bluuebunny/crossref_metadata_2025 huggingface dataset:
Fully Coupled Multi-Scale Model for Gas Extraction from Coal Seam Stimulated by Directional Hydraulic Fracturing
Authors: Ge Zhaolong , Zhang Liang , Sun Juzheng , Hu Jinhong
Published: November 2019

Although numerous studies have tried to explain the mechanism of directional hydraulic fracturing in a coal seam, few of them have been conducted on gas migration stimulated by directional hydraulic fracturing during coal mine methane extraction. In this study, a fully coupled multi-scale model to stimulate gas extraction from a coal seam stimulated by directional hydraulic fracturing was developed and calculated by a finite element approach. The model considers gas flow and heat transfer within the hydraulic fractures, the coal matrix, and cleat system, and it accounts for coal deformation. The model was verified using gas amount data from the NO.8 coal seam at Fengchun mine, Chongqing, Southwest China. Model simulation results show that slots and hydraulic fracture can expand the area of gas pressure drop and decrease the time needed to complete the extraction. The evolution of hydraulic fracture apertures and permeability in coal seams is greatly influenced by the effective stress and coal matrix deformation. A series of sensitivity analyses were performed to investigate the impacts of key factors on gas extraction time of completion. The study shows that hydraulic fracture aperture and the cleat permeability of coal seams play crucial roles in gas extraction from a coal seam stimulated by directional hydraulic fracturing. In addition, the reasonable arrangement of directional boreholes could improve the gas extraction efficiency. A large coal seam dip angle and high temperature help to enhance coal mine methane extraction from the coal seam.
A Near–Far-Field Model for Bubbles Influenced by External Electrical Fields
Authors: Geiser Juergen , Mertin Paul
Published: November 2019

In this paper, we present a model that is based on near–far-field charged bubble formation and transportation in an underlying dielectric liquid. The bubbles are controlled by the dielectric liquid, which is influenced by an external electrical field. This allows us to control the shape and volume of the bubbles in the dielectric liquid, such as water. These simulations are important to close the gap between the formation of charged bubbles, which is a fine-scale model and their transport in the underlying liquid, which is a coarse-scale model. In the fine-scale model, the formation of the bubbles and their influence of the electric-stress is approached by a near-field model, which is done by the Young–Laplace equation plus additional force-terms. In the coarse-scale model, the transport of the bubbles is approached by a far-field model, which is done with a convection-diffusion equation. The models are coupled with a bubble in cell scheme, which interpolates between the fine and coarse scales of the different models. Such a scale-dependent approach allows us to apply optimal numerical solvers for the different fine and coarse time and space scales and help to foresee the fluctuations of the charged bubbles in the E-field. We discuss the modeling approaches, numerical solver methods and we present the numerical results for the near–far-field bubble formation and transport model in a dielectric carrier fluid.
Experimental Study on Seismic Behavior of Steel Frames with Infilled Recycled Aggregate Concrete Shear Walls
Authors: Sun Lijian , Guo Hongchao , Liu Yunhe
Published: November 2019

