bluuebunny/crossref_metadata_2025 huggingface dataset:
Integrating large language models for improved failure mode and effects analysis (FMEA): a framework and case study
Authors: Hassani Ibtissam El , Masrour Tawfik , Kourouma Nouhan , Motte Damien , Tavčar Jože
Published: May 2024

The manual execution of failure mode and effects analysis (FMEA) is time-consuming and error-prone. This article presents an approach in which large language models (LLMs) are integrated into FMEA. LLMs improve and accelerate FMEA with human in the loop. The discussion looks at software tools for FMEA and emphasizes that the tools must be tailored to the needs of the company. Our framework combines data collection, pre-processing and reliability assessment to automate FMEA. A case study validates this framework and demonstrates its efficiency and accuracy compared to manual FMEA.
A low-cost non-intrusive spatial hand tracking pipeline for product-process interaction
Authors: Gopsill James , Kukreja Aman , Cox Christopher Michael Jason , Snider Chris
Published: May 2024

Hands are the sensors and actuators for many design tasks. While several tools exist to capture human interaction and pose, many are expensive and require intrusive measurement devices to be placed on participants and often takes them out of the natural working environment. This paper reports a novel workflow that combines computer vision, several Machine Learning algorithms, and geometric transformations to provide a low-cost non-intrusive means of spatially tracking hands. A ±3mm position accuracy was attained across a series of 3-dimensional follow the path studies.
Aligning production requirements with product and production maturities: enhancing production preparation during product development
Authors: Koroth Rohith Areth , Elgh Fredrik , Lennartsson Martin , Raudberget Dag
Published: May 2024

Product development is multidisciplinary with high uncertainties necessitating coordinated decision-making between design and production. This paper presents a method to work with production requirements to support production preparation during product development aligned with different product and production maturities. The work was conducted in collaboration with two global manufacturing firms. The method supports identification, definition, and structuring of production requirements and the collaboration between design and production engineers for requirement prioritization and follow-up.
Towards a process for the creation of synthetic training data for AI-computer vision models utilizing engineering data
Authors: Schwoch Sebastian , Dammann Maximilian Peter , Bartl Johannes Georg , Kretzschmar Maximilian , Saske Bernhard , Paetzold-Byhain Kristin
Published: May 2024

Artificial Intelligence-based Computer Vision models (AI-CV models) for object detection can support various applications over the entire lifecycle of machines and plants such as monitoring or maintenance tasks. Despite ongoing research on using engineering data to synthesize training data for AI-CV model development, there is a lack of process guidelines for the creation of such data. This paper proposes a synthetic training data creation process tailored to the particularities of an engineering context addressing challenges such as the domain gap and methods like domain randomization.
Towards digital representations for brownfield factories using synthetic data generation and 3D object detection
Authors: Toro Javier Villena , Bolin Lars , Eriksson Jacob , Wiberg Anton
Published: May 2024

This study emphasizes the importance of automatic synthetic data generation in data-driven applications, especially in the development of a 3D computer vision system for engineering contexts such as brownfield factory projects, where no data is readily available. Key points: (1) A successful integration of a synthetic data generator with the S3DIS dataset, leading to a significant enhancement in object detection of previous classes and enabling recognition of new ones; (2) A proposal for a CAD-based configurator for efficient and customizable scene reconstruction from LiDAR scanner point clouds.
Territorial design: ethological design or political design or both?
Authors: Hémon Stéphanie , Gentès Annie
Published: May 2024

Based on 4 codesign cases and 15 designer interviews, this article presents how territorial design serves as a catalyst for shared values in community living. Examining user experience and design goals, it reveals how ethological and political values shape territories and the design process. Participants explore new work methodologies, redefine collective activities and navigate in tensions, power issues and political dimensions. The codesign space transforms political interactions, shifting from controversy to conception, offering a new experience and perspective on territorial discussions.
Analyzing the dimensional aspects of 3D volumetric spaces: a product-oriented perspective
Authors: Rana Vighneshkumar , Singh Vishal
Published: May 2024

The concept of volumetric spaces has evolved in the Architecture, Engineering, and Construction (AEC) sector, ranging from traditional onsite built spaces to modern modular houses and portable architecture. Despite this diversity, there lacks a comprehensive framework to analyze volumetric space products across dimensions. This paper presents a conceptual framework based on abductive reasoning and qualitative analysis, aiming to explore interdependencies among dimensions. It hypothesizes that volumetric space dimensions are perceived differently and demonstrate interdependencies.
Supporting modular product family representations by methodically utilising meta-models
Authors: Berschik Markus Christian , Laukotka Fabian Niklas , Züfle Marc , Krause Dieter
Published: May 2024

Due to the rising multidisciplinarity and connectivity of products especially modular product families, a sophisticated handling of the information is crucial for reducing complexity during the development. System modelling techniques have evolved to assist engineers with managing information. However, nowadays, it is rarely focusing on modular product families. This paper introduces a meta-model based on an ontology, which improves the creation and management of modular product family and its occurring data. The meta-model is presented using the example of a Passenger Service Unit (PSU).
Leveraging design thinking in MBSE: mitigating data and information uncertainties – an integration model approach
Authors: Gadzo Emir , Michalides Marvin , Koch Alexander
Published: May 2024

