bluuebunny/crossref_metadata_2025 huggingface dataset:
Monoalkylated Epigallocatechin-3-gallate (C18-EGCG) as Novel Lipophilic EGCG Derivative: Characterization and Antioxidant Evaluation
Authors: Minnelli Cristina , Galeazzi Roberta , Laudadio Emiliano , Amici Adolfo , Rusciano Dario , Armeni Tatiana , Cantarini Mattia , Stipa Pierluigi , Mobbili Giovanna
Published: March 2020

Epigallocatechin-3-gallate (EGCG) has the highest antioxidant activity compared to the others catechins of green tea. However, the beneficial effects are mainly limited by its poor membrane permeability. A derivatization strategy to increase the EGCG interaction with lipid membranes is considered as one feasible approach to expand its application in lipophilic media, in particular the cellular absorption. At this purpose the hydrophilic EGCG was modified by inserting an aliphatic C18 chain linked to the gallate ring by an ethereal bond, the structure determined by NMR (Nuclear Magnetic Resonance) and confirmed by Density Functional Theory (DFT) calculations. The in vitro antioxidant activity of the mono-alkylated EGCG (C18-EGCG) was studied by the DPPH and Thiobarbituric Acid Reactive Substances (TBARS) assays, and its ability to protect cells towards oxidative stress was evaluated in Adult Retinal Pigmented Epithelium (ARPE-19) cells. Molecular Dynamics (MD) simulation and liposomal/buffer partition were used to study the interaction of the modified and unmodified antioxidants with a cell membrane model: the combined experimental-in silico approach shed light on the higher affinity of C18-EGCG toward lipid bilayer. Although the DPPH assay stated that the functionalization decreases the EGCG activity against free radicals, from cellular experiments it resulted that the lipid moiety increases the antioxidant protection of the new lipophilic derivative.
Wideband UHF Antenna for Partial Discharge Detection
Authors: Cui Zhen , Park Seungyong , Choo Hosung , Jung Kyung-Young
Published: March 2020

This paper presents a ultra-high frequency (UHF) antenna for partial discharge (PD) detection and the antenna sensor can be used near a conducting ground wire. The proposed UHF antenna has advantages of easy setup and higher-frequency detection over the high-frequency current transformer (HFCT) sensor. First, a variety of loop-shaped antennas are designed to compare each near field coupling capability. Then, a new UHF antenna is designed based on the loop-shaped antenna, which has the best near field coupling capability. Finally, the proposed UHF antenna is fabricated and measured. It provides a wide impedance bandwidth of 760 MHz (740–1500 MHz). Its simple setup configuration and wide bandwidth frequency response in the UHF band can provide a more efficient means for PD detection.
Combining Machine Learning and Social Network Analysis to Reveal the Organizational Structures
Authors: Nurek Mateusz , Michalski Radosław
Published: March 2020

Formation of a hierarchy within an organization is a natural way of assigning the duties, delegating responsibilities and optimizing the flow of information. Only for the smallest companies the lack of the hierarchy, that is, a flat one, is possible. Yet, if they grow, the introduction of a hierarchy is inevitable. Most often, its existence results in different nature of the tasks and duties of its members located at various organizational levels or in distant parts of it. On the other hand, employees often send dozens of emails each day, and by doing so, and also by being engaged in other activities, they naturally form an informal social network where nodes are individuals and edges are the actions linking them. At first, such a social network seems distinct from the organizational one. However, the analysis of this network may lead to reproducing the organizational hierarchy of companies. This is due to the fact that that people holding a similar position in the hierarchy possibly share also a similar way of behaving and communicating attributed to their role. The key concept of this work is to evaluate how well social network measures when combined with other features gained from the feature engineering align with the classification of the members of organizational social network. As a technique for answering this research question, machine learning apparatus was employed. Here, for the classification task, Decision Trees, Random Forest, Neural Networks and Support Vector Machines have been evaluated, as well as a collective classification algorithm, which is also proposed in this paper. The used approach allowed to compare how traditional methods of machine learning classification, while supported by social network analysis, performed in comparison to a typical graph algorithm. The results demonstrate that the social network built using the metadata on communication highly exposes the organizational structure.
A Control Strategy for Suppressing Zero-Sequence Circulating Current in Paralleled Three-Phase Voltage-Source PWM Converters
Authors: Han Zhao , Wang Xiaoli , Jiang Baochen , Chen Jingru
Published: March 2020

In microgrids, paralleled converters can increase the system capacity and conversion efficiency but also generate zero-sequence circulating current, which will distort the AC-side current and increase power losses. Studies have shown that, for two paralleled three-phase voltage-source pulse width modulation (PWM) converters with common DC bus controlled by space vector PWM, the zero-sequence circulating current is mainly related to the difference of the zero-sequence duty ratio between the converters. Therefore, based on the traditional control ideal of zero-vector action time adjustment, this paper proposes a zero-sequence circulating current suppression strategy using proportional–integral quasi-resonant control and feedforward compensation control. Firstly, the dual-loop decoupled control was utilized in a single converter. Then, in order to reduce the amplitude and main harmonic components of the circulating current, a zero-vector duty ratio adjusting factor was initially generated by a proportional–integral quasi-resonant controller. Finally, to eliminate the difference of zero-sequence duty ratio between the converters, the adjusting factor was corrected by a feedforward compensation link. The simulation mode of Matlab/Simulink was constructed for the paralleled converters based on the proposed control strategy. The results verify that this strategy can effectively suppress the zero-sequence circulating current and improve power quality.
Analysis of Effects of Rock Physical Properties Changes from Freeze-Thaw Weathering in Ny-Ålesund Region: Part 1—Experimental Study
Authors: Park Keunbo , Kim Kiju , Lee Kichoel , Kim Dongwook
Published: March 2020

