the integration of genetic, genomic, and behavioral information included in these important datasets. Systems pharmacology considers drug effects as the outcome of the complex network of interactions a drug has rather than a single drug-molecule interaction. Computational strategies based on this principle that integrate gene expression signatures of pharmaceuticals and disease states have shown promise for identifying treatments that ameliorate disease symptoms (called in silico gene mapping or connectivity mapping). In this review, we suggest that gene expression profiling for in silico mapping is critical to improve drug repurposing and discovery for AUD and other psychiatric illnesses. We highlight studies that successfully apply gene mapping computational approaches to identify or repurpose pharmaceutical treatments for psychiatric illnesses. Furthermore, we address important challenges that must be overcome to maximize the potential of these strategies to translate to the clinic and improve healthcare outcomes.

Translational relevance of rodent models of hypothalamic-pituitary-adrenal function and stressors in adolescence

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Cheryl M. McCormick

2017-02-01

Full Text Available Elevations in glucocorticoids that result from environmental stressors can have programming effects on brain structure and function when the exposure occurs during sensitive periods that involve heightened neural development. In recent years, adolescence has gained increasing attention as another sensitive period of development, a period in which pubertal transitions may increase the vulnerability to stressors. There are similarities in physical and behavioural development between humans and rats, and rats have been used effectively as an animal model of adolescence and the unique plasticity of this period of ontogeny. This review focuses on benefits and challenges of rats as a model for translational research on hypothalamic-pituitary-adrenal (HPA function and stressors in adolescence, highlighting important parallels and contrasts between adolescent rats and humans, and we review the main stress procedures that are used in investigating HPA stress responses and their consequences in adolescence in rats. We conclude that a greater focus on timing of puberty as a factor in research in adolescent rats may increase the translational relevance of the findings.

Interprofessional education in pharmacology using high-fidelity simulation.

Science.gov (United States)

Meyer, Brittney A; Seefeldt, Teresa M; Ngorsuraches, Surachat; Hendrickx, Lori D; Lubeck, Paula M; Farver, Debra K; Heins, Jodi R

2017-11-01

This study examined the feasibility of an interprofessional high-fidelity pharmacology simulation and its impact on pharmacy and nursing students' perceptions of interprofessionalism and pharmacology knowledge. Pharmacy and nursing students participated in a pharmacology simulation using a high-fidelity patient simulator. Faculty-facilitated debriefing included discussion of the case and collaboration. To determine the impact of the activity on students' perceptions of interprofessionalism and their ability to apply pharmacology knowledge, surveys were administered to students before and after the simulation. Attitudes Toward Health Care Teams scale (ATHCT) scores improved from 4.55 to 4.72 on a scale of 1-6 (p = 0.005). Almost all (over 90%) of the students stated their pharmacology knowledge and their ability to apply that knowledge improved following the simulation. A simulation in pharmacology is feasible and favorably affected students' interprofessionalism and pharmacology knowledge perceptions. Pharmacology is a core science course required by multiple health professions in early program curricula, making it favorable for incorporation of interprofessional learning experiences. However, reports of high-fidelity interprofessional simulation in pharmacology courses are limited. This manuscript contributes to the literature in the field of interprofessional education by demonstrating that an interprofessional simulation in pharmacology is feasible and can favorably affect students' perceptions of interprofessionalism. This manuscript provides an example of a pharmacology interprofessional simulation that faculty in other programs can use to build similar educational activities. Copyright © 2017 Elsevier Inc. All rights reserved.

Applications of stable isotopes in clinical pharmacology

NARCIS (Netherlands)

Schellekens, Reinout C A; Stellaard, Frans; Woerdenbag, Herman J; Frijlink, Henderik W; Kosterink, Jos G W

2011-01-01

This review aims to present an overview of the application of stable isotope technology in clinical pharmacology. Three main categories of stable isotope technology can be distinguished in clinical pharmacology. Firstly, it is applied in the assessment of drug pharmacology to determine the

Pauses by Student and Professional Translators in Translation Process

Directory of Open Access Journals (Sweden)

Rusdi Noor Rosa

2018-01-01

Full Text Available Translation as a process of meaning making activity requires a cognitive process one of which is realized in a pause, a temporary stop or a break indicating doing other than typing activities in a certain period of translation process. Scholars agree that pauses are an indicator of cognitive process without which there will never be any translation practices. Despite such agreement, pauses are debatable as well, either in terms of their length or in terms of the activities managed by a translator while taking pauses. This study, in particular, aims at finding out how student translators and professional translators managed the pauses in a translation process. This was a descriptive research taking two student translators and two professional translators as the participants who were asked to translate a text from English into bahasa Indonesia. The source text (ST was a historical recount text entitled ‘Early History of Yellowstone National Park’ downloaded from http://www.nezperce.com/yelpark9.html composed of 230-word long from English into bahasa Indonesia. The data were collected using Translog protocols, think aloud protocols (TAPs and screen recording. Based on the data analysis, it was found that student translators took the longest pauses in the drafting phase spent to solve the problems related to finding out the right equivalent for the ST words or terms and to solve the difficulties encountered in encoding their ST understanding in the TL; meanwhile, professional translators took the longest pauses in the pos-drafting phase spent to ensure whether their TT had been natural and whether their TT had corresponded to the prevailing grammatical rules of the TL.

Pharmacological stress agents in nuclear cardiology

International Nuclear Information System (INIS)

Buscombe, J.R.

2004-01-01

Treadmill test combined with myocardial perfusion scintigraphy (MPS) is a commonly used technique in the assessment of coronary artery disease. However there are a group of patients who may not be able to undergo treadmill tests. Patients with underlying conditions like neuromuscular disease, musculoskeletal disorder, heart failure and end-stage renal disease (ESRD) on renal dialysis would find it difficult to perform exercise on a treadmill or bicycle ergometer. These conditions prevent them from performing adequate exercise. Such patients would benefit from pharmacological stress procedures combined with MPS. Nuclear medicine departments use various pharmacological agents while performing stress tests on cardiac patients. The most commonly used pharmacological agents for cardiac stress are coronary vasodilators and catecholamines. In addition to these agents, adjuvant use of nitrates and atropine is also a common practice in nuclear cardiology. This review addresses various physiological and pharmacological properties of the commonly used pharmacological stress agents in MPS and critically analyses their advantages and disadvantages, as well as their safety and efficacy. (author)

TRANSLATING ECONOMICS TEXTBOOKS: A CASE STUDY OF EPISTEMICIDE

Directory of Open Access Journals (Sweden)

KARNEDI

2015-01-01

Full Text Available As part of discourse in the social sciences, economics textbooks written in English in which knowledge has been transferred to other languages through translation have brought a certain impact on both the target language and the target culture. In terms of ideology, this article argues about the hegemonic status of the dominant language or culture that creates socalled epistemicide or the erosion of knowledge, partly due to translation strategies adopted by the translator. Investigation is done using the corpusbased approach, theories of translation strategies and the comparative model. The study reveals that the translator in the macro-level text adopts the ideology of foreignising strategy rather than domesticating strategy when translating an economics textbook from English into Indonesian. This is supported by the use of the number of the source language-orientated translation techniques leading to two translation methods (i.e. literal translation and faithful translation adopted in the micro-level text. This research strongly supports another relevant study pertaining to the globalisation of knowledge through translation and also the translation theories of equivalence (i.e. overt and covert translation. The research findings also have some pedagogical implications on teaching English for Specific Purposes in higher education.

Machine translation

Energy Technology Data Exchange (ETDEWEB)

Nagao, M

1982-04-01

Each language has its own structure. In translating one language into another one, language attributes and grammatical interpretation must be defined in an unambiguous form. In order to parse a sentence, it is necessary to recognize its structure. A so-called context-free grammar can help in this respect for machine translation and machine-aided translation. Problems to be solved in studying machine translation are taken up in the paper, which discusses subjects for semantics and for syntactic analysis and translation software. 14 references.

Narrative review of frameworks for translating research evidence into policy and practice

Directory of Open Access Journals (Sweden)

Ben Li

2017-02-01

Full Text Available Background: A significant challenge in research translation is that interested parties interpret and apply the associated terms and conceptual frameworks in different ways. The purpose of this review was to: a examine different research translation frameworks; b examine the similarities and differences between the frameworks; and c identify key strengths and weaknesses of the models when they are applied in practice. Methods: The review involved a keyword search of PubMed. The search string was (translational research OR knowledge translation OR evidence to practice AND (framework OR model OR theory AND (public health OR health promotion OR medicine. Included studies were published in English between January 1990 and December 2014, and described frameworks, models or theories associated with research translation. Results: The final review included 98 papers, and 41 different frameworks and models were identified. The most frequently applied knowledge translation framework in the literature was RE-AIM, followed by the knowledge translation continuum or ‘T’ models, the Knowledge to Action framework, the PARiHS framework, evidence based public health models, and the stages of research and evaluation model. Conclusion: The models identified in this review stem from different fields, including implementation science, basic and medical sciences, health services research and public health, and propose different but related pathways to closing the research–practice gap.

Animal Models for the Study of Female Sexual Dysfunction

Science.gov (United States)

Marson, Lesley; Giamberardino, Maria Adele; Costantini, Raffaele; Czakanski, Peter; Wesselmann, Ursula

2017-01-01

Introduction Significant progress has been made in elucidating the physiological and pharmacological mechanisms of female sexual function through preclinical animal research. The continued development of animal models is vital for the understanding and treatment of the many diverse disorders that occur in women. Aim To provide an updated review of the experimental models evaluating female sexual function that may be useful for clinical translation. Methods Review of English written, peer-reviewed literature, primarily from 2000 to 2012, that described studies on female sexual behavior related to motivation, arousal, physiological monitoring of genital function and urogenital pain. Main Outcomes Measures Analysis of supporting evidence for the suitability of the animal model to provide measurable indices related to desire, arousal, reward, orgasm, and pelvic pain. Results The development of female animal models has provided important insights in the peripheral and central processes regulating sexual function. Behavioral models of sexual desire, motivation, and reward are well developed. Central arousal and orgasmic responses are less well understood, compared with the physiological changes associated with genital arousal. Models of nociception are useful for replicating symptoms and identifying the neurobiological pathways involved. While in some cases translation to women correlates with the findings in animals, the requirement of circulating hormones for sexual receptivity in rodents and the multifactorial nature of women’s sexual function requires better designed studies and careful analysis. The current models have studied sexual dysfunction or pelvic pain in isolation; combining these aspects would help to elucidate interactions of the pathophysiology of pain and sexual dysfunction. Conclusions Basic research in animals has been vital for understanding the anatomy, neurobiology, and physiological mechanisms underlying sexual function and urogenital pain

An Overview of Models, Methods, and Reagents Developed for Translational Autoimmunity Research in the Common Marmoset (Callithrix jacchus)

NARCIS (Netherlands)

Jagessar, S. Anwar; Vierboom, Michel; Blezer, Erwin L. A.; Bauer, Jan; 't Hart, Bert A.; Kap, Yolanda S.

The common marmoset (Callithrix jacchus) is a small-bodied Neotropical primate and a useful preclinical animal model for translational research into autoimmune-mediated inflammatory diseases (AIMID), such as rheumatoid arthritis (RA) and multiple sclerosis (MS). The animal model for MS established

An overview of models, methods, and reagents developed for translational autoimmunity research in the common marmoset (Callithrix jacchus)

NARCIS (Netherlands)

S.A. Jagessar (Anwar); M.P.M. Vierboom (Michel); E. Blezer (Erwin); J. Bauer; B.A. 't Hart (Bert); Y.S. Kap (Yolanda)

2013-01-01

textabstractThe common marmoset (Callithrix jacchus) is a small-bodied Neotropical primate and a useful preclinical animal model for translational research into autoimmune-mediated inflammatory diseases (AIMID), such as rheumatoid arthritis (RA) and multiple sclerosis (MS). The animal model for MS

9.4 T small animal MRI using clinical components for direct translational studies.

Science.gov (United States)

Felder, Jörg; Celik, A Avdo; Choi, Chang-Hoon; Schwan, Stefan; Shah, N Jon

2017-12-28

Magnetic resonance is a major preclinical and clinical imaging modality ideally suited for longitudinal studies, e.g. in pharmacological developments. The lack of a proven platform that maintains an identical imaging protocol between preclinical and clinical platforms is solved with the construction of an animal scanner based on clinical hard- and software. A small animal magnet and gradient system were connected to a clinical MR system. Several hardware components were either modified or built in-house to achieve compatibility. The clinical software was modified to account for the different field-of-view of a preclinical MR system. The established scanner was evaluated using clinical QA protocols, and platform compatibility for translational research was verified against clinical scanners of different field strength. The constructed animal scanner operates with the majority of clinical imaging sequences. Translational research is greatly facilitated as protocols can be shared between preclinical and clinical platforms. Hence, when maintaining sequences parameters, maximum similarity between pulses played out on a human or an animal system is maintained. Coupling of a small animal magnet with a clinical MR system is a flexible, easy to use way to establish and advance translational imaging capability. It provides cost and labor efficient translational capability as no tedious sequence reprogramming between moieties is required and cross-platform compatibility of sequences facilitates multi-center studies.

Recent Advances in the Discovery and Development of Marine Natural Products with Cardiovascular Pharmacological Effects.

Science.gov (United States)

Zhou, Jie-Bin; Luo, Rong; Zheng, Ying-Lin; Pang, Ji-Yan

2018-01-01

Numerous studies have indicated that marine natural products are one of the most important sources of the lead compounds in drug discovery for their unique structures, various bioactivities and less side effects. In this review, the marine natural products with cardiovascular pharmacological effects reported after 2000 will be presented. Their structural types, relevant biological activities, origin of isolation and information of strain species will be discussed in detail. Finally, by describing our studies as an example, we also discuss the chances and challenges for translating marine-derived compounds into preclinical or clinical trials. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Eigenvectors determination of the ribosome dynamics model during mRNA translation using the Kleene Star algorithm

Science.gov (United States)

Ernawati; Carnia, E.; Supriatna, A. K.

2018-03-01

Eigenvalues and eigenvectors in max-plus algebra have the same important role as eigenvalues and eigenvectors in conventional algebra. In max-plus algebra, eigenvalues and eigenvectors are useful for knowing dynamics of the system such as in train system scheduling, scheduling production systems and scheduling learning activities in moving classes. In the translation of proteins in which the ribosome move uni-directionally along the mRNA strand to recruit the amino acids that make up the protein, eigenvalues and eigenvectors are used to calculate protein production rates and density of ribosomes on the mRNA. Based on this, it is important to examine the eigenvalues and eigenvectors in the process of protein translation. In this paper an eigenvector formula is given for a ribosome dynamics during mRNA translation by using the Kleene star algorithm in which the resulting eigenvector formula is simpler and easier to apply to the system than that introduced elsewhere. This paper also discusses the properties of the matrix {B}λ \\otimes n of model. Among the important properties, it always has the same elements in the first column for n = 1, 2,… if the eigenvalue is the time of initiation, λ = τin , and the column is the eigenvector of the model corresponding to λ.