The evolving needs of customers and stakeholders necessitate the collaboration of diverse system elements within a cyber-physical, socio-technical network. Socio-technical systems are characterized by numerous complex interdependencies as well as by endogenous and exogenous influences. A key issue that developers must address is the mitigation of data and information uncertainties. The authors introduce an approach that operationalizes Design Thinking as a supporting sufficient condition within the context of designing system models in the realm of Model-Based Systems Engineering.
Principles for the design of system of systems exemplified using modularisation
Authors: Günther Matthias , Seidenberg Tobias , Anacker Harald , Dumitrescu Roman
Published: May 2024

In the context of system of systems (SoS) engineering, the incorporation of design principles is critical to guide the engineering process. This paper presents a systematic literature review to synthesize a list of principles tailored for SoS. 26 principles were identified as generic principles and 39 were mapped to the specific challenges in SoS engineering. Through an evaluation using the principle of modularisation in the design of a charging infrastructure, the study offers insights into the real-world effectiveness of these principles, showing their relevance in SoS engineering tasks.
Exploring space manufacturing: designing a lunar factory for space-bound products in the new space economy
Authors: Francesco Eva De , Ettorre Anna , Acerbi Federica , Sullivan Brendan P.
Published: May 2024

This study proposes a Moon-based factory for space-bound products, aiming to revolutionize space exploration through In-Space Manufacturing (ISM). It defines key elements for lunar manufacturing by adapting Earth-based factory models to lunar conditions.
Utilization of the system architecture in the context of validation in the business-to-business (B2B) sector
Authors: Humpert Lynn , Wilke Daria , Brueggemann Sarah , Anacker Harald , Dumitrescu Roman
Published: May 2024

The European Green Deal aims to reduce global emissions by minimizing the use of resources. Early validation of products helps to reduce rework, costs and therefore resources. However, validation of complex mechatronic products is challenging due to interdependencies. Companies are applying systems engineering to meet this challenge. Current validation approaches are insufficient in the early design phases. This paper presents an approach to validation using the system architecture in the B2B sector. A machine tool and a custom built machine are presented as evaluation examples.
Exploring indicators of system-of-systems resilience: outcomes of a health systems design workshop at an international conference
Authors: Pannunzio Valeria , Komashie Alexander , Walsh Sebastian , Milne Richard , Kipouros Timoleon , Lamé Guillaume , Maier Anja , Brayne Carol , Clarkson P. John
Published: May 2024

This contribution departs from an existing model, the Design Framework for Systems-of-Systems Resilience, to explore systems resilience issues across the health, environmental, and economic domains. The reported research activities include 1) a rapid review to collect a set of systems indicators and 2) a design workshop employing causal loop diagramming to map expected causal influences between indicators. Through this exercise, we examine key themes in this research domain and outline directions for further enquiry, while involving members of the design research community in an open dialogue.
The sustainability and social entrepreneurship fellowship: transdisciplinary and multicultural problem-based engineering education
Authors: Krauss Gordon , Rennick Chris , Ibrahim Nadine , Bedi Sanjeev
Published: May 2024

The nine-week Sustainability and Social Entrepreneurship Fellowship at the University of Waterloo addressed urban habitation sustainability in London, Ontario, via a multicultural, trans-disciplinary approach. Undergraduate engineering students addressed housing and transportation environmental and social sustainability, guided by expert lectures and fieldwork. The program highlights the importance of diversity in engineering education and the need for structured cultural and educational management. Students proposed engineering solutions to sustainably improve the housing development process.
Learning in a digital fabrication course on building tangible artefacts
Authors: Nanjappan Vijayakumar , Georgiev Georgi V. , Casakin Hernan , Soomro Sohail Ahmed
Published: May 2024

This paper examines how students' ideas evolve into physical prototypes within a digital fabrication design course. Examining the materials used, customization approaches, iterations, and team dynamics of 26 student projects reveals interplays between ideas, available tools, materials and constraints. Findings show the predominance of techniques, design preferences, concept refinement, and teamwork challenges. The implications highlight the value of hands-on iteration for alignment with reality and the need to support collaboration skills alongside technical prototype development.
A generative toolkit to help raise industrial design students’ awareness of low metal recycling rates
Authors: Schoch Konrad , Hemmert Fabian , Liedtke Christa
Published: May 2024

Education for Sustainable Development requires raising individuals' awareness of problems relevant to the environment. We designed a Generative Toolkit that supports industrial design students carrying out a Speculative Design task and through this process initiates greater problem awareness of low metal recycling rates. In this paper we give insights into the Toolkit's theoretical derivation and the design process. Findings from testing suggest that there are several opportunities for improvement, such as considering further content-related competencies in the Toolkit's design.
Circularity in product engineering – towards a forward-looking approach across product generations
Authors: Albers Albert , Tusch Leonard , Jäckle Michael , Seidler Moritz , Kempf Christoph
Published: May 2024