In order to investigate the weathering characteristics of rocks in response to freeze-thaw conditions in northern latitudes, we analysed meteorological data from the Ny-Ålesund region in Norway, and observed changes in the physical and mechanical properties of rocks of dolomite and quartzite. To assess the effects of freeze-thaw weathering on these rock properties, 900 cycles of long-term freeze-thaw tests were conducted for the sampled rocks in two locations. P-wave velocity, absorption, shore hardness, and the uniaxial compressive strength of the sampled rocks were measured at every 150 cycles in order to analyse physical and mechanical mediator variables of freeze-thaw weathering. It was found that an increasing number of freeze-thaw cycle on the sampled rocks decreases uniaxial compressive strength, shore hardness, and P-wave velocity and increases absorption.
HI-Sky: Hash Index-Based Skyline Query Processing
Authors: Choi Jong-Hyeok , Hao Fei , Nasridinov Aziz
Published: March 2020

The skyline query has recently attracted a considerable amount of research interest in several fields. The query conducts computations using the domination test, where “domination” means that a data point does not have a worse value than others in any dimension, and has a better value in at least one dimension. Therefore, the skyline query can be used to construct efficient queries based on data from a variety of fields. However, when the number of dimensions or the amount of data increases, naïve skyline queries lead to a degradation in overall performance owing to the higher cost of comparisons among data. Several methods using index structures have been proposed to solve this problem but have not improved the performance of skyline queries because their indices are heavily influenced by the dimensionality and data amount. Therefore, in this study, we propose HI-Sky, a method that can perform quick skyline computations by using the hash index to overcome the above shortcomings. HI-Sky effectively manages data through the hash index and significantly improves performance by effectively eliminating unnecessary data comparisons when computing the skyline. We provide the theoretical background for HI-Sky and verify its improvement in skyline query performance through comparisons with prevalent methods.
Simultaneous Determination of 12 Marker Components in Yeonkyopaedok-san Using HPLC–PDA and LC–MS/MS
Authors: Seo Chang-Seob , Shin Hyeun-Kyoo
Published: March 2020

Yeonkyopaedok-san is a traditional Korean medicine used in the early treatment of boils. In the present study, its 12 marker components for quality control were determined using high-performance liquid chromatography (HPLC) with photodiode array detection and ultra-performance liquid chromatography–mass spectrometry with tandem mass spectrometry (UPLC–MS/MS). The investigated 12 marker components of Yeonkyopaedok-san were as follows: 3-caffeoylquinic acid, cimifugin 7-glucoside, liquiritin apioside, ferulic acid, narirutin, 5-O-methylvisammioside, naringin, neohesperidin, oxypeucedanin hydrate, arctigenin, glycyrrhizic acid, and 6-gingerol. The analytical column used for the separation of the 12 marker analytes in Yeonkyopaedok-san was a Waters SunFire C18 column (4.6 mm × 250 mm, 5 μm). The two mobile phases used were 0.1% (v/v) aqueous formic acid and 0.1% (v/v) formic acid in acetonitrile. In the UPLC–MS/MS analysis, all components were separated using a Waters ACQUITY UPLC BEH C18 column (2.1 mm × 100 mm, 1.7 μm). The two mobile phases used were 0.1% (v/v) aqueous formic acid and acetonitrile. The coefficient of determination of the calibration curves in both analysis systems showed good linearity (>0.99). The amounts of the 12 marker components in Yeonkyopaedok-san determined using HPLC–photodiode array detection and UPLC–MS/MS analyses were found to be 0.14–9.00 mg/g and 2.35–853.11 μg/g, respectively.
Design and Implementation of Quad-Port MIMO Antenna with Dual-Band Elimination Characteristics for Ultra-Wideband Applications
Authors: Kumar Pawan , Urooj Shabana , Alrowais Fadwa
Published: March 2020

A planar, microstrip line-fed, quad-port, multiple-input-multiple-output (MIMO) antenna with dual-band rejection features is proposed for ultra-wideband (UWB) applications. The proposed MIMO antenna design consists of four identical octagonal-shaped radiating elements, which are placed orthogonally to each other. The dual-band rejection property (3.5 GHz and 5.5 GHz corresponding to Wi-MAX and WLAN bands) was obtained by introducing a hexagonal-shaped complementary split-ring resonator (HCSRR) in the radiators of the designed antenna. The MIMO antenna was etched on low-cost FR-4 dielectric substrate of size 58 × 58 × 0.8 mm3. Isolation higher than 18 dB and envelope correlation coefficient (ECC) lesser than 0.07 was observed for the MIMO/diversity antenna in the operating range of 3–16 GHz. The presented four-port UWB MIMO antenna configuration was fabricated, and the experimental results validate the simulation outcomes.
PET/CT Radiomics in Lung Cancer: An Overview
Authors: Bianconi Francesco , Palumbo Isabella , Spanu Angela , Nuvoli Susanna , Fravolini Mario Luca , Palumbo Barbara
Published: March 2020

