bluuebunny/crossref_metadata_2025 huggingface dataset:
Reviewing the suitability of ICT-centered design methods for smart PSS development
Authors: Paliyenko Yevgeni , Roth Daniel , Kreimeyer Matthias
Published: May 2024

The emergence of smart Product-Service Systems (smart PSS) presents numerous challenges for enterprises. The complexity of designing smart PSS adds to the need for consistent support for manufacturers. Both academia and practitioners highlight the importance of methodological support for successful development of smart PSS. This paper therefore investigates the suitability of existing support for smart PSS. Based on a systematic literature review, 17 support methods are identified and their key characteristics are discussed in the context of real PSS use cases.
Bridging simulation granularity in system-of-systems: conjunct application of discrete element method and discrete event simulations in construction equipment design
Authors: Ur Rehman Mubeen , Machchhar Raj Jiten , Bertoni Alessandro
Published: May 2024

The paper addresses a critical challenge in System-of-Systems (SoS) simulations arising from the different granularity levels in SoS simulations, integrating non-coupled Discrete Element Method results into SoS-level Discrete Event Simulations using surrogate modeling. Illustrated with a wheel loader bucket use-case in mining, it enhances early design decision-making and lays the groundwork for improving SoS simulations in construction equipment design. This paves the way for broader research and application across diverse engineering design domains.
Design for robotic disassembly
Authors: Ricard Lykke Margot , Folkmann Emilie , Sørensen Lars Carøe , Hybel Sofie Bach , de Nóbrega Roberto , Petersen Henrik Gordon
Published: May 2024

This study envisions a unified paradigm for design for automated disassembly. The goal is to integrate disassembly insights related to precious material recovery with the design phase for sustainable lifecycle management.Targeting plastic products with embedded electronics, the collaboration between design and robotic engineers aims to program a robot for disassembly for the LEGO® motor (45603) as demonstration, emphasizing a disassembly map as a vital tool. By considering the limitations and strengths of robots, this research pioneers a design for disassembly framework.
Human-centred engineering design: a cross-disciplinary product innovation practice
Authors: Eikevåg Sindre Wold , Auernhammer Jan , Elverum Christer W. , Dybvik Henrikke , Steinert Martin
Published: May 2024

This article introduces a Human-centred Engineering Design (HcED) practice, which values human aspects. This practice engages deeply into (1) human geometry and motion for specific tasks, (2) product and manufacturing complexities through rapid prototyping, and (3) the broader human task context. This cross-disciplinary method combines ergonomics, AM, sensor applications, and multiple design practices. The framework provides concrete tasks to drive innovative designs in engineering. The study, grounded in design research case studies, led to five new Paralympic Rowing world records.
Interdisciplinary system lifecycle management – a systematic literature review
Authors: Wyrwich Fabian , Kharatyan Aschot , Dumitrescu Roman
Published: May 2024

The increasing proportion of software in technical products means that both the products and the associated development processes are becoming more complex. An integration of the existing lifecycle considerations Application Lifecycle Management and Product Lifecycle Management into an interdisciplinary System Lifecycle Management promises to make the complexity manageable. To obtain an overview of the current benefits, challenges, requirements, approaches and open research gaps in the context of an ALM-PLM integration, this contribution presents the results of a Systematic Literature Review.
Approach of a virtual reality didactic toolkit – implementation and reflection
Authors: Balzerkiewitz Hans-Patrick , Stechert Carsten , Inkermann David
Published: May 2024

Virtual reality plays an increasingly important role in design education. However, a holistic view, starting with the didactic concept, the selection of a VR tool suitable for the learning task and a final reflective evaluation of the learning experience, rarely takes place. In this paper, the authors present an approach for a VR didactics toolkit that covers and takes into account all three points as a whole. The application and research environment here was the bachelor's degree module Ergonomics and Industrial Design at the Ostfalia University of Applied Sciences.
Challenges in design methods: perspectives of design students
Authors: Mayookh Mayank , Srinivasan V.
Published: May 2024

The aim of this study is to identify: (a) challenges in understanding and using design methods, and (b) features expected in an enhanced repository of design methods, by design students. These are identified through interviews and a survey. The major findings are (a) less (time for) practice leads to weak understanding and challenges in using design methods and (b) students expect to have a method recommendation system based on problem context. The findings from this study will guide in developing a user-centric, enhanced repository of design methods to aid design practice and pedagogy.
Optimization of the potting design using an approach for load path optimized designs of sandwich structures
Authors: Schellhorn Johann , Schwan Lukas , Krause Dieter
Published: May 2024

In sandwich structures, mass can be reduced or mechanical properties increased if the challenging local load distribution can be improved. Through numerical optimizations, novel designs can be determined and investigated in physical and virtual tests. This paper presents an approach for load path-optimized design of sandwich structures and novel design concepts. The approach is applied to the design concept of honeycombs filled with potting compound. Due to the shown transferability to higher structural levels, it can be used as a basis for the design optimization of any sandwich structure.
Towards a method for human-centred analysis of external variety
Authors: Sankowski Olga , Krause Dieter
Published: May 2024