Experiments were performed on four specimens of steel frames with infilled recycled aggregate concrete shear walls (SFIRACSWs), one specimen of infilled ordinary concrete wall, and one pure-steel frame were conducted under horizontal low cyclic loading. The influence of the composite forms of steel frames and RACSWs (namely, infilled cast-in-place and infilled prefabricated) on the failure modes, transfer mechanisms of lateral force, bearing capacity, and ductility of SFIRACSWs is discussed, and the concrete type and connecting stiffness of beam–column joints (BCJs) are also considered. Test results showed that infilled RACSWs can increase the bearing capacity and lateral stiffness of SFIRACSWs. The connecting stiffness of BCJs slightly influences the seismic behavior of SFIRACSWs. In the infilled cast-in-place RACSWs, the wall cracks mainly extended along the diagonal direction. The bearing capacity was 2.4 times higher than in the pure steel frame, the initial stiffness was 4.3 times higher, and the displacement ductility factors were 2.44–2.69 times higher. In the infilled prefabricated RACSWs, the wall cracks mainly extended along the connection between the embedded T-shape connectors and walls before finally connecting along the horizontal direction. Moreover, shear failure occurred in the specimens. The bearing capacity was 1.44 times higher than that of the pure steel frame, the initial stiffness was 2.8 times higher, and the displacement ductility factors were 3.32–3.40 times higher. The degradation coefficients of the bearing capacity were more than 0.85, indicating that the specimens demonstrated a high safety reserve.
Near-IR Emitting Si Nanocrystals Fabricated by Thermal Annealing of SiNx/Si3N4 Multilayers
Authors: Zhigunov D. M. , Popov A. A. , Chesnokov Yu. M. , Vasiliev A. L. , Lebedev A. M. , Subbotin I. A. , Yakunin S. N. , Shalygina O. A. , Kamenskikh I. A.
Published: November 2019

Silicon nanocrystals in silicon nitride matrix are fabricated by thermal annealing of SiNx/Si3N4 multilayered thin films, and characterized by transmission electron microscopy, X-ray reflectivity and diffraction analysis, photoluminescence and X-ray photoelectron spectroscopy techniques. Si nanocrystals with a mean size of about 4 nm are obtained, and their properties are studied as a function of SiNx layer thickness (1.6–2 nm) and annealing temperature (900–1250 °C). The effect of coalescence of adjacent nanocrystals throughout the Si3N4 barrier layers is observed, which results in formation of distinct ellipsoidal-shaped nanocrystals. Complete intermixing of multilayered film accompanied by an increase of nanocrystal mean size for annealing temperature as high as 1250 °C is shown. Near-IR photoluminescence with the peak at around 1.3–1.4 eV is detected and associated with quantum confined excitons in Si nanocrystals: Photoluminescence maximum is red shifted upon an increase of nanocrystal mean size, while the measured decay time is of order of microsecond. The position of photoluminescence peak as compared to the one for Si nanocrystals in SiO2 matrix is discussed.
Design Methodology for Soft Wearable Devices—The MOSAR Case
Authors: Dávila-Vilchis Juana-Mariel , LAZ-Avilés  , Ávila Vilchis Juan Carlos , Vilchis-González Adriana H.
Published: November 2019

This paper proposes a methodology from the conception to the manufacture of soft wearable devices (SWD). This methodology seeks to unify medical, therapeutic and engineering guidelines for research, development and innovation. The aforementioned methodology is divided into two stages (A and B) and four phases. Stage A only includes phase 1 to identify the main necessity for a patient that will define the target of its associated device. Stage B encompasses phases 2, 3 and 4. The development of three models (virtual, mathematical and experimental physical) of the required device is addressed in phase 2. Phase 3 concerns the control and manufacture of the experimental physical model (EPM). Phase 4 focuses on the EPM experimental validation. As a result of this methodology, 13 mobility, 11 usability and 3 control iterative design criteria for SWD are reported. Moreover, more than 50 products are provided on a technological platform with modular architectures that facilitate SWD diversification. A case study related to a soft mobilizer for upper limb rehabilitation is reported. Nevertheless, this methodology can be implemented in different areas and accelerates the transition from development to innovation.
A Case-Based Reasoning Model for Retrieving Window Replacement Costs through Industry Foundation Class
Authors: Kim Hyunjoo , Kim Jonghyeob
Published: November 2019

Building information modeling (BIM) provides facility managers with a large database consisting of 3D geometric data as well as management data. In particular, Industry Foundation Class (IFC) has been applied in many studies as it provides extensive and diverse information regarding building components. With the use of BIM combined with case-based reasoning (CBR), in this study, a model was developed to estimate replacement costs by retrieving cost information from IFC. This study focused on the replacement of windows for office buildings, and the costs associated with that replacement. Two main advantages were identified in the proposed approach. First, the replacement information required for the comparison of different cases is automatically obtained from a BIM file and parsed for predicting a cost estimate using IFC. Next, the accuracy is increased by matching various cost-related data such as contractors and manufacturers in the estimation of replacement costs with the help of CBR.
Efficient Caching for Data-Driven IoT Applications and Fast Content Delivery with Low Latency in ICN
Authors: Hasan Kamrul , Jeong Seong-Ho
Published: November 2019

