An Efficient Mechanism for Cross-border Support of Renewable Electricity in the European Union

The ability to exchange renewable electricity (RES-e) capacity between EU member states improves the welfare of all member states since potentials and demands for RES-e capacity vary across the EU. This notion is reflected in the promotion of so-called cooperation mechanisms by the European Commission. The existing mechanisms appear, unfortunately, to be insufficient to facilitate an efficient level of trade in capacity across the EU; only a small quantity of energy is expected to be subject to cooperation mechanisms (Klessmann et al. 2010). In order to address these challenges, in this paper we propose a new mechanism for cross-border support of renewable electricity in EU. The guiding idea is that the cross-border mechanism allocates new RES-e generating capacity across EU Member States to where it is most valuable. This can, but need not, coincide with the most cost efficient allocation. The mechanism consists of two main elements. Firstly, a cross-border impact matrix that indicates the spill-over of benefits between member states induced from the power injection of additional RES-e generating capacity. Secondly, an EU wide auction in which member states and generators of RES-e bid prices indicating their willingness to pay for additional RES-e generating capacity. Then for given parameters the auctioneer selects the set of bids that maximizes an EU-wide surplus. We find that the mechanism leads to a decentralized optimization of RES-e support in the EU, by matching high willingness to pay of member states with low cost potentials of RES-e generation, but only if the benefits of RES-e are actually delivered for the member state paying for it. Moreover, the mechanism offers the potential to significantly reduce the barriers of the current cooperation mechanism, such as transaction costs or uncertainty about costs and benefits

Neuronal avalanches recorded in the awake and sleeping monkey do not show a power law but can be reproduced by a self-organized critical model

Poster presentation: Self-organized critical (SOC) systems are complex dynamical systems that may express cascades of events, called avalanches [1]. The SOC state was proposed to govern brain function, because of its activity fluctuations over many orders of magnitude, its sensitivity to small input and its long term stability [2,3]. In addition, the critical state is optimal for information storage and processing [4]. Both hallmark features of SOC systems, a power law distribution f(s) for the avalanche size s and a branching parameter (bp) of unity, were found for neuronal avalanches recorded in vitro [5]. However, recordings in vivo yielded contradictory results [6]. Electrophysiological recordings in vivo only cover a small fraction of the brain, while criticality analysis assumes that the complete system is sampled. We hypothesized that spatial subsampling might influence the observed avalanche statistics. In addition, SOC models can have different connectivity, but always show a power law for f(s) and bp = 1 when fully sampled. This may not be the case under subsampling, however. Here, we wanted to know whether a state change from awake to asleep could be modeled by changing the connectivity of a SOC model without leaving the critical state. We simulated a SOC model [1] and calculated f(s) and bp obtained from sampling only the activity of a set of 4 × 4 sites, representing the electrode positions in the cortex. We compared these results with results obtained from multielectrode recordings of local field potentials (LFP) in the cortex of behaving monkeys. We calculated f(s) and bp for the LFP activity recorded while the monkey was either awake or asleep and compared these results to results obtained from two subsampled SOC model with different connectivity. f(s) and bp were very similar for both the experiments and the subsampled SOC model, but in contrast to the fully sampled model, f(s) did not show a power law and bp was smaller than unity. With increasing the distance between the sampling sites, f(s) changed from "apparently supercritical" to "apparently subcritical" distributions in both the model and the LFP data. f(s) and bp calculated from LFP recorded during awake and asleep differed. These changes could be explained by altering the connectivity in the SOC model. Our results show that subsampling can prevent the observation of the characteristic power law and bp in SOC systems, and misclassifications of critical systems as sub- or supercritical are possible. In addition, a change in f(s) and bp for different states (awake/asleep) does not necessarily imply a change from criticality to sub- or supercriticality, but can also be explained by a change in the effective connectivity of the network without leaving the critical state

7-(2-Chloro­phen­yl)-2,6,9-trimethyl­dibenzo[b,h][1,6]naphthyridine

In the title compound, C25H19ClN2, the dibenzo[b,h][1,6]naphthyridine system is planar to within 0.16 (2) Å, and the chloro­phenyl ring is inclined to it by 82.53 (7)°. In the crystal, mol­ecules are linked by C—H⋯N hydrogen bonds, forming chains propagating in [100]. There are also a number of weak π–π stacking inter­actions present [centroid–centroid distances = 3.8531 (1) and 3.7631 (1) Å]

Inter-laboratory proficiency testing scheme for tumour next-generation sequencing in Ontario: A pilot study

Background A pilot inter-laboratory proficiency scheme for 5 Ontario clinical laboratories testing tumour samples for the Ontario-wide Cancer Targeted Nucleic Acid Evaluation (OCTANE) study was undertaken to assess proficiency in the identification and reporting of next-generation sequencing (NGS) test results in solid tumour testing from archival formalin-fixed, paraffin-embedded (FFPE) tissue. Methods One laboratory served as the reference centre and provided samples to 4 participating laboratories. An analyte-based approach was applied: each participating laboratory received 10 FFPE tissue specimens profiled at the reference centre, with tumour site and histology provided. Laboratories performed testing per their standard NGS tumour test protocols. Items returned for assessment included genes and variants that would be typically reported in routine clinical testing and variant call format (VCF) files to allow for assessment of NGS technical quality. Results Two main aspects were assessed: Technical quality and accuracy of identification of exonic variants Site-specific reporting practices Technical assessment included evaluation of exonic variant identification, quality assessment of the VCF files to evaluate base calling, variant allele frequency, and depth of coverage for all exonic variants. Concordance at 100% was observed from all sites in the technical identification of 98 exonic variants across the 10 cases. Variability between laboratories in the choice of variants considered clinically reportable was significant. Of the 38 variants reported as clinically relevant by at least 1 site, only 3 variants were concordantly reported by all participating centres as clinically relevant. Conclusions Although excellent technical concordance for NGS tumour profiling was observed across participating institutions, differences in the reporting of clinically relevant variants were observed, highlighting reporting as a gap where consensus on the part of Ontario laboratories is needed

