bluuebunny/crossref_metadata_2025 huggingface dataset:
Error-Bounded Learned Scientific Data Compression with Preservation of Derived Quantities
Authors: Lee Jaemoon , Gong Qian , Choi Jong , Banerjee Tania , Klasky Scott , Ranka Sanjay , Rangarajan Anand
Published: July 2022

Scientific applications continue to grow and produce extremely large amounts of data, which require efficient compression algorithms for long-term storage. Compression errors in scientific applications can have a deleterious impact on downstream processing. Thus, it is crucial to preserve all the “known” Quantities of Interest (QoI) during compression. To address this issue, most existing approaches guarantee the reconstruction error of the original data or primary data (PD), but cannot directly control the problem of preserving the QoI. In this work, we propose a physics-informed compression technique that is composed of two parts: (i) reduction of the PD with bounded errors and (ii) preservation of the QoI. In the first step, we combine tensor decompositions, autoencoders, product quantizers, and error-bounded lossy compressors to bound the reconstruction error at high levels of compression. In the second step, we use constraint satisfaction post-processing followed by quantization to preserve the QoI. To illustrate the challenges of reducing the reconstruction errors of the PD and QoI, we focus on simulation data generated by a large-scale fusion code, XGC, which can produce tens of petabytes in a single day. The results show that our approach can achieve a high compression amount while accurately preserving the QoI within scientifically acceptable bounds.
Current Advances in the Concept of Quorum Sensing-Based Prevention of Spoilage of Fish Products by Pseudomonads
Authors: Tomaś Natalia , Myszka Kamila
Published: July 2022

Microbial spoilage of fish is attributed to quorum sensing (QS)-based activities. QS is a communication process between the cells in which microorganisms secrete and sense the specific chemicals (autoinductors, AIs) that regulate proteolysis, lipolysis, and biofilm formation. These activities change the organoleptic characteristics and reduce the safety of the products. Although the microbial community of fish is diverse and may consist of a range of bacterial strains, the deterioration of fish-based products is attributed to the growth and activity of Pseudomonas spp. This work summarizes recent advancements to assess the influence of QS mechanisms on seafood spoilage by Pseudomonas spp. The quorum sensing inhibition (QSI) in the context of fish preservation has also been discussed. Detailed recognition of this phenomenon is crucial in establishing effective strategies to prevent the premature deterioration of fish-based products.
The Approximate Solution of Nonlinear Flexure of a Cantilever Beam with the Galerkin Method
Authors: Zhang Jun , Wu Rongxing , Wang Ji , Ma Tingfeng , Wang Lihong
Published: July 2022

For the optimal design and accurate prediction of structural behavior, the nonlinear analysis of large deformation of elastic beams has broad applications in various engineering fields. In this study, the nonlinear equation of flexure of an elastic beam, also known as an elastica, was solved by the Galerkin method for a highly accurate solution. The numerical results showed that the third-order solution of the rotation angle at the free end of the beam is more accurate and efficient in comparison with results of other approximate methods, and is perfectly consistent with the exact solution in elliptic functions. A general procedure with the Galerkin method is demonstrated for efficient solutions of nonlinear differential equations with the potential for adoption and implementation in more applications.
The Design of a Smart Lower-Limb Prosthesis Supporting People with Transtibial Amputation—A Data Acquisition System
Authors: Pană Cristina Floriana , Manta Liviu Florin , Vladu Ionel Cristian , Cismaru Ștefan Irinel , Petcu (Besnea) Florina Luminița , Cojocaru Dorian , Bîzdoacă Nicu
Published: July 2022

For people with amputated lower limbs, it is imperative to make high-performance prostheses that reproduce, as accurately as possible, the functions of the amputated limb. In this case, a preliminary study of the lower limbs from a kinematic and dynamic point of view is necessary. This paper proposes a prosthesis design and a system for acquiring the information needed to determine the stepping phase kinematic and dynamic parameters of the legs. This system consists of a sensory system attached to the legs and a acquisition data unit built around a microcontroller. The sensory system is based on a sensory system for determining the weight distribution on the sole, made of resistive pressure sensors. The sensory system will be subjected to measurement repeatability and homogeneity tests to evaluate and validate the accuracy and error of the proposed solution. The data obtained by the sensory system is transmitted in real-time, via wi-fi, to a computer system for interpretation. After processing and interpreting the data using standard data sets for comparison, the position of the legs, the type of gait and the phase of movement can be determined. Constructively, the system is configurable and can be adapted to any person, male or female, regardless of shoe size.
Automated Geological Features Detection in 3D Seismic Data Using Semi-Supervised Learning
Authors: Pratama Hadyan , Latiff Abdul Halim Abdul
Published: July 2022

A geological interpretation plays an important role to gain information about the structural and stratigraphic of hydrocarbon reservoirs. However, this is a time-consuming task due to the complexity and size of seismic data. We propose a semi-supervised learning technique to automatically and accurately delineate the geological features from 3D seismic data. To generate labeling data for training the supervised Convolutional Neural Network (CNN) model, we propose an efficient workflow based on unsupervised learning. This workflow utilized seismic attributes and KernelPCA to enhance the visualization of geological targets and clustering the features into binary classes using K-means approach. With this workflow, we are able to develop a data-driven model and reduce human subjectivity. We applied this technique in two cases with different geological settings. The synthetic data and the real seismic investigation from the A Field in the Malay Basin. From this application, we demonstrate that our CNN-based model is highly accurate and consistent with the previous manual interpretation in both cases. In addition to qualitatively evaluating the interpretations, we further extract the predicted result into a 3D geobody. This result could help the interpreter focus on tasks requiring human expertise and aid the model’s prediction in the next studies.
Analysis of Acoustic Emissions for Determination of the Mechanical Effects of Scratch Tests
Authors: Devenport Timothy , Rolfe Bernard , Pereira Michael , Griffin James M.
Published: July 2022