Addressing VUCA challenges in product development, the Human-Centred Analysis of External Variety (HAV) method is introduced. Focusing on the early stages of new product development, HAV provides a structured approach, reducing uncertainty through quick market analysis, customer engagement, and goal setting. HAV is illustrated using a cargo bike product family case study and emphasizes its role in aligning human-centred methods with project goals. The first steps of the HAV method are presented, but also the need for further action towards a validated and elaborated method is discussed.
Understanding and definition of scanning and monitoring of the future space in the context of the product engineering process
Authors: Albers Albert , Thümmel Carsten , Schmidt Jessica , Schwarz Stefan Eric , Schlegel Michael , Siebe Andreas , Düser Tobias
Published: May 2024

Using foresight methods such as scenarios, possible futures can be described and anticipated. Needs and requirements as well as product properties can be derived from that, which is necessary to plan successful products for future customers. Changes that occur in the future development can be identified with monitoring and the expected future can be adjusted. A consistent understanding of the use of monitoring for the product engineering process does not exist and is developed in this paper. Thereby, monitoring is considered in the context of validation and located in iPeM.
Automatic knowledge graph creation from engineering standards using the example of formulas
Authors: Luttmer Janosch , Kandel Mostafa , Ehring Dominik , Nagarajah Arun
Published: May 2024

Engineering standards are an important source of knowledge in product development. Despite the increasing digitalisation, the provision and usage of standards is characterised by lots of manual steps. This research paper aims at applying automatic knowledge graph creation in the domain of engineering standards to enable machine-actionable standards. For this, a formula knowledge graph ontology as well as suitable information extraction techniques are developed. The concept is validated using the example of DIN ISO 281, showing the overall capability of automatic knowledge graph creation.
How to facilitate comparability among product models: applying a standardizing description approach
Authors: Paehler Lukas , Matthiesen Sven
Published: May 2024

During a design process, designers are supported by several purposive product models. To enable designers to switch between them, researchers need to consider the linking of product models during their development. To assist researchers in doing so, the capabilities of a standardizing description approach, stances towards product models, was investigated. The results show that the description approach was able to identify indicators of linking possibilities by facilitating comparability. This is a step towards assisting researchers in considering the linking of product models systematically.
Integration of product development data for further ontological utilization
Authors: Pickel Jessica , Bickel Sebastian , Goetz Stefan , Wartzack Sandro
Published: May 2024

The amount of data within the product development process requires a structured approach to coordinate them. Knowledge management solutions, such as ontologies, are a suitable way of linking data and representing semantic relationships. However, making all relevant data usable to ensure their target-oriented application is still a challenge. Thus, this contribution presents an approach to identify and classify heterogeneous data in product development. Besides this single ontology approach, interface solutions for data integration into an ontology are proposed.
Introducing a framework to translate user scenarios into engineering specifications with “action steps”
Authors: Ismatullaev Ulugbek Vahobjon Ugli , Kim KwanMyung
Published: May 2024

This study presents a three-stage framework to translate user scenarios into engineering specifications. We introduced 'Action Steps' as an intermediate tool to help convert user scenarios into functional requirements and engineering specifications. It facilitates aligning specifications with user needs by filling in the essential product information not revealed in user scenarios. Preliminary testing revealed that the proposed framework improved team understanding and reduced information gaps, showcasing its potential to enhance specification development and process efficiency.
Modeling uncertain requirements
Authors: Block Lukas
Published: May 2024

Anticipating all technical requirements that a product must meet throughout its lifespan has become difficult due to a rise in market, regulatory, and technological uncertainty. As a result, the attribute values of these requirements may be highly uncertain at the start of product development. We propose a mathematical model that captures and quantifies this uncertainty in a clear and comprehensive manner. We evaluate the approach by encoding uncertain requirements for an automotive project. Misconceptions regarding probabilities are alleviated and the requirements are unambiguously defined.
Using cluster analysis to enhance a method for the management of disturbance factors via product structures
Authors: Breimann Richard , Sun Laura Luran , Kirchner Eckhard
Published: May 2024

To achieve higher functionality in mechatronic systems, the management of disturbance factors plays a crucial role. For this purpose, a method was developed in prior works to address this management via the optimisation of product structures. However, this method lacks applicability due to the complexity of one step of the method. It is the goal of this paper to present a software tool, utilizing cluster-analysis to sort components into assemblies, with which this step is supported. Additionally, the method is generally adapted to address a wider spectrum of phenomena in mechatronic systems.
Challenges of the integrative product and production system development
Authors: Disselkamp Jan-Philipp , Schütte Ben , Dumitrescu Roman
Published: May 2024

Shorter product lifecycles and a shift from mechatronic to cyber-physical systems are leading to greater product complexity. This complexity can be addressed by more intensive cooperation between product and production system development. Despite intensive development in recent years, these process models have not been able to establish themselves in corporate practice. Therefore, this paper analyses the existing integrative product and production methods to identify the reasons for their lack of use in practice. The analysis has shown that there are nine barriers.
Innovation of meaning: design-driven study based on the interpretive theory of new meaning
Authors: Kushi Shotaro , Yanagisawa Hideyoshi
Published: May 2024

