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Multi-omic analyses reveal a differential contribution of chromatin-associated PP1 holoenzymes to mitotic exit and G1 re-establishment
Highlights:
• Multi-omic profiling uncovers divergent PP1-holoenzyme functions at the M-to-G1 transition
• Repo-Man loss accelerates mitotic exit by weakening SAC signaling
• Ki-67 depletion disrupts centromere compaction and CENP-B/C loading
• PNUTS degradation increases RNA Pol II-S5 phosphorylation, R-loops, and DNA damageResource availability:
Lead contact:
Requests for further information and resources should be directed to and will be fulfilled by the lead contact, Paola Vagnarelli ([email protected]).
Materials availability:
All unique/stable reagents generated in this study are available from the lead contact with a completed materials transfer agreement.
Data and code availability:
• ATAC-seq, RNA-seq, and ChIP-seq data have been deposited at ArrayExpress as E-MTAB-13826, E-MTAB-13827, and E-MTAB-15533 and are publicly available as of the date of publication. Mass spectrometry data have been deposited at PRIDE as PXD049319 and are publicly available as of the date of publication.
• This paper analyzes existing, publicly available data, accessible at GEO: GSE186206 (Ki-67), GEO: GSE54170 (Repo-Man and PNUTS), GEO: GSE84035 (in vitro binding sequencing data for Repo-Man), GEO: GSM8413578 (PNUTS ChIP dataset), GEO: GSE86667 (H3K9me3), and GEO: GSM5640483 (LMNB1).
• This paper does not report original code.
• Any additional information required to reanalyze the data reported in this paper is available from the lead contact upon request.Mitotic exit is an important part of the cell cycle, requiring the coordination of many chromatin and cytoskeleton remodeling events to successfully complete cell division and maintain cell identity. Protein dephosphorylation is a key step in directing mitotic exit, and protein phosphatase 1 (PP1) is essential to this process; however, the specific contribution of its numerous targeting subunits is still unknown. Here, we have investigated the function of three chromatin-associated PP1-targeting subunits in mitosis exit: Repo-Man, Ki-67, and protein phosphatase 1 nuclear targeting subunit (PNUTS). We generated endogenously tagged, auxin-degradable alleles for each subunit in the human cell line HCT116 and used a multi-omic approach to address their specific contributions toward transcription resumption, chromatin accessibility, and protein dephosphorylation at the transition from mitosis to G1. This approach identified their distinct role in mitotic exit, provided datasets for the cell-cycle community, and highlighted functions for Ki-67 and Repo-Man in genome stability and organization.The work was supported by the Wellcome Trust Investigator Award 210742/Z/18/Z to P.V., BBSRC BB/V013920/1 to P.V., and a CHMLS PhD scholarship (Brunel University London) to K.S
Fair Benchmarking in Short‐Term Load Forecasting
Data Availability Statement:
The data that support the findings of this study are available from the corresponding author upon reasonable request.Performance comparisons in short-term load forecasting are often confounded by differences in preprocessing pipelines rather than reflecting intrinsic architectural capability. Variations in feature engineering, scaling, temporal windowing and data partitioning can dominate reported accuracy and obscure the actual behaviour of forecasting models. This study examines preprocessing–architecture interaction by benchmarking random forest, LightGBM, long short-term memory (LSTM), transformer and Temporal Fusion Transformer (TFT) under a shared tabular preprocessing pipeline, ensuring strict control over data handling and evaluation conditions. Under this controlled setting, tree-based models exhibit strong predictive performance, whereas deep sequence models experience substantial degradation when temporal continuity is not explicitly represented. To isolate architectural sensitivity from preprocessing effects, we further conduct a within-architecture analysis by retraining an identical LSTM under a sequence-aware pipeline aligned with its temporal inductive bias. This realignment yields an order-of-magnitude reduction in RMSE, demonstrating that preprocessing design is a first-order determinant of deep sequence model performance. The results establish a transparent and reproducible benchmarking framework and highlight the importance of aligning data representation with model assumptions when interpreting comparative performance in time series forecasting.The authors have nothing to report
Design of micro-channel based actively cooled thermal shields for ultra-high temperature applications
Data availability:
