bluuebunny/crossref_metadata_2025 huggingface dataset:
Using Optimisation Meta-Heuristics for the Roughness Estimation Problem in River Flow Analysis
Authors: Agresta Antonio , Baioletti Marco , Biscarini Chiara , Caraffini Fabio , Milani Alfredo , Santucci Valentino
Published: November 2021

Climate change threats make it difficult to perform reliable and quick predictions on floods forecasting. This gives rise to the need of having advanced methods, e.g., computational intelligence tools, to improve upon the results from flooding events simulations and, in turn, design best practices for riverbed maintenance. In this context, being able to accurately estimate the roughness coefficient, also known as Manning’s n coefficient, plays an important role when computational models are employed. In this piece of research, we propose an optimal approach for the estimation of ‘n’. First, an objective function is designed for measuring the quality of ‘candidate’ Manning’s coefficients relative to specif cross-sections of a river. Second, such function is optimised to return coefficients having the highest quality as possible. Five well-known meta-heuristic algorithms are employed to achieve this goal, these being a classic Evolution Strategy, a Differential Evolution algorithm, the popular Covariance Matrix Adaptation Evolution Strategy, a classic Particle Swarm Optimisation and a Bayesian Optimisation framework. We report results on two real-world case studies based on the Italian rivers ‘Paglia’ and ‘Aniene’. A comparative analysis between the employed optimisation algorithms is performed and discussed both empirically and statistically. From the hydrodynamic point of view, the experimental results are satisfactory and produced within significantly less computational time in comparison to classic methods. This shows the suitability of the proposed approach for optimal estimation of the roughness coefficient and, in turn, for designing optimised hydrological models.
Blockchain-Based Healthcare Information Preservation Using Extended Chaotic Maps for HIPAA Privacy/Security Regulations
Authors: Lee Tian-Fu , Chang I-Pin , Kung Ting-Shun
Published: November 2021

A healthcare information system allows patients and other users to remotely login to medical services to access health data through the Internet. To protect the privacy of patients and security over the public network, secure communication is required. Therefore, the security of data in transmission has been attracting increasing attention. In recent years, blockchain technology has also attracted more attention. Relevant research has been published at a high rate. Most methods of satisfying relevant security-related regulations use modular and exponential calculation. This study proposes a medical care information preservation mechanism that considers the entire process of data storage in devices from wearable devices to mobile devices to medical center servers. The entire process is protected and complies with HIPAA privacy and security regulations. The proposed scheme uses extended chaotic map technology to develop ID-based key negotiation for wearable devices, and thereby reduces the amount of computing that must be carried out by wearable devices and achieve lightness quantify. It also uses the non-tamperability of the blockchain to ensure that the data have not been tampered with, improving data security. The proposed mechanism can resist a variety of attacks and is computationally lighter than the elliptic curve point multiplication that has been used elsewhere, while retaining its security characteristics.
Validation of Smartphone Sway Analysis for Fall Prevention
Authors: Cimera Matthew , Voloshin Arkady
Published: November 2021

Analysis of the balance and sway of the elderly remains a field continuously studied for additional means of assessing the risks of falls. Almost 50% of falls among the elderly lead to serious injuries, and falls are the leading cause of death for the elderly. Thus, the development of a convenient method to assess the risks of falling would be beneficial in helping to diminish these risks. We recorded the sway data by using the widely acceptable force plate and simultaneously compared it to the angular orientation measured by a cell phone’s accelerometer attached to the subject. It was found that the correlation of the average path length and average velocity between the results from the force plate and the phone application were 0.83 and 0.86 respectively. Overall, the direction of the strongest correlation was in the anterior–posterior (AP) direction that is mostly associated with falls. The smart phone application was able to represent the results that were gathered by the force plate, thus opening the door to a simpler way to track sway variables in the elderly without the necessity to come to a doctor’s office.
Approximation of Capacity for Downlink Multi-User System with Combination of Precoding and NOMA Methods
Authors: Son Vu Van , Cuong Nguyen Le , Phuong Nguyen Thu , Hoang Tran Manh , Thanh Hiep Pham
Published: November 2021

Enhancing performance of downlink MU systems is an attractive and important research for future wireless systems. The non-orthogonal multiple access (NOMA) method was proposed to improve the performance of MU systems. In order to further improve the outage probability (OP) and ergodic capacity (EC) of downlink NOMA MU systems, we propose the combination of precoding and NOMA methods, and then the OP and EC of MU systems with our novel method are derived in scenarios of perfect and imperfect successive interference cancellation (SIC) scheme. Moreover, the closed-form expression of OP and EC for both scenarios is theoretically derived and compared with Monte Carlo simulations. The results show that, the analysis method is accurate, and the proposed combining precoding and NOMA can further enhance the performance of MU systems in comparing with the original orthogonal multiple access method.
Turbulent Flow over Confined Backward-Facing Step: PIV vs. DNS
Authors: Zajec Boštjan , Matkovič Marko , Kosanič Nejc , Oder Jure , Mikuž Blaž , Kren Jan , Tiselj Iztok
Published: November 2021

