bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fatty acid desaturation by stearoyl-CoA desaturase-1 controls regulatory T cell differentiation and autoimmunity
Authors: Grajchen Elien , Loix Melanie , Baeten Paulien , Côrte-Real Beatriz F. , Hamad Ibrahim , Vanherle Sam , Haidar Mansour , Dehairs Jonas , Broos Jelle Y. , Ntambi James M. , Zimmermann Robert , Breinbauer Rolf , Stinissen Piet , Hellings Niels , Verberk Sanne G. S. , Kooij Gijs , Giera Martin , Swinnen Johannes V. , Broux Bieke , Kleinewietfeld Markus , Hendriks Jerome J. A. , Bogie Jeroen F. J. 
Published: April 2023

AbstractThe imbalance between pathogenic and protective T cell subsets is a cardinal feature of autoimmune disorders such as multiple sclerosis (MS). Emerging evidence indicates that endogenous and dietary-induced changes in fatty acid metabolism have a major impact on both T cell fate and autoimmunity. To date, however, the molecular mechanisms that underlie the impact of fatty acid metabolism on T cell physiology and autoimmunity remain poorly understood. Here, we report that stearoyl-CoA desaturase-1 (SCD1), an enzyme essential for the desaturation of fatty acids and highly regulated by dietary factors, acts as an endogenous brake on regulatory T-cell (Treg) differentiation and augments autoimmunity in an animal model of MS in a T cell-dependent manner. Guided by RNA sequencing and lipidomics analysis, we found that the absence of Scd1 in T cells promotes the hydrolysis of triglycerides and phosphatidylcholine through adipose triglyceride lipase (ATGL). ATGL-dependent release of docosahexaenoic acid enhanced Treg differentiation by activating the nuclear receptor peroxisome proliferator-activated receptor gamma. Our findings identify fatty acid desaturation by SCD1 as an essential determinant of Treg differentiation and autoimmunity, with potentially broad implications for the development of novel therapeutic strategies and dietary interventions for autoimmune disorders such as MS.
DAXX drives de novo lipogenesis and contributes to tumorigenesis
Authors: Mahmud Iqbal , Tian Guimei , Wang Jia , Hutchinson Tarun E. , Kim Brandon J. , Awasthee Nikee , Hale Seth , Meng Chengcheng , Moore Allison , Zhao Liming , Lewis Jessica E. , Waddell Aaron , Wu Shangtao , Steger Julia M. , Lydon McKenzie L. , Chait Aaron , Zhao Lisa Y. , Ding Haocheng , Li Jian-Liang , Purayil Hamsa Thayele , Huo Zhiguang , Daaka Yehia , Garrett Timothy J. , Liao Daiqing 
Published: April 2023

AbstractCancer cells exhibit elevated lipid synthesis. In breast and other cancer types, genes involved in lipid production are highly upregulated, but the mechanisms that control their expression remain poorly understood. Using integrated transcriptomic, lipidomic, and molecular studies, here we report that DAXX is a regulator of oncogenic lipogenesis. DAXX depletion attenuates, while its overexpression enhances, lipogenic gene expression, lipogenesis, and tumor growth. Mechanistically, DAXX interacts with SREBP1 and SREBP2 and activates SREBP-mediated transcription. DAXX associates with lipogenic gene promoters through SREBPs. Underscoring the critical roles for the DAXX-SREBP interaction for lipogenesis, SREBP2 knockdown attenuates tumor growth in cells with DAXX overexpression, and DAXX mutants unable to bind SREBP1/2 have weakened activity in promoting lipogenesis and tumor growth. Remarkably, a DAXX mutant deficient of SUMO-binding fails to activate SREBP1/2 and lipogenesis due to impaired SREBP binding and chromatin recruitment and is defective of stimulating tumorigenesis. Hence, DAXX’s SUMO-binding activity is critical to oncogenic lipogenesis. Notably, a peptide corresponding to DAXX’s C-terminal SUMO-interacting motif (SIM2) is cell-membrane permeable, disrupts the DAXX-SREBP1/2 interactions, and inhibits lipogenesis and tumor growth. These results establish DAXX as a regulator of lipogenesis and a potential therapeutic target for cancer therapy.
Inducible expression of interleukin-12 augments the efficacy of affinity-tuned chimeric antigen receptors in murine solid tumor models
Authors: Yang Yanping , Yang Huan , Alcaina Yago , Puc Janusz , Birt Alyssa , Vedvyas Yogindra , Gallagher Michael , Alla Srinija , Riascos Maria Cristina , McCloskey Jaclyn E. , Du Karrie , Gonzalez-Valdivieso Juan , Min Irene M. , de Stanchina Elisa , Britz Matt , von Hofe Eric , Jin Moonsoo M. 
Published: April 2023