Data will be made available on request.In this study, novel designs of high-temperature thermal shields that can be actively cooled by circulating water through a bioinspired internal microchannel network are numerically evaluated. The level of cooling that can be achieved and the thermal stresses developed in the shield material are analysed using computational fluid dynamics and finite element modelling. From the comparative analysis of those results, design guidelines for the development of such actively cooled thermal shields (ACTS) are proposed: (i) channel design plays only a minor role on the coolant mass needed to produce a desired level of cooling but (ii) small channels around the regions of maximum temperature gradient and stress concentrators like sharp corners should be avoided to prevent cracking of the shield material; and (iii) high temperature tolerance and high thermal conductivity are key parameters for the shield material. Thus, ultra-high temperature ceramics (UHTC) such as ZrB2 appear to be optimal candidates for the additive fabrication of such ACTS elements, provided they can survive the thermal cycling without cracking. Water was confirmed as an excellent coolant for such an application, enabling the development of reusable solutions for aerospace re-entry shields, involving coolant masses that could become competitive against current single-use ablative shields. Similar systems could provide suitable thermal protection or heat exchange solutions in many other demanding industrial applications.This study was carried out in the framework of the M-ERA.Net3 project AM-ACTS, grant PCI2022-132933, funded by MCIN/AEI/10.13039/501100011033 and the European Union NextGenerationEU/PRTR
Energy resilience and decarbonization via hybrid renewable energy systems: A techno-economic study
Global energy systems remain dominated by fossil fuels, accounting for over 80% of primary supply and driving severe climate impacts through greenhouse gas emissions. The transition to renewable sources such as solar and wind is hindered by their intermittency — daily generation can fluctuate by more than 70%, with strong seasonal variability — leading to continued reliance on fossil-based backup generation. Achieving near-complete energy autonomy while maintaining economic viability therefore remains a major challenge. This study evaluates the techno-economic feasibility of hybrid solar–wind–battery–hydrogen systems across nine configurations using a Rule-Based Heuristic Dispatch Algorithm (RB-HDA). System performance was assessed through four key metrics: demand met, fossil-fuel reliance, and economic feasibility via Levelized Cost of Energy (LCOE) and Levelized Cost of Hydrogen (LCOH). Hybrid solar–wind–battery systems met 99.89% of demand with an LCOE of 0.39–2.32 AUD/kWh, but remained limited by seasonal deficits. Integrating hydrogen storage improved resilience to 99.999% demand met with only one fossil-fuel backup hour annually, achieving an LCOH of 0.04 AUD/kg while maintaining an LCOE of 2.32 AUD/kWh. The results demonstrate hydrogen’s role as a pivotal enabler of long-term energy autonomy and a scalable, high-reliability alternative to fossil-based generation.This work has been supported by the Future Energy Exports Cooperative Research Centre (FEnEx CRC) , whose activities are funded by the Australian Government’s Cooperative Research Centre Program
Aligning Socio-Technical Systems: Rethinking AI Adoption and Digital Transformation in SMEs
Supplemental material: Supplemental data for this article can be accessed online at https://ndownloader.figstatic.com/files/60856876 .This study examines how SMEs adopt AI using a qualitative design informed by Socio-Technical Systems Theory. The findings indicate that AI adoption is shaped by the interaction of technical constraints, organizational routines, and external pressures such as client expectations and policy uncertainty. Leadership engagement, data infrastructure, and workforce dynamics play a central role in influencing implementation progress. The study provides practical guidance for supporting more context-sensitive and adaptive approaches to AI-enabled transformation in SMEs.No funding was received
Optimizing AI-Based Traffic Sign Recognition in Electric Vehicles with GELU-Activated CNNs
Data Availability Statement:
The data used in this study are from the German Traffic Sign Recognition Benchmark (GTSRB), a publicly available multi-class image classification benchmark. The dataset is available at https://benchmark.ini.rub.de/gtsrb_dataset.html (accessed on 10 October 2025).Traffic sign recognition is critical for intelligent transportation systems and autonomous driving. Conventional convolutional neural networks (CNNs) typically utilize the ReLU activation function for its computational efficiency; however, alternative activation functions can improve computing effectiveness capacity in recognition tasks. In this study, we propose a CNNs model enhanced with the Gaussian Error Linear Unit (GELU) activation function. We evaluate its performance on benchmark datasets and compare it against both ReLU and Leaky ReLU baseline. Experimental results show that the proposed GELU-activated CNNs achieves a recognition accuracy of 99.75% and provides small but consistent improvements over ReLU and Leaky ReLU models, particularly under challenging conditions such as occlusion and low lighting. These findings highlight GELU’s potential to enhance the robustness and reliability of traffic sign recognition in Electric Vehicles for autonomous driving applications.This research received no external funding
