EC Contract Research Articles

Multiscale Immune System Simulator for the Onset of Type-2 Diabetes for use in online decision support and coaching tools

Event Abstract Back to Event Multiscale Immune System Simulator for the Onset of Type-2 Diabetes for use in online decision support and coaching tools Albert De Graaf1* 1 TNO, Risk Analysis for Products in Development, Netherlands Background: To empower patients to optimize lifestyle factors and compliance in intervention strategies, predictive personalised simulation models such as developed in the framework of the Virtual Physiological Human initiative (http://www.vph-institute.org/) are a potential important asset. Aim:The FP7 EU project MISSION-T2D aims to develop and validate a computer model incorporating genetic, metabolic, and nutritional data for the simulation and prediction of the onset and progression of T2D. The model should include immunological/inflammatory processes contributing to insulin resistance and beta cell function loss, functionally interacting with energy intake/expenditure-associated metabolic regulatory mechanisms. Methods: The overall architecture of the model interconnects and integrates an already established immune system simulator with newly developed and/or adapted discrete and continuous mathematical simulation models for relevant processes as detailed below. The model is programmed in ANSI/C. Results: Model sections are as follows: 1) GUT MICROBIOTA: predicts how different dietary components affect the relative abundance of important gut bacteria, thus influencing butyrate production, and thereby modulating TNF, IL-6 and IL-1β; 2) PANCREATIC BETA CELL employs mTOR signaling as a central mechanism and predicts the beta cell survival and –functionality as a function of concentration of macrophages, acivated macrophages, and beta cell antigenic proteins; 3) WHOLE BODY METABOLISM describes seven tissue compartments: brain, heart, liver, gastrointestinal tract, skeletal muscle, and adipose tissue, by dynamic mass balances for major cellular metabolic reactions involving glucose, lactate, pyruvate, alanine, free fatty acids, triglycerides, glycerol and ATP as driven by macronutrient meal intake and hormonal control by insulin, glucagon and epinphrine; 4) PHYSICAL ACTIVITY predicts epinephrine concentration and IL-6 as a function of exercise intensity; 5) IMMUNE SYSTEM simulates Th differentiation and macrophage MA1/MA2 differentiation as a function of (and influencing) cytokine concentrations. The integrated model generates simulations of the integrated effects of physical activity and nutrition on metabolism and inflammation with 15 min time resolution and a maximum 6 months total time span. Conclusions: An integrated immune system-metabolism model relevant for simulation of the onset of type-2 diabetes was developed. This model combined with a personal health tracking system and other sources of data (personal health records, wearables, apps) should find application in mobile-based self management and diagnosis support tools. Acknowledgements This work was supported under the EC contract FP7-ICT-2011-9, No.600803 (MISSION-T2D). Website: http://www.mission-t2d.eu/ Keywords: Computer simulations of complex biological systems, Metaflammation, type-2 diabetes, Insulin Resistance, prediction Conference: 2nd Behaviour Change Conference: Digital Health and Wellbeing, London, United Kingdom, 24 Feb - 25 Feb, 2016. Presentation Type: Poster presentation Topic: Academic Citation: De Graaf A (2016). Multiscale Immune System Simulator for the Onset of Type-2 Diabetes for use in online decision support and coaching tools. Front. Public Health. Conference Abstract: 2nd Behaviour Change Conference: Digital Health and Wellbeing. doi: 10.3389/conf.FPUBH.2016.01.00084 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 27 Nov 2015; Published Online: 09 Jan 2016. * Correspondence: Dr. Albert De Graaf, TNO, Risk Analysis for Products in Development, Zeist, 3704 HE, Netherlands, albert.degraaf@tno.nl Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Albert De Graaf Google Albert De Graaf Google Scholar Albert De Graaf PubMed Albert De Graaf Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. 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Benthic habitats modelling and mapping of Galicia Bank (NE Atlantic)

Benthic habitats modelling and mapping of Galicia Bank (NE Atlantic)

Implantation Temperature Effects on the Nanoscale Optical Pattern Fabrication in a-SiC:H Films by Ga+Focused Ion Beams

This work has been supported by the European Community as an Integrating Activity “Support of Public and Industrial Research using Ion Beam Technology (SPIRIT)” under EC contract No. 227012. The support of EC funded project BG051PO001/3.3.-05.001 for this publication is gratefully acknowledged. The Marie Curie Fellowship for T. Tsvetkova was also supported by the European Community under the contract PIEF-GA-2009-251845. The help of D. Dimova-Malinovska and O. Angelov with the samples preparation and useful discussions is also gratefully acknowledged.