AbstractThe limited number of targetable tumor-specific antigens and the immunosuppressive nature of the microenvironment within solid malignancies represent major barriers to the success of chimeric antigen receptor (CAR)-T cell therapies. Here, using epithelial cell adhesion molecule (EpCAM) as a model antigen, we used alanine scanning of the complementarity-determining region to fine-tune CAR affinity. This allowed us to identify CARs that could spare primary epithelial cells while still effectively targeting EpCAMhigh tumors. Although affinity-tuned CARs showed suboptimal antitumor activity in vivo, we found that inducible secretion of interleukin-12 (IL-12), under the control of the NFAT promoter, can restore CAR activity to levels close to that of the parental CAR. This strategy was further validated with another affinity-tuned CAR specific for intercellular adhesion molecule-1 (ICAM-1). Only in affinity-tuned CAR-T cells was NFAT activity stringently controlled and restricted to tumors expressing the antigen of interest at high levels. Our study demonstrates the feasibility of specifically gearing CAR-T cells towards recognition of solid tumors by combining inducible IL-12 expression and affinity-tuned CAR.
WHIM Syndrome-linked CXCR4 mutations drive osteoporosis
Authors: Anginot Adrienne , Nguyen Julie , Abou Nader Zeina , Rondeau Vincent , Bonaud Amélie , Kalogeraki Maria , Boutin Antoine , Lemos Julia P. , Bisio Valeria , Koenen Joyce , Hanna Doumit Sakr Lea , Picart Amandine , Coudert Amélie , Provot Sylvain , Dulphy Nicolas , Aurrand-Lions Michel , Mancini Stéphane J. C. , Lazennec Gwendal , McDermott David H. , Guidez Fabien , Blin-Wakkach Claudine , Murphy Philip M. , Cohen-Solal Martine , Espéli Marion , Rouleau Matthieu , Balabanian Karl 
Published: April 2023

AbstractWHIM Syndrome is a rare immunodeficiency caused by gain-of-function CXCR4 mutations. Here we report a decrease in bone mineral density in 25% of WHIM patients and bone defects leading to osteoporosis in a WHIM mouse model. Imbalanced bone tissue is observed in mutant mice combining reduced osteoprogenitor cells and increased osteoclast numbers. Mechanistically, impaired CXCR4 desensitization disrupts cell cycle progression and osteogenic commitment of skeletal stromal/stem cells, while increasing their pro-osteoclastogenic capacities. Impaired osteogenic differentiation is evidenced in primary bone marrow stromal cells from WHIM patients. In mice, chronic treatment with the CXCR4 antagonist AMD3100 normalizes in vitro osteogenic fate of mutant skeletal stromal/stem cells and reverses in vivo the loss of skeletal cells, demonstrating that proper CXCR4 desensitization is required for the osteogenic specification of skeletal stromal/stem cells. Our study provides mechanistic insights into how CXCR4 signaling regulates the osteogenic fate of skeletal cells and the balance between bone formation and resorption.
Future strengthening of the Nordic Seas overturning circulation
Authors: Årthun Marius , Asbjørnsen Helene , Chafik Léon , Johnson Helen L. , Våge Kjetil 
Published: April 2023

AbstractThe overturning circulation in the Nordic Seas involves the transformation of warm Atlantic waters into cold, dense overflows. These overflow waters return to the North Atlantic and form the headwaters to the deep limb of the Atlantic meridional overturning circulation (AMOC). The Nordic Seas are thus a key component of the AMOC. However, little is known about the response of the overturning circulation in the Nordic Seas to future climate change. Here we show using global climate models that, in contrast to the North Atlantic, the simulated density-space overturning circulation in the Nordic Seas increases throughout most of the 21st century as a result of enhanced horizontal circulation and a strengthened zonal density gradient. The increased Nordic Seas overturning is furthermore manifested in the overturning circulation in the eastern subpolar North Atlantic. A strengthened Nordic Seas overturning circulation could therefore be a stabilizing factor in the future AMOC.
Assessing the impact of the global subsea telecommunications network on sedimentary organic carbon stocks
Authors: Clare M. A. , Lichtschlag A. , Paradis S. , Barlow N. L. M. 
Published: April 2023