Acoustic Emission (AE) is a promising technique for measuring tool wear online and in real time. In this work, scratch tests were conducted to better understand the “pre-wear” AE response based on loading conditions that were not sufficient to generate galling. The scratch tests used the same type of indenter against two different sheet materials: aluminum and steel. The results showed that AE parameters such as the mean frequency, Centroid frequency and Shannon entropy outperformed other frequency domain techniques by discriminating between the two sheet materials in scratch tests. From the literature, the frequency region of interest was expected to be sub 300 kHz. However, in this study, activity below this threshold was found to be noise, whereas distinct frequencies were found at much higher frequencies than expected. These results are compared against single grit “SG” tests of both mild steel- and nickel-based superalloys to allow comparison of the two test methods and materials used. This comparison showed that the SG tests excited the acoustic emission in ways in which the scratch tests did not. Another factor when using acoustic emissions to monitor sheet metal forming is the differences obtained in energy–frequency mapping, where many report the galling phenomena between a certain amplitude and frequency range. Such results are specific to the setup and the materials/geometries used. Further work presented here compares different scratch tests where energy–frequency mapping is different for different materials/geometries.
A Hybrid Neural Network Model for Predicting Bottomhole Pressure in Managed Pressure Drilling
Authors: Zhu Zhaopeng , Song Xianzhi , Zhang Rui , Li Gensheng , Han Liang , Hu Xiaoli , Li Dayu , Yang Donghan , Qin Furong
Published: July 2022

Managed pressure drilling (MPD) is an essential technology for safe and efficient drilling in deep high-temperature and high-pressure formations with narrow safety pressure windows. However, the complex conditions in deep wells make the mechanism of multiphase flow in drilling annulus complicated and increase the difficulty for accurate prediction of bottomhole pressure (BHP). Recently, an increasing volume of research shows that intelligent technology is an efficient means of accurately predicting BHP. However, few studies have focused on the temporal properties and variation mechanism of BHP. In this paper, hybrid neural network prediction models based on the multi-branch parallel are established by combining the different advantages of back propagation (BP), long short-term memory (LSTM), and a one-dimensional convolutional neural network (1DCNN) model. The results show that the relative error of the best model is about 70% lower than the optimal single intelligent model. Preliminary experimental results reveal that the hybrid models combine the advantages of different single models, which is more accurate and robust for extracting the temporal features of MWD. Finally, based on the trend analysis, the validity of the hybrid model is further verified. This study provides a reference for solving the problem of optimizing temporal characteristics and guidance for fine pressure control in complex formations.
Tilted Implants and Sinus Floor Elevation Techniques Compared in Posterior Edentulous Maxilla: A Retrospective Clinical Study over Four Years of Follow-Up
Authors: Gherlone Enrico , D’Orto Bianca , Nagni Matteo , Capparè Paolo , Vinci Raffaele
Published: July 2022

The aim of this study was to evaluate the implant survival rate, marginal bone loss, and surgical and prosthetic complications of implants placed through sinus floor elevation and tilted implants engaged in basal bone to bypass the maxillary sinus. Sixty patients were enrolled for this study. According to the residual bone height of the posterior maxilla, the sample was divided into three groups of 20 patients: Group A (lateral sinus floor elevation), Group B (transcrestal sinus floor elevation), and Group C (tilted implants employed to bypass the sinus floor). Follow-up visits were performed one week after surgery, at three and six months, and then once a year for the next 4 years. The outcomes were the implant survival rate, marginal bone loss, and surgical and prosthetic complications. Although Groups A, B, and C demonstrated implant survival rates of 83.3%, 86.7%, and 98.3%, respectively, the statistical analysis showed no statistically significant difference between groups. Statistically significant differences between groups were also not found concerning marginal bone loss, as recorded by intra-oral X-ray measurements during follow-up examinations. Regarding complications, it was not possible to perform a statistical analysis. To reduce possible surgical risks, implant placement in basal bone could be preferred.
ExCrowd: A Blockchain Framework for Exploration-Based Crowdsourcing
Authors: Kodjiku Seth Larweh , Fang Yili , Han Tao , Asamoah Kwame Omono , Aggrey Esther Stacy E. B. , Sey Collins , Aidoo Evans , Ejianya Victor Nonso , Wang Xun
Published: July 2022