Quantitative extraction of imaging features from medical scans (‘radiomics’) has attracted a lot of research attention in the last few years. The literature has consistently emphasized the potential use of radiomics for computer-assisted diagnosis, as well as for predicting survival and response to treatment. Radiomics is appealing in that it enables full-field analysis of the lesion, provides nearly real-time results, and is non-invasive. Still, a lot of studies suffer from a series of drawbacks such as lack of standardization and repeatability. Such limitations, along with the unmet demand for large enough image datasets for training the algorithms, are major hurdles that still limit the application of radiomics on a large scale. In this paper, we review the current developments, potential applications, limitations, and perspectives of PET/CT radiomics with specific focus on the management of patients with lung cancer.
Computational Atomistic Modeling in Carbon Flatland and Other 2D Nanomaterials
Authors: Champagne Aurélie , Dechamps Samuel , Dubois Simon M.-M. , Lherbier Aurélien , Nguyen Viet-Hung , Charlier Jean-Christophe
Published: March 2020

As in many countries, the rise of nanosciences in Belgium has been triggered in the eighties in the one hand, by the development of scanning tunneling and atomic force microscopes offering an unprecedented possibility to visualize and manipulate the atoms, and in the other hand, by the synthesis of nano-objects in particular carbon nanostructures such as fullerene and nanotubes. Concomitantly, the increasing calculating power and the emergence of computing facilities together with the development of DFT-based ab initio softwares have brought to nanosciences field powerful simulation tools to analyse and predict properties of nano-objects. Starting with 0D and 1D nanostructures, the floor is now occupied by the 2D materials with graphene being the bow of this 2D ship. In this review article, some specific examples of 2D systems has been chosen to illustrate how not only density functional theory (DFT) but also tight-binding (TB) techniques can be daily used to investigate theoretically the electronic, phononic, magnetic, and transport properties of these atomically thin layered materials.
Generative Adversarial Network for Image Super-Resolution Combining Texture Loss
Authors: Jiang Yuning , Li Jinhua
Published: March 2020

Objective: Super-resolution reconstruction is an increasingly important area in computer vision. To alleviate the problems that super-resolution reconstruction models based on generative adversarial networks are difficult to train and contain artifacts in reconstruction results, we propose a novel and improved algorithm. Methods: This paper presented TSRGAN (Super-Resolution Generative Adversarial Networks Combining Texture Loss) model which was also based on generative adversarial networks. We redefined the generator network and discriminator network. Firstly, on the network structure, residual dense blocks without excess batch normalization layers were used to form generator network. Visual Geometry Group (VGG)19 network was adopted as the basic framework of discriminator network. Secondly, in the loss function, the weighting of the four loss functions of texture loss, perceptual loss, adversarial loss and content loss was used as the objective function of generator. Texture loss was proposed to encourage local information matching. Perceptual loss was enhanced by employing the features before activation layer to calculate. Adversarial loss was optimized based on WGAN-GP (Wasserstein GAN with Gradient Penalty) theory. Content loss was used to ensure the accuracy of low-frequency information. During the optimization process, the target image information was reconstructed from different angles of high and low frequencies. Results: The experimental results showed that our method made the average Peak Signal to Noise Ratio of reconstructed images reach 27.99 dB and the average Structural Similarity Index reach 0.778 without losing too much speed, which was superior to other comparison algorithms in objective evaluation index. What is more, TSRGAN significantly improved subjective visual evaluations such as brightness information and texture details. We found that it could generate images with more realistic textures and more accurate brightness, which were more in line with human visual evaluation. Conclusions: Our improvements to the network structure could reduce the model’s calculation amount and stabilize the training direction. In addition, the loss function we present for generator could provide stronger supervision for restoring realistic textures and achieving brightness consistency. Experimental results prove the effectiveness and superiority of TSRGAN algorithm.
Mean Age of Air in Natural Ventilated Buildings: Experimental Evaluation and CO2 Prediction by Artificial Neural Networks
Authors: Buratti Cinzia , Palladino Domenico
Published: March 2020

