bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human foot force reveals different balance control strategies between healthy younger and older adults
Authors: Shiozawa Kaymie , Sugimoto-Dimitrova Rika , Gruben Kreg G. , Hogan Neville 
Published: April 2024

ABSTRACTAging can cause the decline of balance ability, which can lead to increased falls and decreased mobility. This work aimed to discern differences in balance control strategies between healthy older and younger adults. Foot force data of 38 older and 65 younger participants (older and younger than 60 years, respectively) were analyzed. To first determine whether the two groups exhibited any differences, this study incorporated the orientation of the foot-ground interaction force in addition to its point of application. Specifically, the frequency-dependence of the “intersection point” of the lines of actions of the foot-ground interaction force were evaluated. Results demonstrated that, like the mean center-of-pressure speed, a traditionally-employed measure, the intersection-point analysis could distinguish between the two participant groups. Then, to further explore age-specific control strategies, simulations of standing balance were conducted. An optimal controller stabilized a double-inverted-pendulum model with torque-actuated ankle and hip joints corrupted with white noise. The experimental data were compared to the simulation results to identify the controller parameters that best described the human data. Older participants showed significantly more use of the ankle than hip compared to younger participants. Best-fit controller gains suggested diminished intrinsic muscle stiffness in older adults, indicative of muscle strength loss, that was likely compensated by increased neural feedback. These results underscore the advantages of the intersection-point analysis to quantify shifts in interjoint control strategies with age, thus highlighting its potential to be used as a balance assessment tool in research and clinical settings.NEW & NOTEWORTHYAge groups were distinguished by analyzing foot-ground force data during quiet standing in older and younger adults to calculate the foot-force vector intersection point that emerges across frequency bands. Modeling balance and comparing the simulations’ outcomes with experimental results suggested that older adults increased reliance on neural feedback, possibly compensating for muscle strength deficiency. This novel analysis also quantified controllers for each participant, highlighting its potential to be implemented as a balance assessment tool.
Drug-loaded nanoparticles for cancer therapy: a high-throughput multicellular agent-based modeling study
Authors: Wang Yafei , Bucher Elmar , Rocha Heber , Jadhao Vikram , Metzcar John , Heiland Randy , Frieboes Hermann B. , Macklin Paul 
Published: April 2024

AbstractInteractions between biological systems and engineered nanomaterials have become an important area of study due to the application of nanomaterials in medicine. In particular, the application of nanomaterials for cancer diagnosis or treatment presents a challenging opportunity due to the complex biology of this disease spanning multiple time and spatial scales. A system-level analysis would benefit from mathematical modeling and computational simulation to explore the interactions between anticancer drug-loaded nanoparticles (NPs), cells, and tissues, and the associated parameters driving this system and a patient’s overall response. Although a number of models have explored these interactions in the past, few have focused on simulating individual cell-NP interactions. This study develops a multicellular agent-based model of cancer nanotherapy that simulates NP internalization, drug release within the cell cytoplasm, “inheritance” of NPs by daughter cells at cell division, cell pharmacodynamic response to the intracellular drug, and overall drug effect on tumor dynamics. A large-scale parallel computational framework is used to investigate the impact of pharmacokinetic design parameters (NP internalization rate, NP decay rate, anticancer drug release rate) and therapeutic strategies (NP doses and injection frequency) on the tumor dynamics. In particular, through the exploration of NP “inheritance” at cell division, the results indicate that cancer treatment may be improved when NPs are inherited at cell division forcytotoxicchemotherapy. Moreover, smaller dosage ofcytostaticchemotherapy may also improve inhibition of tumor growth when cell division is not completely inhibited.This work suggests that slow delivery by “heritable” NPs can drive new dimensions of nanotherapy design for more sustained therapeutic response.
Genomic surveillance reveals that the dengue 2 virus lineage responsible for the 2023-2024 epidemic in the French Caribbean Islands is resistant to Mosnodenvir
Authors: Bouzidi Hawa Sophia , Sen Selin , Piorkowski Géraldine , Pezzi Laura , Ayhan Nazli , Fontaine Albin , Canivez Thomas , Gueulen Manon , Amaral Rayane , Grard Gilda , Durand Guillaume André , de Lamballerie Xavier , Touret Franck , Klitting Raphaëlle 
Published: April 2024

