RUNX1 regulates a transcription program that affects the dynamics of cell cycle entry of naive resting B cells

RUNX1 is a transcription factor that plays key roles in hematopoietic development and in hematopoiesis and lymphopoiesis. In this article, we report that RUNX1 regulates a gene expression program in naive mouse B cells that affects the dynamics of cell cycle entry in response to stimulation of the BCR. Conditional knockout of Runx1 in mouse resting B cells resulted in accelerated entry into S-phase after BCR engagement. Our results indicate that Runx1 regulates the cyclin D2 (Ccnd2) gene, the immediate early genes Fosl2, Atf3, and Egr2, and the Notch pathway gene Rbpj in mouse B cells, reducing the rate at which transcription of these genes increases after BCR stimulation. RUNX1 interacts with the chromatin remodeler SNF-2-related CREB-binding protein activator protein (SRCAP), recruiting it to promoter and enhancer regions of the Ccnd2 gene. BCR-mediated activation triggers switching between binding of RUNX1 and its paralog RUNX3 and between SRCAP and the switch/SNF remodeling complex member BRG1. Binding of BRG1 is increased at the Ccnd2 and Rbpj promoters in the Runx1 knockout cells after BCR stimulation. We also find that RUNX1 exerts positive or negative effects on a number of genes that affect the activation response of mouse resting B cells. These include Cd22 and Bank1, which act as negative regulators of the BCR, and the IFN receptor subunit gene Ifnar1 The hyperresponsiveness of the Runx1 knockout B cells to BCR stimulation and its role in regulating genes that are associated with immune regulation suggest that RUNX1 could be involved in regulating B cell tolerance

The effect of nitric oxide on the pressure of the acutely obstructed ureter

Acute ureteral obstruction leads to changes in pressure inside the ureter, interrupting ureter function. The aim of our study is to explore the relationship between nitric oxide (NO) concentration and pressure in the ureter and to observe the effects of nitric oxide on the revival of renal function. We created the animal models by embedding balloons in the lower ureters of anesthetized dogs and expanding them to simulate acute ureteral obstruction. First, the test animals were pre-treated intravenously with different doses of L-NAME (non-selective nitric oxide synthase inhibitor) to inhibit nitric oxide synthase (NOS), and 10 min later, each subject was administered an intravenous dose of isoproterenol (10 μg/kg). We measured ureter pressure (UP), total and peak concentrations of NO (using an NO monitor, model inNO-T) in ureteral urine, and the volume of the urine (UFV) leaking from the balloon edge. After a certain amount of time had elapsed, it became clear that the dose of L-NAME was inversely related to the total and peak concentrations of NO, the rate of change in UP, and the volume of urine produced. We conclude that L-NAME prevents the NOS from inhibiting the release of NO, then inhibits the effect of isoproterenol reducing the pressure of the acute obstructive ureter. Inversely, we think that NO can reduce the pressure of the acute obstructive ureter and make the obstructive ureter recanalization. And when more the concentration of nitric oxide, the more the pressure will be reduced, and more urine will be collected

Acupressure for smoking cessation – a pilot study

BACKGROUND: Tobacco smoking is a serious risk to health: several therapies are available to assist those who wish to stop. Smokers who approach publicly funded stop-smoking clinics in the UK are currently offered nicotine replacement therapy (NRT) or bupropion, and group behaviour therapy, for which there is evidence of effectiveness. Acupuncture and acupressure are also used to help smokers, though a systematic review of the evidence of their effectiveness was inconclusive. The aim of this pilot project was to determine the feasibility of a study to test acupressure as an adjunct to one anti-smoking treatment currently offered, and to inform the design of the study. METHODS: An open randomised controlled pilot study was conducted within the six week group programme offered by the Smoking Advice Service in Plymouth, UK. All participants received the usual treatment with NRT and group behavioural therapy, and were randomised into three groups: group A with two auricular acupressure beads, group B with one bead, and group C with no additional therapy. Participants were taught to press the beads when they experienced cravings. Beads were worn in one ear for four weeks, being replaced as necessary. The main outcome measures assessed in the pilot were success at quitting (expired CO ≤ 9 ppm), the dose of NRT used, and the rating of withdrawal symptoms using the Mood and Symptoms Scale. RESULTS: From 49 smokers attending four clinics, 24 volunteered to participate, 19 attended at least once after quitting, and seven remained to the final week. Participants who dropped out reported significantly fewer previous quit attempts, but no other significant differences. Participants reported stimulating the beads as expected during the initial days after quitting, but most soon reduced the frequency of stimulation. The discomfort caused by the beads was minor, and there were no significant side effects. There were technical problems with adhesiveness of the dressing. Reporting of NRT consumption was poor, with much missing data, but reporting of ratings of withdrawal symptom scores was nearly complete. However, these showed no significant changes or differences between groups for any week. CONCLUSION: Any effects of acupressure on smoking withdrawal, as an adjunct to the use of NRT and behavioural intervention, are unlikely to be detectable by the methods used here and further preliminary studies are required before the hypothesis can be tested