To enable a truly circular economy in product engineering, the development of products in generations must be considered. Thus, we strive to enable a forward-looking circularity approach, proposing the integration of system generation engineering (SGE) with circular economy principles. By analysing the qualitative interrelations among product generations driven by distinct value preservation strategies on various value creation tiers ("R-strategies"), we extend prior SGE research to advance model theory and support practical application of circular product engineering.
Analysis of collaborative CAD user actions in design sprint: insights from an educational setting
Authors: Šklebar Jelena , Martinec Tomislav , Škec Stanko , Štorga Mario
Published: May 2024

Design sprints complement traditional teaching methods, especially in project-based learning courses. While this approach can potentially change Computer-Aided Design (CAD) usage, it is still underexplored. Therefore, this study explores the influence of design sprints on embodiment-focused CAD activities in project-based learning by examining differences in patterns of CAD user actions, focusing on design space and action types. The case involves two higher-graded and two lower-graded student design teams monitored with a non-invasive method across a two-day design sprint event.
Nurture employees’ creative behaviors: unveiling the impact of design thinking on human organizational behavior
Authors: Melazzini Michele , Carella Gianluca
Published: May 2024

This research explores the impact of Design Thinking (DT) on Organizational Behaviour, explicitly focusing on individual employees, the micro-level of the organization. The research runs a single-case study within an Italian bank adopting DT through its HR department. The study proposes a model illustrating how DT adoption influences specific individual behavioral constructs: motivations, attitudes, capabilities, and creative behaviors. The study finds that fostering confidence in the creative process enhances human engagement and proactivity.
The relation between service and digital transition: implications for designers
Authors: Monti Teresa , Colombo Samuele , Montagna Francesca , Cascini Gaetano
Published: May 2024

Service and digital transitions create a range of solutions by combining their features and introducing both human and automated agents as intermediaries. The paper classifies non/digital product/service and explores how these transitions change user involvement. A model is proposed to assess the user's role with human (service) and automated (digital) intermediaries. Utilizing user journey phases, the model is applied to four case studies, revealing commonalities in transition occurrences. Evidence suggest a potential adoption in design identifying the key phases per each transitions.
Visualizing and analysing data-driven shift from decentralized to centralized automotive E/E architectures
Authors: Phadnis Tejas Pravin , Feyerabend Nils , Axmann Joachim
Published: May 2024

Decentralized E/E architectures (EEAs) are facing challenges and bottlenecks in implementing new features and technologies. The shift towards centralized EEAs has many challenges and needs to be handled pragmatically by considering concurrency with the existing EEAs. To address the challenges of architectural shift, the paper showcases the quantitative comparison of EEAs and visualizes the flow of shifting sub-function and hardware blocks using the Sankey diagram. The observations from the diagram as a result will support OEMs to analyse and take decisions on the shift while developing EEAs.
Virtual design hackathons: a data collection framework
Authors: Martinec Tomislav , Valjak Filip , Horvat Nikola , Goudswaard Mark , Nygård Ege Daniel , Ballantyne Robert , Berg Martin Francis , Glaser Tobias , Grosse Cornelius , Lipšinić Zvonimir , Lukačević Fanika , Lukasiewicz Marek S. , Mašović Robert , McClenaghan Adam , Monti Teresa , Øvrebø Henrik H. , Schmitt Pascal , Stubberud Vegar , Taiwo Emmanuel TJ , Lisac Ana
Published: May 2024

Design hackathons offer a unique research opportunity to study time-pressured collaborative design. At the same time, research on design hackathons faces unique methodological challenges, prompting the exploration of new research approaches. This paper proposes a new data-collection framework that leverages a virtual format of hackathon events and enables a deeper insight into hackathon dynamics. The framework applicability is presented through a case study of the IDEA challenge hackathon, in which different intrusive and non-intrusive data collection approaches were used.
Reducing uncertainty regarding customer expectations for a sustainable car interior design integrated in a data-informed design approach
Authors: Quattelbaum Bastian , Geiger Lara Amelie , Stylidis Kostas , Söderberg Rikard
Published: May 2024

Sustainability is influencing the automotive industry. Car manufacturers are increasingly prioritizing sustainable materials. The production of these still pose environmental challenges. This paper addresses the trends related to sustainable car interiors. It emphasizes the importance of understanding how customers perceive these new materials. Seven in-depth interviews were conducted, followed by a survey with 106 participants to obtain generalized insights. The results will reduce the uncertainty regarding customer expectations for sustainable car interiors.
Chronobiology of pupil dilation in design students during idea generation
Authors: Colombo Samuele , Gero John S. , Mazza Alessandro , Cantamessa Marco
Published: May 2024

Chronobiology studies physiological variations due to the time of day, an unexplored factor in design research. This paper explores the effect of time of day on designers' physiological responses in idea generation. Convergent (CT) and divergent (DT) thinking, as building blocks of designing, are explored using pupil dilation as a proxy for cognitive load. Time of day and educational background are explored for engineering and industrial designers. Results show a larger pupil diameter in the afternoon than in the morning, especially for DT, with higher values for industrial designers.
Design strategies to facilitate second-hand clothing acquisition
Authors: Das Marie , Moons Ingrid , Du Bois Els
Published: May 2024