AbstractDengue fever is the most important arbovirosis for public health, with more than 5 million cases worldwide in 2023. Mosnodenvir is the first anti-dengue compound with very high preclinical pan-serotype activity, currently undergoing phase 2 clinical evaluation. Here, by analyzing dengue virus (DENV) genomes from the ongoing epidemic in the French Caribbean Islands, we show that they all exhibit mutation NS4B:V91A, previously associated with strong resistance to mosnodenvirin vitro. Using antiviral activity tests on clinical and reverse-genetic strains, we confirm a 600-fold decrease in mosnodenvir sensitivity. Finally, combining phylogenetic analysis and experimental testing for resistance, we find that the V91A resistance mutation likely emerged multiple times over the last 30 years in DENV-2 and DENV-3. These results call for increased genomic surveillance, in particular to track lineages with resistance mutations. These efforts should allow to better assess the activity profile of DENV treatments in development against circulating strains.
Splitting ratio in sevoflurane vapouriser-a relook on calculations
Authors: Menon D Girijanandan , George Manjit , Salim Salih V , Sreekumar R. , Philip Sam , Mathew Roshin K , Bju Princymol , Mathai Merin Helen 
Published: April 2024

AbstractTextbooks of anaesthesia describe in detail the calculations associated with splitting ratios created invariable bypass vapourisers. These calculations are based on assumptions of carrier gas flow (eg:assume 150 ml) as practised withmeasured flow vaporizers[1,2]. Carrier gas flow in a variable bypass vaporizer is agent specific,dynamic,unknown and operator independent.Therefore assuming carrier gas flow in calculations related to variable bypass vaporisers is without rationale[3]. In spite of technological advance,the amount of vapour produced is calculated based on clinically impractical assumptions. A simple method and formula is suggested for the quick estimate of vapour output, carrier gas flow and determine the splitting ratio while operating a sevoflurane variable bypass vaporizer.
The intracellular bacteriumOrientia tsutsugamushihijacks the adaptor protein BICD2 for dynein-based motility
Authors: Manigrasso Giulia , Saharat Kittirat , Kullapanich Chitrasak , Boulanger Jerome , Morgan Tomos E. , Kramer Holger , Salje Jeanne , Carter Andrew P. 
Published: April 2024

ABSTRACTThe intracellular bacteriumOrientia tsutsugamushirelies on the microtubule cytoskeleton and the motor protein dynein to traffic to the perinuclear region within infected cells. However, it remains unclear how the bacterium is coupled to the dynein machinery and how transport is regulated. Here, we discover thatO. tsutsugamushiuses its autotransporter protein ScaC to recruit the dynein adaptor BICD2 to the bacterial surface. We show that ScaC is sufficient to engage dynein-based motility in the absence of other bacterial proteins and that BICD2 is required for efficient movement ofO. tsutsugamushiduring infection. Using TIRF single-molecule assays, we demonstrate that ScaC induces BICD2 to adopt an open conformation which activates the assembly of dynein-dynactin complexes. Our results reveal a novel role for BICD2 during bacterial infection and provide mechanistic insights into the life cycle of an important human pathogen.
Novel roles for pirin proteins and a 2-ketoglutarate: ferredoxin oxidoreductase ortholog inBacteroides fragiliscentral metabolism and comparison of metabolic mutants susceptibility to metronidazole and amixicile
Authors: Gough Andrea M. , Parker Anita C. , O’Bryan Patricia J. , Whitehead Terence R. , Roy Sourav , Garcia Brandon L. , Hoffman Paul S. , Jeffrey Smith C. , Rocha Edson R. 
Published: April 2024

