bluuebunny/crossref_metadata_2025_split huggingface dataset:
SMOC2 promotes aggressive behavior of fibroblast-like synoviocytes in rheumatoid arthritis through transcriptional and post-transcriptional regulating MYO1C
Authors: Liu Di , Li Ruiru , Xu Siqi , Shi Maohua , Kuang Yu , Wang Jingnan , Shen Chuyu , Qiu Qian , Liang Liuqin , Xiao Youjun , Xu Hanshi 
Published: December 2022

AbstractFibroblast-like synoviocytes (FLSs), play a key role in perpetuating synovial inflammation and bone erosion in rheumatoid arthritis (RA), however, the underlying mechanism(s) of RA FLSs activation and aggression remain unclear. Identifying endogenous proteins that selectively target FLSs is urgently needed. Here, we systematically identified that secreted modular calcium-binding protein 2 (SMOC2), was significantly increased in RA FLSs and synovial tissues. SMOC2 knockdown specifically regulated cytoskeleton remodeling and decreased the migration and invasion of RA FLSs. Mechanistically, cytoskeleton-related genes were significantly downregulated in RA FLSs with reduced SMOC2 expression, especially the motor protein myosin1c (MYO1C). SMOC2 controlled MYO1C expression by SRY-related high-mobility group box 4 (SOX4) and AlkB homolog 5 (ALKHB5) mediated-m6A modification through transcriptional and post-transcriptional regulation. Furthermore, intra-articular Ad-shRNA-SMOC2 treatment attenuated synovial inflammation as well as bone and cartilage erosion in rats with collagen-induced arthritis (CIA). Our findings suggest that increased SMOC2 expression in FLSs may contribute to synovial aggression and joint destruction in RA. SMOC2 may serve as a potential target against RA.
BET protein inhibition sensitizes glioblastoma cells to temozolomide treatment by attenuating MGMT expression
Authors: Tancredi Alessandro , Gusyatiner Olga , Bady Pierre , Buri Michelle C. , Lomazzi Rémy , Chiesi Davide , Messerer Mahmoud , Hegi Monika E. 
Published: December 2022

AbstractBromodomain and extra-terminal tail (BET) proteins have been identified as potential epigenetic targets in cancer, including glioblastoma. These epigenetic modifiers link the histone code to gene transcription that can be disrupted with small molecule BET inhibitors (BETi). With the aim of developing rational combination treatments for glioblastoma, we analyzed BETi-induced differential gene expression in glioblastoma derived-spheres, and identified 6 distinct response patterns. To uncover emerging actionable vulnerabilities that can be targeted with a second drug, we extracted the 169 significantly disturbed DNA Damage Response genes and inspected their response pattern. The most prominent candidate with consistent downregulation, was the O-6-methylguanine-DNA methyltransferase (MGMT) gene, a known resistance factor for alkylating agent therapy in glioblastoma. BETi not only reduced MGMT expression in GBM cells, but also inhibited its induction, typically observed upon temozolomide treatment. To determine the potential clinical relevance, we evaluated the specificity of the effect on MGMT expression and MGMT mediated treatment resistance to temozolomide. BETi-mediated attenuation of MGMT expression was associated with reduction of BRD4- and Pol II-binding at the MGMT promoter. On the functional level, we demonstrated that ectopic expression of MGMT under an unrelated promoter was not affected by BETi, while under the same conditions, pharmacologic inhibition of MGMT restored the sensitivity to temozolomide, reflected in an increased level of γ-H2AX, a proxy for DNA double-strand breaks. Importantly, expression of MSH6 and MSH2, which are required for sensitivity to unrepaired O6-methylguanine-lesions, was only briefly affected by BETi. Taken together, the addition of BET-inhibitors to the current standard of care, comprising temozolomide treatment, may sensitize the 50% of patients whose glioblastoma exert an unmethylated MGMT promoter.
Deep brain stimulation creates informational lesion through membrane depolarization in mouse hippocampus
Authors: Lowet Eric , Kondabolu Krishnakanth , Zhou Samuel , Mount Rebecca A. , Wang Yangyang , Ravasio Cara R. , Han Xue 
Published: December 2022