The mean age of air (MAA) is one of the most useful parameters in evaluating indoor air quality in natural ventilated buildings. Its evaluation is generally based on the CO2 monitoring within the environment; however, other methods can be found in the literature, but they have not always led to satisfactory results. In this context, the present paper is focused on two main topics: the effect of the windows airtightness and of the environmental conditions on MAA and the application of artificial neural network (ANN) for the CO2 prediction within the room. Two case studies (case study 1 located in Terni and case study 2 located in Perugia) were investigated, which differ in geometric dimensions (useful area, volume, window area) and in airtightness of windows. The indoor and outdoor environmental conditions (air temperature, pressure, relative humidity, air velocity, and indoor CO2 concentration) were monitored in 33 experimental campaigns, in four room configurations: open door-open window (OD-OW); closed door-open window (CD-OW); open door-closed window (OD-CW); closed door-closed window (CD-CW). Tracer decay methodology, according to ISO 16000-8:2007 standard, was compiled during all the experimental campaigns. A feedforward ANN, able to simulate the indoor CO2 concentration within the rooms, was then implemented; the monitored environmental conditions (air temperature, pressure, relative humidity, and air velocity), the geometric dimensions (useful area, volume, window area), and the airtightness of windows were provided as input data, while the CO2 concentration was used as target. In particular, data of 19 experimental campaigns were provided for the training process of the network, while 14 were only used for testing the reliability of ANN. The CO2 concentration predicted by ANN was then used for the MAA calculation in the four room configurations. Experimental results show that MAA of case study 2 is always higher, in all the examined configurations, due to the higher airtightness characteristics of the window and to the higher volume of the room. When the difference between indoor and outdoor temperature increases, the MAA increases too, in almost all the investigated configurations. Finally, the CO2 concentration predicted by ANN was compared with experimental data; results show a good accuracy of the network both in CO2 prediction and in the MAA calculation. The predicted CO2 concentration at the beginning of experimental campaigns (time step 0) always differs less than 2% from experimental data, while a mean percentage difference of −18.8% was found considering the maximum CO2 concentration. The MAA calculated using the predicted CO2 of ANN was greater than the one obtained from experimental data, with a difference in the 0.5–1.3 min range, depending on the configuration. According to the results, the developed ANN can be considered an alternative and valuable tool for a preliminary evaluation of MAA.
Distributed Adaptive Neural Network Control Applied to a Formation Tracking of a Group of Low-Cost Underwater Drones in Hazardous Environments
Authors: Pham Hoang Anh , Soriano Thierry , Ngo Van Hien , Gies Valentin
Published: March 2020

This paper addresses a formation tracking problem of multiple low-cost underwater drones by implementing distributed adaptive neural network control (DANNC). It is based on a leader-follower architecture to operate in hazardous environments. First, unknown parameters of underwater vehicle dynamics, which are important requirements for real-world applications, are approximated by a neural network using a radial basis function. More specifically, those parameters are only calculated by local information, which can be obtained by an on-board camera without using an external positioning system. Secondly, a potential function is employed to ensure there is no collision between the underwater drones. We then propose a desired configuration of a group of unmanned underwater vehicles (UUVs) as a time-variant function so that they can quickly change their shape between them to facilitate the crossing in a narrow area. Finally, three UUVs, based on a robot operating system (ROS) platform, are used to emphasize the realistic low-cost aspect of underwater drones. The proposed approach is validated by evaluating in different experimental scenarios.
The Effectiveness of Embodied Pedagogical Agents and Their Impact on Students Learning in Virtual Worlds
Authors: Grivokostopoulou Foteini , Kovas Konstantinos , Perikos Isidoros
Published: March 2020

Over the last years, the successful integration of virtual reality in distance education contexts has led to the development of various frameworks related to the virtual learning approaches. 3D virtual worlds are an integral part of the landscape of education and demonstrate novel learning possibilities that can open new directions in education. An important aspect of virtual worlds relates to the intelligent, embodied pedagogical agents that are employed to enhance the interaction with students and improve their overall learning experience. The proper design and integration of embodied pedagogical agents in virtual learning environments are highly desirable. Although virtual agents constitute a vital part of virtual environments, their exact impact needs are yet to be addressed and assessed. The aim of the present study is to thoroughly examine and deeply understand the effect that embodied pedagogical agents have on the learning experience of students as well as on their performance. We examine how students perceive the role of pedagogical agents as learning companions during specific game-based activities and the effect that their assistance has on students’ learning. A concrete experimental study was conducted in AVARES, a 3D virtual world educational environment that teaches the domain of environmental engineering and energy generation. The results of the study point out that embodied pedagogical agents can improve students’ learning experience, enhance their engagement with learning activities and, most of all, improve their knowledge construction and performance.
Automated Detection of Multiple Lesions on Chest X-ray Images: Classification Using a Neural Network Technique with Association-Specific Contexts
Authors: Xu Shuaijing , Guo Junqi , Zhang Guangzhi , Bie Rongfang
Published: March 2020

Automated detection of lung lesions on Chest X-ray images shows good performance to reduce lung cancer mortality. However, it is difficult to detect multiple lesions of single image well and truly, and additional efforts are needed to improve diagnostic efficiency and quality. In this paper, a multi-label classification model combining attention-based neural networks and association-specific contexts is proposed for the detection of multiple lesions on chest X-ray images. A convolutional neural network and a long short-term memory network are first aligned by an attention mechanism to take advantage of both image and text information for the detection, called CNN-ATTENTION-LSTM (CAL) network. In addition, a mining method of implicit association strength to obtain an association network of chest lesions (CLA) network is designed to guide the training of CAL network. The CLA network provides possible clinical relationships between lesions to help the CAL network obtain better predictions. Experimental results on ChestX-ray14 dataset show that our method outperforms some state-of-the-art models under the metrics of area under curve (AUC), precision, recall, and F-score and achieves up to 85.4% in the case of atelectasis and infiltration. It indicates that the method may be useful in the computer-aided detection of multiple lesions on chest X-ray images.
Recent Developments of Solar Cells from PbS Colloidal Quantum Dots
Authors: Blachowicz Tomasz , Ehrmann Andrea
Published: March 2020