Contract Formation and Mistake in European Contract Law: A Genetic Comparison of Transnational Model Rules

The article examines how the rules on formation of contract and on mistake, contained in the various transnational model rules that have been published over the past two decades, have taken shape. The approach adopted here is based on an analysis of the ‘textual stratification’ of European private law. The relevant instruments (Convention on Contracts for the International Sale of Goods, Principles of European Contract Law, UNIDROIT Principles of International Commercial Contracts, Draft Common Frame of Reference, Principes contractuels communs) are analysed and compared in their historical sequence. To what extent and why have the texts been transformed in the process? The article demonstrates that there is a very considerable common ground reflecting the state of the art of comparative research in these fields over the past hundred years. It also highlights issues on which consensus must still be reached and it suggests patterns towards reaching such consensus. It is argued that the Principles of European Contract Law, rather than the Draft Common Frame of Reference, should provide the point of departure for future discussions. The scene for the article is set by a critical examination of the concepts of contract and legal act, as used in the Draft Common Frame of Reference. * Nils Jansen is Professor of Roman Law, Legal History, German and European Private Law at the Institute for Legal History, Westfalische Wilhelms-Universitat Munster. Email: nils.jansen@uni-muenster.de Reinhard Zimmermann is Director at the Max Planck Institute for Comparative and International Private Law, Hamburg. Email: r.zimmermann@mpipriv.de. A German version of this article has appeared in (2010) 210 Archiv fur die civilistische Praxis (hereafter AcP) 196. We would like to thank Sandy Steel, Cambridge, for assisting us with the preparation of the English text. The model rules under discussion are abbreviated throughout as follows: ACQP I/II: the Research Group on the Existing EC Private Law (Acquis Group), Principles of the Existing EC Contract Law (Acquis Principles): Contract I (Sellier 2007); Contract II (Sellier 2009). DCFR: C von Bar and E Clive (eds), Principles, Definitions and Model Rules of European Private Law: Draft Common Frame of Reference (DCFR), Full Edition, 6 vols (Sellier 2009). PCC: Association Henri Capitant, Societe de Legislation Comparee, Projet de Cadre Commun de Reference—Principes contractuels communs (Societe de Legislation Comparee 2008); for an English version (black-letter rules only) see B Fauvarque-Cosson and D Mazeaud (eds), European Contract Law. Materials for a Common Frame of Reference: Terminology, Guiding Principles, Model Rules (Sellier 2008) 573–614. PECL: Principles of European Contract Law, O Lando and H Beale (eds), Principles of European Contract Law, Parts I and II (Kluwer 2000); O Lando, E Clive, A Prum and R Zimmermann (eds), Principles of European Contract Law, Part III (Kluwer 2003). The Author 2011. Published by Oxford University Press. All rights reserved. For permissions, please contact the authors. Oxford Journal of Legal Studies Advance Access published September 20, 2011 at U nirsity of O lo Lrary on S etem er 2, 2011 ojls.oxjournals.org D ow nladed fom