AbstractDeep brain stimulation (DBS) is a promising neuromodulation therapy, but the neurophysiological mechanisms of DBS remain unclear. In awake mice, we performed high-speed membrane voltage fluorescence imaging of individual hippocampal CA1 neurons during DBS delivered at 40 Hz or 140 Hz, free of electrical interference. DBS powerfully depolarized somatic membrane potentials without suppressing spike rate, especially at 140 Hz. Further, DBS paced membrane voltage and spike timing at the stimulation frequency and reduced timed spiking output in response to hippocampal network theta-rhythmic (3–12 Hz) activity patterns. To determine whether DBS directly impacts cellular processing of inputs, we optogenetically evoked theta-rhythmic membrane depolarization at the soma. We found that DBS-evoked membrane depolarization was correlated with DBS-mediated suppression of neuronal responses to optogenetic inputs. These results demonstrate that DBS produces powerful membrane depolarization that interferes with the ability of individual neurons to respond to inputs, creating an informational lesion.
Gene augmentation prevents retinal degeneration in a CRISPR/Cas9-based mouse model of PRPF31 retinitis pigmentosa
Authors: Xi Zhouhuan , Vats Abhishek , Sahel José-Alain , Chen Yuanyuan , Byrne Leah C. 
Published: December 2022

AbstractMutations in PRPF31 cause autosomal dominant retinitis pigmentosa, an untreatable form of blindness. Gene therapy is a promising treatment for PRPF31-retinitis pigmentosa, however, there are currently no suitable animal models in which to develop AAV-mediated gene augmentation. Here we establish Prpf31 mutant mouse models using AAV-mediated CRISPR/Cas9 knockout, and characterize the resulting retinal degeneration phenotype. Mouse models with early-onset morphological and functional impairments like those in patients were established, providing new platforms in which to investigate pathogenetic mechanisms and develop therapeutic methods. AAV-mediated PRPF31 gene augmentation restored the retinal structure and function in a rapidly degenerating mouse model, demonstrating the first in vivo proof-of-concept for AAV-mediated gene therapy to treat PRPF31-retinitis pigmentosa. AAV-CRISPR/Cas9-PRPF31 knockout constructs also mediated efficient PRPF31 knockout in human and non-human primate retinal explants, laying a foundation for establishing non-human primate models using the method developed here.
Microbiome-mediated fructose depletion restricts murine gut colonization by vancomycin-resistant Enterococcus
Authors: Isaac Sandrine , Flor-Duro Alejandra , Carruana Gloria , Puchades-Carrasco Leonor , Quirant Anna , Lopez-Nogueroles Marina , Pineda-Lucena Antonio , Garcia-Garcera Marc , Ubeda Carles 
Published: December 2022

AbstractMultidrug-resistant organisms (MDRO) are a major threat to public health. MDRO infections, including those caused by vancomycin-resistantEnterococcus(VRE), frequently begin by colonization of the intestinal tract, a crucial step that is impaired by the intestinal microbiota. However, the specific members of the microbiota that suppress MDRO colonization and the mechanisms of such protection are largely unknown. Here, using metagenomics and mouse models that mimic the patients’ exposure to antibiotics, we identified commensal bacteria associated with protection against VRE colonization. We further found a consortium of five strains that was sufficient to restrict VRE gut colonization in antibiotic treated mice. Transcriptomics in combination with targeted metabolomics and in vivo assays indicated that the bacterial consortium inhibits VRE growth through nutrient depletion, specifically by reducing the levels of fructose, a carbohydrate that boosts VRE growth in vivo. Finally, in vivo RNA-seq analysis of each strain of the consortium in combination with ex vivo and in vivo assays demonstrated that a single bacterium (Olsenella sp.) could recapitulate the effect of the consortium. Our results indicate that nutrient depletion by specific commensals can reduce VRE intestinal colonization, which represents a novel non-antibiotic based strategy to prevent infections caused by this multidrug-resistant organism.
Onset of Bloch oscillations in the almost-strong-field regime
Authors: Reislöhner Jan , Kim Doyeong , Babushkin Ihar , Pfeiffer Adrian N. 
Published: December 2022

