bluuebunny/crossref_metadata_2025 huggingface dataset:
A New Lithium-Ion Battery SOH Estimation Method Based on an Indirect Enhanced Health Indicator and Support Vector Regression in PHMs
Authors: Liu Zhengyu , Zhao Jingjie , Wang Hao , Yang Chao
Published: February 2020

An accurate lithium-ion battery state of health (SOH) estimate is a key factor in guaranteeing the reliability of electronic equipment. This paper proposes a new method that is based on an indirect enhanced health indicator (HI) and uses support vector regression (SVR) to estimate SOH values. First, three original features that can describe the dynamic changes of the battery charging and discharging processes are extracted. Considering the coupling relationship between pairs of the original health indicators, we use the differential evolution (DE) algorithm to optimize their corresponding feature parameters and combine them to form an enhanced health indicator. Second, this paper modifies the kernel function of the SVR model to describe the trend of SOH as the number of cycles increases, with simultaneous hyperparameters optimization via DE algorithm. Third, the proposed model and other published methods are compared in terms of accuracy on the same NASA datasets. We also evaluated the generalization performance of the model in dynamic discharging experiments. The simulation results demonstrate that the proposed method can provide more accurate SOH estimation values.
Accuracy Analysis of DNN-Based Pose-Categorization Model and Activity-Decision Algorithm
Authors: Park Bo Rang , Choi Eun Ji , Choi Young Jae , Moon Jin Woo
Published: February 2020

The objective of this study is to develop (1) a pose-categorization model that classifies the poses of an occupant based on their image in an indoor space and (2) an activity-decision algorithm that identifies the activity being performed by the occupant. For developing an automated intelligent model, a deep neural network is adopted. The model considers the coordinates of the joints of the occupant in the image as input data and returns the pose of the occupant. Datasets composed of indoor images of home and office environments are used for training and testing the model. The training and testing accuracies of the optimized model were 100% for both the home and office environments. A representative activity of an occupant for a certain period has to be decided to control an indoor environment for comfort. The activity-decision algorithm employs a frequency-based method to determine the representative activity type for real-time occupant poses using the pose-categorization model. This study highlights the potential of the developed model and algorithm to determine the activity of occupants to provide an optimal thermal environment corresponding to the individual’s metabolic rate.
Pulsating Flow of CNT–Water Nanofluid Mixed Convection in a Vented Trapezoidal Cavity with an Inner Conductive T-Shaped Object and Magnetic Field Effects
Authors: Chamkha Ali J. , Selimefendigil Fatih , Oztop Hakan F.
Published: February 2020

Mixed convection of carbon-nanotube/water nanofluid in a vented cavity with an inner conductive T-shaped object was examined under pulsating flow conditions under magnetic field effects with finite element method. Effects of different parameters such as Richardson number (between 0.05 and 50), Hartmann number (between 0 and 30), cavity wall inclination (between 0 ∘ and 10 ∘ ), size (between 0.1 H and 0.4 H) and orientation (between −90 ∘ and 90 ∘ ) of the T-shaped object, and amplitude (between 0.5 and 0.9) and frequency (Strouhal number between 0.25 and 5) of pulsating flow on the convective flow features were studied. It was observed that the average Nusselt number enhanced with the rise of strength of magnetic field, solid nanoparticle volume fraction, and amplitude of the pulsation, while the effect was opposite for higher values of Ri number and cavity wall inclination angle. The presence of the T-shaped object and adjusting its size and orientation had significant impact on the main flow stream from inlet to outlet and recirculations around the T-shaped object and in the vicinity of hot wall of the cavity along with the magnetic field strength. Pulsating flow resulted in heat transfer enhancement as compared to steady flow case for all configurations. However, the amount of increment was different depending on the variation of the parameters of interest. Heat transfer enhancements were 41.85% and 20.81% when the size of the T-shaped object was increased from 0.1 H to 0.4 H. The T-shaped object can be utilized in the vented cavity as an excellent tool for convective heat transfer control. As highly conductive CNT particles were used in water, significant enhancements in the average Nusselt number between 97% and 108% were obtained both in steady flow and in pulsating flow cases when magnetic field was absent or present.
Numerical Study on the Elastic Deformation and the Stress Field of Brittle Rocks under Harmonic Dynamic Load
Authors: Li Siqi , Tian Shenglei , Li Wei , Ling Xin , Kapitaniak Marcin , Vaziri Vahid
Published: February 2020

In order to study the deformation displacement and the stress field of brittle rocks under harmonic dynamic loading, a series of systematic numerical simulations are conducted in this paper. A 3D uniaxial compression simulation is carried out to calibrate and determine the property parameters of sandstone and a model of the cylindrical indenter intruding the rock is proposed to analyze the process of elastic deformation. Four main parameters are taken into account, namely the position on the rock, the frequency and the amplitude of dynamic load, the type of indenter and the loading conditions (static and static-dynamic). Based on the analysis undertaken, it can be concluded that both of the deformation displacement and stress field of the rock change in a harmonic manner under the static-dynamic loads. The frequency and the amplitude of harmonic dynamic load determine the period and the magnitude of the rock response, respectively. In addition, the existence of harmonic dynamic load can aggravate the fatigue damage of the rock and allow a reduction in static load. Our investigations confirm that the static-dynamic loads are more conducive to rock fracture than static load.
Condition Assessment of HV Bushings with Solid Insulation based on the SVM and the FDS Methods
Authors: Subocz Jan , Mrozik Andrzej , Bohatyrewicz Patryk , Zenker Marek
Published: February 2020