The European Union Development of European Property Law

These are exiting times for European Private Law. In 2007 and 2008 the Study Group on a European Civil Code and the Research Group on Existing EC Contract Law presented the outline editions of the Draft Common Frame of Reference (DCFR), completed in 2009 with the full edition. Although the DCFR mainly concerns contract law, other fields of private law are also included. These include tort, unjust enrichment and property law. Starting out as a contract law project to answer the call of the European Commission for a more coherent contract law, the drafters soon saw that other fields of private had to be in included to complete the effectiveness of the set of principles and rules they were preparing. The result is an impressive body of principles and rules that can serve as the basis for the development of future European Private Law.European Property law is a part of this development. For many decades the law of property law left alone mainly because the differences between the legal systems of the Member States were considered to be too diverse to reach easy harmonisation. Different from contract law where many legal systems share a common heritage or have developed in a similar direction over time, the law of property in each Member State has remained static and somewhat unique. When legal scholarship mostly focused on comparative law, the law of property was therefore less interesting to many. Of course, a select group of researchers in Europe also compared systems of property law and research results were often surprising. This research has led to the identification of princilpes and leading rules of property law, leaving many other aspects classiefied as technical rules. Such analysis enables us to move beyond the technical differences and focus on the making of European property law. Moreover, it also enables us to look beyond national law to European Union law and the effect this supranational system has on the property law systems of the Member State. Examples of these include initiatives in emmission trading, wills and succession and matrimonial property law. When considering the making of European Private Law, these effects should not be neglected. In fact, the political reality of making European private law often means that through technical regulation more effects can be achieved. This is therefore, not direct but indirect making of European Property Law. The following will provide a short discussion on the direct making of European Property Law after focusing on some prime examples of indirect making of European Property Law. Emission trading, wills and successions and matrimonial law will be used as examples of how often technical rules require substantive and doctrinal changes in the property law systems of the Member States.

Common Frame of Reference (CFR), the EU Consumer ACQUIS and European Property Law

When, at the end of 2007, the outline interim edition of the Draft Common Frame of Reference (DCFR) on European Contract Law was presented to the European Commission and at the beginning of 2008 to the European Parliament, the work of the joined network on European Private Law on the review of European Contract became public. From the very beginning of the European Commission’s initiatives to revise European private law, as can best be seen from the Green Paper of the European Commission on European Contract Law and the revision of the acquis: the way forward, the focus has been almost exclusively on contract law. However, already in the early proposals of the European Commission, aspects of property law have also been considered. These aspects concerned movable property law in the form of retention of title and possibly property security rights in respect to movables. Property law is part of the internal market. Freedom of ownership forms the basis of a free market economy, including the internal market of the European Union. The free movement of goods, persons, services and capital all require a well functioning property law that does not impose obstacles. If any of these obstacles are found, they can be removed through internal market law, even if these rules are national mandatory property law rules.The publication of the results of the Study Group on a European Civil Code and the Research Group on Existing EC Contract Law brings the need to take a closer look at some of the effects contract law has on the law of property. First, after a short discussion of the interrelatedness of contract and property, a closer look at the CFR from a property law point of view is taken. Second, the principles underlying the CFR are brought into relation with general principles underlying property law, which in most legal systems are the same as the principles underlying contract law. The analysis of this ‘core’ of the CFR will bring a short analysis of the property aspects that the CFR deals with and the direct effects on the law of property. Finally, an attempt is made to make the indirect influences of the CFR on the law of property visible. This is done through a short quantitative and qualitative survey of the existing EU Consumer Law Acquis that underlies the work of the Research Group on Existing EC Contract Law.

EC Financial Services and Contract Law – Developments 2007–2010

The contribution is a follow-up on the overview published in ERCL 2008, 45 and covers the latest developments from 2007 through the first half of 2010. The law with respect to prudential supervision has changed little; there are, however, changes underway as a reaction to the financial crisis (see section I). More importantly, however, contract law developed considerably. Important new legislation has been adopted in the area of commercial banking, while the Market in Financial Instruments Directive of 2004 (MiFID) and its transposition were at the centre of the last report. New legislation has now been adopted in the other two important sectors of banking business and thus the series of second generation of banking law directives is complete. In the area of bank loans, harmonisation has changed considerably with the new EU Consumer Credit Directive of 2008. In the area of the payment business, changes have been even more drastic, as virtually all payment instruments have now been harmonised with the new EU Payments Systems Directive of late 2007, and this not only for the consumer area. This directive now covers: credit transfers, credit and debit cards, and direct debits. The importance of the new material makes it necessary to concentrate on these two measures mainly (sections II and III) and to add only two short sections on important developments under the MiFID (section IV) and on some general considerations concerning the overall picture now reached in European Banking Contract Law (section V).