Particle Image Velocimetry measurements of the liquid velocity fields in the flow over the backward-facing step were performed in the same flow configuration as in the existing Direct Numerical Simulation (DNS). The experiment and the simulation were performed in an identical cross-section geometry with step expansion rate 2.25 and the square shape of the outlet duct at the Reynolds number in an inlet part of the section 7100. The experiment was performed in transparent test section, 1.2 m long, with 20 × 45 mm2 cross-section upstream and 45 × 45 mm2 downstream, while a domain that was three times shorter was used in the DNS. A 2D-2C PIV system with a single high-speed camera and a pulse laser was used for a series of two-dimensional measurements of the velocity field at several cross-sections from two different perspectives. Variables analyzed in the experiment are time-averaged fluid velocities, velocity RMS fluctuations and two components of the Reynolds stress tensor. The key novelty is the comparison of two very accurate approaches, PIV and DNS, in the same cross-section geometry. Comparison of the similarities, and especially the differences between the two approaches, elucidates uncertainties of both studies and answers the question on what kind of agreement is expected when two very accurate approaches are compared.
A Review of Bioinspired Vibration Control Technology
Authors: Shi Xiaojie , Chen Tingkun , Zhang Jinhua , Su Bo , Cong Qian , Tian Weijun
Published: November 2021

Due to huge demand in engineering, vibration control technology and related studies have always been at the frontiers of research. Although traditional vibration control methods are stable and reliable, they have obvious shortcomings. Through evolution and natural selection, certain body-parts of animals in the natural world have been cleverly constructed and well designed. This provides a steady stream of inspiration for the design of vibration control equipment. The prime objective of this review is to highlight recent advances in the bionic design of vibration control devices. Current bionic vibration control devices were classified, and their bionic principles were briefly described. One kind was the bionic device based on the brain structure of the woodpecker, which is mostly used to reduce vibration at high frequencies. Another kind of bionic device was based on animal leg structure and showed outstanding performance in low frequency vibration reduction. Finally, we briefly listed the problems that need to be solved in current bionic vibration control technology and gave recommendations for future research direction.
Prediction of Shear Strength of Reinforced High-Strength Concrete Beams Using Compatibility-Aided Truss Model
Authors: Kim Sang-Woo
Published: November 2021

This study proposes an analytical model applicable to the shear analysis of reinforced high-strength concrete beams. The proposed model satisfies the equilibrium and compatibility conditions and constitutive laws of the materials. The proposed model is based on the fixed angle theory and allows the principal stress to rotate as the load increases, so that the RC beams can be analyzed more realistically. High-strength material models were used in the proposed model to consider the characteristics of high-strength concrete. The concrete shear contribution at crack surfaces was calculated from Mohr’s circle. The proposed model considers the effect of bending moment on shear by reducing the amount of longitudinal reinforcement resisting shear. To verify the accuracy of the proposed model, a total of 64 experimental results were collected from the literature. A comparison with previous experimental results confirmed that the proposed model can be predicted relatively accurately with an average of 0.98 and a coefficient of variation of 12.1%.
Virtual Reality Research: Design Virtual Education System for Epidemic (COVID-19) Knowledge to Public
Authors: Xing Yongkang , Liang Zhanti , Fahy Conor , Shell Jethro , Guan Kexin , Liu Yuxi , Zhang Qian
Published: November 2021

Advances in information and communication technologies have created a range of new products and services for the well-being of society. Virtual Reality (VR) technology has shown enormous potential in educational, commercial, and medical fields. The recent COVID-19 outbreak highlights a poor global performance in communicating epidemic knowledge to the public. Considering the potential of VR, the research starts from analyzing how to use VR technology to improve public education in COVID-19. The research uses Virtual Storytelling Technology (VST) to promote enthusiasm in user participation. A Plot-based VR education system is proposed in order to provide an immersive, explorative, educational experiences. The system includes three primary modules: the Tutorial Module, the Preparation Module, and the Investigation Module. To remove any potential confusion in the user, the research aims to avoid extremely complicated medical professional content and uses interactive, entertainment methods to improve user participation. In order to evaluate the performance efficiency of the system, we conducted performance evaluations and a user study with 80 participants. Compared with traditional education, the experimental results show that the VR education system can used as an effective educational tool for epidemic (COVID-19) fundamental knowledge. The VR technology can assist government agencies and public organizations to increase public understanding of the spread the epidemic (COVID-19).
Employer’s Information Requirements: A Case Study Implementation of BIM on the Example of Selected Construction Projects in Poland
Authors: Zima Krzysztof , Mitera-Kiełbasa Ewelina
Published: November 2021

Case studies available in the literature clearly point to the numerous benefits of BIM (Building Information Modeling), in addition to the barriers that participants of such projects may face. This paper is a case study of Employer’s Information Requirements (EIR) for preparing and managing BIM models in the design and construction of selected large public construction projects: the Cogiteon Lesser Poland Science Center (LPSC Cogiteon), the Krakow Music Center (KMC) and the Copernican Revolution Studio (CRS). The paper presents the main aspects included in EIRs. It discusses the technical (e.g., requirements for the Common Data Environment platform—CDE), management (including the scopes of responsibility of staff in charge of BIM) and strategic sections (primary expectations concerning Data Drops) of the EIR. Projects executed using BIM by public institutions allow for the application of insight gained as a result of their completion and the creation of a knowledge base or checklist for future projects. The projects discussed here, carried out using advanced BIM solutions, could potentially be developed further by the proposed content extension concerning levels of detail (this paper cites potential guidelines that can be applied), component elements concerning price and qualifications, so as to easily generate bills of costs, and information used in facility management which can also encourage facility manager cooperation. Examples of EIR provisions are presented based on an analysis of three completed construction projects carried out using advanced BIM solutions. BIM is still a new form of management and this paper expands the range of available EIR standards, in addition to presenting guidelines for their practical application in the construction industry.
Optimizing Kinematic Modeling and Self-Collision Detection of a Mobile Manipulator Robot by Considering the Actual Physical Structure
Authors: Qiao Lijun , Luo Xiao , Luo Qingsheng , Li Minghao , Jiang Jianfeng
Published: November 2021