This paper presents the dielectric response of the insulation of bushings as an effect of the simulated long-term aging process. The experiment was conducted under a condition of a high temperature difference between the current circuit and the cover. The dielectric response was measured with the FDS (Frequency Dielectric Spectroscopy) and the SVM (Step Voltage Measurement) methods. The research has shown the correlation between the aging time and some parameters obtained with the FDS and SVM analysis.
Optimization of Continuous Solid-State Distillation Process for Cost-Effective Bioethanol Production
Authors: Li Hongshen , Li Shizhong
Published: February 2020

To improve the efficiency of bioethanol production, an advanced process was required to extract ethanol from solid-state fermented feedstock. With regard to the characteristics of no fluidity of solid biomass, a continuous solid-state distillation (CSSD) column was designed with a proprietary rotary baffle structure and discharging system. To optimize the operation condition, fermented sweet sorghum bagasse was prepared as feedstock for a batch distillation experiment. The whole distillation time was divided into heating and extracting period which was influenced by loading height and steam flow rate simultaneously. A total of 16 experiments at four loading height and four steam flow rate levels were conducted, respectively. Referring to packing, rectifying column, mass, and heat transfer models of the solid-state distillation heating process were established on the basis of analyzing the size distribution of sweet sorghum bagasse. The specific heat capacity and thermal conductivity value of fermented sweet sorghum bagasse were tested and served to calculate the ethanol yielding point and concentration distribution in the packing. The extracting process is described as the ethanol desorption from porous media absorbent and the pseudo-first-order desorption dynamic model was verified by an experiment. Benefit (profit/time) was applied as objective function and solved by successive quadratic programming. The optimal solution of 398 mm loading height and 8.47 m3/h steam flow rate were obtained to guide a 4 m in diameter column design. One heating and two extracting trays with 400 mm effective height were stacked up in an industrial CSSD column. The steam mass flow rate of 0.5 t/h was determined in each tray and further optimized to half the amount on the third tray based on desorption equation.
The Dynamic Impacts of Oil Price on China’s Natural Gas Consumption under the Change of Global Oil Market Patterns: An Analysis from the Perspective of Total Consumption and Structure
Authors: Chai Jian , Jin Ying
Published: February 2020

In recent years, China’s energy structure has been adjusted unceasingly, where the proportion of natural gas has been increasing year by year, and its external dependence has also been increasing. Therefore, it is necessary to discuss the correlation between China’s natural gas market and the international energy market. This paper studies the dynamic relationship between China’s total natural gas consumption, consumption structure, and the international price of oil from the perspectives of mutation and time-variance, using the cointegration test with regime shifts and a state space model. The results show that during the global financial crisis in 2008, the cointegration relationship between China’s total natural gas consumption and the international oil price has undergone structural changes. January 2012 and March 2015 are potential structural mutation points. After the structural mutation, the impact of the international price of oil on China’s total natural gas consumption has weakened. From a structural point of view, urban gas and power generation gas have both been greatly affected by the change of oil price, while industrial gas and chemical gas are less affected. The conclusion here will provide an important empirical reference for optimizing the structure of natural gas consumption and maintaining energy security in China.
Numerical Modeling of Bifacial PV String Performance: Perimeter Effect and Influence of Uniaxial Solar Trackers
Authors: Ricco Galluzzo Fabio , Zani Pier Enrico , Foti Marina , Canino Andrea , Gerardi Cosimo , Lombardo Salvatore
Published: February 2020

The bifacial photovoltaic (PV) systems have recently met large interest. The performance of such systems heavily depends on the installation conditions and, in particular, on the albedo radiation collected by the module rear side. Therefore, it is of crucial importance to have an accurate performance model. To date, in the scientific literature, numerous models have been proposed and experimental data collected to study and optimize bifacial PV system performance. Currently, 3D and 2D models of bifacial PV devices exist. Though the former are more mathematically complex, they can lead to more accurate results, since they generally allow to fully consider the main aspects influencing a bifacial PV system performance. Recently, we have proposed and validated through experimental data a 3D model tested as a function of module height, tilt angle, and ground albedo. In this work, through such a model, we studied the role played by the perimeter zones surrounding the PV string, by considering PV strings of 30 or 60 modules. We considered the cases of fixed installation with optimal PV module tilt and of installation with uniaxial horizontal solar tracker. We evaluated the PV energy yield as a function of the size of the perimeter zones for the two cases, i.e., both with and without the solar tracker. In optimal perimeter conditions, we then studied the behavior of bifacial and mono-facial PV strings by varying the geographical location in a large latitude range.
Study on Methods to Control Interstory Deflections
Authors: Khatami Seyed Mohammad , Naderpour Hosein , Razavi Seyed Mohammad Nazem , Barros Rui Carneiro , Jakubczyk-Gałczyńska Anna , Jankowski Robert
Published: February 2020