Internet media and depression in older adults experiencing pain: Evidence from a five-year longitudinal study (2018–2023)
Data availability statement:
The original data presented in the study are openly available in the China Longitudinal Aging Social Survey (CLASS) repository at http://class.ruc.edu.cn/English/Home.htm (accessed on 8 July 2025). Pre-registration is not mandatory. Formal permission to use the CLASS data and pre-registration were obtained on June 10, 2025.Background:
Pain is a significant risk factor for depression among older adults. While prior studies suggest that internet media may improve mental well-being, it remains unclear whether such media can reduce pain-related depression.
Objectives:
This five-year longitudinal study explores the potential moderating effect of internet media on the relationship between pain and depression among older adults.
Methods:
Participants were sourced from 2018, 2020, and 2023 waves of the China Longitudinal Aging Social Survey, and this study utilized 3240 “person-year” observations from 1080 respondents. An individual fixed effects model was employed. The presence of pain, depression (measured by the CES-D scale), and media preference (measured by comparing internet and traditional media use frequency) were assessed. Subgroup heterogeneity was also explored.
Results:
The findings revealed that media preference significantly moderated the relationship between pain and depression among older adults (β = −0.725, p < .01). Compared with traditional media, internet media was more effective in alleviating depression in individuals experiencing pain. The engagement breadth of internet media also exhibited a buffering effect. Heterogeneity analysis further illustrated that the beneficial effects of internet media were more pronounced among older adults who were less educated (β = −0.865, p < .01) and retired (β = −0.887, p < .01).
Conclusion:
This study enhances the understanding of the theoretical and practical aspects of internet media's moderating role in depression among older adults. It also highlights heterogeneous effects in vulnerable subpopulations. The findings offer insights for developing non-pharmacological interventions to address depression associated with pain, contributing to promoting mental health in the aging population.This work was supported by the National Natural Science Foundation of China (Grant Number 52308010). The funding bodies did not influence this paper in any way prior to circulation
Do Synoptic Assessments Lead to Authentic Learning? A Critical Perspective on Integration and Intentionality in Higher Education Assessment Design
Data Availability Statement:
No new data were created or analyzed in this study.Synoptic assessment has gained prominence in higher education as a way to bridge fragmented curricula by enabling students to synthesize knowledge across modules. However, structural integration through assessment does not automatically produce authentic learning. Drawing on theoretical analysis and three reflective case studies from UK undergraduate programmes, this paper offers a critical practitioner perspective on how synoptic assessment and authentic learning intersect in practice. We argue that integration and authenticity represent distinct pedagogical imperatives that require deliberate alignment. Through comparative analysis of successful, partially successful, and unsuccessful implementations of assessment strategies, we demonstrate that authentic learning emerges not from integration per se, but from intentional design embedding real-world relevance, developmental scaffolding, clear purpose, and student agency. Our case studies reveal that without such intentionality, synoptic assessments risk becoming structurally coherent but pedagogically hollow exercises that fail to engage students meaningfully. Key challenges include inconsistent staff understanding, inadequate contextual framing, and insufficient attention to progressive capability development. We propose practical design principles grounded in practitioner experience: embedding authenticity through professional relevance, scaffolding complexity appropriately, enabling open-ended student responses, and establishing strong programme-level leadership with authority over assessment strategy. The core contribution of the paper is to articulate these design principles for embedding authenticity within synoptic assessment at programme level, particularly in increasingly modularised and flexible curricula, such as those designed to enable lifelong learning. By positioning integration as necessary but insufficient for authentic learning, we advance critical understanding of assessment reform and address emerging tensions between programme coherence and increasingly modularized curricula serving diverse learner pathways.This research received no external funding