Adipocyte-specific protein tyrosine phosphatase 1B deletion increases lipogenesis, adipocyte cell size and is a minor regulator of glucose homeostasis

Peer reviewedPublisher PD

Carotid Artery Wall Imaging: Perspective and Guidelines from the ASNR Vessel Wall Imaging Study Group and Expert Consensus Recommendations of the American Society of Neuroradiology

SUMMARY: Identification of carotid artery atherosclerosis is conventionally based on measurements of luminal stenosis and surface irregularities using in vivo imaging techniques including sonography, CT and MR angiography, and digital subtraction angiography. However, histopathologic studies demonstrate considerable differences between plaques with identical degrees of stenosis and indicate that certain plaque features are associated with increased risk for ischemic events. The ability to look beyond the lumen using highly developed vessel wall imaging methods to identify plaque vulnerable to disruption has prompted an active debate as to whether a paradigm shift is needed to move away from relying on measurements of luminal stenosis for gauging the risk of ischemic injury. Further evaluation in randomized clinical trials will help to better define the exact role of plaque imaging in clinical decision-making. However, current carotid vessel wall imaging techniques can be informative. The goal of this article is to present the perspective of the ASNR Vessel Wall Imaging Study Group as it relates to the current status of arterial wall imaging in carotid artery disease

Concordance of sibling's recall of measures of childhood socioeconomic position

<p>Abstract</p> <p>Background</p> <p>Studies of socioeconomic determinants of health often rely on recalled information on childhood socioeconomic position, despite limited evidence of the validity of this information. This study examined concordance between siblings of recalled measures of childhood socioeconomic position.</p> <p>Methods</p> <p>This cross-sectional study examined reports by 1280 adult sibling pairs in the National Survey of Midlife Development in the United States of seven measures of childhood socioeconomic position: father's occupation (in 9 categories), father having a professional occupation, father being a supervisor at work, father's education level, mother's education level, receipt of welfare payments, and subjective appraisal of being better or worse off financially than others.</p> <p>Results</p> <p>Concordance was high for father's professional occupation (0.97; 95% confidence interval (CI) 0.96, 0.98), father's occupation in 9 categories (0.76; 95% CI 0.73, 0.80), and receipt of welfare payments (0.95; 95% CI 0.93, 0.97). Concordance was lower for father's and mother's education level, and lowest for subjective appraisal of socioeconomic position (0.60; 95% CI 0.57, 0.64). Concordance of parental education was lower for sibling pairs with high school educations or less.</p> <p>Conclusion</p> <p>Concordance of recalled measures of childhood socioeconomic position by siblings is generally but not uniformly high.</p

MRI of the lung (2/3). Why … when … how?

Background Among the modalities for lung imaging, proton magnetic resonance imaging (MRI) has been the latest to be introduced into clinical practice. Its value to replace X-ray and computed tomography (CT) when radiation exposure or iodinated contrast material is contra-indicated is well acknowledged: i.e. for paediatric patients and pregnant women or for scientific use. One of the reasons why MRI of the lung is still rarely used, except in a few centres, is the lack of consistent protocols customised to clinical needs. Methods This article makes non-vendor-specific protocol suggestions for general use with state-of-the-art MRI scanners, based on the available literature and a consensus discussion within a panel of experts experienced in lung MRI. Results Various sequences have been successfully tested within scientific or clinical environments. MRI of the lung with appropriate combinations of these sequences comprises morphological and functional imaging aspects in a single examination. It serves in difficult clinical problems encountered in daily routine, such as assessment of the mediastinum and chest wall, and even might challenge molecular imaging techniques in the near future. Conclusion This article helps new users to implement appropriate protocols on their own MRI platforms. Main Messages • MRI of the lung can be readily performed on state-of-the-art 1.5-T MRI scanners. • Protocol suggestions based on the available literature facilitate its use for routine • MRI offers solutions for complicated thoracic masses with atelectasis and chest wall invasion. • MRI is an option for paediatrics and science when CT is contra-indicate

