Comparing energy system optimization models and integrated assessment models: Relevance for energy policy advice

Background: The transition to a climate neutral society such as that envisaged in the European Union Green Deal requires careful and comprehensive planning. Integrated assessment models (IAMs) and energy system optimisation models (ESOMs) are both commonly used for policy advice and in the process of policy design. In Europe, a vast landscape of these models has emerged and both kinds of models have been part of numerous model comparison and model linking exercises. However, IAMs and ESOMs have rarely been compared or linked with one another. Methods: This study conducts an explorative comparison and identifies possible flows of information between 11 of the integrated assessment and energy system models in the European Climate and Energy Modelling Forum. The study identifies and compares regional aggregations and commonly reported variables. We define harmonised regions and a subset of shared result variables that enable the comparison of scenario results across the models. Results: The results highlight how power generation and demand development are related and driven by regional and sectoral drivers. They also show that demand developments like for hydrogen can be linked with power generation potentials such as onshore wind power. Lastly, the results show that the role of nuclear power is related to the availability of wind resources. Conclusions: This comparison and analysis of modelling results across model type boundaries provides modellers and policymakers with a better understanding of how to interpret both IAM and ESOM results. It also highlights the need for community standards for region definitions and information about reported variables to facilitate future comparisons of this kind. The comparison shows that regional aggregations might conceal differences within regions that are potentially of interest for national policy makers thereby indicating a need for national-level analysis

Transduction of Brain Dopamine Neurons by Adenoviral Vectors Is Modulated by CAR Expression: Rationale for Tropism Modified Vectors in PD Gene Therapy

Gene-based therapy is a new paradigm for the treatment of Parkinson disease (PD) and offers considerable promise for precise targeting and flexibility to impact multiple pathobiological processes for which small molecule agents are not available. Some success has been achieved utilizing adeno-associated virus for this approach, but it is likely that the characteristics of this vector system will ultimately create barriers to progress in clinical therapy. Adenovirus (Ad) vector overcomes limitations in payload size and targeting. The cellular tropism of Ad serotype 5 (Ad5)-based vectors is regulated by the Ad attachment protein binding to its primary cellular receptor, the coxsackie and adenovirus receptor (CAR). Many clinically relevant tissues are refractory to Ad5 infection due to negligible CAR levels but can be targeted by tropism-modified, CAR-independent forms of Ad. Our objective was to evaluate the role of CAR protein in transduction of dopamine (DA) neurons in vivo.Ad5 was delivered to the substantia nigra (SN) in wild type (wt) and CAR transgenic animals. Cellular tropism was assessed by immunohistochemistry (IHC) in the SN and striatal terminals. CAR expression was assessed by western blot and IHC. We found in wt animals, Ad5 results in robust transgene expression in astrocytes and other non-neuronal cells but poor infection of DA neurons. In contrast, in transgenic animals, Ad5 infects SNc neurons resulting in expression of transduced protein in their striatal terminals. Western blot showed low CAR expression in the ventral midbrain of wt animals compared to transgenic animals. Interestingly, hCAR protein localizes with markers of post-synaptic structures, suggesting synapses are the point of entry into dopaminergic neurons in transgenic animals.These findings demonstrate that CAR deficiency limits infection of wild type DA neurons by Ad5 and provide a rationale for the development of tropism-modified, CAR-independent Ad-vectors for use in gene therapy of human PD

ECEMF Diagnostic Scenarios, version 2.0

This dataset compiles diagnostic scenarios from several Integrated Assessment Models (IAM) and Energy System Models (ESM) to facilitate systematic comparison of a broad range of results across these models. These diagnostic scenarios were developed in the Horizon 2020 project ECEMF (https://ecemf.eu). Visit the ECEMF Scenario Explorer hosted by IIASA at https://data.ece.iiasa.ac.at/ecemf for more information and interactive user interface to work with the scenario data

Challenges and Promises in the Development of Neurotrophic Factor-Based Therapies for Parkinson’s Disease

© Springer International Publishing Switzerland 2014Parkinson's disease (PD) is a chronic movement disorder typically coupled to progressive degeneration of dopaminergic neurons in the substantia nigra (SN). The treatments currently available are satisfactory for symptomatic management, but the efficacy tends to decrease as neuronal loss progresses. Neurotrophic factors (NTFs) are endogenous proteins known to promote neuronal survival, even in degenerating states. Therefore, the use of these factors is regarded as a possible therapeutic approach, which would aim to prevent PD or to even restore homeostasis in neurodegenerative disorders. Intriguingly, although favorable results in in vitro and in vivo models of the disease were attained, clinical trials using these molecules have failed to demonstrate a clear therapeutic benefit. Therefore, the development of animal models that more closely reproduce the mechanisms known to underlie PD-related neurodegeneration would be a major step towards improving the capacity to predict the clinical usefulness of a given NTF-based approach in the experimental setting. Moreover, some adjustments to the design of clinical trials ought to be considered, which include recruiting patients in the initial stages of the disease, improving the efficacy of the delivery methods, and combining synergetic NTFs or adding NTF-boosting drugs to the already available pharmacological approaches. Despite the drawbacks on the road to the use of NTFs as pharmacological tools for PD, very relevant achievements have been reached. In this article, we review the current status of the potential relevance of NTFs for treating PD, taking into consideration experimental evidence, human observational studies, and data from clinical trials.This work was supported by a Fundação para a Ciência e a Tecnologia (FCT) project grant. André Jerónimo-Santos is supported by an FCT fellowship grant (SFRH/BD/62828/2009) and Tiago Fleming Outeiro is supported by the DFG Center for Nanoscale Microscopy and Molecular Physiology of the Brain.info:eu-repo/semantics/publishedVersio