Corporate governance, CEO characteristics and earnings management: Evidence from UK listed companies
This thesis was submitted for the award of Doctor of Philosophy and was awarded by Brunel University LondonThis research a novel contribution by explicitly quantifying the impact of behavioural CEO traits, specifically greed and narcissism on earnings management, extending traditional agency theory to a behavioural governance framework within a UK institutional setting. The findings demonstrate that CEOs exhibiting higher levels of greed and narcissism are significantly more likely to engage in earnings management, even in firms that formally comply with established corporate governance codes. This evidence indicates that structural governance compliance alone is insufficient to constrain opportunistic financial reporting when behavioural risks at the executive level are present.
From a policy perspective, the results suggest that UK regulators such as the Financial Reporting Council (FRC) and the Financial Conduct Authority (FCA) should move beyond a narrow focus on formal board structures and strengthen the behavioural dimension of corporate governance oversight. Specifically, governance codes and stewardship guidelines could be enhanced by encouraging greater transparency around CEO incentive intensity, power concentration, and behavioural risk indicators, particularly in firms with high discretionary reporting environments. The findings also support closer regulatory scrutiny of remuneration schemes that amplify short-term performance incentives for CEOs displaying behavioural traits associated with opportunism.
From a practical governance standpoint, the research provides clear recommendations for boards and nomination committees. CEO selection, evaluation, and succession planning should explicitly incorporate behavioural screening alongside traditional measures of experience and competence. Boards should apply heightened monitoring during early CEO tenure and when behavioural indicators of greed or narcissism are present, for example through stronger audit committee engagement, such as, more frequent performance reviews. Furthermore, separating the roles of CEO and chair and strengthening audit committee independence are shown to be particularly effective in mitigating the earnings management risks associated with such behavioural traits.
For institutional investors, especially foreign institutions with active stewardship mandates, the findings highlight the value of integrating behavioural CEO risk assessments into engagement strategies, voting decisions, and portfolio monitoring. Recognising greed and narcissism as systematic risk factors can improve stewardship effectiveness and enhance long-term investment value. Overall, this research contributes to original UK-based empirical evidence demonstrating that CEO greed and narcissism are economically meaningful drivers of earnings management, and that effective governance requires a behaviourally informed policy and monitoring approach, rather than reliance on formal compliance alone
Motivating Human Resources to Foster Innovation Elements of Smart Workplace Design in Qatar
This paper examines the role of human resource management (HRM) in facilitating the transition to smart workplaces within the unique context of Qatar's Vision 2030. While existing literature mostly focuses on technological aspects, this study addresses a critical gap by exploring the strategic, cultural, and motivational dimensions of HRM. Using a systematic literature review (SLR) of 68 peer-reviewed articles and key policy documents published between 2014 and 2025, this research synthesizes evidence on smart workplaces' implications for employee well-being, sustainability, and innovation. The analysis moves beyond description to develop an integrated HRM framework for smart workplaces in transitional economies. This framework theorizes that successful smart workplace implementation centres around the synergistic alignment of technology-enabled HRM systems (data-driven performance management, virtual training), cultural adaptation (balancing global tech trends with local values), and strategic HRM outcomes (well-being, innovation, and sustainability). The paper argues that Qatar's experience, as a rapidly modernizing nation with a diverse work-force, provides an important example for HRM scholars and practitioners in similar contexts worldwide, as it demonstrates how strategic HRM can bridge technological potential with human and organizational outcomes