Search Results
This looks More Like that: Enhancing Self-Explaining Models by prototypical relevance propagation: This Looks More Like That
2022, Gautam, Srishti, Höhne, Marina M.-C., Hansen, Stine, Jenssen, Robert, Kampffmeyer, Michael
Current 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.
Gas plasma–oxidized sodium chloride acts via hydrogen peroxide in a model of peritoneal carcinomatosis
2022, Miebach, Lea, Freund, Eric, Clemen, Ramona, Kersting, Stephan, Partecke, Lars-Ivo, Bekeschus, Sander
Gas 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.
Design–functionality relationships for adhesion/growth-regulatory galectins
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, Virgil
Glycan-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.
Phylodynamic signatures in the emergence of community-associated MRSA
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, Emma
Community-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.
Reply to Ruhl and Craig: Assessing and governing extreme climate risks needs to be legitimate and democratic
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]
Trajectories of the Earth System in the Anthropocene
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 Joachim
We 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.
Analysis of riboflavin/ultraviolet a corneal cross-linking by molecular spectroscopy
2023, Melcher, Steven, Zimmerer, Cordelia, Galli, Roberta, Golde, Jonas, Herber, Robert, Raiskup, Frederik, Koch, Edmund, Steiner, Gerald
Corneal 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.
Reply to Burgess et al: Catastrophic climate risks are neglected, plausible, and safe to study
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.
Stewardship of global collective behavior
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.
Hydrothermal carbonization as an alternative sanitation technology: Process optimization and development of low-cost reactor
2022, Chung, Jae Wook, Gerner, Gabriel, Ovsyannikova, Ekaterina, Treichler, Alexander, Baier, Urs, Libra, Judy, Krebs, Rolf
Background: 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.