bluuebunny/crossref_metadata_2025 huggingface dataset:
Experimental study of the turbulent characteristics in the wake of tall building clusters
Authors: Mishra Abhishek , Carpentieri Matteo , Robins Alan , Placidi Marco
Published: October 2024

This manuscript mainly explores the characteristics of turbulence quantities in the wake of tall building clusters of different array size (

$N$

) and building spacing (

$W_S$

) arranged in an aligned and regular grid in the flow direction. Velocity fields are measured in a wind tunnel using three-dimensional laser Doppler anemometry. Results show a delayed recovery of

$u_{rms}$

and

$v_{rms}$

(defined as the root-mean-square of the streamwise and lateral velocities, respectively) in the wake flow compared with the mean flow. Based on the turbulent fluctuations, the extents of the near-, transition- and far-wake regions in Mishra et al. (Boundary-Layer Meteorol., vol. 189, 2023, pp. 1–25) are revisited. In the near wake, we observe a significant reduction in

$u_{rms}$

and

$v_{rms}$

in the wake of a

$4\times 4$

cluster compared with that of a single building. In the transition region, the turbulence intensity magnitudes within the cluster reduce to below their free-stream counterpart; this reduction is associated with the slowly varying nature of the normalised wake deficit in the streamwise direction. The recovery of the root mean square in the far-wake region is observed for

$x \geq 2.5W_A$

(where

$W_A$

is the width of the cluster), with the mutual interaction of the wakes formed behind the individual buildings reducing with an increase in

$W_S$

, resulting in a faster recovery of the turbulent fluctuations. Finally, wavelet analysis suggests the existence of multi-scale vortex-shedding frequencies downwind of tall building clusters.
Introduction to Part 2 of the Themed Issue, ‘Racism and Colonialism in Hegel's Philosophy’: Common Objections and Questions for Future Research
Authors: James Daniel , Knappik Franz
Published: October 2024

In the first part of our editorial introduction to the themed issue ‘Racism and Colonialism in Hegel's Philosophy’ we outlined its rationale and some of its main topics. Here we address some common objections against research of this kind and formulate questions for further research.
IMPROVED UPPER BOUNDS ON DIOPHANTINE TUPLES WITH THE PROPERTY
$D(n)$
Authors: YIP CHI HOI
Published: October 2024

Let n be a nonzero integer. A set S of positive integers is a Diophantine tuple with the property

$D(n)$

if

$ab+n$

is a perfect square for each

$a,b \in S$

with

$a \neq b$

. It is of special interest to estimate the quantity

$M_n$

, the maximum size of a Diophantine tuple with the property

$D(n)$

. We show the contribution of intermediate elements is

$O(\log \log |n|)$

, improving a result by Dujella [‘Bounds for the size of sets with the property

$D(n)$

’, Glas. Mat. Ser. III39(59)(2) (2004), 199–205]. As a consequence, we deduce that

$M_n\leq (2+o(1))\log |n|$

, improving the best known upper bound on

$M_n$

by Becker and Murty [‘Diophantine m-tuples with the property

$D(n)$

’, Glas. Mat. Ser. III54(74)(1) (2019), 65–75].
Barriers and enablers to salt intake reduction in Australian adults with high blood pressure
Authors: Khalesi Saman , Williams Edwina , Johnson David W. , Webster Jacqui , Fewings Abbie , Vandelanotte Corneel
Published: October 2024

High dietary salt intake is a known risk factor for hypertension. However, Australians continue to consume excessive amounts of salt. The purpose of this study was to identify barriers, enablers and strategies to reduce salt in a sample of Australian adults with hypertension. This was a qualitative study. Participants were asked a set of open-ended questions during focus groups conducted between October 2020 and April 2021. Sessions were recorded and transcribed. Using an inductive approach, the transcript data from the focus groups were thematically analysed. This involved checking accuracy, becoming familiar with the data, coding responses based on questions, identifying themes through common patterns and validating themes by grouping similar questions that represented the data and study aim effectively. Thirty-one adults (55 % females) with high blood pressure participated in the focus group discussions. Participants demonstrated good knowledge of high blood pressure risk factors but lacked an understanding of recommended salt intake levels and sources of hidden salt. Challenges in reducing salt intake included the limited availability of low-salt commercial foods. Participants suggested improved food labelling and the use of technology-based interventions to promote healthier choices. Findings highlight the need for behavioural interventions, policy reforms and collaborations between the government, food industries and health organisations to address high salt intake in the population.
Congruence between co-occurrence and trait-based networks is scale-dependent: a case study with flea parasites of small mammalian hosts
Authors: Krasnov Boris R. , Khokhlova Irina S. , Korallo-Vinarskaya Natalya P. , Laudisoit Anne , López Berrizbeitia M. Fernanda , Matthee Sonja , Sanchez Julliana P. , Stanko Michal , van der Mesht Luther , Vinarski Maxim V.
Published: October 2024