ABSTRACTThe regulation of the central metabolism and fermentation pathways and its effect on antimicrobial susceptibility in the anaerobic pathogenBacteroides fragilisis not completely understood. In this study we show thatB. fragilisencodes for two iron-dependent redox-sensitive regulatory pirin protein genes,pir1andpir2,whose mRNA expression are upregulated following oxygen exposure and growth in iron-limiting conditions.Δpir1andΔpir2mutants showed altered short-chain fatty acids production compared to the parent strain. Overexpression of Pir1 and Pir2 increased susceptibility to metronidazole (MTZ), and to amixicile (AMIX), a novel inhibitor of pyruvate:ferredoxin oxidoreductase (PFOR) in anaerobes. We hypothesized these observations were a result of a modulatory effect of Pir1 and Pir2 proteins. Consistent with this, we showed that Pir1 forms direct protein-protein interactions with PFOR. In addition, AlphaFold2-based structural analysis predicts that Pir1 and Pir2 form stable interactions with several enzymes of the central metabolism including the 2-ketoglutate:ferredoxin oxidoreductases (KFOR), Kor1AB and Kor2CDAEBG. A series of metabolic mutants and electron transport chain inhibitors were used to show a wide-ranging effect of bacterial metabolism on MTZ and AMIX susceptibility. There was no cross-resistance between MTZ resistant strains with AMIX susceptibility. Furthermore, we show that AMIX is an effective antimicrobial againstB. fragilisin an experimental model of intra-abdominal infection. This investigation led to the discovery that thekor2AEBGgenes are essential for growth, and we present evidence thatkor2AEBGgenes have dual-functions including the reductive synthesis of 2-ketoglutarate via reverse TCA cycle. Support for a novel Kor2AEBG activity comes from the findings showing that addition of compounds containing oleic acid stimulated growth of theΔkor2AEBGmutant. However, the metabolic activity that bypasses KorAEBG function remains to be defined. Collectively our investigation reveals new information onB. fragiliscentral metabolism and its modulatory control by pirin proteins. These data provide new genetic and metabolic knowledge which may be leveraged for the future development of new narrow-spectrum antimicrobials.
Molecular interplay between HURP and Kif18A in mitotic spindle regulation
Authors: Perez-Bertoldi Juan M. , Zhao Yuanchang , Thawani Akanksha , Yildiz Ahmet , Nogales Eva 
Published: April 2024

AbstractDuring mitosis, microtubule dynamics are regulated to ensure proper alignment and segregation of chromosomes. The dynamics of kinetochore-attached microtubules are regulated by hepatoma-upregulated protein (HURP) and the mitotic kinesin-8 Kif18A, but the underlying mechanism remains elusive. Using single-molecule imagingin vitro, we demonstrate that Kif18A motility is regulated by HURP. While sparse decoration of HURP activates the motor, higher concentrations hinder processive motility. To shed light on this behavior, we determined the binding mode of HURP to microtubules using Cryo-EM. The structure reveals that one HURP motif spans laterally across β-tubulin, while a second motif binds between adjacent protofilaments. HURP partially overlaps with the microtubule-binding site of the Kif18A motor domain, indicating that excess HURP inhibits Kif18A motility by steric exclusion. We also observed that HURP and Kif18A function together to suppress dynamics of the microtubule plus-end, providing a mechanistic basis for how they collectively serve in spindle length control.
Identification of drug-like molecules targeting the ATPase activity of dynamin-like EHD4
Authors: Mohd Saif , Oder Andreas , Specker Edgar , Neuenschwander Martin , Von Kries Jens Peter , Daumke Oliver 
Published: April 2024

