bluuebunny/crossref_metadata_2025 huggingface dataset:
Design and Assessment of a Linear Drive‐Controlled Tilt‐Roll Heliostat with Sun Tracking Algorithm for Small‐Scale Solar Installation
Authors: TR Adithyan , Kalpathy Sreeram K. , Thomas Tiju
Published: December 2024

Heliostats are devices used for solar concentration that use mirrors oriented according to the position of the sun. A heliostat's main function is to redirect sunlight for use in a variety of applications, including heating, lighting, scientific research, and solar power generation. The two‐axis tracking employed in the device ensures that the reflected irradiance is aimed at a predetermined target. The design and evaluation of a tilt‐roll two‐axis tracking heliostat are presented in this article. The model consists of a mirror 0.45 m in width and 0.45 m in length installed on a pedestal of height 0.75 m. The motion of the heliostat is controlled using two separate linear drives via a sun‐tracking algorithm implemented in a microcontroller. A small‐scale tilt‐roll design with a reflective area (mirror) of 0.2025 m2 is established. This novel design eliminates the need for commercially available solar tracking systems and can be deployed in areas of limited installation space. Dual‐axis heliostat design used here provides an effective way to track the sun's movement for maximum solar energy capture by combining tilt and roll mechanisms. This design ensures tracking precision for optimal solar energy concentration making it well‐suited for experimental and smaller‐scale deployments.
Modulation of Energy Band Positions in Sb2S3 Thin Films for Enhanced Photovoltaic Performance of FTO/TiO2/Sb2S3/P3HT/Au Solar Cell
Authors: Gunasekaran Nithyapremini , Nagarajan Deepan Chakravarthi , Nataraj Devaraj , Prabakar Kandasamy
Published: December 2024

Antimony sulfide (Sb2S3) has the potential as an absorber material in photovoltaics due to its suitable bandgap and favorable optoelectronic properties. However, its energy band positions are not extensively explored which are essential for effective charge separation and transfer. This study examines the energy band positions of Sb2S3 thin films as a function of annealing temperature. Sb2S3 thin films are grown by a combination of successive ionic layer adsorption and reaction (SILAR) and chemical bath deposition (CBD) method to enhance the crystallinity, tune the bandgap, and overall quality of Sb2S3 films to enhance the photovoltaic performance. Optical bandgap decreases from 2.41 to 1.67 eV from the as‐deposited films to annealed at 300 °C due to changes in interatomic distances. Energy band positions of Sb2S3 films are measured both by cost‐effective electrochemical cyclic voltammetry and Mott–Schottky analysis and validated the findings using ultraviolet photoelectron spectroscopy (UPS). The conductivity of Sb2S3 is found to be n‐type. Thin‐film solar cells are then fabricated by employing Sb2S3 as an absorber layer in an FTO/TiO2/Sb2S3/P3HT/Au structure, achieving an enhanced power conversion efficiency, increasing from 0.4 to 2.8% after annealing. These findings demonstrate the potential of Sb2S3 as a low‐cost absorber material for thin‐film photovoltaics.
Extended Multivariate EGARCH Model: A Model for Zero‐Return and Negative Spillovers
Authors: Xu Yongdeng
Published: December 2024

This paper introduces an extended multivariate EGARCH model that overcomes the zero‐return problem and allows for negative news and volatility spillover effects, making it an attractive tool for multivariate volatility modeling. Despite limitations, such as noninvertibility and unclear asymptotic properties of the QML estimator, our Monte Carlo simulations indicate that the standard QML estimator is consistent and asymptotically normal for larger sample sizes (i.e., ). Two empirical examples demonstrate the model's superior performance compared to multivariate GJR‐GARCH and Log‐GARCH models in volatility modeling. The first example analyzes the daily returns of three stocks from the DJ30 index, while the second example investigates volatility spillover effects among the bond, stock, crude oil, and gold markets. Overall, this extended multivariate EGARCH model offers a flexible and comprehensive framework for analyzing multivariate volatility and spillover effects in empirical finance research.
Diagnosis Related Payment for Inpatient Mental Health Care: Hospital Selection and Effects on Length of Stay
Authors: Valder Franziska , Reif Simon , Tauchmann Harald
Published: December 2024

We study a policy introducing diagnosis related payment for inpatient mental health care in Germany with rates decreasing over length of stay. Using data on all hospital cases, we first examine which hospitals voluntarily opt into the new scheme. We show that specialized hospitals that treat more complicated cases and are reimbursed more highly under the new scheme select into it. Second, we study the effect of diagnosis related payment on length of stay. We find that diagnosis related payment is associated with large reductions in length of stay but has no effect on mortality, post‐acute care, or the ambulatory sector. We argue that the reductions in length of stay are driven by the fact that diagnoses related reimbursement is higher for more complex cases and by payment decreasing over length of stay. This novel evidence contributes to a scarce literature on the role of payment systems for inpatient mental health care and provides important insights for policymakers.
Communication‐Efficient Distributed Gradient Descent via Random Projection
Authors: Qi Haobo , Gao Yuan
Published: December 2024

