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- ItemThis looks More Like that: Enhancing Self-Explaining Models by prototypical relevance propagation: This Looks More Like That(Amsterdam : Elsevier, 2022) Gautam, Srishti; Höhne, Marina M.-C.; Hansen, Stine; Jenssen, Robert; Kampffmeyer, MichaelCurrent machine learning models have shown high efficiency in solving a wide variety of real-world problems. However, their black box character poses a major challenge for the comprehensibility and traceability of the underlying decision-making strategies. As a remedy, numerous post-hoc and self-explanation methods have been developed to interpret the models’ behavior. Those methods, in addition, enable the identification of artifacts that, inherent in the training data, can be erroneously learned by the model as class-relevant features. In this work, we provide a detailed case study of a representative for the state-of-the-art self-explaining network, ProtoPNet, in the presence of a spectrum of artifacts. Accordingly, we identify the main drawbacks of ProtoPNet, especially its coarse and spatially imprecise explanations. We address these limitations by introducing Prototypical Relevance Propagation (PRP), a novel method for generating more precise model-aware explanations. Furthermore, in order to obtain a clean, artifact-free dataset, we propose to use multi-view clustering strategies for segregating the artifact images using the PRP explanations, thereby suppressing the potential artifact learning in the models.
- ItemRegional income and wave energy deployment in Ireland(Oxford : Wiley-Blackwell, 2020) Farrell, Niall; O'Donoghue, Cathal; Morrissey, KarynAlongside environmental benefits, renewable energy deployment is often evaluated on grounds of regional development. Focusing on wave energy deployment in Ireland, this paper quantifies employment-related welfare change net of associated subsidy costs. Although the added employment reduces inter-regional inequality, certain subsidies increase total income inequality by a greater extent. Total inequality increases by 0.25% in the preferred scenario. This pattern of incidence persists under an optimistic scenario where all manufacturing activity is carried out locally. This finding highlights that policies of regional development should consider the spatial distribution of associated subsidy costs.
- ItemEuropean H2020 Project WORTECS Wireless Mixed Reality Prototyping(Oulu : Academy Publisher, 2020) Bouchet, Olivier; O'Brien, Dominic; Singh, Ravinder; Faulkner, Grahame; Ghoraishi, Mir; Garcia-Marquez, Jorge; Vercasson, Guillaume; Brzozowski, Marcin; Sark, VladicaThis paper presents European collaborative project WORTECS objectives and reports on the development of several radio and optical wireless prototypes and a demonstrator targeting mixed reality (MR) application. The aim is to achieve a net throughput of up to Tbps in an indoor heterogeneous network for the MR use case, which seems to be a high throughput "killer application" beyond 5G. A special routing device is associated with the demonstrator to select the most suitable wireless access technology. Post introduction to the project, an overview of the demonstrator is presented with details of the current progress of the prototypes.
- ItemReply to Ruhl and Craig: Assessing and governing extreme climate risks needs to be legitimate and democratic(Washington, DC : National Acad. of Sciences, 2022) Kemp, Luke; Xu, Chi; Depledge, Joanna; Ebi, Kristie L.; Gibbins, Goodwin; Kohler, Timothy A.; Rockström, Johan; Scheffer, Marten; Schellnhuber, Hans Joachim; Steffen, Will; Lenton, Timothy M.[No abstract available]
- ItemReply to Burgess et al: Catastrophic climate risks are neglected, plausible, and safe to study(Washington, DC : National Acad. of Sciences, 2022) Kemp, Luke; Xu, Chi; Depledge, Joanna; Ebi, Kristie L.; Gibbins, Goodwin; Kohler, Timothy A.; Rockström, Johan; Scheffer, Marten; Schellnhuber, Hans Joachim; Steffen, Will; Lenton, Timothy M.