Edge computing is a key paradigm for the various data-intensive Internet of Things (IoT) applications where caching plays a significant role at the edge of the network. This paradigm provides data-intensive services, computational activities, and application services to the proximity devices and end-users for fast content retrieval with a very low response time that fulfills the ultra-low latency goal of the 5G networks. Information-centric networking (ICN) is being acknowledged as an important technology for the fast content retrieval of multimedia content and content-based IoT applications. The main goal of ICN is to change the current location-dependent IP network architecture to location-independent and content-centric network architecture. ICN can fulfill the needs for caching to the vicinity of the edge devices without further storage deployment. In this paper, we propose an architecture for efficient caching at the edge devices for data-intensive IoT applications and a fast content access mechanism based on new clustering and caching procedures in ICN. The proposed cluster-based efficient caching mechanism provides the solution to the problem of the existing hash and on-path caching mechanisms, and the proposed content popularity mechanism increases the content availability at the proximity devices for reducing the content transfer time and packet loss ratio. We also provide the simulation results and mathematical analysis to prove that the proposed mechanism is better than other state-of-the-art caching mechanisms and the overall network efficiencies are increased.
Cross-Layer and SDN Based Routing Scheme for P2P Communication in Vehicular Ad-Hoc Networks
Authors: You Ziyi , Cheng Guixian , Wang Yi , Chen Pu , Chen Shiguo
Published: November 2019

Conventional routing protocols proposed for Vehicular Ad-hoc Network (VANET) are usually inefficient and vulnerable for multi-hop data forwarding due to the unavailability of global information and inefficiencies in their route discovering schemes. However, with the recently emerged software defined vehicular network (SDVN) technologies, link stability can be better improved through the availability of global network information. Thus, in this paper, we present a novel software-defined network (SDN) based routing scheme for P2P connection under urban inter-vehicle networks that can find a global optimal route between source and destination. This is a cross-layer routing protocol in VANETs, which utilizes metrics not only considering the position and velocity of vehicles, but also channel allocation and link duration when selecting the relay vehicles. Consequently, it starts a route discovery process which can improve the network performance in terms of end-to-end delay and low overhead. Furthermore, packet loss is largely minimized by the relatively stable paths. With the help of realistic simulation, we show that the proposed routing framework performs better than other three latest SDVN and conventional VANET protocols in routing overhead, average end-to-end delay, packet drop ratio, and average throughput. Therefore, our routing scheme is more suitable for 5G-enabled vehicular ad-hoc networks in future.
Solving the Manufacturing Cell Design Problem through an Autonomous Water Cycle Algorithm
Authors: Soto Ricardo , Crawford Broderick , Lanza-Gutierrez Jose M. , Olivares Rodrigo , Camacho Pablo , Astorga Gino , de la Fuente-Mella Hanns , Paredes Fernando , Castro Carlos
Published: November 2019

Metaheuristics are multi-purpose problem solvers devoted to particularly tackle large instances of complex optimization problems. However, in spite of the relevance of metaheuristics in the optimization world, their proper design and implementation to reach optimal solutions is not a simple task. Metaheuristics require an initial parameter configuration, which is dramatically relevant for the efficient exploration and exploitation of the search space, and therefore to the effective finding of high-quality solutions. In this paper, the authors propose a variation of the water cycle inspired metaheuristic capable of automatically adjusting its parameter by using the autonomous search paradigm. The goal of our proposal is to explore and to exploit promising regions of the search space to rapidly converge to optimal solutions. To validate the proposal, we tested 160 instances of the manufacturing cell design problem, which is a relevant problem for the industry, whose objective is to minimize the number of movements and exchanges of parts between organizational elements called cells. As a result of the experimental analysis, the authors checked that the proposal performs similarly to the default approach, but without being specifically configured for solving the problem.
Spotted Hyena Optimizer and Ant Lion Optimization in Predicting the Shear Strength of Soil
Authors: Moayedi Hossein , Tien Bui Dieu , Anastasios Dounis , Kalantar Bahareh
Published: November 2019