This study conducts design-driven meaning innovation research based on an interpretation of new meaning through qualitative and quantitative research rooted in design practice and builds design-driven theories, methodology, and highly replicable methods. It presents a new design approach to design thinking called ‘design methodology and method of meaningful products’. The design process and framework integrate words, visuals, and functions to interpret and create new meanings. It highlights the importance of design semiotics in overcoming the limitations of traditional approaches.
Data-driven support for CAD parts modelling based on automated estimated production planning – approach and user research
Authors: Erler Martin , Langula Sebastian , Wölfel Christian , Schneider Julia , Kunath Christiane , Königs Michael
Published: May 2024

We present a data-driven approach to support decision-making in CAD modelling and to improve design for manufacturing. Based on automated estimated production planning, information is provided on possible design actions and their impact. A study was conducted on perspectives on and visualizations in CAD modelling. Requirements for a user interface of the described support system were identified. The results serve as basis for further research and development on the interaction of engineering designers with data-driven decision-making support in CAD modelling.
Future-robust product design – validating influencing factors on upgradeable mechatronic systems
Authors: Kuebler Maximilian , Lange Carolin , Glasmacher Bastian , Düser Tobias , Albers Albert
Published: May 2024

This paper examines upgradability through modular product design, aiming to extend lifecycles and promote cross-generational use. It builds up on a preceding work, a systematic literature- review identifying four fields of action in future-robust product design. The paper itself contains an in-depth interview study with 17 experts from industry and research to validate and expand the literature-based fields of action. The results provide insights into the application and employment of future-robust product design, with a focus on adaptable product architectures.
Engineering designers’ CAD performance when modelling from isometric and orthographic projections
Authors: Lukačević Fanika , Becattini Niccolò , Škec Stanko
Published: May 2024

The presented study investigates differences in engineering designers' CAD performance when modelling from two types of projections in technical drawings – isometric and orthographic. The results revealed significant differences in the percentage of correctly replicated components' size and shape, indicating better CAD outcomes when generating CAD models from the orthographic projection. In addition, a comparison of duration, as well as the number and type of sketch entities, sketch relations, and CAD features, showed that CAD modelling processes were similar in both conditions.
Designing lab-on-a-chip systems with attribute dependency graphs
Authors: Soika Johannes , Wanninger Tobias , Muschak Patrick , Schwaminger Sebastian , Berensmeier Sonja , Zimmermann Markus
Published: May 2024

Lab-on-a-Chip (LOC) products for point-of-care diagnostics have gained significant attention. However, there is a lack of systematic approaches for LOC product development. To address this, we introduce an Attribute Dependency Graph exemplary for a magnetophoretic LOC system for pathogen detection. This model organizes dependencies between the design variables and crucial quantities of interest, such as detectability, cost per test, and test duration. The obtained model helps to manage design complexity and can be adapted to other LOC approaches.
A model to describe logistics service architecture based on product architecture
Authors: Strøm Erika Marie , Münsberg Tine Meidahl , Hvam Lars
Published: May 2024

The growth in e-commerce has led to increased demand for logistics services. This puts a pressure on third-party logistics (3PL) providers who struggle with increasing operating costs and heightened competition. These providers could potentially exploit the advantages of modularisation, but few studies address the design of modular logistics services. This study explores modular design of logistics services and proposes a model to describe logistics service architecture based on product architecture. A case study shows that warehousing services can be described in three domains.
Data-informed design in the automotive industry: customer acceptance study in Sweden and China on radical car design
Authors: Stylidis Kostas , Quattelbaum Bastian , Konrad Florian , Simpson Joe , Lorin Samuel , Söderberg Rikard
Published: May 2024

This study explores the alignment between automotive design innovation and consumer acceptance, particularly in the context of two significant trends: electrification and digitalization. We probed the acceptance of replacing rear window with wide-angle camera We surveyed 1,546 potential customers from China and Sweden to assess their openness to such a radical design. Findings suggest a consensus on its futuristic appeal but diverge in adoption willingness. The study offers insights to bridge the design preference gap, positioning customer acceptance as key for car design strategy.
Human- and design-centric source: comparison using requirements checklist
Authors: Naik Gouri , Srinivasan V.
Published: May 2024

The overall aim is to assess the superior of human- or design-centric source. This research compares the categories covered in a checklist by pain-points and needs identified individually using human- and design-centric sources. Data from 6 projects of a design course is used. It is found that there is no significant difference in the number of categories covered by pain-points and needs but the categories are not the same. This calls for integrating both sources in comparison to using only one source for designing which can potentially help to identify diverse and relevant outcomes.
Breaking cultural barriers: an integrated methodology for challenge-driven co-creation projects
Authors: Bastian Annika , Kempf Christoph , Rudolph Paulin , Albers Albert
Published: May 2024

The fact that successful Industry-Academia Collaborations (IACs) are beneficial for the participants is widely accepted. However, without a target-oriented methodology, the chances for success are low. This paper's focus is the early phase in the creation of such a methodology which is done in a structured way. Furthermore, the goal is to understand the great influence culture plays in creative problem-solving in distributed teams in IACs.
Narrative drives design decision-making
Authors: Ferguson Scott , Retzlaff Lisa , Bryden Kris , Bryden Kenneth Mark
Published: May 2024