Maintaining Sentiment Polarity in Translation of User-Generated Content

Directory of Open Access Journals (Sweden)

Lohar Pintu

2017-06-01

Full Text Available The advent of social media has shaken the very foundations of how we share information, with Twitter, Facebook, and Linkedin among many well-known social networking platforms that facilitate information generation and distribution. However, the maximum 140-character restriction in Twitter encourages users to (sometimes deliberately write somewhat informally in most cases. As a result, machine translation (MT of user-generated content (UGC becomes much more difficult for such noisy texts. In addition to translation quality being affected, this phenomenon may also negatively impact sentiment preservation in the translation process. That is, a sentence with positive sentiment in the source language may be translated into a sentence with negative or neutral sentiment in the target language. In this paper, we analyse both sentiment preservation and MT quality per se in the context of UGC, focusing especially on whether sentiment classification helps improve sentiment preservation in MT of UGC. We build four different experimental setups for tweet translation (i using a single MT model trained on the whole Twitter parallel corpus, (ii using multiple MT models based on sentiment classification, (iii using MT models including additional out-of-domain data, and (iv adding MT models based on the phrase-table fill-up method to accompany the sentiment translation models with an aim of improving MT quality and at the same time maintaining sentiment polarity preservation. Our empirical evaluation shows that despite a slight deterioration in MT quality, our system significantly outperforms the Baseline MT system (without using sentiment classification in terms of sentiment preservation. We also demonstrate that using an MT engine that conveys a sentiment different from that of the UGC can even worsen both the translation quality and sentiment preservation.

Style and ideology in translation

CERN Document Server

Munday, Jeremy

2013-01-01

Adopting an interdisciplinary approach, this book investigates the style, or 'voice,' of English language translations of twentieth-century Latin American writing, including fiction, political speeches, and film. Existing models of stylistic analysis, supported at times by computer-assisted analysis, are developed to examine a range of works and writers, selected for their literary, cultural, and ideological importance. The style of the different translators is subjected to a close linguistic investigation within their cultural and ideological framework.

Pharmacological approach to acute pancreatitis

DEFF Research Database (Denmark)

Bang, U.C.; Semb, S.; Nøjgaard, Camilla

2008-01-01

The aim of the present review is to summarize the current knowledge regarding pharmacological prevention and treatment of acute pancreatitis (AP) based on experimental animal models and clinical trials. Somatostatin (SS) and octreotide inhibit the exocrine production of pancreatic enzymes and may...... be useful as prophylaxis against post endoscopic retrograde cholangiopancreatography pancreatitis (PEP). The protease inhibitor gabexate mesilate (GM) is used routinely as treatment to AP in some countries, but randomized clinical trials and a meta-analysis do not support this practice. Nitroglycerin (NGL...

Cardiovascular outcomes after pharmacologic stress myocardial perfusion imaging.

Science.gov (United States)

Lee, Douglas S; Husain, Mansoor; Wang, Xuesong; Austin, Peter C; Iwanochko, Robert M

2016-04-01

While pharmacologic stress single photon emission computed tomography myocardial perfusion imaging (SPECT-MPI) is used for noninvasive evaluation of patients who are unable to perform treadmill exercise, its impact on net reclassification improvement (NRI) of prognosis is unknown. We evaluated the prognostic value of pharmacologic stress MPI for prediction of cardiovascular death or non-fatal myocardial infarction (MI) within 1 year at a single-center, university-based laboratory. We examined continuous and categorical NRI of pharmacologic SPECT-MPI for prediction of outcomes beyond clinical factors alone. Six thousand two hundred forty patients (median age 66 years [IQR 56-74], 3466 men) were studied and followed for 5963 person-years. SPECT-MPI variables associated with increased risk of cardiovascular death or non-fatal MI included summed stress score, stress ST-shift, and post-stress resting left ventricular ejection fraction ≤50%. Compared to a clinical model which included age, sex, cardiovascular disease, risk factors, and medications, model χ(2) (210.5 vs. 281.9, P statistic (0.74 vs. 0.78, P stress score, stress ST-shift and stress resting left ventricular ejection fraction). SPECT-MPI predictors increased continuous NRI by 49.4% (P 3% annualized risk of cardiovascular death or non-fatal MI, yielded a 15.0% improvement in NRI (95% CI 7.6%-27.6%, P stress MPI substantially improved net reclassification of cardiovascular death or MI risk beyond that afforded by clinical factors. Copyright © 2016 Elsevier Inc. All rights reserved.

Analysis of MultiWord Expression Translation Errors in Statistical Machine Translation

DEFF Research Database (Denmark)

Klyueva, Natalia; Liyanapathirana, Jeevanthi

2015-01-01

In this paper, we analyse the usage of multiword expressions (MWE) in Statistical Machine Translation (SMT). We exploit the Moses SMT toolkit to train models for French-English and Czech-Russian language pairs. For each language pair, two models were built: a baseline model without additional MWE...... data and the model enhanced with information on MWE. For the French-English pair, we tried three methods of introducing the MWE data. For Czech-Russian pair, we used just one method – adding automatically extracted data as a parallel corpus....

Pills or push-ups? Effectiveness and public perception of pharmacological and non-pharmacological cognitive enhancement

Directory of Open Access Journals (Sweden)

Lucius eCaviola

2015-12-01

Full Text Available We review work on the effectiveness of different forms of cognitive enhancement, both pharmacological and non-pharmacological. We consider caffeine, methylphenidate, and modafinil for pharmacological cognitive enhancement (PCE and computer training, physical exercise, and sleep for non-pharmacological cognitive enhancement (NPCE. We find that all of the techniques described can produce significant beneficial effects on cognitive performance. However, effect sizes are moderate, and consistently dependent on individual and situational factors as well as the cognitive domain in question. Although meta-analyses allowing a quantitative comparison of effectiveness across techniques are lacking to date, we can conclude that PCE is not more effective than NPCE. We discuss the physiological reasons for this limited effectiveness.We then propose that even though their actual effectiveness seems similar, in the general public PCE is perceived as fundamentally different from NPCE, in terms of effectiveness, but also in terms of acceptability. We illustrate the potential consequences such a misperception of PCE can have.

Understanding the organization of cognitive approaches to translation

DEFF Research Database (Denmark)

Serban, Maria

2017-01-01

Cognitive approaches to translation studies are driven by three interrelated aims: to understand the structure and organization of the capacities of cognitive agents involved in processes of translation, to build better theories and models of translation, and to develop more efficient methods...... theory, it is more descriptively adequate and more fruitful to understand it as a family of projects based on multiple theories that are relevant for studying different aspects of the translation process. This perspective allows us to extract the erotetic structure of these programs which are organized...

Translational profiling in childhood acute lymphoblastic leukemia: no evidence for glucocorticoid regulation of mRNA translation.

Science.gov (United States)

Aneichyk, Tatsiana; Bindreither, Daniel; Mantinger, Christine; Grazio, Daniela; Goetsch, Katrin; Kofler, Reinhard; Rainer, Johannes

2013-12-01

Glucocorticoids (GCs) are natural stress induced steroid hormones causing cell cycle arrest and cell death in lymphoid tissues. Therefore they are the central component in the treatment of lymphoid malignancies, in particular childhood acute lymphoblastic leukemia (chALL). GCs act mainly via regulating gene transcription, which has been intensively studied by us and others. GC control of mRNA translation has also been reported but has never been assessed systematically. In this study we investigate the effect of GCs on mRNA translation on a genome-wide scale. Childhood T- (CCRF-CEM) and precursor B-ALL (NALM6) cells were exposed to GCs and subjected to "translational profiling", a technique combining sucrose-gradient fractionation followed by Affymetrix Exon microarray analysis of mRNA from different fractions, to assess the translational efficiency of the expressed genes. Analysis of GC regulation in ribosome-bound fractions versus transcriptional regulation revealed no significant differences, i.e., GC did not entail a significant shift between ribosomal bound and unbound mRNAs. In the present study we analyzed for the first time possible effects of GC on the translational efficiency of expressed genes in two chALL model systems employing whole genome polysome profiling. Our results did not reveal significant differences in translational efficiency of expressed genes thereby arguing against a potential widespread regulatory effect of GCs on translation at least in the investigated in vitro systems.

Chinese translation norms for 1,429 English words.

Science.gov (United States)

Wen, Yun; van Heuven, Walter J B

2017-06-01

We present Chinese translation norms for 1,429 English words. Chinese-English bilinguals (N = 28) were asked to provide the first Chinese translation that came to mind for 1,429 English words. The results revealed that 71 % of the English words received more than one correct translation indicating the large amount of translation ambiguity when translating from English to Chinese. The relationship between translation ambiguity and word frequency, concreteness and language proficiency was investigated. Although the significant correlations were not strong, results revealed that English word frequency was positively correlated with the number of alternative translations, whereas English word concreteness was negatively correlated with the number of translations. Importantly, regression analyses showed that the number of Chinese translations was predicted by word frequency and concreteness. Furthermore, an interaction between these predictors revealed that the number of translations was more affected by word frequency for more concrete words than for less concrete words. In addition, mixed-effects modelling showed that word frequency, concreteness and English language proficiency were all significant predictors of whether or not a dominant translation was provided. Finally, correlations between the word frequencies of English words and their Chinese dominant translations were higher for translation-unambiguous pairs than for translation-ambiguous pairs. The translation norms are made available in a database together with lexical information about the words, which will be a useful resource for researchers investigating Chinese-English bilingual language processing.

An Overall Perspective of Machine Translation with its Shortcomings

Directory of Open Access Journals (Sweden)

Alireza Akbari

2014-01-01

Full Text Available The petition for language translation has strikingly augmented recently due to cross-cultural communication and exchange of information. In order to communicate well, text should be translated correctly and completely in each field such as legal documents, technical texts, scientific texts, publicity leaflets, and instructional materials. In this connection, Machine translation is of great importance in translation. The term “Machine Translation” was first proposed by George Artsrouni and Smirnov Troyanski (1933 to design a storage design on paper tape. This paper sought to investigate an overall perspective of Machine Translation models and its metrics in detail. Finally, it scrutinized the ins and outs shortcomings of Machine Translation.

Knowledge translation of research findings

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Grimshaw Jeremy M

2012-05-01

Full Text Available Abstract Background One of the most consistent findings from clinical and health services research is the failure to translate research into practice and policy. As a result of these evidence-practice and policy gaps, patients fail to benefit optimally from advances in healthcare and are exposed to unnecessary risks of iatrogenic harms, and healthcare systems are exposed to unnecessary expenditure resulting in significant opportunity costs. Over the last decade, there has been increasing international policy and research attention on how to reduce the evidence-practice and policy gap. In this paper, we summarise the current concepts and evidence to guide knowledge translation activities, defined as T2 research (the translation of new clinical knowledge into improved health. We structure the article around five key questions: what should be transferred; to whom should research knowledge be transferred; by whom should research knowledge be transferred; how should research knowledge be transferred; and, with what effect should research knowledge be transferred? Discussion We suggest that the basic unit of knowledge translation should usually be up-to-date systematic reviews or other syntheses of research findings. Knowledge translators need to identify the key messages for different target audiences and to fashion these in language and knowledge translation products that are easily assimilated by different audiences. The relative importance of knowledge translation to different target audiences will vary by the type of research and appropriate endpoints of knowledge translation may vary across different stakeholder groups. There are a large number of planned knowledge translation models, derived from different disciplinary, contextual (i.e., setting, and target audience viewpoints. Most of these suggest that planned knowledge translation for healthcare professionals and consumers is more likely to be successful if the choice of knowledge

Knowledge translation of research findings.

Science.gov (United States)

Grimshaw, Jeremy M; Eccles, Martin P; Lavis, John N; Hill, Sophie J; Squires, Janet E

2012-05-31

One of the most consistent findings from clinical and health services research is the failure to translate research into practice and policy. As a result of these evidence-practice and policy gaps, patients fail to benefit optimally from advances in healthcare and are exposed to unnecessary risks of iatrogenic harms, and healthcare systems are exposed to unnecessary expenditure resulting in significant opportunity costs. Over the last decade, there has been increasing international policy and research attention on how to reduce the evidence-practice and policy gap. In this paper, we summarise the current concepts and evidence to guide knowledge translation activities, defined as T2 research (the translation of new clinical knowledge into improved health). We structure the article around five key questions: what should be transferred; to whom should research knowledge be transferred; by whom should research knowledge be transferred; how should research knowledge be transferred; and, with what effect should research knowledge be transferred? We suggest that the basic unit of knowledge translation should usually be up-to-date systematic reviews or other syntheses of research findings. Knowledge translators need to identify the key messages for different target audiences and to fashion these in language and knowledge translation products that are easily assimilated by different audiences. The relative importance of knowledge translation to different target audiences will vary by the type of research and appropriate endpoints of knowledge translation may vary across different stakeholder groups. There are a large number of planned knowledge translation models, derived from different disciplinary, contextual (i.e., setting), and target audience viewpoints. Most of these suggest that planned knowledge translation for healthcare professionals and consumers is more likely to be successful if the choice of knowledge translation strategy is informed by an assessment of the

Translating Inclusion

DEFF Research Database (Denmark)

Fallov, Mia Arp; Birk, Rasmus

2018-01-01

The purpose of this paper is to explore how practices of translation shape particular paths of inclusion for people living in marginalized residential areas in Denmark. Inclusion, we argue, is not an end-state, but rather something which must be constantly performed. Active citizenship, today......, is not merely a question of participation, but of learning to become active in all spheres of life. The paper draws on empirical examples from a multi-sited field work in 6 different sites of local community work in Denmark, to demonstrate how different dimensions of translation are involved in shaping active...... citizenship. We propose the following different dimensions of translation: translating authority, translating language, translating social problems. The paper takes its theoretical point of departure from assemblage urbanism, arguing that cities are heterogeneous assemblages of socio-material interactions...

PATSTAGS - PATRAN-STAGSC-1 TRANSLATOR

Science.gov (United States)

Otte, N. E.

1994-01-01

PATSTAGS translates PATRAN finite model data into STAGS (Structural Analysis of General Shells) input records to be used for engineering analysis. The program reads data from a PATRAN neutral file and writes STAGS input records into a STAGS input file and a UPRESS data file. It is able to support translations of nodal constraints, nodal, element, force and pressure data. PATSTAGS uses three files: the PATRAN neutral file to be translated, a STAGS input file and a STAGS pressure data file. The user provides the names for the neutral file and the desired names of the STAGS files to be created. The pressure data file contains the element live pressure data used in the STAGS subroutine UPRESS. PATSTAGS is written in FORTRAN 77 for DEC VAX series computers running VMS. The main memory requirement for execution is approximately 790K of virtual memory. Output blocks can be modified to output the data in any format desired, allowing the program to be used to translate model data to analysis codes other than STAGSC-1 (HQN-10967). This program is available in DEC VAX BACKUP format on a 9-track magnetic tape or TK50 tape cartridge. Documentation is included in the price of the program. PATSTAGS was developed in 1990. DEC, VAX, TK50 and VMS are trademarks of Digital Equipment Corporation.

CADAT network translator

Science.gov (United States)

Pitts, E. R.

1981-01-01

Program converts cell-net data into logic-gate models for use in test and simulation programs. Input consists of either Place, Route, and Fold (PRF) or Place-and-Route-in-Two-Dimensions (PR2D) layout data deck. Output consists of either Test Pattern Generator (TPG) or Logic-Simulation (LOGSIM) logic circuitry data deck. Designer needs to build only logic-gate-model circuit description since program acts as translator. Language is FORTRAN IV.