One of the possibilities to prevent building pounding between two adjacent structures is to consider appropriate in-between separation distance. Another approach might be focused on controlling the relative displacements during seismic excitations. Although the majority of building codes around the world recommend the use of some equations of various distances between structures to avoid pounding; a lot of reports after earthquakes have obviously shown that safety situation or economic consideration is not always provided due to the collisions between buildings and high cost of land; respectively. The aim of the present paper is to focus the analysis on the properties of structures and conduct an in-depth analysis of available methods to control interstory deflections so as to prevent pounding. For this purpose, a numerical lumped mass model of the five-story building has been considered and its response under different earthquake records has been investigated. Firstly, the influence of the change in structural properties (story stiffness; mass and damping) has been examined. Then the application of tuned mass damper, base isolation and base isolation with rubber bumpers has been considered. The results of comparative analyses clearly indicate that using base isolation, with the addition of bumpers, can be selected as the best method to control building deflections and decrease absolute lateral displacement between two buildings so as to prevent their pounding during earthquakes
Effects of Women’s Work-Family Multiple Role and Role Combination on Depressive Symptoms in Korea
Authors: Kang Ji-won , Jang Soong-nang
Published: February 2020

This study set out to investigate the effects of multiple roles on depressive symptoms in women. The role of women was divided into worker, household worker, spouse, parent, and caregiver roles to identify the differences in depressive symptoms according to the number of roles, role-fulfillment, and role-combination. Using the sixth raw data of the 2016 Korean Longitudinal Survey of Women and Families for analysis, the data had 6198 respondents who did not have missing values in the major variables. There are three main findings of this study: (1) as the number of roles increased, depressive symptoms of women was decreased. In addition, role-combination was a more meaningful element; (2) women who did not have any roles tended to be more depressed; (3) the caregiver role showed a negative effect on depressive symptoms of women. This study was to include the various aspects of women’s roles and to determine the effects of multi-roles on depressive symptoms in women.
Size Matters: A Latent Class Analysis of Workplace Health Promotion Knowledge, Attitudes, Practices and Likelihood of Action in Small Workplaces
Authors: Jessiman-Perreault Geneviève , Alberga Amanda , Jorge Fatima , Makwarimba Edward , Allen Scott Lisa
Published: February 2020

Workplace health programs (WHPs) have been shown to improve employee health behaviours and outcomes, increase productivity, and decrease work-related costs over time. Nonetheless, organizational characteristics, including size, prevent certain workplaces from implementing these programs. Past research has examined the differences between small and large organizations. However, these studies have typically used a cut-off better suited to large countries such as the USA. Generalizing such studies to countries that differ based on population size, scale of economies, and health systems is problematic. We investigated differences in WHP knowledge, attitudes, and practices between organizations with under 20 employees, 20–99 employees, and more than 100 employees. In 2017–2018, a random sample of employers from 528 workplaces in Alberta, Canada, were contacted for participation in a cross-sectional survey. Latent Class Analysis (LCA) was used to identify underlying response pattern and to group clusters of similar responses to categorical variables focused on WHP knowledge, attitudes, practices and likelihood of action. Compared to large organizations, organizations with fewer than 20 employees were more likely to be members of the Medium–Low Knowledge of WHP latent class (p = 0.01), the Low Practices for WHP latent class (p < 0.001), and more likely to be members of Low Likelihood of Action in place latent class (p = 0.033). While the majority of workplaces, regardless of size, recognized the importance and benefits of workplace health, capacity challenges limited small employers’ ability to plan and implement WHP programs. The differences in capacity to implement WHP in small organizations are masked in the absence of a meaningful cut-off that reflects the legal and demographic reality of the region of study.
The Impact of Education on Household Income in Rural Vietnam
Authors: Van Vu Hung
Published: February 2020

Using data from the 2018 Vietnam Household Living Standard Survey, our study investigates the impact of education on household income in rural Vietnam. Both mean and quantile regression analyses were employed to analyze the impact of education. We found that education has a positive effect on the household income after controlling for various factors in the models. However, quantile regression analysis reveals that the effect of schooling years increases with quantiles, suggesting that education bring higher returns for richer households. We also found that households with the heads having higher qualifications or vocational education tend to earn higher income levels. Combined together, these findings imply that while education was found to increase household income, it increases income inequality in rural Vietnam. Our research findings suggest that improving the access of poor households to better education is expected to increase their income and reduce inequality in rural Vietnam.
Atomistic Insights of Calmodulin Gating of Complete Ion Channels
Authors: Núñez Eider , Muguruza-Montero Arantza , Villarroel Alvaro
Published: February 2020

Intracellular calcium is essential for many physiological processes, from neuronal signaling and exocytosis to muscle contraction and bone formation. Ca2+ signaling from the extracellular medium depends both on membrane potential, especially controlled by ion channels selective to K+, and direct permeation of this cation through specialized channels. Calmodulin (CaM), through direct binding to these proteins, participates in setting the membrane potential and the overall permeability to Ca2+. Over the past years many structures of complete channels in complex with CaM at near atomic resolution have been resolved. In combination with mutagenesis-function, structural information of individual domains and functional studies, different mechanisms employed by CaM to control channel gating are starting to be understood at atomic detail. Here, new insights regarding four types of tetrameric channels with six transmembrane (6TM) architecture, Eag1, SK2/SK4, TRPV5/TRPV6 and KCNQ1–5, and its regulation by CaM are described structurally. Different CaM regions, N-lobe, C-lobe and EF3/EF4-linker play prominent signaling roles in different complexes, emerging the realization of crucial non-canonical interactions between CaM and its target that are only evidenced in the full-channel structure. Different mechanisms to control gating are used, including direct and indirect mechanical actuation over the pore, allosteric control, indirect effect through lipid binding, as well as direct plugging of the pore. Although each CaM lobe engages through apparently similar alpha-helices, they do so using different docking strategies. We discuss how this allows selective action of drugs with great therapeutic potential.
Central and Peripheral Mechanisms in ApoE4-Driven Diabetic Pathology
Authors: Koren-Iton Amit , Salomon-Zimri Shiran , Smolar Alex , Shavit-Stein Efrat , Dori Amir , Chapman Joab , Michaelson Daniel M.
Published: February 2020