In this paper, an optimized kinematic modeling method to accurately describe the actual structure of a mobile manipulator robot with a manipulator similar to the universal robot (UR5) is developed, and an improved self-collision detection technology realized for improving the description accuracy of each component and reducing the time required for approximating the whole robot is introduced. As the primary foundation for trajectory tracking and automatic navigation, the kinematic modeling technology of the mobile manipulator has been the subject of much interest and research for many years. However, the kinematic model established by various methods is different from the actual physical model due to the fact that researchers have mainly focused on the relationship between driving joints and the end positions while ignoring the physical structure. To improve the accuracy of the kinematic model, we present a kinematic modeling method with the addition of key points and coordinate systems to some components that failed to model the physical structure based on the classical method. Moreover, self-collision detection is also a primary problem for successfully completing the specified task of the mobile manipulator. In traditional self-collision detection technology, the description of each approximation is determined by the spatial transformation of each corresponding component in the mobile manipulator robot. Unlike the traditional technology, each approximation in the paper is directly established by the physical structure used in the kinematic modeling method, which significantly reduces the complicated analysis and shortens the required time. The numerical simulations prove that the kinematic model with the addition of key point technology is similar to the actual structure of mobile manipulator robots, and the self-collision detection technology proposed in the article effectively improves the performance of self-collision detection. Additionally, the experimental results prove that the kinematic modeling method and self-collision detection technology outlined in this paper can optimize the inverse kinematics solution.
Biological Activity Evaluation and In Silico Studies of Polyprenylated Benzophenones from Garcinia celebica
Authors: Pasaribu Yenni Pintauli , Fadlan Arif , Fatmawati Sri , Ersam Taslim
Published: November 2021

This study aimed to isolate polyprenylated benzophenones from the rootbark of Garcinia celebica and assess their activities in vitro and in silico. The antioxidant activity was evaluated by the DPPH, ABTS, and FRAP methods. The cytotoxicity was evaluated against HeLa, MCF-7, A549, and B16 cancer cell lines. The antiplasmodial activity was performed against the chloroquine-sensitive Plasmodium falciparum strain 3D7. Molecular docking was analyzed on alpha-estrogen receptor (3ERT) and P. falciparum lactate dehydrogenase enzyme (1CET). The prediction of ADMET for the compounds was also studied. For the first time, (-)-cycloxanthochymol, isoxanthochymol, and xanthochymol were isolated from the root bark of Garcinia celebica. The antioxidant and cytotoxicity evaluation showed that all benzophenones exhibited antioxidant activity compared to gallic acid and quercetin as positive controls and also exhibited strong activity against HeLa, MCF-7, A549, and B16 cell lines compared to cisplatin as the positive control. The antiplasmodial evaluation showed that isoxanthochymol exhibited activity against the chloroquine-sensitive P. falciparum strain 3D7. In addition, the in silico molecular docking study supported in vitro activities. The ADMET analysis also indicated the isolated benzophenones are potential oral drug candidates.
Pathological Significance of Macrophages in Erectile Dysfunction Including Peyronie’s Disease
Authors: Miyata Yasuyoshi , Matsuo Tomohiro , Nakamura Yuichiro , Mitsunari Kensuke , Ohba Kojiro , Sakai Hideki
Published: November 2021

Erectile function is regulated by complex mechanisms centered on vascular- and nerve-related systems. Hence, dysregulation of these systems leads to erectile dysfunction (ED), which causes mental distress and decreases the quality of life of patients and their partners. At the molecular level, many factors, such as fibrosis, lipid metabolism abnormalities, the immune system, and stem cells, play crucial roles in the etiology and development of ED. Although phosphodiesterase type 5 (PDE5) inhibitors are currently the standard treatment agents for patients with ED, they are effective only in a subgroup of patients. Therefore, further insight into the pathological mechanism underlying ED is needed to discuss ED treatment strategies. In this review, we focused on the biological and pathological significance of macrophages in ED because the interaction of macrophages with ED-related mechanisms have not been well explored, despite their important roles in vasculogenic and neurogenic diseases. Furthermore, we examined the pathological significance of macrophages in Peyronie’s disease (PD), a cause of ED characterized by penile deformation (visible curvature) during erection and pain. Although microinjury and the subsequent abnormal healing process of the tunica albuginea are known to be important processes in this disease, the detailed etiology and pathophysiology of PD are not fully understood. This is the first review on the pathological role of macrophages in PD.
Silicon Nanowire Field-Effect Transistor as Label-Free Detection of Hepatitis B Virus Proteins with Opposite Net Charges
Authors: Yong Suh Kuan , Shen Shang-Kai , Chiang Chia-Wei , Weng Ying-Ya , Lu Ming-Pei , Yang Yuh-Shyong
Published: November 2021