Analysis of the market for diesel PEM fuel cell auxiliary power units onboard long-haul trucks and of its implications for the large-scale adoption of PEM FCs

Proton exchange membrane fuel cells (PEM FCs) offer a promising alternative to internal combustion engines in road transport. During the last decade PEM FC research, development and demonstration (RD&D) activities have been steadily increasing worldwide, and targets have been set to begin their commercialisation in road transport by 2015–2020. However, there still is considerable uncertainty on whether these targets will actually be met. The picture is complex and market and technology issues are closely interlinked; investment in RD&D projects is essential but not sufficient; the development of suitable early markets is also necessary and policy is set to play an important role. Auxiliary power units (APUs) are generally regarded as one important early market for FCs in transport. This paper analyses the possible future market for diesel PEM FC APUs onboard long-haul trucks and its implications for the development of PEM FCs in general. The analysis, part of the project HyTRAN (EC Contract no. 502577), is aided by the use of a dynamic simulation model of technology and markets developed by the author. Results suggest that an interesting window of opportunity for diesel PEM FC APUs exists but this is subject to additional research particularly targeted at the rapid development of fuel processors.

Reiner Schulze (red.): Common Frame of Reference and Existing EC Contract Law

Reiner Schulze (red.): Common Frame of Reference and Existing EC Contract Law

Reiner Schulze (ed.), Common Frame of Reference and Existing EC Contract Law

Reiner Schulze (ed.), Common Frame of Reference and Existing EC Contract Law

The Legnaro National Laboratories of INFN

The Legnaro National Laboratories (LNL) are a research center that houses a system of ion sources, accelerators, and target stations dedicated to basic and applied research. LNL is one of the four national user facilities provided by the Istituto Nazionale di Fisica Nucleare in Italy, committed to support a high quality research program developed by outside users as well as by staff members. It is a European research infrastructure providing access to outside users within the EC contract EURONS RII3-CT-2004-506065.

Restating the Acquis Communautaire? A Critical Examination of the ‘Principles of the Existing EC Contract Law’

The article examines the ‘Principles of the Existing EC Contract Law’ (Acquis Principles) published by the European Research Group on the Existing EC Contract Law (Acquis Group), a key player within the academic network charged with the preparation of a ‘Common Frame of Reference’. The Acquis Principles may therefore have a considerable impact on the shape and development of EC Contract Law. It is argued that the Acquis Principles do not constitute merely a restatement, or systematic revision, of existing EC private law. To a significant extent, the Acquis Group has drafted ‘desirable rules’, based on ‘political’ decisions that may even entail a transformation towards a regulatory model of private law. At the same time, the Acquis Principles clearly demonstrate that the acquis communautaire is not a coherent system of contract law that can be taken to have emancipated itself from the acquis commun.