Extensive research found many barriers and drivers in second-hand clothing (SHC) acquisition. This study explores their relationships and the role of design in enhancing SHC experiences. 16 semi-structured interviews revealed insights into personal experiences and emotions. Customer journey mapping highlighted 5 design interventions: a. effective branding and marketing, b. appealing clothing presentation, c. facilitating garment search, d. aiding quality inspection, and e. optimizing price-quality balance. Future, quantitative, research is needed to confirm the findings for a wider public.
A Representation of the Inauguration Ceremony of the Restored Temple? A (Tentative) Reinterpretation of the Bar Kokhba Tetradrachm
Authors: Bourgel Jonathan (Yonatan)
Published: May 2024

The coinage of Bar Kosiba (Bar Kokhba), the leader of the Second Jewish Revolt (132–135/6 CE), has long been acknowledged as a source of data for understanding the ideology and goals of the rebel regime he headed. In particular, the imagery and legends on Bar Kosiba’s tetradrachms have been the subject of many interpretations and controversies. This article proposes that the facade of the temple on the obverse of Bar Kosiba’s tetradrachms and the four species on its reverse side are complementary symbols, joined together to represent the future inauguration ceremony of the restored temple. Furthermore, this imagery on the tetradrachms may have been intended to respond to the coins issued to commemorate the founding of the colony of Aelia Capitolina on the site of Jerusalem.
Images Above All: Richard Kroner and the Religious Imagination
Authors: Hendrickson Caleb
Published: May 2024

This essay returns to a largely forgotten achievement of mid-twentieth-century philosophical theology, Richard Kroner’s Culture and Faith (1951) and the “philosophy of faith” presented therein. It focuses on Kroner’s idea of religious imagination as the inspired medium of revelation. It considers implications of this idea with regard to religious epistemology and theological language. In doing so, it puts Kroner in conversation with John Caputo, Iain McGilchrist, and Kroner’s friend and colleague Paul Tillich.
“Probably the Most Perfect Symbol of Our Democracy”: The Army, Sports, and the Re-education of German Youth during the Early American Occupation of Germany, 1945–1946
Authors: TOON WENDY
Published: May 2024

During World War II, Germany and the United States fought it out on the battlefields, but once the Allies were victorious, American attention quickly turned to the playing fields. Despite recent enmity, in the spirit of amity GIs quickly started recreational games with German youngsters. This seemingly natural development was at odds with both American expectations of the Germans and vice versa. Reeducation of Germany, and especially its Nazi-indoctrinated youth, was viewed as essential to peace, and the army, through sports, became perhaps unlikely early reeducators. This article outlines sports’ inherent Americanness, this impromptu playing, and its relationship to the formal army program of youth activities.
Uncertainty shocks and monetary policy rules in a small open economy
Authors: Gupta Sargam
Published: May 2024

Post the great financial crisis (GFC) of 2008–2009, there has been a surge in the macroeconomics literature on aggregate uncertainty. Although the recent literature has recognized the adverse real effects of global uncertainty shocks in emerging market economies (EMEs), the role of monetary policy in offsetting these adverse effects and their link with the exchange rates is not explored in the literature. We find that the currently followed interest rate rules (IRRs) under a flexible inflation-targeting regime are ineffective in stabilizing the domestic economy during periods of high global uncertainty in the EMEs. Using a small open economy new Keynesian DSGE model with Epstein–Zin preferences and second-moment demand shocks, we compare and propose alternate monetary policy rules that significantly reduce welfare losses. We find that the best monetary policy rule in terms of welfare depends on the nature of shock that is, first-moment or second-moment shock.
How to Detect Abusive Constitutional Practices
Authors: Petrov Jan
Published: May 2024

The challenge of distinguishing between abusive and non-abusive constitutional practices – Main ways of detecting abuse: analyses of intent and effects – Obstacles to detecting bad faith intent in constitutional law – Structured and focused analysis of the effects of abusive constitutionalism: introducing the foreseeable effects test – Normative benchmark: substantial diminishment of accountability – Step 1: probability of harm, analysing the tested constitutional measure’s foreseeable effects on operability and autonomy of an accountability mechanism – Step 2: seriousness of potential harm, analysing the constitutional measure’s effects in the broader constitutional context (including interaction effects) – Step 3: harm mitigation, analysing the existence and adequacy of harm-mitigating safeguards accompanying the constitutional measure – Strengths and limits of the foreseeable effects test
Partisanship, Independence, and the Constitutive Representation of Women in the Canadian Senate
Authors: McCallion Elizabeth
Published: May 2024

This article investigates legislators’ willingness to talk about gender and women during policy making discussions, asking whether it is conditional on their sex or partisanship in environments where party discipline does not constrain their speech. The Canadian Senate offers a case of a legislature with low or absent party discipline. A quantitative content analysis of nearly 1,000 Senate committee meetings confirms that sex is a primary indicator of legislators’ inclination to talk about gender and women. Moreover, women senators who sit on committees with a critical mass of women members (30% or greater) are more likely to talk about gender and women, making the case for the importance of women’s descriptive representation. Partisanship and independence had no significant effect on senators’ propensity to discuss women. The findings suggest that partisanship does not constrain legislators’ representation of women in environments with low party discipline.
Water quality management in aquaculture
Authors: Yusoff Fatimah M. , Umi Wahidah A. D. , Ramli Norulhuda M. , Harun Razif
Published: May 2024