Because of the rise of cryptocurrencies and decentralized apps, blockchain technology has generated a lot of interest. Among these is the emergent blockchain-based crowdsourcing paradigm, which eliminates the centralized conventional mechanism servers in favor of smart contracts for task and reward allocation. However, there are a few crucial challenges that must be resolved properly. For starters, most reputation-based systems favor high-performing employees. Secondly, the crowdsourcing platform’s expensive service charges may obstruct the growth of crowdsourcing. Finally, unequal evaluation and reward allocation might lead to job dissatisfaction. As a result, the aforementioned issues will substantially impede the development of blockchain-based crowdsourcing systems. In this study, we introduce ExCrowd, a blockchain-based crowdsourcing system that employs a smart contract as a trustworthy authority to properly select workers, assess inputs, and award incentives while maintaining user privacy. Exploration-based crowdsourcing employs the hyperbolic learning curve model based on the conduct of workers and analyzes worker performance patterns using a decision tree technique. We specifically present the architecture of our framework, on which we establish a concrete scheme. Using a real-world dataset, we implement our model on the Ethereum public test network leveraging its reliability, adaptability, scalability, and rich statefulness. The results of our experiments demonstrate the efficiency, usefulness, and adaptability of our proposed system.
Remote Sensing of the Water Quality Parameters for a Shallow Dam Reservoir
Authors: Bielski Andrzej , Toś Cezary
Published: July 2022

This study examines the chlorophyll a content and turbidity in the shallow dam reservoir of Lake Dobczyce. The analysis of satellite images for thirteen wavelength ranges enabled the selection of wavelengths applicable for a remote determination of chlorophyll a and turbidity. The selection was completed as the test of the significance of the coefficients in the equation, which calculates the values of the parameters on the basis of reflectance. The reflectance of the reservoir surface differs from the reflectance of individual water components, and the overlapping of spectral curves makes it difficult to isolate the significant reflectance. In the case of Lake Dobczyce, the significant reflectance was for wavelengths 665, 705, 740, and 842 nm (chlorophyll a) and for wavelengths 705, 740, and 783 nm (turbidity). In the model, the natural logarithm of chlorophyll a or turbidity was a linear combination of the natural log reflectance and the squares of those logarithms. A lake surface reflectance also includes the bottom reflectance. The reflectance obtained from the Sentinel-2 satellite was corrected with a bottom reflectance determined using the Lambert–Beer equation. The reflectance of a given surface may vary with the position of both the satellite and the sun, atmospheric pollution, and other factors. Correction of reflectance from satellite measurements was performed, as reflectance changes for the reference surface; the reference reflectance was assumed as the first reflectance of the reference surface observed during the study. The models helped to develop the maps of turbidity and chlorophyll a content in the lake.
Experimental Determination of Lamb-Wave Attenuation Coefficients
Authors: Ono Kanji
Published: July 2022

This work determined the attenuation coefficients of Lamb waves of ten engineering materials and compared the results with calculated Lamb-wave attenuation coefficients, α–S and α–A. The Disperse program and a parametric method based on Disperse results were used for calculations. Bulk-wave attenuation coefficients, αL and αT, were required as input parameters to the Disperse calculations. The calculated α–S and α–A values were found to be dominated by the αT contribution. Often α–Ao coincided with αT. The values of αL and αT were previously obtained or newly measured. Attenuation measurement relied on Lamb-wave generation by pulsed excitation of ultrasonic transducers and on surface-displacement detection with point contact receivers. The frequency used ranged from 10 kHz to 1 MHz. A total of 14 sheet and plate samples were evaluated. Sample materials ranged from steel, Al, and silicate glass with low attenuation to polymers and a fiber composite with much higher attenuation. Experimentally obtained Lamb-wave attenuation coefficients, α–S and α–A, for symmetric and asymmetric modes, were mostly for the zeroth mode. Plots of α–So and α–Ao values against frequency were found to coincide reasonably well to theoretically calculated curves. This study confirmed that the Disperse program predicts Lamb-wave attenuation coefficients for elastically isotropic materials within the limitation of the contact ultrasonic techniques used. Further refinements in experimental methods are needed, as large deviations often occurred, especially at low and high frequencies. Methods of refinement are suggested. Displacement measurements were quantified using Rayleigh wave calibration. For signals below 300 kHz, 1-mV receiver output corresponded to 1-pm displacement. Peak displacements after 200-mm propagation were found to range from 10 pm to 1.5 nm. With the use of signal averaging, the point-contact sensor was capable of detecting 1-pm displacement with 40 dB signal-to-noise ratio and had equivalent noise of 4.3 fm/√Hz. Approximate expressions for α–So and α–Ao were obtained, and an empirical correlation was found between bulk-wave attenuation coefficients, i.e., αT = 2.79 αL, for over 150 materials.
Solar Ultraviolet Radiation Temporal Variability Analysis from 2-Year of Continuous Observation in an Amazonian City of Brazil
Authors: Reis Gabriela , Souza Samuel , Neto Helvécio , Branches Rardiles , Silva Rodrigo , Peres Lucas , Pinheiro Damaris , Lamy Kevin , Bencherif Hassan , Portafaix Thierry
Published: July 2022