Two novel hybrid predictors are suggested as the combination of artificial neural network (ANN), coupled with spotted hyena optimizer (SHO) and ant lion optimization (ALO) metaheuristic techniques, to simulate soil shear strength (SSS). These algorithms were applied to the ANN for counteracting the computational drawbacks of this model. As a function of ten key factors of the soil (including depth of the sample, percentage of sand, percentage of loam, percentage of clay, percentage of moisture content, wet density, liquid limit, plastic limit, plastic Index, and liquidity index), the SSS was considered as the response variable. Followed by development of the ALO–ANN and SHO–ANN ensembles, the best-fitted structures were determined by a trial and error process. The results demonstrated the efficiency of both applied algorithms, as the prediction error of the ANN was reduced by around 35% and 18% by the ALO and SHO, respectively. A comparison between the results revealed that the ALO–ANN (Error = 0.0619 and Correlation = 0.9348) performs more efficiently than the SHO–ANN (Error = 0.0874 and Correlation = 0.8866). Finally, an SSS predictive formula is presented for use as an alternative to the difficult traditional methods.
Shear Rate-Dependent Rheological Properties of Mine Tailings: Determination of Dynamic and Static Yield Stresses
Authors: Jeong Sueng-Won
Published: November 2019

In this paper, shear rate-dependent rheological properties of mine tailings taken from abandoned mine deposits prone to mass movements are examined using a commercial ball-measuring rheological system. The yield stresses (i.e., dynamic and static yield stresses) and viscosity of sand-rich materials are examined by the shear rate-controlled flow curve and time-dependent stress growth methods. Before yielding, the shear stress reaches a peak value (i.e., yield stress) observed for all flow curves. In the steady-state condition, the materials have a minimum shear stress (i.e., dynamic yield stress). The static yield stress can be determined under a constant applied shear rate with different initial values ranging from 10−4 to 10−1 s−1. As a result, the Bingham yield stress and viscosity can be used as a first approximation for estimating the debris flow mobility of post-failure materials. However, the Bingham yield stress is competitive with the static yield stress measured from stress growth methods. Upon comparison of the dynamic and static yield stresses, the static yield stress is approximately 35–45 times greater than the dynamic yield stress, and may be strongly related to microstructural changes (i.e., thixotropy). In this context, special attention must be paid to the determination of yield stresses in debris flow mitigation programs.
Effect of Characteristics of Different Types of Bauxite Clinker on Adhesion
Authors: Wu Xirong , Zhen Nanxiang , Kong Fansheng
Published: November 2019

Based on the fact that bauxite clinker has minor thermal conductivity and better skid resistance and wear-resisting property, it can be used in HFST (high friction surface treatment) or the abrasion layer of asphalt mixture to replace or partly replace the existing aggregate. Bauxite clinker is classified into mainly six types according to different chemical composition contents. The selection of bauxite clinker as aggregate is not only for the economic value, but also for improving the adhesion between aggregate and asphalt, which has a certain blindness This study evaluated the characteristics of different types of bauxite clinker. The adhesion of different types of bauxite clinker with asphalt was evaluated by means of agitating hydrostatic adsorption method and surface free energy theory. The effect of characteristic parameters of bauxite clinker on adhesion was evaluated by grey correlation entropy analysis. The results show that Type B and D bauxite clinker aggregates have the best adhesion to asphalt. The outcome of grey entropy correlation analysis shows that the parameters which characterize the structural indexes of bauxite clinker, such as porosity, water absorption and apparent density, have the greatest effect on the adhesion. The results of study can provide some reference for the selection of bauxite clinker, which is used in different types of highway construction, and a theoretical reference for the applicability research of bauxite clinker in asphalt mixture and the improvement of skid resistance and durability of pavement.
Urban Layout Optimization Based on Genetic Algorithm for Microclimate Performance in the Cold Region of China
Authors: Xu Xiaodong , Liu Yupeng , Wang Wei , Xu Ning , Liu Ke , Yu Gang
Published: November 2019

