986 results on '"Schewe, P."'
Search Results
2. Learning Atoms from Crystal Structure
- Author
-
Vasylenko, Andrij, Antypov, Dmytro, Schewe, Sven, Daniels, Luke M., Claridge, John B., Dyer, Matthew S., and Rosseinsky, Matthew J.
- Subjects
Condensed Matter - Materials Science ,Condensed Matter - Disordered Systems and Neural Networks ,Physics - Computational Physics - Abstract
Computational modelling of materials using machine learning, ML, and historical data has become integral to materials research. The efficiency of computational modelling is strongly affected by the choice of the numerical representation for describing the composition, structure and chemical elements. Structure controls the properties, but often only the composition of a candidate material is available. Existing elemental descriptors lack direct access to structural insights such as the coordination geometry of an element. In this study, we introduce Local Environment-induced Atomic Features, LEAFs, which incorporate information about the statistically preferred local coordination geometry for atoms in crystal structure into descriptors for chemical elements, enabling the modelling of materials solely as compositions without requiring knowledge of their crystal structure. In the crystal structure, each atomic site can be described by similarity to common local structural motifs; by aggregating these features of similarity from the experimentally verified crystal structures of inorganic materials, LEAFs formulate a set of descriptors for chemical elements and compositions. The direct connection of LEAFs to the local coordination geometry enables the analysis of ML model property predictions, linking compositions to the underlying structure-property relationships. We demonstrate the versatility of LEAFs in structure-informed property predictions for compositions, mapping of chemical space in structural terms, and prioritising elemental substitutions. Based on the latter for predicting crystal structures of binary ionic compounds, LEAFs achieve the state-of-the-art accuracy of 86 per cent. These results suggest that the structurally informed description of chemical elements and compositions developed in this work can effectively guide synthetic efforts in discovering new materials., Comment: 10 pages, 4 figures, supplementary information
- Published
- 2024
3. Sparse Sub-gaussian Random Projections for Semidefinite Programming Relaxations
- Author
-
Guedes-Ayala, Monse, Poirion, Pierre-Louis, Schewe, Lars, and Takeda, Akiko
- Subjects
Mathematics - Optimization and Control - Abstract
Random projection, a dimensionality reduction technique, has been found useful in recent years for reducing the size of optimization problems. In this paper, we explore the use of sparse sub-gaussian random projections to approximate semidefinite programming (SDP) problems by reducing the size of matrix variables, thereby solving the original problem with much less computational effort. We provide some theoretical bounds on the quality of the projection in terms of feasibility and optimality that explicitly depend on the sparsity parameter of the projector. We investigate the performance of the approach for semidefinite relaxations appearing in polynomial optimization, with a focus on combinatorial optimization problems. In particular, we apply our method to the semidefinite relaxations of MAXCUT and MAX-2-SAT. We show that for large unweighted graphs, we can obtain a good bound by solving a projection of the semidefinite relaxation of MAXCUT. We also explore how to apply our method to find the stability number of four classes of imperfect graphs by solving a projection of the second level of the Lasserre Hierarchy. Overall, our computational experiments show that semidefinite programming problems appearing as relaxations of combinatorial optimization problems can be approximately solved using random projections as long as the number of constraints is not too large.
- Published
- 2024
4. DFAMiner: Mining minimal separating DFAs from labelled samples
- Author
-
Dell'Erba, Daniele, Li, Yong, and Schewe, Sven
- Subjects
Computer Science - Formal Languages and Automata Theory ,Computer Science - Machine Learning ,F.4.3 ,I.2.6 - Abstract
We propose DFAMiner, a passive learning tool for learning minimal separating deterministic finite automata (DFA) from a set of labelled samples. Separating automata are an interesting class of automata that occurs generally in regular model checking and has raised interest in foundational questions of parity game solving. We first propose a simple and linear-time algorithm that incrementally constructs a three-valued DFA (3DFA) from a set of labelled samples given in the usual lexicographical order. This 3DFA has accepting and rejecting states as well as don't-care states, so that it can exactly recognise the labelled examples. We then apply our tool to mining a minimal separating DFA for the labelled samples by minimising the constructed automata via a reduction to solving SAT problems. Empirical evaluation shows that our tool outperforms current state-of-the-art tools significantly on standard benchmarks for learning minimal separating DFAs from samples. Progress in the efficient construction of separating DFAs can also lead to finding the lower bound of parity game solving, where we show that DFAMiner can create optimal separating automata for simple languages with up to 7 colours. Future improvements might offer inroads to better data structures., Comment: 24 pages including appendices and references; version for LearnAut workshop
- Published
- 2024
5. Regional impacts poorly constrained by climate sensitivity
- Author
-
Swaminathan, Ranjini, Schewe, Jacob, Walton, Jeremy, Zimmermann, Klaus, Jones, Colin, Betts, Richard A., Burton, Chantelle, Jones, Chris D., Mengel, Matthias, Reyer, Christopher P. O., Turner, Andrew G., and Weigel, Katja
- Subjects
Physics - Atmospheric and Oceanic Physics - Abstract
Climate risk assessments must account for a wide range of possible futures, so scientists often use simulations made by numerous global climate models to explore potential changes in regional climates and their impacts. Some of the latest-generation models have high effective climate sensitivities or EffCS. It has been argued these so-called hot models are unrealistic and should therefore be excluded from analyses of climate change impacts. Whether this would improve regional impact assessments, or make them worse, is unclear. Here we show there is no universal relationship between EffCS and projected changes in a number of important climatic drivers of regional impacts. Analysing heavy rainfall events, meteorological drought, and fire weather in different regions, we find little or no significant correlation with EffCS for most regions and climatic drivers. Even when a correlation is found, internal variability and processes unrelated to EffCS have similar effects on projected changes in the climatic drivers as EffCS. Model selection based solely on EffCS appears to be unjustified and may neglect realistic impacts, leading to an underestimation of climate risks., Comment: Preprint, 30 pages, 4 figures and 2 tables
- Published
- 2024
6. An Objective Improvement Approach to Solving Discounted Payoff Games
- Author
-
Dell'Erba, Daniele, Dumas, Arthur, and Schewe, Sven
- Subjects
Computer Science - Data Structures and Algorithms - Abstract
While discounted payoff games and classic games that reduce to them, like parity and mean-payoff games, are symmetric, their solutions are not. We have taken a fresh view on the properties that optimal solutions need to have, and devised a novel way to converge to them, which is entirely symmetric. We achieve this by building a constraint system that uses every edge to define an inequation, and update the objective function by taking a single outgoing edge for each vertex into account. These edges loosely represent strategies of both players, where the objective function intuitively asks to make the inequation to these edges sharp. In fact, where they are not sharp, there is an `error' represented by the difference between the two sides of the inequation, which is 0 where the inequation is sharp. Hence, the objective is to minimise the sum of these errors. For co-optimal strategies, and only for them, it can be achieved that all selected inequations are sharp or, equivalently, that the sum of these errors is zero. While no co-optimal strategies have been found, we step-wise improve the error by improving the solution for a given objective function or by improving the objective function for a given solution. This also challenges the gospel that methods for solving payoff games are either based on strategy improvement or on value iteration., Comment: arXiv admin note: substantial text overlap with arXiv:2310.01008
- Published
- 2024
7. Comparison of elements and state-variable transfer methods for quasi-incompressible material behaviour in the particle finite element method
- Author
-
Schewe, Markus, Bartel, Thorsten, and Menzel, Andreas
- Published
- 2024
- Full Text
- View/download PDF
8. A Complete Fragment of LTL(EB)
- Author
-
Ferrarotti, Flavio, Rivière, Peter, Schewe, Klaus-Dieter, Singh, Neeraj Kumar, and Ameur, Yamine Aït
- Subjects
Computer Science - Logic in Computer Science ,68Q60, 68N30 - Abstract
The verification of liveness conditions is an important aspect of state-based rigorous methods. This article investigates this problem in a fragment $\square$LTL of the logic LTL(EB), the integration of the UNTIL-fragment of Pnueli's linear time temporal logic (LTL) and the logic of Event-B, in which the most commonly used liveness conditions can be expressed. For this fragment a sound set of derivation rules is developed, which is also complete under mild restrictions for Event-B machines., Comment: 22 pages
- Published
- 2024
9. Choiceless Polynomial Space
- Author
-
Ferrarotti, Flavio and Schewe, Klaus-Dieter
- Subjects
Computer Science - Logic in Computer Science ,68Q15, 68Q10, 03D15 - Abstract
Abstract State Machines (ASMs) provide a model of computations on structures rather than strings. Blass, Gurevich and Shelah showed that deterministic PTIME-bounded ASMs define the choiceless fragment of PTIME, but cannot capture PTIME. In this article deterministic PSPACE-bounded ASMs are introduced, and it is proven that they cannot capture PSPACE. The key for the proof is a characterisation by partial fixed-point formulae over the St\"ark/Nanchen logic for deterministic ASMs and a construction of transitive structures, in which such formulae must hold. This construction exploits that the decisive support theorem for choiceless polynomial time holds under slightly weaker assumptions., Comment: 12 pages. arXiv admin note: substantial text overlap with arXiv:2005.04598
- Published
- 2024
10. Omega-Regular Decision Processes
- Author
-
Hahn, Ernst Moritz, Perez, Mateo, Schewe, Sven, Somenzi, Fabio, Trivedi, Ashutosh, and Wojtczak, Dominik
- Subjects
Computer Science - Logic in Computer Science ,Computer Science - Machine Learning - Abstract
Regular decision processes (RDPs) are a subclass of non-Markovian decision processes where the transition and reward functions are guarded by some regular property of the past (a lookback). While RDPs enable intuitive and succinct representation of non-Markovian decision processes, their expressive power coincides with finite-state Markov decision processes (MDPs). We introduce omega-regular decision processes (ODPs) where the non-Markovian aspect of the transition and reward functions are extended to an omega-regular lookahead over the system evolution. Semantically, these lookaheads can be considered as promises made by the decision maker or the learning agent about her future behavior. In particular, we assume that, if the promised lookaheads are not met, then the payoff to the decision maker is $\bot$ (least desirable payoff), overriding any rewards collected by the decision maker. We enable optimization and learning for ODPs under the discounted-reward objective by reducing them to lexicographic optimization and learning over finite MDPs. We present experimental results demonstrating the effectiveness of the proposed reduction.