We applied a novel framework based on network theory and a concept of modularity that estimates congruence between trait-based ( = functional) co-occurrence networks, thus allowing the inference of co-occurrence patterns and the determination of the predominant mechanism of community assembly. The aim was to investigate the relationships between species co-occurrence and trait similarity in flea communities at various scales (compound communities: across regions within a biogeographic realm or across sampling sites within a geographic region; component communities: across sampling sites within a geographic region; and infracommunities: within a sampling site). We found that compound communities within biogeographic realms were assembled via environmental or host-associated filtering. In contrast, functional and spatial/host-associated co-occurrence networks, at the scale of regional compound communities, mostly indicated either stochastic processes or the lack of dominance of any deterministic process. Analyses of congruence between functional and either spatial (for component communities) or host-associated (for infracommunities) co-occurrence networks demonstrated that assembly rules in these communities varied among host species. In component communities, stochastic processes prevailed, whereas environmental filtering was indicated in 4 and limiting similarity/competition in 9 of 31 communities. Limiting similarity/competition processes dominated in infracommunities, followed by stochastic mechanisms. We conclude that assembly processes in parasite communities are scale-dependent, with different mechanisms acting at different scales.
Optimisation of synchronisation control parameters for enhanced bilateral teleoperation system
Authors: Kumar Naveen , Thakur Niharika , Gupta Yogita
Published: October 2024

Bilateral teleoperation systems encounter challenges in achieving synchronisation between master and slave robots due to communication time delays. This paper addresses the instability caused by these delays and proposes a solution through advanced control algorithms. Nonlinear optimisation algorithms might only sometimes deliver solutions in the allotted time, particularly when handling complicated, high-dimensional issues or when optimisation iterations are extensive. The study first develops a comprehensive mathematical model encompassing the dynamics and communication intricacies of both master and slave sides in teleoperation. By recognising the limitations of existing proportional-derivative controllers in compensating for communication errors, a sequential quadratic programming-proportional-integral-derivative (SQP-PID) controller is introduced. This controller accumulates and rectifies synchronisation delay errors, ensuring precise control without steady-state deviations. The proposed SQP-PID controller stands out for its ability to handle steady-state errors effectively, offering swift response and maintaining stability. Leveraging the SQP optimisation algorithm, it intelligently tunes the parameters, minimising synchronisation errors. The approach capitalises on the simplicity, performance, and robustness of the SQP-PID controller, providing a promising avenue for enhancing bilateral teleoperation systems’ accuracy and stability, maintaining initial discrepancy with a best fitness value of 0.98 % in varied operating conditions.
Speaking like a ‘good student’: Norms and deviations in contemporary upper secondary education in Denmark
Authors: Larsen Anne
Published: October 2024

Based on a linguistic ethnographic study of student–teacher classroom interactions, this article sheds light on language norms in a contemporary Danish STX school (upper secondary education, also known as gymnasiums). The analysis reveals that neither classrooms with the explicit teaching of an ‘academic register’ nor classrooms where teachers orient towards a youth norm constitute spaces where students have equal access to perform as good students. Even when students can decode and reproduce the language preferred by the teachers, they do not experience an equal opportunity to conform to this. It is argued that performing linguistically as good and competent students is more complex than just adapting to a specific school norm, as the students have to navigate different teacher’s norms as well as peer norms emphasising authenticity.
The neural mechanisms of race priming in American politics
Authors: Gonzalez Frank J. , Haas Ingrid J.
Published: October 2024

What are the psychological mechanisms of racial “dog whistles” in American politics? Literature on race priming in American politics argues when race is primed implicitly, racial biases influence political evaluations, but when race is made salient, individuals can use controlled processing to inhibit automatic biases and abide by egalitarian norms. However, the neural mechanisms underlying these processes have yet to be examined directly. In a 2 × 2 within-groups experiment using functional magnetic resonance imaging, we examine these neural mechanisms. We find brain areas associated with conflict detection, evaluative processing, and controlled processing are more active when race is primed explicitly rather than implicitly, as expected, although we do not find substantial brain activation associated with automatic responses to be more active during implicit than explicit primes. Results are discussed in terms of understanding how racial cues influence political evaluations while considering America’s ever-changing racial norms.
Unpacking “Social Vulnerability” and “Equity”: Critical Insights From Stormwater Climate Adaptation Research in the US Gulf Coast
Authors: Domingue S. J. , Goto E. , Maillard L. , Harrison T. , Basaraba A.
Published: October 2024

This paper assesses how the concepts of social vulnerability and equity are discursively constructed in co‐production research settings with a co‐created decision support tool. The data was collected during workshops (32 communities represented) and interviews (24 communities represented) with stormwater managers and stakeholders (SMS) working in small cities, counties/parishes, and villages and towns within 100 miles of the US Gulf Coast. Findings from participant observation of workshops show that SMS express similar viewpoints regarding indicators of social vulnerability to climate‐related hazards, often defining vulnerable people as less physically mobile or as having few monetary resources. Individuals articulated “community” through a lens of homeownership and often described their relationship to residents as strained. Findings from interviews reveal divergent viewpoints on the imperative and rationale for integrating social vulnerability data into stormwater assessments and planning. Interviews also generated more critical reflection than was present in workshops regarding racial disparities in flood hazard exposure. A key insight from this article is that tools and team composition matter but there is nuance in the degree to which they matter considering a range of contextual factors. The article argues that co‐production teams must plan for alternatives and different scenarios given the messiness of co‐production in practice and that research is needed to reveal the conditions under which specific tools matter for equity in terms of both process and outcomes.
Frictional Strength and Frictional Instability of Glaucophane Gouges at Blueschist Temperatures Support Diverse Modes of Fault Slip From Slow Slip Events to Moderate‐Sized Earthquakes
Authors: An Mengke , Zhang Fengshou , Yin Zhen‐Yu , Huang Rui , Elsworth Derek , Marone Chris
Published: October 2024