Apolipoprotein E (APOE) ε4 gene allele and type 2 diabetes mellitus (T2DM) are prime risk factors for Alzheimer’s disease (AD). Despite evidence linking T2DM and apoE4, the mechanism underlying their interaction is yet to be determined. In the present study, we employed a model of APOE-targeted replacement mice and high-fat diet (HFD)-induced insulin resistance to investigate diabetic mechanisms associated with apoE4 pathology and the extent to which they are driven by peripheral and central processes. Results obtained revealed an intriguing pattern, in which under basal conditions, apoE4 mice display impaired glucose and insulin tolerance and decreased insulin secretion, as well as cognitive and sensorimotor characteristics relative to apoE3 mice, while the HFD impairs apoE3 mice without significantly affecting apoE4 mice. Measurements of weight and fasting blood glucose levels increased in a time-dependent manner following the HFD, though no effect of genotype was observed. Interestingly, sciatic electrophysiological and skin intra-epidermal nerve fiber density (IENFD) peripheral measurements were not affected by the APOE genotype or HFD, suggesting that the observed sensorimotor and cognitive phenotypes are related to central nervous system processes. Indeed, measurements of hippocampal insulin receptor and glycogen synthase kinase-3β (GSK-3β) activation revealed a pattern similar to that obtained in the behavioral measurements while Akt activation presented a dominant effect of diet. HFD manipulation induced genotype-independent hyperlipidation of apoE, and reduced levels of brain apoE in apoE3 mice, rendering them similar to apoE4 mice, whose brain apoE levels were not affected by the diet. No such effect was observed in the peripheral plasma levels of apoE, suggesting that the pathological effects of apoE4 under the control diet and apoE3 under HFD conditions are related to the decreased levels of brain apoE. Taken together, our data suggests that diabetic mechanisms play an important role in mediating the pathological effects of apoE4 and that consequently, diabetic-related therapy may be useful in treating apoE4 pathology in AD.
C5, A Cassaine Diterpenoid Amine, Induces Apoptosis via the Extrinsic Pathways in Human Lung Cancer Cells and Human Lymphoma Cells
Authors: Kim Hyo-Jin , Seo Bo-Gyeong , Kim Kwang Dong , Yoo Jiyun , Lee Joon-Hee , Min Byung-Sun , Lee Jeong-Hyung , Hwangbo Cheol
Published: February 2020

Apoptosis pathways in cells are classified into two pathways: the extrinsic pathway, mediated by binding of the ligand to a death receptor and the intrinsic pathway, mediated by mitochondria. Apoptosis is regulated by various proteins such as Bcl-2 (B-cell lymphoma 2) family and cellular FLICE (Fas-associated Death Domain Protein Interleukin-1β-converting enzyme)-inhibitory protein (c-FLIP), which have been reported to inhibit caspase-8 activity. In this study, it was found that C5 (3β-Acetyl-nor-erythrophlamide), a compound of cassaine diterpene amine from Erythrophleum fordii, induced cell apoptosis in a variety of types of cancer cells. Induction of apoptosis in cancer cells by C5 was inversely related to the level of Bcl-2 expression. Overexpression of Bcl-2 into cancer cells significantly decreased C5-induced apoptosis. It was also found that treatment of cancer cells with a caspase-8 inhibitor significantly suppressed C5-induced apoptosis; however, treatment with caspase-9 inhibitors did not affect C5-induced apoptosis, suggesting that C5 may induce apoptosis via the extrinsic pathway by activating caspase-8. It was confirmed that treatment with C5 alone induced an association of FADD with procaspase-8; however, overexpression of c-FLIP decreased C5-induced caspase-8 activation. In conclusion, C5 could be utilized as a new useful lead compound for the development of an anti-cancer agent that has the goal of apoptosis.
Heterogeneous Network Model to Identify Potential Associations Between Plasmodium vivax and Human Proteins
Authors: Suratanee Apichat , Plaimas Kitiporn
Published: February 2020