AbstractThe sequestration of organic carbon in seafloor sediments plays a key role in regulating global climate; however, human activities can disturb previously-sequestered carbon stocks, potentially reducing the capacity of the ocean to store CO2. Recent studies revealed profound seafloor impacts and sedimentary carbon loss due to fishing and shipping, yet most other human activities in the ocean have been overlooked. Here, we present an assessment of organic carbon disturbance related to the globally-extensive subsea telecommunications cable network. Up to 2.82–11.26 Mt of organic carbon worldwide has been disturbed as a result of cable burial, in water depths of up to 2000 m. While orders of magnitude lower than that disturbed by bottom fishing, it is a non-trivial amount that is absent from global budgets. Future offshore developments that disturb the seafloor should consider the safeguarding of carbon stocks, across the full spectrum of Blue Economy industries.
The fragmentation-induced fluidisation of pyroclastic density currents
Authors: Breard Eric C. P. , Dufek Josef , Charbonnier Sylvain , Gueugneau Valentin , Giachetti Thomas , Walsh Braden 
Published: April 2023

AbstractPyroclastic density currents (PDCs) are the most lethal volcanic process on Earth. Forecasting their inundation area is essential to mitigate their risk, but existing models are limited by our poor understanding of their dynamics. Here, we explore the role of evolving grain-size distribution in controlling the runout of the most common PDCs, known as block-and-ash flows (BAFs). Through a combination of theory, analysis of deposits and experiments of natural mixtures, we show that rapid changes of the grain-size distribution transported in BAFs result in the reduction of pore volume (compaction) within the first kilometres of their runout. We then use a multiphase flow model to show how the compressibility of granular mixtures leads to fragmentation-induced fluidisation (FIF) and excess pore-fluid pressure in BAFs. This process dominates the first ~2 km of their runout, where the effective friction coefficient is progressively reduced. Beyond that distance, transport is modulated by diffusion of the excess pore pressure. Fragmentation-induced fluidisation provides a physical basis to explain the decades-long use of low effective friction coefficients used in depth-averaged simulations required to match observed flow inundation.
Unsteady natural convection flow of blood Casson nanofluid (Au) in a cylinder: nano-cryosurgery applications
Authors: Azmi Wan Faezah Wan , Mohamad Ahmad Qushairi , Jiann Lim Yeou , Shafie Sharidan 
Published: April 2023

AbstractNano-cryosurgery is one of the effective ways to treat cancerous cells with minimum harm to healthy adjacent cells. Clinical experimental research consumes time and cost. Thus, developing a mathematical simulation model is useful for time and cost-saving, especially in designing the experiment. Investigating the Casson nanofluid's unsteady flow in an artery with the convective effect is the goal of the current investigation. The nanofluid is considered to flow in the blood arteries. Therefore, the slip velocity effect is concerned. Blood is a base fluid with gold (Au) nanoparticles dispersed in the base fluid. The resultant governing equations are solved by utilising the Laplace transform regarding the time and the finite Hankel transform regarding the radial coordinate. The resulting analytical answers for velocity and temperature are then displayed and visually described. It is found that the temperature enhancement occurred by arising nanoparticles volume fraction and time parameter. The blood velocity increases as the slip velocity, time parameter, thermal Grashof number, and nanoparticles volume fraction increase. Whereas the velocity decreases with the Casson parameter. Thus, by adding Au nanoparticles, the tissue thermal conductivity enhanced which has the consequence of freezing the tissue in nano-cryosurgery treatment significantly.
A small fishing vessel recognition method using transfer learning based on laser sensors
Authors: Zheng Jianli , Cao Jianjun , Yuan Kun , Liu Yang 
Published: April 2023