PbS (lead sulfide) colloidal quantum dots consist of crystallites with diameters in the nanometer range with organic molecules on their surfaces, partly with additional metal complexes as ligands. These surface molecules are responsible for solubility and prevent aggregation, but the interface between semiconductor quantum dots and ligands also influences the electronic structure. PbS quantum dots are especially interesting for optoelectronic applications and spectroscopic techniques, including photoluminescence, photodiodes and solar cells. Here we concentrate on the latter, giving an overview of the optical properties of solar cells prepared with PbS colloidal quantum dots, produced by different methods and combined with diverse other materials, to reach high efficiencies and fill factors.
Horizontal Temperature Fluxes in the Arctic in CMIP5 Model Results Analyzed with Self-Organizing Maps
Authors: Mewes Daniel , Jacobi Christoph
Published: March 2020

The meridional temperature gradient between mid and high latitudes decreases by Arctic amplification. Following this decrease, the circulation in the mid latitudes may change and, therefore, the meridional flux of heat and moisture increases. This might increase the Arctic temperatures even further. A proxy for the vertically integrated atmospheric horizontal energy flux was analyzed using the self-organizing-map (SOM) method. Climate Model Intercomparison Project Phase 5 (CMIP5) model data of the historical and Representative Concentration Pathway 8.5 (RCP8.5) experiments were analyzed to extract horizontal flux patterns. These patterns were analyzed for changes between and within the respective experiments. It was found that the general horizontal flux patterns are reproduced by all models and in all experiments in comparison with reanalyses. By comparing the reanalysis time frame with the respective historical experiments, we found that the general occurrence frequencies of the patterns differ substantially. The results show that the general structure of the flux patterns is not changed when comparing the historical and RCP8.5 results. However, the amplitudes of the fluxes are decreasing. It is suggested that the amplitudes are smaller in the RCP8.5 results compared to the historical results, following a greater meandering of the jet stream, which yields smaller flux amplitudes of the cluster mean.
The Aerosol-Radiation Interaction Effects of Different Particulate Matter Components during Heavy Pollution Periods in China
Authors: Wen Wei , Ma Xin , Guo Chunwei , Zhao Xiujuan , Xu Jing , Liu Lei , Wu Huacheng , Zhou Weiqing , Zhang Zijian
Published: March 2020

The Beijing-Tianjin-Hebei (BTH) region experienced heavy air pollution in December 2015, which provided a good opportunity to explore the aerosol-radiation interaction (ARI) effects of different particulate matter (PM) components (sulfate, nitrate, and black carbon (BC)). In this study, five tests were conducted by the Weather Research and Forecasting—Chemistry (WRF-Chem) model. The tests included scenario 1 simulation with ARI turned on, scenario 2 simulation with ARI turned off, scenario3 simulation without NOx/NO3− emissions and with ARI turned on, scenario 4 simulation without SO2/SO42− emissions and with ARI turned on, and scenario 5 simulation without BC emissions and with ARI turned on. The ARI decreased the downward shortwave radiation (SWDOWN) and the temperature at 2 m (T2), reduced the planetary boundary layer (PBL) height (PBLH), and increased the relative humidity (RH) at 2 m in the region. These factors also contribute to pollution accumulation. The results revealed that BC aerosols have a stronger effect on the reduction in SWDOWN than sulfate (SO42−) and nitrate (NO3−). BC aerosols produce both cooling and heating effects, while SO42− aerosols produce only cooling effects. The PBL decreased and RH2 increased due to the aerosol feedback effect of sulfate, nitrate, and BC. The ARI effect on meteorological factors during the nonheavy pollution period was much smaller than that during the pollution period.
Biliverdin Reductase A (BVRA) Knockout in Adipocytes Induces Hypertrophy and Reduces Mitochondria in White Fat of Obese Mice
Authors: Stec David E. , Gordon Darren M. , Nestor-Kalinoski Andrea L. , Donald Matthew C. , Mitchell Zachary L. , Creeden Justin F. , Hinds Terry D.
Published: March 2020

Biliverdin reductase (BVR) is an enzymatic and signaling protein that has multifaceted roles in physiological systems. Despite the wealth of knowledge about BVR, no data exist regarding its actions in adipocytes. Here, we generated an adipose-specific deletion of biliverdin reductase-A (BVRA) (BlvraFatKO) in mice to determine the function of BVRA in adipocytes and how it may impact adipose tissue expansion. The BlvraFatKO and littermate control (BlvraFlox) mice were placed on a high-fat diet (HFD) for 12 weeks. Body weights were measured weekly and body composition, fasting blood glucose and insulin levels were quantitated at the end of the 12 weeks. The data showed that the percent body fat and body weights did not differ between the groups; however, BlvraFatKO mice had significantly higher visceral fat as compared to the BlvraFlox. The loss of adipocyte BVRA decreased the mitochondrial number in white adipose tissue (WAT), and increased inflammation and adipocyte size, but this was not observed in brown adipose tissue (BAT). There were genes significantly reduced in WAT that induce the browning effect such as Ppara and Adrb3, indicating that BVRA improves mitochondria function and beige-type white adipocytes. The BlvraFatKO mice also had significantly higher fasting blood glucose levels and no changes in plasma insulin levels, which is indicative of decreased insulin signaling in WAT, as evidenced by reduced levels of phosphorylated AKT (pAKT) and Glut4 mRNA. These results demonstrate the essential role of BVRA in WAT in insulin signaling and adipocyte hypertrophy.
TSPAN8 as a Novel Emerging Therapeutic Target in Cancer for Monoclonal Antibody Therapy
Authors: Heo Kyun , Lee Sukmook
Published: March 2020