- Published
- 2023
11. The sarcoma ring trial: a case-based analysis of inter-center agreement across 21 German-speaking sarcoma centers
- Author
-
Roohani, Siyer, Handtke, Jolina, Hummedah, Kamal, Albertsmeier, Markus, Andreou, Dimosthenis, Apostolidis, Leonidas, Augustin, Marinela, Bauer, Sebastian, Billner, Moritz, Bösch, Florian, Deinzer, Christoph K. W., Deventer, Niklas, Duprée, Anna, Eckert, Franziska, Engel, Lars, Fechner, Katja, Fritzsche, Hagen, Gaidzik, Verena, Ghani, Saeed, Grützmann, Robert, Guder, Wiebke K., Hamacher, Rainer, Hecker, Judith S., Hendricks, Anne, Hillmann, Axel, Houben, Philipp, Hübner, Georg, Ivanyi, Philipp, Jentsch, Christina, Jordan, Maren, Kappl, Peter, Kaths, Moritz, Kessler, Torsten, Kirchberg, Johanna, Knebel, Carolin, Krempien, Robert, Lehner, Burkhard, Lenze, Ulrich, Lindner, Lars H., Lörsch, Alisa Martina, Maguire, Nadia, Müller, Sophie, Piso, Pompiliu, Potkrajcic, Vlatko, Reichardt, Peter, Richter, Stephan, Schewe, Simone, Schiffmann, Lars M., Scholten, Felicitas, Striefler, Jana Käthe, Schwarzbach, Matthias, Seidensaal, Katharina, Semrau, Sabine, Szkandera, Joanna, Szuszies, Christoph J., Timmermann, Beate, Tuscherer, Armin, Wiegering, Armin, Winkelmann, Moritz T., Kaul, David, and Jakob, Jens
- Published
- 2025
- Full Text
- View/download PDF
12. The serum biomarkers NSE and S100B predict intracranial complications and in-hospital survival in patients undergoing veno-venous ECMO
- Author
-
Walther, Janine, Schmandt, Mathias, Muenster, Stefan, Kreyer, Stefan Franz X., Thudium, Marcus, Lehmann, Felix, Zimmermann, Julian, Putensen, Christian, Schewe, Jens-Christian, Weller, Johannes, and Ehrentraut, Stefan Felix
- Published
- 2024
- Full Text
- View/download PDF
13. Ion occupancy of the selectivity filter controls opening of a cytoplasmic gate in the K2P channel TALK-2
- Author
-
Neelsen, Lea C., Riel, Elena B., Rinné, Susanne, Schmid, Freya-Rebecca, Jürs, Björn C., Bedoya, Mauricio, Langer, Jan P., Eymsh, Bisher, Kiper, Aytug K., Cordeiro, Sönke, Decher, Niels, Baukrowitz, Thomas, and Schewe, Marcus
- Published
- 2024
- Full Text
- View/download PDF
14. Atomistic mechanism of coupling between cytosolic sensor domain and selectivity filter in TREK K2P channels
- Author
-
Türkaydin, Berke, Schewe, Marcus, Riel, Elena Barbara, Schulz, Friederike, Biedermann, Johann, Baukrowitz, Thomas, and Sun, Han
- Published
- 2024
- Full Text
- View/download PDF
15. Extracellular modulation of TREK-2 activity with nanobodies provides insight into the mechanisms of K2P channel regulation
- Author
-
Rödström, Karin E. J., Cloake, Alexander, Sörmann, Janina, Baronina, Agnese, Smith, Kathryn H. M., Pike, Ashley C. W., Ang, Jackie, Proks, Peter, Schewe, Marcus, Holland-Kaye, Ingelise, Bushell, Simon R., Elliott, Jenna, Pardon, Els, Baukrowitz, Thomas, Owens, Raymond J., Newstead, Simon, Steyaert, Jan, Carpenter, Elisabeth P., and Tucker, Stephen J.
- Published
- 2024
- Full Text
- View/download PDF
16. Limited progress in global reduction of vulnerability to flood impacts over the past two decades
- Author
-
Sauer, Inga J., Mester, Benedikt, Frieler, Katja, Zimmermann, Sandra, Schewe, Jacob, and Otto, Christian
- Published
- 2024
- Full Text
- View/download PDF
17. Quantifying motor adaptation in a sport-specific table tennis setting
- Author
-
Carius, Daniel, Kaminski, Elisabeth, Clauß, Martina, Schewe, Yannick, Ryk, Lenja, and Ragert, Patrick
- Published
- 2024
- Full Text
- View/download PDF
18. An Objective Improvement Approach to Solving Discounted Payoff Games
- Author
-
Dell'Erba, Daniele, Dumas, Arthur, and Schewe, Sven
- Subjects
Computer Science - Data Structures and Algorithms - Abstract
While discounted payoff games and classic games that reduce to them, like parity and mean-payoff games, are symmetric, their solutions are not. We have taken a fresh view on the constraints that optimal solutions need to satisfy, and devised a novel way to converge to them, which is entirely symmetric. It also challenges the gospel that methods for solving payoff games are either based on strategy improvement or on value iteration., Comment: In Proceedings GandALF 2023, arXiv:2309.17318
- Published
- 2023
- Full Text
- View/download PDF
19. Omega-Regular Reward Machines
- Author
-
Hahn, Ernst Moritz, Perez, Mateo, Schewe, Sven, Somenzi, Fabio, Trivedi, Ashutosh, and Wojtczak, Dominik
- Subjects
Computer Science - Machine Learning ,Computer Science - Artificial Intelligence ,Computer Science - Formal Languages and Automata Theory - Abstract
Reinforcement learning (RL) is a powerful approach for training agents to perform tasks, but designing an appropriate reward mechanism is critical to its success. However, in many cases, the complexity of the learning objectives goes beyond the capabilities of the Markovian assumption, necessitating a more sophisticated reward mechanism. Reward machines and omega-regular languages are two formalisms used to express non-Markovian rewards for quantitative and qualitative objectives, respectively. This paper introduces omega-regular reward machines, which integrate reward machines with omega-regular languages to enable an expressive and effective reward mechanism for RL. We present a model-free RL algorithm to compute epsilon-optimal strategies against omega-egular reward machines and evaluate the effectiveness of the proposed algorithm through experiments., Comment: To appear in ECAI-2023
- Published
- 2023
20. Scenario setup and forcing data for impact model evaluation and impact attribution within the third round of the Inter-Sectoral Model Intercomparison Project (ISIMIP3a)
- Author
-
Frieler, Katja, Volkholz, Jan, Lange, Stefan, Schewe, Jacob, Mengel, Matthias, del Rocío Rivas López, María, Otto, Christian, Reyer, Christopher PO, Karger, Dirk Nikolaus, Malle, Johanna T, Treu, Simon, Menz, Christoph, Blanchard, Julia L, Harrison, Cheryl S, Petrik, Colleen M, Eddy, Tyler D, Ortega-Cisneros, Kelly, Novaglio, Camilla, Rousseau, Yannick, Watson, Reg A, Stock, Charles, Liu, Xiao, Heneghan, Ryan, Tittensor, Derek, Maury, Olivier, Büchner, Matthias, Vogt, Thomas, Wang, Tingting, Sun, Fubao, Sauer, Inga J, Koch, Johannes, Vanderkelen, Inne, Jägermeyr, Jonas, Müller, Christoph, Rabin, Sam, Klar, Jochen, del Valle, Iliusi D Vega, Lasslop, Gitta, Chadburn, Sarah, Burke, Eleanor, Gallego-Sala, Angela, Smith, Noah, Chang, Jinfeng, Hantson, Stijn, Burton, Chantelle, Gädeke, Anne, Li, Fang, Gosling, Simon N, Schmied, Hannes Müller, Hattermann, Fred, Wang, Jida, Yao, Fangfang, Hickler, Thomas, Marcé, Rafael, Pierson, Don, Thiery, Wim, Mercado-Bettín, Daniel, Ladwig, Robert, Ayala-Zamora, Ana Isabel, Forrest, Matthew, and Bechtold, Michel
- Subjects
Earth Sciences ,Atmospheric Sciences ,Climate Action ,Earth sciences - Abstract
Abstract. This paper describes the rationale and the protocol of the first component of the third simulation round of the Inter-Sectoral Impact Model Intercomparison Project (ISIMIP3a, http://www.isimip.org, last access: 2 November 2023) and the associated set of climate-related and direct human forcing data (CRF and DHF, respectively). The observation-based climate-related forcings for the first time include high-resolution observational climate forcings derived by orographic downscaling, monthly to hourly coastal water levels, and wind fields associated with historical tropical cyclones. The DHFs include land use patterns, population densities, information about water and agricultural management, and fishing intensities. The ISIMIP3a impact model simulations driven by these observation-based climate-related and direct human forcings are designed to test to what degree the impact models can explain observed changes in natural and human systems. In a second set of ISIMIP3a experiments the participating impact models are forced by the same DHFs but a counterfactual set of atmospheric forcings and coastal water levels where observed trends have been removed. These experiments are designed to allow for the attribution of observed changes in natural, human, and managed systems to climate change, rising CH4 and CO2 concentrations, and sea level rise according to the definition of the Working Group II contribution to the IPCC AR6.