AbstractThe management of small vessels has always been key to maritime administration. This paper presents a novel method for recognizing small fishing vessels based on laser sensors. Using four types of small fishing vessels as targets, a recognition method for small fishing vessels based on Markov transition field (MTF) time-series images and VGG-16 transfer learning is proposed. In contrast to conventional methods, this study uses polynomial fitting to obtain the contours of a fishing vessel and transforms one-dimensional vessel contours into two-dimensional time-series images using the MTF coding method. The VGG-16 model is used for the recognition process, and migration learning is applied to improve the results. The UCR time-series public dataset is used as a transfer learning dataset for the MTF time-series image encoding. The experiment demonstrates that the proposed method exhibits higher accuracy and performance than 1D-CNN and other general neural network models, and the highest accuracy rate is 98.92%.
Hierarchical data structures for flowchart
Authors: Zhang Peng , Dou Wenzhang , Liu Huaping 
Published: April 2023

AbstractFlowcharts have broad applications in the fields of software development, engineering design, and scientific experimentation. Current flowchart data structure is mainly based on the adjacency list, cross-linked list, and adjacency matrix of the graph structure. Such design originated from the fact that any two nodes could have a connection relationship. But flowcharts have clear regularities, and their nodes have a certain inflow or outflow relationship. When graph structures such as an adjacency table or an adjacency matrix are used to store a flowchart, there is a large room for optimization in terms of traversal time and storage complexities, as well as usage convenience. In this paper we propose two hierarchical data structures for flowchart design. In the proposed structures, a flowchart is composed of levels, layers, and numbered nodes. The nodes between layers are connected according to a certain set of systematic design rules. Compared with the traditional graph data structures, the proposed schemes significantly reduce the storage space, improve the traversal efficiency, and resolve the problem of nesting between sub-charts. Experimental data based on flowchart examples used in this paper show that, compared with adjacency list, the hierarchical table data structure reduces the traversal time by 50% while their storage spaces are similar; compared with adjacency matrix, the hierarchical matrix data structure reduces the traversal time by nearly 70% and saves the storage space by about 50%. The proposed structures could have broad applications in flowchart-based software development, such as low-code engineering for smart industrial manufacturing.
Optimal dose of normal saline for confirming correct peripheral venous access with precordial Doppler ultrasonography in children
Authors: Omori Ayaka , Otaki Yuji , Tanaka Motoi , Miyazu Mitsunori , Ohde Sachiko , Kojima Taiki 
Published: April 2023

AbstractPrecordial Doppler ultrasound technology can be utilized to confirm correct peripheral intravenous vascular (PIV) access in children during surgery. This study aimed to determine the minimally required dose of normal saline (NS) for confirming correct PIV access. Healthy children were randomly allocated to receive a 0.1 mL/kg, 0.3 mL/kg, or 0.5 mL/kg dose of NS injected via PIV access. Two independent raters judged the change in the recorded precordial Doppler sound test (S-test) before and after NS injection. Typically, rapid injection of NS increased the pitch of the heartbeat as the injection volume increased. Changes in blood flow velocity test (V-test) results were evaluated using a cut-off value of 1 cm/s. Both in the S- and V-tests, the detection rate of correct PIV access was lower with 0.1 mL/kg NS than with 0.3 mL/kg or 0.5 mL/kg. Logistic regression analysis showed that the positive results in both the S- and V-tests were significantly decreased with a 0.1 mL/kg NS; no significant difference was observed with a 0.3 mL/kg NS (reference dose: 0.5 mL/kg). These results suggest 0.3 mL/kg is the minimally required dose of NS for confirming correct PIV access. This study is registered with the University Hospital Medical Information Network (UMIN000041330).
Hierarchical settlement behaviours of coral larvae to common coralline algae
Authors: Abdul Wahab M. A. , Ferguson S. , Snekkevik V. K. , McCutchan G. , Jeong S. , Severati A. , Randall C. J. , Negri A. P. , Diaz-Pulido G. 
Published: April 2023