AbstractIn the field of high-order harmonic generation from solids, the electron motion typically exceeds the edge of the first Brillouin zone. In conventional nonlinear optics, on the other hand, the excursion of band electrons is negligible. Here, we investigate the transition from conventional nonlinear optics to the regime where the crystal electrons begin to explore the first Brillouin zone. It is found that the nonlinear optical response changes abruptly already before intraband currents due to ionization become dominant. This is observed by an interference structure in the third-order harmonic generation of few-cycle pulses in a non-collinear geometry. Although approaching Keldysh parameter γ = 1, this is not a strong-field effect in the original sense, because the iterative series still converges and reproduces the interference structure. The change of the nonlinear interband response is attributed to Bloch motion of the reversible (or transient or virtual) population, similar to the Bloch motion of the irreversible (or real) population which affects the intraband currents that have been observed in high-order harmonic generation.
Risk of the hydrogen economy for atmospheric methane
Authors: Bertagni Matteo B. , Pacala Stephen W. , Paulot Fabien , Porporato Amilcare 
Published: December 2022

AbstractHydrogen (H2) is expected to play a crucial role in reducing greenhouse gas emissions. However, hydrogen losses to the atmosphere impact atmospheric chemistry, including positive feedback on methane (CH4), the second most important greenhouse gas. Here we investigate through a minimalist model the response of atmospheric methane to fossil fuel displacement by hydrogen. We find that CH4concentration may increase or decrease depending on the amount of hydrogen lost to the atmosphere and the methane emissions associated with hydrogen production. Green H2can mitigate atmospheric methane if hydrogen losses throughout the value chain are below 9 ± 3%. Blue H2can reduce methane emissions only if methane losses are below 1%. We address and discuss the main uncertainties in our results and the implications for the decarbonization of the energy sector.
Functional crosstalk between the cohesin loader and chromatin remodelers
Authors: Muñoz Sofía , Jones Andrew , Bouchoux Céline , Gilmore Tegan , Patel Harshil , Uhlmann Frank 
Published: December 2022

AbstractThe cohesin complex participates in many structural and functional aspects of genome organization. Cohesin recruitment onto chromosomes requires nucleosome-free DNA and the Scc2-Scc4 cohesin loader complex that catalyzes topological cohesin loading. Additionally, the cohesin loader facilitates promoter nucleosome clearance in a yet unknown way, and it recognizes chromatin receptors such as the RSC chromatin remodeler. Here, we explore the cohesin loader-RSC interaction. Amongst multi-pronged contacts by Scc2 and Scc4, we find that Scc4 contacts a conserved patch on the RSC ATPase motor module. The cohesin loader directly stimulates in vitro nucleosome sliding by RSC, providing an explanation how it facilitates promoter nucleosome clearance. Furthermore, we observe cohesin loader interactions with a wide range of chromatin remodelers. Our results provide mechanistic insight into how the cohesin loader recognizes, as well as influences, the chromatin landscape, with implications for our understanding of human developmental disorders including Cornelia de Lange and Coffin-Siris syndromes.
Finger-palm synergistic soft gripper for dynamic capture via energy harvesting and dissipation
Authors: Zhang Yin , Zhang Wang , Gao Pan , Zhong Xiaoqing , Pu Wei 
Published: December 2022

AbstractRobotic grippers, inspired by human hands, show an extraordinary ability to manipulate objects of various shapes, sizes, or materials. However, capturing objects with varying kinetic energy remains challenging, regardless of the classical rigid-bodied or frontier soft-bodied grippers. Here, we demonstrate a rapid energy harvesting and dissipation mechanism for the soft grippers leveraging the finger-palm synergy. Theoretically and experimentally, this mechanism enables a soft gripper to reliably capture high-speed targets by dissipating and harvesting almost all the target’s kinetic energy within 30 milliseconds. The energy harvesting and dissipating capability are adjustable and can be enhanced by inflating pressure. Additionally, the harvested energy is autonomously transferred into fingers to enhance their grasping force and reduce the response time. To highlight, the grippers we developed are integrated into a six-rotor drone and successfully capture flying objects in an outdoor experiment. These results significantly advance robotics development in achieving dynamic capture of dynamic targets.
The MetroPT dataset for predictive maintenance
Authors: Veloso Bruno , Ribeiro Rita P. , Gama João , Pereira Pedro Mota 
Published: December 2022