Considerations about quality in model-driven engineering

The final publication is available at Springer via http://dx.doi.org/10.1007/s11219-016-9350-6The virtue of quality is not itself a subject; it depends on a subject. In the software engineering field, quality means good software products that meet customer expectations, constraints, and requirements. Despite the numerous approaches, methods, descriptive models, and tools, that have been developed, a level of consensus has been reached by software practitioners. However, in the model-driven engineering (MDE) field, which has emerged from software engineering paradigms, quality continues to be a great challenge since the subject is not fully defined. The use of models alone is not enough to manage all of the quality issues at the modeling language level. In this work, we present the current state and some relevant considerations regarding quality in MDE, by identifying current categories in quality conception and by highlighting quality issues in real applications of the model-driven initiatives. We identified 16 categories in the definition of quality in MDE. From this identification, by applying an adaptive sampling approach, we discovered the five most influential authors for the works that propose definitions of quality. These include (in order): the OMG standards (e.g., MDA, UML, MOF, OCL, SysML), the ISO standards for software quality models (e.g., 9126 and 25,000), Krogstie, Lindland, and Moody. We also discovered families of works about quality, i.e., works that belong to the same author or topic. Seventy-three works were found with evidence of the mismatch between the academic/research field of quality evaluation of modeling languages and actual MDE practice in industry. We demonstrate that this field does not currently solve quality issues reported in industrial scenarios. The evidence of the mismatch was grouped in eight categories, four for academic/research evidence and four for industrial reports. These categories were detected based on the scope proposed in each one of the academic/research works and from the questions and issues raised by real practitioners. We then proposed a scenario to illustrate quality issues in a real information system project in which multiple modeling languages were used. For the evaluation of the quality of this MDE scenario, we chose one of the most cited and influential quality frameworks; it was detected from the information obtained in the identification of the categories about quality definition for MDE. We demonstrated that the selected framework falls short in addressing the quality issues. Finally, based on the findings, we derive eight challenges for quality evaluation in MDE projects that current quality initiatives do not address sufficiently.F.G, would like to thank COLCIENCIAS (Colombia) for funding this work through the Colciencias Grant call 512-2010. This work has been supported by the Gene-ralitat Valenciana Project IDEO (PROMETEOII/2014/039), the European Commission FP7 Project CaaS (611351), and ERDF structural funds.Giraldo-Velásquez, FD.; España Cubillo, S.; Pastor López, O.; Giraldo, WJ. (2016). Considerations about quality in model-driven engineering. Software Quality Journal. 1-66. https://doi.org/10.1007/s11219-016-9350-6S166(1985). Iso information processing—documentation symbols and conventions for data, program and system flowcharts, program network charts and system resources charts. ISO 5807:1985(E) (pp. 1–25).(2011). Iso/iec/ieee systems and software engineering – architecture description. ISO/IEC/IEEE 42010:2011(E) (Revision of ISO/IEC 42010:2007 and IEEE Std 1471-2000) (pp. 1–46).Abran, A., Moore, J.W., Bourque, P., Dupuis, R., & Tripp, L.L. (2013). Guide to the Software Engineering Body of Knowledge (SWEBOK) version 3 public review. IEEE. ISO Technical Report ISO/IEC TR 19759.Agner, L.T.W., Soares, I.W., Stadzisz, P.C., & Simão, J.M. (2013). A brazilian survey on {UML} and model-driven practices for embedded software development. Journal of Systems and Software, 86(4), 997–1005. {SI} : Software Engineering in Brazil: Retrospective and Prospective Views.Amstel, M.F.V. (2010). The right tool for the right job: assessing model transformation quality. pages 69–74. Affiliation: Eindhoven University of Technology, P.O. Box 513, 5600 