Heliyon

Journal: Heliyon

Publisher

Cell Press

ISSN

2405-8440

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Publications 1 - 8 of 8

Nano-scale characterization of iron-carbohydrate complexes by cryogenic scanning transmission electron microscopy: Building the bridge to biorelevant characterization
Digigow, Reinaldo; Burgert, Michael; Luechinger, Marco; et al. (2024)
Heliyon
Iron deficiency and iron deficiency anemia pose significant health challenges worldwide. Iron carbohydrate nanoparticles administered intravenously are a mainstay of treatment to deliver elemental iron safely and effectively. However, despite decades of clinical use, a complete understanding of their physical structure and the significance for their behavior, particularly at the nano-bio interface, is still lacking, underscoring the need to employ more sophisticated characterization methods. Our study used cryogenic Scanning Transmission Electron Microscopy (cryo-STEM) to examine iron carbohydrate nanoparticle morphology. This method builds upon previous research, where direct visualization of the iron cores in these complexes was achieved using cryogenic Transmission Electron Microscopy (cryo-TEM). Our study confirms that the average size of the iron cores within these nanoparticles is approximately 2 nm across all iron-based products studied. Furthermore, our investigation revealed the existence of discernible cluster-like morphologies, not only for ferumoxytol, as previously reported, but also within all the examined iron-carbohydrate products. The application of cryo-STEM for the analyses of product morphologies provides high-contrast and high-resolution images of the nanoparticles, and facilitates the characterization at liquid nitrogen temperature, thereby preserving the structural integrity of these complex samples. The findings from this study offer valuable insights into the physical structure of iron-carbohydrate nanoparticles, a crucial step towards unraveling the intricate relationship between the structure and function of this widely used drug class in treating iron deficiency. Additionally, we developed and utilized the self-supervised machine learning workflow for the image analysis of iron-carbohydrate complexes, which might be further expanded into a useful characterization tool for comparability studies.
Comparative safety performance of autonomous- and human drivers: A real-world case study of the Waymo Driver
Di Lillo, Luigi; Gode, Tilia; Zhou, Xilin; et al. (2024)
Heliyon
After several years of public road testing, the commercial deployment of fully autonomous vehicles—or Automated Driving Systems (ADS)—is poised to scale substantially following significant technological advancements and recent regulatory approvals. However, the fundamental question of whether an ADS is safer than its human counterparts remain largely unsolved due to several challenges in establishing an appropriate real-world safety comparison method. As scaling ensues, the lack of an established method can contribute to misinterpretations or uncertainties regarding ADS safety and impede the continuous and consistent assessment of ADS performance. This study introduces three research developments to define a robust and replicable safety comparison method to address this critical methodological gap. First, we introduce the use of liability insurance claims data to measure the comparative safety between ADS and human drivers. Second, we use Swiss Re insurance claims data to establish the first zip code- and responsibility-calibrated human performance benchmark, composed of over 600,000 private passenger vehicle claims and 125 billion miles of driving exposure. Third, we perform a case study by applying the developed baseline to evaluate the safety impact of the Waymo Driver. We find that when benchmarked against zip code-calibrated human baselines, the Waymo Driver significantly improves safety towards other road users. The comparison method established in this study can be replicated for other regions or ADS deployments to aid the decision-making of ADS safety stakeholders such as regulators, and instill trust in the general public.
The computer, a choreographer? Aesthetic responses to randomly-generated dance choreography by a computer
Darda, Kohinoor M.; Cross, Emily S. (2023)
Heliyon