Integration of multiple sources and data levels provides a great insight into the complex associations between human and malaria systems. In this study, a meta-analysis framework was developed based on a heterogeneous network model for integrating human-malaria protein similarities, a human protein interaction network, and a Plasmodium vivax protein interaction network. An iterative network propagation was performed on the heterogeneous network until we obtained stabilized weights. The association scores were calculated for qualifying a novel potential human-malaria protein association. This method provided a better performance compared to random experiments. After that, the stabilized network was clustered into association modules. The potential association candidates were then thoroughly analyzed by statistical enrichment analysis with protein complexes and known drug targets. The most promising target proteins were the succinate dehydrogenase protein complex in the human citrate (TCA) cycle pathway and the nicotinic acetylcholine receptor in the human central nervous system. Promising associations and potential drug targets were also provided for further studies and designs in therapeutic approaches for malaria at a systematic level. In conclusion, this method is efficient to identify new human-malaria protein associations and can be generalized to infer other types of association studies to further advance biomedical science.
Role of Mycoplasma Chaperone DnaK in Cellular Transformation
Authors: Benedetti Francesca , Cocchi Fiorenza , Latinovic Olga S. , Curreli Sabrina , Krishnan Selvi , Munawwar Arshi , Gallo Robert C. , Zella Davide
Published: February 2020

Studies of the human microbiome have elucidated an array of complex interactions between prokaryotes and their hosts. However, precise bacterial pathogen–cancer relationships remain largely elusive, although several bacteria, particularly those establishing persistent intra-cellular infections, like mycoplasmas, can alter host cell cycles, affect apoptotic pathways, and stimulate the production of inflammatory substances linked to DNA damage, thus potentially promoting abnormal cell growth and transformation. Consistent with this idea, in vivo experiments in several chemically induced or genetically deficient mouse models showed that germ-free conditions reduce colonic tumor formation. We demonstrate that mycoplasma DnaK, a chaperone protein belonging to the Heath shock protein (Hsp)-70 family, binds Poly-(ADP-ribose) Polymerase (PARP)-1, a protein that plays a critical role in the pathways involved in recognition of DNA damage and repair, and reduces its catalytic activity. It also binds USP10, a key p53 regulator, reducing p53 stability and anti-cancer functions. Finally, we showed that bystander, uninfected cells take up exogenous DnaK—suggesting a possible paracrine function in promoting cellular transformation, over and above direct mycoplasma infection. We propose that mycoplasmas, and perhaps certain other bacteria with closely related DnaK, may have oncogenic activity, mediated through the inhibition of DNA repair and p53 functions, and may be involved in the initiation of some cancers but not necessarily involved nor necessarily even be present in later stages.
Influence of Residualizing Properties of the Radiolabel on Radionuclide Molecular Imaging of HER3 Using Affibody Molecules
Authors: Rinne Sara S. , Xu Tianqi , Dahlsson Leitao Charles , Ståhl Stefan , Löfblom John , Orlova Anna , Tolmachev Vladimir , Vorobyeva Anzhelika
Published: February 2020

Human epidermal growth factor receptor type 3 (HER3) is an emerging therapeutic target in several malignancies. To select potential responders to HER3-targeted therapy, radionuclide molecular imaging of HER3 expression using affibody molecules could be performed. Due to physiological expression of HER3 in normal organs, high imaging contrast remains challenging. Due to slow internalization of affibody molecules by cancer cells, we hypothesized that labeling (HE)3-ZHER3:08698-DOTAGA affibody molecule with non-residualizing [125I]-N-succinimidyl-4-iodobenzoate (PIB) label would improve the tumor-to-normal organs ratios compared to previously reported residualizing radiometal labels. The [125I]I-PIB-(HE)3-ZHER3:08698-DOTAGA was compared side-by-side with [111In]In-(HE)3-ZHER3:08698-DOTAGA. Both conjugates demonstrated specific high-affinity binding to HER3-expressing BxPC-3 and DU145 cancer cells. Biodistribution in mice bearing BxPC-3 xenografts at 4 and 24 h pi showed faster clearance of the [125I]I-PIB label compared to the indium-111 label from most tissues, except blood. This resulted in higher tumor-to-organ ratios in HER3-expressing organs for [125I]I-PIB-(HE)3-ZHER3:08698-DOTAGA at 4 h, providing the tumor-to-liver ratio of 2.4 ± 0.3. The tumor uptake of both conjugates was specific, however, it was lower for the [125I]I-PIB label. In conclusion, the use of non-residualizing [125I]I-PIB label for HER3-targeting affibody molecule provided higher tumor-to-liver ratio than the indium-111 label, however, further improvement in tumor uptake and retention is needed.
RNA Splicing Defects in Hypertrophic Cardiomyopathy: Implications for Diagnosis and Therapy
Authors: Ribeiro Marta , Furtado Marta , Martins Sandra , Carvalho Teresa , Carmo-Fonseca Maria
Published: February 2020

Hypertrophic cardiomyopathy (HCM), the most common inherited heart disease, is predominantly caused by mutations in genes that encode sarcomere-associated proteins. Effective gene-based diagnosis is critical for the accurate clinical management of patients and their family members. However, the introduction of high-throughput DNA sequencing approaches for clinical diagnostics has vastly expanded the number of variants of uncertain significance, leading to many inconclusive results that limit the clinical utility of genetic testing. More recently, developments in RNA analysis have been improving diagnostic outcomes by identifying new variants that interfere with splicing. This review summarizes recent discoveries of RNA mis-splicing in HCM and provides an overview of research that aims to apply the concept of RNA therapeutics to HCM.
Ganglionic Acetylcholine Receptor Antibodies and Autonomic Dysfunction in Autoimmune Rheumatic Diseases
Authors: Imamura Michie , Mukaino Akihiro , Takamatsu Koutaro , Tsuboi Hiroto , Higuchi Osamu , Nakamura Hideki , Abe Saori , Ando Yukio , Matsuo Hidenori , Nakamura Tadashi , Sumida Takayuki , Kawakami Atsushi , Nakane Shunya
Published: February 2020