MB, Eindhoven, Netherlands. Cited By (since 1996):1.Aranda, J., Damian, D., & Borici, A. (2012). Transition to model-driven engineering: what is revolutionary, what remains the same?. In Proceedings of the 15th international conference on model driven engineering languages and systems, MODELS’12 (pp. 692–708). Berlin, Heidelberg: Springer.Arendt, T., & Taentzer, G. (2013). A tool environment for quality assurance based on the eclipse modeling framework. Automated Software Engineering, 20(2), 141–184.Atkinson, C., Bunse, C., & Wüst, J. (2003). Driving component-based software development through quality modelling, volume 2693. Cited By (since 1996):3.Baker, P., Loh, S., & Weil, F. (2005). Model-driven engineering in a large industrial context—motorola case study. In Briand, L., & Williams, C. (Eds.) Model Driven Engineering Languages and Systems, volume 3713 of Lecture Notes in Computer Science (pp. 476–491). Berlin, Heidelberg: Springer.Barišić, A., Amaral, V., Goulão, M., & Barroca, B. (2011). Quality in use of domain-specific languages: a case study. In Proceedings of the 3rd ACM SIGPLAN workshop on evaluation and usability of programming languages and tools, PLATEAU ’11 (pp. 65–72). New York: ACM.Becker, J., Bergener, P., Breuker, D., & Rackers, M. (2010). Evaluating the expressiveness of domain specific modeling languages using the bunge-wand-weber ontology. In 2010 43rd Hawaii international conference on system sciences (HICSS) (pp. 1–10).Bertrand Portier, L.A. (2009). Model driven development misperceptions and challenges.Bézivin, J., & Kurtev, I. (2005). Model-based technology integration with the technical space concept. In Proceedings of the Metainformatics Symposium: Springer.Brambilla, M. (2016). How mature is of model-driven engineering as an engineering discipline @ONLINE.Brambilla, M., & Fraternali, P. (2014). Large-scale model-driven engineering of web user interaction: The webml and webratio experience. Science of Computer Programming, 89 Part B(0), 71 – 87. Special issue on Success Stories in Model Driven Engineering.Brown, A. (2009). Simple and practical model driven architecture (mda) @ONLINE.Bruel, J.-M., Combemale, B., Ober, I., & Raynal, H. (2015). Mde in practice for computational science. Procedia Computer Science, 51, 660–669.Budgen, D., Burn, A.J., Brereton, O.P., Kitchenham, B.A., & Pretorius, R. (2011). Empirical evidence about the uml: a systematic literature review. Software: Practice and Experience, 41(4), 363–392.Burden, H., Heldal, R., & Whittle, J. (2014). Comparing and contrasting model-driven engineering at three large companies. In Proceedings of the 8th ACM/IEEE International Symposium on Empirical Software Engineering and Measurement, ESEM ’14 (pp. 14:1–14:10). New York: ACM.Cabot, J. Has mda been abandoned (by the omg)?Cabot, J. (2009). Modeling will be commonplace in three years time @ONLINE.Cachero, C., Poels, G., Calero, C., & Marhuenda, Y. (2007). Towards a Quality-Aware Engineering Process for the Development of Web Applications. Working Papers of Faculty of Economics and Business Administration, Ghent University, Belgium 07/462, Ghent University, Faculty of Economics and Business Administration.Challenger, M., Kardas, G., & Tekinerdogan, B. (2015). A systematic approach to evaluating domain-specific modeling language environments for multi-agent systems. Software Quality Journal, 1–41.Chaudron, M.V., Heijstek, W., & Nugroho, A. (2012). How effective is uml modeling? Software & Systems Modeling, 11(4), 571–580. J2: Softw Syst Model.Chenouard, R., Granvilliers, L., & Soto, R. (2008). Model-driven constraint programming. pages 236–246. Affiliation: CNRS, LINA, Universit de Nantes, France; Affiliation: Pontificia Universidad Catlica de, Valparaiso, Chile. Cited By (since 1996):8.Clark, T., & Muller, P.