Solar ultraviolet radiation (UVR) is a highly energetic component of the solar spectrum that needs to be monitored because of the effects on human health and on the ecosystems. In Brazil, few cities monitor UVR, especially in the Amazon region which is particularly poor in observation. This work is the first to address the short-term (2-year) time variability of UVR in Santarém (2°25′ S, 54°44′ W, 51 m) using ground-based measurements. The irradiance in the wavelength range of 250–400 nm was investigated on different time scales. Furthermore, to understand how the UVR varies without the influence of clouds, the hours corresponding to the clear sky condition were analyzed as well as the hours in all sky conditions. Regarding the averages, there is a slight variation over the year. In all sky and clear sky conditions, the dry season had a higher average than the rainy season, despite the slight difference. Also, both in all-sky and clear-sky conditions the maximums occurred around local solar noon, and reached a maximum of 87 W/m2 in the dry season under the clear sky condition. Further understanding of the radiative effects of the clouds in UVR time variability is considered essential for future research. This study can serve as a reference for UVR levels in this region where no other ground-based UVR measurements are made.
Improved Chen’s Inequalities for Submanifolds of Generalized Sasakian-Space-Forms
Authors: Li Yanlin , Khatri Mohan , Singh Jay Prakash , Chaubey Sudhakar K.
Published: July 2022

In this article, we derive Chen’s inequalities involving Chen’s δ-invariant δM, Riemannian invariant δ(m1,⋯,mk), Ricci curvature, Riemannian invariant Θk(2≤k≤m), the scalar curvature and the squared of the mean curvature for submanifolds of generalized Sasakian-space-forms endowed with a quarter-symmetric connection. As an application of the obtain inequality, we first derived the Chen inequality for the bi-slant submanifold of generalized Sasakian-space-forms.
Upgrading the Properties of Ceramic-Coated Separators for Lithium Secondary Batteries by Changing the Mixing Order of the Water-Based Ceramic Slurry Components
Authors: Kennedy Ssendagire , Kim Jeong-Tae , Lee Yong Min , Phiri Isheunesu , Ryou Sun-Yul
Published: July 2022

Developing uniform ceramic-coated separators in high-energy Li secondary batteries has been a challenging task because aqueous ceramic coating slurries have poor dispersion stability and coating quality on the hydrophobic surfaces of polyolefin separators. In this study, we develop a simple but effective strategy for improving the dispersion stability of aqueous ceramic coating slurries by changing the mixing order of the ceramic slurry components. The aqueous ceramic coating slurry comprises ceramics (Al2O3), polymeric binders (sodium carboxymethyl cellulose, CMC), surfactants (disodium laureth sulfosuccinate, DLSS), and water. The interaction between the ceramic slurry components is studied by changing the mixing order of the ceramic slurry components and quantitatively evaluating the dispersion stability of the ceramic coating slurry using a Lumisizer. In the optimized mixing sequence, Al2O3 and DLSS premixed in aqueous Al2O3-DLSS micelles through strong surface interactions, and they repel each other due to steric repulsion. The addition of CMC in this state does not compromise the dispersion stability of aqueous ceramic coating slurries and enables uniform ceramic coating on polyethylene (PE) separators. The prepared Al2O3 ceramic-coated separators (Al2O3–CCSs) exhibit improved physical properties, such as high wettability electrolyte uptake and ionic conductivity, compared to the bare PE separators. Furthermore, Al2O3–CCSs exhibit improved electrochemical performance, such as rate capability and cycling performance. The half cells (LiMn2O4/Li metal) comprising Al2O3–CCSs retain 90.4% (88.4 mAh g−1) of initial discharge capacity after 150 cycles, while 27.6% (26.4 mAh g−1) for bare PE. Furthermore, the full cells (LiMn2O4/graphite) consisting of Al2O3–CCSs exhibit 69.8% (72.2 mAh g−1) of the initial discharge capacity and 24.9% (25.0 mAh g−1) for bare PE after 1150 cycles.
Atto488-Agitoxin 2—A Fluorescent Ligand with Increased Selectivity for Kv1.3 Channel Binding Site
Authors: Denisova Kristina R. , Orlov Nikita A. , Yakimov Sergey A. , Kirpichnikov Mikhail P. , Feofanov Alexey V. , Nekrasova Oksana V.
Published: July 2022

Fluorescently labeled peptide blockers of ion channels are useful probes in studying the localization and functioning of the channels and in the performance of a search for new channel ligands with bioengineering screening systems. Here, we report on the properties of Atto488-agitoxin 2 (A-AgTx2), a derivative of the Kv1 channel blocker agitoxin 2 (AgTx2), which was N-terminally labeled with Atto 488 fluorophore. The interactions of A-AgTx2 with the outer binding sites of the potassium voltage-gated Kv1.x (x = 1, 3, 6) channels were studied using bioengineered hybrid KcsA–Kv1.x (x = 1, 3, 6) channels. In contrast to AgTx2, A-AgTx2 was shown to lose affinity for the Kv1.1 and Kv1.6 binding sites but to preserve it for the Kv1.3 site. Thus, Atto488 introduces two new functionalities to AgTx2: fluorescence and the selective targeting of the Kv1.3 channel, which is known for its pharmacological significance. In the case of A-AgTx2, fluorescent labeling served as an alternative to site-directed mutagenesis in modulating the pharmacological profile of the channel blocker. Although the affinity of A-AgTx2 for the Kv1.3 binding site was decreased as compared to the unlabeled AgTx2, its dissociation constant value was within a low nanomolar range (4.0 nM). The properties of A-AgTx2 allow one to use it for the search and study of Kv1.3 channel blockers as well as to consider it for the imaging of the Kv1.3 channel in cells and tissues.
Ontogenetic Patterning of Human Subchondral Bone Microarchitecture in the Proximal Tibia
Authors: Goliath Jesse R. , Gosman James H. , Stout Sam D. , Ryan Timothy M.
Published: July 2022