Tetraspanin 8 (TSPAN8) is a member of the tetraspanin superfamily that forms TSPAN8-mediated protein complexes by interacting with themselves and other various cellular signaling molecules. These protein complexes help build tetraspanin-enriched microdomains (TEMs) that efficiently mediate intracellular signal transduction. In physiological conditions, TSPAN8 plays a vital role in the regulation of biological functions, including leukocyte trafficking, angiogenesis and wound repair. Recently, reports have increasingly shown the functional role and clinical relevance of TSPAN8 overexpression in the progression and metastasis of several cancers. In this review, we will highlight the physiological and pathophysiological roles of TSPAN8 in normal and cancer cells. Additionally, we will cover the current status of monoclonal antibodies specifically targeting TSPAN8 and the importance of TSPAN8 as an emerging therapeutic target in cancers for monoclonal antibody therapy.
Modeling the Genetic Basis of Individual Differences in Susceptibility to Gulf War Illness
Authors: Jones Byron C. , Miller Diane B. , Lu Lu , Zhao Wenyuan , Ashbrook David G. , Xu Fuyi , Mulligan Megan K. , Williams Robert W. , Zhuang Daming , Torres-Rojas Carolina , O’Callaghan James P.
Published: March 2020

Between 25% and 30% of the nearly one million military personnel who participated in the 1991 Persian Gulf War became ill with chronic symptoms ranging from gastrointestinal to nervous system dysfunction. This disorder is now referred to as Gulf War Illness (GWI) and the underlying pathophysiology has been linked to exposure-based neuroinflammation caused by organophosphorous (OP) compounds coupled with high circulating glucocorticoids. In a mouse model of GWI we developed, corticosterone was shown to act synergistically with an OP (diisopropylflurophosphate) to dramatically increase proinflammatory cytokine gene expression in the brain. Because not all Gulf War participants became sick, the question arises as to whether differential genetic constitution might underlie individual differences in susceptibility. To address this question of genetic liability, we tested the impact of OP and glucocorticoid exposure in a genetic reference population of 30 inbred mouse strains. We also studied both sexes. The results showed wide differences among strains and overall that females were less sensitive to the combined treatment than males. Furthermore, we identified one OP-glucocorticoid locus and nominated a candidate gene—Spon1—that may underlie the marked differences in response.
The Rolling Shear Influence on the Out-of-Plane Behavior of CLT Panels: A Comparative Analysis
Authors: Sandoli Antonio , Calderoni Bruno
Published: March 2020

This paper deals with the influence of the rolling shear deformation on the flexural behavior of CLT (Cross-Laminated Timber) panels. The morphological configuration of the panels, which consist of orthogonal overlapped layers of boards, led to a particular shear behavior when subjected to out-of-plane loadings: the low value of the shear modulus in orthogonal to grain direction (i.e., rolling shear modulus) gives rise to significant shear deformations in the transverse layers of boards, whose grains direction is perpendicular with respect to the tangential stresses direction. This produces increases of deflections and vibrations under service loads, creating discomfort for the users. Different analytical methods accounting for this phenomenon have been already developed and presented in literature. Comparative analyses among the results provided by some of these methods have been carried out in the present paper and the influence of the rolling shear deformations, with reference to different span-to-depth (L/H) ratios investigated. Moreover, the analytical results have also been compared with those obtained by more accurate 2D finite element models. The results show that, at the service limit states, the influence of the rolling shear can be significant when the aspect ratios became less than L/H = 30, and the phenomenon must be accurately considered in both deflection and stress analysis of CLT floors. Contrariwise, in the case of higher aspect ratios (slender panels), the deflections and stresses can be evaluated neglecting the rolling shear influence, assuming the layers of boards as fully-connected.
Serine Biosynthesis Pathway Supports MYC–miR-494–EZH2 Feed-Forward Circuit Necessary to Maintain Metabolic and Epigenetic Reprogramming of Burkitt Lymphoma Cells
Authors: Białopiotrowicz Emilia , Noyszewska-Kania Monika , Kachamakova-Trojanowska Neli , Łoboda Agnieszka , Cybulska Magdalena , Grochowska Aleksandra , Kopczyński Michał , Mikula Michał , Prochorec-Sobieszek Monika , Firczuk Małgorzata , Graczyk-Jarzynka Agnieszka , Zagożdżon Radosław , Ząbek Adam , Młynarz Piotr , Dulak Józef , Górniak Patryk , Szydłowski Maciej , Pyziak Karolina , Martyka Justyna , Sroka-Porada Agnieszka , Jabłońska Ewa , Polak Anna , Kowalczyk Piotr , Szumera-Ciećkiewicz Anna , Chapuy Bjoern , Rzymski Tomasz , Brzózka Krzysztof , Juszczyński Przemysław
Published: March 2020