AbstractEps15 (epidermal growth factor receptor pathway substrate 15) homology domain-containing proteins (EHDs) comprise a family of eukaryotic dynamin-related ATPases that participate in various endocytic membrane trafficking pathways. Dysregulation of EHDs function has been implicated in various diseases, including cancer. The lack of small molecule inhibitors which acutely target individual EHD members has hampered progress in dissecting their detailed cellular membrane trafficking pathways and their function during disease. Here, we established a Malachite green-based assay compatible with high throughput screening to monitor the liposome-stimulated ATPase of EHD4. In this way, we identified a drug-like molecule that inhibited EHD4’s liposome-stimulated ATPase activity. Structure activity relationship (SAR) studies indicated sites of preferred substitutions for more potent inhibitor synthesis. Moreover, the assay optimization in this work can be applied to other dynamin family members showing a weak and liposome-dependent nucleotide hydrolysis activity.
Design and early operation of a new-generation internal beam dump for CERN’s Super Proton Synchrotron
Authors: Francia A. Romero , Marcone A. Perillo , Pianese S. , Andersen K. , Izquierdo G. Arnau , Briz J. A. , Perez D. Carbajo , Carlier E. , Coiffet T. , Esposito L. S. , Grenard J. L. , Grenier D. , Humbert J. , Kershaw K. , Lendaro J. , Rolo A. Ortega , Scibor K. , Senajova D. , Sgobba S. , Sharp C. , Steyaert D. , Velotti F. M. , Vincke H. , Vlachoudis V. , Calviani M. 
Published: April 2024

The Super Proton Synchrotron (SPS) is the last stage in the injector chain for CERN’s Large Hadron Collider, and it also provides proton and ion beams for several fixed-target experiments. The SPS has been in operation since 1976, and it has been upgraded over the years. For the SPS to operate safely, its internal beam dump must be able to repeatedly absorb the energy of the circulating beams without sustaining damage that would affect its function. The latest upgrades of the SPS led to the requirement for its beam dump to absorb proton beams with a momentum spectrum from 14 to 450  GeV/c and an average beam power of up to ∼270  kW. This paper presents the technical details of a new design of the SPS beam dump that was installed in one of the long straight sections of the SPS during the 2019–2020 shutdown of CERN’s accelerator complex within the framework of the Large Hadron Collider Injectors Upgrade Project. This new beam dump has been in the operation since May 2021, and it is foreseen that it will operate with a lifetime of 20 years. The key challenges in the design of the beam dump were linked to the high levels of thermal energy to be dissipated—to avoid overheating and damage to the beam dump itself—and high induced levels of radiation, which have implications for personnel access to monitor the beam dump and repair any problems occurring during operation. The design process, therefore, included extensive thermomechanical finite-element simulations of the beam-dump core and its cooling system’s response to normal operation and worst-case scenarios for beam dumping. To ensure high thermal conductivity between the beam-dump core and its water-cooling system, hot isostatic pressing techniques were used in its manufacturing process. A comprehensive set of instrumentation was installed in the beam dump to monitor it during operation and to cross-check the numerical models with operational feedback. The beam dump and its infrastructure design were also optimized to ensure it can be maintained, repaired, or replaced while minimizing the radiation doses received by personnel.

Published by the American Physical Society
2024
Three Puzzles with Covariance and Supertranslation Invariance of Angular Momentum Flux and Their Solutions
Authors: Javadinezhad Reza , Porrati Massimo 
Published: April 2024

We describe and solve three puzzles arising in covariant and supertranslation-invariant formulas for the flux of angular momentum and other Lorentz charges in asymptotically flat spacetimes: (i) Supertranslation invariance and covariance imply invariance under spacetime translations; (ii) the flux depends on redundant auxiliary degrees of freedom that cannot be set to zero in all Lorentz frames without breaking Lorentz covariance; (iii) supertranslation-invariant Lorentz charges do not generate the transformations of the Bondi mass aspect implied by the isometries of the asymptotic metric. In this Letter, we solve the first two puzzles by presenting covariant formulas that unambiguously determine the auxiliary degrees of freedom and clarify the last puzzle by explaining the different roles played by covariant and canonical charges. Our construction makes explicit the choice of reference frame underpinning seemingly unambiguous results presented in the current literature.