Autonomic neuropathy has been reported in autoimmune rheumatic diseases (ARD) including Sjögren’s syndrome, systemic sclerosis, rheumatoid arthritis, and systemic lupus erythematosus. However, the pathophysiological mechanism underlying autonomic dysfunction remains unknown to researchers. On the other hand, autoimmune autonomic ganglionopathy (AAG) is an acquired immune-mediated disorder, which causes dysautonomia that is mediated by autoantibodies against ganglionic acetylcholine receptors (gAChRs). The purpose of this review was to describe the characteristics of autonomic disturbance through previous case reports and the functional tests used in these studies and address the importance of anti-gAChR antibodies. We have established luciferase immunoprecipitation systems to detect antibodies against gAChR in the past and determined the prevalence of gAChR antibodies in various autoimmune diseases including AAG and rheumatic diseases. Autonomic dysfunction, which affects lower parasympathetic and higher sympathetic activity, is usually observed in ARD. The anti-gAChR antibodies may play a crucial role in autonomic dysfunction observed in ARD. Further studies are necessary to determine whether anti-gAChR antibody levels are correlated with the severity of autonomic dysfunction in ARD.
Artocarpus lakoocha Extract Inhibits LPS-Induced Inflammatory Response in RAW 264.7 Macrophage Cells
Authors: Hankittichai Phateep , Buacheen Pensiri , Pitchakarn Pornsiri , Na Takuathung Mingkwan , Wikan Nitwara , Smith Duncan R. , Potikanond Saranyapin , Nimlamool Wutigri
Published: February 2020

Artocarpus lakoocha Roxb. (AL) has been known for its high content of stilbenoids, especially oxyresveratrol. AL has been used in Thai traditional medicine for centuries. However, the role of AL in regulating inflammation has not been elucidated. Here we investigated the molecular mechanisms underlying the anti-inflammation of AL ethanolic extract in RAW 264.7 murine macrophage cell line. The HPLC results revealed that this plant was rich in oxyresveratrol, and AL ethanolic extract exhibited anti-inflammatory properties. In particular, AL extract decreased lipopolysaccharide (LPS)-mediated production and secretion of cytokines and chemokine, including IL-6, TNF-α, and MCP-1. Consistently, the extract inhibited the production of nitric oxide (NO) in the supernatants of LPS-stimulated cells. Data from the immunofluorescence study showed that AL extract suppressed nuclear translocation of nuclear factor-kappa B (NF-κB) upon LPS induction. Results from Western blot analysis further confirmed that AL extract strongly prevented the LPS-induced degradation of IκB which is normally required for the activation of NF-κB. The protein expression of iNOS and COX-2 in response to LPS stimulation was significantly decreased with the presence of AL extract. AL extract was found to play an anti-inflammatory role, in part through inhibiting LPS-induced activation of Akt. The extract had negligible impact on the activation of mitogen-activated protein kinase (MAPK) pathways. Specifically, incubation of cells with the extract for only 3 h demonstrated the rapid action of AL extract on inhibiting the phosphorylation of Akt, but not ERK1/2. Longer exposure (24 h) to AL extract was required to mildly reduce the phosphorylation of ERK1/2, p38, and JNK MAPKs. These results indicate that AL extract manipulates its anti-inflammatory effects mainly through blocking the PI3K/Akt and NF-κB signal transduction pathways. Collectively, we believe that AL could be a potential alternative agent for alleviating excessive inflammation in many inflammation-associated diseases.
Activation of Transposable Elements in Immune Cells of Fibromyalgia Patients
Authors: Ovejero Tamara , Sadones Océane , Sánchez-Fito Teresa , Almenar-Pérez Eloy , Espejo José Andrés , Martín-Martínez Eva , Nathanson Lubov , Oltra Elisa
Published: February 2020

Advancements in nucleic acid sequencing technology combined with an unprecedented availability of metadata have revealed that 45% of the human genome constituted by transposable elements (TEs) is not only transcriptionally active but also physiologically necessary. Dysregulation of TEs, including human retroviral endogenous sequences (HERVs) has been shown to associate with several neurologic and autoimmune diseases, including Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). However, no study has yet addressed whether abnormal expression of these sequences correlates with fibromyalgia (FM), a disease frequently comorbid with ME/CFS. The work presented here shows, for the first time, that, in fact, HERVs of the H, K and W types are overexpressed in immune cells of FM patients with or without comorbid ME/CFS. Patients with increased HERV expression (N = 14) presented increased levels of interferon (INF-β and INF-γ) but unchanged levels of TNF-α. The findings reported in this study could explain the flu-like symptoms FM patients present with in clinical practice, in the absence of concomitant infections. Future work aimed at identifying specific genomic loci differentially affected in FM and/or ME/CFS is warranted.
Localization of Annexin A6 in Matrix Vesicles During Physiological Mineralization
Authors: Veschi Ekeveliny Amabile , Bolean Maytê , Strzelecka-Kiliszek Agnieszka , Bandorowicz-Pikula Joanna , Pikula Slawomir , Granjon Thierry , Mebarek Saida , Magne David , Ramos Ana Paula , Rosato Nicola , Millán José Luis , Buchet Rene , Bottini Massimo , Ciancaglini Pietro
Published: February 2020