Burkitt lymphoma (BL) is a rapidly growing tumor, characterized by high anabolic requirements. The MYC oncogene plays a central role in the pathogenesis of this malignancy, controlling genes involved in apoptosis, proliferation, and cellular metabolism. Serine biosynthesis pathway (SBP) couples glycolysis to folate and methionine cycles, supporting biosynthesis of certain amino acids, nucleotides, glutathione, and a methyl group donor, S-adenosylmethionine (SAM). We report that BLs overexpress SBP enzymes, phosphoglycerate dehydrogenase (PHGDH) and phosphoserine aminotransferase 1 (PSAT1). Both genes are controlled by the MYC-dependent ATF4 transcription factor. Genetic ablation of PHGDH/PSAT1 or chemical PHGDH inhibition with NCT-503 decreased BL cell lines proliferation and clonogenicity. NCT-503 reduced glutathione level, increased reactive oxygen species abundance, and induced apoptosis. Consistent with the role of SAM as a methyl donor, NCT-503 decreased DNA and histone methylation, and led to the re-expression of ID4, KLF4, CDKN2B and TXNIP tumor suppressors. High H3K27me3 level is known to repress the MYC negative regulator miR-494. NCT-503 decreased H3K27me3 abundance, increased the miR-494 level, and reduced the expression of MYC and MYC-dependent histone methyltransferase, EZH2. Surprisingly, chemical/genetic disruption of SBP did not delay BL and breast cancer xenografts growth, suggesting the existence of mechanisms compensating the PHGDH/PSAT1 absence in vivo.
Fatty Acid Hydratases: Versatile Catalysts to Access Hydroxy Fatty Acids in Efficient Syntheses of Industrial Interest
Authors: Löwe Jana , Gröger Harald
Published: March 2020

The utilization of hydroxy fatty acids has gained more and more attention due to its applicability in many industrial building blocks that require it, for example, polymers or fragrances. Furthermore, hydroxy fatty acids are accessible from biorenewables, thus contributing to a more sustainable raw material basis for industrial chemicals. Therefore, a range of investigations were done on fatty acid hydratases (FAHs), since these enzymes catalyze the addition of water to an unsaturated fatty acid, thus providing an elegant route towards hydroxy-substituted fatty acids. Besides the discovery and characterization of fatty acid hydratases (FAHs), the design and optimization of syntheses with these enzymes, the implementation in elaborate cascades, and the improvement of these biocatalysts, by way of mutation in terms of the substrate scope, has been investigated. This mini-review focuses on the research done on process development using fatty acid hydratases as a catalyst. It is notable that biotransformations, running at impressive substrate loadings of up to 280 g L−1, have been realized. A further topic of this mini-review is the implementation of fatty acid hydratases in cascade reactions. In such cascades, fatty acid hydratases were, in particular, combined with alcohol dehydrogenases (ADH), Baeyer-Villiger monooxygenases (BVMO), transaminases (TA) and hydrolases, thus enabling access to a broad variety of molecules that are of industrial interest.
Biocatalytic Synthesis of a Novel Bioactive Ginsenoside Using UDP-Glycosyltransferase from Bacillus subtilis 168
Authors: Hu Yumei , Li Hao , Qu Yingying , Zhang Xiao , Zhang Juankun , Dai Longhai
Published: March 2020

Ginsenoside Rg3 is a bioactive compound from Panax ginseng and exhibits diverse notable biological properties. Glycosylation catalyzed by uridine diphosphate-dependent glycosyltransferase (UGT) is the final biosynthetic step of ginsenoside Rg3 and determines its diverse pharmacological activities. In the present study, promiscuous UGT Bs-YjiC from Bacillus subtilis 168 was expressed in Escherichia coli and purified via one-step nickel chelate affinity chromatography. The in vitro glycosylation reaction demonstrated Bs-Yjic could selectively glycosylate the C12 hydroxyl group of ginsenoside Rg3 to synthesize an unnatural ginsenoside Rd12. Ginsenoside Rd12 was about 40-fold more water-soluble than that of ginsenoside Rg3 (90 μM). Furthermore, in vitro cytotoxicity of ginsenoside Rd12 against diverse cancer cells was much stronger than that of ginsenoside Rg3. Our studies report the UGT-catalyzed synthesis of unnatural ginsenoside Rd12 for the first time. Ginsenoside Rd12 with antiproliferative activity might be further exploited as a potential anticancer drug.
Small Molecule Wnt Pathway Modulators from Natural Sources: History, State of the Art and Perspectives
Authors: Blagodatski Artem , Klimenko Antonina , Jia Lee , Katanaev Vladimir L.
Published: March 2020

The Wnt signaling is one of the major pathways known to regulate embryonic development, tissue renewal and regeneration in multicellular organisms. Dysregulations of the pathway are a common cause of several types of cancer and other diseases, such as osteoporosis and rheumatoid arthritis. This makes Wnt signaling an important therapeutic target. Small molecule activators and inhibitors of signaling pathways are important biomedical tools which allow one to harness signaling processes in the organism for therapeutic purposes in affordable and specific ways. Natural products are a well known source of biologically active small molecules with therapeutic potential. In this article, we provide an up-to-date overview of existing small molecule modulators of the Wnt pathway derived from natural products. In the first part of the review, we focus on Wnt pathway activators, which can be used for regenerative therapy in various tissues such as skin, bone, cartilage and the nervous system. The second part describes inhibitors of the pathway, which are desired agents for targeted therapies against different cancers. In each part, we pay specific attention to the mechanisms of action of the natural products, to the models on which they were investigated, and to the potential of different taxa to yield bioactive molecules capable of regulating the Wnt signaling.
Multifaceted Aspects of Metabolic Plasticity in Human Cholangiocarcinoma: An Overview of Current Perspectives
Authors: Pastore Mirella , Lori Giulia , Gentilini Alessandra , Taddei Maria Letizia , Di Maira Giovanni , Campani Claudia , Recalcati Stefania , Invernizzi Pietro , Marra Fabio , Raggi Chiara
Published: March 2020

Cholangiocarcinoma (CCA) is a deadly tumor without an effective therapy. Unique metabolic and bioenergetics features are important hallmarks of tumor cells. Metabolic plasticity allows cancer cells to survive in poor nutrient environments and maximize cell growth by sustaining survival, proliferation, and metastasis. In recent years, an increasing number of studies have shown that specific signaling networks contribute to malignant tumor onset by reprogramming metabolic traits. Several evidences demonstrate that numerous metabolic mediators represent key-players of CCA progression by regulating many signaling pathways. Besides the well-known Warburg effect, several other different pathways involving carbohydrates, proteins, lipids, and nucleic acids metabolism are altered in CCA. The goal of this review is to highlight the main metabolic processes involved in the cholangio-carcinogeneis that might be considered as potential novel druggable candidates for this disease.
Inter-Organelle Membrane Contact Sites and Mitochondrial Quality Control during Aging: A Geroscience View
Authors: Picca Anna , Calvani Riccardo , Coelho-Junior Hélio José , Landi Francesco , Bernabei Roberto , Marzetti Emanuele
Published: March 2020

Mitochondrial dysfunction and failing mitochondrial quality control (MQC) are major determinants of aging. Far from being standalone organelles, mitochondria are intricately related with cellular other compartments, including lysosomes. The intimate relationship between mitochondria and lysosomes is reflected by the fact that lysosomal degradation of dysfunctional mitochondria is the final step of mitophagy. Inter-organelle membrane contact sites also allow bidirectional communication between mitochondria and lysosomes as part of nondegradative pathways. This interaction establishes a functional unit that regulates metabolic signaling, mitochondrial dynamics, and, hence, MQC. Contacts of mitochondria with the endoplasmic reticulum (ER) have also been described. ER-mitochondrial interactions are relevant to Ca2+ homeostasis, transfer of phospholipid precursors to mitochondria, and integration of apoptotic signaling. Many proteins involved in mitochondrial contact sites with other organelles also participate to degradative MQC pathways. Hence, a comprehensive assessment of mitochondrial dysfunction during aging requires a thorough evaluation of degradative and nondegradative inter-organelle pathways. Here, we present a geroscience overview on (1) degradative MQC pathways, (2) nondegradative processes involving inter-organelle tethering, (3) age-related changes in inter-organelle degradative and nondegradative pathways, and (4) relevance of MQC failure to inflammaging and age-related conditions, with a focus on Parkinson’s disease as a prototypical geroscience condition.
Probing the Environment of Emerin by Enhanced Ascorbate Peroxidase 2 (APEX2)-Mediated Proximity Labeling
Authors: Müller Marret , James Christina , Lenz Christof , Urlaub Henning , Kehlenbach Ralph H.
Published: March 2020

Emerin is one of the best characterized proteins of the inner nuclear membrane, but can also occur at the level of the endoplasmic reticulum. We now use enhanced ascorbate peroxidase 2 (APEX2) to probe the environment of emerin. APEX2 can be used as a genetic tag that produces short-lived yet highly reactive biotin species, allowing the modification of proteins that interact with or are in very close proximity to the tagged protein. Biotinylated proteins can be isolated using immobilized streptavidin and analyzed by mass spectrometry. As an alternative to the standard approach with a genetic fusion of APEX2 to emerin, we also used RAPIDS (rapamycin- and APEX-dependent identification of proteins by SILAC), a method with improved specificity, where the peroxidase interacts with the protein of interest (i.e., emerin) only upon addition of rapamycin to the cells. We compare these different approaches, which, together, identify well-known interaction partners of emerin like lamin A and the lamina associated polypeptide 1 (LAP1), as well as novel proximity partners.
Using the SITAR Method to Estimate Age at Peak Height Velocity of Children in Rural South Africa: Ellisras Longitudinal Study
Authors: Nembidzane Chris , Lesaoana Maseka , Monyeki Kotsedi , Boateng Alexander , Makgae Phuti
Published: March 2020

Various studies have been conducted on children using the Ellisras Longitudinal Study Survey in South Africa, but none of these has addressed growth variations of children in this rural location. The aim of this paper is to assess the age at peak height velocity using the superimposition by translation and rotation (SITAR) method for both boys and girls in rural South Africa. The study is part of the on-going Ellisras Longitudinal Study, and has employed secondary data during the period from November 1996 to November 2003. The data was collected biannually in May and November each year. The Ellisras study initially followed a cluster sampling method. All participating children underwent a series of anthropometric measurements of height and weight according to the standard procedures recommended by the International Society for the Advancement of Kinanthropometry. The analysis was done using the SITAR model. Age at peak height velocity for Ellisras rural children was at 14.45 years for boys at 11.82 years for girls. Ellisras rural girls had their age at peak height velocity way earlier than Ellisras rural boys did by an estimated 2.63 years. Ellisras rural children and their growth variations were comparable to other studies.