The gradient descent algorithm is one type of communication‐efficient algorithm in distributed computing as it only requires transmitting the gradient vectors to update parameters. However, as the dimensionality of model parameters increases, even transmitting the gradients alone can result in a significant amount of communication costs. On the other hand, many local computers in the distributed system may suffer from communication bandwidth limitations, so the transmission of the full gradients are practically prohibited. Therefore, reducing the communication cost of gradient descent algorithms, particularly the communication bandwidth, becomes an important issue. To address this problem, we propose a randomly projected gradient descent (RPGD) algorithm. The proposed algorithm consists of three main steps. First, the gradient computed by the local computers is compressed into a low‐dimensional vector using a random matrix. Then, these projected gradients are transmitted to the central computer, aggregated and broadcasted back to the local ones. Finally, the local computers recover the gradients to their original dimensions and update the parameters. By employing random projection, we can reduce the communication bandwidth requirements in distributed computing while we can also provide better privacy protection for local computers. We have provided a theoretical convergence analysis of the RPGD algorithm. Extensive numerical studies have been conducted to demonstrate the finite sample performance of the proposed method.
Dynamical implications of the Kerr multipole moments for spinning black holes
Authors: Scheopner T. , Vines J.
Published: December 2024

Abstract

Previously the linearized stress tensor of a stationary Kerr black hole has been used to determine some of the values of gravitational couplings for a spinning black hole to linear order in the Riemann tensor in the action (worldline or quantum field theory). In particular, the couplings on operators containing derivative structures of the form (𝑆 ∙ ∇)𝑛 acting on the Riemann tensor were fixed, with 𝑆𝜇 the spin vector of the black hole. In this paper we find that the Kerr solution determines all of the multipole moments in the sense of Dixon of a stationary spinning black hole and that these multipole moments determine all linear in 𝑅 couplings. For example, additional couplings beyond the previously mentioned are fixed on operators containing derivative structures of the form 𝑆2𝑛(𝑝 ∙ ∇)2𝑛 acting on the Riemann tensor with 𝑝𝜇 the momentum vector of the black hole. These additional operators do not contribute to the three-point amplitude, and so do not contribute to the linearized stress tensor for a stationary black hole. However, we find that they do contribute to the Compton amplitude. Additionally, we derive formal expressions for the electromagnetic and gravitational Compton amplitudes of generic spinning bodies to all orders in spin in the worldline formalism and evaluated expressions for these amplitudes to 𝒪(𝑆3) in electromagnetism and 𝒪(𝑆5) in gravity.
Key factors influencing cycling performance and overall race time in the Ironman 70.3 for amateur athletes
Authors: Vivan Lavínia , dos Anjos Souza Vinicius Ribeiro , Engelke Paulo , de Lira Claudio Andre Barbosa , Vancini Rodrigo Luiz , Weiss Katja , Knechtle Beat , Andrade Marilia Santos
Published: December 2024

Purpose

Previous study has shown that cycling is the most predictive modality in the Ironman 70.3 triathlon distance. As a result, understanding the physiological and anthropometric variables that are mostly closely related to cycling performance can help coaches and athletes to direct their training programs. This study aimed to investigate the physiological, anthropometric, and general training characteristics influencing overall race time and cycling split time in Ironman 70.3. The present study also investigated the significance of body composition as a performance-related variable.

Methods

A questionnaire was used to assess training characteristics in 12 athletes (six men and six women), body composition in dual X-ray absorptiometry, and physiological variables in an incremental cardiopulmonary test. Ironman 70.3 São Paulo–Brazil 2023 was completed by all participants. The relationship between performance and the variables measured were investigated, and a multiple regression model for cycling split time and overall race time was developed.

Results

Functional threshold power (FTP) can predict cycling split time in Ironman 70.3 (r2 = 0.638, p = 0.002). Maximal oxygen uptake ($$\dot{\text{V}}$$

V
˙

O2max) (r2 = 0.667, p = 0.001) can predict overall race time. FTP and $$\dot{\text{V}}$$

V
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O2max are also strongly related to lean mass and fat mass percentage.

Conclusion

While FTP is the most important predictor of cycling split time, $$\dot{\text{V}}$$

V
˙

O2max is the most important predictor of overall race time in an Ironman 70.3. Furthermore, because body composition (fat mass %) and muscle mass (kg) are variables strongly related to FTP and $$\dot{\text{V}}$$

V
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O2max, we recommend that coaches and athletes consider to conduct a body composition assessment.
Assessing the Long-Term Sustainability of Germanium Supply and Price Using the WORLD7 Integrated Assessment Model
Authors: Sverdrup Harald Ulrik , Haraldsson Hördur Valdimar
Published: December 2024

