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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.
- 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.
- 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.
- 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.
- ItemDesign and Evaluation of Radiation-Hardened Standard Cell Flip-Flops(New York, NY : Institute of Electrical and Electronics Engineers, 2021) Schrape, Oliver; Andjelkovic, Marko; Breitenreiter, Anselm; Zeidler, Steffen; Balashov, Alexey; Krstic, MilosUse of a standard non-rad-hard digital cell library in the rad-hard design can be a cost-effective solution for space applications. In this paper we demonstrate how a standard non-rad-hard flip-flop, as one of the most vulnerable digital cells, can be converted into a rad-hard flip-flop without modifying its internal structure. We present five variants of a Triple Modular Redundancy (TMR) flip-flop: baseline TMR flip-flop, latch-based TMR flip-flop, True-Single Phase Clock (TSPC) TMR flip-flop, scannable TMR flip-flop and self-correcting TMR flip-flop. For all variants, the multi-bit upsets have been addressed by applying special placement constraints, while the Single Event Transient (SET) mitigation was achieved through the usage of customized SET filters and selection of optimal inverter sizes for the clock and reset trees. The proposed flip-flop variants feature differing performance, thus enabling to choose the optimal solution for every sensitive node in the circuit, according to the predefined design constraints. Several flip-flop designs have been validated on IHP’s 130nm BiCMOS process, by irradiation of custom-designed shift registers. It has been shown that the proposed TMR flip-flops are robust to soft errors with a threshold Linear Energy Transfer (LET) from ( 32.4 (MeV⋅cm2/mg) ) to ( 62.5 (MeV⋅cm2/mg) ), depending on the variant.
- ItemHydrothermal carbonization as an alternative sanitation technology: Process optimization and development of low-cost reactor(Brussels : European Commission, 2022) Chung, Jae Wook; Gerner, Gabriel; Ovsyannikova, Ekaterina; Treichler, Alexander; Baier, Urs; Libra, Judy; Krebs, RolfBackground: The provision of safe sanitation services is essential for human well-being and environmental integrity, but it is often lacking in less developed communities with insufficient financial and technical resources. Hydrothermal carbonization (HTC) has been suggested as an alternative sanitation technology, producing value-added products from faecal waste. We evaluated the HTC technology for raw human waste treatment in terms of resource recovery. In addition, we constructed and tested a low-cost HTC reactor for its technical feasibility. Methods: Raw human faeces were hydrothermally treated in a mild severity range (≤ 200 °C and ≤ 1 hr). The total energy recovery was analysed from the energy input, higher heating value (HHV) of hydrochar and biomethane potential of process water. The nutrient contents were recovered through struvite precipitation employing process water and acid leachate from hydrochar ash. A bench-scale low-cost reactor (BLR) was developed using widely available materials and tested for human faeces treatment. Results: The hydrochar had HHVs (23.2 - 25.2 MJ/kg) comparable to bituminous coal. The calorific value of hydrochar accounted for more than 90% of the total energy recovery. Around 78% of phosphorus in feedstock was retained in hydrochar ash, while 15% was in process water. 72% of the initial phosphorus can be recovered as struvite when deficient Mg and NH 4 are supplemented. The experiments with BLR showed stable operation for faecal waste treatment with an energy efficiency comparable to a commercial reactor system. Conclusions: This research presents a proof of concept for the hydrothermal treatment of faecal waste as an alternative sanitation technology, by providing a quantitative evaluation of the resource recovery of energy and nutrients. The experiments with the BLR demonstrate the technical feasibility of the low-cost reactor and support its further development on a larger scale to reach practical implementation.
- ItemReply to Bhowmik et al.: Democratic climate action and studying extreme climate risks are not in tension(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]
- ItemPhylodynamic signatures in the emergence of community-associated MRSA(Washington, DC : National Acad. of Sciences, 2022) Steinig, Eike; Aglua, Izzard; Duchene, Sebastian; Meehan, Michael T.; Yoannes, Mition; Firth, Cadhla; Jaworski, Jan; Drekore, Jimmy; Urakoko, Bohu; Poka, Harry; Wurr, Clive; Ebos, Eri; Nangen, David; MĂĽller, Elke; Mulvey, Peter; Jackson, Charlene; Blomfeldt, Anita; Aamot, Hege Vangstein; Laman, Moses; Manning, Laurens; Earls, Megan; Coleman, David C.; Greenhill, Andrew; Ford, Rebecca; Stegger, Marc; Syed, Muhammad Ali; Jamil, Bushra; Monecke, Stefan; Ehricht, Ralf; Smith, Simon; Pomat, William; Horwood, Paul; Tong, Steven Y. C.; McBryde, EmmaCommunity-associated, methicillin-resistant Staphylococcus aureus (MRSA) lineages have emerged in many geographically distinct regions around the world during the past 30 y. Here, we apply consistent phylodynamic methods across multiple community-associated MRSA lineages to describe and contrast their patterns of emergence and dissemination. We generated whole-genome sequencing data for the Australian sequence type (ST) ST93-MRSA-IV from remote communities in Far North Queensland and Papua New Guinea, and the Bengal Bay ST772-MRSA-V clone from metropolitan communities in Pakistan. Increases in the effective reproduction number (Re) and sustained transmission (Re > 1) coincided with spread of progenitor methicillin-susceptible S. aureus (MSSA) in remote northern Australian populations, dissemination of the ST93-MRSA-IV genotype into population centers on the Australian East Coast, and subsequent importation into the highlands of Papua New Guinea and Far North Queensland. Applying the same phylodynamic methods to existing lineage datasets, we identified common signatures of epidemic growth in the emergence and epidemiological trajectory of community-associated S. aureus lineages from America, Asia, Australasia, and Europe. Surges in Re were observed at the divergence of antibiotic-resistant strains, coinciding with their establishment in regional population centers. Epidemic growth was also observed among drug-resistant MSSA clades in Africa and northern Australia. Our data suggest that the emergence of community-associated MRSA in the late 20th century was driven by a combination of antibiotic-resistant genotypes and host epidemiology, leading to abrupt changes in lineage-wide transmission dynamics and sustained transmission in regional population centers.