Scholars in economics, psychology, and business have recently defined narrative as the underlying mechanism by which humans internally process information and drive a decision forward. In this paper, we study narrative's use in design across Design Society publications. We discuss how narrative's role as the driver of design decision-making is an important, but missing, element of the design literature. We explain how engineers will be expected to move the design process forward despite facing decisions where the information is simultaneously too much to process, conflicting, and incomplete.
Stereographic compactification and affine bi-Lipschitz homeomorphisms
Authors: Grandjean Vincent , Oliveira Roger
Published: May 2024

Let
$\sigma _q \,:\,{{\mathbb{R}}^q} \to{\textbf{S}}^q\setminus N_q$
be the inverse of the stereographic projection with center the north pole
$N_q$
. Let
$W_i$
be a closed subset of
${\mathbb{R}}^{q_i}$
, for
$i=1,2$
. Let
$\Phi \,:\,W_1 \to W_2$
be a bi-Lipschitz homeomorphism. The main result states that the homeomorphism
$\sigma _{q_2}\circ \Phi \circ \sigma _{q_1}^{-1}$
is a bi-Lipschitz homeomorphism, extending bi-Lipschitz-ly at
$N_{q_1}$
with value
$N_{q_2}$
whenever
$W_1$
is unbounded.

As two straightforward applications in the polynomially bounded o-minimal context over the real numbers, we obtain for free a version at infinity of: (1) Sampaio’s tangent cone result and (2) links preserving re-parametrization of definable bi-Lipschitz homeomorphisms of Valette.
The Role of Copyright Law in the Attainment of Inclusive and Equitable Quality Education in English-Speaking West African Countries
Authors: Olubiyi Ifeoluwa Ayokunle , Khali Allahmagani
Published: May 2024

Education is a prerequisite for the attainment of sustainable development, with multiplier effects on society. This study examines the possibility of achieving inclusive and equitable education under the UN Sustainable Development Goal (SDG) 4, AU Agenda 2063 and ECOWAS Vision 2050. Copyright plays an essential role in either encouraging or barring access to educational materials, which are necessary for the attainment of SDG 4. Through a desk study using the laws and policies of English-speaking West African countries (Gambia, Ghana, Liberia, Nigeria and Sierra Leone), the article examines the copyright laws of these jurisdictions in order to determine how they facilitate or stop access to knowledge. It finds that most of the jurisdictions (except Nigeria) have not maximized the flexibilities available for access to knowledge through copyright limitations and exceptions, thereby barring access to educational materials. It recommends a review of national copyright legislations in line with a developmental perspective.
Mediation and the Structural Interdict as Legal Options to Resolve Service Delivery Failures in South Africa
Authors: Wright Johandri
Published: May 2024

South African municipalities are entrusted to perform various functions, including providing basic services to communities. Recently, the auditor-general has raised concern about municipalities’ overall functionality and ability to fulfil their obligations. Municipalities’ service delivery failures have led to disputes between them and their communities. Moreover, South African courts have drawn attention to the impact of service delivery failures and described their catastrophic and devastating effects on communities and their local economies. In addition, it is said that the consequences of these municipal failures are more severe for the communities than any other stakeholder. For this reason, communities require legal options to resolve such disputes. This article puts forward two legal options (and potentially a third) to which communities can turn. The article examines mediation and structural interdicts and argues why these options are suitable methods for resolving disputes between a community and its municipality.
Direct stellarator coil design using global optimization: application to a comprehensive exploration of quasi-axisymmetric devices
Authors: Giuliani Andrew
Published: May 2024

Many stellarator coil design problems are plagued by multiple minima, where the locally optimal coil sets can sometimes vary substantially in performance. As a result, solving a coil design problem a single time with a local optimization algorithm is usually insufficient and better optima likely do exist. To address this problem, we propose a global optimization algorithm for the design of stellarator coils and outline how to apply box constraints to the physical positions of the coils. The algorithm has a global exploration phase that searches for interesting regions of design space and is followed by three local optimization algorithms that search in these interesting regions (a ‘global-to-local’ approach). The first local algorithm (phase I), following the globalization phase, is based on near-axis expansions and finds stellarator coils that optimize for quasisymmetry in the neighbourhood of a magnetic axis. The second local algorithm (phase II) takes these coil sets and optimizes them for nested flux surfaces and quasisymmetry on a toroidal volume. The final local algorithm (phase III) polishes these configurations for an accurate approximation of quasisymmetry. Using our global algorithm, we study the trade-off between coil length, aspect ratio, rotational transform and quality of quasi-axisymmetry. The database of stellarators, which comprises approximately 200 000 coil sets, is available online and is called QUASR, for ‘quasi-symmetric stellarator repository’.
The Seventh Dalai Lama's residence in Kham: Gartar Monastery interactions with indigenous chiefs and the Qing court
Authors: Tsomu Yudru , Chashingtsang Bugang
Published: May 2024

