Adhesion between oppositely-charged polyelectrolytes

The adhesion between a grafted polyelectrolyte layer (brush) and a gel of an oppositely charged polyelectrolyte has been measured as a function of applied pressure, and the interface has been traced using neutron reflectometry. The interface (in aqueous medium at pH 6) between the (polycationic) brush and the (polyanionic) gel has a limited pressure-dependence, with a small amount of deformation of the interface at the brush-gel contact. Brushes with a dry thickness of up to 13 nm exhibit weak adhesion (measured using a mechanical force tester) with an adhesive failure when the gel is detached. Thicker brushes result in the gel exhibiting cohesive failure. Reversing the geometry, whereby a polycationic brush is replaced with a polyanion and the polyanionic gel is replaced with a polycation reveals that the pH-dependence of the adhesion is moderately symmetric about pH 6, but that the maximum force required to separate the polycation gel from the polyanion brush over the range of pH is greater than that for the polycation brush and polyanion gel. The polyanion used is poly(methacrylic acid) (PMAA) and polycations of poly[2-(diethyl amino)ethyl methacrylate] (PDEAEMA) and poly[2-(dimethyl amino)ethyl methacrylate] (PDMAEMA) were used

A Pain Research Agenda for the 21st Century

Chronic pain represents an immense clinical problem. With tens of millions of people in the United States alone suffering from the burden of debilitating chronic pain, there is a moral obligation to reduce this burden by improving the understanding of pain and treatment mechanisms, developing new therapies, optimizing and testing existing therapies, and improving access to evidence-based pain care. Here, we present a goal-oriented research agenda describing the American Pain Society’s vision for pain research aimed at tackling the most pressing issues in the field

Aquatic community response to volcanic eruptions on the Ecuadorian Andean flank: evidence from the palaeoecological record

Aquatic ecosystems in the tropical Andes are under increasing pressure from human modification of the landscape (deforestation and dams) and climatic change (increase of extreme events and 1.5 °C on average temperatures are projected for AD 2100). However, the resilience of these ecosystems to perturbations is poorly understood. Here we use a multi-proxy palaeoecological approach to assess the response of aquatic ecosystems to a major mechanism for natural disturbance, volcanic ash deposition. Specifically, we present data from two Neotropical lakes located on the eastern Andean flank of Ecuador. Laguna Pindo (1°27.132′S–78°04.847′W) is a tectonically formed closed basin surrounded by a dense mid-elevation forest, whereas Laguna Baños (0°19.328′S–78°09.175′W) is a glacially formed lake with an inflow and outflow in high Andean Páramo grasslands. In each lake we examined the dynamics of chironomids and other aquatic and semi-aquatic organisms to explore the effect of thick (> 5 cm) volcanic deposits on the aquatic communities in these two systems with different catchment features. In both lakes past volcanic ash deposition was evident from four large tephras dated to c.850 cal year BP (Pindo), and 4600, 3600 and 1500 cal year BP (Baños). Examination of the chironomid and aquatic assemblages before and after the ash depositions revealed no shift in composition at Pindo, but a major change at Baños occurred after the last event around 1500 cal year BP. Chironomids at Baños changed from an assemblage dominated by Pseudochironomus and Polypedilum nubifer-type to Cricotopus/Paratrichocladius type-II, and such a dominance lasted for approximately 380 years. We suggest that, despite potential changes in the water chemistry, the major effect on the chironomid community resulted from the thickness of the tephra being deposited, which acted to shallow the water body beyond a depth threshold. Changes in the aquatic flora and fauna at the base of the trophic chain can promote cascade effects that may deteriorate the ecosystem, especially when already influenced by human activities, such as deforestation and dams, which is frequent in the high Andes

Memory Phenotype CD4 T Cells Undergoing Rapid, Nonburst-Like, Cytokine-Driven Proliferation Can Be Distinguished from Antigen-Experienced Memory Cells

Contrary to the current paradigm that nearly all memory T cells proliferate in response to antigenic stimulation, this paper shows that an important population of CD4 T lymphocytes achieves memory/effector status independent of antigenic stimulation

Estimating cumulative pathway effects on risk for age-related macular degeneration using mixed linear models

BACKGROUND: Age-related macular degeneration (AMD) is the leading cause of irreversible visual loss in the elderly in developed countries and typically affects more than 10 % of individuals over age 80. AMD has a large genetic component, with heritability estimated to be between 45 % and 70 %. Numerous variants have been identified and implicate various molecular mechanisms and pathways for AMD pathogenesis but those variants only explain a portion of AMD’s heritability. The goal of our study was to estimate the cumulative genetic contribution of common variants on AMD risk for multiple pathways related to the etiology of AMD, including angiogenesis, antioxidant activity, apoptotic signaling, complement activation, inflammatory response, response to nicotine, oxidative phosphorylation, and the tricarboxylic acid cycle. While these mechanisms have been associated with AMD in literature, the overall extent of the contribution to AMD risk for each is unknown. METHODS: In a case–control dataset with 1,813 individuals genotyped for over 600,000 SNPs we used Genome-wide Complex Trait Analysis (GCTA) to estimate the proportion of AMD risk explained by SNPs in genes associated with each pathway. SNPs within a 50 kb region flanking each gene were also assessed, as well as more distant, putatively regulatory SNPs, based on DNaseI hypersensitivity data from ocular tissue in the ENCODE project. RESULTS: We found that 19 previously associated AMD risk SNPs contributed to 13.3 % of the risk for AMD in our dataset, while the remaining genotyped SNPs contributed to 36.7 % of AMD risk. Adjusting for the 19 risk SNPs, the complement activation and inflammatory response pathways still explained a statistically significant proportion of additional risk for AMD (9.8 % and 17.9 %, respectively), with other pathways showing no significant effects (0.3 % – 4.4 %). DISCUSSION: Our results show that SNPs associated with complement activation and inflammation significantly contribute to AMD risk, separately from the risk explained by the 19 known risk SNPs. We found that SNPs within 50 kb regions flanking genes explained additional risk beyond genic SNPs, suggesting a potential regulatory role, but that more distant SNPs explained less than 0.5 % additional risk for each pathway. CONCLUSIONS: From these analyses we find that the impact of complement SNPs on risk for AMD extends beyond the established genome-wide significant SNPs. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12859-015-0760-4) contains supplementary material, which is available to authorized users