DW4TR: A Data Warehouse for Translational Research.

Science.gov (United States)

Hu, Hai; Correll, Mick; Kvecher, Leonid; Osmond, Michelle; Clark, Jim; Bekhash, Anthony; Schwab, Gwendolyn; Gao, De; Gao, Jun; Kubatin, Vladimir; Shriver, Craig D; Hooke, Jeffrey A; Maxwell, Larry G; Kovatich, Albert J; Sheldon, Jonathan G; Liebman, Michael N; Mural, Richard J

2011-12-01

The linkage between the clinical and laboratory research domains is a key issue in translational research. Integration of clinicopathologic data alone is a major task given the number of data elements involved. For a translational research environment, it is critical to make these data usable at the point-of-need. Individual systems have been developed to meet the needs of particular projects though the need for a generalizable system has been recognized. Increased use of Electronic Medical Record data in translational research will demand generalizing the system for integrating clinical data to support the study of a broad range of human diseases. To ultimately satisfy these needs, we have developed a system to support multiple translational research projects. This system, the Data Warehouse for Translational Research (DW4TR), is based on a light-weight, patient-centric modularly-structured clinical data model and a specimen-centric molecular data model. The temporal relationships of the data are also part of the model. The data are accessed through an interface composed of an Aggregated Biomedical-Information Browser (ABB) and an Individual Subject Information Viewer (ISIV) which target general users. The system was developed to support a breast cancer translational research program and has been extended to support a gynecological disease program. Further extensions of the DW4TR are underway. We believe that the DW4TR will play an important role in translational research across multiple disease types. Copyright © 2011 Elsevier Inc. All rights reserved.

Targeted pharmacological treatment of autism spectrum disorders: fragile X and Rett syndromes

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Hansen eWang

2015-02-01

Full Text Available Autism spectrum disorders (ASDs are genetically and clinically heterogeneous and lack effective medications to treat their core symptoms. Studies of syndromic ASDs caused by single gene mutations have provided insights into the pathophysiology of autism. Fragile X and Rett syndromes belong to the syndromic ASDs in which preclinical studies have identified rational targets for drug therapies focused on correcting underlying neural dysfunction. These preclinical discoveries are increasingly translating into exciting human clinical trials. Since there are significant molecular and neurobiological overlaps among ASDs, targeted treatments developed for fragile X and Rett syndromes may be helpful for autism of different etiologies. Here, we review the targeted pharmacological treatment of fragile X and Rett syndromes and discuss related issues in both preclinical studies and clinical trials of potential therapies for the diseases.

Targeted pharmacological treatment of autism spectrum disorders: fragile X and Rett syndromes

Science.gov (United States)

Wang, Hansen; Pati, Sandipan; Pozzo-Miller, Lucas; Doering, Laurie C.

2015-01-01

Autism spectrum disorders (ASDs) are genetically and clinically heterogeneous and lack effective medications to treat their core symptoms. Studies of syndromic ASDs caused by single gene mutations have provided insights into the pathophysiology of autism. Fragile X and Rett syndromes belong to the syndromic ASDs in which preclinical studies have identified rational targets for drug therapies focused on correcting underlying neural dysfunction. These preclinical discoveries are increasingly translating into exciting human clinical trials. Since there are significant molecular and neurobiological overlaps among ASDs, targeted treatments developed for fragile X and Rett syndromes may be helpful for autism of different etiologies. Here, we review the targeted pharmacological treatment of fragile X and Rett syndromes and discuss related issues in both preclinical studies and clinical trials of potential therapies for the diseases. PMID:25767435

Identity approach in translation : sociocultural implications

Directory of Open Access Journals (Sweden)

Alicja Żuchelkowska

2012-01-01

Full Text Available The objective of this text consists in presenting how it is necessary for contemporary translators and interpreters (both literary and specialised to acquire and develop the ability to recognize elements of identity discourse in translated texts. Nowadays, the need for inter-cultural exchange is inevitably connected with the necessity of establishing harmonious co-existence for numerous cultures and identities. Therefore, it is crucial to educate translators in a way that enables them to pay special attention to identity and cultural perturbations present in translated texts (culture and language hybridisation, multiple identity, cultural dislocation, presence in linguistic and political discourse of minority cultures, regardless of their genre or form. Such a strong emphasis on identity problems in the translation is especially relevant in the European context, where the attention of researchers and politicians directed at identity problems stemming from ethnical and cultural issues sets the framework for a new cultural paradigm that determines the future development of the Eu. Becoming acquainted with this paradigm which emphasises fl uency, identity unmarkedness and the new model of European collectivity is indispensable for a translator aspiring to become a true cultural mediator.

Clinical pharmacology quality assurance program: models for longitudinal analysis of antiretroviral proficiency testing for international laboratories.

Science.gov (United States)

DiFrancesco, Robin; Rosenkranz, Susan L; Taylor, Charlene R; Pande, Poonam G; Siminski, Suzanne M; Jenny, Richard W; Morse, Gene D

2013-10-01

Among National Institutes of Health HIV Research Networks conducting multicenter trials, samples from protocols that span several years are analyzed at multiple clinical pharmacology laboratories (CPLs) for multiple antiretrovirals. Drug assay data are, in turn, entered into study-specific data sets that are used for pharmacokinetic analyses, merged to conduct cross-protocol pharmacokinetic analysis, and integrated with pharmacogenomics research to investigate pharmacokinetic-pharmacogenetic associations. The CPLs participate in a semiannual proficiency testing (PT) program implemented by the Clinical Pharmacology Quality Assurance program. Using results from multiple PT rounds, longitudinal analyses of recovery are reflective of accuracy and precision within/across laboratories. The objectives of this longitudinal analysis of PT across multiple CPLs were to develop and test statistical models that longitudinally: (1) assess the precision and accuracy of concentrations reported by individual CPLs and (2) determine factors associated with round-specific and long-term assay accuracy, precision, and bias using a new regression model. A measure of absolute recovery is explored as a simultaneous measure of accuracy and precision. Overall, the analysis outcomes assured 97% accuracy (±20% of the final target concentration of all (21) drug concentration results reported for clinical trial samples by multiple CPLs). Using the Clinical Laboratory Improvement Act acceptance of meeting criteria for ≥2/3 consecutive rounds, all 10 laboratories that participated in 3 or more rounds per analyte maintained Clinical Laboratory Improvement Act proficiency. Significant associations were present between magnitude of error and CPL (Kruskal-Wallis P Kruskal-Wallis P < 0.001).

Cross-Language Translation Priming Asymmetry with Chinese-English Bilinguals: A Test of the Sense Model

Science.gov (United States)

Chen, Baoguo; Zhou, Huixia; Gao, Yiwen; Dunlap, Susan

2014-01-01

The present study aimed to test the Sense Model of cross-linguistic masked translation priming asymmetry, proposed by Finkbeiner et al. ("J Mem Lang" 51:1-22, 2004), by manipulating the number of senses that bilingual participants associated with words from both languages. Three lexical decision experiments were conducted with…

Unlocking the potential of translation for FLT

Directory of Open Access Journals (Sweden)

Alenka Kocbek

2014-12-01

Full Text Available The paper proposes unlocking the potential of translation for foreign language teaching (FLT by seeking to create synergies with the related discipline of translation science (TS. This aim is in keeping with the guidelines for language teaching provided in the Common European Framework of Languages, which introduced a model of communicative competences including communicative language competences as those which enable a person to act by drawing on specific linguistic means. First, an overview of the changing status of translation in FLT is presented – from its being considered a fundamental teaching method and basic skill in the Grammar-Translation Method, to its being all but outlawed in more recent communicative and task-based approaches, to its final rehabilitation in recent decades. It is then shown that, in the development of FLT, the parallel evolution of TS somehow failed to be acknowledged and, consequently, the opportunity to create valuable synergies between the two disciplines was missed. Following the stance of authors who have advocated the use of translation in FLT, it is argued that translation can effectively supplement the development of the four traditional language skills and, moreover, that some of the insights developed by TS can effectively be integrated into FLT as strategies aimed at enhancing leaners’ cross-cultural communicative competences. To this purpose, selected insights from TS (e.g. the functional approach and the skopos theory, the cultureme model, the theory of memes are discussed and their potential for creating synergies with FLT are explored. Finally, the paper discusses the omnipresence of different forms of translation and interpreting in contemporary societies and shows that this naturally and logically calls for a systematic inclusion of translation in FLT.

Adiabatic translation factors in slow ion-atom collisions

International Nuclear Information System (INIS)

Vaaben, J.; Taulbjerg, K.

1981-01-01

The general properties of translation factors in slow atomic collisions are discussed. It is emphasised that an acceptable form of translation factors must be conceptually consistent with the basic underlying assumption of the molecular model; i.e. translation factors must relax adiabatically at intermediate and small internuclear separations. A simple physical argument is applied to derive a general parameter-free expression for the translation factor pertinent to an electron in a two-centre Coulomb field. Within the present approach the adiabatic translation factor is considered to be a property of the two-centre field independently of the molecular state under consideration. The generalisation to many-electron systems is therefore readily made. (author)

CloudLM: a Cloud-based Language Model for Machine Translation

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Ferrández-Tordera Jorge

2016-04-01

Full Text Available Language models (LMs are an essential element in statistical approaches to natural language processing for tasks such as speech recognition and machine translation (MT. The advent of big data leads to the availability of massive amounts of data to build LMs, and in fact, for the most prominent languages, using current techniques and hardware, it is not feasible to train LMs with all the data available nowadays. At the same time, it has been shown that the more data is used for a LM the better the performance, e.g. for MT, without any indication yet of reaching a plateau. This paper presents CloudLM, an open-source cloud-based LM intended for MT, which allows to query distributed LMs. CloudLM relies on Apache Solr and provides the functionality of state-of-the-art language modelling (it builds upon KenLM, while allowing to query massive LMs (as the use of local memory is drastically reduced, at the expense of slower decoding speed.

Translation and Culture:Translation as a Cross-cultural Mediation

Institute of Scientific and Technical Information of China (English)

叶谋锦

2013-01-01

Translation is a complex activity which involves language competence as well as proficiency in multiculturalism. From the perspective of multiculturalism, translation resembles recreation of source text by grasping essential meanings to produce a sub-tle target text which can be clearly perceived by target readers. Ignoring cultural issues can present serious mistranslations in the field of advertising translation. This paper aims to explore the significance of connotation confined by the framework of culture and point out that verbal translation is a dangerous inclination by illustrating three business examples. This paper argues that cross-cultural mediation plays an important role in translation.

Pharmacology Students' Perceptions of Creating Multimodal Digital Explanations

Science.gov (United States)

Nielsen, W.; Hoban G.; Hyland, C. J. T.

2017-01-01

Students can now digitally construct their own representations of scientific concepts using a variety of modes including writing, diagrams, 2-D and 3-D models, images or speech, all of which communicate meaning. In this study, final-year chemistry students studying a pharmacology subject created a ''blended media'' digital product as an assignment…

α-Mangostin from Garcinia mangostana Linn: An updated review of its pharmacological properties

Directory of Open Access Journals (Sweden)

Mohamed Yousif Ibrahim

2016-05-01

Full Text Available Over the past decades, various studies have highlighted the pure natural compound, α-mangostin as their main topic. The compound’s pre-clinical and pharmacological properties have been recognized and defined in these studies. α-Mangostin shows strong pharmacological effects in in vitro and in vivo model systems by targeting a number of vital cellular factors through various mechanisms of action. Despite its important molecular versatility, the α-mangostin still has limited clinical application. In order to optimize the conditions of this compound as a chemotherapeutic and chemopreventive agent, for instance in diseases such as cancer, obesity, diabetes as well as inflammatory disorders, the recent tendency is to limit the range of its pharmacological properties. The present work reviews recent studies on the central and potential pharmacological principles as well as the preclinical applications of the α-mangostin.

Human resources management in a translation process

OpenAIRE

Rogelj, Jure

2015-01-01

The purpose of the web application development is the modernization of the current data acquisition and management model for new and existing translators in the company Iolar d.o.o. Previously data on translators who signed up to work in the company were entered multiple times as they were entered through several entry points. The acquired data were then manually entered into an MS Excel sheet and the Projetex program. We analyzed the current data acquisition and management model as well ...

Human resources management in a translation process

OpenAIRE

Rogelj, Jure

2014-01-01

The purpose of the web application development is the modernization of the current data acquisition and management model for new and existing translators in the company Iolar d.o.o. Previously data on translators who signed up to work in the company were entered multiple times as they were entered through several entry points. The acquired data were then manually entered into an MS Excel sheet and the Projetex program. We analyzed the current data acquisition and management model as well ...

Integrating source-language context into phrase-based statistical machine translation

NARCIS (Netherlands)

Haque, R.; Kumar Naskar, S.; Bosch, A.P.J. van den; Way, A.

2011-01-01

The translation features typically used in Phrase-Based Statistical Machine Translation (PB-SMT) model dependencies between the source and target phrases, but not among the phrases in the source language themselves. A swathe of research has demonstrated that integrating source context modelling

Efficiency of Iranian Translation Syllabus at BA Level; Deficiency: A New Comprehensive Model

Science.gov (United States)

Sohrabi, Sarah; Rahimi, Ramin; Arjmandi, Masoume

2015-01-01

This study aims at investigating the practicality of the current curriculum for translation studies at national level (Iranian curriculum). It is going to have a comprehensive idea of translation students and teachers (university lecturers) over the current translation syllabus at BA level in Iran. A researcher-made CEQ questionnaire (Curriculum…

Anticancer activities against cholangiocarcinoma, toxicity and pharmacological activities of Thai medicinal plants in animal models.