Fluid overpressure from the water released by subducted sediments and oceanic crust is an important mechanism for generating earthquakes via brittle failure and frictional instability. If unstable, such fault materials may also host diverse fault reactivation mechanisms from slow slip events to moderate‐sized earthquakes in cold subduction zones. We examine this hypothesis for glaucophane gouge ‐ a key index minerals for blueschist facies ‐ at lower confining stresses where behavior is poorly understood. We measure friction and stability at temperatures of 100°C–500°C and effective normal stresses of 50–200 MPa, to explore the controls of temperature, stresses and excess pore fluid pressures on fault friction. The frictional coefficient of glaucophane at representative temperatures and stresses is ∼0.70, insensitive to temperature but with a slight increase at lower effective stresses. Elevating temperature promotes a transition from velocity‐strengthening to weak velocity‐weakening behavior, indicating the destabilizing effect of high temperature downdip in subduction zones. Reducing effective normal stress or concomitantly elevating pore fluid pressure further strengthens the velocity‐weakening response and would be manifest as moderate‐sized earthquakes. Our results support the potential for enhanced unstable sliding of glaucophane gouges at lower effective stresses and blueschist facies temperatures ‐ with weak to moderate velocity‐weakening responses upon fluid pressurization vital for understanding the abundance of slow slip to moderate‐sized earthquakes apparent in cold subduction zones.
Magnetospheric Line Radiation: Temporal Modulation Corresponding to a Bouncing Wave
Authors: Němec F. , Santolík O. , Hospodarsky G. B. , Kurth W. S.
Published: October 2024

Magnetospheric line radiation (MLR) is a peculiar type of whistler‐mode emissions formed by several similarly spaced spectral lines, whose frequencies may vary with time. These emissions typically occur at frequencies between about 1 and 8 kHz and are observed in both ground‐based and satellite measurements. However, their origin and source locations are not yet understood, as their detection by spacecraft instruments is challenging due to the limited frequency resolution of onboard wave measurements. We use high‐resolution multicomponent wave data obtained by the Van Allen Probes to demonstrate that, in addition to the frequency modulation, MLR events possess a temporal modulation with periods on the order of seconds, which may be related to the wave bouncing between hemispheres. Observed modulation periods are used to estimate a tentative source L‐shell. The modulation periods are shorter for events with larger frequency spacing, and the estimated source L‐shells correlate with model plasmapause locations.
A Case Study of Thermospheric Exospheric Temperature Responses During the G‐Condition at Mohe and Beijing Stations
Authors: Li Shaoyang , Ren Zhipeng , Yu Tingting , Zhao Biqiang , Liu Libo , Li Guozhu , Yue Xinan , Wei Yong , Hu Lianhuan
Published: October 2024

The G‐condition (NmF2 ≤ NmF1) was observed by ground‐based ionosondes at Mohe and Beijing during the geomagnetic storm occurred on 23 and 24 April 2023. We studied exospheric temperature (Tex) responses during the G‐condition. Tex was derived from electron density (Ne) profiles (∼150–200 km) by the method proposed by Li et al. (2023, https://doi.org/10.1029/2022ja030988). The retrieved Tex showed obvious enhancements, with relative deviation of ∼10%–35% and ∼3%–20% at Mohe and Beijing, respectively. Additionally, chemical reaction rate increased by ∼15%–100% and ∼13%–30%, and O/N2 decreased by ∼17%–35% and ∼23%–30% at Mohe and Beijing, respectively. Under photochemical equilibrium assumption, peak Ne is inversely proportional to chemical reaction rate and proportional to O/N2. Increased chemical reaction rate and decreased O/N2 indicate a decrease in peak Ne. Compared to the increased Tex, the relative enhancement in Tex is more significantly associated with the G‐condition, with relative deviation above ∼10% during the G‐condition.
Phase‐Transition Variations in Granular Materials Under Multi‐Period Vibrations: Implications for Triggering Landslides After Multiple Earthquakes
Authors: Luo Hui , Hu Wei , Xu Qiang , Huang Runqiu , McSaveney Mauri , Zhou Li , Yang Wenrui
Published: October 2024

Earthquake‐triggered landslides are widely recognized. Despite extensive research on the seismic responses of landslides triggered by single earthquakes, there is a lack of understanding of the seismic responses of landslides due to earthquake sequences and multiple earthquakes, and the mechanisms of dynamic weakening under multiple earthquakes still lack support from experimental results. To explore their seismic response characteristics and triggering mechanism, a series of multi‐period vibrations ring shear tests and dynamic triaxial‐bender tests were conducted with glass spheres. The experimental results show that the co‐vibration slip occurred during the vibration process, and as the vibration periods increased, the sample gradually slipped after vibration, eventually leading to accelerated instability. The sample exhibited a transition from a solid‐semi‐solid state to a liquid state due to the increase in vibration periods. Further results show that the shear modulus progressively weakened with successive vibration periods. The weakening of the shear strength of the sample caused by multi‐periods vibration was affected by the amplitude, the vibration time, and the interval time between two periods of vibration. Our study provided insights into how multiple earthquakes of seismic sequence and seismically active area trigger landslides.
A Field‐Based Estimation of the Variability of Particle Entrainment in Coarse‐Bed Rivers
Authors: Vázquez‐Tarrío Daniel , Carrero‐Carralero Estrella , López Raúl , Ville Fanny , Vericat Damià , Batalla Ramon J.
Published: October 2024