AbstractNatural regeneration of degraded reefs relies on the recruitment of larvae to restore populations. Intervention strategies are being developed to enhance this process through aquaculture production of coral larvae and their deployment as spat. Larval settlement relies on cues associated with crustose coralline algae (CCA) that are known to induce attachment and metamorphosis. To understand processes underpinning recruitment, we tested larval settlement responses of 15 coral species, to 15 species of CCA from the Great Barrier Reef (GBR). CCA in the family Lithophyllaceae were overall the best inducer across most coral species, with Titanoderma cf. tessellatum being the most effective species that induced at least 50% settlement in 14 of the coral species (mean 81%). Taxonomic level associations were found, with species of Porolithon inducing high settlement in the genus Acropora; while a previously understudied CCA, Sporolithon sp., was a strong inducer for the Lobophyllidae. Habitat-specific associations were detected, with CCA collected from similar light environment as the coral inducing higher levels of settlement. This study revealed the intimate relationships between coral larvae and CCA and provides optimal coral-algal species pairings that could be utilized to increase the success of larval settlement to generate healthy spat for reef restoration.
Cynomolgus monkey’s retina volume reference database based on hybrid deep learning optical coherence tomography segmentation
Authors: Denk Nora , Freichel Christian , Valmaggia Philippe , Inglin Nadja , Scholl Hendrik P. N. , Kaiser Pascal , Wise Sylvie , Vezina Marc , Maloca Peter M. 
Published: April 2023

AbstractCynomolgus monkeys (Macaca fascicularis) are commonly used in pre-clinical ocular studies. However, studies that report the morphological features of the macaque retina are based only on minimal sample sizes; therefore, little is known about the normal distribution and background variation. This study was conducted using optical coherence tomography (OCT) imaging to investigate the variations in retinal volumes of healthy cynomolgus monkeys and the effects of sex, origin, and eye side on the retinal volumes to establish a comprehensive reference database. A machine-learning algorithm was employed to segment the retina within the OCT data (i.e., generated pixel-wise labels). Furthermore, a classical computer vision algorithm has identified the deepest point in a foveolar depression. The retinal volumes were determined and analyzed based on this reference point and segmented retinal compartments. Notably, the overall foveolar mean volume in zone 1, which is the region of the sharpest vision, was 0.205 mm3 (range 0.154–0.268 mm3), with a relatively low coefficient of variation of 7.9%. Generally, retinal volumes exhibit a relatively low degree of variation. However, significant differences in the retinal volumes due to the monkey’s origin were identified. Additionally, sex had a significant impact on the paracentral retinal volume. Therefore, the origin and sex of cynomolgus monkeys should be considered when evaluating the macaque retinal volumes based on this dataset.
Modeling the propagation of very-high-energyγ-rays with the CRbeam code: Comparison with CRPropa and ELMAG codes
Authors: Kalashev O. , Korochkin A. , Neronov A. , Semikoz D. 
Published: April 2023

Context.Very-high-energyγ-rays produce electron positron pairs in interactions with low-energy photons of extragalactic background light during propagation through the intergalactic medium. The electron-positron pairs generate secondaryγ-rays detectable byγ-ray telescopes. This secondary emission can be used to detect intergalactic magnetic fields (IGMF) in the voids of large-scale structure.Aims.A newγ-ray observatory, namely, Cherenkov Telescope Array (CTA), will provide an increase in sensitivity for detections of these secondaryγ-ray emission and enable the measurement of its properties for sources at cosmological distances. The interpretation of the CTA data, including the detection of IGMF and study of its properties and origins, will require precision modeling of the primary and secondaryγ-ray fluxes.Methods.We assess the precision of the modeling of the secondaryγ-ray emission using model calculations with publicly available Monte Carlo codes CRPropa and ELMAG and compare their predictions with theoretical expectations and with model calculations of a newly developed CRbeam code.Results.We find that model predictions of different codes differ by up to 50% for low-redshift sources, with discrepancies increasing up to order-of-magnitude level with the increasing source redshifts. We identify the origin of these discrepancies and demonstrate that after eliminating the inaccuracies found, the discrepancies between the three codes are reduced to 10% when modeling nearby sources withz ~0.1. We argue that the new CRbeam code provides reliable predictions for the spectral, timing, and imaging properties of the secondaryγ-ray signal for both nearby and distant sources withz~ 1. Thus, it can be used to study gamma-ray sources and IGMF with a level of precision that is appropriate for the prospective CTA study of the effects ofγ-ray propagation through the intergalactic medium.