Science.gov (United States)

Plengsuriyakarn, Tullayakorn; Viyanant, Vithoon; Eursitthichai, Veerachai; Picha, Porntipa; Kupradinun, Piengchai; Itharat, Arunporn; Na-Bangchang, Kesara

2012-03-27

Chemotherapy of cholangiocarcinoma (CCA), a devastating cancer with increasing worldwide incidence and mortality rates, is largely ineffective. The discovery and development of effective chemotherapeutics is urgently needed. The study aimed at evaluating anticancer activities, toxicity, and pharmacological activities of the curcumin compound (CUR), the crude ethanolic extracts of rhizomes of Zingiber officinale Roscoe (Ginger: ZO) and Atractylodes lancea thung. DC (Khod-Kha-Mao: AL), fruits of Piper chaba Hunt. (De-Plee: PC), and Pra-Sa-Prao-Yhai formulation (a mixture of parts of 18 Thai medicinal plants: PPF) were investigated in animal models. Anti-cholangiocarcinoma (anti-CCA) was assessed using CCA-xenograft nude mouse model. The antihypertensive, analgesic, anti-inflammatory, antipyretic, and anti-ulcer activities and effects on motor coordination were investigated using Rota-rod test, CODA tail-cuff system, writhing and hot plate tests, carrageenan-induced paw edema test, brewer's yeast test, and alcohol-induced gastric ulcer test, respectively. Acute and subacute toxicity tests were performed according to the OECD guideline for testing of chemicals with modification. Promising anticancer activity against CCA in nude mouse xenograft model was shown for the ethanolic extract of AL at all oral dose levels (1000, 3000, and 5000 mg/kg body weight) as well as the extracts of ZO, PPF, and CUR compound at the highest dose level (5000, 4000, and 5000 mg/kg body weight, respectively). PC produced no significant anti-CCA activity. Results from acute and subacute toxicity tests both in mice and rats indicate safety profiles of all the test materials in a broad range of dose levels. No significant toxicity except stomach irritation and general CNS depressant signs were observed. Investigation of pharmacological activities of the test materials revealed promising anti-inflammatory (ZO, PPF, and AL), analgesic (CUR and PPF), antipyretic (CUR and AL), antihypertensive (ZO

Contribution of Post-translational Phosphorylation to Sarcomere-linked Cardiomyopathy Phenotypes

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Margaret V Westfall

2016-09-01

Full Text Available Secondary shifts develop in post-translational phosphorylation of sarcomeric proteins in multi¬ple animal models of inherited cardiomyopathy. These signaling alterations together with the primary mutation are predicted to contribute to the overall cardiac phenotype. As a result, identification and integration of post-translational myofilament signaling responses are identified as priorities for gaining insights into sarcomeric cardiomyopathies. However, significant questions remain about the nature and contribution of post-translational phosphorylation to structural remodeling and cardiac dysfunction in animal models and human patients. This perspective essay discusses specific goals for filling critical gaps about post-translational signaling in response to these inherited mutations, especially within sarcomeric proteins. The discussion focuses primarily on pre-clinical analysis of animal models and defines challenges and future directions in this field.

The Effect of Translators' Emotional Intelligence on Their Translation Quality

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Varzande, Mohsen; Jadidi, Esmaeil

2015-01-01

Translators differ from each other in many ways in terms of their knowledge, professional and psychological conditions that may directly influence their translation. The present study aimed at investigating the impact of translators' Emotional Intelligence on their translation quality. Following a "causal-comparative study," a sample of…

Expanding the knowledge translation metaphor.

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Engebretsen, Eivind; Sandset, Tony Joakim; Ødemark, John

2017-03-13

Knowledge translation (KT) is a buzzword in modern medical science. However, there has been little theoretical reflection on translation as a process of meaning production in KT. In this paper, we argue that KT will benefit from the incorporation of a more theoretical notion of translation as an entangled material, textual and cultural process. We discuss and challenge fundamental assumptions in KT, drawing on theories of translation from the human sciences. We show that the current construal of KT as separate from and secondary to the original scientific message is close to the now deeply compromised literary view of translation as the simple act of copying the original. Inspired by recent theories of translation, we claim that KT can be more adequately understood in terms of a 'double supplement' - on the one hand, KT offers new approaches to the communication of scientific knowledge to different groups in the healthcare system with the aim of supplementing a lack of knowledge among clinicians (and patients). On the other, it demonstrates that a textual and cultural supplement, namely a concern with target audiences (clinicians and patients), is inevitable in the creation of an 'autonomous' science. Hence, the division between science and its translation is unproductive and impossible to maintain. We discuss some possible implications of our suggested shift in concept by drawing on pharmaceutical interventions for the prevention of HIV as a case. We argue that such interventions are based on a supplementary and paradoxical relation to the target audiences, both presupposing and denying their existence. More sophisticated theories of translation can lay the foundation for an expanded model of KT that incorporates a more adequate and reflective description of the interdependency of scientific, cultural, textual and material practices.

HEPATOKIN1 is a biochemistry-based model of liver metabolism for applications in medicine and pharmacology.

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Berndt, Nikolaus; Bulik, Sascha; Wallach, Iwona; Wünsch, Tilo; König, Matthias; Stockmann, Martin; Meierhofer, David; Holzhütter, Hermann-Georg

2018-06-19

The epidemic increase of non-alcoholic fatty liver diseases (NAFLD) requires a deeper understanding of the regulatory circuits controlling the response of liver metabolism to nutritional challenges, medical drugs, and genetic enzyme variants. As in vivo studies of human liver metabolism are encumbered with serious ethical and technical issues, we developed a comprehensive biochemistry-based kinetic model of the central liver metabolism including the regulation of enzyme activities by their reactants, allosteric effectors, and hormone-dependent phosphorylation. The utility of the model for basic research and applications in medicine and pharmacology is illustrated by simulating diurnal variations of the metabolic state of the liver at various perturbations caused by nutritional challenges (alcohol), drugs (valproate), and inherited enzyme disorders (galactosemia). Using proteomics data to scale maximal enzyme activities, the model is used to highlight differences in the metabolic functions of normal hepatocytes and malignant liver cells (adenoma and hepatocellular carcinoma).

Personalized translational epilepsy research - Novel approaches and future perspectives: Part II: Experimental and translational approaches.

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Bauer, Sebastian; van Alphen, Natascha; Becker, Albert; Chiocchetti, Andreas; Deichmann, Ralf; Deller, Thomas; Freiman, Thomas; Freitag, Christine M; Gehrig, Johannes; Hermsen, Anke M; Jedlicka, Peter; Kell, Christian; Klein, Karl Martin; Knake, Susanne; Kullmann, Dimitri M; Liebner, Stefan; Norwood, Braxton A; Omigie, Diana; Plate, Karlheinz; Reif, Andreas; Reif, Philipp S; Reiss, Yvonne; Roeper, Jochen; Ronellenfitsch, Michael W; Schorge, Stephanie; Schratt, Gerhard; Schwarzacher, Stephan W; Steinbach, Joachim P; Strzelczyk, Adam; Triesch, Jochen; Wagner, Marlies; Walker, Matthew C; von Wegner, Frederic; Rosenow, Felix

2017-11-01

Despite the availability of more than 15 new "antiepileptic drugs", the proportion of patients with pharmacoresistant epilepsy has remained constant at about 20-30%. Furthermore, no disease-modifying treatments shown to prevent the development of epilepsy following an initial precipitating brain injury or to reverse established epilepsy have been identified to date. This is likely in part due to the polyetiologic nature of epilepsy, which in turn requires personalized medicine approaches. Recent advances in imaging, pathology, genetics, and epigenetics have led to new pathophysiological concepts and the identification of monogenic causes of epilepsy. In the context of these advances, the First International Symposium on Personalized Translational Epilepsy Research (1st ISymPTER) was held in Frankfurt on September 8, 2016, to discuss novel approaches and future perspectives for personalized translational research. These included new developments and ideas in a range of experimental and clinical areas such as deep phenotyping, quantitative brain imaging, EEG/MEG-based analysis of network dysfunction, tissue-based translational studies, innate immunity mechanisms, microRNA as treatment targets, functional characterization of genetic variants in human cell models and rodent organotypic slice cultures, personalized treatment approaches for monogenic epilepsies, blood-brain barrier dysfunction, therapeutic focal tissue modification, computational modeling for target and biomarker identification, and cost analysis in (monogenic) disease and its treatment. This report on the meeting proceedings is aimed at stimulating much needed investments of time and resources in personalized translational epilepsy research. This Part II includes the experimental and translational approaches and a discussion of the future perspectives, while the diagnostic methods, EEG network analysis, biomarkers, and personalized treatment approaches were addressed in Part I [1]. Copyright © 2017

UPF1 silenced cellular model systems for screening of read-through agents active on β039 thalassemia point mutation.

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Salvatori, Francesca; Pappadà, Mariangela; Breveglieri, Giulia; D'Aversa, Elisabetta; Finotti, Alessia; Lampronti, Ilaria; Gambari, Roberto; Borgatti, Monica

2018-05-15

Nonsense mutations promote premature translational termination, introducing stop codons within the coding region of mRNAs and causing inherited diseases, including thalassemia. For instance, in β 0 39 thalassemia the CAG (glutamine) codon is mutated to the UAG stop codon, leading to premature translation termination and to mRNA destabilization through the well described NMD (nonsense-mediated mRNA decay). In order to develop an approach facilitating translation and, therefore, protection from NMD, ribosomal read-through molecules, such as aminoglycoside antibiotics, have been tested on mRNAs carrying premature stop codons. These findings have introduced new hopes for the development of a pharmacological approach to the β 0 39 thalassemia therapy. While several strategies, designed to enhance translational read-through, have been reported to inhibit NMD efficiency concomitantly, experimental tools for systematic analysis of mammalian NMD inhibition by translational read-through are lacking. We developed a human cellular model of the β 0 39 thalassemia mutation with UPF-1 suppressed and showing a partial NMD suppression. This novel cellular model could be used for the screening of molecules exhibiting preferential read-through activity allowing a great rescue of the mutated transcripts.

Pharmacological Evaluation of the SCID T Cell Transfer Model of Colitis: As a Model of Crohn's Disease

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Thomas Lindebo Holm

2012-01-01

Full Text Available Animal models are important tools in the development of new drug candidates against the inflammatory bowel diseases (IBDs Crohn's disease and ulcerative colitis. In order to increase the translational value of these models, it is important to increase knowledge relating to standard drugs. Using the SCID adoptive transfer colitis model, we have evaluated the effect of currently used IBD drugs and IBD drug candidates, that is, anti-TNF-α, TNFR-Fc, anti-IL-12p40, anti-IL-6, CTLA4-Ig, anti-α4β7 integrin, enrofloxacin/metronidazole, and cyclosporine. We found that anti-TNF-α, antibiotics, anti-IL-12p40, anti-α4β7 integrin, CTLA4-Ig, and anti-IL-6 effectively prevented onset of colitis, whereas TNFR-Fc and cyclosporine did not. In intervention studies, antibiotics, anti-IL-12p40, and CTLA4-Ig induced remission, whereas the other compounds did not. The data suggest that the adoptive transfer model and the inflammatory bowel diseases have some main inflammatory pathways in common. The finding that some well-established IBD therapeutics do not have any effect in the model highlights important differences between the experimental model and the human disease.

Pharmacological evaluation of bee venom and melittin

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Camila G. Dantas

Full Text Available The objective of this study was to identify the pharmacological effects of bee venom and its major component, melittin, on the nervous system of mice. For the pharmacological analysis, mice were treated once with saline, 0.1 or 1.2 mg/kg of bee venom and 0.1 mg/kg of melittin, subcutaneously, 30 min before being submitted to behavioral tests: locomotor activity and grooming (open-field, catalepsy, anxiety (elevated plus-maze, depression (forced swimming test and apomorphine-induced stereotypy. Haloperidol, imipramine and diazepam were administered alone (positive control or as a pre-treatment (haloperidol.The bee venom reduced motor activity and promoted cataleptic effect, in a similar manner to haloperidol.These effects were decreased by the pretreatment with haloperidol. Both melittin and bee venom decreased the apomorphine-induced stereotypies. The data indicated the antipsychotic activity of bee venom and melittin in a murine model.

Translating India

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Kothari, Rita

2014-01-01

The cultural universe of urban, English-speaking middle class in India shows signs of growing inclusiveness as far as English is concerned. This phenomenon manifests itself in increasing forms of bilingualism (combination of English and one Indian language) in everyday forms of speech - advertisement jingles, bilingual movies, signboards, and of course conversations. It is also evident in the startling prominence of Indian Writing in English and somewhat less visibly, but steadily rising, activity of English translation from Indian languages. Since the eighties this has led to a frenetic activity around English translation in India's academic and literary circles. Kothari makes this very current phenomenon her chief concern in Translating India.   The study covers aspects such as the production, reception and marketability of English translation. Through an unusually multi-disciplinary approach, this study situates English translation in India amidst local and global debates on translation, representation an...

The Impact of Translators' Academic Experience on Their Translation Quality

Science.gov (United States)

Varzande, Mohsen; Jadidi, Esmaeil

2015-01-01

Translators differ from each other in many ways in terms of their knowledge and professional conditions that may directly influence their translation. The present study aimed at investigating the impact of translators' academic experience on their translation quality. Following a "causal-comparative study", a sample of 100 male and…

The utrophin A 5'-UTR drives cap-independent translation exclusively in skeletal muscles of transgenic mice and interacts with eEF1A2.

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Miura, P; Coriati, A; Bélanger, G; De Repentigny, Y; Lee, J; Kothary, R; Holcik, M; Jasmin, B J

2010-04-01

The molecular mechanisms regulating expression of utrophin A are of therapeutic interest since upregulating its expression at the sarcolemma can compensate for the lack of dystrophin in animal models of Duchenne Muscular Dystrophy (DMD). The 5'-UTR of utrophin A has been previously shown to drive cap-independent internal ribosome entry site (IRES)-mediated translation in response to muscle regeneration and glucocorticoid treatment. To determine whether the utrophin A IRES displays tissue specific activity, we generated transgenic mice harboring control (CMV/betaGAL/CAT) or utrophin A 5'-UTR (CMV/betaGAL/UtrA/CAT) bicistronic reporter transgenes. Examination of multiple tissues from two CMV/betaGAL/UtrA/CAT lines revealed that the utrophin A 5'-UTR drives cap-independent translation of the reporter gene exclusively in skeletal muscles and no other examined tissues. This expression pattern suggested that skeletal muscle-specific factors are involved in IRES-mediated translation of utrophin A. We performed RNA-affinity chromatography experiments combined with mass spectrometry to identify trans-factors that bind the utrophin A 5'-UTR and identified eukaryotic elongation factor 1A2 (eEF1A2). UV-crosslinking experiments confirmed the specificity of this interaction. Regions of the utrophin A 5'-UTR that bound eEF1A2 also mediated cap-independent translation in C2C12 muscle cells. Cultured cells lacking eEF1A2 had reduced IRES activity compared with cells overexpressing eEF1A2. Together, these results suggest an important role for eEF1A2 in driving cap-independent translation of utrophin A in skeletal muscle. The trans-factors and signaling pathways driving skeletal-muscle specific IRES-mediated translation of utrophin A could provide unique targets for developing pharmacological-based DMD therapies.

[Contribution of animal experimentation to pharmacology].

Science.gov (United States)

Sassard, Jean; Hamon, Michel; Galibert, Francis

2009-11-01

Animal experimentation is of considerable importance in pharmacology and cannot yet be avoided when studying complex, highly integrated physiological functions. The use of animals has been drastically reduced in the classical phases of pharmacological research, for example when comparing several compounds belonging to the same pharmacological class. However, animal experiments remain crucial for generating and validating new therapeutic concepts. Three examples of such research, conducted in strict ethical conditions, will be used to illustrate the different ways in which animal experimentation has contributed to human therapeutics.

Supercapacitive transport of pharmacologic agents using nanoporous gold electrodes.

Science.gov (United States)

Gittard, Shaun D; Pierson, Bonnie E; Ha, Cindy M; Wu, Chung-An Max; Narayan, Roger J; Robinson, David B

2010-02-01

In this study, nanoporous gold supercapacitors were produced by electrochemical dealloying of gold-silver alloy. Scanning electron microscopy and energy dispersive X-ray spectroscopy confirmed completion of the dealloying process and generation of a porous gold material with approximately 10 nm diameter pores. Cyclic voltammetry and chronoamperometry of the nanoporous gold electrodes indicated that these materials exhibited supercapacitor behavior. The storage capacity of the electrodes measured by chronoamperometry was approximately 3 mC at 200 mV. Electrochemical storage and voltage-controlled delivery of two model pharmacologic agents, benzylammonium and salicylic acid, was demonstrated. These results suggest that capacitance-based storage and delivery of pharmacologic agents may serve as an alternative to conventional drug delivery methods.