The WORLD7 model was used to assess the sustainability of production and market supply of germanium. The model incorporates dynamic market dynamics, mass balance, and endogenous dynamic market prices based on supply and demand dynamics. The results suggest that there will be germanium scarcity in the near future, and a price increase is predicted. Future demand for germanium for the photovoltaic technologies can only partially be met. The total global extractable potential for germanium was estimated to be about 342,000 tons in 2022 from a geological presence of about 5.5 million tons. The major obstacle for germanium supply is the opportunity for extraction from mother metals, the availability of the required infrastructure, and low extraction yields. Germanium is extracted as a secondary metal from zinc and fly-ash today, but potential new sources are lead, copper, nickel refining residuals, and Bayer liquid from bauxite processing. The maximum germanium production rate was estimated to be about 1250 ton/year. The actual 2023 global extraction rate is about 210 ton/year. With respect to supply sustainability, germanium may suffer from a scarcity of supply and limit the application of key technologies in the future. The supply per person peaks in 2053 and declines to 2020 level by 2200. A doubling of demand above business-as-usual would imply germanium shortages in the market. The recycling rate for germanium is far too low for a circular society, and the supply situation may be significantly improved if the recycling rate can be increased substantially. The implications for the EU imaginaries indicate that four policy pathway approaches would be necessary to address the scarcity of germanium: regulation and innovation, investment in local solutions, market-driven adaptations, and community engagement/conservation.
Localized Ultra‐Low Velocity Zone as a Strong Scatterer at the Core‐Mantle Boundary Beneath Central America
Authors: Li Jiewen , Sun Daoyuan , Tian Dongdong
Published: December 2024

Small‐scale scatterers in the lower mantle contain key information on the recycling process in the whole mantle. Resolving the fine structures of these scatterers is crucial for understanding the dynamic evolution in the deep Earth. Here, we search for scatterers in the lower mantle beneath Central America and the northwestern Pacific Ocean by events in South America and PKP recordings in Japan. In this work, we perform migration of PKP precursors on the source and receiver sides by raytracing to obtain the distribution map of scatterers, after considering 3D heterogeneous structures. Furthermore, we locate a distinct scatterer at the core‐mantle boundary (CMB) beneath Central America that generates strong PKP precursors with unique slowness and back‐azimuth by array processing, which is compatible with the migration result. Based on waveform modeling, this scatterer is essentially a localized ultra‐low velocity zone (ULVZ) with approximately P‐wave velocity reduction of 6% and a lateral extent of 3°. Heated up of the subducted lithosphere by the core or partial melting of the subducted oceanic crust are plausible sources of the localized ULVZ at the CMB we detect here in the subduction region.
A game‐theoretic cooperative path planning strategy using hybrid heuristic optimization algorithm
Authors: Zhu Yutong , Zhang Ye
Published: December 2024

A novel method based on game theory and LCD‐SCA optimization algorithm is proposed for solving the cooperative path planning challenge for multiple UAVs in a desired formation configuration. The cooperative path planning problem is solved by identifying the optimal strategy for the Stackelberg‐Nash game. The conventional sine‐cosine algorithm method is enhanced by incorporating linear differential decrement, chaos theory, and differential evolution, and the proposed heuristic method is integrated into the path planning problem. An optimal strategy for finding the game by minimising the global cost function via the heuristic method is integrated. Extensive simulation and comparison results are provided to evaluate the performance through simulation, compared with the previous work on path planning.
Pothole detection‐you only look once: Deformable convolution based road pothole detection
Authors: Tang Pei , Lv Mao , Ding Zhenyu , Xu Weikai , Jiang Minnan
Published: December 2024

The detection of road potholes plays a crucial role in ensuring passenger comfort and the structural safety of vehicles. To address the challenges of pothole detection in complex road environments, this paper proposes a model focusing on shape features (pothole detection you only look once, PD‐YOLO). The model aims to overcome the limitations of multi‐scale feature learning caused by the use of fixed convolutional kernels in the baseline model, by constructing a feature extraction module that better adapts to variations in the shape of potholes. Subsequently, a cross‐stage partial network was designed using a one‐time aggregation method, simplifying the model while enabling the network to fuse information between feature maps at different stages. Additionally, a dynamic sparse attention mechanism is introduced to select relevant features, reducing redundancy and suppressing background noise. Experiments conducted on the VOC2007 and GRDDC2020_Pothole datasets reveal that compared to the baseline model YOLOv8, PD‐YOLO achieves improvements of 3.9% and 2.8% in mean average precision, with a frame rate of approximately 290 frames per second, effectively meeting the accuracy and real‐time requirements for pothole detection. The code and dataset for this paper are located at: https://github.com/woyijiankou/PD‐YOLO.
An odd [1, b]-factor in a graph from signless Laplacian spectral radius
Authors: Zhou Sizhong , Pan Quanru
Published: December 2024

An odd [1, b]-factor of a graph G is a spanning subgraph F of G such that dF (u) is odd and 1 ≤ dF (u) ≤ b for every u ∈ V (G), where b is a positive odd integer. The matrix Q(G) = D(G) + A(G) is called the signless Laplacian matrix of G, where D(G) denotes the degree diagonal matrix of G and A(G) denotes the adjacency matrix of G. Let q1(G) denote the signless Laplacian spectral radius of G. In this paper, we study the existence of an odd [1, b]-factor of a graph G and derive a signless Laplacian spectral radius condition for a graph to possess an odd [1, b]-factor.
Hunters’ knowledge, perceived risks, and agency trust associated with chronic wasting disease, and beliefs about CWD management
Authors: Vaske Jerry J. , Miller Craig A.
Published: December 2024