The Seventh Dalai Lama's residence at Gartar Monastery, which began in 1730, greatly affected the relationship between the Kham region and the Tibetan government as well as the Qing court's control over Kham. The Dalai Lama's interactions with various indigenous leaders, local monasteries, monks and lay people increased the influence of the Geluk school in Kham, and also inspired their support for the Dalai Lama. Measures adopted by the Qing court to protect the Dalai Lama, such as stationing troops and inspecting checkpoints, also strengthened Qing control of Kham. After the Dalai Lama left for Tibet in 1735, Gartar Monastery continued to serve as a religious and cultural centre of northern Kham, with the purpose of “civilizing” and “enlightening” the neighbouring regions that were far away from the political centre. Successive abbots of Gartar Monastery – right up to 1920 – came from Drepung Monastery in Lhasa; they and the Gartar monks influenced, interfered with and controlled the local affairs of Gartar and other regions in Kham. In particular, in the late nineteenth and early twentieth centuries, Gartar Monastery, together with the Tibetan commissioner in Nyarong, was able to assist in the Tibetan government's efforts to extend its sphere of influence in Kham.
A systematic review of the cost and cost-effectiveness of immunoglobulin treatment in patients with hematological malignancies
Authors: Carrillo de Albornoz Sara , Chai Khai Li , Higgins Alisa M. , Petrie Dennis , Wood Erica M. , McQuilten Zoe K.
Published: May 2024

Objectives

Patients with hematological malignancies are likely to develop hypogammaglobulinemia. Immunoglobulin (Ig) is commonly given to prevent infections, but its overall costs and cost-effectiveness are unknown.

Methods

A systematic review was conducted following the PRISMA guidelines to assess the evidence on the costs and cost-effectiveness of Ig, administered intravenously (IVIg) or subcutaneously (SCIg), in adults with hematological malignancies.

Results

Six studies met the inclusion criteria, and only two economic evaluations were identified; one cost-utility analysis (CUA) of IVIg versus no Ig, and another comparing IVIg with SCIg. The quality of the evidence was low. Compared to no treatment, Ig reduced hospitalization rates. One study reported no significant change in hospitalizations following a program to reduce IVIg use, and an observational study comparing IVIg with SCIg suggested that there were more hospitalizations with SCIg but lower overall costs per patient. The CUA comparing IVIg versus no Ig suggested that IVIg treatment was not cost-effective, and the other CUA comparing IVIg to SCIg found that home-based SCIg was more cost-effective than IVIg, but both studies had serious limitations.

Conclusions

Our review highlighted key gaps in the literature: the cost-effectiveness of Ig in patients with hematological malignancies is very uncertain. Despite increasing Ig use worldwide, there are limited data regarding the total direct and indirect costs of treatment, and the optimal use of Ig and downstream implications for healthcare resource use and costs remain unclear. Given the paucity of evidence on the costs and cost-effectiveness of Ig treatment in this population, further health economic research is warranted.
How Do Toothless Tigers Bite? Extra-institutional Governance and Internet Censorship by Local Governments in China
Authors: Zhang Tony Huiquan , Xu Jianhua , Liu Jinjin
Published: May 2024

China has constructed a rigorous state apparatus to control its online social content. To date, research has largely focused on the central government's cyber control, but the less studied local cyberspace administrative forces are also important. Our fieldwork and interviews at a county-level cyberspace administration office (CAO) in east China reveal that the local CAO had been rendered a “toothless tiger” with insufficient technology, power and labour. However, it has made up for these deficiencies by utilizing systems such as outsourced surveillance, organized mass reporting and personnel secondment. We contend that these practices, which we label “extra-institutional governance” (EIG), emerge when bureaucracies with limited resources face external pressures. The findings shed light on how censorship machines operate in local governments in China and reveal the general dynamics of how bureaucratic organizations adapt to environmental pressures.
Full-length transcriptome and co-expression network analysis reveal molecular mechanisms of seed development in Elymus sibiricus
Authors: Zheng Yuying , Lin Xiaoshan , Xie Wengang , Liu Wenxian
Published: May 2024

Grass seeds play a critical and fundamental role in grass breeding and production. Elymus sibiricus L. is a widespread Poaceae forage grass in northern Eurasia which is used for ecological restoration and forage production. Sucrose is the main source of substrate and energy required for starch synthesis in the seeds, so the hydrolysis of sucrose determines and influences starch synthesis and filling in the seeds, especially Poaceae. However, the process behind carbohydrate metabolism during E. sibiricus seed development remains unclear. This study addresses a significant gap in our understanding of the carbohydrate metabolism during seed development in E. sibiricus by employing full-length transcriptome sequencing across five developmental stages for the first time. Full-length transcriptome sequencing was performed on E. sibiricus seeds at five developmental stages (S5, S9, S15, S20, S25) to get better molecular insights. We identified 13,205 differentially expressed genes, with 7,471 up-regulated and 5,734 down-regulated. Through KEGG enrichment analysis, genes were enriched in ‘starch and sucrose metabolism’, ‘photosynthetic-related’ and ‘hormone signal transduction’ pathways. Gene ontology enrichment analysis showed that genes were enriched in the ‘beta-amylase activity’ term of molecular functions. In addition, top 21 transcription factor families were identified as involved in seed development. The homologous genes of ABSCISIC ACID-INSENSITIVE 3 (ABI3), NUCLEAR FACTOR-YB1 (NF-YB1), STARCH SYNTHASE I (SSI) were identified as candidate genes of seed development in E. sibiricus. Combined with physiological index, transcriptome analyses, weighted gene co-expression network analysis and real-time quantitative PCR, the mechanism of starch and sucrose content of seed development was revealed and ten hub genes were identified. Overall, this study provides the molecular bases to understand seed development and starch and sucrose metabolism at the different seed developmental stages in E. sibiricus.
Periods of low renal perfusion pressure are associated with acute kidney injury following paediatric cardiac surgery
Authors: Penk Jamie S. , Gist Katja M. , Barhight Matthew , Migally Karl , Borasino Santiago , Torres Wendy F. , Dong Siyuan , Marino Bradley S. , Krawczeski Catherine D.
Published: May 2024