Protecting children in low-income and middle-income countries from COVID-19

CITATION: Ahmed, S. et al. 2020. Protecting children in low-income and middle-income countries from COVID-19. BMJ Global Health, 5:e002844. doi:10.1136/bmjgh-2020-002844.The original publication is available at https://gh.bmj.comA saving grace of the COVID-19 pandemic in high-income and upper middle-income countries has been the relative sparing of children. As the disease spreads across low-income and middle-income countries (LMICs), long-standing system vulnerabilities may tragically manifest, and we worry that children will be increasingly impacted, both directly and indirectly. Drawing on our shared child pneumonia experience globally, we highlight these potential impacts on children in LMICs and propose actions for a collective response.https://gh.bmj.com/content/5/5/e002844.abstractPublisher's versio

Rapamycin Pharmacokinetic and Pharmacodynamic Relationships in Osteosarcoma: A Comparative Oncology Study in Dogs

Signaling through the mTOR pathway contributes to growth, progression and chemoresistance of several cancers. Accordingly, inhibitors have been developed as potentially valuable therapeutics. Their optimal development requires consideration of dose, regimen, biomarkers and a rationale for their use in combination with other agents. Using the infrastructure of the Comparative Oncology Trials Consortium many of these complex questions were asked within a relevant population of dogs with osteosarcoma to inform the development of mTOR inhibitors for future use in pediatric osteosarcoma patients.This prospective dose escalation study of a parenteral formulation of rapamycin sought to define a safe, pharmacokinetically relevant, and pharmacodynamically active dose of rapamycin in dogs with appendicular osteosarcoma. Dogs entered into dose cohorts consisting of 3 dogs/cohort. Dogs underwent a pre-treatment tumor biopsy and collection of baseline PBMC. Dogs received a single intramuscular dose of rapamycin and underwent 48-hour whole blood pharmacokinetic sampling. Additionally, daily intramuscular doses of rapamycin were administered for 7 days with blood rapamycin trough levels collected on Day 8, 9 and 15. At Day 8 post-treatment collection of tumor and PBMC were obtained. No maximally tolerated dose of rapamycin was attained through escalation to the maximal planned dose of 0.08 mg/kg (2.5 mg/30 kg dog). Pharmacokinetic analysis revealed a dose-dependent exposure. In all cohorts modulation of the mTOR pathway in tumor and PBMC (pS6RP/S6RP) was demonstrated. No change in pAKT/AKT was seen in tumor samples following rapamycin therapy.Rapamycin may be safely administered to dogs and can yield therapeutic exposures. Modulation pS6RP/S6RP in tumor tissue and PBMCs was not dependent on dose. Results from this study confirm that the dog may be included in the translational development of rapamycin and potentially other mTOR inhibitors. Ongoing studies of rapamycin in dogs will define optimal schedules for their use in cancer and evaluate the role of rapamycin use in the setting of minimal residual disease

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

Observed controls on resilience of groundwater to climate variability in sub-Saharan Africa

Groundwater in sub-Saharan Africa supports livelihoods and poverty alleviation1,2, maintains vital ecosystems, and strongly influences terrestrial water and energy budgets. Yet the hydrological processes that govern groundwater recharge and sustainability—and their sensitivity to climatic variability—are poorly constrained4. Given the absence of firm observational constraints, it remains to be seen whether model-based projections of decreased water resources in dry parts of the region4 are justified. Here we show, through analysis of multidecadal groundwater hydrographs across sub-Saharan Africa, that levels of aridity dictate the predominant recharge processes, whereas local hydrogeology influences the type and sensitivity of precipitation–recharge relationships. Recharge in some humid locations varies by as little as five per cent (by coefficient of variation) across a wide range of annual precipitation values. Other regions, by contrast, show roughly linear precipitation–recharge relationships, with precipitation thresholds (of roughly ten millimetres or less per day) governing the initiation of recharge. These thresholds tend to rise as aridity increases, and recharge in drylands is more episodic and increasingly dominated by focused recharge through losses from ephemeral overland flows. Extreme annual recharge is commonly associated with intense rainfall and flooding events, themselves often driven by large-scale climate controls. Intense precipitation, even during years of lower overall precipitation, produces some of the largest years of recharge in some dry subtropical locations. Our results therefore challenge the ‘high certainty’ consensus regarding decreasing water resources in such regions of sub-Saharan Africa. The potential resilience of groundwater to climate variability in many areas that is revealed by these precipitation–recharge relationships is essential for informing reliable predictions of climate-change impacts and adaptation strategies