Context Wildlife agencies spend considerable effort developing comprehensive communication programs to educate various publics about chronic wasting disease (CWD). Deer hunters are important in CWD management, especially regarding surveillance and testing. Aims This article examined the influence of the number of years CWD had been in a state on hunters’ knowledge of the disease. Knowledge level was then related to perceived risks associated with CWD, trust in the agency responsible for managing CWD and beliefs about CWD management. Methods Survey data were obtained from resident deer hunters in the US states of Kansas (n = 1170), North Dakota (n = 3242) and Illinois (n = 1237). State of residence served as one independent variable. The second independent variable was knowledge of CWD. Respondents were asked eight true/false questions regarding CWD (0 = incorrect, 1 = correct). A knowledge index was created by summing the correct responses. The index was categorized as low, medium, and high knowledge. There were four multiple-item dependent variables: risk to deer, risk to humans, hunters’ trust in the CWD management agency, and beliefs about CWD management. Key results Kansas hunters had the highest knowledge, followed by North Dakota, then Illinois. As knowledge increased, perceived risk to humans decreased, and perceived risk to deer increased. There was a positive relationship between knowledge and trust in agency information. Across beliefs, high knowledge hunters agreed with positively worded statements and disagreed with negatively worded items more than either of the other two knowledge groups. Low knowledge respondents always reported the lowest belief scores, and the middle knowledge group was always in between the other two groups. All tests were statistically significant, but effect sizes were minimal. Conclusions CWD existed in Kansas for only 4 years when the study was conducted. Kansas hunters reported the highest percentage of correct knowledge questions. By comparison, the disease had existed in Illinois for 20 years; Illinois hunters reported the lowest percentage of correct responses. Knowledge is influenced by the newness of a disease. With a new disease, people attend to information campaigns. Over time, experience tempers concerns and knowledge about diseases. Implications Findings highlight complexities managers should consider when designing communication strategies to influence wildlife disease knowledge.
Determining the impacts of conservation fencing on woma pythons (Aspidites ramsayi)
Authors: Magro Joshua , Pedler Reece , Read John , West Rebecca
Published: December 2024

Context Fenced conservation reserves are an effective management tool for the conservation of many threatened species. However, conservation fencing is known to inadvertently affect non-target species, ranging from barrier effects to direct mortality. There is a paucity of information on the negative impacts of fencing on reptiles. Aims Using the woma python, a species of conservation significance, this research aimed to improve our knowledge of how reptiles interact with fences. Methods The spatial ecology of womas was explored in relation to fencing at the Wild Deserts project partnership site, a rabbit-, cat- and fox-proof fenced area of Sturt National Park in arid Australia. A 6-year dataset of opportunistic observations of womas at the study site were analysed for demographic, spatial and temporal patterns in woma fence interactions. Nine adult pythons were radiotracked over a year to assess space use in relation to fencing. Key results Twenty-two per cent of all opportunistic woma observations at the site were mortalities associated with entanglements. All 20 entanglement deaths were in 30-mm netting despite 50-mm netting comprising lower segments of 21% of the fence network. Fencing encounters were greatest in dune habitats and during summer and autumn. Fence crossings were infrequent among telemetered pythons and most encounters did not result in entanglement, with four of the nine individuals recorded to have crossed the fence successfully, despite one mortality. Conclusions Thirty-millimetre netting, particularly in areas of netting overlap, represents an entanglement risk to womas. Implications This research is applicable to the management of conservation fences and can be extended to other large snake and reptile species. The impacts of small-aperture netting on large snakes and other non-target species should be considered in the planning phases for conservation fencing and mitigation strategies should be sought in the planning phases where possible. Large-aperture netting is preferable to 30-mm netting for pythons, where exclusion of rabbits is not necessary. However, larger netting apertures may disproportionately affect other non-target species such as bearded dragons.
Rethinking Paradoxical Bulging of the Masseter Muscle Following Botulinum Toxin Injection: An Ultrasound Evaluation
Authors: Lin Frank , Roberts Stefania , Magnusson Mark
Published: December 2024

Background

Paradoxical masseter bulge (PMB) is an uncommon complication following treatment with botulinum neurotoxin-A (BoNT-A). This is currently believed to be caused by the uneven distribution of BoNT-A within the masseter, resulting in stronger, compensatory, contraction of the superficial head relative to its deeper heads.

Objectives

To visualize under ultrasound which part of the masseter muscle is chiefly responsible for PMB and to propose a framework for assessment and prevention of the complication.

Methods

A case series of 6 patients presenting with PMB were identified in the practice of 2 experienced doctors over 24 months. Case notes, photographs, and videos were reviewed along with static and dynamic ultrasound examinations to assess masseter architecture and patterns of contraction.

Results

In 7 of 8 affected masseter muscles, PMB was associated with retained movement of a deeper portion of the masseter bulging superficially during contraction. In all cases, the bulge appeared to originate from anterior or posterior compartments of the muscle. This supports the concept that masseter contraction can be classified functionally by anterior or posterior compartments, rather than anatomically by the traditional superficial, deep, and intermediate heads.

Conclusions

Paradoxical muscle bulging of the masseter may originate from the deeper portion of the muscle bulging superficially. In addition, the authors propose that masseters can be considered functionally as having anterior and posterior functional units. This classification may enable clinical and ultrasound preassessment for anterior or posterior dominance and the injection technique to be adjusted to minimize the risk of PMB.