Translating Legal Collocations in Contract Agreements by Iraqi EFL Students-Translators

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Muntaha A. Abdulwahid

2017-01-01

Full Text Available Legal translation of contract agreements is a challenge to translators as it involves combining the literary translation with the technical terminological precision. In translating legal contract agreements, a legal translator must utilize the lexical or syntactic precision and, more importantly, the pragmatic awareness of the context. This will guarantee an overall communicative process and avoid inconsistency in legal translation. However, the inability of the translator to meet these two functions in translating the contract item not only affects the contractors’ comprehension of the contract item but also affects the parties’ contractual obligations. In light of this, the purpose of this study was to find out how legal collocations used in contract agreements are translated from Arabic into English by student-translators in terms of (1 purely technical, (2 semi-technical, and (3 everyday vocabulary collocations. For the data collection, a multiple-choice collocation test was used to be answered by 35 EFL Iraqi undergraduate translator-students to decide on the aspects of weaknesses and strengths of their translation, thus decide on the aspects of correction. The findings showed that these students had serious problems in translating legal collocations as they lack the linguistic knowledge and pragmatic awareness needed to achieve the legal meaning and effect. They were also unable to make a difference among the three categories of legal collocations, purely technical, semi-technical, and everyday vocabulary collocations. These students should be exposed to more legal translation practices to obtain the required experience needed for their future career.

Translation Analysis on Civil Engineering Text Produced by Machine Translator

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Sutopo Anam

2018-01-01

Full Text Available Translation is extremely needed in communication since people have serious problem in the language used. Translation activity is done by the person in charge for translating the material. Translation activity is also able to be done by machine. It is called machine translation, reflected in the programs developed by programmer. One of them is Transtool. Many people used Transtool for helping them in solving the problem related with translation activities. This paper wants to deliver how important is the Transtool program, how effective is Transtool program and how is the function of Transtool for human business. This study applies qualitative research. The sources of data were document and informant. This study used documentation and in dept-interviewing as the techniques for collecting data. The collected data were analyzed by using interactive analysis. The results of the study show that, first; Transtool program is helpful for people in translating the civil engineering text and it functions as the aid or helper, second; the working of Transtool software program is effective enough and third; the result of translation produced by Transtool is good for short and simple sentences and not readable, not understandable and not accurate for long sentences (compound, complex and compound complex thought the result is informative. The translated material must be edited by the professional translator.

Translation Analysis on Civil Engineering Text Produced by Machine Translator

Science.gov (United States)

Sutopo, Anam

2018-02-01

Translation is extremely needed in communication since people have serious problem in the language used. Translation activity is done by the person in charge for translating the material. Translation activity is also able to be done by machine. It is called machine translation, reflected in the programs developed by programmer. One of them is Transtool. Many people used Transtool for helping them in solving the problem related with translation activities. This paper wants to deliver how important is the Transtool program, how effective is Transtool program and how is the function of Transtool for human business. This study applies qualitative research. The sources of data were document and informant. This study used documentation and in dept-interviewing as the techniques for collecting data. The collected data were analyzed by using interactive analysis. The results of the study show that, first; Transtool program is helpful for people in translating the civil engineering text and it functions as the aid or helper, second; the working of Transtool software program is effective enough and third; the result of translation produced by Transtool is good for short and simple sentences and not readable, not understandable and not accurate for long sentences (compound, complex and compound complex) thought the result is informative. The translated material must be edited by the professional translator.

Parkinson’s Disease Impulsive-Compulsive Disorders Questionnaire – Current Short (QUIP-CS – Translation and validation of content of Portuguese Version

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Débora Mascella Krieger

Full Text Available ABSTRACT Objective Parkinson’s disease (PD management is usually successfully reached with proper pharmacological treatment. However, PD patients can manifest neuropsychiatric symptoms secondary to medical therapy, including impulse control disorders (ICD, presenting as pathological gambling, hypersexuality, compulsive buying, drinking or eating disorders. We translated and validated the Portuguese version of the gold-standard questionnaire Parkinson’s Disease Impulsive-Compulsive Disorders Questionnaire, or (QUIP for identifying ICDs in PD patients. Methods Translation, back translation and submission to instrument developer was performed, that approved its new version comparing it to his original, validated version, with no loss of it’s original properties. Then, the Portuguese version was administered to 30 PD patients. They also were asked to rate from 1 to 5 the level of comprehensibility of the questions. Results The average level of comprehension was 4.06 ± 0.69 DP, considering 3 or more as acceptable. No patient has answered 1 or 2. Conclusion Our results on Portuguese version of QUIP-CS show that QUIP-CS translated and corrected version was easily understood and easily self-applied.

Multiscale Modeling in the Clinic: Drug Design and Development

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Clancy, Colleen E.; An, Gary; Cannon, William R.; Liu, Yaling; May, Elebeoba E.; Ortoleva, Peter; Popel, Aleksander S.; Sluka, James P.; Su, Jing; Vicini, Paolo; Zhou, Xiaobo; Eckmann, David M.

2016-02-17

A wide range of length and time scales are relevant to pharmacology, especially in drug development, drug design and drug delivery. Therefore, multi-scale computational modeling and simulation methods and paradigms that advance the linkage of phenomena occurring at these multiple scales have become increasingly important. Multi-scale approaches present in silico opportunities to advance laboratory research to bedside clinical applications in pharmaceuticals research. This is achievable through the capability of modeling to reveal phenomena occurring across multiple spatial and temporal scales, which are not otherwise readily accessible to experimentation. The resultant models, when validated, are capable of making testable predictions to guide drug design and delivery. In this review we describe the goals, methods, and opportunities of multi-scale modeling in drug design and development. We demonstrate the impact of multiple scales of modeling in this field. We indicate the common mathematical techniques employed for multi-scale modeling approaches used in pharmacology and present several examples illustrating the current state-of-the-art regarding drug development for: Excitable Systems (Heart); Cancer (Metastasis and Differentiation); Cancer (Angiogenesis and Drug Targeting); Metabolic Disorders; and Inflammation and Sepsis. We conclude with a focus on barriers to successful clinical translation of drug development, drug design and drug delivery multi-scale models.

In Silico Systems Pharmacology to Assess Drug's Therapeutic and Toxic Effects

DEFF Research Database (Denmark)

Orozco, Alejandro Aguayo; Audouze, Karine; Brunak, Soren

2016-01-01

For many years, the "one target, one drug" paradigm has been the driving force behind developments in pharmaceutical research. With the recent advances in molecular biology and genomics technologies, the focus is shifting toward "drug-holistic" systems based approaches (i.e. systems pharmacology......). The integration of large and diverse amount of data from chemistry and biology coupled with the development and the application of network-based approaches to cope with these data is the next paradigm of drug discovery. Systems pharmacology offers a novel way of approaching drug discovery by developing models...

Non Pharmacological Cognitive Enhancers - Current Perspectives.

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Sachdeva, Ankur; Kumar, Kuldip; Anand, Kuljeet Singh

2015-07-01

Cognition refers to the mental processes involved in thinking, knowing, remembering, judging, and problem solving. Cognitive dysfunctions are an integral part of neuropsychiatric disorders as well as in healthy ageing. Cognitive Enhancers are molecules that help improve aspects of cognition like memory, intelligence, motivation, attention and concentration. Recently, Non Pharmacological Cognitive Enhancers have gained popularity as effective and safe alternative to various established drugs. Many of these Non Pharmacological Cognitive Enhancers seem to be more efficacious compared to currently available Pharmacological Cognitive Enhancers. This review describes and summarizes evidence on various Non Pharmacological Cognitive Enhancers such as physical exercise, sleep, meditation and yoga, spirituality, nutrients, computer training, brain stimulation, and music. We also discuss their role in ageing and different neuro-psychiatric disorders, and current status of Cochrane database recommendations. We searched the Pubmed database for the articles and reviews having the terms 'non pharmacological and cognitive' in the title, published from 2000 till 2014. A total of 11 results displayed, out of which 10 were relevant to the review. These were selected and reviewed. Appropriate cross-references within the articles along with Cochrane reviews were also considered and studied.

Revisiting interaction in knowledge translation

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Zackheim Lisa

2007-10-01

Full Text Available Abstract Background Although the study of research utilization is not new, there has been increased emphasis on the topic over the recent past. Science push models that are researcher driven and controlled and demand pull models emphasizing users/decision-maker interests have largely been abandoned in favour of more interactive models that emphasize linkages between researchers and decisionmakers. However, despite these and other theoretical and empirical advances in the area of research utilization, there remains a fundamental gap between the generation of research findings and the application of those findings in practice. Methods Using a case approach, the current study looks at the impact of one particular interaction approach to research translation used by a Canadian funding agency. Results Results suggest there may be certain conditions under which different levels of decisionmaker involvement in research will be more or less effective. Four attributes are illuminated by the current case study: stakeholder diversity, addressability/actionability of results, finality of study design and methodology, and politicization of results. Future research could test whether these or other variables can be used to specify some of the conditions under which different approaches to interaction in knowledge translation are likely to facilitate research utilization. Conclusion This work suggests that the efficacy of interaction approaches to research translation may be more limited than current theory proposes and underscores the need for more completely specified models of research utilization that can help address the slow pace of change in this area.

High-Throughput Screening of Ototoxic and Otoprotective Pharmacological Drugs

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Kalinec, Federico

2005-01-01

Drug ototoxicity research has relied traditionally on animal models for the discovery and development of therapeutic interventions. More than 50 years of research, however, has delivered few--if any--successful clinical strategies for preventing or ameliorating the ototoxic effects of common pharmacological drugs such as aminoglycoside…

Fear Extinction as a Model for Translational Neuroscience: Ten Years of Progress

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Milad, Mohammed R.; Quirk, Gregory J.

2016-01-01

The psychology of extinction has been studied for decades. Approximately 10 years ago, however, there began a concerted effort to understand the neural circuits of extinction of fear conditioning, in both animals and humans. Progress during this period has been facilitated by an unusual degree of coordination between rodent and human researchers examining fear extinction. This successful research program could serve as a model for translational research in other areas of behavioral neuroscience. Here we review the major advances and highlight new approaches to understanding and exploiting fear extinction. PMID:22129456

Universal Reconfigurable Translator Module (URTM) Final Report

Science.gov (United States)

Leventhal, Edward; Machan, Roman; Jones, Rob

2009-01-01

This report describes the Universal Reconfigurable Translation Module, or URTM. The URTM was developed by Sigma Space Corporation for NASA in order to translate specific serial protocols, both logically and physically. At present, the prototype configuration has targeted MIL-STD-1553B (RT and BC), IEEE 1394b (Firewire), and ECSS-E-50-12A (SpaceWire). The objectives of this program were to study the feasibility of a configurable URTM to translate serial link data as might be used in a space-flight mission and to design, develop, document, and deliver an engineering prototype model of the URTM with a path to spaceflight. By simply connecting two of the three Physical Interface Modules (PIM) on either end of the RPTM (Reconfigurable Protocol Translator Module), the URTM then self configures via a library of interface translation functions, thereby allowing the two data links to communicate seamlessly.

Translation: between what can be translated and what must be translated

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Magda Jeanrenaud

2016-02-01

Full Text Available Starting from a disconcerting interpretation of Jacques Derrida, our analysis aims at investigating and also tries to explain the blockage which appears in the English, French and Romanian translations (signed by Maurice de Gandillac, Antoine Berman, Laurent Lamy, Alexis Nouss, Harry Zohn, Steven Rendall, Martine Broda, Catrinel Pleșu etc. of a well-known text of Walter Benjamin, Die Aufgabe des Übersetzers, when translators transpose in their target languages the two quotations given by Benjamin: one of Mallarmé, left untranslated in the source text, and another, signed by Pannwitz. The fact is that both quotations have something in common: a discoursive form which results from an unusual syntax, as if they were already, in a certain sense, „translations”. As if the translators feared—a feature of the translator’s psychology?—not to render their text sufficiently accessible, even when the source text is not intended to be accessible. Hence the painful dilemma of the intentional fallacy (not only of the text to be translated.

Placebo response of non-pharmacological and pharmacological trials in major depression: a systematic review and meta-analysis.

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André Russowsky Brunoni

Full Text Available BACKGROUND: Although meta-analyses have shown that placebo responses are large in Major Depressive Disorder (MDD trials; the placebo response of devices such as repetitive transcranial magnetic stimulation (rTMS has not been systematically assessed. We proposed to assess placebo responses in two categories of MDD trials: pharmacological (antidepressant drugs and non-pharmacological (device- rTMS trials. METHODOLOGY/PRINCIPAL FINDINGS: We performed a systematic review and meta-analysis of the literature from April 2002 to April 2008, searching MEDLINE, Cochrane, Scielo and CRISP electronic databases and reference lists from retrieved studies and conference abstracts. We used the keywords placebo and depression and escitalopram for pharmacological studies; and transcranial magnetic stimulation and depression and sham for non-pharmacological studies. All randomized, double-blinded, placebo-controlled, parallel articles on major depressive disorder were included. Forty-one studies met our inclusion criteria - 29 in the rTMS arm and 12 in the escitalopram arm. We extracted the mean and standard values of depression scores in the placebo group of each study. Then, we calculated the pooled effect size for escitalopram and rTMS arm separately, using Cohen's d as the measure of effect size. We found that placebo response are large for both escitalopram (Cohen's d - random-effects model - 1.48; 95%C.I. 1.26 to 1.6 and rTMS studies (0.82; 95%C.I. 0.63 to 1. Exploratory analyses show that sham response is associated with refractoriness and with the use of rTMS as an add-on therapy, but not with age, gender and sham method utilized. CONCLUSIONS/SIGNIFICANCE: We confirmed that placebo response in MDD is large regardless of the intervention and is associated with depression refractoriness and treatment combination (add-on rTMS studies. The magnitude of the placebo response seems to be related with study population and study design rather than the intervention

Overview of the Inland California Translational Consortium

Science.gov (United States)

Malkas, Linda H.

2017-05-01

The mission of the Inland California Translational Consortium (ICTC), an independent research consortium comprising a unique hub of regional institutions (City of Hope [COH], California Institute of Technology [Caltech], Jet Propulsion Laboratory [JPL], University of California Riverside [UCR], and Claremont Colleges Keck Graduate Institute [KGI], is to institute a new paradigm within the academic culture to accelerate translation of innovative biomedical discoveries into clinical applications that positively affect human health and life. The ICTC actively supports clinical translational research as well as the implementation and advancement of novel education and training models for the translation of basic discoveries into workable products and practices that preserve and improve human health while training and educating at all levels of the workforce using innovative forward-thinking approaches.

The Dutch vision of clinical pharmacology

NARCIS (Netherlands)

Schellens, J H M; Grouls, R; Guchelaar, H J; Touw, D J; Rongen, G A; de Boer, A; Van Bortel, L M

Recent position papers addressing the profession of clinical pharmacology have expressed concerns about the decline of interest in the field among clinicians and medical educators in the United Kingdom and other Western countries, whether clinical pharmacology is actually therapeutics, and whether

(Con)figuring gender in Bible translation: Cultural, translational and ...