Decontamination of nuclear graphite

Graphite is used in gas-cooled reactors (e.g. AGR, MAGNOX, HTR) and Russian RMBK reactors as a moderator and reflector. About 250,000 Mg of irradiated graphite (i-graphite) has to be considered as radioactive waste in the next few centuries. Fission products and activation of impurities in the graphite contaminate this graphite during reactor operation. Key nuclides for waste management are Co-60 during decommissioning, if decommissioning is performed immediately after reactor shutdown, and the long living radionuclides 14C and 36Cl for long-term safety in the case of direct disposal. Most radioisotopes can, in principle, be removed by using the purification methods already applied during the manufacture of nuclear graphite. However, due to the same chemical behaviour as 12C, this does not seem to be applicable to 14C. Contaminated graphite cannot be stored in low-level surface disposal facilities such as Centre de L’Aube, in France, due to the long half-life of 14C [Millington, D.N., Sneyers, A., Mouliney, M.H., Abram, T., Brücher, H., 2006. Report on the International Regulation as regards HTR/VHTR Waste Management, Deliverable D-BF1.1 of the Raphael Project, EC Contract 516508, Confidential report]. Furthermore, the 14C activity of the graphite reflectors from the two German HTR reactors (AVR and THTR) would amount to more than 90% of the total 14C activity licensed for the underground disposal site Konrad in Germany for non-heat-generating radioactive waste [Brennecke, P., October 1993. Anforderungen an endzulagernde radioaktive Abfälle (Vorläufige Endlagerbedingungen, Stand: April 1990 in der Fassung vom Oktober 1993) – Schachtanlage Konrad –, BfS-ET-3/90-REV-2, Salzgitter, p. 51]. The burning of nuclear graphite would be an efficient method for volume reduction, but would not be accepted by the public as long as all the 14C were emitted into the atmosphere in the form of CO 2. The required separation of the 14C from the off-gas is difficult and not economic because this carbon isotope has the same chemical properties as the 12C from the graphite matrix. The solidification of the whole amount of CO 2 would cancel out the volume reduction advantage of burning. Thus, a process is required which benefits from the inhomogeneous distribution of the 14C in the graphite matrix leading to 14C-enriched and 14C-depleted off gas streams (Schmidt, P.C., 1979. Alternativen zur Verminderung der C-14-Emission bei der Wiederaufarbeitung von HTR-Brennelementen, JÜL-1567]. Tritium and other radioisotopes, including 36Cl and 129I, can be removed from graphite by thermal treatment. Even significant parts of the 14C inventory can be selectively extracted because most of the 14C may be adsorbed on the surface of the crystallites in the pore structure and not integrated into the crystal lattice. This has recently been demonstrated in principle by the HTR-N/N1 project. As an accompaniment to thermal treatments, steam reforming is an alternative method for decontaminating graphite from radionuclides. The decontamination rates are even higher in comparison to pure thermal treatment in an inert atmosphere, as was first evidenced by basic experiments in the HTR-N/N1 project.

Conference ‘CFR and Existing EC Contract Law’, Münster,10–11 December 2007

Conference ‘CFR and Existing EC Contract Law’, Münster,10–11 December 2007

Principles of the Existing EC Contract Law by the Acquis Group

Principles of the Existing EC Contract Law by the Acquis Group

Deterministic Safety Technology for RBMK Reactors

The present paper deals with the description of the technical activities conducted within the TACIS Project R2.03/97, 2 EC Contract no. 30303, related to RBMK. The project activities are focused toward the setting-up of a chain of computational tools suitable for the analysis of transients expected in the RBMK nuclear power plant (NPP). The accident leading to the rupture of one pressure channel, with fuel melting or high temperature damage, creep and brittle failure of the pressure tube and of graphite bricks with possibility of rupture propagation, constitutes the reference scenario for the project. However, a series of expected scenarios has been selected to prove the capability of the individual codes or chains of code in simulating the envisaged phenomenology. The paper summarizes the activities performed at NIKIET in Moscow and at University of Pisa (UNIPI) in Pisa. A top-down approach is pursued in structuring the executive summary that includes the following sections: (i) the safety needed for the RBMK NPP, (ii) the roadmap, (iii) the adopted computational tools, (iv) key findings, (v) Emphasis is given to the multiple pressure tube rupture (MPTR) issue and the individual channel monitoring (ICM) proposal.

EC Financial Services and Contract Law – Developments 2005–2007

The contribution is a follow-up of the overview published in ERCL 2005, 482. While the law with respect to prudential supervision changed little, contract law developed considerably. This is so despite the fact that no important new legislation has been adopted: In the area of commercial banking, the new Consumer Credit Directive is still under discussion. There is, however, an ambitious project to regulate all payment instruments in one sole legal measure, namely: credit transfers, credit and debit cards and direct debit. In the area of investment banking, the Market in Financial Instruments Directive of 2004 (MiFID) had to be transposed in the Member States until 1st November 2007. This is important because the so-called Lamfalussy regulatory architecture which was used for this directive is about integrating more coherently EC legislation, national transposition and effective implementation. Therefore, while giving a general overview as well, the article concentrates on these two developments: the proposal for a payments directive and the transposition of the MiFID.