The determination of critical shear stresses is fundamental to bedload sediment transport prediction in gravel‐bed rivers. Due to the heterogeneous shape and arrangement of the individual clasts in a riverbed, critical shear stresses typically show a large spatial variability, which is not adequately captured by the reach‐averaged description followed in common studies. In this regard, there is a general paucity of field data on this spatial variability of the critical shear stress, largely due to the lack of a standardized measurement method. In an attempt to fill this gap, we propose a field‐based workflow to estimate the frequency distribution of dimensionless critical shear stress (also named critical Shields number), which is based on the measurement of a series of variables related to the position, orientation and resistance to motion of individual clasts in a gravel‐bed river, combined with a probabilistic approximation to drag and lift coefficients. Following this workflow, the patch‐scale variability of particle incipient‐motion conditions was determined in a gravel bar of the Upper Cinca River, Spain. The results are consistent with what is known about sediment entrainment in gravel‐bed rivers. We consider this method to have great potential to advance our understanding of particle initiation of motion in gravel‐bed rivers as it provides valuable systematic field information.
Towards Interpretable Physical‐Conceptual Catchment‐Scale Hydrological Modeling Using the Mass‐Conserving‐Perceptron
Authors: Wang Yuan‐Heng , Gupta Hoshin V.
Published: October 2024

We investigate the applicability of machine learning technologies to the development of parsimonious, interpretable, catchment‐scale hydrologic models using directed‐graph architectures based on the mass‐conserving perceptron (MCP) as the fundamental computational unit. Here, we focus on architectural complexity (depth) at a single location, rather than universal applicability (breadth) across large samples of catchments. The goal is to discover a minimal representation (numbers of cell‐states and flow paths) that represents the dominant processes that can explain the input‐state‐output behaviors of a given catchment, with particular emphasis given to simulating the full range (high, medium, and low) of flow dynamics. We find that a “HyMod Like” architecture with three cell‐states and two major flow pathways achieves such a representation at our study location, but that the additional incorporation of an input‐bypass mechanism significantly improves the timing and shape of the hydrograph, while the inclusion of bi‐directional groundwater mass exchanges significantly enhances the simulation of baseflow. Overall, our results demonstrate the importance of using multiple diagnostic metrics for model evaluation, while highlighting the need for properly selecting and designing the training metrics based on information‐theoretic foundations that are better suited to extracting information across the full range of flow dynamics. This study sets the stage for interpretable regional‐scale MCP‐based hydrological modeling (using large sample data) by using neural architecture search to determine appropriate minimal representations for catchments in different hydroclimatic regimes.
Quantitative and spatially resolved detection of multiplexed microRNA from plant tissue via hybridization to hydrogel-bound DNA probes in nanoliter well arrays
Authors: Fang Jennifer , Doyle Patrick S.
Published: October 2024

Understanding complex regulatory networks in plant systems requires elucidating the roles of various gene regulators under a spatial landscape. MicroRNA are key regulators that impart high information value through their tissue specificity and stability when using expression patterns for evaluating network outcomes. However, current techniques that utilize spatial multiplexing and quantitation of microRNA are limited to primarily mammalian systems. Here, we present a method to spatially resolve and quantify multiple endogenous microRNA in situ using ethanol fixed, paraffin embedded model plant species. This method utilizes target-specific microRNA capture along with universal ligating and labelling, all within functionalized hydrogel posts containing DNA probes in nanoliter well arrays. We demonstrate the platform’s multiplexing capabilities through analyzing three endogenous microRNA in Arabidopsis thaliana rosettes which provide useful answers to fundamental plant growth and development from the unique expression patterns. The spatial tissue technique is also validated using non-spatial small RNA assays to demonstrate the versatility of the well array platform. Our new platform expands the toolkit of spatial omics technologies for plants.
Intrinsic cardiomyopathy in pediatric Marfan syndrome: predictive factors and risk assessments
Authors: Kneußel Jonas , Olfe Jakob , Stark Veronika C. , von Kodolitsch Yskert , Kozlik-Feldmann Rainer G. , Friehs Ingeborg , Kutsche Kerstin , Hübler Michael , Mir Thomas S. , Diaz-Gil Daniel
Published: October 2024

Background

Marfan syndrome (MFS) is associated with cardiovascular complications, particularly valvulopathies; however, its association with primary cardiomyopathy remains unclear.

Methods

This retrospective cohort study examined the cardiomyopathy characteristics (CMCs) in pediatric patients with MFS. CMCs were defined as meeting at least one of the following echocardiography or clinical parameters: (1) cardiac index (CI) too low for patient’s age, (2) ejection fraction (EF) <50%, and (3) diastolic dysfunction. The predictive factors for CMCs were determined using a multivariable logistic regression model.