The prevalence of hepatitis B virus (HBV) is a global healthcare threat, particularly chronic hepatitis B (CHB) that might lead to hepatocellular carcinoma (HCC) should not be neglected. Although many types of HBV diagnosis detection methods are available, some technical challenges, such as the high cost or lack of practical feasibility, need to be overcome. In this study, the polycrystalline silicon nanowire field-effect transistors (pSiNWFETs) were fabricated through commercial process technology and then chemically functionalized for sensing hepatitis B virus surface antigen (HBsAg) and hepatitis B virus X protein (HBx) at the femto-molar level. These two proteins have been suggested to be related to the HCC development, while the former is also the hallmark for HBV diagnosis, and the latter is an RNA-binding protein. Interestingly, these two proteins carried opposite net charges, which could serve as complementary candidates for evaluating the charge-based sensing mechanism in the pSiNWFET. The measurements on the threshold voltage shifts of pSiNWFETs showed a consistent correspondence to the polarity of the charges on the proteins studied. We believe that this report can pave the way towards developing an approachable tool for biomedical applications.
Patient and Therapist In-Session Cortisol as Predictor of Post-Session Patient Reported Affect
Authors: Levi Eyal , Fischer Susanne , Fisher Hadar , Admon Roee , Zilcha-Mano Sigal
Published: November 2021

The importance of the role of affect in psychotherapy for major depressive disorder (MDD) is well established, but the common use of self-reported measures may limit our understanding of its underlying mechanisms. A promising predictor of patient affect is the stress hormone cortisol. To date, no studies have studied in-session changes in cortisol in psychotherapy for MDD. We investigated whether an increase in patient cortisol over the course of a session correlated with higher negative and lower positive affect. Given previous findings on healthy individuals on the contagious nature of stress, an additional aim was to examine whether these relationships are moderated by therapist cortisol. To this end, 40 dyads (including 6 therapists) provided saliva samples before and after four pre-specified sessions (616 samples). After each session, the patients provided retrospective reports of in-session affect. We found no association between patient cortisol and affect. However, increases in patient cortisol predicted negative affect when the therapists exhibited decreases in cortisol, and increases in patient cortisol predicted positive affect when the therapists showed increases. Our study provides initial evidence for the importance of the social context in the cortisol–affect relationship in MDD.
Liquid Biopsies beyond Mutation Calling: Genomic and Epigenomic Features of Cell-Free DNA in Cancer
Authors: Angeles Arlou Kristina , Janke Florian , Bauer Simone , Christopoulos Petros , Riediger Anja Lisa , Sültmann Holger
Published: November 2021

Cell-free DNA (cfDNA) analysis using liquid biopsies is a non-invasive method to gain insights into the biology, therapy response, mechanisms of acquired resistance and therapy escape of various tumors. While it is well established that individual cancer treatment options can be adjusted by panel next-generation sequencing (NGS)-based evaluation of driver mutations in cfDNA, emerging research additionally explores the value of deep characterization of tumor cfDNA genomics and fragmentomics as well as nucleosome modifications (chromatin structure), and methylation patterns (epigenomics) for comprehensive and multi-modal assessment of cfDNA. These tools have the potential to improve disease monitoring, increase the sensitivity of minimal residual disease identification, and detection of cancers at earlier stages. Recent progress in emerging technologies of cfDNA analysis is summarized, the added potential clinical value is highlighted, strengths and limitations are identified and compared with conventional targeted NGS analysis, and current challenges and future directions are discussed.
Enzymatic Production of Ecodiesel by Using a Commercial Lipase CALB, Immobilized by Physical Adsorption on Mesoporous Organosilica Materials
Authors: Luna Carlos , Gascón-Pérez Victoria , López-Tenllado Francisco J. , Bautista Felipa M. , Verdugo-Escamilla Cristóbal , Aguado-Deblas Laura , Calero Juan , Romero Antonio A. , Luna Diego , Estévez Rafael
Published: November 2021

The synthesis of two biocatalysts based on a commercial Candida antarctica lipase B, CALB enzyme (E), physically immobilized on two silica supports, was carried out. The first support was a periodic mesoporous organosilica (PMO) and the second one was a commercial silica modified with octyl groups (octyl-MS3030). The maximum enzyme load was 122 mg enzyme/g support on PMO and 288 mg enzyme/g support on octyl-MS3030. In addition, the biocatalytic efficiency was corroborated by two reaction tests based on the hydrolysis of p-nitrophenylacetate (p-NPA) and tributyrin (TB). The transesterification of sunflower oil with ethanol was carried out over the biocatalysts synthesized at the following reaction conditions: 6 mL sunflower oil, 1.75 mL EtOH, 30 °C, 25 μL NaOH 10 N and 300 rpm, attaining conversion values over 80% after 3 h of reaction time. According to the results obtained, we can confirm that these biocatalytic systems are viable candidates to develop, optimize and improve a new methodology to achieve the integration of glycerol in different monoacylglycerol molecules together with fatty acid ethyl esters (FAEE) molecules to obtain Ecodiesel.
CD46 Genetic Variability and HIV-1 Infection Susceptibility
Authors: Serrano-Rísquez Carmen , Omar Mohamed , Gómez-Vidal María Amparo , Real Luis Miguel , Pineda Juan Antonio , Rivero Antonio , Rivero-Juárez Antonio , Forthal Donald , Márquez Francisco J. , Lo Caputo Sergio , Clerici Mario , Biasin Mara , Caruz Antonio
Published: November 2021