Introduction:

Acute kidney injury is associated with worse outcomes after cardiac surgery. The haemodynamic goals to ameliorate kidney injury are not clear. Low post-operative renal perfusion pressure has been associated with acute kidney injury in adults. Inadequate oxygen delivery may also cause kidney injury. This study evaluates pressure and oximetric haemodynamics after paediatric cardiac surgery and their association with acute kidney injury.

Materials and Methods:

Retrospective case–control study at a children’s hospital. Patients were < 6 months of age who underwent a Society of Thoracic Surgery-European Association for Cardio-Thoracic Surgery Congenital Heart Surgery categories ≥ 3. Low renal perfusion pressure was time and depth below several tested thresholds. The primary outcome was serum creatine-defined acute kidney injury in the first 7 days.

Results:

Sixty-six patients (median age 8 days) were included. Acute kidney injury occurred in 36%. The time and depth of renal perfusion pressure < 42 mmHg in the first 24 hours was greater in acute kidney injury patients (94 versus 35 mmHg*minutes of low renal perfusion pressure/hour, p = 0.008). In the multivariable model, renal perfusion pressure < 42 mmHg was associated with acute kidney injury (aOR: 2.07, 95%CI: 1.25–3.82, p = 0.009). Mean arterial pressure, central venous pressure, and measures of inadequate oxygen delivery were not associated with acute kidney injury.

Conclusion:

Periods of low renal perfusion pressure (<42 mmHg) in the first 24 post-operative hours are associated with acute kidney injury. Renal perfusion pressure is a potential modifiable target that may mitigate the impact of acute kidney injury after paediatric cardiac surgery.
Human Labor and Natural Labor in Henry David Thoreau's Works
Authors: Israeli Alec
Published: May 2024

This article argues that Thoreau's concept of “labor” presented as a defense of poiesis—any generative, world-altering activity. Thoreau understood Nature's labor as the ultimate creation for humans to imitate. Human labor best approached this ideal in the absence of market-based divisions of labor, particularly when mental and physical labor were united (even undifferentiated beyond their contemporary, reified distinction, a distinction which deeply troubled Thoreau). Thoreau's epistemology undergirds my discussion of his theory of labor. As I argue, his attempts to transcend divisions between subject and object, between ideal and material—divisions pertinent to his intellectual influences and interlocutors—were isomorphic to his attempts to transcend divisions of mental and physical labor, insofar as sensuous knowing itself was laborious. As Thoreau sought to know Nature and bring human labor closer to it, he expressed a consistent, dialectically complex philosophy, in which political economy and aesthetics, science and poetry, ran in parallel.
Hypercriticism: A Case Study in the Rhetoric of Vice
Authors: Paul Herman
Published: May 2024

This article traces the history of a scholarly vice of little renown: hypercriticism. Focusing on classical philologists and biblical scholars in nineteenth-century Germany, it examines how Hyperkritik developed from a technical philological term into a pejorative label that was widely invoked to discredit the latest trends in classical philology and, especially, biblical scholarship. Methodologically, this broad use of the term challenges historians’ preference for treating scholarly virtues and vices as norms tied to scholars’ research practices. The article therefore develops a rhetorical approach, complementary to the praxeological one, in which scholarly vice terms are interpreted as parts of a repertoire of scholarly “don'ts” on which both specialists and nonspecialists could draw in addressing the perceived ills of scholarly work.
META-CLASSICAL NON-CLASSICAL LOGICS
Authors: BARRIO EDUARDO , FIORE CAMILLO , PAILOS FEDERICO
Published: May 2024

Recently, it has been proposed to understand a logic as containing not only a validity canon for inferences but also a validity canon for metainferences of any finite level. Then, it has been shown that it is possible to construct infinite hierarchies of ‘increasingly classical’ logics—that is, logics that are classical at the level of inferences and of increasingly higher metainferences—all of which admit a transparent truth predicate. In this paper, we extend this line of investigation by taking a somehow different route. We explore logics that are different from classical logic at the level of inferences, but recover some important aspects of classical logic at every metainferential level. We dub such systems meta-classical non-classical logics. We argue that the systems presented deserve to be regarded as logics in their own right and, moreover, are potentially useful for the non-classical logician.
Localized Tidal Energy Extraction in Puget Sound Can Adjust Estuary Reflection and Friction, Modifying Barotropic Tides System‐Wide
Authors: Spicer Preston , MacCready Parker , Yang Zhaoqing
Published: May 2024