Level of Evidence: 5 (Diagnostic)
Research and Application of Adhesion Optimization Control in the Traction System of Permanent Magnet High-Speed EMU Trains
Authors: Gan Weiwei , Wu Yeqing , Bai Zhonghao , Human Yunqin , Hou Zhaowen , Li Xueming , Chen Ke
Published: December 2024

When the permanent magnet high-speed EMU(Electrical Multiple Unit) train runs at extremely high speeds, it is necessary to solve the problem of optimal exertion of wheel-rail adhesion to ensure the adhesion utilization rate of the train and the smooth and safe operation of the vehicle. To improve the adhesion utilization rate of the train and passenger comfort, this paper proposes an adaptive adhesion utilization control strategy for permanent magnet high-speed EMU trains. This method automatically identifies the wheel-rail state, matches the wheel-rail adhesion characteristics, automatically adjusts the adhesion control parameters according to the wheelset idling and sliding state, reduces the fluctuation range of traction force, improves the stability of traction force exertion, and effectively improves the adhesion utilization control performance of the permanent magnet high-speed EMU train. Both simulation and experimental tests demonstrate this method's superiority over traditional control methods. It has been shown to enhance adhesion utilization efficiency by over 5% and to significantly narrow the traction force adjustment range by more than 10%. It also improves passenger comfort indicators such as train stability and comfort, and enhances the safety of train operation.
A scientific case for revisiting the embryonic chicken model in biomedical research
Authors: McGrew Mike J , Holmes Tana , Davey Megan G
Published: December 2024

The availability of fertilised chicken eggs and the accessibility and rapid development of the avian embryo, have been utilised in biomedical scientific research to make fundamental discoveries including of developmental processes that are common to all vertebrates, advances in teratology, the understanding of tumour growth and metastasis, angiogenesis, cancer drug assessment and vaccine development as well as advances in understanding avian specific biology. However, recent innovations in chicken transgenesis, genome engineering and surrogate host technology in chickens have only been utilised in a few of these fields of research, specifically some areas of developmental biology, avian sex determination and immunology. To understand why other biomedical fields have not adopted modern chicken transgenic tools, we investigated the non-technical summaries of projects granted in the UK under the Animals (Scientific Procedures) Act 1986 between 2017-2023 to assess when and how chicken embryos are used in research, and if they were considered as a Replacement model for other species.

Highlights

Evidence for a lack of uptake of the chicken embryo as a partial replacement model

Case examples of the reduction in animal numbers when chicken models are used

Proposed action plan for the avian developmental biology community

Abstract Figure
Engineered human lymph node stroma model for examining interstitial fluid flow and T cell egress
Authors: Hammel Jennifer H , Arneja Abhinav , Cunningham Jessica , Wang Maosen , Schumaecker Sophia , Orihuela Yamilet Macias , Ozulumba Tochukwu , Zatorski Jonathan , Braciale Thomas J , Luckey Chance John , Pompano Rebecca R , Munson Jennifer M
Published: December 2024

The lymph node (LN) performs essential roles in immunosurveillance throughout the body. Developing in vitro models of this key tissue is of great importance to enhancing physiological relevance in immunoengineering. The LN consists of stromal populations and immune cells, which are highly organized and bathed in constant interstitial flow. The stroma, notably the fibroblastic reticular cells (FRCs) and the lymphatic endothelial cells (LECs), play crucial roles in guiding T cell migration and are known to be sensitive to fluid flow. During inflammation, interstitial fluid flow rates drastically increase in the LN. It is unknown how these altered flow rates impact crosstalk and cell behavior in the LN, and most existingin vitromodels focus on the interactions between T cells, B cells, and dendritic cells rather than with the stroma. To address this gap, we developed a human engineered model of the LN stroma consisting of FRC-laden hydrogel above a monolayer of LECs in a tissue culture insert with gravity-driven interstitial flow. We found that FRCs had enhanced coverage and proliferation in response to high flow rates, while LECs experienced decreased barrier integrity. We added CD4+ and CD8+ T cells and found that their egress was significantly decreased in the presence of interstitial flow, regardless of magnitude. Interestingly, 3.0 µm/s flow, but not 0.8 µm/s flow, correlated with enhanced inflammatory cytokine secretion in the LN stroma. Overall, we demonstrate that interstitial flow is an essential consideration in the lymph node for modulating LN stroma morphology, T cell migration, and inflammation.
Centella asiaticaTissue Culture-Derived Extracellular Vesicles: A Multifaceted Approach to Skincare Applications
Authors: Chang Tsong-Min , Wu Chung-Chin , Huang Huey-Chun , Wang Shr-Shiuan , Chuang Ching-Hua , Kao Pei-Lun , Tang Wei-Hsuan , Liu Luke Tzu-Chi , Qiu Wei-Yin , Percec Ivona , Chen Charles , Kuo Tsun-Yung
Published: December 2024

Background

Centella asiaticahas long been used as a medicinal herb in traditional Asian medicine. Its wound healing, skin improvement, and neuroprotective properties have been widely studied. Extracellular vesicles (EVs) are secreted by cells and contain bioactive components with therapeutic properties.

Objectives

This study aims to characterize EVs isolated fromC. asiaticatissue culture and investigate their therapeutic properties usingin-vitroassays.