Results

Among 83 patients with MFS (age, median [range], 12.5 [0.4–22.3] years), 39.8% exhibited CMCs. Only 4 patients (5%) showed heart failure symptoms (NYHA > 1). Independent predictors for CMCs included a systemic score of ≥7 (revised Ghent criteria) and likely pathogenic or pathogenic variants in FBN1, including variants that introduce a premature stop codon, splice site variants, and missense variants involving cysteine. A multivariable score was constructed with an AUC of 0.733.

Conclusion

This study offers valuable insights into the prevalence and predictors of CMC in pediatric patients with MFS and presents potential strategies for risk assessment of cardiomyopathy.

Impact

The objective of this study was to elucidate the contentious issue of intrinsic cardiomyopathy in Marfan syndrome and demonstrate its notable occurrence even in pediatric patients who do not exhibit heart failure symptoms or valvular complications.

We highlighted the importance of specific FBN1 variants and higher systemic scores in identifying the potential for intrinsic cardiomyopathy in pediatric patients with Marfan syndrome.
Quantum-accurate machine learning potentials for metal-organic frameworks using temperature driven active learning
Authors: Sharma Abhishek , Sanvito Stefano
Published: October 2024

Understanding structural flexibility of metal-organic frameworks (MOFs) via molecular dynamics simulations is crucial to design better MOFs. Density functional theory (DFT) and quantum-chemistry methods provide highly accurate molecular dynamics, but the computational overheads limit their use in long time-dependent simulations. In contrast, classical force fields struggle with the description of coordination bonds. Here we develop a DFT-accurate machine-learning spectral neighbor analysis potentials for two representative MOFs. Their structural and vibrational properties are then studied and tightly compared with available experimental data. Most importantly, we demonstrate an active-learning algorithm, based on mapping the relevant internal coordinates, which drastically reduces the number of training data to be computed at the DFT level. Thus, the workflow presented here appears as an efficient strategy for the study of flexible MOFs with DFT accuracy, but at a fraction of the DFT computational cost.
Sex differences in motivational biases over instrumental actions
Authors: Degni Luigi A. E. , Garofalo Sara , Finotti Gianluca , Starita Francesca , Robbins Trevor W. , di Pellegrino Giuseppe
Published: October 2024

Motivational (i.e., appetitive or aversive) cues can bias value-based decisions by affecting either direction and intensity of instrumental actions. Despite several findings describing important interindividual differences in these biases, whether biological sex can also play a role is still up to debate. By comparing females and males in both appetitive and aversive Pavlovian-to-Instrumental Transfer paradigms we found that, while motivational cues similarly bias the direction of instrumental actions in both sexes, the intensity of such actions is increased by the cue in male participants only. The present results constitute compelling evidence that a crucial motivational bias of daily actions directed to obtaining rewards or avoiding punishments is modulated by biological sex. This evidence sheds new light on the role of sex in motivational processes that underlie decision-making, highlighting the importance of considering sex as a crucial factor in future research on this topic.
Potent neutralization of SARS-CoV-2 variants by RBD nanoparticle and prefusion-stabilized spike immunogens
Authors: Miranda Marcos C. , Kepl Elizabeth , Navarro Mary Jane , Chen Chengbo , Johnson Max , Sprouse Kaitlin R. , Stewart Cameron , Palser Anne , Valdez Adian , Pettie Deleah , Sydeman Claire , Ogohara Cassandra , Kraft John C. , Pham Minh , Murphy Michael , Wrenn Sam , Fiala Brooke , Ravichandran Rashmi , Ellis Daniel , Carter Lauren , Corti Davide , Kellam Paul , Lee Kelly , Walls Alexandra C. , Veesler David , King Neil P.
Published: October 2024

We previously described a two-component protein nanoparticle vaccine platform that displays 60 copies of the SARS-CoV-2 spike protein RBD (RBD-NP). The vaccine, when adjuvanted with AS03, was shown to elicit robust neutralizing antibody and CD4 T cell responses in Phase I/II clinical trials, met its primary co-endpoints in a Phase III trial, and has been licensed by multiple regulatory authorities under the brand name SKYCovioneTM. Here we characterize the biophysical properties, stability, antigenicity, and immunogenicity of RBD-NP immunogens incorporating mutations from the B.1.351 (β) and P.1 (γ) variants of concern (VOCs) that emerged in 2020. We also show that the RBD-NP platform can be adapted to the Omicron strains BA.5 and XBB.1.5. We compare β and γ variant and E484K point mutant nanoparticle immunogens to the nanoparticle displaying the Wu-1 RBD, as well as to soluble prefusion-stabilized (HexaPro) spike trimers harboring VOC-derived mutations. We find the properties of immunogens based on different SARS-CoV-2 variants can differ substantially, which could affect the viability of variant vaccine development. Introducing stabilizing mutations in the linoleic acid binding site of the RBD-NPs resulted in increased physical stability compared to versions lacking the stabilizing mutations without deleteriously affecting immunogenicity. The RBD-NP immunogens and HexaPro trimers, as well as combinations of VOC-based immunogens, elicited comparable levels of neutralizing antibodies against distinct VOCs. Our results demonstrate that RBD-NP-based vaccines can elicit neutralizing antibody responses against SARS-CoV-2 variants and can be rapidly designed and stabilized, demonstrating the potential of two-component RBD-NPs as a platform for the development of broadly protective coronavirus vaccines.
Emergent actin flows explain distinct modes of gliding motility
Authors: Hueschen Christina L. , Segev-Zarko Li-av , Chen Jian-Hua , LeGros Mark A. , Larabell Carolyn A. , Boothroyd John C. , Phillips Rob , Dunn Alexander R.
Published: October 2024