2,9-Dimethyl-7-phenyl-N-(4-methyl­phen­yl)dibenzo[b,h][1,6]naphthyridin-6-amine

The title compound, C31H25N3, was synthesized from 6,4′,4′′-trimethyl-2,4-bis­(N-phenyl­amino)­quinoline and is the first structural example containing a phenyl and phenyl­amino fragment attached to a fused dibenzo[1,6]naphthyridine moiety. The fused tetra­cyclic ring system is essentially planar [r.m.s. deviation = 0.08 (3) Å]. The phenyl ring and the phenyl­amino group are inclined by 82.68 (6) and 35.31 (5)°, respectively, to the mean plane of the fused tetra­cyclic ring system. A weak intra­molecular N—H⋯π(arene) inter­action may in part influence the conformation of the mol­ecule. In the crystal, mol­ecules are linked by weak inter­molecular C—H⋯N hydrogen bonds into centrosymmetric dimers. Additional stabilization is provided by weak C—H⋯π and π–π stacking inter­actions [centroid–centroid distances = 3.834 (2) and 3.898 (1) Å]

A framework to rank genomic alterations as targets for cancer precision medicine: the ESMO Scale for Clinical Actionability of molecular Targets (ESCAT)

Background: In order to facilitate implementation of precision medicine in clinical management of cancer, there is a need to harmonise and standardise the reporting and interpretation of clinically relevant genomics data. / Methods: The European Society for Medical Oncology (ESMO) Translational Research and Precision Medicine Working Group (TR and PM WG) launched a collaborative project to propose a classification system for molecular aberrations based on the evidence available supporting their value as clinical targets. A group of experts from several institutions was assembled to review available evidence, reach a consensus on grading criteria and present a classification system. This was then reviewed, amended and finally approved by the ESMO TR and PM WG and the ESMO leadership. / Results: This first version of the ESMO Scale of Clinical Actionability for molecular Targets (ESCAT) defines six levels of clinical evidence for molecular targets according to the implications for patient management: tier I, targets ready for implementation in routine clinical decisions; tier II, investigational targets that likely define a patient population that benefits from a targeted drug but additional data are needed; tier III, clinical benefit previously demonstrated in other tumour types or for similar molecular targets; tier IV, preclinical evidence of actionability; tier V, evidence supporting co-targeting approaches; and tier X, lack of evidence for actionability. / Conclusions: The ESCAT defines clinical evidence-based criteria to prioritise genomic alterations as markers to select patients for targeted therapies. This classification system aims to offer a common language for all the relevant stakeholders in cancer medicine and drug development

Earth system science frontiers - an early career perspective

The exigencies of the global community toward Earth system science will increase in the future as the human population, economies, and the human footprint on the planet continue to grow. This growth, combined with intensifying urbanization, will inevitably exert increasing pressure on all ecosystem services. A unified interdisciplinary approach to Earth system science is required that can address this challenge, integrate technical demands and long-term visions, and reconcile user demands with scientific feasibility. Together with the research arms of the World Meteorological Organization, the Young Earth System Scientists community has gathered early-career scientists from around the world to initiate a discussion about frontiers of Earth system science. To provide optimal information for society, Earth system science has to provide a comprehensive understanding of the physical processes that drive the Earth system and anthropogenic influences. This understanding will be reflected in seamless prediction systems for environmental processes that are robust and instructive to local users on all scales. Such prediction systems require improved physical process understanding, more high-resolution global observations, and advanced modeling capability, as well as high-performance computing on unprecedented scales. At the same time, the robustness and usability of such prediction systems also depend on deepening our understanding of the entire Earth system and improved communication between end users and researchers. Earth system science is the fundamental baseline for understanding the Earth’s capacity to accommodate humanity, and it provides a means to have a rational discussion about the consequences and limits of anthropogenic influence on Earth. Without its progress, truly sustainable development will be impossible. © 2017 American Meteorological Society. For information regarding reuse of this content and general copyright information, consult the AMS Copyright Policy (www.ametsoc.org/PUBSReuseLicenses)

Enhanced Immunogenicity of Mitochondrial-Localized Proteins in Cancer Cells.

Epitopes derived from mutated cancer proteins elicit strong antitumor T-cell responses that correlate with clinical efficacy in a proportion of patients. However, it remains unclear whether the subcellular localization of mutated proteins influences the efficiency of T-cell priming. To address this question, we compared the immunogenicity of NY-ESO-1 and OVA localized either in the cytosol or in mitochondria. We showed that tumors expressing mitochondrial-localized NY-ESO-1 and OVA proteins elicit significantdly higher frequencies of antigen-specific CD8+ T cells in vivo. We also demonstrated that this stronger immune response is dependent on the mitochondrial location of the antigenic proteins, which contributes to their higher steady-state amount, compared with cytosolic localized proteins. Consistent with these findings, we showed that injection of mitochondria purified from B16 melanoma cells can protect mice from a challenge with B16 cells, but not with irrelevant tumors. Finally, we extended these findings to cancer patients by demonstrating the presence of T-cell responses specific for mutated mitochondrial-localized proteins. These findings highlight the utility of prioritizing epitopes derived from mitochondrial-localized mutated proteins as targets for cancer vaccination strategies.S