Methods

EVs were isolated fromC. asiaticatissue culture and their properties were characterized by cell-free chemical assays which investigated free radical activity, metal chelation, and total polyphenol content. Mouse melanoma, human fibroblast and keratinocyte cell cultures were used to characterize cell viability, intracellular reactive oxygen species (ROS), intracellular melanin and tyrosinase assay, skin integrity and pro-inflammatory gene expression level by quantitative PCR.

Results

C. asiaticaEVs were found to contain high levels of polyphenol, which contributed to their radical scavenging and metal chelating properties and mitigated hydrogen peroxide-induced intracellular ROS. The EVs were further able to reduce intracellular melanin content and tyrosinase activity, and upregulate skin barrier genes procollagen type I, aquaporin 3, and filaggrin. The inhibitory effect ofC. asiaticaEVs on inflammation was evident in downregulation of expression of pro-inflammatory genes COX2 as well as nitric oxide production.

Conclusions

The beneficial effects ofC. asiaticaEVs warrant further studies as promising formulations in skin care applications.
Distinct differentiation trajectories leave lasting impacts on gene regulation and function of V2a interneurons
Authors: Elder Nicholas H. , Majd Alireza , Bulger Emily A. , Samuel Ryan M. , Zholudeva Lyandysha V. , McDevitt Todd C. , Fattahi Faranak
Published: December 2024

During development, early regionalization segregates lineages and directs diverse cell fates. Sometimes, however, distinct progenitors produce analogous cell types. For example, V2a neurons, are excitatory interneurons that emerge from different anteroposterior progenitors. V2a neurons demonstrate remarkable plasticity after spinal cord injury and improve motor function, showing potential for cell therapy. To examine how lineage origins shape their properties, we differentiated V2a neurons from hPSC-derived progenitors with distinct anteroposterior identities. Single-nucleus multiomic analysis revealed lineage-specific transcription factor motifs and numerous differentially expressed genes related to axon growth and calcium handling. Bypassing lineage patterning via transcription factor-induced differentiation yielded neurons distinct from both developmentally relevant populations and human tissue, emphasizing the need to follow developmental steps to generate authentic cell identities. Usingin silicoandin vitroloss-of-function analyses, we identified CREB5 and TCF7L2 as regulators specific to posterior identities, underscoring the critical role of lieage origins in determining cell states and functions.
High KIR diversity in Uganda and Botswana children living with HIV
Authors: Mukisa John , Kyobe Samuel , Amujal Marion , Katagirya Eric , Diphoko Thabo , Sebetso Gaseene , Mwesigwa Savannah , Mboowa Gerald , Retshabile Gaone , Williams Lesedi , Mlotshwa Busisiwe , Matshaba Mogomotsi , Jjingo Daudi , Kateete David P. , Joloba Moses L. , Mardon Graeme , Hanchard Neil , Hollenbach Jill A.
Published: December 2024

Killer-cell immunoglobulin-like receptors (KIRs) are essential components of the innate immune system found on the surfaces of natural killer (NK) cells. TheKIRs encoding genes are located on chromosome 19q13.4 and are genetically diverse across populations.KIRs are associated with various disease states including HIV progression, and are linked to transplantation rejection and reproductive success. However, there is limited knowledge on the diversity ofKIRs from Uganda and Botswana HIV-infected paediatric cohorts, with high endemic HIV rates. We used next-generation sequencing technologies on 312 (246 Uganda, 66 Botswana) samples to generateKIRallele data and employed customised bioinformatics techniques for allelic, allotype and disease association analysis. We show that these sample sets from Botswana and Uganda have different KIRs of different diversities. In Uganda, we observed 147 vs 111 alleles in the Botswana cohort, which had a more than 1 % frequency. We also found significant deviation towards homozygosity for theKIR3DL2gene for both rapid (RPs) and long-term non-progressors (LTNPs)in the Ugandan cohort. The frequency of the bw4-80I ligand was also significantly higher among the LTNPs than RPs (8.9 % Vs 2.0%, P-value: 0.032). In the Ugandan cohort,KIR2DS4*001(OR: 0.671, 95 % CI: 0.481-0.937, FDR adjusted Pc=0.142) andKIR2DS4*006(OR: 2.519, 95 % CI: 1.085-5.851, FDR adjusted Pc=0.142) were not associated with HIV disease progression after adjustment for multiple testing. Our study results provide additional knowledge of the genetic diversity ofKIRs in African populations and provide evidence that will inform future immunogenetics studies concerning human disease susceptibility, evolution and host immune responses.
Phantom epistasis through the lens of genealogies
Authors: Ignatieva Anastasia , Ferreira Lino A. F.
Published: December 2024

