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D.2.1 is the first deliverable of WP2 in the NOVIMOVE project. WP2’s mission is to develop a simulation model for today’s IWT container logistics system on the Rhine-Alpine corridor which will also allow detailed analyses of the impact of the NOVIMOVE innovations improving the IWT container logistics. Next to that, new approaches (functions) to improve the current IWT container logistics are developed. WP2 objectives are developing: •A simulation model for the IWT container logistics chains that: orepresents the current situation and delivers a benchmark scenario for NOVIMOVE innovations; oincorporates the NOVIMOVE innovations and determines their impact on the overall performance of the IWT container logistics chain over the Rhine-Alpine route, with respect to the benchmark scenario; •New logistics approaches (functions) to improve the current IWT container logistics: oEnhanced load factors through cargo reconstruction; oImproved port logistics; •Serious game based on the NOVIMOVE transport simulation model to: oTrain/educate actors, stakeholders, and decision-makers in the transport chain to allow for the market uptake of the NOVIMOVE developments; oBe included in academic teaching for transport engineering and transport economics students, awakening their interest and enhancing their competence in IWT integration in logistics planning. In this first deliverable, the detailed requirements of the initial transport model are developed within the domain established in WP1 (Task T1.1). In order to do this a good understanding of the current IWT container logistics system and of the other transport modes (road, rail) for the Rhine-Alpine corridor is obtained. These obtained insights helped define detailed requirements for the logistics model, defining the type of modelling, the model scope, the relevant actors and the necessary data. In this deliverable a literature study was developed and on top of that a questionnaire was developed with which the insights from the main stakeholders could be taken into account. The results of the survey confirm the conclusions from the literature and reveal that inefficient handling of barges, poor planning and coordination, lack of flexibility in container barge transport and low water levels are the most important challenges that the smooth operations container barge transport currently face. Additionally, the survey revealed the major stakeholders within container barge transport operations as barge owners, barge operators, shippers and waterway managers. It is based on this that the system boundary for each of the actors will be developed in the WP2 world model. The main important actors within the sector and their modes of operation that are taken into account are actors related to the shippers (cargo owners): shippers, freight forwarders and logistics services providers. Next to that also barge owners, inland and deep-sea terminal operators and waterway managers are taken into account. Finally, also the conditions at the end of the chain (distribution centres) are taken into account. The data needed for the model is identified. This data are cargo flow data for IWT, road and rail transport on the Rhine Alpine corridor. Next to that, also the sources for the cost data for all modes are determined. The modelling method that was chosen is a discrete event modelling approach. The simulation model requires a modular infrastructure in order to be able to incorporate the innovations from WP2, WP3 and WP4. In this deliverable also the KPIs are determined which should be computed by the NOVIMOVE transport model. These KPIs are determined at both the overall logistics level as well as the individual NOVIMOVE innovation level. The KPIs can be decomposed into different individual performance indicators and extended by further relevant performance indicators (e.g., additional transportation, handling, or financial indicators). This provides the various stakeholders with a holistic and relevant picture and enables them the performance monitoring of the innovations in their respective application context. Based on these developments the scope, data and functionalities and main outputs of the NOVIMOVE transport model can be developed.

The formation of reactive oxygen species (ROS) is linked to the pathogenesis of neurodegenerative diseases. Here we have investigated the effect of soluble and aggregated amyloid-ß (Aß) and a-synuclein (aS), associated with Alzheimer''s and Parkinson''s diseases, respectively, on the Cu2+-catalyzed formation of ROS in vitro in the presence of a biological reductant. We find that the levels of ROS, and the rate by which ROS is generated, are significantly reduced when Cu2+ is bound to Aß or aS, particularly when they are in their oligomeric or fibrillar forms. This effect is attributed to a combination of radical scavenging and redox silencing mechanisms. Our findings suggest that the increase in ROS associated with the accumulation of aggregated Aß or aS does not result from a particularly ROS-active form of these peptides, but rather from either a local increase of Cu2+ and other ROS-active metal ions in the aggregates or as a downstream consequence of the formation of the pathological amyloid structures.