High-resolution computed tomography images were acquired for 31 proximal human tibiae, age 8 to 37.5 years, from Norris Farms #36 cemetery site (A.D. 1300). Morphometric analysis of subchondral cortical and trabecular bone architecture was performed between and within the tibial condyles. Kruskal–Wallis and Wilcoxon signed-rank tests were used to examine the association between region, age, body mass, and each morphometric parameter. The findings indicate that age-related changes in mechanical loading have varied effects on subchondral bone morphology. With age, trabecular microstructure increased in bone volume fraction (p = 0.033) and degree of anisotropy (p = 0.012), and decreased in connectivity density (p = 0.001). In the subchondral cortical plate, there was an increase in thickness (p < 0.001). When comparing condylar regions, only degree of anisotropy differed (p = 0.004) between the medial and lateral condyles. Trabeculae in the medial condyle were more anisotropic than in the lateral region. This research represents an innovative approach to quantifying both cortical and trabecular subchondral bone microarchitecture in archaeological remains.
Role of Pyroptosis in Gynecological Oncology and Its Therapeutic Regulation
Authors: Huang Yi , Li Ruiyun , Yang Yuan
Published: July 2022

With the continuous advances in molecular biotechnology, many new cell death methods have been discovered. Pyroptosis is a programmed cell death process that differs from apoptosis and autophagy in cell morphology and function. Compared with apoptosis and autophagy, pyroptosis is primarily mediated by intracellular inflammasome and gasdermin D of the gasdermin protein family and involves the release of numerous inflammatory factors. Pyroptosis has been found to be involved in the occurrence and development of infectious diseases and other diseases involving the nervous system and the cardiovascular system. Recent studies have also reported the occurrence of pyroptosis in tumor cells. Accordingly, exploring its effect on tumors has become one of the research hotspots. Herein, recent research progress on pyroptosis is reviewed, especially its role in the development of gynecological tumors. As the pathogenesis of gynecological tumor is better understood, new targets have been introduced for the prevention and clinical treatment of gynecological tumors.
The Multifaceted Role of the Ubiquitin Proteasome System in Pathogenesis and Diseases
Authors: Stekel Zane , Sheng Yi , Zhang Wei
Published: July 2022

Ubiquitin is a small protein that is conjugated to target proteins to signal a great number of critical biological processes. Impaired ubiquitin signaling and defects in the ubiquitin proteasome system (UPS) surveillance are implicated in many human diseases, including cancer. Characterization of the physiological roles of UPS components and their regulatory mechanisms is therefore vital for the identification of therapeutic targets and the development of tools and paradigms to better understand and treat human diseases. In this Special Issue, we assembled seven original research and review articles to provide insights on the multifaceted role of the UPS in pathogenesis and disease, covering the areas of molecular and cellular mechanisms of UPS enzymes, biochemical and biophysical characterization strategies, drug development, and targeted protein degradation.
Physicochemical and Techno-Functional Properties of Dried and Defatted Porcine Liver
Authors: Abril Blanca , Sánchez-Torres Eduardo A. , Toldrà Mònica , Benedito Jose , García-Pérez Jose V.
Published: July 2022

Porcine liver has a high nutritional value and is rich in proteins, minerals, and vitamins, making it an interesting co-product to alleviate the growing global demand for protein. The objective of this study was to analyze how the drying and defatting processes of porcine liver affect the physicochemical and techno-functional properties of its proteins. Two drying temperatures (40 and 70 °C) were studied, and dried samples were defatted using organic solvents. The drying process turned out to be an effective method for the stabilization of the protein fraction; however, when the drying temperature was high (70 °C), greater protein degradation was found compared to drying at a moderate temperature (40 °C). Regarding the defatting stage, it contributed to an improvement in certain techno-functional properties of the liver proteins, such as the foaming capacity (the average of the dried and defatted samples was 397% higher than the dried samples), with the degree of foaming stability in the liver dried at 40 °C and defatted being the highest (13.76 min). Moreover, the emulsifying capacity of the different treatments was not found to vary significantly (p > 0.05). Therefore, the conditions of the drying and defatting processes conducted prior to the extraction of liver proteins must be properly adjusted to maximize the stability, quality, and techno-functional properties of the proteins.
NMR Reveals Specific Tracts within the Intrinsically Disordered Regions of the SARS-CoV-2 Nucleocapsid Protein Involved in RNA Encountering
Authors: Pontoriero Letizia , Schiavina Marco , Korn Sophie M. , Schlundt Andreas , Pierattelli Roberta , Felli Isabella C.
Published: July 2022

The SARS-CoV-2 nucleocapsid (N) protein is crucial for the highly organized packaging and transcription of the genomic RNA. Studying atomic details of the role of its intrinsically disordered regions (IDRs) in RNA recognition is challenging due to the absence of structure and to the repetitive nature of their primary sequence. IDRs are known to act in concert with the folded domains of N and here we use NMR spectroscopy to identify the priming events of N interacting with a regulatory SARS-CoV-2 RNA element. 13C-detected NMR experiments, acquired simultaneously to 1H detected ones, provide information on the two IDRs flanking the N-terminal RNA binding domain (NTD) within the N-terminal region of the protein (NTR, 1–248). We identify specific tracts of the IDRs that most rapidly sense and engage with RNA, and thus provide an atom-resolved picture of the interplay between the folded and disordered regions of N during RNA interaction.
MicroRNAs at the Crossroad between Immunoediting and Oncogenic Drivers in Hepatocellular Carcinoma
Authors: Gramantieri Laura , Fornari Francesca , Giovannini Catia , Trerè Davide
Published: July 2022