Harvesting energy via tidal stream turbines is being increasingly considered as a renewable energy resource in estuaries with strong tidal currents. It remains unclear how localized energy extraction changes basic tidal physics throughout real systems. Here, we analyze the influence of an extensive synthetic tidal turbine array on barotropic tides in the Salish Sea, a complex, tidally energetic estuary, using a realistic numerical model. Tidal energy fluxes are calculated at 15 sections throughout the system and decomposed into incident and reflected components, as well as by frequency. Results show the dominant semidiurnal constituent, M2, controls the total tidal energy flux everywhere. When turbines are placed in Tacoma Narrows, the M2 energy flux is enhanced at sections seaward of the array in Puget Sound and reduced landward. The principal diurnal constituent, K1, contributes little to the total energy flux, but behaves similarly. Changes to each constituent are primarily attributed to turbine enhanced frictional dissipation which reduces the estuary's natural resonant period (∼10 hr) amplification. Being close to the semidiurnal frequencies, the resonance adjustment reduces M2 tidal reflection seaward of the turbines and free surface amplitude (particularly landward of the turbines) thereby increasing (decreasing) tidal energy fluxes at seaward (landward) locations. K1 is further from the natural frequency and insensitive to resonance changes. We hypothesize K1 is directly sensitive to increased frictional dissipation which acts to reduce reflection and tidal amplitude, regardless of the estuary natural frequency. Spatial variability in dynamics is discussed, as well as potential environmental implications.
Water Transport in the Mars Northern Winter Polar Atmosphere: Observations and Simulations
Authors: Gillespie H. E. , McCleese D. J. , Kleinböhl A. , Kass D. M. , Greybush S. J. , Wilson R. J.
Published: May 2024

This study involving both observations and simulations furthers our understanding of water transport in the Martian northern polar region, a critical component of the global water cycle, and explores strengths and weaknesses in simulations of the polar atmosphere. Observations of the northern polar winter by the Mars Climate Sounder (MCS) onboard the Mars Reconnaissance Orbiter show extensive water ice clouds over the polar ice cap throughout the 300–3 Pa (∼10–50 km) vertical column within the vortex during the entire winter season. The observations also indicate that the vortex evolves throughout its depth on a broad range of timescales, from sub‐diurnal to seasonal. Time sequences of these data together with results from a Mars global circulation model and Ensemble Mars Atmosphere Reanalysis System reanalysis (EMARS) are used to study the evolution of the winter polar atmosphere and to examine dynamic mechanisms for transporting water across the vortex boundary. Model simulations and reanalysis show a similar temperature structure to observations, although they struggle to reproduce some of the detailed features such as the extent of polar warming above the vortex and the magnitude of the temperature minima inside the vortex. The free run simulation also fails to capture the vertically distributed water ice cloud due to a general absence of transport across the vortex boundary. EMARS results, with assimilated MCS temperatures, show a greater amount of water entering the vortex at pressures below 200 Pa, leading to a more vertically extended cloud within the vortex and improving agreement with observations.
Global Flash Droughts Characteristics: Onset, Duration, and Extent at Watershed Scales
Authors: Neelam Maheshwari , Hain Christopher
Published: May 2024

Addressing impacts of flash droughts (FDs) on the water‐food nexus requires a understanding of FD mechanisms and drivers at the watershed level. Examining climatic drivers, dry and wet spell lengths from 1980 to 2019, we analyzed FD spatial and temporal characteristics, emphasizing areal extent, onset time, and duration. Our findings reveal substantial variations in FDs among different watersheds. Notably, watersheds in the Southern Hemisphere are witnessing expanding, faster‐developing, and longer‐lasting FDs, aligning with climate variations in precipitation and temperature. Additionally, at the watershed scale, the onset and duration of FDs are more influenced by the intensity (magnitude and variability) of climatic drivers than the average length of wet and dry periods. FD‐extents, however, correlate with both climatic conditions and wet and dry periods, underscoring watershed connectivity. Ultimately, our results underscore the necessity for research to comprehend the interplay between FDs and watershed characteristics and how it manifests in overall water resource management.
Asciminib monotherapy in patients with chronic-phase chronic myeloid leukemia with the T315I mutation after ≥1 prior tyrosine kinase inhibitor: 2-year follow-up results
Authors: Cortes Jorge E. , Sasaki Koji , Kim Dong-Wook , Hughes Timothy P. , Etienne Gabriel , Mauro Michael J. , Hochhaus Andreas , Lang Fabian , Heinrich Michael C. , Breccia Massimo , Deininger Michael , Goh Yeow Tee , Janssen Jeroen J.W.M. , Talpaz Moshe , de Soria Valle Gomez Garcia , le Coutre Philipp , DeAngelo Daniel J. , Damon Andrea , Cacciatore Silvia , Polydoros Fotis , Agrawal Nithya , Rea Delphine
Published: May 2024