CD46 is the main receptor for complement protein C3 and plays an important role in adaptive immune responses. CD46 genetic variants are associated with susceptibility to several infectious and autoimmune diseases. Additionally, CD46 function can be subverted by HIV-1 to evade attack by complement, a strategy shared by viruses of other families. We sought to determine the association between CD46 gene variants and HIV-1 acquired through intravenous drug use (IDU) and sexual routes (n = 823). Study subjects were of European ancestry and were HIV-1 infected (n = 438) or exposed but seronegative (n = 387). Genotyping of the rs2796265 SNP located in the CD46 gene region was done by allele-specific real-time PCR. A meta-analysis merging IDU and sexual cohorts indicates that the minor genotype (CC) was associated with increased resistance to HIV-1 infection OR = 0.2, 95% CI (0.07–0.61), p = 0.004. The HIV-1-protective genotype is correlated with reduced CD46 expression and alterations in the ratio of CD46 mRNA splicing isoforms.
NK Cell Regulation in Cervical Cancer and Strategies for Immunotherapy
Authors: Gutiérrez-Hoya Adriana , Soto-Cruz Isabel
Published: November 2021

Cervical cancer is one of the most prevalent gynaecological malignancies worldwide and is related to human papillomavirus (HPV) infection, viral persistence, progression, and invasion. Therefore, the immune response is linked to HPV status. Natural killer (NK) cells play a central role against virus-infected cells and tumours through a delicate balance between activating and inhibitory receptors and secretion of cytokines and chemokines. These cells also play a crucial role in tumour immunosurveillance. For these reasons, there is growing interest in harnessing NK cells as an immunotherapy for cervical cancer. These studies are diverse and include many strategies such as transferring activated autologous or allogeneic NK cells, improving the activation and cytolytic activity of NK cells using cytokines or analogues and modifying chimeric antigen receptors to increase specificity and targeting NK cells. However, research regarding the application of NK cells in immunotherapy is limited. This article focuses on recent discoveries about using NK cells to prevent and treat cervical cancer and the possibility of cellular immunotherapy becoming one of the best strategies to exploit the immune system to fight tumours.
Phosphoprotein Phosphatase 1 but Not 2A Activity Modulates Coupled-Clock Mechanisms to Impact on Intrinsic Automaticity of Sinoatrial Nodal Pacemaker Cells
Authors: Sirenko Syevda Tagirova , Zahanich Ihor , Li Yue , Lukyanenko Yevgeniya O. , Lyashkov Alexey E. , Ziman Bruce D. , Tarasov Kirill V. , Younes Antoine , Riordon Daniel R. , Tarasova Yelena S. , Yang Dongmei , Vinogradova Tatiana M. , Maltsev Victor A. , Lakatta Edward G.
Published: November 2021

Spontaneous AP (action potential) firing of sinoatrial nodal cells (SANC) is critically dependent on protein kinase A (PKA) and Ca2+/calmodulin-dependent protein kinase II (CaMKII)-dependent protein phosphorylation, which are required for the generation of spontaneous, diastolic local Ca2+ releases (LCRs). Although phosphoprotein phosphatases (PP) regulate protein phosphorylation, the expression level of PPs and phosphatase inhibitors in SANC and the impact of phosphatase inhibition on the spontaneous LCRs and other players of the oscillatory coupled-clock system is unknown. Here, we show that rabbit SANC express both PP1, PP2A, and endogenous PP inhibitors I-1 (PPI-1), dopamine and cyclic adenosine 3′,5′-monophosphate (cAMP)-regulated phosphoprotein (DARPP-32), kinase C-enhanced PP1 inhibitor (KEPI). Application of Calyculin A, (CyA), a PPs inhibitor, to intact, freshly isolated single SANC: (1) significantly increased phospholamban (PLB) phosphorylation (by 2–3-fold) at both CaMKII-dependent Thr17 and PKA-dependent Ser16 sites, in a time and concentration dependent manner; (2) increased ryanodine receptor (RyR) phosphorylation at the Ser2809 site; (3) substantially increased sarcoplasmic reticulum (SR) Ca2+ load; (4) augmented L-type Ca2+ current amplitude; (5) augmented LCR’s characteristics and decreased LCR period in intact and permeabilized SANC, and (6) increased the spontaneous basal AP firing rate. In contrast, the selective PP2A inhibitor okadaic acid (100 nmol/L) had no significant effect on spontaneous AP firing, LCR parameters, or PLB phosphorylation. Application of purified PP1 to permeabilized SANC suppressed LCR, whereas purified PP2A had no effect on LCR characteristics. Our numerical model simulations demonstrated that PP inhibition increases AP firing rate via a coupled-clock mechanism, including respective increases in the SR Ca2+ pumping rate, L-type Ca2+ current, and Na+/Ca2+-exchanger current. Thus, PP1 and its endogenous inhibitors modulate the basal spontaneous firing rate of cardiac pacemaker cells by suppressing SR Ca2+ cycling protein phosphorylation, the SR Ca2+ load and LCRs, and L-type Ca2+ current.
Apparent Yield Stress of Sputum as a Relevant Biomarker in Cystic Fibrosis
Authors: Ghanem Rosy , Roquefort Philippe , Ramel Sophie , Laurent Véronique , Haute Tanguy , Le Gall Tony , Aubry Thierry , Montier Tristan
Published: November 2021