-A. (2012). Exploiting model driven technology: a tale of two startups. Software and Systems Modeling, 11(4), 481–493.Corneliussen, L. (2008). What do you think of model-driven software development?Costal, D., Gómez, C., & Guizzardi, G. (2011). Formal semantics and ontological analysis for understanding subsetting, specialization and redefinition of associations in uml. In Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics), 6998 LNCS:189–203. cited By (since 1996)3.Cruz-Lemus, J.A., Maes, A., Género, M., Poels, G., & Piattini, M. (2010). The impact of structural complexity on the understandability of uml statechart diagrams. Information Sciences, 180(11), 2209–2220. Cited By (since 1996):14.Cuadrado, J.S., Izquierdo, J.L.C., & Molina, J.G. (2014). Applying model-driven engineering in small software enterprises. Science of Computer Programming, 89 Part B(0), 176 – 198. Special issue on Success Stories in Model Driven Engineering.Da Silva, A.R. (2015). Model-driven engineering: a survey supported by the unified conceptual model. Computer Languages Systems and Structures, 43, 139–155.Da Silva Teixeira, D.G.M., Quirino, G.K., Gailly, F., De Almeida Falbo, R., Guizzardi, G., & Perini Barcellos, M. (2016). PoN-S: a Systematic Approach for Applying the Physics of Notation (PoN), (pp. 432–447). Cham: Springer International Publishing.Davies, I., Green, P., Rosemann, M., Indulska, M., & Gallo, S. (2006). How do practitioners use conceptual modeling in practice? Data and Knowledge Engineering, 58(3), 358 – 380. Including the special issue : {ER} 2004ER 2004.Davies, J., Milward, D., Wang, C.-W., & Welch, J. (2015). Formal model-driven engineering of critical information systems. Science of Computer Programming, 103(0), 88 – 113. Selected papers from the First International Workshop on Formal Techniques for Safety-Critical Systems (FTSCS 2012).De Oca, I.M.-M., Snoeck, M., Reijers, H.A., & Rodríguez-Morffi, A. (2015). A systematic literature review of studies on business process modeling quality. Information and Software Technology, 58, 187–205.DenHaan, J. (2009). 8 reasons why model driven development is dangerous @ONLINE.DenHaan, J. (2010). Model driven engineering vs the commando pattern @ONLINE.DenHaan, J. (2011a). Why aren’t we all doing model driven development yet @ONLINE.DenHaan, J. (2011b). Why there is no future model driven development @ONLINE.Di Ruscio, D., Iovino, L., & Pierantonio, A. (2013). Managing the coupled evolution of metamodels and textual concrete syntax specifications. cited By (since 1996)0.Dijkman, R.M., Dumas, M., & Ouyang, C. (2008). Semantics and analysis of business process models in {BPMN}. Information and Software Technology, 50(12), 1281–1294.Domínguez-Mayo, F.J., Escalona, M.J., Mejías, M., Ramos, I., & Fernández, L. (2011). A framework for the quality evaluation of mdwe methodologies and information technology infrastructures. International Journal of Human Capital and Information Technology Professionals, 2(4), 11–22.Domínguez-Mayo, F.J., Escalona, M.J., Mejías, M., & Torres, A.H. (2010). A quality model in a quality evaluation framework for mdwe methodologies. pages 495–506. Affiliation: Departamento de Lenguajes y Sistemas Informíticos, University of Seville, Seville, Spain., Cited By (since 1996):1.Dubray, J.-J. (2011). Why did mde miss the boat?.Escalona, M.J., Gutiérrez, J.J., Pérez-Pérez, M., Molina, A., Domínguez-Mayo, E., & Domínguez-Mayo, F.J. (2011). Measuring the Quality of Model-Driven Projects with NDT-Quality, (pp. 307–317). New York: Springer.Espinilla, M., Domínguez-Mayo, F.J., Escalona, M.J., Mejías, M., Ross, M., & Staples, G. (2011). A Method Based on AHP to Define the Quality Model of QuEF (Vol. 123, pp. 685–694). Berlin, Heidelberg: Springer.Fabra, J., Castro, V.D., Álvarez, P., & Marcos, E. (2012). Automatic execution of business process models: exploiting the benefits of model-driven engineering approaches. Journal of Systems and Software, 85(3), 607–625. Novel approaches in the design and implementation of systems/software architecture.Falkenberg, E.D., Hesse, W., Lindgreen, P., Nilsson, B.E., Oei, J.L.H., Rolland, C., Stamper, R.K., Assche, F.J.M.V., Verrijn-Stuart, A.A., & Voss, K. (1996). Frisco: a framework of information system concepts. Technical report, The IFIP WG 8. 1 Task Group FRISCO.Fettke, P., Houy, C., Vella, A.