- Published
- 2024
21. Spatial Variation in Agricultural BMPs and Relationships with Nutrient Yields Across New York State Watersheds
- Author
-
Schewe, Rebecca, Iavorivska, Lidiia, and Kelleher, Christa
- Published
- 2024
- Full Text
- View/download PDF
22. On the Succinctness of Good-for-MDPs Automata
- Author
-
Schewe, Sven and Tang, Qiyi
- Subjects
Computer Science - Formal Languages and Automata Theory - Abstract
Good-for-MDPs and good-for-games automata are two recent classes of nondeterministic automata that reside between general nondeterministic and deterministic automata. Deterministic automata are good-for-games, and good-for-games automata are good-for-MDPs, but not vice versa. One of the question this raises is how these classes relate in terms of succinctness. Good-for-games automata are known to be exponentially more succinct than deterministic automata, but the gap between good-for-MDPs and good-for-games automata as well as the gap between ordinary nondeterministic automata and those that are good-for-MDPs have been open. We establish that these gaps are exponential, and sharpen this result by showing that the latter gap remains exponential when restricting the nondeterministic automata to separating safety or unambiguous reachability automata., Comment: 18 pages
- Published
- 2023
23. A novel family of finite automata for recognizing and learning $\omega$-regular languages
- Author
-
Li, Yong, Schewe, Sven, and Tang, Qiyi
- Subjects
Computer Science - Formal Languages and Automata Theory - Abstract
Families of DFAs (FDFAs) have recently been introduced as a new representation of $\omega$-regular languages. They target ultimately periodic words, with acceptors revolving around accepting some representation $u\cdot v^\omega$. Three canonical FDFAs have been suggested, called periodic, syntactic, and recurrent. We propose a fourth one, limit FDFAs, which can be exponentially coarser than periodic FDFAs and are more succinct than syntactic FDFAs, while they are incomparable (and dual to) recurrent FDFAs. We show that limit FDFAs can be easily used to check not only whether {\omega}-languages are regular, but also whether they are accepted by deterministic B\"uchi automata. We also show that canonical forms can be left behind in applications: the limit and recurrent FDFAs can complement each other nicely, and it may be a good way forward to use a combination of both. Using this observation as a starting point, we explore making more efficient use of Myhill-Nerode's right congruences in aggressively increasing the number of don't-care cases in order to obtain smaller progress automata. In pursuit of this goal, we gain succinctness, but pay a high price by losing constructiveness., Comment: 30 pages, accepted at ATVA 2023
- Published
- 2023
24. Singly Exponential Translation of Alternating Weak B\'uchi Automata to Unambiguous B\'uchi Automata
- Author
-
Li, Yong, Schewe, Sven, and Vardi, Moshe Y.
- Subjects
Computer Science - Formal Languages and Automata Theory ,F.4.3 - Abstract
We introduce a method for translating an alternating weak B\"uchi automaton (AWA), which corresponds to a Linear Dynamic Logic (LDL) formula, to an unambiguous B\"uchi automaton (UBA). Our translations generalise constructions for Linear Temporal Logic (LTL), a less expressive specification language than LDL. In classical constructions, LTL formulas are first translated to alternating \emph{very weak} automata (AVAs) -- automata that have only singleton strongly connected components (SCCs); the AVAs are then handled by efficient disambiguation procedures. However, general AWAs can have larger SCCs, which complicates disambiguation. Currently, the only available disambiguation procedure has to go through an intermediate construction of nondeterministic B\"uchi automata (NBAs), which would incur an exponential blow-up of its own. We introduce a translation from \emph{general} AWAs to UBAs with a \emph{singly} exponential blow-up, which also immediately provides a singly exponential translation from LDL to UBAs. Interestingly, the complexity of our translation is \emph{smaller} than the best known disambiguation algorithm for NBAs (broadly $(0.53n)^n$ vs. $(0.76n)^n$), while the input of our construction can be exponentially more succinct., Comment: 23 pages
- Published
- 2023
25. Ion occupancy of the selectivity filter controls opening of a cytoplasmic gate in the K2P channel TALK-2
- Author
-
Lea C. Neelsen, Elena B. Riel, Susanne Rinné, Freya-Rebecca Schmid, Björn C. Jürs, Mauricio Bedoya, Jan P. Langer, Bisher Eymsh, Aytug K. Kiper, Sönke Cordeiro, Niels Decher, Thomas Baukrowitz, and Marcus Schewe
- Subjects
Science - Abstract
Abstract Two-pore domain K+ (K2P) channel activity was previously thought to be controlled primarily via a selectivity filter (SF) gate. However, recent crystal structures of TASK-1 and TASK-2 revealed a lower gate at the cytoplasmic pore entrance. Here, we report functional evidence of such a lower gate in the K2P channel K2P17.1 (TALK-2, TASK-4). We identified compounds (drugs and lipids) and mutations that opened the lower gate allowing the fast modification of pore cysteine residues. Surprisingly, stimuli that directly target the SF gate (i.e., pHe., Rb+ permeation, membrane depolarization) also opened the cytoplasmic gate. Reciprocally, opening of the lower gate reduced the electric work to open the SF via voltage driven ion binding. Therefore, it appears that the SF is so rigidly locked into the TALK-2 protein structure that changes in ion occupancy can pry open a distant lower gate and, vice versa, opening of the lower gate concurrently promote SF gate opening. This concept might extent to other K+ channels that contain two gates (e.g., voltage-gated K+ channels) for which such a positive gate coupling has been suggested, but so far not directly demonstrated.
- Published
- 2024
- Full Text
- View/download PDF
26. History-deterministic Timed Automata
- Author
-
Bose, Sougata, Henzinger, Thomas A., Lehtinen, Karoliina, Schewe, Sven, and Totzke, Patrick
- Subjects
Computer Science - Formal Languages and Automata Theory ,Computer Science - Logic in Computer Science - Abstract
We explore the notion of history-determinism in the context of timed automata (TA) over infinite timed words. History-deterministic (HD) automata are those in which nondeterminism can be resolved on the fly, based on the run constructed thus far. History-determinism is a robust property that admits different game-based characterisations, and HD specifications allow for game-based verification without an expensive determinization step. We show that the class of timed $\omega$-languages recognized by HD timed automata strictly extends that of deterministic ones, and is strictly included in those recognised by fully non-deterministic TA. For non-deterministic timed automata it is known that universality is already undecidable for safety/reachability TA. For history-deterministic TA with arbitrary parity acceptance, we show that timed universality, inclusion, and synthesis all remain decidable and are EXPTIME-complete. For the subclass of TA with safety or reachability acceptance, one can decide (in EXPTIME) whether such an automaton is history-deterministic. If so, it can effectively determinized without introducing new automaton states.