The mucus obstructing the airways of Cystic Fibrosis (CF) patients is a yield stress fluid. Linear and non-linear rheological analyses of CF sputa can provide relevant biophysical markers, which could be used for the management of this disease. Sputa were collected from CF patients either without any induction or following an aerosol treatment with the recombinant human DNAse (rhDNAse, Pulmozyme®). Several sample preparations were considered and multiple measurements were performed in order to assess both the repeatability and the robustness of the rheological measurements. The linear and non-linear rheological properties of all CF sputa were characterized. While no correlation between oscillatory shear linear viscoelastic properties and clinical data was observed, the steady shear flow data showed that the apparent yield stress of sputum from CF patients previously treated with rhDNAse was approximately one decade lower than that of non-treated CF patients. Similar results were obtained with sputa from non-induced CF patients subjected ex vivo to a Pulmozyme® aerosol treatment. The results demonstrate that the apparent yield stress of patient sputa is a relevant predictive/prognostic biomarker in CF patients and could help in the development of new mucolytic agents.
Comparative Analyses of Single-Cell Transcriptomic Profiles between In Vitro Totipotent Blastomere-like Cells and In Vivo Early Mouse Embryonic Cells
Authors: Lin Po-Yu , Yang Denny , Chuang Chi-Hsuan , Lin Hsuan , Chen Wei-Ju , Chen Chia-Ying , Chuang Trees-Juen , Lai Chien-Ying , Li Long-Yuan , Schuyler Scott C. , Lu Frank Leigh , Liu Yu-Chuan , Lu Jean
Published: November 2021

The developmental potential within pluripotent cells in the canonical model is restricted to embryonic tissues, whereas totipotent cells can differentiate into both embryonic and extraembryonic tissues. Currently, the ability to culture in vitro totipotent cells possessing molecular and functional features like those of an early embryo in vivo has been a challenge. Recently, it was reported that treatment with a single spliceosome inhibitor, pladienolide B (plaB), can successfully reprogram mouse pluripotent stem cells into totipotent blastomere-like cells (TBLCs) in vitro. The TBLCs exhibited totipotency transcriptionally and acquired expanded developmental potential with the ability to yield various embryonic and extraembryonic tissues that may be employed as novel mouse developmental cell models. However, it is disputed whether TBLCs are ‘true’ totipotent stem cells equivalent to in vivo two-cell stage embryos. To address this question, single-cell RNA sequencing was applied to TBLCs and cells from early mouse embryonic developmental stages and the data were integrated using canonical correlation analyses. Differential expression analyses were performed between TBLCs and multi-embryonic cell stages to identify differentially expressed genes. Remarkably, a subpopulation within the TBLCs population expressed a high level of the totipotent-related genes Zscan4s and displayed transcriptomic features similar to mouse two-cell stage embryonic cells. This study underscores the subtle differences between in vitro derived TBLCs and in vivo mouse early developmental cell stages at the single-cell transcriptomic level. Our study has identified a new experimental model for stem cell biology, namely ‘cluster 3’, as a subpopulation of TBLCs that can be molecularly defined as near totipotent cells.
RALBP1 in Oxidative Stress and Mitochondrial Dysfunction in Alzheimer’s Disease
Authors: Awasthi Sanjay , Hindle Ashly , Sawant Neha A. , George Mathew , Vijayan Murali , Kshirsagar Sudhir , Morton Hallie , Bunquin Lloyd E. , Palade Philip T. , Lawrence J. Josh , Khan Hafiz , Bose Chhanda , Reddy P. Hemachandra , Singh Sharda P.
Published: November 2021

The purpose of our study is to understand the role of the RALBP1 gene in oxidative stress (OS), mitochondrial dysfunction and cognition in Alzheimer’s disease (AD) pathogenesis. The RALPB1 gene encodes the 76 kDa protein RLIP76 (Rlip). Rlip functions as a stress-responsive/protective transporter of glutathione conjugates (GS-E) and xenobiotic toxins. We hypothesized that Rlip may play an important role in maintaining cognitive function. The aim of this study is to determine whether Rlip deficiency in mice is associated with AD-like cognitive and mitochondrial dysfunction. Brain tissue obtained from cohorts of wildtype (WT) and Rlip+/− mice were analyzed for OS markers, expression of genes that regulate mitochondrial fission/fusion, and synaptic integrity. We also examined mitochondrial ultrastructure in brains obtained from these mice and further analyzed the impact of Rlip deficiency on gene networks of AD, aging, stress response, mitochondrial function, and CREB signaling. Our studies revealed a significant increase in the levels of OS markers and alterations in the expression of genes and proteins involved in mitochondrial biogenesis, dynamics and synapses in brain tissues from these mice. Furthermore, we compared the cognitive function of WT and Rlip+/− mice. Behavioral, basic motor and sensory function tests in Rlip+/− mice revealed cognitive decline, similar to AD. Gene network analysis indicated dysregulation of stress-activated gene expression, mitochondrial function and CREB signaling genes in the Rlip+/− mouse brain. Our results suggest that Rlip deficiency-associated increases in OS and mitochondrial dysfunction could contribute to the development or progression of OS-related AD processes.
Phagocyte Chemoattraction Is Induced through the Mcp-1–Ccr2 Axis during Efferocytosis
Authors: Lee Sang-Ah , Kim Deokhwan , Min Chanhyuk , Moon Byeongjin , Lee Juyeon , Moon Hyunji , Yang Susumin , Lee Chang Sup , Lee Gwangrog , Park Daeho
Published: November 2021