Treatments aimed to reverse the tumor-induced immune tolerance represent a promising approach for advanced hepatocellular carcinoma (HCC). Notwithstanding, primary nonresponse, early, and late disease reactivation still represent major clinical challenges. Here, we focused on microRNAs (miRNAs) acting both as modulators of cancer cell hallmarks and immune system response. We outlined the bidirectional function that some oncogenic miRNAs play in the differentiation and program activation of the immune system development and, at the same time, in the progression of HCC. Indeed, the multifaceted spectrum of miRNA targets allows the modulation of both immune-associated factors and oncogenic or tumor suppressor drivers at the same time. Understanding the molecular changes contributing to disease onset, progression, and resistance to treatments might help to identify possible novel biomarkers for selecting patient subgroups, and to design combined tailored treatments to potentiate antitumor approaches. Preliminary findings seem to argue in favor of a bidirectional function of some miRNAs, which enact an effective modulation of molecular pathways driving oncogenic and immune-skipping phenotypes associated with cancer aggressiveness. The identification of these miRNAs and the characterization of their ‘dual’ role might help to unravel novel biomarkers identifying those patients more likely to respond to immune checkpoint inhibitors and to identify possible therapeutic targets with both antitumor and immunomodulatory functions. In the present review, we will focus on the restricted panel of miRNAs playing a bidirectional role in HCC, influencing oncogenic and immune-related pathways at once. Even though this field is still poorly investigated in HCC, it might represent a source of candidate molecules acting as both biomarkers and therapeutic targets in the setting of immune-based treatments.
Prediction of circRNA-Disease Associations Based on the Combination of Multi-Head Graph Attention Network and Graph Convolutional Network
Authors: Cao Ruifen , He Chuan , Wei Pijing , Su Yansen , Xia Junfeng , Zheng Chunhou
Published: July 2022

Circular RNAs (circRNAs) are covalently closed single-stranded RNA molecules, which have many biological functions. Previous experiments have shown that circRNAs are involved in numerous biological processes, especially regulatory functions. It has also been found that circRNAs are associated with complex diseases of human beings. Therefore, predicting the associations of circRNA with disease (called circRNA-disease associations) is useful for disease prevention, diagnosis and treatment. In this work, we propose a novel computational approach called GGCDA based on the Graph Attention Network (GAT) and Graph Convolutional Network (GCN) to predict circRNA-disease associations. Firstly, GGCDA combines circRNA sequence similarity, disease semantic similarity and corresponding Gaussian interaction profile kernel similarity, and then a random walk with restart algorithm (RWR) is used to obtain the preliminary features of circRNA and disease. Secondly, a heterogeneous graph is constructed from the known circRNA-disease association network and the calculated similarity of circRNAs and diseases. Thirdly, the multi-head Graph Attention Network (GAT) is adopted to obtain different weights of circRNA and disease features, and then GCN is employed to aggregate the features of adjacent nodes in the network and the features of the nodes themselves, so as to obtain multi-view circRNA and disease features. Finally, we combined a multi-layer fully connected neural network to predict the associations of circRNAs with diseases. In comparison with state-of-the-art methods, GGCDA can achieve AUC values of 0.9625 and 0.9485 under the results of fivefold cross-validation on two datasets, and AUC of 0.8227 on the independent test set. Case studies further demonstrate that our approach is promising for discovering potential circRNA-disease associations.
Effects of In Vivo Intracellular ATP Modulation on Neocortical Extracellular Potassium Concentration
Authors: EbrahimAmini Azin , Stefanovic Bojana , Carlen Peter L.
Published: July 2022

Neuronal and glial activity are dependent on the efflux of potassium ions into the extracellular space. Efflux of K is partly energy-dependent as the activity of pumps and channels which are involved in K transportation is ATP-dependent. In this study, we investigated the effect of decreased intracellular ATP concentration ([ATP]i) on the extracellular potassium ion concentration ([K]o). Using in vivo electrophysiological techniques, we measured neocortical [K]o and the local field potential (LFP) while [ATP]i was reduced through various pharmacological interventions. We observed that reducing [ATP]i led to raised [K]o and DC-shifts resembling spreading depolarization-like events. We proposed that most likely, the increased [K]o is mainly due to the impairment of the Na/K ATPase pump and the ATP-sensitive potassium channel in the absence of sufficient ATP, because Na/K ATPase inhibition led to increased [K]o and ATP-sensitive potassium channel impairment resulted in decreased [K]o. Therefore, an important consequence of decreased [ATP]i is an increased [K]o. The results of this study acknowledge one of the mechanisms involved in [K]o dynamics.
Creating an Optimal In Vivo Environment to Enhance Outcomes Using Cell Therapy to Repair/Regenerate Injured Tissues of the Musculoskeletal System
Authors: Hart David A. , Nakamura Norimasa
Published: July 2022