- Published
- 2023
- Full Text
- View/download PDF
27. Fostering Shared Decision-Making Between Patients and Health Care Professionals in Clinical Practice Guidelines: Protocol for a Project to Develop and Test a Tool for Guideline Developers
- Author
-
Lena Fischer, Fülöp Scheibler, Corinna Schaefer, Torsten Karge, Thomas Langer, Leon Vincent Schewe, Ivan D Florez, Andrew Hutchinson, Sheyu Li, Marta Maes-Carballo, Zachary Munn, Lilisbeth Perestelo-Perez, Livia Puljak, Anne Stiggelbout, and Dawid Pieper
- Subjects
Medicine ,Computer applications to medicine. Medical informatics ,R858-859.7 - Abstract
BackgroundClinical practice guidelines (CPGs) are designed to assist health care professionals in medical decision-making, but they often lack effective integration of shared decision-making (SDM) principles to reflect patient values and preferences, particularly in the context of preference-sensitive CPG recommendations. To address this shortcoming and foster SDM through CPGs, the integration of patient decision aids (PDAs) into CPGs has been proposed as an important strategy. However, methods for systematically identifying and prioritizing CPG recommendations relevant to SDM and related decision support tools are currently lacking. ObjectiveThe aim of the project is to develop (1) a tool for systematically identifying and prioritizing CPG recommendations for which SDM is considered particularly relevant and (2) a platform for PDAs to support practical SDM implementation. MethodsThe project consists of 6 work packages (WPs). It is embedded in the German health care context but has an international focus. In WP 1, we will conduct a scoping review in bibliographic databases and gray literature sources to identify methods used to foster SDM via PDAs in the context of CPGs. In WP 2, we will conduct semistructured interviews with CPG experts to better understand the concepts of preference sensitivity and identify strategies for fostering SDM through CPGs. WP 3, a modified Delphi study including surveys and focus groups with SDM experts, aims to define and operationalize preference sensitivity. Based on the results of the Delphi study, we will develop a methodology for prioritizing key questions in CPGs. In WP 4, the tool will be developed. A list of relevant items to identify CPG recommendations for which SDM is most relevant will be created, tested, and iteratively refined, accompanied by the development of a user manual. In WP 5, a platform for creating and digitizing German-language PDAs will be developed to support the practical application of SDM during clinical encounters. WP 6 will conclude the project by testing the tool with newly developed and revised CPGs. ResultsThe Brandenburg Medical School Ethics Committee approved the project (165122023-ANF). An international multidisciplinary advisory board is involved to guide the tool development on CPGs and SDM. Patient partners are involved throughout the project, considering the essential role of the patient perspective in SDM. As of February 20, 2024, we are currently assessing literature references to determine eligibility for inclusion in the scoping review (WP 1). We expect the project to be completed by December 31, 2026. ConclusionsThe tool will enable CPG developers to systematically incorporate aspects of SDM into CPG development, thereby providing guideline-based support for the patient-practitioner interaction. Together, the tool for CPGs and the platform for PDAs will create a systematic link between CPGs, SDM, and PDAs, which may facilitate SDM in clinical practice. International Registered Report Identifier (IRRID)DERR1-10.2196/57611
- Published
- 2024
- Full Text
- View/download PDF
28. Understanding the biases to sepsis surveillance and quality assurance caused by inaccurate coding in administrative health data
- Author
-
Schwarzkopf, Daniel, Rose, Norman, Fleischmann-Struzek, Carolin, Boden, Beate, Dorow, Heike, Edel, Andreas, Friedrich, Marcus, Gonnert, Falk A., Götz, Jürgen, Gründling, Matthias, Heim, Markus, Holbeck, Kirill, Jaschinski, Ulrich, Koch, Christian, Künzer, Christian, Le Ngoc, Khanh, Lindau, Simone, Mehlmann, Ngoc B., Meschede, Jan, Meybohm, Patrick, Ouart, Dominique, Putensen, Christian, Sander, Michael, Schewe, Jens-Christian, Schlattmann, Peter, Schmidt, Götz, Schneider, Gerhard, Spies, Claudia, Steinsberger, Ferdinand, Zacharowski, Kai, Zinn, Sebastian, and Reinhart, Konrad
- Published
- 2024
- Full Text
- View/download PDF
29. Extraction of nanometer-scale displacements from noisy signals at frequencies down to 1 mHz obtained by differential laser Doppler vibrometry
- Author
-
D. Kohlmann, M. Schewe, H. Wulfmeier, C. Rembe, and H. Fritze
- Subjects
Technology - Abstract
A method is presented by which very small, slow, anharmonic signals can be extracted from measurement data overlaid with noise that is orders of magnitude larger than the signal of interest. To this end, a multi-step filtering process is applied to a time signal containing the time-dependent displacement of the surface of a sample, which is determined with a contactless measurement method, differential laser Doppler vibrometry (D-LDV), at elevated temperatures. The time signal contains the phase difference of the measurement and reference laser beams of the D-LDV, already greatly reducing noise from, e.g., length fluctuations, heat haze, and mechanical vibrations. In postprocessing of the data, anharmonic signal contributions are identified and extracted to show the accurate displacement originating from thickness changes of thin films and related sample bending. The approach is demonstrated on a Pr0.1Ce0.9O2−δ (PCO) thin film deposited on a single-crystalline ZrO2-based substrate. The displacement extracted from the data is ca. 38 % larger and the uncertainty ca. 35 % lower than those calculated directly from the D-LDV spectrum.
- Published
- 2024
- Full Text
- View/download PDF
30. Atomistic mechanism of coupling between cytosolic sensor domain and selectivity filter in TREK K2P channels
- Author
-
Berke Türkaydin, Marcus Schewe, Elena Barbara Riel, Friederike Schulz, Johann Biedermann, Thomas Baukrowitz, and Han Sun
- Subjects
Science - Abstract
Abstract The two-pore domain potassium (K2P) channels TREK-1 and TREK-2 link neuronal excitability to a variety of stimuli including mechanical force, lipids, temperature and phosphorylation. This regulation involves the C-terminus as a polymodal stimulus sensor and the selectivity filter (SF) as channel gate. Using crystallographic up- and down-state structures of TREK-2 as a template for full atomistic molecular dynamics (MD) simulations, we reveal that the SF in down-state undergoes inactivation via conformational changes, while the up-state structure maintains a stable and conductive SF. This suggests an atomistic mechanism for the low channel activity previously assigned to the down state, but not evident from the crystal structure. Furthermore, experimentally by using (de-)phosphorylation mimics and chemically attaching lipid tethers to the proximal C-terminus (pCt), we confirm the hypothesis that moving the pCt towards the membrane induces the up-state. Based on MD simulations, we propose two gating pathways by which movement of the pCt controls the stability (i.e., conductivity) of the filter gate. Together, these findings provide atomistic insights into the SF gating mechanism and the physiological regulation of TREK channels by phosphorylation.
- Published
- 2024
- Full Text
- View/download PDF
31. Extracellular modulation of TREK-2 activity with nanobodies provides insight into the mechanisms of K2P channel regulation
- Author
-
Karin E. J. Rödström, Alexander Cloake, Janina Sörmann, Agnese Baronina, Kathryn H. M. Smith, Ashley C. W. Pike, Jackie Ang, Peter Proks, Marcus Schewe, Ingelise Holland-Kaye, Simon R. Bushell, Jenna Elliott, Els Pardon, Thomas Baukrowitz, Raymond J. Owens, Simon Newstead, Jan Steyaert, Elisabeth P. Carpenter, and Stephen J. Tucker
- Subjects
Science - Abstract
Abstract Potassium channels of the Two-Pore Domain (K2P) subfamily, KCNK1-KCNK18, play crucial roles in controlling the electrical activity of many different cell types and represent attractive therapeutic targets. However, the identification of highly selective small molecule drugs against these channels has been challenging due to the high degree of structural and functional conservation that exists not only between K2P channels, but across the whole K+ channel superfamily. To address the issue of selectivity, here we generate camelid antibody fragments (nanobodies) against the TREK-2 (KCNK10) K2P K+ channel and identify selective binders including several that directly modulate channel activity. X-ray crystallography and CryoEM data of these nanobodies in complex with TREK-2 also reveal insights into their mechanisms of activation and inhibition via binding to the extracellular loops and Cap domain, as well as their suitability for immunodetection. These structures facilitate design of a biparatropic inhibitory nanobody with markedly improved sensitivity. Together, these results provide important insights into TREK channel gating and provide an alternative, more selective approach to modulation of K2P channel activity via their extracellular domains.