-L., & Loos, P. (2012). Towards the Reconstruction and Evaluation of Conceptual Model Quality Discourses – Methodical Framework and Application in the Context of Model Understandability, volume 113 of Lecture Notes in Business Information Processing, chapter 28, pages 406–421, Springer, Berlin, Heidelberg.Finnie, S. (2015). Modeling community: Are we missing something?Fournier, C. (2008). Is uml [email protected], R., & Rumpe, B. (2007). Model-driven development of complex software: a research roadmap. In Future of Software Engineering, 2007, FOSE ’07 (pp. 37–54).Gallego, M., Giraldo, F.D., & Hitpass, B. (2015). Adapting the pbec-otss software selection approach for bpm suites: an application case. In 2015 34th International Conference of the Chilean Computer Science Society (SCCC) (pp. 1–10).Galvão, I., & Goknil, A. (2007). Survey of traceability approaches in model-driven engineering. cited By (since 1996)22.Giraldo, F., España, S., Giraldo, W., & Pastor, O. (2015). Modelling language quality evaluation in model-driven information systems engineering: a roadmap. In 2015 IEEE 9th International Conference on Research Challenges in Information Science (RCIS) (pp. 64–69).Giraldo, F., España, S., & Pastor, O. (2014). Analysing the concept of quality in model-driven engineering literature: a systematic review. In 2014 IEEE Eighth International Conference on Research Challenges in Information Science (RCIS) (pp. 1–12).Giraldo, F.D., España, S., & Pastor, O. (2016). Evidences of the mismatch between industry and academy on modelling language quality evaluation. arXiv: 1606.02025 .González, C., & Cabot, J. (2014). Formal verification of static software models in mde: a systematic review. Information and Software Technology, 56(8), 821–838. cited By (since 1996)0.González, C.A., Büttner, F., Clarisó, R., & Cabot, J. (2012). Emftocsp: a tool for the lightweight verification of emf models. pages 44–50. Affiliation: cole des Mines de Nantes, INRIA, LINA, Nantes, France; Affiliation: Universitat Oberta de Catalunya, Barcelona, Spain. Cited By (since 1996):1.Gorschek, T., Tempero, E., & Angelis, L. (2014). On the use of software design models in software development practice: an empirical investigation. Journal of Systems and Software, 95(0), 176– 193.Goulão, M., Amaral, V., & Mernik, M. (2016). Quality in model-driven engineering: a tertiary study. Software Quality Journal, 1–33.Grobshtein, Y., & Dori, D. (2011). Generating sysml views from an opm model: design and evaluation. Systems Engineering, 14(3), 327–340.Haan, J.d. (2008). 8 reasons why model-driven approaches (will) fail.Harel, D., & Rumpe, B. (2000). Modeling languages: Syntax, semantics and all that stuff, part i: The basic stuff, Israel. Technical report Jerusalem Israel.Harel, D., & Rumpe, B. (2004). Meaningful modeling: what’s the semantics of semantics? Computer, 37(10), 64–72.Hebig, R., & Bendraou, R. (2014). On the need to study the impact of model driven engineering on software processes. In Proceedings of the 2014 International Conference on Software and System Process, ICSSP 2014 (pp. 164–168). New York: ACM.Heidari, F., & Loucopoulos, P. (2014). Quality evaluation framework (qef): modeling and evaluating quality of business processes. International Journal of Accounting Information Systems, 15(3), 193–223. Business Process Modeling.Heymans, P., Schobbens, P.Y., Trigaux, J.C., Bontemps, Y., Matulevicius, R., & Classen, A. (2008). Evaluating formal properties of feature diagram languages. Software, IET, 2(3), 281–302. ID 2.Hindawi, M., Morel, L., Aubry, R., & Sourrouille, J.-L. (2009). Description and Implementation of a UML Style Guide (Vol. 5421, pp. 291–302). Berlin: Springer.Hoang, D. (2012). Current limitations of mdd and its implications @ONLINE.Hodges, W. (2013). Model theory Zalta, E.N. (Ed.) The Stanford Encyclopedia of Philosophy. Fall 2013 edition.Hutchinson, J., Rouncefield, M., & Whittle, J. (2011a). Model-driven engineering practices in industry. In Proceedings of the 33rd International Conference on Software Engineering, ICSE’11 (pp. 633–642). New York: ACM.Hutchinson, J., Whittle, J., & Rouncefield, M. (2014). Model-driven engineering practices in industry: social, organizational and managerial factors that lead to success or failure. Science of Computer Programming, 89 Part B(0), 144–161. Special issue on Success Stories in Model Driven Engineering.Hutchinson, J., Whittle, J., Rouncefield, M., & Kristoffersen, S. (2011b). Empirical assessment of mde in industry. In Proceedings of the 33rd International Conference on Software Engineering, ICSE’11 (pp. 471–480). New York: ACM.Igarza, I.M.H., Boada, D.H.G., & Valdés, A.P. (2012). Una introducción al desarrollo de software dirigido por modelos. Serie Científica, 5(3).ISO/IEC (2001). ISO/IEC 9126. Software engineering—Product quality. ISO/IEC.Izurieta, C., Rojas, G., & Griffith, I. (2015). Preemptive