Annexin A6 (AnxA6) is the largest member of the annexin family of proteins present in matrix vesicles (MVs). MVs are a special class of extracellular vesicles that serve as a nucleation site during cartilage, bone, and mantle dentin mineralization. In this study, we assessed the localization of AnxA6 in the MV membrane bilayer using native MVs and MV biomimetics. Biochemical analyses revealed that AnxA6 in MVs can be divided into three distinct groups. The first group corresponds to Ca2+-bound AnxA6 interacting with the inner leaflet of the MV membrane. The second group corresponds to AnxA6 localized on the surface of the outer leaflet. The third group corresponds to AnxA6 inserted in the membrane’s hydrophobic bilayer and co-localized with cholesterol (Chol). Using monolayers and proteoliposomes composed of either dipalmitoylphosphatidylcholine (DPPC) to mimic the outer leaflet of the MV membrane bilayer or a 9:1 DPPC:dipalmitoylphosphatidylserine (DPPS) mixture to mimic the inner leaflet, with and without Ca2+, we confirmed that, in agreement with the biochemical data, AnxA6 interacted differently with the MV membrane. Thermodynamic analyses based on the measurement of surface pressure exclusion (πexc), enthalpy (ΔH), and phase transition cooperativity (Δt1/2) showed that AnxA6 interacted with DPPC and 9:1 DPPC:DPPS systems and that this interaction increased in the presence of Chol. The selective recruitment of AnxA6 by Chol was observed in MVs as probed by the addition of methyl-β-cyclodextrin (MβCD). AnxA6-lipid interaction was also Ca2+-dependent, as evidenced by the increase in πexc in negatively charged 9:1 DPPC:DPPS monolayers and the decrease in ΔH in 9:1 DPPC:DPPS proteoliposomes caused by the addition of AnxA6 in the presence of Ca2+ compared to DPPC zwitterionic bilayers. The interaction of AnxA6 with DPPC and 9:1 DPPC:DPPS systems was distinct even in the absence of Ca2+ as observed by the larger change in Δt1/2 in 9:1 DPPC:DPPS vesicles as compared to DPPC vesicles. Protrusions on the surface of DPPC proteoliposomes observed by atomic force microscopy suggested that oligomeric AnxA6 interacted with the vesicle membrane. Further work is needed to delineate possible functions of AnxA6 at its different localizations and ways of interaction with lipids.
Using Transcriptomic Analysis to Assess Double-Strand Break Repair Activity: Towards Precise in Vivo Genome Editing
Authors: Pasquini Giovanni , Cora Virginia , Swiersy Anka , Achberger Kevin , Antkowiak Lena , Müller Brigitte , Wimmer Tobias , Fraschka Sabine Anne-Kristin , Casadei Nicolas , Ueffing Marius , Liebau Stefan , Stieger Knut , Busskamp Volker
Published: February 2020

Mutations in more than 200 retina-specific genes have been associated with inherited retinal diseases. Genome editing represents a promising emerging field in the treatment of monogenic disorders, as it aims to correct disease-causing mutations within the genome. Genome editing relies on highly specific endonucleases and the capacity of the cells to repair double-strand breaks (DSBs). As DSB pathways are cell-cycle dependent, their activity in postmitotic retinal neurons, with a focus on photoreceptors, needs to be assessed in order to develop therapeutic in vivo genome editing. Three DSB-repair pathways are found in mammalian cells: Non-homologous end joining (NHEJ); microhomology-mediated end joining (MMEJ); and homology-directed repair (HDR). While NHEJ can be used to knock out mutant alleles in dominant disorders, HDR and MMEJ are better suited for precise genome editing, or for replacing entire mutation hotspots in genomic regions. Here, we analyzed transcriptomic in vivo and in vitro data and revealed that HDR is indeed downregulated in postmitotic neurons, whereas MMEJ and NHEJ are active. Using single-cell RNA sequencing analysis, we characterized the dynamics of DSB repair pathways in the transition from dividing cells to postmitotic retinal cells. Time-course bulk RNA-seq data confirmed DSB repair gene expression in both in vivo and in vitro samples. Transcriptomic DSB repair pathway profiles are very similar in adult human, macaque, and mouse retinas, but not in ground squirrel retinas. Moreover, human-induced pluripotent stem-cell-derived neurons and retinal organoids can serve as well suited in vitro testbeds for developing genomic engineering approaches in photoreceptors. Our study provides additional support for designing precise in vivo genome-editing approaches via MMEJ, which is active in mature photoreceptors.
Pollen Protein: Lipid Macronutrient Ratios May Guide Broad Patterns of Bee Species Floral Preferences
Authors: Vaudo Anthony D. , Tooker John F. , Patch Harland M. , Biddinger David J. , Coccia Michael , Crone Makaylee K. , Fiely Mark , Francis Jacob S. , Hines Heather M. , Hodges Mackenzie , Jackson Stephanie W. , Michez Denis , Mu Junpeng , Russo Laura , Safari Maliheh , Treanore Erin D. , Vanderplanck Maryse , Yip Eric , Leonard Anne S. , Grozinger Christina M.
Published: February 2020