- Published
- 2024
- Full Text
- View/download PDF
32. Limited progress in global reduction of vulnerability to flood impacts over the past two decades
- Author
-
Inga J. Sauer, Benedikt Mester, Katja Frieler, Sandra Zimmermann, Jacob Schewe, and Christian Otto
- Subjects
Geology ,QE1-996.5 ,Environmental sciences ,GE1-350 - Abstract
Abstract Global flood impacts have risen in recent decades. While increasing exposure was the dominant driver of surging impacts, counteracting vulnerability reductions have been detected, but were too weak to reverse this trend. To assess the ongoing progress on vulnerability reduction, we combine a recently available dataset of flooded areas derived from satellite imagery for 913 events with four global disaster databases and socio-economic data. Event-specific flood vulnerabilities for assets, fatalities and displacements reveal a lack of progress in reducing global flood vulnerability from 2000—2018. We examine the relationship between vulnerabilities and human development, inequality, flood exposure and local structural characteristics. We find that vulnerability levels are significantly lower in areas with good structural characteristics and significantly higher in low developed areas. However, socio-economic development was insufficient to reduce vulnerabilities over the study period. Nevertheless, the strong correlation between vulnerability and structural characteristics suggests further potential for adaptation through vulnerability reduction.
- Published
- 2024
- Full Text
- View/download PDF
33. Cryogenic Buffer Gas beams of AlF, CaF, MgF, YbF, Al, Ca, Yb and NO -- a comparison
- Author
-
Wright, Sidney C., Doppelbauer, Maximilian, Hofsäss, Simon, Schewe, H. Christian, Sartakov, Boris, Meijer, Gerard, and Truppe, Stefan
- Subjects
Physics - Atomic Physics ,Physics - Chemical Physics - Abstract
Cryogenic buffer gas beams are central to many cold molecule experiments. Here, we use absorption and fluorescence spectroscopy to directly compare molecular beams of AlF, CaF, MgF, and YbF molecules, produced by chemical reaction of laser ablated atoms with fluorine rich reagents. The beam brightness for AlF is measured as $2\times 10^{12}$ molecules per steradian per pulse in a single rotational state, comparable to an Al atomic beam produced in the same setup. The CaF, MgF and YbF beams show an order of magnitude lower brightness than AlF, and far below the brightness of Ca and Yb beams. The addition of either NF$_3$ or SF$_6$ to the cell extinguishes the Al atomic beam, but has a minimal effect on the Ca and Yb beams. NF$_3$ reacts more efficiently than SF$_6$, as a significantly lower flow rate is required to maximise the molecule production, which is particularly beneficial for long-term stability of the AlF beam. We use NO as a proxy for the reactant gas as it can be optically detected. We demonstrate that a cold, rotationally pure NO beam can be generated by laser desorption, thereby gaining insight into the dynamics of the reactant gas inside the buffer gas cell., Comment: 29 pages, 17 figures, 1 table
- Published
- 2022
- Full Text
- View/download PDF
34. Bridging Electrochemistry and Photoelectron Spectroscopy in the Context of Birch Reduction: Detachment Energies and Redox Potentials of Electron, Dielectron, and Benzene Radical Anion in Liquid Ammonia
- Author
-
Nemirovich, Tatiana, Kostal, Vojtech, Copko, Jakub, Schewe, H. Christian, Bohacova, Sona, Martinek, Tomas, Slanina, Tomas, and Jungwirth, Pavel
- Subjects
Physics - Chemical Physics ,Physics - Computational Physics - Abstract
Birch reduction is a time-proven way to hydrogenate aromatic hydrocarbons (such as benzene), which relies on the reducing power of electrons released from alkali metals into liquid ammonia. We have succeeded to characterize the key intermediates of the Birch reduction process - the solvated electron and dielectron and the benzene radical anion - using cyclic voltammetry and photoelectron spectroscopy, aided by electronic structure calculations. In this way, we not only quantify the electron binding energies of these species, which are decisive for the mechanism of the reaction but also use Birch reduction as a case study to directly connect the two seemingly unrelated experimental techniques., Comment: after revision
- Published
- 2022
- Full Text
- View/download PDF
35. Natural Colors of Infinite Words
- Author
-
Ehlers, Rüdiger and Schewe, Sven
- Subjects
Computer Science - Formal Languages and Automata Theory ,Computer Science - Logic in Computer Science ,F.4.3 ,F.4.1 - Abstract
While finite automata have minimal DFAs as a simple and natural normal form, deterministic omega-automata do not currently have anything similar. One reason for this is that a normal form for omega-regular languages has to speak about more than acceptance - for example, to have a normal form for a parity language, it should relate every infinite word to some natural color for this language. This raises the question of whether or not a concept such as a natural color of an infinite word (for a given language) exists, and, if it does, how it relates back to automata. We define the natural color of a word purely based on an omega-regular language, and show how this natural color can be traced back from any deterministic parity automaton after two cheap and simple automaton transformations. The resulting streamlined automaton does not necessarily accept every word with its natural color, but it has a 'co-run', which is like a run, but can once move to a language equivalent state, whose color is the natural color, and no co-run with a higher color exists. The streamlined automaton defines, for every color c, a good-for-games co-B\"uchi automaton that recognizes the words whose natural colors w.r.t. the represented language are at least c. This provides a canonical representation for every $\omega$-regular language, because good-for-games co-B\"uchi automata have a canonical minimal (and cheap to obtain) representation for every co-B\"uchi language.
- Published
- 2022
36. Recursive Reinforcement Learning
- Author
-
Hahn, Ernst Moritz, Perez, Mateo, Schewe, Sven, Somenzi, Fabio, Trivedi, Ashutosh, and Wojtczak, Dominik
- Subjects
Computer Science - Machine Learning ,Computer Science - Artificial Intelligence - Abstract
Recursion is the fundamental paradigm to finitely describe potentially infinite objects. As state-of-the-art reinforcement learning (RL) algorithms cannot directly reason about recursion, they must rely on the practitioner's ingenuity in designing a suitable "flat" representation of the environment. The resulting manual feature constructions and approximations are cumbersome and error-prone; their lack of transparency hampers scalability. To overcome these challenges, we develop RL algorithms capable of computing optimal policies in environments described as a collection of Markov decision processes (MDPs) that can recursively invoke one another. Each constituent MDP is characterized by several entry and exit points that correspond to input and output values of these invocations. These recursive MDPs (or RMDPs) are expressively equivalent to probabilistic pushdown systems (with call-stack playing the role of the pushdown stack), and can model probabilistic programs with recursive procedural calls. We introduce Recursive Q-learning -- a model-free RL algorithm for RMDPs -- and prove that it converges for finite, single-exit and deterministic multi-exit RMDPs under mild assumptions.
- Published
- 2022
37. Alternating Good-for-MDP Automata
- Author
-
Hahn, Ernst Moritz, Perez, Mateo, Schewe, Sven, Somenzi, Fabio, Trivedi, Ashutosh, and Wojtczak, Dominik
- Subjects
Computer Science - Formal Languages and Automata Theory ,Computer Science - Artificial Intelligence ,Computer Science - Logic in Computer Science - Abstract
When omega-regular objectives were first proposed in model-free reinforcement learning (RL) for controlling MDPs, deterministic Rabin automata were used in an attempt to provide a direct translation from their transitions to scalar values. While these translations failed, it has turned out that it is possible to repair them by using good-for-MDPs (GFM) B\"uchi automata instead. These are nondeterministic B\"uchi automata with a restricted type of nondeterminism, albeit not as restricted as in good-for-games automata. Indeed, deterministic Rabin automata have a pretty straightforward translation to such GFM automata, which is bi-linear in the number of states and pairs. Interestingly, the same cannot be said for deterministic Streett automata: a translation to nondeterministic Rabin or B\"uchi automata comes at an exponential cost, even without requiring the target automaton to be good-for-MDPs. Do we have to pay more than that to obtain a good-for-MDP automaton? The surprising answer is that we have to pay significantly less when we instead expand the good-for-MDP property to alternating automata: like the nondeterministic GFM automata obtained from deterministic Rabin automata, the alternating good-for-MDP automata we produce from deterministic Streett automata are bi-linear in the the size of the deterministic automaton and its index, and can therefore be exponentially more succinct than minimal nondeterministic B\"uchi automata.