- ItemGas plasma–oxidized sodium chloride acts via hydrogen peroxide in a model of peritoneal carcinomatosis(Washington, DC : National Acad. of Sciences, 2022) Miebach, Lea; Freund, Eric; Clemen, Ramona; Kersting, Stephan; Partecke, Lars-Ivo; Bekeschus, SanderGas plasma technology generates reactive oxygen and nitrogen species (ROS/RNS), inducing lethal oxidative damage in tumor cells. The transfer of gas plasma–derived ROS/RNS into liquids has been proposed as an innovative anti-cancer strategy targeting peritoneal carcinomatosis (PC). However, the mechanism of action is under debate. To this end, we compared gas plasma–oxidized medical-grade sodium chloride (oxNaCl) with a concentration-matched control (cmc) of NaCl enriched with equivalent concentrations of H2O2 and NO32 in several cell lines and models of PC. Strikingly, oxNaCl and cmc performed equally well in oxidation and cytotoxic activity in tumor cells in two-dimensional cultures, three-dimensional (3D) tumor spheroids, vascularized 3D tumors grown on chicken-embryo chorioallantoic membranes, and a syngeneic PC mouse model in vivo. Given the importance of immunotherapies in oncology today, we focused on immunological consequences of the treatment. Again, to a similar extent, oxNaCl and cmc increased tumor cell immunogenicity and enhanced uptake by and maturation of peripheral blood monocyte–derived dendritic cells together with an inflammatory secretion profile. Furthermore, NanoString gene expression profiling revealed immune system processes and unfolded protein response-related pathways as being linked to the observed anti-tumor effects for both oxNaCl and cmc. In conclusion, gas plasma–generated oxNaCl and cmc showed equal therapeutic efficacy in our PC-related models. In light of the many promising anti-cancer studies of gas plasma–oxidized liquids and the convenient production of corresponding cmcs in large quantities as needed in clinics, our findings may spur research lines based on low-dose oxidants in peritoneal cancer therapy.
- ItemTrajectories of the Earth System in the Anthropocene(Washington, DC : NAS, 2018) Steffen, Will; Rockström, Johan; Richardson, Katherine; Lenton, Timothy M.; Folke, Carl; Liverman, Diana; Summerhayes, Colin P.; Barnosky, Anthony D.; Cornell, Sarah E.; Crucifix, Michel; Donges, Jonathan F.; Fetzer, Ingo; Lade, Steven J.; Scheffer, Marten; Winkelmann, Ricarda; Schellnhuber, Hans JoachimWe explore the risk that self-reinforcing feedbacks could push the Earth System toward a planetary threshold that, if crossed, could prevent stabilization of the climate at intermediate temperature rises and cause continued warming on a “Hothouse Earth” pathway even as human emissions are reduced. Crossing the threshold would lead to a much higher global average temperature than any interglacial in the past 1.2 million years and to sea levels significantly higher than at any time in the Holocene. We examine the evidence that such a threshold might exist and where it might be. If the threshold is crossed, the resulting trajectory would likely cause serious disruptions to ecosystems, society, and economies. Collective human action is required to steer the Earth System away from a potential threshold and stabilize it in a habitable interglacial-like state. Such action entails stewardship of the entire Earth System—biosphere, climate, and societies—and could include decarbonization of the global economy, enhancement of biosphere carbon sinks, behavioral changes, technological innovations, new governance arrangements, and transformed social values.
- ItemStewardship of global collective behavior(Washington, DC : National Acad. of Sciences, 2021) Bak-Coleman, Joseph B.; Alfano, Mark; Barfuss, Wolfram; Bergstrom, Carl T.; Centeno, Miguel A.; Couzin, Iain D.; Donges, Jonathan F.; Galesic, Mirta; Gersick, Andrew S.; Jacquet, Jennifer; Kao, Albert B.; Moran, Rachel E.; Romanczuk, Pawel; Rubenstein, Daniel I.; Tombak, Kaia J.; Van Bavel, Jay J.; Weber, Elke U.Collective behavior provides a framework for understanding how the actions and properties of groups emerge from the way individuals generate and share information. In humans, information flows were initially shaped by natural selection yet are increasingly structured by emerging communication technologies. Our larger, more complex social networks now transfer high-fidelity information over vast distances at low cost. The digital age and the rise of social media have accelerated changes to our social systems, with poorly understood functional consequences. This gap in our knowledge represents a principal challenge to scientific progress, democracy, and actions to address global crises. We argue that the study of collective behavior must rise to a “crisis discipline” just as medicine, conservation, and climate science have, with a focus on providing actionable insight to policymakers and regulators for the stewardship of social systems.