Following most injuries to a musculoskeletal tissue which function in unique mechanical environments, an inflammatory response occurs to facilitate endogenous repair. This is a process that usually yields functionally inferior scar tissue. In the case of such injuries occurring in adults, the injury environment no longer expresses the anabolic processes that contributed to growth and maturation. An injury can also contribute to the development of a degenerative process, such as osteoarthritis. Over the past several years, researchers have attempted to use cellular therapies to enhance the repair and regeneration of injured tissues, including Platelet-rich Plasma and mesenchymal stem/medicinal signaling cells (MSC) from a variety of tissue sources, either as free MSC or incorporated into tissue engineered constructs, to facilitate regeneration of such damaged tissues. The use of free MSC can sometimes affect pain symptoms associated with conditions such as OA, but regeneration of damaged tissues has been challenging, particularly as some of these tissues have very complex structures. Therefore, implanting MSC or engineered constructs into an inflammatory environment in an adult may compromise the potential of the cells to facilitate regeneration, and neutralizing the inflammatory environment and enhancing the anabolic environment may be required for MSC-based interventions to fulfill their potential. Thus, success may depend on first eliminating negative influences (e.g., inflammation) in an environment, and secondly, implanting optimally cultured MSC or tissue engineered constructs into an anabolic environment to achieve the best outcomes. Furthermore, such interventions should be considered early rather than later on in a disease process, at a time when sufficient endogenous cells remain to serve as a template for repair and regeneration. This review discusses how the interface between inflammation and cell-based regeneration of damaged tissues may be at odds, and outlines approaches to improve outcomes. In addition, other variables that could contribute to the success of cell therapies are discussed. Thus, there may be a need to adopt a Precision Medicine approach to optimize tissue repair and regeneration following injury to these important tissues.
Saxagliptin Cardiotoxicity in Chronic Heart Failure: The Role of DPP4 in the Regulation of Neuropeptide Tone
Authors: Vörös Imre , Onódi Zsófia , Tóth Viktória Éva , Gergely Tamás G. , Sághy Éva , Görbe Anikó , Kemény Ágnes , Leszek Przemyslaw , Helyes Zsuzsanna , Ferdinandy Péter , Varga Zoltán V.
Published: July 2022

Dipeptidyl-peptidase-4 (DPP4) inhibitors are novel medicines for diabetes. The SAVOR-TIMI-53 clinical trial revealed increased heart-failure-associated hospitalization in saxagliptin-treated patients. Although this side effect could limit therapeutic use, the mechanism of this potential cardiotoxicity is unclear. We aimed to establish a cellular platform to investigate DPP4 inhibition and the role of its neuropeptide substrates substance P (SP) and neuropeptide Y (NPY), and to determine the expression of DDP4 and its neuropeptide substrates in the human heart. Western blot, radio-, enzyme-linked immuno-, and RNA scope assays were performed to investigate the expression of DPP4 and its substrates in human hearts. Calcein-based viability measurements and scratch assays were used to test the potential toxicity of DPP4 inhibitors. Cardiac expression of DPP4 and NPY decreased in heart failure patients. In human hearts, DPP4 mRNA is detectable mainly in cardiomyocytes and endothelium. Treatment with DPP4 inhibitors alone/in combination with neuropeptides did not affect viability but in scratch assays neuropeptides decreased, while saxagliptin co-administration increased fibroblast migration in isolated neonatal rat cardiomyocyte-fibroblast co-culture. Decreased DPP4 activity takes part in the pathophysiology of end-stage heart failure. DPP4 compensates against the elevated sympathetic activity and altered neuropeptide tone. Its inhibition decreases this adaptive mechanism, thereby exacerbating myocardial damage.
Klotho Modulates Pro-Fibrotic Activities in Human Atrial Fibroblasts through Inhibition of Phospholipase C Signaling and Suppression of Store-Operated Calcium Entry
Authors: Hung Yuan , Chung Cheng-Chih , Chen Yao-Chang , Kao Yu-Hsun , Lin Wei-Shiang , Chen Shih-Ann , Chen Yi-Jen
Published: July 2022