- Published
- 2022
38. Smaller Progress Measures and Separating Automata for Parity Games
- Author
-
Dell'Erba, Daniele and Schewe, Sven
- Subjects
Computer Science - Data Structures and Algorithms - Abstract
Calude et al. have recently shown that parity games can be solved in quasi-polynomial time, a landmark result that has led to a number of approaches with quasi-polynomial complexity. Jurdinski and Lasic have further improved the precise complexity of parity games, especially when the number of priorities is low (logarithmic in the number of positions). Both of these algorithms belong to a class of game solving techniques now often called separating automata: deterministic automata that can be used as witness automata to decide the winner in parity games up to a given number of states and colours. We suggest a number of adjustments to the approach of Calude et al. that lead to smaller statespaces. These include and improve over those earlier introduced by Fearnley et al. We identify two of them that, together, lead to a statespace of exactly the same size Jurdzinski and Lasic's concise progress measures, which currently hold the crown as smallest statespace. The remaining improvements, hence, lead to a further reduction in the size of the statespace, making our approach the most succinct progress measures available for parity games.
- Published
- 2022
- Full Text
- View/download PDF
39. Analysis of Osteosarcoma Cell Lines and Patient Tissue Using a 3D In Vivo Tumor Model—Possible Effects of Punicalagin
- Author
-
Anna Rebecca Dorn, Sara Neff, Sophia Hupp, Melissa Engelhardt, Eric Pion, Ulrich Lenze, Carolin Knebel, Anna Duprée, Simone Schewe, Markus Weber, Christian Wulbrand, Axel Hillmann, Florian Weber, Phillip Clarke, Philipp Kainz, Thiha Aung, and Silke Haerteis
- Subjects
osteosarcoma ,CAM assay ,3D in vivo tumor model ,punicalagin ,MTT assay ,angiogenesis ,Cytology ,QH573-671 - Abstract
Osteosarcomas are the most common primary malignant bone tumors and mostly affect children, adolescents, and young adults. Despite current treatment options such as surgery and polychemotherapy, the survival of patients with metastatic disease remains poor. In recent studies, punicalagin has reduced the cell viability, angiogenesis, and invasion in cell culture trials. The aim of this study was to examine the effects of punicalagin on osteosarcomas in a 3D in vivo tumor model. Human osteosarcoma biopsies and SaOs-2 and MG-63 cells, were grown in a 3D in vivo chorioallantoic membrane (CAM) model. After a cultivation period of up to 72 h, the tumors received daily treatment with punicalagin for 4 days. Weight measurements of the CAM tumors were performed, and laser speckle contrast imaging (LSCI) and a deep learning-based image analysis software (CAM Assay Application v.3.1.0) were used to measure angiogenesis. HE, Ki-67, and Caspase-3 staining was performed after explantation. The osteosarcoma cell lines SaOs-2 and MG-63 and osteosarcoma patient tissue displayed satisfactory growth patterns on the CAM. Treatment with punicalagin decreased tumor weight, proliferation, and tumor-induced angiogenesis, and the tumor tissue showed pro-apoptotic characteristics. These results provide a robust foundation for the implementation of further studies and show that punicalagin offers a promising supplementary treatment option for osteosarcoma patients. The 3D in vivo tumor model represents a beneficial model for the testing of anti-cancer therapies.
- Published
- 2024
- Full Text
- View/download PDF
40. Enhancing Adversarial Training with Second-Order Statistics of Weights
- Author
-
Jin, Gaojie, Yi, Xinping, Huang, Wei, Schewe, Sven, and Huang, Xiaowei
- Subjects
Computer Science - Machine Learning - Abstract
Adversarial training has been shown to be one of the most effective approaches to improve the robustness of deep neural networks. It is formalized as a min-max optimization over model weights and adversarial perturbations, where the weights can be optimized through gradient descent methods like SGD. In this paper, we show that treating model weights as random variables allows for enhancing adversarial training through \textbf{S}econd-Order \textbf{S}tatistics \textbf{O}ptimization (S$^2$O) with respect to the weights. By relaxing a common (but unrealistic) assumption of previous PAC-Bayesian frameworks that all weights are statistically independent, we derive an improved PAC-Bayesian adversarial generalization bound, which suggests that optimizing second-order statistics of weights can effectively tighten the bound. In addition to this theoretical insight, we conduct an extensive set of experiments, which show that S$^2$O not only improves the robustness and generalization of the trained neural networks when used in isolation, but also integrates easily in state-of-the-art adversarial training techniques like TRADES, AWP, MART, and AVMixup, leading to a measurable improvement of these techniques. The code is available at \url{https://github.com/Alexkael/S2O}., Comment: Accepted by CVPR2022
- Published
- 2022
41. Spectroscopic characterization of singlet-triplet doorway states of aluminum monofluoride
- Author
-
Walter, Nicole, Seifert, Johannes, Truppe, Stefan, Schewe, Hanns Christian, Sartakov, Boris, and Meijer, Gerard
- Subjects
Quantum Physics - Abstract
Aluminum monofluoride (AlF) possesses highly favorable properties for laser cooling, both via the A$^1\Pi$ and a$^3\Pi$ states. Determining efficient pathways between the singlet and the triplet manifold of electronic states will be advantageous for future experiments at ultralow temperatures. The lowest rotational levels of the A$^1\Pi, v=6$ and b$^3\Sigma^+, v=5$ states of AlF are nearly iso-energetic and interact via spin-orbit coupling. These levels thus have a strongly mixed spin-character and provide a singlet-triplet doorway. We here present a hyperfine resolved spectroscopic study of the A$^1\Pi, v=6$ // b$^3\Sigma^+, v=5$ perturbed system in a jet-cooled, pulsed molecular beam. From a fit to the observed energies of the hyperfine levels, the fine and hyperfine structure parameters of the coupled states, their relative energies as well as the spin-orbit interaction parameter are determined. The standard deviation of the fit is about 15 MHz. We experimentally determine the radiative lifetimes of selected hyperfine levels by time-delayed ionization, Lamb dip spectroscopy and accurate measurements of the transition lineshapes. The measured lifetimes range between 2 ns and 200 ns, determined by the degree of singlet-triplet mixing for each level., Comment: 12 pages, 11 figures
- Published
- 2022
- Full Text
- View/download PDF
42. Deciding What is Good-for-MDPs
- Author
-
Schewe, Sven, Tang, Qiyi, and Zhanabekova, Tansholpan
- Subjects
Computer Science - Formal Languages and Automata Theory - Abstract
Nondeterministic Good-for-MDP (GFM) automata are for MDP model checking and reinforcement learning what good-for-games automata are for reactive synthesis: a more compact alternative to deterministic automata that displays nondeterminism, but only so much that it can be resolved locally, such that a syntactic product can be analysed. GFM has recently been introduced as a property for reinforcement learning, where the simpler B\"uchi acceptance conditions it allows to use is key. However, while there are classic and novel techniques to obtain automata that are GFM, there has not been a decision procedure for checking whether or not an automaton is GFM. We show that GFM-ness is decidable and provide an EXPTIME decision procedure as well as a PSPACE-hardness proof., Comment: 26 pages, accepted to CONCUR 2023
- Published
- 2022
43. Recurrent DNMT3B rearrangements are associated with unfavorable outcome in dicentric (9;20)-positive pediatric BCP-ALL
- Author
-
Antić, Željko, van Bömmel, Alena, Riege, Konstantin, Lentes, Jana, Schröder, Charlotte, Alten, Julia, Eckert, Cornelia, Fuhrmann, Lara, Steinemann, Doris, Lenk, Lennart, Schewe, Denis M., Zimmermann, Martin, Schrappe, Martin, Schlegelberger, Brigitte, Cario, Gunnar, Hoffmann, Steve, and Bergmann, Anke K.
- Published
- 2023
- Full Text
- View/download PDF
44. An Optimised Live Attenuated Influenza Vaccine Ferret Efficacy Model Successfully Translates H1N1 Clinical Data
- Author
-
Katarzyna E. Schewe, Shaun Cooper, Jonathan Crowe, Steffan Llewellyn, Lydia Ritter, Kathryn A. Ryan, and Oliver Dibben
- Subjects
influenza virus ,live attenuated influenza vaccine ,ferret ,animal model ,clinical translatability ,vaccine efficacy ,Medicine - Abstract
Between 2013 and 2016, the A/H1N1pdm09 component of the live attenuated influenza vaccine (LAIV) produced instances of lower-than-expected vaccine effectiveness. Standard pre-clinical ferret models, using a human-like vaccine dose and focusing on antigenic match to circulating wildtype (wt) strains, were unable to predict these fluctuations. By optimising the vaccine dose and utilising clinically relevant endpoints, we aimed to develop a ferret efficacy model able to reproduce clinical observations. Ferrets were intranasally vaccinated with 4 Log10 FFU/animal (1000-fold reduction compared to clinical dose) of seven historical LAIV formulations with known (19–90%) H1N1 vaccine efficacy or effectiveness (VE). Following homologous H1N1 wt virus challenge, protection was assessed based on primary endpoints of wt virus shedding in the upper respiratory tract and the development of fever. LAIV formulations with high (82–90%) H1N1 VE provided significant protection from wt challenge, while formulations with reduced (19–32%) VE tended not to provide significant protection. The strongest correlation observed was between reduction in wt shedding and VE (R2 = 0.75). Conversely, serum immunogenicity following vaccination was not a reliable indicator of protection (R2 = 0.37). This demonstrated that, by optimisation of the vaccine dose and the use of non-serological, clinically relevant protection endpoints, the ferret model could successfully translate clinical H1N1 LAIV VE data.