During host infection, Toxoplasma gondii and related unicellular parasites move using gliding, which differs fundamentally from other known mechanisms of eukaryotic cell motility. Gliding is thought to be powered by a thin layer of flowing filamentous (F)-actin sandwiched between the plasma membrane and a myosin-covered inner membrane complex. How this surface actin layer drives the various gliding modes observed in experiments—helical, circular, twirling and patch, pendulum or rolling—is unclear. Here we suggest that F-actin flows arise through self-organization and develop a continuum model of emergent F-actin flow within the confines provided by Toxoplasma geometry. In the presence of F-actin turnover, our model predicts the emergence of a steady-state mode in which actin transport is largely directed rearward. Removing F-actin turnover leads to actin patches that recirculate up and down the cell, which we observe experimentally for drug-stabilized actin bundles in live Toxoplasma gondii parasites. These distinct self-organized actin states can account for observed gliding modes, illustrating how different forms of gliding motility can emerge as an intrinsic consequence of the self-organizing properties of F-actin flow in a confined geometry.
Structural basis for Vipp1 membrane binding: from loose coats and carpets to ring and rod assemblies
Authors: Junglas Benedikt , Kartte David , Kutzner Mirka , Hellmann Nadja , Ritter Ilona , Schneider Dirk , Sachse Carsten
Published: October 2024

Vesicle-inducing protein in plastids 1 (Vipp1) is critical for thylakoid membrane biogenesis and maintenance. Although Vipp1 has recently been identified as a member of the endosomal sorting complexes required for transport III superfamily, it is still unknown how Vipp1 remodels membranes. Here, we present cryo-electron microscopy structures of Synechocystis Vipp1 interacting with membranes: seven structures of helical and stacked-ring assemblies at 5–7-Å resolution engulfing membranes and three carpet structures covering lipid vesicles at ~20-Å resolution using subtomogram averaging. By analyzing ten structures of N-terminally truncated Vipp1, we show that helix α0 is essential for membrane tubulation and forms the membrane-anchoring domain of Vipp1. Lastly, using a conformation-restrained Vipp1 mutant, we reduced the structural plasticity of Vipp1 and determined two structures of Vipp1 at 3.0-Å resolution, resolving the molecular details of membrane-anchoring and intersubunit contacts of helix α0. Our data reveal membrane curvature-dependent structural transitions from carpets to rings and rods, some of which are capable of inducing and/or stabilizing high local membrane curvature triggering membrane fusion.
A Multi-Layer Techno-Economic-Environmental Energy Management Optimization in Cooperative Multi-Microgrids with Demand Response Program and Uncertainties Consideration
Authors: Alamir Nehmedo , Kamel Salah , Megahed Tamer F. , Hori Maiya , Abdelkader Sobhy M.
Published: October 2024

This paper presents a multi-layer, multi-objective (MLMO) optimization model for techno-economic-environmental energy management in cooperative multi-Microgrids (MMGs) that incorporates a Demand Response Program (DRP). The proposed MLMO approach simultaneously optimizes operating costs, MMG operator benefits, environmental emissions, and MMG dependency. This paper proposed a new hybrid ε-lexicography–weighted-sum that eliminates the need to normalize or scalarize objectives. The first layer of the model schedules MMG resources with DRP to minimize operating costs (local generation and power transactions with the utility grid) and maximize MMG profit. The second layer achieves the environmental operation of the MMG, while the third layer maximizes MMG reliability. This paper also proposed a new application of a recently developed enhanced equilibrium optimizer (EEO) for solving the three-layer EM problem. In addition, the uncertainties of solar power generation, wind power generation, load demand, and energy prices are considered based on the probabilistic 2m + 1 Point estimation method (PEM) approach. Three case studies are presented to verify the proposed MLMO approach on an MMG test system. In Case I, a deterministic EM is solved to simulate the MMG as a single layer to minimize costs and maximize benefits through DRP, while Case II solves the MLMO optimization problem. Simulation results show that the proposed MLMO technique reduces environmental emissions by 2.45% and 3.5% in its optimization layer and at the final layer, respectively. The independence index is also enhanced by 2.49% and 4.8% in its layer only and as a total increase, respectively. Case III is for the probabilistic EM simulation; due to the uncertain variables effect, the mean value in this case is increased by about 2.6% over Case I.
Oxidation is a potentially significant methane sink in land-terminating glacial runoff
Authors: Strock Kristin E. , Krewson Rachel B. , Hayes Nicole M. , Deemer Bridget R.
Published: October 2024