Apoptotic cells generated during development and for tissue homeostasis are swiftly and continuously removed by phagocytes via a process called efferocytosis. Efficient efferocytosis can be achieved via transcriptional modulation in phagocytes that have engulfed apoptotic cells. However, such modulation and its effect on efferocytosis are not completely understood. Here, we report that phagocytes are recruited to apoptotic cells being cleared through the Mcp-1–Ccr2 axis, which facilitates clearance of apoptotic cells. We identified Mcp-1 as a modulated transcript using a microarray and found that Mcp-1 secretion was augmented in phagocytes engulfing apoptotic cells. This augmented Mcp-1 secretion was impaired by blocking phagolysosomal degradation of apoptotic cells. Conditioned medium from wild type (WT) phagocytes promoted cell migration, but that from Mcp-1−/− phagocytes did not. In addition, blockade of Ccr2, the receptor for Mcp-1, abrogated cell migration to conditioned medium from phagocytes incubated with apoptotic cells. The intrinsic efferocytosis activity of Mcp-1−/− and Ccr2−/− phagocytes was unaltered, but clearance of apoptotic cells was less efficient in the peritoneum of Mcp-1−/− and Ccr2−/− mice than in that of WT mice because fewer Ccr2-positive phagocytes were recruited. Taken together, our findings demonstrate a mechanism by which not only apoptotic cells but also phagocytes induce chemoattraction to recruit phagocytes to sites where apoptotic cells are cleared for efficient efferocytosis.
Can Suboptimal Visual Environments Negatively Affect Children’s Cognitive Development?
Authors: Lavdas Alexandros , Salingaros Nikos
Published: November 2021

There are indications that children born during the period of COVID-19 lockdown have cognitive development issues, without having been affected by the virus. We discuss here the idea that environmental deprivation—and, especially, the lack of appropriate visual stimulation—might be one source of these defects. This thought is in line with previous findings in children brought up in orphanages with poor environmental stimulation, hypothesizing that the minimalist architectural style prevailing for the last several decades is among the potential contributing factors. The process of eliminating organized complexity characteristic of organic forms may prove to be detrimental for humanity’s future, providing suboptimal environmental stimulation and opportunities for interaction during the critical stages of brain development.
Additional Evidence for Neuropsychiatric Manifestations in Mosaic Trisomy 20: A Case Report and Brief Review
Authors: Colizzi Marco , Antolini Giulia , Passarella Laura , Rizzo Valentina , Puttini Elena , Zoccante Leonardo
Published: November 2021

Mosaic trisomy 20 is a genetic condition in which three chromosomes 20 are found in some cells. Its clinical phenotype seems to be highly variable, with most features not reported across all individuals and not considered pathognomonic of the condition. Limited and recent evidence indicates that neuropsychiatric manifestations may be more present in the context of trisomy 20 than was once thought. Here, we present a case of a 14-year-old female adolescent of White/Caucasian ethnicity with mosaic trisomy 20, who was admitted twice to an inpatient Child and Adolescent Neuropsychiatry Unit for persisting self-injury and suicidal ideation. A severe and complex neuropsychiatric presentation emerged at the cognitive, emotional, and behavioral levels, including mild neurodevelopmental issues, isolation, socio-relational difficulties, depressed mood, temper outbursts, irritability, low self-esteem, lack of interest, social anxiety, panic attacks, self-cutting, and low-average-range and heterogeneous intelligence quotient profile. Particularly, the patient was considered at high risk of causing harm, mainly to self, and appeared to be only partially responsive to medication, even when polypharmacy was attempted to improve clinical response. Except for school bullying, no other severe environmental risk factors were present in the patient’s history. The patient received a diagnosis of disruptive mood dysregulation disorder.
Microstructure and Oxidation Behavior of Nb-Si-Based Alloys for Ultrahigh Temperature Applications: A Comprehensive Review
Authors: Shen Fuqiang , Zhang Yingyi , Yu Laihao , Fu Tao , Wang Jie , Wang Hong , Cui Kunkun
Published: November 2021

Nb-Si-based superalloys are considered as the most promising high-temperature structural material to replace the Ni-based superalloys. Unfortunately, the poor oxidation resistance is still a major obstacle to the application of Nb-Si-based alloys. Alloying is a promising method to overcome this problem. In this work, the effects of Hf, Cr, Zr, B, and V on the oxidation resistance of Nb-Si-based superalloys were discussed. Furthermore, the microstructure, phase composition, and oxidation characteristics of Nb-Si series alloys were analyzed. The oxidation reaction and failure mechanism of Nb-Si-based alloys were summarized. The significance of this work is to provide some references for further research on high-temperature niobium alloys.
Numerical Study on the Impact of Gap between Sheets on the Quality of Riveted Single-Strap Butt Joints
Authors: Ke Zhenzheng , Zhang Yongliang , Liu Yuchi , Zhong Zhengwei , Zhu Chunrun , Bi Yunbo
Published: November 2021

Some controllable process parameters in the riveting process such as the gap between sheets, have an important impact on the quality of a riveted butt joint. In this paper, the finite element model of a riveted single-strap butt joint is established with the help of ABAQUS analysis software, and the riveting process is simulated under five kinds of gaps between sheets. From the perspectives of rivet upsetting size, rivet interference, radial deformation of sheet, and analysis of residual stress around the hole of sheet, the influence of the gap between sheets on the connection quality of the riveted butt joint is summarized. The results show that the left and right sheets will contact each other and there is extrusion stress between the sheets when the gap is zero. When the applied tensile load continues to increase, due to the influence of the secondary bending, the strap sheet responsible for the connection produces warping deformation, and there will be no further contact between the sheets. When the gap between sheets increases from 0 to 2 mm, the maximum deformation of strap sheets increases from 0.876 to 0.927 mm, which proves that the gap between sheets have no significant effect on the deformation of the strap sheet.
Properties of Spark Plasma Sintered Compacts and Magnetron Sputtered Coatings Made from Cr, Mo, Re and Zr Alloyed Tungsten Diboride
Authors: Mościcki Tomasz , Psiuk Rafał , Radziejewska Joanna , Wiśniewska Maria , Garbiec Dariusz
Published: November 2021