The aquaculture industry requires good water quality for its successful operation but produces wastes that can cause environmental deterioration and pose high risks to the sector. Adequate waste treatment and recycling are necessary to make aquaculture a sustainable and profitable industry and contribute to the circular economy. Polluted water sources, excess feeding, overstocking, use of antibiotics/chemicals and harmful algal blooms are major causes of water quality deterioration and low production in aquaculture systems. Discharges of untreated wastes would have serious impacts on the receiving water bodies, and eventually on the aquaculture industry itself. Possible solutions include technological innovations in environmentally friendly production systems, use of efficient processes in water quality management and improved legislation and governance. Environmentally feasible aquaculture production technologies such as recycling aquaculture system, integrated multi-trophic aquaculture and aquaponics including features of waste recycling are viable options in aquaculture schemes. Best aquaculture practices integrating advanced water quality treatment processes and technologies, supported by automation and sensors, modeling and artificial intelligence-internet of things are necessary for a sustainable aquaculture environment, production and stable value chain. In general, low-cost technologies for aquaculture waste treatment and environmental impact reduction through good governance are crucial for achieving sustainability in the aquaculture industry and natural environmental management.
The Morphology of Martian Pyroclastic Ramparts and Their Use in Determining Vent‐Proximal Eruption Dynamics
Authors: Pieterek B. , Jones T. J. , Wilson L.
Published: May 2024

High‐resolution investigations of Late Amazonian volcanic landforms provide previously unrevealed insights into the dynamics of Martian volcanic eruptions. On Earth, the formation of vent‐proximal accumulations of spatter deposits is attributed to low‐intensity lava fountaining episodes representing eruptions on the very edge of explosive activity. Martian spatter deposits form small‐scale volcanic landforms that are rarely reported, and thus the dynamics of Martian mafic explosive eruptions are still not fully constrained. We conducted high‐resolution Context Camera‐based mapping coupled with a stereo‐pair‐generated digital elevation model to reconstruct the eruptive history of a fissure system and its associated products south of Ascraeus Mons, Mars. The studied volcanic fissure clearly demonstrates both explosive and effusive deposits and, in addition, is spatially associated with a lava channel. For the first time, these observations allowed us to conduct a comparative analysis of vent‐proximal volcanic products and reconstruct the late‐stage eruption dynamics of a fissure system. We found that the spatial distribution of the pyroclastic (spatter) rampart along the fissure vent is heterogeneous and generated using dynamic eruption processes. Moreover, the lava channel fed from the fissure vent shows evidence of successive lava overspills whose emplacement was topographically controlled. These observations suggest that, in contrast to the general inference that Amazonian‐age volcanism mainly involves effusive eruptions, explosive‐origin landforms might have been overlooked. Therefore, we argue that high‐resolution mapping of pyroclastic deposits may provide critical insights into understanding the dynamic nature of Martian fissure eruptions and explosive‐associated volatile release during the last stages of eruptions.
Global Change Research for a More Secure World
Authors: Preston Benjamin , Levy Hila , Tallis Heather , Schoonover Rod , Lubchenco Jane
Published: May 2024

Orienting global change science so that it informs national security issues will help us develop interventions that promote social stability and ecological well-being.
The Role of Ocean Mesoscale Variability in Air‐Sea CO2 Exchange: A Global Perspective
Authors: Guo Yiming , Timmermans Mary‐Louise
Published: May 2024

Ocean mesoscale flows significantly influence nutrient distribution and biological productivity, yet the scarcity of eddy‐permitting observational data sets and climate modeling hinders understanding their role in carbon sequestration. Using an eddy‐resolving global simulation, this study investigates the significance of ocean mesoscales in air‐sea carbon dioxide (CO2) exchange. Results show over 30% of CO2 flux variance in energetic regions attributed to flows with horizontal scales smaller than 2°. Mesoscale flows can drive a cumulative CO2 flux that is either a net carbon sink or source depending on region, with magnitudes on the order of 105 tonnes of carbon per year. Variations in this mesoscale‐related CO2 flux are correlated with local relative vorticity and the background gradient of ocean partial pressure of CO2. This analysis underscores the importance of considering ocean mesoscales in monitoring carbon flux, highlighting the need to explore the influence of increasing eddy activity on carbon uptake in a changing climate.
Impact of the Spatio‐Temporal Mismatch Between Satellite and In Situ Measurements on Validations of Surface Solar Radiation
Authors: Urraca Ruben , Lanconelli Christian , Gobron Nadine
Published: May 2024