Globally, aquatic ecosystems are one of the largest but most uncertain sources of methane, a potent greenhouse gas. It is unclear how climate change will affect methane emissions, but recent work suggests that glacial systems, which are melting faster with climate change, may be an important source of methane to the atmosphere. Currently, studies quantifying glacial emissions are limited in number, and the role of methanotrophy, or microbial methane oxidizers, in reducing atmospheric emissions from source and receiving waters is not well known. Here we discuss three potential sites for methane oxidation that could mitigate emissions from glaciers into the atmosphere: under ice oxidation, oxidation within proglacial lakes, and oxidation within melt rivers. The research presented here increases the number of glacial sites with methane concentration data and is one of only a few studies to quantify the net microbial activity of methane production and oxidation in two types of land-terminating glacial runoff (lake and river). We find that oxidation in a glacial river may reduce atmospheric methane emissions from glacial melt by as much as 53%. Incorporating methane oxidation in estimates of glacial methane emissions may significantly reduce the estimated magnitude of this source in budgeting exercises.
Frequency and spectrum of mutations in human sperm measured using duplex sequencing correlate with trio-based de novo mutation analyses
Authors: Axelsson Jonatan , LeBlanc Danielle , Shojaeisaadi Habiballah , Meier Matthew J , Fitzgerald Devon M. , Nachmanson Daniela , Carlson Jedidiah , Golubeva Alexandra , Higgins Jake , Smith Thomas , Lo Fang Yin , Pilsner Richard , Williams Andrew , Salk Jesse , Marchetti Francesco , Yauk Carole
Published: October 2024

De novo mutations (DNMs) are drivers of genetic disorders. However, the study of DNMs is hampered by technological limitations preventing accurate quantification of ultra-rare mutations. Duplex Sequencing (DS) theoretically has < 1 error/billion base-pairs (bp). To determine the DS utility to quantify and characterize DNMs, we analyzed DNA from blood and spermatozoa from six healthy, 18-year-old Swedish men using the TwinStrand DS mutagenesis panel (48 kb spanning 20 genic and intergenic loci). The mean single nucleotide variant mutation frequency (MF) was 1.2 × 10− 7 per bp in blood and 2.5 × 10− 8 per bp in sperm, with the most common base substitution being C > T. Blood MF and substitution spectrum were similar to those reported in blood cells with an orthogonal method. The sperm MF was in the same order of magnitude and had a strikingly similar spectrum to DNMs from publicly available whole genome sequencing data from human pedigrees (1.2 × 10− 8 per bp). DS revealed much larger numbers of insertions and deletions in sperm over blood, driven by an abundance of putative extra-chromosomal circular DNAs. The study indicates the strong potential of DS to characterize human DNMs to inform factors that contribute to disease susceptibility and heritable genetic risks.
Coupling Taguchi experimental designs with deep adaptive learning enhanced AI process models for experimental cost savings in manufacturing process development
Authors: Zubair Syed Wasim Hassan , Arafat Syed Muhammad , Khan Sarmad Ali , Niazi Sajawal Gul , Rehan Muhammad , Arshad Muhammad Usama , Hayat Nasir , Aized Tauseef , Uddin Ghulam Moeen , Riaz Fahid
Published: October 2024

The Aluminum alloy AA7075 workpiece material is observed under dry finishing turning operation. This work is an investigation reporting promising potential of deep adaptive learning enhanced artificial intelligence process models for L18 (6133) Taguchi orthogonal array experiments and major cost saving potential in machining process optimization. Six different tool inserts are used as categorical parameter along with three continuous operational parameters i.e., depth of cut, feed rate and cutting speed to study the effect of these parameters on workpiece surface roughness and tool life. The data obtained from special L18 (6133) orthogonal array experimental design in dry finishing turning process is used to train AI models. Multi-layer perceptron based artificial neural networks (MLP-ANNs), support vector machines (SVMs) and decision trees are compared for better understanding ability of low resolution experimental design. The AI models can be used with low resolution experimental design to obtain causal relationships between input and output variables. The best performing operational input ranges are identified for output parameters. AI-response surfaces indicate different tool life behavior for alloy based coated tool inserts and non-alloy based coated tool inserts. The AI-Taguchi hybrid modelling and optimization technique helped in achieving 26% of experimental savings (obtaining causal relation with 26% less number of experiments) compared to conventional Taguchi design combined with two screened factors three levels full factorial experimentation.
Gaze transition entropy as a measure of attention allocation in a dynamic workspace involving automation
Authors: Cui Zixin , Sato Tetsuya , Jackson Austin , Jayarathna Sampath , Itoh Makoto , Yamani Yusuke
Published: October 2024

Real-world work environments require operators to perform multiple tasks with continual support from an automated system. Eye movement is often used as a surrogate measure of operator attention, yet conventional summary measures such as percent dwell time do not capture dynamic transitions of attention in complex visual workspace. This study analyzed eye movement data collected in a controlled a MATB-II task environment using gaze transition entropy analysis. In the study, human subjects performed a compensatory tracking task, a system monitoring task, and a communication task concurrently. The results indicate that both gaze transition entropy and stationary gaze entropy, measures of randomness in eye movements, decrease when the compensatory tracking task required more continuous monitoring. The findings imply that gaze transition entropy reflects attention allocation of operators performing dynamic operational tasks consistently.
Bio-inspired feature selection for early diagnosis of Parkinson’s disease through optimization of deep 3D nested learning
Authors: Priyadharshini S. , Ramkumar K. , Vairavasundaram Subramaniyaswamy , Narasimhan K. , Venkatesh S. , Madhavasarma P. , Kotecha Ketan
Published: October 2024