Asciminib targets the BCR::ABL1 myristoyl pocket, maintaining activity against BCR::ABL1T315I, which is resistant to most approved adenosine triphosphate–competitive tyrosine kinase inhibitors. We report updated phase I results (NCT02081378) assessing safety/tolerability and antileukemic activity of asciminib monotherapy 200 mg twice daily in 48 heavily pretreated patients with T315I-mutated chronic-phase chronic myeloid leukemia (CML-CP; data cutoff: January 6, 2021). With 2 years’ median exposure, 56.3% of patients continued receiving asciminib. Overall, 62.2% of evaluable patients achieved BCR::ABL1 ≤1% on the International Scale (IS); 47.6% and 81.3% of ponatinib-pretreated and -naive patients, respectively, achieved BCR::ABL1IS ≤1%. Of 45 evaluable patients, 48.9% achieved a major molecular response (MMR, BCR::ABL1IS ≤0.1%), including 34.6% and 68.4% of ponatinib-pretreated and -naive patients, respectively. MMR was maintained until data cutoff in 19 of 22 patients who achieved it. The most common grade ≥3 adverse events (AEs) included increased lipase level (18.8%) and thrombocytopenia (14.6%). Five (10.4%) patients experienced AEs leading to discontinuation, including 2 who discontinued asciminib and died due to COVID-19; these were the only deaths reported. These results show asciminib’s effectiveness, including in almost 50% of ponatinib pretreated patients, and confirm its risk-benefit profile, supporting its use as a treatment option for T315I-mutated CML-CP.
E3 ubiquitin ligase UBR5 promotes gemcitabine resistance in pancreatic cancer by inducing O-GlcNAcylation-mediated EMT via destabilization of OGA
Authors: Du Yunyan , Yang Zhangjian , Shi Hao , Chen Zhihan , Chen Rong , Zhou Fan , Peng Xiaogang , Hong Tao , Jiang Liping
Published: May 2024

Pancreatic cancer (PC) is among the deadliest malignancies, with an extremely poor diagnosis and prognosis. Gemcitabine (GEM) remains the first-line drug for treating PC; however, only a small percentage of patients benefit from current immunotherapies or targeted therapies. Resistance to GEM is prevalent and affects long-term survival. We found that ubiquitin-protein ligase E3 module N-recognition 5 (UBR5) is a therapeutic target against GEM resistance. UBR5 was markedly upregulated in clinical GEM-resistant PC samples and GEM-resistant PC cells. UBR5 knockdown markedly increased GEM sensitivity in GEM-resistant PC cell lines. UBR5-mediated GEM resistance was accompanied by activation of epithelial-mesenchymal transition (EMT) and could be mitigated by inhibiting EMT. Further analysis revealed that UBR5 promoted GEM resistance in PC cells by enhancing O-GlcNAcylation-mediated EMT. In addition, UBR5 knockdown resulted in increased O-GlcNAase (OGA) levels, an essential negatively regulated enzyme in the O-GlcNAcylation process. We identified a negative association between OGA and UBR5 levels, which further supported the hypothesis that O-GlcNAcylation-mediated GEM resistance induced by UBR5 is OGA-dependent in PC cells. Mechanistic studies revealed that UBR5 acts as an E3 ubiquitin ligase of OGA and regulates O-GlcNAcylation by binding and modulating OGA, facilitating its degradation and ubiquitination. Additionally, high-throughput compound library screening using three-dimensional protein structure analysis and drug screening identified a Food and Drug Administration drug, Y-39983 dihydrochloride, as a potent GEM sensitiser and UBR5 inhibitor. The combination of Y-39983 dihydrochloride and GEM attenuated tumour growth in a mouse xenograft tumour model. Collectively, these data demonstrated that UBR5 plays a pivotal role in the sensitisation of PC to GEM and provides a potential therapeutic strategy to overcome GEM resistance.
Bone marrow stromal cells induce chromatin remodeling in multiple myeloma cells leading to transcriptional changes
Authors: Binder Moritz , Szalat Raphael E. , Talluri Srikanth , Fulciniti Mariateresa , Avet-Loiseau Hervé , Parmigiani Giovanni , Samur Mehmet K. , Munshi Nikhil C.
Published: May 2024

The natural history of multiple myeloma is characterized by its localization to the bone marrow and its interaction with bone marrow stromal cells. The bone marrow stromal cells provide growth and survival signals, thereby promoting the development of drug resistance. Here, we show that the interaction between bone marrow stromal cells and myeloma cells (using human cell lines) induces chromatin remodeling of cis-regulatory elements and is associated with changes in the expression of genes involved in the cell migration and cytokine signaling. The expression of genes involved in these stromal interactions are observed in extramedullary disease in patients with myeloma and provides the rationale for survival of myeloma cells outside of the bone marrow microenvironment. Expression of these stromal interaction genes is also observed in a subset of patients with newly diagnosed myeloma and are akin to the transcriptional program of extramedullary disease. The presence of such adverse stromal interactions in newly diagnosed myeloma is associated with accelerated disease dissemination, predicts the early development of therapeutic resistance, and is of independent prognostic significance. These stromal cell induced transcriptomic and epigenomic changes both predict long-term outcomes and identify therapeutic targets in the tumor microenvironment for the development of novel therapeutic approaches.