Is artificial intelligence (AI) changing our culture or creating its own? With advancements in AI and machine learning, artistic creativity is moving to a brave new world of possibility and complexity, while at the same time posing challenging questions, such as what defines something as art, what is the role of human creativity in an automated world, and do we evaluate artificial art in the same way as art made by humans? Across two pre-registered and statistically powered experiments we shed light on the nature of aesthetic responses toward computer-generated art by investigating observer prejudices against computer-generated dance choreography, and the impact of expertise and pre-conceived beliefs about the origin of artistic creation. Our results provide substantive evidence that an explicit bias exists among dance experts against computer-generated choreography. The mere belief about a dance work's origin biases aesthetic responses toward artworks among both dance experts and dance naïve participants. The implications of the current study serve to inform several disciplines across the arts and sciences including but not limited to empirical aesthetics, artificial intelligence, engineering, robotics, and social cognition and neuroscience. Along with physical form and content of artificial agents and art productions, the viewers' knowledge and attitudes toward artistic AI and artificial agents will need to be taken into consideration for effective human—computer/human—AI interactions.
Phenotypic alterations in articulating joint cells: Role of mechanically loaded MSC secretome
Ladner, Yann; Menzel, Ursula; Thompson, Keith; et al. (2025)
Heliyon
Improvements in the treatment of cartilage require insights into the secretory profile of mesenchymal stem cells (MSCs). Apart from their differentiation potential, MSCs secrete a multitude of molecules with therapeutic properties that benefit chondrogenesis and immunomodulation. Previously, we employed a small-panel microarray to demonstrate differences within conditioned medium (CM) of MSCs that were mechanically stimulated within a joint-mimicking bioreactor and their unloaded controls. This study analyzed the proteomic content within CM from 4 week mechanically loaded MSCs with a larger protein microarray. We examined the chondrogenic effect of CM by administration to MSC and chondrocyte pellet cultures, as well as functional changes in T cell proliferation. CM from mechanically loaded samples shows a promising push towards chondrogenic phenotypes within both pellet cultures. Inhibition of T cell proliferation was also observed. This in vitro model could enhance our understanding how mechanical load induces changes in MSC secretome benefitting cartilage healing.
Assessing the initial impact of the Russian invasion on Ukrainian agriculture: challenges, policy responses, and future prospects
Nehrey, Maryna; Finger, Robert (2024)
Heliyon
The war in Ukraine has caused significant losses to the Ukrainian agricultural sector and threatened global food security. This study aims to comprehensively analyse the impact of the Russian invasion on Ukrainian agriculture in its initial phase, examine the responses of Ukrainian agricultural policy and outline key elements for the post-war development of the Ukrainian agricultural sector. Using a systematic approach that includes thorough data collection and analysis from official sources, the Ukrainian press, relevant legislation and statistical data, our study focuses on the first five months of the conflict, from 24 February 2022 to 24 July 2022, to identify the main challenges during this period. The agricultural policy analysis shows that the Ukrainian government has adopted a reactive approach, including tax simplification, affordable credit, deregulation, financial support for the agricultural sector, reduced prices for inputs and resources to support farmers, and improvements in logistics. Critical factors identified for post-war development include repatriation and agricultural education, support for small and medium-sized farms, integration into global markets, emphasis on organic practices and sustainable development, and digitalisation in agriculture. The integration of a systematic overview of the Ukrainian agricultural sector and an analysis of key elements of post-war development provides essential insights for policy-makers and researchers concerned with the impact of war on the agricultural sector and food security.
Unsupervised quality monitoring of metal additive manufacturing using Bayesian adaptive resonance
Shevchik, Sergey; Wrobel, Rafal; Qang Tri, Le; et al. (2024)
Heliyon