Parkinson’s disease (PD) is one of the most common neurodegenerative disorders that affect the quality of human life of millions of people throughout the world. The probability of getting affected by this disease increases with age, and it is common among the elderly population. Early detection can help in initiating medications at an earlier stage. It can significantly slow down the progression of this disease, assisting the patient to maintain a good quality of life for a more extended period. Magnetic resonance imaging (MRI)-based brain imaging is an area of active research that is used to diagnose PD disease early and to understand the key biomarkers. The prior research investigations using MRI data mainly focus on volume, structural, and morphological changes in the basal ganglia (BG) region for diagnosing PD. Recently, researchers have emphasized the significance of studying other areas of the human brain for a more comprehensive understanding of PD and also to analyze changes happening in brain tissue. Thus, to perform accurate diagnosis and treatment planning for early identification of PD, this work focuses on learning the onset of PD from images taken from whole-brain MRI using a novel 3D-convolutional neural network (3D-CNN) deep learning architecture. The conventional 3D-Resent deep learning model, after various hyper-parameter tuning and architectural changes, has achieved an accuracy of 90%. In this work, a novel 3D-CNN architecture was developed, and after several ablation studies, the model yielded results with an improved accuracy of 93.4%. Combining features from the 3D-CNN and 3D ResNet models using Canonical Correlation Analysis (CCA) resulted in 95% accuracy. For further enhancements of the model performance, feature fusion with optimization was employed, utilizing various optimization techniques. Whale optimization based on a biologically inspired approach was selected on the basis of a convergence diagram. The performance of this approach is compared to other methods and has given an accuracy of 97%. This work represents a critical advancement in improving PD diagnosis techniques and emphasizing the importance of deep nested 3D learning and bio-inspired feature selection.
Assessment of basic pharmacokinetic parameters of dapagliflozin in TTS formulations in male minipigs
Authors: Paweł Biernat , Balwierz Radosław , Mieszko Dyliński , Mikołaj Kołacki , Micewicz Ewa , Dawid Bursy , Pogorzelec Łukasz
Published: October 2024

Given the extended time over which diabetes treatment is administered, the transdermal delivery system is anticipated to be a more suitable option for older individuals who may experience difficulty swallowing. The continuous delivery of dapagliflozin and more stable plasma levels are anticipated to reduce the incidence of side effects and the frequency of dosing. The objectives of the study were to determine the safety and plasma pharmacokinetics of dapagliflozin in male minipigs following application of the ointment and skin patch. In the initial phase of the study, the potential for transdermal permeation of dapagliflozin from ointment and transdermal patch to blood plasma of 15 male Göttingen minipigs was investigated. In the subsequent phase, the efficacy of utilising patches of varying strengths and sizes was assessed. The LC/MS method was employed to quantify the concentration of the active substance. The transportation of the studied API to the general circulation and accumulation in tissues were confirmed. The maximum drug concentration (122.99 ng/mL) in plasma was observed on the fourth day of application. The highest calculated Cmax was 131.91 ng/mL with a mean AUC0-last of 6620.7 ng h/mL. Following transdermal administration, dapagliflozin is excreted in the urine. The trend between urinary dapagliflozin 3-O-glucuronide levels and urinary glucose excretion was also observed. The transdermal patch has been demonstrated to be an effective drug delivery system for dapagliflozin.
Disease coverage of human genome-wide association studies and pharmaceutical research and development
Authors: Gordillo-Marañón María , Schmidt Amand F. , Warwick Alasdair , Tomlinson Chris , Ytsma Cai , Engmann Jorgen , Torralbo Ana , Maclean Rory , Sofat Reecha , Langenberg Claudia , Shah Anoop D. , Denaxas Spiros , Pirmohamed Munir , Hemingway Harry , Hingorani Aroon D. , Finan Chris
Published: October 2024

Background

Despite the growing interest in the use of human genomic data for drug target identification and validation, the extent to which the spectrum of human disease has been addressed by genome-wide association studies (GWAS), or by drug development, and the degree to which these efforts overlap remain unclear.

Methods

In this study we harmonize and integrate different data sources to create a sample space of all the human drug targets and diseases and identify points of convergence or divergence of GWAS and drug development efforts.

Results

We show that only 612 of 11,158 diseases listed in Human Disease Ontology have an approved drug treatment in at least one region of the world. Of the 1414 diseases that are the subject of preclinical or clinical phase drug development, only 666 have been investigated in GWAS. Conversely, of the 1914 human diseases that have been the subject of GWAS, 1121 have yet to be investigated in drug development.

Conclusions

We produce target-disease indication lists to help the pharmaceutical industry to prioritize future drug development efforts based on genetic evidence, academia to prioritize future GWAS for diseases without effective treatments, and both sectors to harness genetic evidence to expand the indications for licensed drugs or to identify repurposing opportunities for clinical candidates that failed in their originally intended indication.
Integration of paper-based analytical devices with digital microfluidics for colorimetric detection of creatinine
Authors: Velasco Larissa G. , Rocha Danielly S. , de Campos Richard P. S. , Coltro Wendell K. T.
Published: October 2024

Digital microfluidics (DMF) is a platform that allows the automated manipulation of individual droplets, ranging from nanoliters to microliters, and coupling sensing techniques can be facilitated by paper-based devices (PAD).