- ItemDesign–functionality relationships for adhesion/growth-regulatory galectins(Washington, DC : National Acad. of Sciences, 2019) Ludwig, Anna-Kristin; Michalak, Malwina; Xiao, Qi; Gilles, Ulrich; Medrano, Francisco J.; Ma, Hanyue; FitzGerald, Forrest G.; Hasley, William D.; Melendez-Davila, Adriel; Liu, Matthew; Rahimi, Khosrow; Kostina, Nina Yu; Rodriguez-Emmenegger, Cesar; Möller, Martin; Lindner, Ingo; Kaltner, Herbert; Cudic, Mare; Reusch, Dietmar; Kopitz, Jürgen; Romero, Antonio; Oscarson, Stefan; Klein, Michael L.; Gabius, Hans-Joachim; Percec, VirgilGlycan-lectin recognition is assumed to elicit its broad range of (patho)physiological functions via a combination of specific contact formation with generation of complexes of distinct signal-triggering topology on biomembranes. Faced with the challenge to understand why evolution has led to three particular modes of modular architecture for adhesion/growth-regulatory galectins in vertebrates, here we introduce protein engineering to enable design switches. The impact of changes is measured in assays on cell growth and on bridging fully synthetic nanovesicles (glycodendrimersomes) with a chemically programmable surface. Using the example of homodimeric galectin-1 and monomeric galectin-3, the mutual design conversion caused qualitative differences, i.e., from bridging effector to antagonist/from antagonist to growth inhibitor and vice versa. In addition to attaining proof-of-principle evidence for the hypothesis that chimera-type galectin-3 design makes functional antagonism possible, we underscore the value of versatile surface programming with a derivative of the pan-galectin ligand lactose. Aggregation assays with N,N′-diacetyllactosamine establishing a parasite-like surface signature revealed marked selectivity among the family of galectins and bridging potency of homodimers. These findings provide fundamental insights into design-functionality relationships of galectins. Moreover, our strategy generates the tools to identify biofunctional lattice formation on biomembranes and galectin-reagents with therapeutic potential.
- ItemAnalysis of riboflavin/ultraviolet a corneal cross-linking by molecular spectroscopy(London [u.a.] : Elsevier, 2023) Melcher, Steven; Zimmerer, Cordelia; Galli, Roberta; Golde, Jonas; Herber, Robert; Raiskup, Frederik; Koch, Edmund; Steiner, GeraldCorneal cross-linking (CXL) with riboflavin and ultraviolet A light is a therapeutic procedure to restore the mechanical stability of corneal tissue. The treatment method is applied to pathological tissue, such as keratoconus and induces the formation of new cross-links. At present, the molecular mechanisms of induced cross-linking are still not known exactly. In this study, we investigated molecular alterations within porcine cornea tissue after treatment with riboflavin and ultraviolet A light by surface enhanced Raman spectroscopy (SERS). For that purpose, after CXL treatment a thin silver layer was vapor-deposited onto cornea flaps. To explore molecular alterations induced by the photochemical process hierarchical cluster analysis (HCA) was used. The detailed analysis of SERS spectra reveals that there is no general change in collagen secondary structure while modifications on amino acid side chains are the most dominant outcome. The formation of secondary and aromatic amine groups as well as methylene and carbonyl groups were observed. Even though successful cross-linking could not be registered in all treated samples, Raman signals of newly formed chemical groups are already present in riboflavin only treated corneas.