AbstractThe paper describes the MetroPT data set, an outcome of a Predictive Maintenance project with an urban metro public transportation service in Porto, Portugal. The data was collected in 2022 to develop machine learning methods for online anomaly detection and failure prediction. Several analog sensor signals (pressure, temperature, current consumption), digital signals (control signals, discrete signals), and GPS information (latitude, longitude, and speed) provide a framework that can be easily used and help the development of new machine learning methods. This dataset contains some interesting characteristics and can be a good benchmark for predictive maintenance models.
Analysis of second grade hybrid nanofluid flow over a stretching flat plate in the presence of activation energy
Authors: Arif Muhammad , Saeed Anwar , Suttiarporn Panawan , Khan Waris , Kumam Poom , Watthayu Wiboonsak 
Published: December 2022

AbstractThe research of fluid containing nanoparticles for the heat transport characteristics is very famous because of its variety of real-life applications in various thermal systems. Although the thermal efficiency of the nanofluid was effective but still the nano scientists were trying to introduce some new advance class of fluid. Therefore, an advance class of fluid is developed by the dispersion of two different nano sized particles in the conventional base fluid known as “Hybrid nanofluid” which is more effective compared to simple nanofluids in many engineering and industrial applications. Therefore, motivated from the hybrid type of nanofluids in the current research we have taken two-dimensional laminar and steady flow of second grade fluid passing through porous plate. The engine oil base fluid is widely used fluid in the engineering and industrial problems. Keeping these applications in mind the engine oil is considered and two different nanoparticles Copper and aluminum oxide are added in ordered to get the required thermal characteristics. In addition to this the thermal radiation, chemical reaction, activation energy, Brownian motion and thermophoresis are also addressed during the current research. The present proposed higher-order PDE’s is transformed to the non-linear system of ODE’s. For the solution of the proposed high non-linear model HAM method is employed. As the hybrid nanofluid are highlighted on the second-grade fluid flow over a horizontal porous flat plate. During the present analysis and experimental study, it has been proved that the performance of hybrid nanofluid is efficient in many situations compared to nanofluid and regular fluid. For physical interpretation all the flow parameters are discussed through graphs. The impact of volume fraction is also addressed through graphs. Moreover, the comparative analysis between hybrid and nanofluid is carried out and found that hybrid nanofluid performed well as compared to nanofluid and regular fluid. The engineering quantities obtained from the present research have been presented in tables.
Ultrashort spin–orbit torque generated by femtosecond laser pulses
Authors: Janda T. , Ostatnický T. , Němec P. , Schmoranzerová E. , Campion R. , Hills V. , Novák V. , Šobáň Z. , Wunderlich J. 
Published: December 2022

AbstractTo realize the very objective of spintronics, namely the development of ultra-high frequency and energy-efficient electronic devices, an ultrafast and scalable approach to switch magnetic bits is required. Magnetization switching with spin currents generated by the spin–orbit interaction at ferromagnetic/non-magnetic interfaces is one of such scalable approaches, where the ultimate switching speed is limited by the Larmor precession frequency. Understanding the magnetization precession dynamics induced by spin–orbit torques (SOTs) is therefore of great importance. Here we demonstrate generation of ultrashort SOT pulses that excite Larmor precession at an epitaxial Fe/GaAs interface by converting femtosecond laser pulses into high-amplitude current pulses in an electrically biased p-i-n photodiode. We control the polarity, amplitude, and duration of the current pulses and, most importantly, also their propagation direction with respect to the crystal orientation. The SOT origin of the excited Larmor precession was revealed by a detailed analysis of the precession phase and amplitude at different experimental conditions.
Forecasting sub-national trends in COVID-19 vaccine uptake in the UK before vaccine rollout
Authors: de Figueiredo A. 
Published: December 2022

AbstractVaccines have reduced the burden of COVID-19 disease in the UK since their introduction in December 2020. At the time of their introduction, it was unclear the extent to which COVID-19 vaccines would be accepted and how spatial variations in uptake would emerge, driven by socio-demographic characteristics. In this study, data from a large-scale cross-sectional study of over 17,000 adults, surveyed in September and October 2020, was used to provide sub-national forecasts of COVID-19 vaccine uptake across the UK. Bayesian multilevel regression and poststratification was deployed to forecast COVID-19 vaccine acceptance before vaccine rollout across 174 regions of the UK. Although it was found that a majority of the UK adult population would likely take the vaccine, there were substantial heterogeneities in uptake intent across the UK. Large urban areas, including London and North West England, females, Black or Black British ethnicities, and Polish speakers were among the least likely to state an intent to vaccinate. These predicted spatial trends were validated by comparison to observed observed COVID-19 vaccine uptake in late 2021. The methodological approaches deployed in this validated forecasting study may be replicable for the prediction of routine childhood immunisation uptake. Given recent pandemic-induced disruptions to routine immunisation systems, reliable sub-national forecasts of vaccine uptake may provide policymakers and stakeholders early warning signals of potential vaccine confidence issues.
Conventional and synchronous spectrofluorometric determination of the recently administered drugs for treatment of COVID-19 favipiravir and apixaban
Authors: Elama Heba Samir , Zeid Abdallah M. , Shalan Shereen M. , El-Shabrawy Yasser , Eid Manal I. 
Published: December 2022