management of model driven technical debt for improving software quality. In Proceedings of the 11th International ACM SIGSOFT Conference on Quality of Software Architectures, QoSA’15 (pp. 31–36). New York: ACM.Jalali, S., & Wohlin, C. (2012). Systematic literature studies: Database searches vs. backward snowballing. In Proceedings of the ACM-IEEE International Symposium on Empirical Software Engineering and Measurement, ESEM’12 (pp. 29–38). New York: ACM.Kahraman, G., & Bilgen, S. (2013). A framework for qualitative assessment of domain-specific languages. Software & Systems Modeling, 1–22.Kessentini, M., Langer, P., & Wimmer, M. (2013). Searching models, modeling search: On the synergies of sbse and mde (pp. 51–54).Kitchenham, B., & Charters, S. (2007). Guidelines for performing Systematic Literature Reviews in Software Engineering. Technical Report EBSE 2007-001, Keele University and Durham University Joint Report.Kitchenham, B., Pfleeger, S., Pickard, L., Jones, P., Hoaglin, D., El Emam, K., & Rosenberg, J. (2002). Preliminary guidelines for empirical research in software engineering. IEEE Transactions on Software Engineering, 28(8), 721–734.Klinke, M. (2008). Do you use mda/mdd/mdsd, any kind of model-driven approach? Will it be the future?Köhnlein, J. (2013). Eclipse diagram editors from a user’s perspective.Kolovos, D.S., Paige, R.F., & Polack, F.A. (2008). The grand challenge of scalability for model driven engineering. In Models in Software Engineering (pp. 48–53): Springer.Kolovos, D.S., Rose, L.M., Matragkas, N., Paige, R.F., Guerra, E., Cuadrado, J.S., De Lara, J., Ráth, I., Varró, D., Tisi, M., & Cabot, J. (2013). A research roadmap towards achieving scalability in model driven engineering. In Proceedings of the Workshop on Scalability in Model Driven Engineering, BigMDE’13 (pp. 2:1–2:10). New York: ACM.Krill, P. (2016). Uml to be ejected from microsoft visual studio (infoworld).Krogstie, J. (2012a). Model-based development and evolution of information systems: a quality approach, Springer Publishing Company, Incorporated.Krogstie, J. (2012b). Quality of modelling languages, (pp. 249–280). London: Springer.Krogstie, J. (2012c). Quality of models, (pp. 205–247). London: Springer.Krogstie, J. (2012d). Specialisations of SEQUAL, (pp. 281–326). London: Springer.Krogstie, J., Lindland, O.I., & Sindre, G. (1995). Defining quality aspects for conceptual models. In Proceedings of the IFIP International Working Conference on Information System Concepts: Towards a Consolidation of Views (pp. 216–231). London: Chapman & Hall, Ltd.Kruchten, P. (2000). The rational unified process: an introduction, 2nd edn. Boston: Addison-Wesley Longman Publishing Co., Inc.Kruchten, P., Nord, R., & Ozkaya, I. (2012). Technical debt: from metaphor to theory and practice. Software, IEEE, 29(6), 18–21.Kulkarni, V., Reddy, S., & Rajbhoj, A. (2010). Scaling up model driven engineering – experience and lessons learnt. In Petriu, D., Rouquette, N., & Haugen, y. (Eds.) Model Driven Engineering Languages and Systems, volume 6395 of Lecture Notes in Computer Science (pp. 331–345). Berlin, Heidelberg: Springer.Laguna, M.A., & Marqués, J.M. (2010). Uml support for designing software product lines: the package merge mechanism, 16(17), 2313–2332.Lange, C. (2007a). Model size matters. Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics), 4364 LNCS:211–216. cited By (since 1996)1.Lange, C., & Chaudron, M. (2005). Managing Model Quality in UML-Based Software Development. In 13th IEEE International Workshop on Technology and Engineering Practice, 2005 (pp. 7–16).Lange, C., Chaudron, M.R.V., Muskens, J., Somers, L.J., & Dortmans, H.M. (2003). An empirical investigation in quantifying inconsistency and incompleteness of uml designs. In Incompleteness of UML Designs, Proceedings Workshop on Consistency Problems in UML-based Software Development, 6th International Conference on Unified Modeling Language, UML, 2003.Lange, C., DuBois, B., Chaudron, M., & Demeyer, S. (2006). An experimental investigation of uml modeling conventions. In Nierstrasz, O., Whittle, J., Harel, D., & Reggio, G. (Eds.) Model Driven Engineering Languages and Systems, volume 4199 of Lecture Notes in Computer Science (pp. 27–41). Berlin, Heidelberg: Springer.Lange, C.F.J., & Chaudron, M.R.V. (2006). Effe