Satellite and in situ sensors do not observe exactly the same measurand. This introduces a mismatch between both types of measurements in the spatial or temporal. The mismatch differences can be the dominant component in their comparison, so they have to be removed for an adequate validation of satellite products. With this aim, we propose a methodology to characterize the mismatch between satellite and in situ measurements of surface solar radiation, evaluating the impact of the mismatch on validations. The Surface Solar Radiation Data Set—Heliosat (SARAH‐2) and the Baseline Surface Radiation Network are used to characterize the spatial and temporal mismatch, respectively. The mismatch differences in both domains are driven by cloud variability. At least 5 years are needed to characterize the mismatch, which is not constant throughout the year due to seasonal and diurnal cloud cover patterns. Increasing the mismatch can artificially improve the validation metrics under some circumstances, but the mismatch must be always minimized for a correct product assessment. Finally, we test two types of up‐scaling methods based on SARAH‐2 in the validation of degree‐scale products. The fully data‐driven correction removes all the mismatch effects (systematic and random) but fully propagates SARAH‐2 uncertainty to the corrections. The model‐based correction only removes the systematic mismatch difference, but it can correct measurements not covered by the high‐resolution data set and depends less SARAH‐2 uncertainty.
Characterizing Seasonality and Trend From In Situ Time‐Series Observations Using Explainable Deep Learning for Ground Deformation Forecasting
Authors: Ma Zhengjing , Mei Gang , Xu Nengxiong
Published: May 2024

Ground deformation, a critical indicator of geohazard evolution, exhibits both seasonal fluctuations and long‐term trend changes. This study explores interpretable deformation forecasting using an explainable deep learning approach, utilizing field observation data to extract and characterize these critical features from time series. We demonstrate that extracting and utilizing shared, similar seasonal and trend features across multi‐point observations significantly enhances ground deformation forecasting accuracy. Notably, the extracted seasonal features reveal the dominant role of the hydrological response in deformation at seasonal timescales, providing insights into the underlying source of predictability. This proof‐of‐concept study highlights the promise of interpretable ground deformation forecasting, with applications expected to encompass landslide behavior, volcanism, or seismic activity.
Atmospheric Chemistry Surrogate Modeling With Sparse Identification of Nonlinear Dynamics
Authors: Yang Xiaokai , Guo Lin , Zheng Zhonghua , Riemer Nicole , Tessum Christopher W.
Published: May 2024

Modeling atmospheric chemistry is computationally expensive and limits the widespread use of chemical transport models. This computational cost arises from solving high‐dimensional systems of stiff differential equations. Previous work has demonstrated the promise of machine learning (ML) to accelerate air quality model simulations but has suffered from numerical instability during long‐term simulations. This may be because previous ML‐based efforts have relied on explicit Euler time integration—which is known to be unstable for stiff systems—and have used neural networks which are prone to overfitting. We hypothesize that parsimonious models combined with modern numerical integration techniques can overcome this limitation. Using a small‐scale mechanism to explore the potential of these methods, we have created a machine‐learned surrogate by (a) reducing dimensionality using singular value decomposition to create an interpretably‐compressed low‐dimensional latent space and (b) using Sparse Identification of Nonlinear Dynamics (SINDy) to create a differential‐equation‐based representation of the underlying dynamics in the compressed latent space with reduced stiffness. The root mean square error of ML model prediction for ozone concentration over 9 days is 37.8% of the root mean square concentration across all simulations in our testing data set. The surrogate model is 10× faster with 12× fewer integration timesteps compared to reference model and is numerically stable in all tested simulations. Overall, we find that SINDy can be used to create fast, stable, and accurate surrogates of a simple photochemical mechanism. In future work, we will explore the application of this method to more detailed mechanisms and their use in large‐scale simulations.
Immunometabolism in cancer: basic mechanisms and new targeting strategy
Authors: Su Ranran , Shao Yingying , Huang Manru , Liu Donghui , Yu Haiyang , Qiu Yuling
Published: May 2024

Maturing immunometabolic research empowers immune regulation novel approaches. Progressive metabolic adaptation of tumor cells permits a thriving tumor microenvironment (TME) in which immune cells always lose the initial killing capacity, which remains an unsolved dilemma even with the development of immune checkpoint therapies. In recent years, many studies on tumor immunometabolism have been reported. The development of immunometabolism may facilitate anti-tumor immunotherapy from the recurrent crosstalk between metabolism and immunity. Here, we discuss clinical studies of the core signaling pathways of immunometabolism and their inhibitors or agonists, as well as the specific functions of these pathways in regulating immunity and metabolism, and discuss some of the identified immunometabolic checkpoints. Understanding the comprehensive advances in immunometabolism helps to revise the status quo of cancer treatment.
Task-oriented machine learning surrogates for tipping points of agent-based models
Authors: Fabiani Gianluca , Evangelou Nikolaos , Cui Tianqi , Bello-Rivas Juan M. , Martin-Linares Cristina P. , Siettos Constantinos , Kevrekidis Ioannis G.
Published: May 2024

We present a machine learning framework bridging manifold learning, neural networks, Gaussian processes, and Equation-Free multiscale approach, for the construction of different types of effective reduced order models from detailed agent-based simulators and the systematic multiscale numerical analysis of their emergent dynamics. The specific tasks of interest here include the detection of tipping points, and the uncertainty quantification of rare events near them. Our illustrative examples are an event-driven, stochastic financial market model describing the mimetic behavior of traders, and a compartmental stochastic epidemic model on an Erdös-Rényi network. We contrast the pros and cons of the different types of surrogate models and the effort involved in learning them. Importantly, the proposed framework reveals that, around the tipping points, the emergent dynamics of both benchmark examples can be effectively described by a one-dimensional stochastic differential equation, thus revealing the intrinsic dimensionality of the normal form of the specific type of the tipping point. This allows a significant reduction in the computational cost of the tasks of interest.
MAPP unravels frequent co-regulation of splicing and polyadenylation by RNA-binding proteins and their dysregulation in cancer
Authors: Bak Maciej , van Nimwegen Erik , Kouzel Ian U. , Gur Tamer , Schmidt Ralf , Zavolan Mihaela , Gruber Andreas J.
Published: May 2024

Maturation of eukaryotic pre-mRNAs via splicing and polyadenylation is modulated across cell types and conditions by a variety of RNA-binding proteins (RBPs). Although there exist over 1,500 RBPs in human cells, their binding motifs and functions still remain to be elucidated, especially in the complex environment of tissues and in the context of diseases. To overcome the lack of methods for the systematic and automated detection of sequence motif-guided pre-mRNA processing regulation from RNA sequencing (RNA-Seq) data we have developed MAPP (Motif Activity on Pre-mRNA Processing). Applying MAPP to RBP knock-down experiments reveals that many RBPs regulate both splicing and polyadenylation of nascent transcripts by acting on similar sequence motifs. MAPP not only infers these sequence motifs, but also unravels the position-dependent impact of the RBPs on pre-mRNA processing. Interestingly, all investigated RBPs that act on both splicing and 3’ end processing exhibit a consistently repressive or activating effect on both processes, providing a first glimpse on the underlying mechanism. Applying MAPP to normal and malignant brain tissue samples unveils that the motifs bound by the PTBP1 and RBFOX RBPs coordinately drive the oncogenic splicing program active in glioblastomas demonstrating that MAPP paves the way for characterizing pre-mRNA processing regulators under physiological and pathological conditions.
Ser/Leu-swapped cell-free translation system constructed with natural/in vitro transcribed-hybrid tRNA set
Authors: Fujino Tomoshige , Sonoda Ryogo , Higashinagata Taito , Mishiro-Sato Emi , Kano Keiko , Murakami Hiroshi
Published: May 2024

The Ser/Leu-swapped genetic code can act as a genetic firewall, mitigating biohazard risks arising from horizontal gene transfer in genetically modified organisms. Our prior work demonstrated the orthogonality of this swapped code to the standard genetic code using a cell-free translation system comprised of 21 in vitro transcribed tRNAs. In this study, to advance this system for protein engineering, we introduce a natural/in vitro transcribed-hybrid tRNA set. This set combines natural tRNAs from Escherichia coli (excluding Ser, Leu, and Tyr) and in vitro transcribed tRNAs, encompassing anticodon-swapped tRNASerGAG and tRNALeuGGA. This approach reduces the number of in vitro transcribed tRNAs required from 21 to only 4. In this optimized system, the production of a model protein, superfolder green fluorescent protein, increases to 3.5-fold. With this hybrid tRNA set, the Ser/Leu-swapped cell-free translation system will stand as a potent tool for protein production with reduced biohazard concerns in future biological endeavors.
Molecular fingerprinting of biological nanoparticles with a label-free optofluidic platform
Authors: Stollmann Alexia , Garcia-Guirado Jose , Hong Jae-Sang , Rüedi Pascal , Im Hyungsoon , Lee Hakho , Ortega Arroyo Jaime , Quidant Romain
Published: May 2024

Label-free detection of multiple analytes in a high-throughput fashion has been one of the long-sought goals in biosensing applications. Yet, for all-optical approaches, interfacing state-of-the-art label-free techniques with microfluidics tools that can process small volumes of sample with high throughput, and with surface chemistry that grants analyte specificity, poses a critical challenge to date. Here, we introduce an optofluidic platform that brings together state-of-the-art digital holography with PDMS microfluidics by using supported lipid bilayers as a surface chemistry building block to integrate both technologies. Specifically, this platform fingerprints heterogeneous biological nanoparticle populations via a multiplexed label-free immunoaffinity assay with single particle sensitivity. First, we characterise the robustness and performance of the platform, and then apply it to profile four distinct ovarian cell-derived extracellular vesicle populations over a panel of surface protein biomarkers, thus developing a unique biomarker fingerprint for each cell line. We foresee that our approach will find many applications where routine and multiplexed characterisation of biological nanoparticles are required.
Proteostatic reactivation of the developmental transcription factor TBX3 drives BRAF/MAPK-mediated tumorigenesis
Authors: Zhang Zhenlei , Wu Yufan , Fu Jinrong , Yu Xiujie , Su Yang , Jia Shikai , Cheng Huili , Shen Yan , He Xianghui , Ren Kai , Zheng Xiangqian , Guan Haixia , Rao Feng , Zhao Li
Published: May 2024

MAPK pathway-driven tumorigenesis, often induced by BRAFV600E, relies on epithelial dedifferentiation. However, how lineage differentiation events are reprogrammed remains unexplored. Here, we demonstrate that proteostatic reactivation of developmental factor, TBX3, accounts for BRAF/MAPK-mediated dedifferentiation and tumorigenesis. During embryonic development, BRAF/MAPK upregulates USP15 to stabilize TBX3, which orchestrates organogenesis by restraining differentiation. The USP15-TBX3 axis is reactivated during tumorigenesis, and Usp15 knockout prohibits BRAFV600E-driven tumor development in a Tbx3-dependent manner. Deleting Tbx3 or Usp15 leads to tumor redifferentiation, which parallels their overdifferentiation tendency during development, exemplified by disrupted thyroid folliculogenesis and elevated differentiation factors such as Tpo, Nis, Tg. The clinical relevance is highlighted in that both USP15 and TBX3 highly correlates with BRAFV600E signature and poor tumor prognosis. Thus, USP15 stabilized TBX3 represents a critical proteostatic mechanism downstream of BRAF/MAPK-directed developmental homeostasis and pathological transformation, supporting that tumorigenesis largely relies on epithelial dedifferentiation achieved via embryonic regulatory program reinitiation.
Geologically younger ecosystems are more dependent on soil biodiversity for supporting function
Authors: Feng Jiao , Liu Yu-Rong , Eldridge David , Huang Qiaoyun , Tan Wenfeng , Delgado-Baquerizo Manuel
Published: May 2024

Soil biodiversity contains the metabolic toolbox supporting organic matter decomposition and nutrient cycling in the soil. However, as soil develops over millions of years, the buildup of plant cover, soil carbon and microbial biomass may relax the dependence of soil functions on soil biodiversity. To test this hypothesis, we evaluate the within-site soil biodiversity and function relationships across 87 globally distributed ecosystems ranging in soil age from centuries to millennia. We found that within-site soil biodiversity and function relationship is negatively correlated with soil age, suggesting a stronger dependence of ecosystem functioning on soil biodiversity in geologically younger than older ecosystems. We further show that increases in plant cover, soil carbon and microbial biomass as ecosystems develop, particularly in wetter conditions, lessen the critical need of soil biodiversity to sustain function. Our work highlights the importance of soil biodiversity for supporting function in drier and geologically younger ecosystems with low microbial biomass.
Interplay between Mg2+ and Ca2+ at multiple sites of the ryanodine receptor
Authors: Nayak Ashok R. , Rangubpit Warin , Will Alex H. , Hu Yifan , Castro-Hartmann Pablo , Lobo Joshua J. , Dryden Kelly , Lamb Graham D. , Sompornpisut Pornthep , Samsó Montserrat
Published: May 2024

RyR1 is an intracellular Ca2+ channel important in excitable cells such as neurons and muscle fibers. Ca2+ activates it at low concentrations and inhibits it at high concentrations. Mg2+ is the main physiological RyR1 inhibitor, an effect that is overridden upon activation. Despite the significance of Mg2+-mediated inhibition, the molecular-level mechanisms remain unclear. In this work we determined two cryo-EM structures of RyR1 with Mg2+ up to 2.8 Å resolution, identifying multiple Mg2+ binding sites. Mg2+ inhibits at the known Ca2+ activating site and we propose that the EF hand domain is an inhibitory divalent cation sensor. Both divalent cations bind to ATP within a crevice, contributing to the precise transmission of allosteric changes within the enormous channel protein. Notably, Mg2+ inhibits RyR1 by interacting with the gating helices as validated by molecular dynamics. This structural insight enhances our understanding of how Mg2+ inhibition is overcome during excitation.
The nucleic acid binding protein SFPQ represses EBV lytic reactivation by promoting histone H1 expression
Authors: Murray-Nerger Laura A. , Lozano Clarisel , Burton Eric M. , Liao Yifei , Ungerleider Nathan A. , Guo Rui , Gewurz Benjamin E.
Published: May 2024

Epstein-Barr virus (EBV) uses a biphasic lifecycle of latency and lytic reactivation to infect >95% of adults worldwide. Despite its central role in EBV persistence and oncogenesis, much remains unknown about how EBV latency is maintained. We used a human genome-wide CRISPR/Cas9 screen to identify that the nuclear protein SFPQ was critical for latency. SFPQ supported expression of linker histone H1, which stabilizes nucleosomes and regulates nuclear architecture, but has not been previously implicated in EBV gene regulation. H1 occupied latent EBV genomes, including the immediate early gene BZLF1 promoter. Upon reactivation, SFPQ was sequestered into sub-nuclear puncta, and EBV genomic H1 occupancy diminished. Enforced H1 expression blocked EBV reactivation upon SFPQ knockout, confirming it as necessary downstream of SFPQ. SFPQ knockout triggered reactivation of EBV in B and epithelial cells, as well as of Kaposi’s sarcoma-associated herpesvirus in B cells, suggesting a conserved gamma-herpesvirus role. These findings highlight SFPQ as a major regulator of H1 expression and EBV latency.