Rapidly converging adaptive state‐space‐based multichannel active noise control algorithm for reduction of broadband noise

Rapidly changing spectra may lead to performance limitations in adaptive systems for broadband active noise control, especially in multichannel systems. This paper presents techniques to address the negative consequences of two main causes. First, the dynamics of the transfer paths between the noise control sources and the error microphones is compensated for by using a regularized state‐space based adaptive filtered‐error scheme. Second, for the reference signals a modified adaptive scheme is used, taking into account the nonwhiteness of these signals as well as the correlation between the individual signals. Examples are given for simulated data and for real‐time implementations. [This work was partly supported by EC Contract 501084 (InMAR).]

Form and Substance in the Reception of EC Directives into English Contract Law

: In this paper, the author explores some of the difficulties facing English lawyers in implementing EC directives in the area of ‘contract law’ and compares them with those facing lawyers in systems with codified private laws. To do so, he identifies four significant features of the EC contract law directives: the ambiguity of what is meant by ‘contract law’ for this purpose, there being a contrast between a traditional sense of the law governing the rights arising in a contracting party against the other and ‘policing measures’ in relation to the behaviour of contracting parties; the special nature of the regulation which the directives require and the relative absence of ‘general clauses’; the relationship of the contract law rules of the directives to national law distinctions between public and private law; and the particular, ‘European’ nature of the uncertainty which affects many of the concepts which the directives use. The author explains how these features affect the form of the reception of the directives into national laws, identifying differences between laws where codification is important and English law where it is all but absent. However, English law shares with codified laws a number of substantive problems in implementing contract law directives, notably, in terms of the question whether the rules and concepts which the directives use can be melded with existing national legislative rules (often as interpreted by national case-law) so as to achieve a true integration (and not a mere implementation) of the EC regulation into national laws. In dealing with these problems, the minimum nature of the harmonisation required by many contract law directives allows Member States to extend a directive's scheme in a way which permits it to fit into national law more harmoniously, but even where this is so, sometimes the substantive strategy of a directive clashes with much more general strategies of their national laws. Finally, the author sees the clearer definition of concepts used by the directives as contributing significantly to the resolution of some of the problems which he identifies, this allowing Member States a better sense of how to go about the true integration of the regulation which the directives require with the surrounding regulation of national laws.

A reference accelerator scheme for ADS applications

Accelerator Driven Systems (ADS) for transmutation of nuclear waste typically require 350 MeV–1 GeV accelerators delivering proton fluxes of 5–10 mA for demonstrators, and 20–50 mA for large industrial systems. Thus, such machines belong to the category of the so-called HPPA (High-Power Proton Accelerators), with multi-megawatt beam power. HPPA are presently developed and constructed at great pace for their broad utility in fundamental or applied science. Compared to other HPPA, many features and requirements are similar for the ADS driver. However, there is a need for exceptional reliability: because of the induced thermal stress to the sub-critical core, the number of unwanted “beam-trips” should not exceed a few per year, a requirement that is several orders of magnitude above usual performance. Consecutive to the work of the European Technical Working Group (ETWG) on ADS, the Preliminary Design Study of an Experimental ADS (PDS-XADS) was launched in 2001 as a 5th Framework Program EC project. 1 1 EC Contract No FIKW-CT-2001-00179. A special Working Package (WP3) was dedicated to the accelerator design, taking especially into account that the issue of “beam-trips” could be a potential “show-stopper” for ADS technology in general. A reference solution, based on a linear superconducting accelerator with its associated doubly achromatic beam line, has been worked out to some detail. For high reliability, the proposed design is intrinsically fault tolerant, relying on highly modular “de-rated” components associated to a fast digital feedback system. The proposed solution also appears to be robust concerning operational aspects like maintenance and radioprotection. A roadmap for construction as well as the required consolidated budget was elaborated. A program for the remaining R&D, focused on experimental reliability demonstration of prototypical components has been elaborated. This R&D will be performed in the 6th Framework Program EC project EUROTRANS, 2 2 EC Contract No FI6W-516520. which presently is just starting.