Phantom epistasis arises when, in the course of testing for gene-by-gene interactions, the omission of a causal variant (with a purely additive effect on the phenotype) causes the spurious inference of a significant interaction between two SNPs. This is more likely to arise when the two SNPs are in relatively close proximity, so while true epistasis between nearby variants could be commonplace, in practice there is no reliable way of telling apart true epistatic signals from false positives. By considering the causes of phantom epistasis from a genealogy-based perspective, we leverage the rich information contained within reconstructed genealogies (in the form of ancestral recombination graphs) to address this problem. We propose a novel method for explicitly quantifying how likely it is that a given pairwise interaction is the result of phantom epistasis, which can be applied to pairs of SNPs regardless of the genetic distance between them. Our method uses only publicly-available data and so does not require access to the phenotypes and genotypes used for detecting interactions. Using simulations, we show that the method has good sensitivity at even low genetic distances (around 0.5cM), and demonstrate its power to detect phantom epistasis using real data from previous studies. This opens up the exciting possibility of distinguishing spurious interactions incisfrom those reflecting real biological effects.
Comparing Intra- and Inter-individual Correlational Brain Connectivity from Functional and Structural Neuroimaging Data
Authors: Di Xin , Biswal Bharat B ,   Alzheimer's Disease Neuroimaging Initiative
Published: December 2024

Inferring brain connectivity from inter-individual correlations has been applied across various neuroimaging modalities, including positron emission tomography (PET) and MRI. The variability underlying these inter-individual correlations is generally attributed to factors such as genetics, life experiences, and long-term influences like aging. This study leveraged two unique longitudinal datasets to examine intra-individual correlations of structural and functional brain measures across an extended time span. By focusing on intra-individual correlations, we aimed to minimize individual differences and investigate how aging and state-like effects contribute to brain connectivity patterns. Additionally, we compared intra-individual correlations with inter-individual correlations to better understand their relationship. In the first dataset, which included repeated scans from a single individual over 15 years, we found that intra-individual correlations in both regional homogeneity (ReHo) during resting-state and gray matter volumes (GMV) from structural MRI closely resembled resting-state functional connectivity. However, ReHo correlations were primarily driven by state-like variability, whereas GMV correlations were mainly influenced by aging. The second dataset, comprising multiple participants with longitudinal Fludeoxyglucose (18F) FDG-PET and MRI scans, replicated these findings. Both intra- and inter-individual correlations were strongly associated with resting-state functional connectivity, with functional measures (i.e., ReHo and FDG-PET) exhibiting greater similarity to resting-state connectivity than structural measures. This study demonstrated that controlling for various factors can enhance the interpretability of brain correlation structures. While inter- and intra-individual correlation patterns showed similarities, accounting for additional variables may improve our understanding of inter-individual connectivity measures.
The gold complex auranofin sensitizes platinum resistant epithelial ovarian cancer cells to cisplatin
Authors: Abdalbari Farah H , Forgie Benjamin N , Zorychta Edith , Goyeneche Alicia A , Noman Abu Shadat M , Telleria Carlos M
Published: December 2024

Although there are numerous studies on drug development for ovarian cancer (OC), survival rates for this disease remain low due to platinum (Pt) resistance. Following several rounds of Pt- based chemotherapy, OC cells develop resistance by increasing DNA repair and antioxidant systems. This study aimed to design a treatment approach to combat recurrent stages of OC by repurposing the anti-rheumatic gold complex auranofin (AF). Here we demonstrate that AF enhances the efficacy of cisplatin (CDDP) in Pt-resistant epithelial OC (EOC) cells. The drug combination induces mitochondrial-dependent apoptosis, PARP cleavage, DNA damage, and ROS overproduction. These results suggest the high potential for combining AF with CDDP as a second-line therapy for recurrent EOCs.
Tuning mechanicalmilieuxof tissue templates and their cellular inhabitants to guide mechanoadaptation
Authors: Putra Vina D. L. , Sansalone Vittorio , Kilian Kristopher A. , Knothe Tate Melissa L.
Published: December 2024

Mechanomics describes the adaptation of mesenchymal stem cells (MSCs) to their mechanical environment, via cytoskeletal remodeling, as well as changes in shape and volume, ultimately resulting in emergent lineage commitment. Here we elucidated effects of exogenous microtubule stabilization, using paclitaxel (PAX), on stem cells’ capacity to sense and adapt to changes in their local mechanical environment. We studied the interplay between the living, evolving cells and their mechanical environment using established experimental and computational tools for respective delivery and prediction of shape and volume changing stresses. Stiffened and volumetrically larger microtubule-stabilized MSCs and their experienced significantly different normal and shear stress compared to control cells when exposed to identical bulk laminar flow (0.2 dyn/cm2) for one hour. These spatiotemporal mechanical cues transduced to the nucleus via the cytoskeleton, triggering significantly different changes in gene expression indicative of emergent lineage commitment than those observed in control cells. Using a paired computational model, we further predicted a range of mechanoadaptation responses of microtubule-stabilized cells to scaled up flow magnitudes (1 and 2 dyn/cm2). Hence, MSCs adapt to as well as modulate their own mechanical environment via cytoskeletal remodeling and lineage commitment - microtubule stabilization changes not only MSCs’ mechanoadaptive machinery, their capacity to adapt, and their lineage commitment, but also their mechanical environment. Taken as a whole, these studies corroborate our working hypothesis that MSCs and their mechanoadaptive machinery serve as sensors and actuators, intrinsically linked to their lineage potential via mechanoadaptive feedback loops which are sensitive to exogenous modulation via biochemical and biophysical means.