To enhance the properties of tungsten diboride, we have synthesized and characterized solid solutions of this material with chromium, molybdenum, rhenium and zirconium. The obtained materials were subsequently deposited as coatings. Various concentrations of these transition metal elements, ranging from 0.0 to 24.0 at.%, on a metals basis, were made. Spark plasma sintering was used to synthesize these refractory compounds from the pure elements. Elemental and phase purity of both samples (sintered compacts and coatings) were examined using energy dispersive X-ray spectroscopy and X-ray diffraction. Microindentation was utilized to measure the Vickers hardness. X-ray diffraction results indicate that the solubility limit is below 8 at.% for Mo, Re and Zr and below 16 at.% for Cr. Above this limit both diborides (W,TM)B2 are created. Addition of transition metals caused decrease of density and increase of hardness and electrical conductivity of sintered compacts. Deposited coatings W1−xTMxBy (TM = Cr, Mo, Re, Zr; x = 0.2; y = 1.7–2) are homogenous, smooth and hard. The maximal hardness was measured for W-Cr-B films and under the load of 10 g was 50.4 ± 4.7 GPa. Deposited films possess relatively high fracture toughness and for WB2 coatings alloyed with zirconium it is K1c = 2.11 MPa m1/2.
Neck Disability Index Is Better in Classification of Recovery after Whiplash Injury in Comparison with Ultrasound Shear Wave Elastography of Trapezius Muscle
Authors: Barun Blaž , Barišić Igor , Krnić Ana , Benzon Benjamin , Vlak Tonko , Aljinović Jure
Published: November 2021

A prospective observational study comparing shear wave elastography (SWE) of trapezius muscle with Neck Disability Index (NDI) in a prediction model of health status six months after a whiplash injury. Both SWE values, measured by two radiologists, and NDI scores were obtained at baseline and after physical therapy (PT) (6-month period). Those values were compared with a 3-point Likert scale (no, partial or full recovery). Twenty-two subjects completed the study. A decrease in trapezius stiffness was detected by both radiologists, statistically significant for one (Δ10.1 kPa; p = 0.04) but not for the second radiologist (Δ8.63 kPa; p = 0.07). The measurements showed excellent intra-observer (ICC 0.75–0.94) and inter-observer (ICC 0.78–0.88) reliability. After six months, fully recovered patients showed lower NDI scores than partially recovered patients (Δ22.98; p < 0.001). SWE values did not differ with the recovery status (55.6 ± 9.7 vs. 57 ± 15.8, Δ1.45; p = 0.82). The single most accurate variable in classifying health status six months after whiplash injury was the relative change of NDI, and it showed the highest accuracy (73.9%) and low Akaike information criterion (AIC = 39.2). Overall, the most accurate classification was obtained when combining NDI and SWE after physical therapy with an accuracy of 77.3% and a decrease in AIC (32.8).
Prognostic Value of Serum Thyroglobulin and Anti-Thyroglobulin Antibody in Thyroid Carcinoma Patients following Thyroidectomy
Authors: Zahra Hashem O. , Omran Gamal A. , Gewely Ahmed G. , Eldehn Ahmed Fathy , Abdo Walied , Elmahallawy Ehab Kotb , Okda Tarek M.
Published: November 2021

Well-differentiated thyroid cancer (WDTC) is a malignant head and neck tumor with a very high incidence. Thyroidectomized WDTC patients have been referred to nuclear medicine for radioactive iodine (RAI) ablation therapy and/or annual follow-up with diagnostic whole-body imaging. Serum thyroglobulin (TG) and thyroglobulin antibodies (TGAb) are biochemical tumor markers used to monitor WDTC. A global rise in the prevalence of WDTC is increasing the number of thyroidectomized patients requiring lifelong monitoring for persistent or recurrent diseases. The present study aimed to identify the most successful prognostic factors in well-defined thyroid carcinoma patients following total thyroidectomy and RAI therapy, followed by an estimation of the cutoff value of TG and TGAb. In this context, a total of 100 subjects were recruited and classified as follows: 60 thyroid carcinoma patients underwent total thyroidectomy and successful RAI therapy, while 40 normal healthy individuals matched for age, sex, and socioeconomic status constituted the control group. Interestingly, the levels of TG did not differ significantly between the relapsed and non-relapsed cases, but the levels of TGAb differed significantly between the relapsed and non-relapsed cases. Collectively, TG and TGAb are considered the most successful prognostic factors in well-defined thyroid carcinoma patients after total thyroidectomy and RAI therapy. The present study also concluded that the TGAb determination was better than that of the TG level, with a cutoff value of 10 ng/mL. These findings provide baseline information for follow-up and lifelong monitoring of thyroidectomized WDTC patients. Further research is warranted to explore more about serum TG and TGAb in thyroid carcinoma patients on a larger scale.