African Journals Online (AJOL)

The gendered intersection of cultural studies and Bible translation is under acknowledged. Accounting for gender criticism in translation work requires, besides responsible theory and practice of translation, also attention to interwoven gender critical aspects. After a brief investigation of the intersections between biblical, ...

Translation and identity: Translation of the Freedom Charter into ...

African Journals Online (AJOL)

A comparative analysis of the Afrikaans translations reveals how the respective translators struggled sporadically through certain ideological constraints in order to provide a satisfactory narrative. Their inability to internalise the principles contained in the Freedom Charter resulted in them presenting a 'framed' translation ...

Translation Control: A Multifaceted Regulator of Inflammatory Response

Science.gov (United States)

Mazumder, Barsanjit; Li, Xiaoxia; Barik, Sailen

2010-01-01

A robust innate immune response is essential to the protection of all vertebrates from infection, but it often comes with the price tag of acute inflammation. If unchecked, a runaway inflammatory response can cause significant tissue damage, resulting in myriad disorders, such as dermatitis, toxicshock, cardiovascular disease, acute pelvic and arthritic inflammatory diseases, and various infections. To prevent such pathologies, cells have evolved mechanisms to rapidly and specifically shut off these beneficial inflammatory activities before they become detrimental. Our review of recent literature, including our own work, reveals that the most dominant and common mechanism is translational silencing, in which specific regulatory proteins or complexes are recruited to cis-acting RNA structures in the untranslated regions of single or multiple mRNAs that code for the inflammatory protein(s). Enhancement of the silencing function may constitute a novel pharmacological approach to prevent immunity-related inflammation. PMID:20304832

Brake Stops Both Rotation And Translation

Science.gov (United States)

Allred, Johnny W.; Fleck, Vincent J., Jr.

1995-01-01

Combination of braking and positioning mechanisms allows both rotation and translation before brake engaged. Designed for use in positioning model airplane in wind tunnel. Modified version used to position camera on tripod. Brake fast and convenient to use; contains single actuator energizing braking actions against both rotation and translation. Braking actuator electric, but pneumatic actuator could be used instead. Compact and lightweight, applies locking forces close to load, and presents minimal cross section to airflow.

Pharmacological chaperoning: a primer on mechanism and pharmacology.

Science.gov (United States)

Leidenheimer, Nancy J; Ryder, Katelyn G

2014-05-01

Approximately forty percent of diseases are attributable to protein misfolding, including those for which genetic mutation produces misfolding mutants. Intriguingly, many of these mutants are not terminally misfolded since native-like folding, and subsequent trafficking to functional locations, can be induced by target-specific, small molecules variably termed pharmacological chaperones, pharmacoperones, or pharmacochaperones (PCs). PC targets include enzymes, receptors, transporters, and ion channels, revealing the breadth of proteins that can be engaged by ligand-assisted folding. The purpose of this review is to provide an integrated primer of the diverse mechanisms and pharmacology of PCs. In this regard, we examine the structural mechanisms that underlie PC rescue of misfolding mutants, including the ability of PCs to act as surrogates for defective intramolecular interactions and, at the intermolecular level, overcome oligomerization deficiencies and dominant negative effects, as well as influence the subunit stoichiometry of heteropentameric receptors. Not surprisingly, PC-mediated structural correction of misfolding mutants normalizes interactions with molecular chaperones that participate in protein quality control and forward-trafficking. A variety of small molecules have proven to be efficacious PCs and the advantages and disadvantages of employing orthostatic antagonists, active-site inhibitors, orthostatic agonists, and allosteric modulator PCs are considered. Also examined is the possibility that several therapeutic agents may have unrecognized activity as PCs, and this chaperoning activity may mediate/contribute to therapeutic action and/or account for adverse effects. Lastly, we explore evidence that pharmacological chaperoning exploits intrinsic ligand-assisted folding mechanisms. Given the widespread applicability of PC rescue of mutants associated with protein folding disorders, both in vitro and in vivo, the therapeutic potential of PCs is vast

Developing translational medicine professionals : The Marie Skłodowska-Curie action model

NARCIS (Netherlands)

Petrelli, Alessandra; Prakken, Berent J.; Rosenblum, Norman D.

2016-01-01

End goal of translational medicine is to combine disciplines and expertise to eventually promote improvement of the global healthcare system by delivering effective therapies to individuals and society. Well-trained experts of the translational medicine process endowed with profound knowledge of

Word translation entropy in translation

DEFF Research Database (Denmark)

Schaeffer, Moritz; Dragsted, Barbara; Hvelplund, Kristian Tangsgaard

2016-01-01

This study reports on an investigation into the relationship between the number of translation alternatives for a single word and eye movements on the source text. In addition, the effect of word order differences between source and target text on eye movements on the source text is studied....... In particular, the current study investigates the effect of these variables on early and late eye movement measures. Early eye movement measures are indicative of processes that are more automatic while late measures are more indicative of conscious processing. Most studies that found evidence of target...... language activation during source text reading in translation, i.e. co-activation of the two linguistic systems, employed late eye movement measures or reaction times. The current study therefore aims to investigate if and to what extent earlier eye movement measures in reading for translation show...

(Configuring gender in Bible translation: Cultural, translational and gender critical intersections

Directory of Open Access Journals (Sweden)

Jeremy Punt

2014-06-01

Full Text Available The gendered intersection of cultural studies and Bible translation is under acknowledged. Accounting for gender criticism in translation work requires, besides responsible theory and practice of translation, also attention to interwoven gender critical aspects. After a brief investigation of the intersections between biblical, translation and gender studies, translation in a few Pauline texts with bearing on gender and sexuality are investigated.

'Inhabiting' the Translator's Habitus – Antjie Krog as Translator ...

African Journals Online (AJOL)

Drawing on the Bourdieusian concept of habitus and its applicability in the field of translation, this article discusses Antjie Krog's profile in the practice of translation in. South Africa. Bourdieu's conceptualisation of the relationship between the initiating activities of translators and the structures which constrain and enable ...

Pharmacology of human experimental anxiety

Directory of Open Access Journals (Sweden)

F.G. Graeff

2003-04-01

Full Text Available This review covers the effect of drugs affecting anxiety using four psychological procedures for inducing experimental anxiety applied to healthy volunteers and patients with anxiety disorders. The first is aversive conditioning of the skin conductance responses to tones. The second is simulated public speaking, which consists of speaking in front of a video camera, with anxiety being measured with psychometric scales. The third is the Stroop Color-Word test, in which words naming colors are painted in the same or in a different shade, the incongruence generating a cognitive conflict. The last test is a human version of a thoroughly studied animal model of anxiety, fear-potentiated startle, in which the eye-blink reflex to a loud noise is recorded. The evidence reviewed led to the conclusion that the aversive conditioning and potentiated startle tests are based on classical conditioning of anticipatory anxiety. Their sensitivity to benzodiazepine anxiolytics suggests that these models generate an emotional state related to generalized anxiety disorder. On the other hand, the increase in anxiety determined by simulated public speaking is resistant to benzodiazepines and sensitive to drugs affecting serotonergic neurotransmission. This pharmacological profile, together with epidemiological evidence indicating its widespread prevalence, suggests that the emotional state generated by public speaking represents a species-specific response that may be related to social phobia and panic disorder. Because of scant pharmacological data, the status of the Stroop Color-Word test remains uncertain. In spite of ethical and economic constraints, human experimental anxiety constitutes a valuable tool for the study of the pathophysiology of anxiety disorders.

Literal Translation using Google Translate in Translating the Text from French to English in Digital Tourism Brochure “Bienvenue À Paris”

Directory of Open Access Journals (Sweden)

Rila Hilma

2011-05-01

Full Text Available Translation is basically change of form. The form from which the translation is made will be called the source language and the form into which it is to be changed will be called the receptor language. Translation consists of transferring the meaning of the source language into the receptor language. Translating is not an easy job to do because many things to be considered to do this activity because translation means determining the meaning of a text, then reconstructing this same meaning using the appropriate structure and form in the receptor language. Translation is basically divided by two types of translation, one is literal and the other is idiomatic. Literal translation is really strict to the structure and form then often can not well express the true meaning of source language. Idiomatic translation makes every effort to communicate the meaning of the source language text in the natural forms of the receptor language. Then the most popular translation machine, Google Translate, in this study shows the results of translation which remain odd, unnatural, and nonsensical because the unsuccessful of message delivery, which is notably the typically error of literal translation.

Translation of Nutritional Genomics into Nutrition Practice: The Next Step

Directory of Open Access Journals (Sweden)

Chiara Murgia

2017-04-01

Full Text Available Genetics is an important piece of every individual health puzzle. The completion of the Human Genome Project sequence has deeply changed the research of life sciences including nutrition. The analysis of the genome is already part of clinical care in oncology, pharmacology, infectious disease and, rare and undiagnosed diseases. The implications of genetic variations in shaping individual nutritional requirements have been recognised and conclusively proven, yet routine use of genetic information in nutrition and dietetics practice is still far from being implemented. This article sets out the path that needs to be taken to build a framework to translate gene–nutrient interaction studies into best-practice guidelines, providing tools that health professionals can use to understand whether genetic variation affects nutritional requirements in their daily clinical practice.

The ICNP BaT - from translation tool to translation web service.

Science.gov (United States)

Schrader, Ulrich

2009-01-01

The ICNP BaT has been developed as a web application to support the collaborative translation of different versions of the ICNP into different languages. A prototype of a web service is described that could reuse the translations in the database of the ICNP BaT to provide automatic translations of nursing content based on the ICNP terminology globally. The translation web service is based on a service-oriented architecture making it easy to interoperate with different applications. Such a global translation server would free individual institutions from the maintenance costs of realizing their own translation services.

On Various Negative Translations

Directory of Open Access Journals (Sweden)

Gilda Ferreira

2011-01-01

Full Text Available Several proof translations of classical mathematics into intuitionistic mathematics have been proposed in the literature over the past century. These are normally referred to as negative translations or double-negation translations. Among those, the most commonly cited are translations due to Kolmogorov, Godel, Gentzen, Kuroda and Krivine (in chronological order. In this paper we propose a framework for explaining how these different translations are related to each other. More precisely, we define a notion of a (modular simplification starting from Kolmogorov translation, which leads to a partial order between different negative translations. In this derived ordering, Kuroda and Krivine are minimal elements. Two new minimal translations are introduced, with Godel and Gentzen translations sitting in between Kolmogorov and one of these new translations.

On the analysis of complex biological supply chains: From Process Systems Engineering to Quantitative Systems Pharmacology.

Science.gov (United States)

Rao, Rohit T; Scherholz, Megerle L; Hartmanshenn, Clara; Bae, Seul-A; Androulakis, Ioannis P

2017-12-05

The use of models in biology has become particularly relevant as it enables investigators to develop a mechanistic framework for understanding the operating principles of living systems as well as in quantitatively predicting their response to both pathological perturbations and pharmacological interventions. This application has resulted in a synergistic convergence of systems biology and pharmacokinetic-pharmacodynamic modeling techniques that has led to the emergence of quantitative systems pharmacology (QSP). In this review, we discuss how the foundational principles of chemical process systems engineering inform the progressive development of more physiologically-based systems biology models.

Pharmacological interactions of vasoconstrictors.

Science.gov (United States)

Gómez-Moreno, Gerardo; Guardia, Javier; Cutando, Antonio; Calvo-Guirado, José Luis

2009-01-01

This article is the first of a series on pharmacological interactions involving medicaments commonly prescribed and/or used in odontology: vasoconstrictors in local anaesthetics and anti-inflammatory and anti-microbial analgesics. The necessity for the odontologist to be aware of adverse reactions as a result of the pharmacological interactions is due to the increase in medicament consumption by the general population. There is a demographic change with greater life expectancy and patients have increased chronic health problems and therefore have increased medicament intake. The presence of adrenaline (epinephrine) and other vasoconstrictors in local odontological anaesthetics is beneficial in relation to the duration and depth of anaesthesia and reduces bleeding and systemic toxicity of the local anaesthetic. However, it might produce pharmacological interactions between the injected vasoconstrictors and the local anaesthetic and adrenergic medicament administered exogenically which the odontologist should be aware of, especially because of the risk of consequent adverse reactions. Therefore the importance of conducting a detailed clinical history of the general state of health and include all medicaments, legal as well as illegal, taken by the patient.

Translational research: a concept analysis.

Science.gov (United States)

Wendler, M Cecilia; Kirkbride, Geri; Wade, Kristen; Ferrell, Lynne

2013-01-01

BACKGROUND/CONCEPTUAL FRAMEWORK: Little is known about which approaches facilitate adoption and sustainment of evidence-based practice change in the highly complex care environments that constitute clinical practice today. The purpose of this article was to complete a concept analysis of translational research using a modified Walker and Avant approach. DESIGN/DATA COLLECTION: Using a rigorous and thorough review of the recent health care literature generated by a deep electronic search from 2004-2011, 85 appropriate documents were retrieved. Close reading of the articles by three coresearchers yielded an analysis of the emerging concept of translational research. Using the iterative process described by Walker and Avant, a tentative definition of the concept of translational research, along with antecedents and consequences were identified. Implications for health care professionals in education, practice, and research are offered. Further research is needed to determine the adequacy of the definition, to identify empirical referents, and to guide theory development. The study resulted in a theoretical definition of the concept of translational research, along with identification of antecedents and consequences and a description of an ideal or model case to illustrate the definition. Implications for practice and education include the importance of focusing on translational research approaches that may reduce the research-practice gap in health care, thereby improving patient care delivery. Research is needed to determine the usefulness of the definition in health care clinical practice.

Treatment of TBI with Hormonal and Pharmacological Support, Preclinical Validation Using Diffuse and Mechanical TBI Animal Models

Science.gov (United States)

2016-05-01

Award Number: PT075653 (grant) W81XWH-08-2-0153 (contract) TITLE: Treatment of TBI with Hormonal and Pharmacological Support, Preclinical...TITLE AND SUBTITLE 5a. CONTRACT NUMBER W81XWH-08-2-0153 Treatment of TBI with Hormonal and Pharmacological Support, Preclinical Validation Using...rats. Our in vivo tests also included MRI imaging, focusing on edema resolution and reduction of diffuse axonal damage (fractional anisotropy

Lost in translation?

DEFF Research Database (Denmark)

Granas, Anne Gerd; Nørgaard, Lotte Stig; Sporrong, Sofia Kälvemark

2014-01-01

OBJECTIVE: The "Beliefs about Medicines Questionnaire" (BMQ) assess balance of necessity and concern of medicines. The BMQ has been translated from English to many languages. However, the original meaning of statements, such as "My medicine is a mystery to me", may be lost in translation. The aim...... of this study is to compare three Scandinavian translations of the BMQ. (1) How reliable are the translations? (2) Are they still valid after translation? METHODS: Translated Norwegian, Swedish and Danish versions of the BMQ were scrutinized by three native Scandinavian researchers. Linguistic differences...... and ambiguities in the 5-point Likert scale and the BMQ statements were compared. RESULTS: In the Scandinavian translations, the Likert scale expanded beyond the original version at one endpoint (Swedish) or both endpoints (Danish). In the BMQ statements, discrepancies ranged from smaller inaccuracies toward...