Classification

Biological Systems Engineering, Computational Simulations, Cell Biology, Biophysics
SUMO Inhibition Plus CD40 Agonism Increases Anti-Tumor Immunogenicity Through Interferon Mediated Macrophage Activation
Authors: Li Kevin , Courelli Asimina , Lee Hyojae James , de Mendoza Tatiana Hurtado , Martsinkovskiy Alexei , Mose Evangeline , Patel Jay , Ng Izzy , Sun Siming , Tharuka Mohottige Don Neranjan , Tiriac Hervé , Chen Yuan , Lowy Andrew M.
Published: December 2024

Resistance to immunotherapy is a cardinal feature of pancreatic ductal adenocarcinoma (PDAC). Inhibition of Small Ubiquitin-like MOdifier (SUMO), a post-translational modification with important immune regulatory functions, augments responsiveness to immunotherapy in non-PDAC models via pro-immunogenic effects on myeloid cells, cancer cells, and T-cells. Recently, it has been reported that SUMO inhibition has direct immunogenic effects on PDAC. Here, we report that the novel combination of SUMO inhibition with a small molecule, TAK-981, plus antibody-mediated CD40 agonism improves survival in an aggressive orthotopic mouse model of PDAC by enhancing anti-tumoral immunogenicity. This combination amplifies CD8+ T-cell tumor infiltration and induces significant changes among macrophages. TAK-981 also leads to enhanced cancer specific MHC-I expression bothin vitroandin vivoby augmenting interferon signaling. We show that the improvement in survival is mediated by macrophages. Our findings show that SUMO inhibition complements CD40 agonism to enhance immune activity in PDAC via interferon signaling, improving survival in an aggressive pre-clinical model of PDAC and translating previous findings to a characteristically immunosuppressive and highly aggressive solid malignancy.
BindingGYM: A Large-Scale Mutational Dataset Toward Deciphering Protein-Protein Interactions
Authors: Lu Wei , Zhang Jixian , Gu Ming , Zheng Shuangjia
Published: December 2024

Protein-protein interactions are crucial for drug discovery and understanding biological mechanisms. Despite significant advances in predicting the structures of protein complexes, led by AlphaFold3, determining the strength of these interactions accurately remains a challenge. Traditional low-throughput experimental methods do not generate sufficient data for comprehensive benchmarking or training deep learning models. Deep mutational scanning (DMS) experiments provide rich, high-throughput data; however, they are often used incompletely, neglecting to consider the binding partners, and on a per-study basis without assessing the generalization capabilities of fine-tuned models across different assays. To address these limitations, we collected over ten million raw DMS data points and refined them to half a million high-quality points from twenty-five assays, focusing on protein-protein interactions. We intentionally excluded non-PPI DMS data pertaining to intrinsic protein properties, such as fluorescence or catalytic activity. Our dataset meticulously pairs binding energies with thesequencesandstructures of all interacting partnersusing a comprehensive pipeline, recognizing that interactions inherently involve at least two proteins. This curated dataset serves as a foundation for benchmarking and training the next generation of deep learning models focused on protein-protein interactions, thereby opening the door to a plethora of high-impact applications including understanding cellular networks and advancing drug target discovery and development.
Prediction of peptide structural conformations with AlphaFold2
Authors: Ille Alexander M , Markosian Christopher , Burley Stephen K. , Pasqualini Renata , Arap Wadih
Published: December 2024

Protein structure prediction via artificial intelligence/machine learning (AI/ML) approaches has sparked substantial research interest in structural biology and adjacent disciplines. More recently, AlphaFold2 (AF2) has been adapted for the prediction of multiple structural conformations in addition to single-state structures. This novel avenue of research has focused on proteins (typically 50 residues in length or greater), while multi-conformation prediction of shorter peptides has not yet been explored in this context. Here, we report AF2-based structural conformation prediction of a total of 557 peptides (ranging in length from 10 to 40 residues) for a benchmark dataset with corresponding nuclear magnetic resonance (NMR)-determined conformational ensembles. De novo structure predictions were accompanied by structural comparison analyses to assess prediction accuracy. We found that the prediction of conformational ensembles for peptides with AF2 varied in accuracy versus NMR data, with average root-mean-square deviation (RMSD) among structured regions under 2.5 Å and average root-mean-square fluctuation (RMSF) differences under 1.5 Å. Our results reveal notable capabilities of AF2-based structural conformation prediction for peptides but also underscore the necessity for interpretation discretion.
Scaling diversity, abundance and energy: The Equilibrium Theory of Biodiversity Dynamics
Authors: Storch David , Okie Jordan G.
Published: December 2024

This preprint of a book chapter presents the newly proposed Equilibrium Theory of Biodiversity Dynamics (ETBD), whose aim is to conceptualize large-scale dynamics of species richness via addressing the population size-dependence of speciation and extinction rates, the resulting diversity-dependence of these rates, and their modulation by the environment. It provides the most general framework for understanding large-scale biodiversity patterns such as the latitudinal diversity gradient (LDG) and temporal patterns of biodiversity changes. The theory has been published elsewhere in its full form that includes all the derivations (Okie & Storch 2004, American Naturalisthttps://doi.org/10.1086/733103), but here it is presented in a simpler and user-friendly way, focusing on its major implications comprising macroecological scaling relationships between energy (or resource) availability, species richness and community abundance.