Metal additive manufacturing is a recent breakthrough technology that promises automated production of complex geometric shapes at low operating costs. However, its potential is not yet fully exploited due to the low reproducibility of quality in mass production. The monitoring of parts quality directly during manufacturing promises to solve this problem, while machine learning showed efficient performance correlating versatile manufacturing measurements with different quality grades. Today, most monitoring algorithms are based on semi- or supervised learning, thus, requiring a collection and ground-truth validation of training sets. This is costly and time consuming in real-life conditions. Our work is a feasibility study of the application of unsupervised machine learning to monitor different manufacturing regimes and quality in metal additive manufacturing. The algorithm combines the kernel Bayes rule for inference and Bayesian adaptive resonance for structuring the incoming data. Airborne acoustic emission from laser powder bed fusion is used as an algorithm input. The recognition of the main manufacturing regimes (conduction mode, stable, and unstable keyholes) are shown on real-life data, while the self-learning accuracy of developed algorithm exceeds 88 %. Our approach promises future development of plug-and-play quality monitoring systems for laser processing technology, requiring minimum modifications of the existing machines, reducing time/cost for algorithm preparation and providing continuous data driven adaptation of the algorithm to changes in manufacturing conditions.
Elucidating the mechano-molecular dynamics of TRAP activity using CRISPR/Cas9 mediated fluorescent reporter mice
Yılmaz, Dilara; Marques, Francisco C.; Fischer, Yannick; et al. (2024)
Heliyon
Osteoclasts are essential for bone remodeling by adapting their resorptive activity in response to their mechanical in vivo environment. However, the molecular mechanisms underlying this process remain unclear. Here, we demonstrated the role of tartrate-resistant acid phosphatase (TRAP, Acp5), a key enzyme secreted by osteoclasts, in bone remodeling and mechanosensitivity. Using CRISPR/Cas9 reporter mice, we demonstrated bone cell reporter (BCRᴵᵇˢᵖ/ᴬᶜᵖ⁵) mice feature fluorescent TRAP-deficient osteoclasts and examined their activity during mechanically driven trabecular bone remodeling. Although BCRᴵᵇˢᵖ/ᴬᶜᵖ⁵ mice exhibited trabecular bone impairments and reduced resorption capacity in vitro, RNA sequencing revealed unchanged levels of key osteoclast-associated genes such as Ctsk, Mmp9, and Calcr. These findings, in conjunction with serum carboxy-terminal collagen crosslinks (CTX) and in vivo mechanical loading outcomes collectively indicated an unaltered bone resorption capacity of osteoclasts in vivo. Furthermore, we demonstrated similar mechanoregulation during trabecular bone remodeling in BCRᴵᵇˢᵖ/ᴬᶜᵖ⁵ and wild-type (WT) mice. Hence, this study provides valuable insights into the dynamics of TRAP activity in the context of bone remodeling and mechanosensation.
Piezo1 – Serine/threonine-protein phosphatase 2A – Cofilin1 biochemical mechanotransduction axis controls F-actin dynamics and cell migration
Morena, Francesco; Argentati, Chiara; Caponi, Silvia; et al. (2024)
Heliyon
This study sheds light on a ground-breaking biochemical mechanotransduction pathway and reveals how Piezo1 channels orchestrate cell migration. We observed an increased cell migration rate in HEK293T (HEK) cells treated with Yoda1, a Piezo1 agonist, or in HEK cells overexpressing Piezo1 (HEK + P). Conversely, a significant reduction in cell motility was observed in HEK cells treated with GsMTx4 (a channel inhibitor) or upon silencing Piezo1 (HEK-P). Our findings establish a direct correlation between alterations in cell motility, Piezo1 expression, abnormal F-actin microfilament dynamics, and the regulation of Cofilin1, a protein involved in severing F-actin microfilaments. Here, the conversion of inactive pCofilin1 to active Cofilin1, mediated by the serine/threonine-protein phosphatase 2A catalytic subunit C (PP2AC), resulted in increased severing of F-actin microfilaments and enhanced cell migration in HEK + P cells compared to HEK controls. However, this effect was negligible in HEK-P and HEK cells transfected with hsa-miR-133b, which post-transcriptionally inhibited PP2AC mRNA expression. In summary, our study suggests that Piezo1 regulates cell migration through a biochemical mechanotransduction pathway involving PP2AC-mediated Cofilin1 dephosphorylation, leading to changes in F-actin microfilament dynamics.

Publications 1 - 8 of 8

Journal: Heliyon

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