Background: Atrial fibroblasts activation causes atrial fibrosis, which is one major pathophysiological contributor to atrial fibrillation (AF) genesis. Klotho is a pleiotropic protein with remarkable cardiovascular effects, including anti-inflammatory, anti-oxidative, and anti-apoptotic effects. This study investigated whether Klotho can modulate the activity of human atrial fibroblasts and provides an anti-fibrotic effect. Methods: Cell migration assay and proliferation assay were used to investigate fibrogenesis activities in single human atrial fibroblasts with or without treatment of Klotho (10 and 100 pM, 48 h). Calcium fluorescence imaging, the whole-cell patch-clamp, and Western blotting were performed in human atrial fibroblasts treated with and without Klotho (100 pM, 48 h) to evaluate the store-operated calcium entry (SOCE), transient receptor potential (TRP) currents, and downstream signaling. Results: High dose of Klotho (100 pM, 48 h) significantly reduced the migration of human atrial fibroblasts without alternating their proliferation; in addition, treatment of Klotho (100 pM, 48 h) also decreased SOCE and TRP currents. In the presence of BI-749327 (a selective canonical TRP 6 channel inhibitor, 1 μM, 48 h), Klotho (100 pM, 48 h) could not inhibit fibroblast migration nor suppress the TRP currents. Klotho-treated fibroblasts (100 pM, 48 h) had lower phosphorylated phospholipase C (PLC) (p-PLCβ3 Ser537) expression than the control. The PLC inhibitor, U73122 (1 μM, 48 h), reduced the migration, decreased SOCE and TRP currents, and lowered p-PLCβ3 in atrial fibroblasts, similar to Klotho. In the presence of the U73122 (1 μM, 48 h), Klotho (100 pM, 48 h) could not further modulate the migration and collagen synthesis nor suppress the TRP currents in human atrial fibroblasts. Conclusions: Klotho inhibited pro-fibrotic activities and SOCE by inhibiting the PLC signaling and suppressing the TRP currents, which may provide a novel insight into atrial fibrosis and arrhythmogenesis.
Interactions between Obstructive Sleep Apnea Syndrome Severity, Obesity, Sex Difference and Attention-Deficit/Hyperactivity Disorder on Health-Related Quality of Life: A Non-Interventional Prospective Observational Study
Authors: Chen Yu-Hsuan , Wu Ming-Feng , Wen Chih-Yu , Chang Shih-Pei , Lin Ching-Yi , Chen Yi-Chan , Lin Ching-Cheng , Chen Hui-Chen , Huang Wei-Chang , Chang Kai-Ming
Published: July 2022

Obstructive sleep apnea syndrome (OSAS) severity, obesity, sex difference, and attention-deficit/hyperactivity disorder (ADHD) had a complex impact on health-related quality of life (HRQoL). However, the interactive effects among these features on HRQoL remained to be clarified. This study aimed to investigate the individual and interactive associations between the four characteristics of interest and HRQoL as determined by 36-Item Short Form Health Survey, Pittsburgh Sleep Quality Index (PSQI), and Epworth Sleepiness Scale (ESS). This non-interventional, prospective, observational study enrolled a total of 132 patients with suspected OSAS for analysis. While OSAS severity and ADHD detected by adult ADHD Self-Report Scale, termed as screened ADHD, interact with each other, all the four studied features were individually associated with HRQoL. After adjusting for potential physiological and polysomnographic confounders, screened ADHD was independently correlated with PSQI > 5 (OR = 4.126, 95% CI, 1.490–11.424), mental component score < 50 (OR = 5.873, 95% CI, 2.262–15.251) and ESS > 10 (OR = 3.648, 95% CI, 1.738–7.657). Our results show that ADHD detection is necessary and should be incorporated into clinical practice for OSAS management.
Apolipoprotein A-II, a Player in Multiple Processes and Diseases
Authors: Florea Gabriela , Tudorache Irina Florina , Fuior Elena Valeria , Ionita Radu , Dumitrescu Madalina , Fenyo Ioana Madalina , Bivol Violeta Georgeta , Gafencu Anca Violeta
Published: July 2022

Apolipoprotein A-II (apoA-II) is the second most abundant apolipoprotein in high-density lipoprotein (HDL) particles, playing an important role in lipid metabolism. Human and murine apoA-II proteins have dissimilar properties, partially because human apoA-II is dimeric whereas the murine homolog is a monomer, suggesting that the role of apoA-II may be quite different in humans and mice. As a component of HDL, apoA-II influences lipid metabolism, being directly or indirectly involved in vascular diseases. Clinical and epidemiological studies resulted in conflicting findings regarding the proatherogenic or atheroprotective role of apoA-II. Human apoA-II deficiency has little influence on lipoprotein levels with no obvious clinical consequences, while murine apoA-II deficiency causes HDL deficit in mice. In humans, an increased plasma apoA-II concentration causes hypertriglyceridemia and lowers HDL levels. This dyslipidemia leads to glucose intolerance, and the ensuing high blood glucose enhances apoA-II transcription, generating a vicious circle that may cause type 2 diabetes (T2D). ApoA-II is also used as a biomarker in various diseases, such as pancreatic cancer. Herein, we provide a review of the most recent findings regarding the roles of apoA-II and its functions in various physiological processes and disease states, such as cardiovascular disease, cancer, amyloidosis, hepatitis, insulin resistance, obesity, and T2D.
Dirty Jobs: Macrophages at the Heart of Cardiovascular Disease
Authors: Stevens Travis W. , Khalaf Fatimah K. , Soehnlen Sophia , Hegde Prajwal , Storm Kyle , Meenakshisundaram Chandramohan , Dworkin Lance D. , Malhotra Deepak , Haller Steven T. , Kennedy David J. , Dube Prabhatchandra
Published: July 2022

Cardiovascular disease (CVD) is one of the greatest public health concerns and is the leading cause of morbidity and mortality in the United States and worldwide. CVD is a broad yet complex term referring to numerous heart and vascular conditions, all with varying pathologies. Macrophages are one of the key factors in the development of these conditions. Macrophages play diverse roles in the maintenance of cardiovascular homeostasis, and an imbalance of these mechanisms contributes to the development of CVD. In the current review, we provide an in-depth analysis of the diversity of macrophages, their roles in maintaining tissue homeostasis within the heart and vasculature, and the mechanisms through which imbalances in homeostasis may lead to CVD. Through this review, we aim to highlight the potential importance of macrophages in the identification of preventative, diagnostic, and therapeutic strategies for patients with CVD.