Response of the mouse lung transcriptome to welding fume: effects of stainless and mild steel fumes on lung gene expression in A/J and C57BL/6J mice

<p>Abstract</p> <p>Background</p> <p>Debate exists as to whether welding fume is carcinogenic, but epidemiological evidence suggests that welders are an at risk population for the development of lung cancer. Recently, we found that exposure to welding fume caused an acutely greater and prolonged lung inflammatory response in lung tumor susceptible A/J versus resistant C57BL/6J (B6) mice and a trend for increased tumor incidence after stainless steel (SS) fume exposure. Here, our objective was to examine potential strain-dependent differences in the regulation and resolution of the lung inflammatory response induced by carcinogenic (Cr and Ni abundant) or non-carcinogenic (iron abundant) metal-containing welding fumes at the transcriptome level.</p> <p>Methods</p> <p>Mice were exposed four times by pharyngeal aspiration to 5 mg/kg iron abundant gas metal arc-mild steel (GMA-MS), Cr and Ni abundant GMA-SS fume or vehicle and were euthanized 4 and 16 weeks after the last exposure. Whole lung microarray using Illumina Mouse Ref-8 expression beadchips was done.</p> <p>Results</p> <p>Overall, we found that tumor susceptibility was associated with a more marked transcriptional response to both GMA-MS and -SS welding fumes. Also, Ingenuity Pathway Analysis revealed that gene regulation and expression in the top molecular networks differed between the strains at both time points post-exposure. Interestingly, a common finding between the strains was that GMA-MS fume exposure altered behavioral gene networks. In contrast, GMA-SS fume exposure chronically upregulated chemotactic and immunomodulatory genes such as <it>CCL3</it>, <it>CCL4</it>, <it>CXCL2</it>, and <it>MMP12 </it>in the A/J strain. In the GMA-SS-exposed B6 mouse, genes that initially downregulated cellular movement, hematological system development/function and immune response were involved at both time points post-exposure. However, at 16 weeks, a transcriptional switch to an upregulation for neutrophil chemotactic genes was found and included genes such as <it>S100A8</it>, <it>S100A9 </it>and <it>MMP9</it>.</p> <p>Conclusions</p> <p>Collectively, our results demonstrate that lung tumor susceptibility may predispose the A/J strain to a prolonged dysregulation of immunomodulatory genes, thereby delaying the recovery from welding fume-induced lung inflammation. Additionally, our results provide unique insight into strain- and welding fume-dependent genetic factors involved in the lung response to welding fume.</p

Challenges and strategies of children and adolescents with inflammatory bowel disease: a qualitative examination

© 2007 Nicholas et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens