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Direct Arp2/3-vinculin binding is required for pseudopod extension, but only on compliant substrates and in 3D
Full text linkA critical step in cell morphogenesis is the extension of actin-dense pseudopods, controlled by actin-binding proteins (ABPs). While this process is well-understood on glass coverslips, it is less so in compliant three-dimensional environments. Here, we knocked out a series of ABPs in osteosarcoma cells and evaluated their effect on pseudopod extension on glass surfaces (2D) and in collagen gels (3D). Cells lacking the longest Arp3 gene variant, or with attenuated Arp2/3 activity, had the strongest reduction in pseudopod formation between 2D and 3D. This was largely due to reduced activity of the hybrid Arp2/3-vinculin complex, which was dispensable on glass. Our data suggests that concurrent formation of actin branches and nascent adhesions, supported by Arp2/3-vinculin interactions, is essential to form mechanically stable links between fibrous extracellular matrix and actin in 3D. This highlights how experiments on stiff, planar substrates may conceal actin architectural features that are essential for morphogenesis in 3D
The Distribution of Ultrahigh-energy Cosmic Rays along the Supergalactic Plane Measured at the Pierre Auger Observatory
Full text linkUltrahigh-energy cosmic rays are known to be mainly of extragalactic origin, and their propagation is limited by energy losses, so their arrival directions are expected to correlate with the large-scale structure of the local Universe. In this work, we investigate the possible presence of intermediate-scale excesses in the flux of the most energetic cosmic rays from the direction of the supergalactic plane region using events with energies above 20 EeV recorded with the surface detector array of the Pierre Auger Observatory up to 2022 December 31, with a total exposure of 135,000 km2 sr yr. The strongest indication for an excess that we find, with a posttrial significance of 3.1σ, is in the Centaurus region, as in our previous reports, and it extends down to lower energies than previously studied. We do not find any strong hints of excesses from any other region of the supergalactic plane at the same angular scale. In particular, our results do not confirm the reports by the Telescope Array Collaboration of excesses from two regions in the Northern Hemisphere at the edge of the field of view of the Pierre Auger Observatory. With a comparable integrated exposure over these regions, our results there are in good agreement with the expectations from an isotropic distribution
DEVELOPMENT AND VALIDATION OF NOVEL FORCE RECONSTRUCTION ALGORITHM FOR TRACTION FORCE MICROSCOPY
Full text linkTraction Force Microscopy (TFM) is a powerful technique for quantifying cellular traction forces, yet its accuracy is dependent on the force reconstruction algorithm used to recover traction forces from the input substrate deformations. As such, the use cases of TFM are dependent on the types of reconstruction algorithms available. To expand the usability of TFM onto micropatterned substrates, we introduce gFEM, a novel force reconstruction method that incorporates the specific grooved topography of the user’s experimental substrate into the solution process. Unlike other traditionally used models, which assume a flat and continuous substrate, gFEM aims to improve the fidelity of traction recoveries by integrating the substrate geometry into its finite element-based solution. The gFEM method was benchmarked against a reconstruction algorithm which assumes a flat substrate (flatFEM) on synthetic datasets which were generated using a finite element model. The synthetic datasets consisted of direct displacement inputs as well as bead image tracking data. Results show that gFEM produced more accurate traction maps with lower noise sensitivity when compared against the flatFEM method in direct displacement cases. In general, the flatFEM algorithm produced systemic underestimation of traction values compared to the ground truth. This was attributed to the difference in the basis functions of the two methods. However, when applied to synthetic bead images, both models yielded comparable performance with minimal statistically significant differences observed. This outcome was attributed to the poor recovery of displacements within groove valleys during the image correlation-based bead tracking process. Despite this limitation, the gFEM model represents a step towards more accurate force reconstructions on topographically complex substrates. To that end, the current implementation of gFEM is freely available online, as one of the force reconstruction methods in the TFM package, so that others can utilize and improve upon the algorithm. In addition, our future work will focus on improvements to the bead tracking process which will yield better results in subsequent force reconstructions
Predicting cardiac resynchronization therapy response: development and validation of a single photon emission computed tomography-based nomogram
Full text linkBackground: Cardiac resynchronization therapy (CRT) is an effective treatment for patients with drug-refractory heart failure. However, more than thirty percent of patients do not benefit from CRT. This study aimed to develop and validate a novel model based on single photon emission computed tomography (SPECT) phase analysis features to predict CRT response. Methods: We identified 163 CRT patients who received gated resting SPECT myocardial perfusion imaging (MPI) between 2010 and 2020 at The First Affiliated Hospital of Nanjing Medical University. All variables were first processed by univariate logistic regression, and those with a P value \u3c 0.05 were retained. The selected variables were subsequently used in the least absolute shrinkage and selection operator (LASSO) regression to construct a predictive model, which was then represented as a nomogram. Nomogram performance was assessed via receiver operating characteristic (ROC) curves, calibration curves, and decision curve analyses (DCAs). Internal validation was performed by bootstrapping with 1,000 replicates. Results: Of the 163 patients, 93 (57.1%) responded to CRT during follow-up. Responders had a wider QRS complex duration (QRSd) (164.80 vs. 154.51 ms, P=0.003), fewer premature ventricular contractions (PVCs) (1,392.98 vs. 2,283.60, P=0.003), lower prevalence of non-sustained ventricular tachycardia (NS-VT) (45.2% vs. 77.1%, P\u3c 0.001), and better cardiac function [based on N-terminal pro-B-type natriuretic peptide (NT-proBNP), New York Heart Association (NYHA), and left ventricle (LV) parameters] compared to non-responders. Univariate logistic regression revealed 14 variables significantly associated with CRT response (all P\u3c 0.05). The area under the ROC curve (AUC) value for the nomogram was 0.845 [95% confidence interval (CI): 0.785–0.906; sensitivity: 0.771; specificity: 0.849]. Internal validation yielded a mean AUC of 0.814 (95% CI: 0.777–0.836). The calibration curve demonstrated strong consistency between the predicted and observed outcomes. DCA revealed that the nomogram consistently provides a net benefit over the baseline, demonstrating its high practical value in clinical decision-making. A web-based dynamic nomogram (https:// jzw20000624.shinyapps.io/CRTpredictionmodel/) was developed for clinical application. Conclusions: We developed and validated a SPECT-based prediction model for predicting CRT response, which can assist clinicians in optimizing CRT candidacy preoperatively. Pacing at the latest contraction and relaxation segments, while avoiding scarred regions and optimizing preoperative status, is anticipated to improve CRT response
A comprehensive evaluation of steel slag asphalt mixtures: performance, functional applications, and ecological considerations
No full textSteel slag offers a sustainable alternative to traditional aggregates in road construction. This review highlights the performance, environmental risks and economic benefits of steel slag asphalt mixture. Key findings indicate that steel slag-asphalt adhesion surpasses that of natural aggregates, enhancing the road performance of steel slag asphalt mixtures. Physical treatments provide only temporary control over volume expansion, while chemical treatments offer permanent solutions. Furthermore, steel slag asphalt mixtures exhibit superior heating and self-healing capabilities under microwave conditions compared to induction heating. Steel slag’s inherent surface porosity and electrical conductivity afford them enhanced functionality over conventional aggregates. Despite their environmental advantages and economic viability, challenges persist concerning the long-term leaching of heavy metals, high specific gravity, and increased asphalt content. Future research should prioritize the development of cost-effective chemical treatments to address volume expansion and optimize asphalt content. In addition, establishing comprehensive testing for heavy metal and gaseous emissions in trial sections and conducting detailed life cycle assessments (LCAs) are recommended to facilitate the broader adoption of steel slag asphalt pavements
Detecting Manipulated Digital Entities Through Real-World Anchors
No full textAs the digital and physical worlds become increasingly intertwined, manipulating digital entities, such as avatars, digital twins, and virtual environments, poses significant challenges for forensic analysis. Traditional digital forensics often lacks the mechanisms to detect sophisticated alterations within these virtual constructs. This paper presents a novel framework called DeepAnchor that establishes real-world anchors for effective forensic analysis in digital domains. DeepAnchor adopts a Feature-Integrated and Attention-Enhanced digital watermarking mechanism based on GAN (FIAE-GAN). By creating verifiable links between digital entities and their physical counterparts, DeepAnchor facilitates the detection of manipulations that might otherwise go unnoticed. Through a series of case studies, we demonstrate FIAE-GAN’s ability to detect and analyze manipulated digital entities accurately. DeepAnchor lays the foundation for future forensic strategies to preserve authenticity and trust in an era of increasingly accessible and widespread digital manipulation
Francophone Labour and Migrations in and out of the Industrial Keweenaw Peninsula
No full textThis study builds on previous scholarship on French-Canadian migration in Michigan during the industrial period to analyse how Francophone labour changed over time in one of the earliest and largest mining regions in the United States. This study analyses a sample of Francophones in Michigan’s Houghton and Keweenaw Counties classified from the U.S. Census between 1870 and 1940. The sample features multiple subcategories to allow for nuanced definitions of Francophones and French Canadians, which facilitate an examination of changing occupations across two generations, as well as out-migration at the beginning of deindustrialization. Overall findings indicate that Francophones gained skills within the region’s copper mining industry, which some transferred to other industrial regions over time
Stochastic sound speed profile and transmission loss models for the New England shelf
No full textThe proximity of the New England Shelfbreak to Gulf Stream warm-core ring eddies, along with its bathymetry, makes the area one of the most complex ocean environments in the world. Its physical oceanographic complexity extends to the shelf, which can be a valuable study case for algorithms designed to recognize stochastic patterns in large datasets. Empirical Orthogonal Function (EOF) analysis, or Principal Component Analysis (PCA), has historically been the standard statistical method for detecting spatiotemporal patterns in data. Recently, sparse dictionary learning methods like the K-SVD (singular value decomposition with k-means clustering) have begun to supplant EOF analysis for this application. Pattern recognition results from these techniques are particularly useful to underwater acoustic propagation models that require realistic environmental data input to produce useful approximations of the underwater soundscape. Using in-situ Conductivity-Temperature-Depth (CTD) measurements taken on the New England Shelf and archived in the World Ocean Database (WOD), two stochastic models were developed based on EOF analysis and the K-SVD method. Both models were used to produce stochastic realizations of sound speed profiles (SSPs) and compared with each other. These SSP realizations were further used to calculate range-dependent probability density functions of Transmission Loss (TL) over a given sound propagation path. The analysis has shown that the K-SVD method can produce SSP and TL ensembles with fewer bases compared to the EOF method. Hence, a stochastic K-SVD model can better inform probabilistic underwater acoustic propagation simulations
Meaningful engagement in transitions research: Care and value in research partnerships
No full textIn recent years, there has been a growing consensus that energy transitions research should incorporate considerations of equity and justice and that energy systems directly and indirectly impact food and water systems (FEWs). Additionally, there is a shared understanding that meaningful engagement with community partners involves ensuring equity and justice considerations are included in both research processes and outcomes. While there has been an increasing number of studies on the best practices in community and stakeholder engagement, there have been limited studies evaluating projects that are implementing engagement in their research processes. In this study, we apply the EngageINFEWS conceptual framework, which outlines best practices for engagement in FEWs research, to eleven ongoing projects within the same Environmental Protection Agency funding program investigating the drivers and impacts of energy transitions in underserved communities. We analyzed semi-structured interview data (n = 12) and publicly available project abstracts (n = 11) based on the 10 elements of the EngageINFEWS framework, and despite the diversity of project contexts, aims, and deliverables, four common themes emerged: (i) emphasis on production of meaningful research outputs; (ii) importance of navigating power dynamics; (iii) the role of effective communication systems in project success; and (iv) the need for increased funding and resources. The insights gained from empirically evaluating the goals and activities involving engagement from these particular projects based on the EngageINFEWS conceptual framework can be applied to better understand stakeholder and community engaged research across diverse contexts and offer valuable lessons on how scholars can effectively collaborate with underserved communities while providing policy-relevant recommendations to facilitate community engagement processes that enhance justice and equity through processes and outcomes
Multiscale Modeling of Thermoplastics Using Atomistic-Informed Micromechanics
No full textA multiscale repeating unit cell model of a single spherulite containing four disparate length scales was developed to predict the thermoelastic behavior of semicrystalline thermoplastic materials for composite aerospace applications. The continuum level scales were fully coupled and modeled using the generalized method of cells and the high-fidelity generalized method of cells micromechanics theories. Data from molecular dynamics simulations were used as inputs for the amorphous and crystalline constituents in the multiscale continuum models. Effective Young’s modulus, shear modulus, Poisson’s ratio, coefficient of thermal expansion, and thermal conductivity were predicted for polyether ether ketone and polyether ketone ketone, showing good agreement with the available experimental data from the open literature. Moreover, it is shown that predicted properties are fairly insensitive to the fidelity of the micromechanics model used at the highest continuum scale or the assumed shape of the spherulite