AbstractCOVID-19 is a fast-spreading pandemic that is caused by SARS-CoV-2 viral pathogen. Combination therapy of the antiviral favipiravir and the anticoagulant apixaban is one of the efficient treatment regimens. Therefore, development of novel and sensitive methods for simultaneous analysis of such combination is highly advantageous. Herein, two eco-friendly, simple, rapid, and cost-effective spectrofluorometric methods were evolved for the estimation of favipiravir and apixaban in pharmaceutical and biological matrices. Method I was based on analysis of favipiravir and apixaban by the first-order derivative of the conventional fluorescence spectra obtained after excitation at 300 nm, where favipiravir and apixaban were detected at 468.8 and 432.0 nm, respectively. Method II relied on dual scan synchronous spectrofluorometry, in which favipiravir was determined at 364 nm using Δλ = 60 nm while apixaban was analyzed at 274 nm using Δλ = 200 nm. Method optimization was performed for selecting the optimum conditions at which maximum sensitivity and selectivity were obtained. This report is the first one that describes simultaneous analysis of favipiravir and apixaban by synchronous spectrofluorometry. The developed methods were successfully applied to evaluate favipiravir and apixaban in spiked human plasma and in pharmaceutical dosages with high %recoveries and low RSD.
Robust meal delivery service for the elderly: a case study in Hong Kong
Authors: Lin Shaochong , Bakker Monique , Leung Eman 
Published: December 2022

AbstractService providers in a community center in Hong Kong deliver meals to community-dwelling elderly, first from a central kitchen to intermediate depots by a van and then to the homes of the elderly via walking. We propose a modified two-echelon vehicle routing model with concerns of both delivery efficiency and workload fairness among workers, incorporating important practical aspects, such as continuity of care and unique features of buildings and served elderly. Notably, we employ robust optimization to address service time uncertainties that differentiate between frail and ordinary elderly. The robust model can be transformed into a mixed integer program, for which we provide two decomposition-based approaches to accelerate computation. Through a real-data case study, we verify the effectiveness of the proposed models. We show that robust solutions can protect against service time variations and achieve better performance while incurring a small additional cost over deterministic ones. We provide insights into choosing the level of conservatism and human resource planning for practitioners.
Juvenile zebrafish (Danio rerio) are able to recover from lordosis
Authors: Printzi A. , Mazurais D. , Witten P. E. , Madec L. , Gonzalez A.-A. , Mialhe X. , Zambonino-Infante J.-L. , Koumoundouros G. 
Published: December 2022

AbstractHaemal lordosis, a frequent skeletal deformity in teleost fish, has long been correlated with increased mechanical loads induced by swimming activity. In the present study, we examine whether juvenile zebrafish can recover from haemal lordosis and explore the musculoskeletal mechanisms involved. Juveniles were subjected to a swimming challenge test (SCT) that induced severe haemal lordosis in 49% of the animals and then immediately transferred them to 0.0 total body lengths (TL) per second of water velocity for a week. The recovery from lordosis was examined by means of whole mount staining, histology and gene expression analysis. Results demonstrate that 80% of the lordotic zebrafish are capable of internal and external recovery within a week after the SCT. Recovered individuals presented normal shape of the vertebral centra, maintaining though distorted internal tissue organization. Through the transcriptomic analysis of the affected haemal regions, several processes related to chromosome organization, DNA replication, circadian clock and transcription regulation were enriched within genes significantly regulated behind this musculoskeletal recovery procedure. Genes especially involved in adipogenesis, bone remodeling and muscular regeneration were regulated. A remodeling tissue-repair hypothesis behind haemal lordosis recovery is raised. Limitations and future possibilities for zebrafish as a model organism to clarify mechanically driven musculoskeletal changes are discussed.