- Published
- 2024
- Full Text
- View/download PDF
45. Weight Expansion: A New Perspective on Dropout and Generalization
- Author
-
Jin, Gaojie, Yi, Xinping, Yang, Pengfei, Zhang, Lijun, Schewe, Sven, and Huang, Xiaowei
- Subjects
Computer Science - Machine Learning ,Statistics - Machine Learning - Abstract
While dropout is known to be a successful regularization technique, insights into the mechanisms that lead to this success are still lacking. We introduce the concept of \emph{weight expansion}, an increase in the signed volume of a parallelotope spanned by the column or row vectors of the weight covariance matrix, and show that weight expansion is an effective means of increasing the generalization in a PAC-Bayesian setting. We provide a theoretical argument that dropout leads to weight expansion and extensive empirical support for the correlation between dropout and weight expansion. To support our hypothesis that weight expansion can be regarded as an \emph{indicator} of the enhanced generalization capability endowed by dropout, and not just as a mere by-product, we have studied other methods that achieve weight expansion (resp.\ contraction), and found that they generally lead to an increased (resp.\ decreased) generalization ability. This suggests that dropout is an attractive regularizer, because it is a computationally cheap method for obtaining weight expansion. This insight justifies the role of dropout as a regularizer, while paving the way for identifying regularizers that promise improved generalization through weight expansion., Comment: TMLR
- Published
- 2022
46. Imaging of chemical kinetics at the water-water interface in a free-flowing liquid flat-jet
- Author
-
Schewe, H. Christian, Credidio, Bruno, Ghrist, Aaron M., Malerz, Sebastian, Ozga, Christian, Knie, André, Haak, Henrik, Meijer, Gerard, Winter, Bernd, and Osterwalder, Andreas
- Subjects
Physics - Chemical Physics ,Physics - Fluid Dynamics - Abstract
We present chemical kinetics measurements of the luminol oxydation chemiluminescence reaction at the interface between two aqueous solutions, using liquid jet technology. Free-flowing iquid microjets are a relatively recent development that has found its way into a growing number of applications in spectroscopy and dynamics. A variant thereof, called flat-jet, is obtained when two cylindrical jets of a liquid are crossed, leading to a chain of planar leaf-shaped structures of the flowing liquid. We here show that in the first leaf of this chain the fluids do not exhibit turbulent mixing, providing a clean interface between the liquids from the impinging jets. We also show, using the example of the luminol chemiluminescence reaction, how this setup can be used to obtain kinetics information from friction-less flow and by circumventing the requirement for rapid mixing but by intentionally suppressing all turbulent mixing and instead relying on diffusion.
- Published
- 2022
47. Reliability Assessment and Safety Arguments for Machine Learning Components in System Assurance
- Author
-
Dong, Yi, Huang, Wei, Bharti, Vibhav, Cox, Victoria, Banks, Alec, Wang, Sen, Zhao, Xingyu, Schewe, Sven, and Huang, Xiaowei
- Subjects
Computer Science - Software Engineering ,Computer Science - Artificial Intelligence ,Computer Science - Machine Learning ,Computer Science - Robotics - Abstract
The increasing use of Machine Learning (ML) components embedded in autonomous systems -- so-called Learning-Enabled Systems (LESs) -- has resulted in the pressing need to assure their functional safety. As for traditional functional safety, the emerging consensus within both, industry and academia, is to use assurance cases for this purpose. Typically assurance cases support claims of reliability in support of safety, and can be viewed as a structured way of organising arguments and evidence generated from safety analysis and reliability modelling activities. While such assurance activities are traditionally guided by consensus-based standards developed from vast engineering experience, LESs pose new challenges in safety-critical application due to the characteristics and design of ML models. In this article, we first present an overall assurance framework for LESs with an emphasis on quantitative aspects, e.g., breaking down system-level safety targets to component-level requirements and supporting claims stated in reliability metrics. We then introduce a novel model-agnostic Reliability Assessment Model (RAM) for ML classifiers that utilises the operational profile and robustness verification evidence. We discuss the model assumptions and the inherent challenges of assessing ML reliability uncovered by our RAM and propose solutions to practical use. Probabilistic safety argument templates at the lower ML component-level are also developed based on the RAM. Finally, to evaluate and demonstrate our methods, we not only conduct experiments on synthetic/benchmark datasets but also scope our methods with case studies on simulated Autonomous Underwater Vehicles and physical Unmanned Ground Vehicles., Comment: Preprint Accepted by ACM Transactions on Embedded Computing Systems
- Published
- 2021
- Full Text
- View/download PDF
48. Increased impairment of cerebral autoregulation in COVID-19 associated pulmonary failure requiring extracorporeal membrane oxygenation
- Author
-
Marcus Thudium, Jochen Kappler, Maximilian J. G. Oremek, Stefan Felix Ehrentraut, Evgeniya Kornilov, Milka Marinova, Christian Putensen, Martin Soehle, and Jens-Christian Schewe
- Subjects
ECMO ,SARS-CoV-2 ,ARDS ,cerebral autoregulation ,NIRS ,Medicine (General) ,R5-920 - Abstract
IntroductionCerebrovascular complications are feared but also commonly reported in patients with COVID-19 requiring extracorporeal membrane oxygenation (ECMO) support therapy. Besides other reasons, a connection between impaired cerebral autoregulation and SARS-CoV-2 infection as a mechanism for an increase in cerebrovascular complications has been hypothesized.MethodsIn an observational single-center study, we investigated a cohort of 48 patients requiring veno-venous ECMO support therapy with (n = 31) and without SARS-CoV-2 infection (n = 17). Cerebral autoregulation was assessed with the cerebral oximetry-derived autoregulation index (ORx) based on a moving correlation between arterial pressure and cerebral oximetry.ResultsPatients with ECMO support therapy and SARS-CoV-2 experienced more time with impaired cerebral autoregulation than without SARS-CoV-2 [17 ± 9 vs. 13 ± 9% (p = 0.027)]. Patients with SARS-CoV-2 suffering from cerebrovascular complications had more time with impaired autoregulation than non SARS-CoV-2 patients with these complications (19 ± 9 vs. 10 ± 4%, p = 0.032).ConclusionOur results suggest a connection between SARS-CoV-2 and impaired cerebral autoregulation as well as cerebrovascular complications in SARS-CoV-2 patients.
- Published
- 2024
- Full Text
- View/download PDF
49. Rare HCV subtypes and retreatment outcomes in a cohort of European DAA-experienced patients
- Author
-
Julia Dietz, Christiana Graf, Christoph P. Berg, Kerstin Port, Katja Deterding, Peter Buggisch, Kai-Henrik Peiffer, Johannes Vermehren, Georg Dultz, Andreas Geier, Florian P. Reiter, Tony Bruns, Jörn M. Schattenberg, Elena Durmashkina, Thierry Gustot, Christophe Moreno, Janina Trauth, Thomas Discher, Janett Fischer, Thomas Berg, Andreas E. Kremer, Beat Müllhaupt, Stefan Zeuzem, Christoph Sarrazin, C. Antoni, A. Teufel, R. Vogelmann, M. Ebert, J. Balavoine, E. Giostra, M. Berning, J. Hampe, T. Boettler, C. Neumann-Haefelin, R. Thimme, A. De Gottardi, A. Rauch, N. Semmo, V. Ellenrieder, M. Gress, A. Herrmann, A. Stallmach, D. Hoffmann, U. Protzer, A. Kodal, M. Löbermann, T. Götze, V. Keitel-Anselmino, C.M. Lange, R. Zachoval, J. Mayerle, A. Maieron, P. Michl, U. Merle, D. Moradpour, J.-P. Chave, M. Muche, H.-J. Epple, M. Müller-Schilling, F. Kocheise, T. Müller, F. Tacke, E. Roeb, J. Rissland, M. Krawczyk, P. Schulze, D. Semela, U. Spengler, J. Rockstroh, C.P. Strassburg, J. Siebler, J. Schulze zur Wiesch, F. Piecha, J. von Felden, S. Jordan, A. Lohse, M. Sprinzl, P. Galle, R. Stauber, B. Strey, W. Steckstor, W. Schmiegel, N.H. Brockmeyer, A. Canbay, C. Trautwein, F. Uschner, J. Trebicka, T. Weber, H. Wedemeyer, M. Cornberg, M. Manns, P. Wietzke-Braun, R. Günther, K. Willuweit, G. Hilgard, H. Schmidt, E. Zizer, J. Backhus, T. Seufferlein, O. Al-Taie, W. Angeli, S. Beckebaum, A. Erhardt, A. Garrido-Lüneburg, H. Gattringer, D. Genné, M. Gschwantler, F. Gundling, S. Hametner, R. Schöfl, S. Haag, H. Heinzow, T. Heyer, C. Hirschi, A. Jussios, S. Kanzler, N. Kordecki, M. Kraus, U. Kullig, S. Wollschläger, L. Magenta, B. Terziroli Beretta-Piccoli, M. Menges, L. Mohr, K. Muehlenberg, C. Niederau, B. Paulweber, A. Petrides, M. Pinkernell, R. Piso, W. Rambach, L. Reinhardt, M. Reiser, B. Riecken, A. Rieke, J. Roth, M. Schelling, P. Schlee, A. Schneider, D. Scholz, E. Schott, M. Schuchmann, U. Schulten-Baumer, A. Seelhoff, A. Stich, F. Stickel, J. Ungemach, E. Walter, A. Weber, H. Wege, T. Winzer, W. Abels, M. Adler, F. Audebert, C. Baermann, E. Bästlein, R. Barth, K. Barthel, W. Becker, J. Behrends, J. Benninger, F. Berger, D. Berzow, T. Beyer, M. Bierbaum, O. Blaukat, A. Bodtländer, G. Böhm, N. Börner, U. Bohr, B. Bokemeyer, H.R. Bruch, D. Bucholz, P. Buggisch, K. Matschenz, J. Petersen, O. Burkhard, N. Busch, C. Chirca, R. Delker, J. Diedrich, M. Frank, M. Diehl, A.O. Tal, M. Schneider, A. Dienethal, P. Dietel, N. Dikopoulos, M. Dreck, F. Dreher, L. Drude, K. Ende, U. Ehrle, K. Baumgartl, F. Emke, R. Glosemeyer, G. Felten, D. Hüppe, J. Fischer, U. Fischer, D. Frederking, B. Frick, G. Friese, B. Gantke, P. Geyer, H.R. Schwind, M. Glas, T. Glaunsinger, F. Goebel, U. Göbel, B. Görlitz, R. Graf, H. Gruber, C. Hartmann, C. Klag, G. Härter, M. Herder, T. Heuchel, S. Heuer, H. Hinrichsen, B. Seegers, K.-H. Höffl, H. Hörster, J.-U. Sonne, W.P. Hofmann, F. Holst, M. Hunstiger, A. Hurst, E. Jägel-Guedes, C. John, M. Jung, B. Kallinowski, B. Kapzan, W. Kerzel, P. Khaykin, M. Klarhof, U. Klüppelberg, Wolfratshausen, K. Klugewitz, B. Knapp, U. Knevels, T. Kochsiek, A. Körfer, A. Köster, M. Kuhn, A. Langekamp, B. Künzig, R. Link, M. Littman, H. Löhr, T. Lutz, P. Gute, G. Knecht, U. Lutz, D. Mainz, I. Mahle, P. Maurer, S. Mauss, C. Mayer, H. Möller, R. Heyne, D. Moritzen, M. Mroß, M. Mundlos, U. Naumann, O. Nehls, K, R. Ningel, A. Oelmann, H. Olejnik, K. Gadow, E. Pascher, A. Philipp, M. Pichler, F. Polzien, R. Raddant, M. Riedel, S. Rietzler, M. Rössle, W. Rufle, A. Rump, C. Schewe, C. Hoffmann, D. Schleehauf, W. Schmidt, G. Schmidt-Heinevetter, J. Schmidtler-von Fabris, L. Schneider, A. Schober, S. Niehaus-Hahn, J. Schwenzer, T. Seidel, G. Seitel, C. Sick, K. Simon, D. Stähler, F. Stenschke, H. Steffens, K. Stein, M. Steinmüller, T. Sternfeld, K. Svensson, W. Tacke, G. Teuber, K. Teubner, J. Thieringer, A. Tomesch, U. Trappe, J. Ullrich, G. Urban, S. Usadel, A. von Lucadou, F. Weinberger, M. Werheid-Dobers, P. Werner, T. Winter, E. Zehnter, and A. Zipf
- Subjects
Direct-acting antivirals ,Hepatitis C Virus ,rare HCV genotypes ,resistance-associated substitutions ,treatment response ,Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Background and Aims: Data on the prevalence and characteristics of so-called rare HCV genotypes (GTs) in larger cohorts is limited. This study investigates the frequency of rare GT and resistance-associated substitutions and the efficacy of retreatment in a European cohort. Methods: A total of 129 patients with rare GT1-6 were included from the European resistance database. NS3, NS5A, and NS5B were sequenced and clinical parameters and retreatment efficacies were collected retrospectively. Results: Overall 1.5% (69/4,656) of direct-acting antiviral (DAA)-naive and 4.4% (60/1,376) of DAA-failure patients were infected with rare GT. Although rare GTs were almost equally distributed throughout GT1-6 in DAA-naive patients, we detected mainly rare GT4 (47%, 28/60 GT4; of these n = 17, subtype 4r) and GT3 (25%, 15/60 GT3, of these n = 8, subtype 3b) among DAA-failures. A total of 62% (37/60) of DAA failures had not responded to first-generation regimes and the majority was infected with rare GT4 (57%, 21/37). In contrast, among patients with failure to pangenotypic DAA regimens (38%, 23/60), infections with rare GT3 were overrepresented (57%, 13/23). Although NS5A RASs were uncommon in rare GT2, GT5a, and GT6, we observed combined RASs in rare GT1, GT3, and GT4 at positions 28, 30, 31, which can be considered as inherent. DAA failures with completed follow-up of retreatment, achieved a high SVR rate (94%, 45/48 modified intention-to-treat analysis; 92%, 45/49 intention-to-treat). Three patients with GT4f, 4r, or 3b, respectively, had virological treatment failure. Conclusions: In this European cohort, rare HCV GT were uncommon. Accumulation of specific rare GT in DAA-failure patients suggests reduced antiviral activities of DAA regimens. The limited global availability of pangenotypic regimens for first line therapy as well as multiple targeted regimens for retreatment could result in HCV elimination targets being delayed. Impact and implications: Data on the prevalence and characteristics of rare HCV genotypes (GT) in larger cohorts are still scarce. This study found low rates of rare HCV GTs among European HCV-infected patients. In direct-acting antiviral (DAA)-failure patients, rare GT3 subtypes accumulated after pangenotypic DAA treatment and rare GT4 after first generation DAA failure and viral resistance was detected at NS5A positions 28, 30, and 31. The limited global availability of pangenotypic DAA regimens for first line therapy as well as multiple targeted regimens for retreatment could result in HCV elimination targets being delayed.
- Published
- 2024
- Full Text
- View/download PDF
50. Robust Market Equilibria under Uncertain Cost
- Author
-
Biefel, Christian, Liers, Frauke, Rolfes, Jan, Schewe, Lars, and Zöttl, Gregor
- Subjects
Mathematics - Optimization and Control ,90C33 ,G.1.6 - Abstract
This work studies equilibrium problems under uncertainty where firms maximize their profits in a robust way when selling their output. Robust optimization plays an increasingly important role when best guaranteed objective values are to be determined, independently of the specific distributional assumptions regarding uncertainty. In particular, solutions are to be determined that are feasible regardless of how the uncertainty manifests itself within some predefined uncertainty set. Our mathematical analysis adopts the robust optimization perspective in the context of equilibrium problems. First, we present structural insights for a single-stage, nonadjustable robust setting. We then go one step further and study the more complex two-stage or adjustable case where a part of the variables can adjust to the realization of the uncertainty. We compare equilibrium outcomes with the corresponding centralized robust optimization problem where thesum of all profits are maximized. As we find, the market equilibrium for the perfectly competitive firms differs from the solution of the robust central planner, which is in stark contrast to classical results regarding the efficiency of market equilibria with perfectly competitive firms. For the different scenarios considered, we furthermore are able to determine the resulting price of anarchy. In the case of non-adjustable robustness, for fixed demand in every time step the price of anarchy is bounded whereas it is unbounded if the buyers are modeled by elastic demand functions. For the two-stage adjustable setting, we show how to compute subsidies for the firms that lead to robust welfareoptimal equilibria., Comment: 26 pages
- Published
- 2021
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.