Pollinator nutritional ecology provides insights into plant–pollinator interactions, coevolution, and the restoration of declining pollinator populations. Bees obtain their protein and lipid nutrient intake from pollen, which is essential for larval growth and development as well as adult health and reproduction. Our previous research revealed that pollen protein to lipid ratios (P:L) shape bumble bee foraging preferences among pollen host-plant species, and these preferred ratios link to bumble bee colony health and fitness. Yet, we are still in the early stages of integrating data on P:L ratios across plant and bee species. Here, using a standard laboratory protocol, we present over 80 plant species’ protein and lipid concentrations and P:L values, and we evaluate the P:L ratios of pollen collected by three bee species. We discuss the general phylogenetic, phenotypic, behavioral, and ecological trends observed in these P:L ratios that may drive plant–pollinator interactions; we also present future research questions to further strengthen the field of pollination nutritional ecology. This dataset provides a foundation for researchers studying the nutritional drivers of plant–pollinator interactions as well as for stakeholders developing planting schemes to best support pollinators.
Design of a Measuring Device and Winch Structure for Detecting the Distance and Direction of Two Seabed Pipelines
Authors: Wang Zhuo , Lan Di , Wang Tao , Zhang Bo
Published: February 2020

To measure the distance and direction between the flanges of two seabed pipelines, a measuring device for pulling a rope in seawater was designed. Addressing the sealing problem of the key equipment the rotating shaft of the rope winch, we used the magnetic coupling principle to transfer the driving moment, and converted the dynamic seal into a static seal structure to reliably seal the motor. Through an experiment measuring two pipelines with the underwater rope pulling device, we verified that the measuring accuracy of the device meets the design requirements, and confirmed the feasibility of applying magnetic coupling technology in winches.
Reflection Analysis of Impermeable Slopes under Bimodal Sea Conditions
Authors: Orimoloye Stephen , Karunarathna Harshinie , Reeve Dominic E.
Published: February 2020

Understanding of the reflection characteristics of coastal seawalls is crucial for design. Wave reflection can cause difficulties in small vessel manoeuvring at harbour entrances; this can cause damage to the toe of coastal structures by scouring. Previous studies have examined the reflection characteristics of coastal seawalls under random wind-generated waves without considering the effects of wave bimodality created by the presence of swell waves. This present study focuses on the influence of random wave bimodality on the reflective characteristics of coastal seawalls. 823 experimental tests were conducted to examine the reflection performance of impermeable sloping seawalls under bimodal waves. Reflection coefficients were computed from each test. The analysis of the results suggests that both unimodal and bimodal waves give similar reflection characteristics. However, the reflection coefficient in bimodal sea states seems to be more prolonged than in the unimodal sea states. It was found that the reflection coefficients of coastal seawalls are strongly influenced by the seawall slope, the wave steepness, the relative water depth, and the surf similarity parameters. A new empirical reflection equation to describe the influence of wave bimodality on the reflection characteristics of coastal seawalls has been formulated based on this study.
Preparation and Characterization of Soap-Free Vinyl Acetate/Butyl Acrylate Copolymer Latex
Authors: Zhang Yifu , Bei Wenkai , Qin Zhiyong
Published: February 2020

The soap-free emulsion of vinyl acetate (VAc)/butyl acrylate (BA) copolymer was prepared by a semi-continuous and pre-emulsification polymerization method, using ammonium sulfate allyloxy nonylphenoxy poly(ethyleneoxy) (10) ether (DNS-86) as a reactive emulsifier. The effects of DNS-86 on the stability of the emulsion and the properties of the latex film were investigated. The infrared spectrum, thermal stability, glass transition temperature and micromorphology of latex were also studied. The results showed that the emulsion had the best stability and the conversion rate reached a maximum of 98.46% when the DNS-86 amount was 4 wt % of the total amount of monomers. Compared with the PVAc latex synthesized with octylphenol polyoxyethylene ether (10) (OP-10), the latex prepared with DNS-86 has higher thermal stability and ionic stability, whereas the latex film has better water resistance.
Experimental Study on Preparation of Ferropericlase by Oxalate Coprecipitation
Authors: Xiao Yanjun , Sun Tong , Zhao Yong-Hong
Published: February 2020

It is always a goal of scientists to develop new techniques to identify the composition of mantle materials and understand geodynamic processes accurately. Ferropericlase (Mg,Fe)O is a prominent mineral in the lower mantel. It is a common practice in the research community to prepare ferropericlase using a solid-phase synthesis method or high-pressure experiment synthesis method. This conventional method contains a number of ambiguities a great deal of time is needed. In this paper, we have addressed the drawbacks of the conventional technique using a liquid-phase synthesis method to prepare ferropericlase. During the experiment, oxalic acid was added to a mixed solution of ferrous sulfate and magnesium chloride and mixed according to the molar ratio. The formed magnesium iron oxalate precipitate was sintered and reduced into the final sample. Furthermore, the final sample was analyzed using XRD and SEM. Compared to the solid-phase method, this coprecipitation method could produce ferropericlase with a shorter sintering time, lower sintering temperature, and a reduction in the amount of gas consumed. XRD and SEM results show that the liquid-phase method produced samples with better composition homogeneity.