Reassessment of the role of TSC, mTORC1 and microRNAs in amino acids-meditated translational control of TOP mRNAs.

Directory of Open Access Journals (Sweden)

Ilona Patursky-Polischuk

Full Text Available TOP mRNAs encode components of the translational apparatus, and repression of their translation comprises one mechanism, by which cells encountering amino acid deprivation downregulate the biosynthesis of the protein synthesis machinery. This mode of regulation involves TSC as knockout of TSC1 or TSC2 rescued TOP mRNAs translation in amino acid-starved cells. The involvement of mTOR in translational control of TOP mRNAs is demonstrated by the ability of constitutively active mTOR to relieve the translational repression of TOP mRNA upon amino acid deprivation. Consistently, knockdown of this kinase as well as its inhibition by pharmacological means blocked amino acid-induced translational activation of these mRNAs. The signaling of amino acids to TOP mRNAs involves RagB, as overexpression of active RagB derepressed the translation of these mRNAs in amino acid-starved cells. Nonetheless, knockdown of raptor or rictor failed to suppress translational activation of TOP mRNAs by amino acids, suggesting that mTORC1 or mTORC2 plays a minor, if any, role in this mode of regulation. Finally, miR10a has previously been suggested to positively regulate the translation of TOP mRNAs. However, we show here that titration of this microRNA failed to downregulate the basal translation efficiency of TOP mRNAs. Moreover, Drosha knockdown or Dicer knockout, which carries out the first and second processing steps in microRNAs biosynthesis, respectively, failed to block the translational activation of TOP mRNAs by amino acid or serum stimulation. Evidently, these results are questioning the positive role of microRNAs in this mode of regulation.

An Evergreen Challenge for Translators – The Translation of Idioms

Directory of Open Access Journals (Sweden)

Kovács Gabriella

2016-12-01

Full Text Available Translating idioms has always been a challenging decision-making process for translators mainly because not all idioms have direct equivalents in the target language. Translators usually and ideally have a solid knowledge of the target language and its cultural aspects, but even so they cannot match the ability of a native speaker in deciding when – i.e. in what context and text type – an idiom would or would not be appropriate. This study aims to explore the main characteristics of idioms and the difficulties which might occur when translating them. A needs analysis will also be presented, where the various solutions which a group of translator trainees chose while translating certain idioms from the novel “A Game of Thrones” by George R. R. Martin into Hungarian are examined. Their strategies and the appropriateness of their choices are analysed and compared with the options of the experienced literary translator (Tamás Pétersz. We consider this an important endeavour because, based on our experience, we believe that the topic of the translation of idioms should be included into the curriculum and appropriate materials and tasks should be designed to develop the translator trainees’ knowledge and skills in this domain. Therefore, the aim of this analysis is to obtain a clearer view of the difficulties they are dealing with and bear them in mind when designing teaching materials for them.

Translation in Language Teaching: Insights from Professional Translator Training

Science.gov (United States)

Carreres, Angeles; Noriega-Sanchez, Maria

2011-01-01

The past three decades have seen vast changes in attitudes towards translation, both as an academic discipline and as a profession. The insights we have gained in recent years, in particular in the area of professional translator training, call for a reassessment of the role of translation in language teaching. Drawing on research and practices in…

Lost in translation

DEFF Research Database (Denmark)

Hedegaard, Steffen; Simonsen, Jakob Grue

2011-01-01

of translated texts. Our results suggest (i) that frame-based classifiers are usable for author attribution of both translated and untranslated texts; (ii) that framebased classifiers generally perform worse than the baseline classifiers for untranslated texts, but (iii) perform as well as, or superior...... to the baseline classifiers on translated texts; (iv) that—contrary to current belief—naïve classifiers based on lexical markers may perform tolerably on translated texts if the combination of author and translator is present in the training set of a classifier....

A mediation model for the translation of radio news texts in a ...

African Journals Online (AJOL)

Broadcast journalists in South Africa are media workers, editors and translators simultaneously producing news for bilingual or multilingual audiences. News texts are translated from English into one or more of the other official languages, depending on the target audience of the broadcaster. This article aims to indicate how ...

Hurdles in Basic Science Translation

Directory of Open Access Journals (Sweden)

Christina J. Perry

2017-07-01

Full Text Available In the past century there have been incredible advances in the field of medical research, but what hinders translation of this knowledge into effective treatment for human disease? There is an increasing focus on the failure of many research breakthroughs to be translated through the clinical trial process and into medical practice. In this mini review, we will consider some of the reasons that findings in basic medical research fail to become translated through clinical trials and into basic medical practices. We focus in particular on the way that human disease is modeled, the understanding we have of how our targets behave in vivo, and also some of the issues surrounding reproducibility of basic research findings. We will also look at some of the ways that have been proposed for overcoming these issues. It appears that there needs to be a cultural shift in the way we fund, publish and recognize quality control in scientific research. Although this is a daunting proposition, we hope that with increasing awareness and focus on research translation and the hurdles that impede it, the field of medical research will continue to inform and improve medical practice across the world.

Writing Through: Practising Translation

Directory of Open Access Journals (Sweden)

Joel Scott

2010-05-01

Full Text Available This essay exists as a segment in a line of study and writing practice that moves between a critical theory analysis of translation studies conceptions of language, and the practical questions of what those ideas might mean for contemporary translation and writing practice. Although the underlying preoccupation of this essay, and my more general line of inquiry, is translation studies and practice, in many ways translation is merely a way into a discussion on language. For this essay, translation is the threshold of language. But the two trails of the discussion never manage to elude each other, and these concatenations have informed two experimental translation methods, referred to here as Live Translations and Series Translations. Following the essay are a number of poems in translation, all of which come from Blanco Nuclear by the contemporary Spanish poet, Esteban Pujals Gesalí. The first group, the Live Translations consist of transcriptions I made from audio recordings read in a public setting, in which the texts were translated in situ, either off the page of original Spanish-language poems, or through a process very much like that carried out by simultaneous translators, for which readings of the poems were played back to me through headphones at varying speeds to be translated before the audience. The translations collected are imperfect renderings, attesting to a moment in language practice rather than language objects. The second method involves an iterative translation process, by which three versions of any one poem are rendered, with varying levels of fluency, fidelity and servility. All three translations are presented one after the other as a series, with no version asserting itself as the primary translation. These examples, as well as the translation methods themselves, are intended as preliminary experiments within an endlessly divergent continuum of potential methods and translations, and not as a complete representation of

An Efficient Translation of Timed-Arc Petri Nets to Networks of Timed Automata

DEFF Research Database (Denmark)

Byg, Joakim; Jørgensen, Kenneth Yrke; Srba, Jiri

2009-01-01

Bounded timed-arc Petri nets with read-arcs were recently proven equivalent to networks of timed automata, though the Petri net model cannot express urgent behaviour and the described mutual trans- lations are rather inefficient. We propose an extension of timed-arc Petri nets with invariants...... to enforce urgency and with transport arcs to generalise the read-arcs. We also describe a novel translation from the extended timed-arc Petri net model to networks of timed automata. The translation is implemented in the tool TAPAAL and it uses UPPAAL as the verification engine. Our experiments confirm...... the efficiency of the translation and in some cases the translated models verify significantly faster than the native UPPAAL models do....

Diffusion-accomodated rigid-body translations along grain boundaries in nanostructured materials

International Nuclear Information System (INIS)

Bachurin, D.V.; Nazarov, A.A.; Shenderova, O.A.; Brenner, D.W.

2003-01-01

A model for the structural relaxation of grain boundaries (GBs) in nanostructured materials (NSMs) by diffusion-accommodated rigid body translations along GBs is proposed. The model is based on the results of recent computer simulations that have demonstrated that the GBs in NSMs retain a high-energy structure with random translational states due to severe geometrical constraints applied from neighboring grains (J. Appl. Phys. 78 (1995) 847; Scripta Metall. Mater. 33 (1995) 1245). The shear stresses within a GB caused by non-optimized rigid-body translations (RBTs) can be accommodated by diffusive flow of atoms along a GB. This mechanism is particularly important for low-angle and vicinal GBs, the energy of which noticeably depends on the rigid body translations. At moderate and high temperatures the model yields relaxation times that are very short and therefore GBs in NSMs can attain an equilibrium structure with optimized rigid body translations. In contrast, at room temperature the model predicts that in some metals non-equilibrium structures can be preserved for a long time, which may result in the observation of grain boundary structures different from those in coarse grained polycrystals

Translating and transforming (a) CALL for leadership for learning

DEFF Research Database (Denmark)

Weinreich, Elvi; Bjerg, Helle

2015-01-01

"The paper pursues the argument that the process of translation is not solely a linguistic exercise. It also implies methodological and conceptual questions related to the translation and as such transformation of general and theoretical research based models of leadership for learning...

Speaking your Translation

DEFF Research Database (Denmark)

Dragsted, Barbara; Mees, Inger M.; Gorm Hansen, Inge

2011-01-01

In this article we discuss the translation processes and products of 14 MA students who produced translations from Danish (L1) into English (L2) under different working conditions: (1) written translation, (2) sight translation, and (3) sight translation with a speech recognition (SR) tool. Audio......, since students were dictating in their L2, we looked into the number and types of error that occurred when using the SR software. Items that were misrecognised by the program could be divided into three categories: homophones, hesitations, and incorrectly pronounced words. Well over fifty per cent...

Translation in language learning: a ‘what for’ approach

Directory of Open Access Journals (Sweden)

Paolo E. Balboni

2017-12-01

Full Text Available Literature about translation in language learning and teaching shows the prominence of the ‘for and against’ approach, while a ‘what for’ approach would be more profitable. In order to prevent the latter approach from becoming a random list of the potential benefits of the use of translation in language teaching, this essay suggests the use of a formal model of communicative competence, to see which of its components can profit of translation activities. The result is a map of the effects of translation in the wide range of competences and abilities which constitute language learning.

Advancing Transdisciplinary and Translational Research Practice: Issues and Models of Doctoral Education in Public Health

Directory of Open Access Journals (Sweden)

Linda Neuhauser

2007-01-01

Full Text Available Finding solutions to complex health problems, such as obesity, violence, and climate change, will require radical changes in cross-disciplinary education, research, and practice. The fundamental determinants of health include many interrelated factors such as poverty, culture, education, environment, and government policies. However, traditional public health training has tended to focus more narrowly on diseases and risk factors, and has not adequately leveraged the rich contributions of sociology, anthropology, economics, geography, communication, political science, and other disciplines. Further, students are often not sufficiently trained to work across sectors to translate research findings into effective, large-scale sustainable actions.During the past 2 decades, national and international organizations have called for more effective interdisciplinary, transdisciplinary, and translational approaches to graduate education. Although it has been difficult to work across traditional academic boundaries, some promising models draw on pedagogical theory and feature cross-disciplinary training focused on real-world problems, linkage between research, professional practice, community action, and cultivation of leadership skills.We describe the development the Doctor of Public Health program at the University of California, Berkeley, USA and its efforts to improve transdisciplinary and translational research education. We stress the need for international collaboration to improve educational approaches and better evaluate their impact.

Experimental annotation of post-translational features and translated coding regions in the pathogen Salmonella Typhimurium

Energy Technology Data Exchange (ETDEWEB)

Ansong, Charles; Tolic, Nikola; Purvine, Samuel O.; Porwollik, Steffen; Jones, Marcus B.; Yoon, Hyunjin; Payne, Samuel H.; Martin, Jessica L.; Burnet, Meagan C.; Monroe, Matthew E.; Venepally, Pratap; Smith, Richard D.; Peterson, Scott; Heffron, Fred; Mcclelland, Michael; Adkins, Joshua N.

2011-08-25

Complete and accurate genome annotation is crucial for comprehensive and systematic studies of biological systems. For example systems biology-oriented genome scale modeling efforts greatly benefit from accurate annotation of protein-coding genes to develop proper functioning models. However, determining protein-coding genes for most new genomes is almost completely performed by inference, using computational predictions with significant documented error rates (> 15%). Furthermore, gene prediction programs provide no information on biologically important post-translational processing events critical for protein function. With the ability to directly measure peptides arising from expressed proteins, mass spectrometry-based proteomics approaches can be used to augment and verify coding regions of a genomic sequence and importantly detect post-translational processing events. In this study we utilized “shotgun” proteomics to guide accurate primary genome annotation of the bacterial pathogen Salmonella Typhimurium 14028 to facilitate a systems-level understanding of Salmonella biology. The data provides protein-level experimental confirmation for 44% of predicted protein-coding genes, suggests revisions to 48 genes assigned incorrect translational start sites, and uncovers 13 non-annotated genes missed by gene prediction programs. We also present a comprehensive analysis of post-translational processing events in Salmonella, revealing a wide range of complex chemical modifications (70 distinct modifications) and confirming more than 130 signal peptide and N-terminal methionine cleavage events in Salmonella. This study highlights several ways in which proteomics data applied during the primary stages of annotation can improve the quality of genome annotations, especially with regards to the annotation of mature protein products.

Struggling with Translations

DEFF Research Database (Denmark)

Obed Madsen, Søren

This paper shows empirical how actors have difficulties with translating strategy texts. The paper uses four cases as different examples of what happens, and what might be difficult, when actors translate organizational texts. In order to explore this, it draws on a translation training method from...... translation theory. The study shows that for those who have produced the text, it is difficult to translate a strategy where they have to change the words so others who don’t understand the language in the text can understand it. It also shows that for those who haven’t been a part of the production, it very...... challenge the notion that actors understand all texts and that managers per se can translate a text....

Pharmacology Goes Concept-Based: Course Design, Implementation, and Evaluation.

Science.gov (United States)

Lanz, Amelia; Davis, Rebecca G

Although concept-based curricula are frequently discussed in the nursing education literature, little information exists to guide the development of a concept-based pharmacology course. Traditionally, nursing pharmacology courses are taught with an emphasis on drug class where a prototype drug serves as an exemplar. When transitioning pharmacology to a concept-based course, special considerations are in order. How can educators successfully integrate essential pharmacological content into a curriculum structured around nursing concepts? This article presents one approach to the design and implementation of a concept-based undergraduate pharmacology course. Planning methods, supportive teaching strategies, and course evaluation procedures are discussed.

an overview of recent developments in translation studies

African Journals Online (AJOL)

and pragmatics to conceptualise translation on the model of Gricean con- versation. In these terms, translation ..... chain, trying to fix a signified that can be no more than an interpretation according to the intelligibilities and ..... reader, but is of enormous value to some of the readers. This is pre-eminently the situation in many ...