Published by the American Physical Society
2024
Work integrated learning and trending areas for future studies: a systematic literature review and bibliometric analysis
Authors: Amarathunga Buddhini 
Published: April 2024

PurposeThis study intends to conceptually and technically examine the literature on work integrated learning (WIL) through a systematic literature review and bibliometric analysis. The present study addresses eight distinct research questions: (1) descriptive features of the extracted literature on WIL, (2) publications trends and thematic evolution in the field of WIL, (3) the most relevant and high-impact sources on WIL, (4) the most global cited articles on WIL, (5) the most relevant and high-impact authors on WIL, (6) the most relevant countries on WIL, (7) outcomes of Bradford’s Law of Scattering and Lotka’s Law of Scientific Productivity and (8) trending research avenues for future studies in the field of WIL.Design/methodology/approachThe present study employed systematic literature review (SLR) and bibliometric analysis mapping techniques to analyze 1,295 articles extracted from the Scopus database. The analysis utilized Biblioshiny software and VOSviewer software as the primary tools.FindingsThe findings reveal that WIL constitutes a steadily expanding subject discipline, showcasing a notable 23.28% annual growth in scientific production spanning from 2002 to 2023 (July). Australia, South Africa and Canada emerged as the most productive countries within the field of WIL, as evidenced by their cumulative scientific production. The thematic map of keyword analysis suggests several burgeoning avenues for future researchers in the WIL domain, including education, reflective practices, curriculum, employability skills, international students, learning and self-efficacy.Originality/valueThis study contributes to the WIL discourse by providing a comprehensive literature review. The present study’s findings hold significance for graduates, universities, employers, the higher education industry, policymakers, regulators and the broader community.
The collaborative approaches of the knowledge-based performance management system and lean six sigma to improve contractor productivity and safety performances
Authors: Bayu Sejati Rahadian Haryo , Wibisono Dermawan , Adhiutama Akbar 
Published: April 2024

Purpose
This paper aims to design a hybrid model of knowledge-based performance management system (KBPMS) for facilitating Lean Six-Sigma (L6s) application to increase contractor productivity without compromising human safety in Indonesian upstream oil field operations that manage ageing and life extension (ALE) facilities.

Design/methodology/approach
The research design applies a pragmatic paradigm by employing action research strategy with qualitative-quantitative methodology involving 385 of 1,533 workers. The KBPMS-L6s conceptual framework is developed and enriched with the Analytical Hierarchy Process (AHP) to prioritize fit-for-purpose Key Performance Indicators. The application of L6s with Human Performance Modes analysis is used to provide a statistical baseline approach for pre-assessment of the contractor’s organizational capabilities. A comprehensive literature review is given for the main pillars of the contextual framework.

Findings
The KBPMS-L6s concept has given an improved hierarchy for strategic and operational levels to achieve a performance benchmark to manage ALE facilities in Indonesian upstream oil field operations. To increase quality management practices in managing ALE facilities, the L6s application requires an assessment of the organizational capability of contractors and an analysis of Human Performance Modes (HPM) to identify levels of construction workers’ productivity based on human competency and safety awareness that have never been done in this field.

Research limitations/implications
The action research will only focus on the contractors’ productivity and safety performances that are managed by infrastructure maintenance programs for managing integrity of ALE facilities in Indonesian upstream of oil field operations. Future research could go toward validating this approach in other sectors.

Practical implications
This paper discusses the implications of developing the hybrid KBPMS- L6s enriched with AHP methodology and the application of HPM analysis to achieve a 14% reduction in inefficient working time, a 28% reduction in supervision costs, a 15% reduction in schedule completion delays, and a 78% reduction in safety incident rates of Total Recordable Incident Rate (TRIR), Days Away Restricted or Job Transfer (DART) and Motor Vehicle Crash (MVC), as evidence of achieving fit-for-purpose KPIs with safer, better, faster, and at lower costs.

Social implications
This paper does not discuss social implications

Originality/value
This paper successfully demonstrates a novel use of Knowledge-Based system with the integration AHP and HPM analysis to develop a hybrid KBPMS-L6s concept that successfully increases contractor productivity without compromising human safety performance while implementing ALE facility infrastructure maintenance program in upstream oil field operations.