Pharmacological study on traditional Chinese medicine and natural product in China

Institute of Scientific and Technical Information of China (English)

Yong-xiang ZHANG

2017-01-01

China is abundant in natural medicinal resources. Natural medicine (NP), especially traditional Chinese medicine (TCM), have been widely employed in prevention and treatment of diseases in China for thousands of years, which make a great contribution to health care of Chinese people and the prosperity of the Chinese nation. TCM is the excellence culture inheritance of China and a medicine system with long history, tradition and unique theory and technique. Prescriptions or formula are the main form of TCM and the compatibility and composition of them are made up following the theory of TCM among which the theory of compatibility is the essential part. Clinical application and modern pharmacological study both demonstrated that TCM prescription possesses unique effect in comparison with chemical drugs. However, the pharmacological study of TCM prescription is very difficult due to multiple herbs which contain complicated chemical components in the prescription. So, the key point for the pharmacological study of TCM prescription is to elucidate its integrative effect and the mechanism of action. In recent years, great advances have been achieved in the research on TCM prescription and modern study of TCM prescription, including pharmacological and chemical studies, has becoming a hot research field in China. The pharmacological studies of TCM and NP are conducted with different ways and methods including holistic approaches in various experimental model animals and in vitro experiments in tissue, organ and cell models. In addition, a lot of new technics and methods such as″ omics″ technologies were employed in the molecular level studies, for example, researches on the mechanism of action of TCM and NP. In addition, a lot of new drugs have been developed from TCM prescriptions in China. The classical preparations of TCM, including decoction, pill, powder, ointment and pellet, etc, are prepared with traditional methods. While, the new preparations are similar to

Syntactic Variance and Priming Effects in Translation

DEFF Research Database (Denmark)

Bangalore, Srinivas; Behrens, Bergljot; Carl, Michael

2016-01-01

The present work investigates the relationship between syntactic variation and priming in translation. It is based on the claim that languages share a common cognitive network of neural activity. When the source and target languages are solicited in a translation context, this shared network can...... lead to facilitation effects, so-called priming effects. We suggest that priming is a default setting in translation, a special case of language use where source and target languages are constantly co-activated. Such priming effects are not restricted to lexical elements, but do also occur...... on the syntactic level. We tested these hypotheses with translation data from the TPR database, more specifically for three language pairs (English-German, English-Danish, and English-Spanish). Our results show that response times are shorter when syntactic structures are shared. The model explains this through...

Is translational research compatible with preclinical publication strategies?

International Nuclear Information System (INIS)

Linder, Stig; Shoshan, Maria C

2006-01-01

The term 'translational research' is used to describe the transfer of basic biological knowledge into practical medicine, a process necessary for motivation of public spending. In the area of cancer therapeutics, it is becoming increasingly evident that results obtained in vitro and in animal models are difficult to translate into clinical medicine. We here argue that a number of factors contribute to making the translation process inefficient. These factors include the use of sensitive cell lines and fast growing experimental tumors as targets for novel therapies, and the use of unrealistic drug concentrations and radiation doses. We also argue that aggressive interpretation of data, successful in hypothesis-building biological research, does not form a solid base for development of clinically useful treatment modalities. We question whether 'clean' results obtained in simplified models, expected for publication in high-impact journals, represent solid foundations for improved treatment of patients. Open-access journals such as Radiation Oncology have a large mission to fulfill by publishing relevant data to be used for making actual progress in translational cancer research

The IGNITE (investigation to guide new insight into translational effectiveness trial: Protocol for a translational study of an evidenced-based wellness program in fire departments

Directory of Open Access Journals (Sweden)

MacKinnon David P

2010-10-01

Full Text Available Abstract Background Worksites are important locations for interventions to promote health. However, occupational programs with documented efficacy often are not used, and those being implemented have not been studied. The research in this report was funded through the American Reinvestment and Recovery Act Challenge Topic 'Pathways for Translational Research,' to define and prioritize determinants that enable and hinder translation of evidenced-based health interventions in well-defined settings. Methods The IGNITE (investigation to guide new insights for translational effectiveness trial is a prospective cohort study of a worksite wellness and injury reduction program from adoption to final outcomes among 12 fire departments. It will employ a mixed methods strategy to define a translational model. We will assess decision to adopt, installation, use, and outcomes (reach, individual outcomes, and economic effects using onsite measurements, surveys, focus groups, and key informant interviews. Quantitative data will be used to define the model and conduct mediation analysis of each translational phase. Qualitative data will expand on, challenge, and confirm survey findings and allow a more thorough understanding and convergent validity by overcoming biases in qualitative and quantitative methods used alone. Discussion Findings will inform worksite wellness in fire departments. The resultant prioritized influences and model of effective translation can be validated and manipulated in these and other settings to more efficiently move science to service.

[Application progress of proteomic in pharmacological study of Chinese medicinal formulae].

Science.gov (United States)

Liu, Yu-Qian; Zhan, Shu-Yu; Ruan, Yu-Er; Zuo, Zhi-Yan; Ji, Xiao-Ming; Wang, Shuai-Jie; Ding, Bao-Yue

2017-10-01

Chinese medicinal formulae are the important means of clinical treatment in traditional Chinese medicine. It is urgent to use modern advanced scientific and technological means to reveal the complicated mechanism of Chinese medicinal formulae because they have the function characteristics of multiple components, multiple targets and integrated regulation. The systematic and comprehensive research model of proteomic is in line with the function characteristics of Chinese medicinal formulae, and proteomic has been widely used in the study of pharmacological mechanism of Chinese medicinal formulae. The recent applications of proteomic in pharmacological study of Chinese medicinal formulae in anti-cardiovascular and cerebrovascular diseases, anti-liver disease, antidiabetic, anticancer, anti-rheumatoid arthritis and other diseases were reviewed in this paper, and then the future development direction of proteomic in pharmacological study of Chinese medicinal formulae was put forward. This review is to provide the ideas and method for proteomic research on function mechanism of Chinese medicinal formulae. Copyright© by the Chinese Pharmaceutical Association.

A Comparative Study of "Google Translate" Translations: An Error Analysis of English-to-Persian and Persian-to-English Translations

Science.gov (United States)

Ghasemi, Hadis; Hashemian, Mahmood

2016-01-01

Both lack of time and the need to translate texts for numerous reasons brought about an increase in studying machine translation with a history spanning over 65 years. During the last decades, Google Translate, as a statistical machine translation (SMT), was in the center of attention for supporting 90 languages. Although there are many studies on…

Developing a new model for the invention and translation of neurotechnologies in academic neurosurgery.

Science.gov (United States)

Leuthardt, Eric C

2013-01-01

There is currently an acceleration of new scientific and technical capabilities that create new opportunities for academic neurosurgery. To engage these changing dynamics, the Center for Innovation in Neuroscience and Technology (CINT) was created on the premise that successful innovation of device-related ideas relies on collaboration between multiple disciplines. The CINT has created a unique model that integrates scientific, medical, engineering, and legal/business experts to participate in the continuum from idea generation to translation. To detail the method by which this model has been implemented in the Department of Neurological Surgery at Washington University in St. Louis and the experience that has been accrued thus far. The workflow is structured to enable cross-disciplinary interaction, both intramurally and extramurally between academia and industry. This involves a structured method for generating, evaluating, and prototyping promising device concepts. The process begins with the "invention session," which consists of a structured exchange between inventors from diverse technical and medical backgrounds. Successful ideas, which pass a separate triage mechanism, are then sent to industry-sponsored multidisciplinary fellowships to create functioning prototypes. After 3 years, the CINT has engaged 32 clinical and nonclinical inventors, resulting in 47 ideas, 16 fellowships, and 12 patents, for which 7 have been licensed to industry. Financial models project that if commercially successful, device sales could have a notable impact on departmental revenue. The CINT is a model that supports an integrated approach from the time an idea is created through its translational development. To date, the approach has been successful in creating numerous concepts that have led to industry licenses. In the long term, this model will create a novel revenue stream to support the academic neurosurgical mission.

SPEECH ACT OF ILTIFAT AND ITS INDONESIAN TRANSLATION PROBLEMS

Directory of Open Access Journals (Sweden)

Zaka Al Farisi

2015-01-01

Full Text Available Abstract: Iltifat (shifting speech act is distinctive and considered unique style of Arabic. It has potential errors when it is translated into Indonesian. Therefore, translation of iltifat speech act into another language can be an important issue. The objective of the study is to know translation procedures/techniques and ideology required in dealing with iltifat speech act. This research is directed at translation as a cognitive product of a translator. The data used in the present study were the corpus of Koranic verses that contain iltifat speech act along with their translation. Data analysis typically used descriptive-evaluative method with content analysis model. The data source of this research consisted of the Koran and its translation. The purposive sampling technique was employed, with the sample of the iltifat speech act contained in the Koran. The results showed that more than 60% of iltifat speech act were translated by using literal procedure. The significant number of literal translation of the verses asserts that the Ministry of Religious Affairs tended to use literal method of translation. In other words, the Koran translation made by the Ministry of Religious Affairs tended to be oriented to the source language in dealing with iltifat speech act. The number of the literal procedure used shows a tendency of foreignization ideology. Transitional pronouns contained in the iltifat speech act can be clearly translated when thick translations were used in the form of description in parentheses. In this case, explanation can be a choice in translating iltifat speech act.

Bean Soup Translation: Flexible, Linguistically-Motivated Syntax for Machine Translation

Science.gov (United States)

Mehay, Dennis Nolan

2012-01-01

Machine translation (MT) systems attempt to translate texts from one language into another by translating words from a "source language" and rearranging them into fluent utterances in a "target language." When the two languages organize concepts in very different ways, knowledge of their general sentence structure, or…

Amyloid β production is regulated by β2-adrenergic signaling-mediated post-translational modifications of the ryanodine receptor.

Science.gov (United States)

Bussiere, Renaud; Lacampagne, Alain; Reiken, Steven; Liu, Xiaoping; Scheuerman, Valerie; Zalk, Ran; Martin, Cécile; Checler, Frederic; Marks, Andrew R; Chami, Mounia

2017-06-16

Alteration of ryanodine receptor (RyR)-mediated calcium (Ca 2+ ) signaling has been reported in Alzheimer disease (AD) models. However, the molecular mechanisms underlying altered RyR-mediated intracellular Ca 2+ release in AD remain to be fully elucidated. We report here that RyR2 undergoes post-translational modifications (phosphorylation, oxidation, and nitrosylation) in SH-SY5Y neuroblastoma cells expressing the β-amyloid precursor protein (βAPP) harboring the familial double Swedish mutations (APPswe). RyR2 macromolecular complex remodeling, characterized by depletion of the regulatory protein calstabin2, resulted in increased cytosolic Ca 2+ levels and mitochondrial oxidative stress. We also report a functional interplay between amyloid β (Aβ), β-adrenergic signaling, and altered Ca 2+ signaling via leaky RyR2 channels. Thus, post-translational modifications of RyR occur downstream of Aβ through a β2-adrenergic signaling cascade that activates PKA. RyR2 remodeling in turn enhances βAPP processing. Importantly, pharmacological stabilization of the binding of calstabin2 to RyR2 channels, which prevents Ca 2+ leakage, or blocking the β2-adrenergic signaling cascade reduced βAPP processing and the production of Aβ in APPswe-expressing SH-SY5Y cells. We conclude that targeting RyR-mediated Ca 2+ leakage may be a therapeutic approach to treat AD. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Introducing the Interactive Model for the Training of Audiovisual Translators and Analysis of Multimodal Texts

Directory of Open Access Journals (Sweden)

Pietro Luigi Iaia

2015-07-01

Full Text Available Abstract – This paper introduces the ‘Interactive Model’ of audiovisual translation developed in the context of my PhD research on the cognitive-semantic, functional and socio-cultural features of the Italian-dubbing translation of a corpus of humorous texts. The Model is based on two interactive macro-phases – ‘Multimodal Critical Analysis of Scripts’ (MuCrAS and ‘Multimodal Re-Textualization of Scripts’ (MuReTS. Its construction and application are justified by a multidisciplinary approach to the analysis and translation of audiovisual texts, so as to focus on the linguistic and extralinguistic dimensions affecting both the reception of source texts and the production of target ones (Chaume 2004; Díaz Cintas 2004. By resorting to Critical Discourse Analysis (Fairclough 1995, 2001, to a process-based approach to translation and to a socio-semiotic analysis of multimodal texts (van Leeuwen 2004; Kress and van Leeuwen 2006, the Model is meant to be applied to the training of audiovisual translators and discourse analysts in order to help them enquire into the levels of pragmalinguistic equivalence between the source and the target versions. Finally, a practical application shall be discussed, detailing the Italian rendering of a comic sketch from the American late-night talk show Conan.Abstract – Questo studio introduce il ‘Modello Interattivo’ di traduzione audiovisiva sviluppato durante il mio dottorato di ricerca incentrato sulle caratteristiche cognitivo-semantiche, funzionali e socio-culturali della traduzione italiana per il doppiaggio di un corpus di testi comici. Il Modello è costituito da due fasi: la prima, di ‘Analisi critica e multimodale degli script’ (MuCrAS e la seconda, di ‘Ritestualizzazione critica e multimodale degli script’ (MuReTS, e la sua costruzione e applicazione sono frutto di un approccio multidisciplinare all’analisi e traduzione dei testi audiovisivi, al fine di esaminare le

Translation of overlay models of student knowledge for relative domains based on domain ontology mapping

DEFF Research Database (Denmark)

Sosnovsky, Sergey; Dolog, Peter; Henze, Nicola

2007-01-01

The effectiveness of an adaptive educational system in many respects depends on the precision of modeling assumptions it makes about a student. One of the well-known challenges in student modeling is to adequately assess the initial level of student's knowledge when s/he starts working...... with a system. Sometimes potentially handful data are available as a part of user model from a system used by the student before. The usage of external user modeling information is troublesome because of differences in system architecture, knowledge representation, modeling constraints, etc. In this paper, we...... argue that the implementation of underlying knowledge models in a sharable format, as domain ontologies - along with application of automatic ontology mapping techniques for model alignment - can help to overcome the "new-user" problem and will greatly widen opportunities for student model translation...

[PROFESSOR VLADIMIR V. NIKOLAEV AND RUSSIAN PHARMACOLOGY.

Science.gov (United States)

Bondarchuk, N G; Fisenko, V P

2016-01-01

Various stages of scientific research activity of Prof. Vladimir V. Nikolaev are analyzed. The importance of Prof. Nikolaev's discovery of the two-neuron parasympathetic nervous system and some new methods of pharmacological substances evaluation is shown. Prof. Nikolaev is known as the editor of the first USSR Pharmacopoeia. Peculiarities of pharmacology teaching at the First Moscow Medical institute under conditions of changing social demands are described. Successful research of Prof. Nikolaev with colleagues in studying new mechanisms of drug action and developing original pharmacological substances is summarized.

Establishment, maintenance and in vitro and in vivo applications of primary human glioblastoma multiforme (GBM) xenograft models for translational biology studies and drug discovery.

Science.gov (United States)

Carlson, Brett L; Pokorny, Jenny L; Schroeder, Mark A; Sarkaria, Jann N

2011-03-01

Development of clinically relevant tumor model systems for glioblastoma multiforme (GBM) is important for advancement of basic and translational biology. One model that has gained wide acceptance in the neuro-oncology community is the primary xenograft model. This model entails the engraftment of patient tumor specimens into the flank of nude mice and subsequent serial passage of these tumors in the flank of mice. These tumors are then used to establish short-term explant cultures or intracranial xenografts. This unit describes detailed procedures for establishment, maintenance, and utilization of a primary GBM xenograft panel for the purpose of using them as tumor models for basic or translational studies.

Review of the Chemistry and Pharmacology of 7-Methyljugulone ...