A performance-driven sustainable urban design is an important step in adapting to local climates and improving outdoor comfort level. This study proposed investigating an urban layout optimization method, validated in an urban area in Shenyang City, a cold region, that comprises nine urban blocks. This study selected an urban block type and street width as optimization input indices and defined the percentage of acceptable universal thermal comfort index (UTCI) range as the objective. The genetic algorithm is applied to optimize and generate an urban block to maximize the percentage of acceptable UTCI range at urban block level and street level. When the comfort level is set as −17–20 °C, optimization can achieve 87.7% of acceptable UTCI in the urban block level and 90.3% at urban street level. To attain an urban layout with higher than 85% acceptable UTCI range, results found, in a cold region, multistory blocks are more suitable than high-rise blocks and open spaces; it would be better to place multistory blocks with high building enclosures on the north side to block cold wind.
Siamese Reconstruction Network: Accurate Image Reconstruction from Human Brain Activity by Learning to Compare
Authors: Jiang Lingyun , Qiao Kai , Wang Linyuan , Zhang Chi , Chen Jian , Zeng Lei , Bu Haibing , Yan Bin
Published: November 2019

Decoding human brain activities, especially reconstructing human visual stimuli via functional magnetic resonance imaging (fMRI), has gained increasing attention in recent years. However, the high dimensionality and small quantity of fMRI data impose restrictions on satisfactory reconstruction, especially for the reconstruction method with deep learning requiring huge amounts of labelled samples. When compared with the deep learning method, humans can recognize a new image because our human visual system is naturally capable of extracting features from any object and comparing them. Inspired by this visual mechanism, we introduced the mechanism of comparison into deep learning method to realize better visual reconstruction by making full use of each sample and the relationship of the sample pair by learning to compare. In this way, we proposed a Siamese reconstruction network (SRN) method. By using the SRN, we improved upon the satisfying results on two fMRI recording datasets, providing 72.5% accuracy on the digit dataset and 44.6% accuracy on the character dataset. Essentially, this manner can increase the training data about from n samples to 2n sample pairs, which takes full advantage of the limited quantity of training samples. The SRN learns to converge sample pairs of the same class or disperse sample pairs of different class in feature space.
A Systematic Error Compensation Method Based on an Optimized Extreme Learning Machine for Star Sensor Image Centroid Estimation
Authors: Wei Xin , Wen Desheng , Song Zongxi , Xi Jiangbo , Zhang Weikang , Liu Gang , Li Zhixin
Published: November 2019

As an important error in star centroid location estimation, the systematic error greatly restricts the accuracy of the three-axis attitude supplied by a star sensor. In this paper, an analytical study about the behavior of the systematic error in the center of mass (CoM) centroid estimation method under different Gaussian widths of starlight energy distribution is presented by means of frequency field analysis and numerical simulations. Subsequently, an optimized extreme learning machine (ELM) based on the bat algorithm (BA) is adopted to predict the systematic error of the actual star centroid position and then compensate the systematic error from the CoM method. In the BA-ELM model, the input weights matrix and hidden layer biases parameters are encoded as microbat’s locations and optimized by utilizing the strong global search capacity of BA, which significantly improves the performance of ELM in terms of prediction accuracy. The simulation result indicates that our method can reduce the systematic error to less than 3.0 × 10−7 pixels, and its compensation accuracy is two or three orders of magnitude higher than that of other methods for estimating a star centroid location under a 3 × 3 pixel sampling window.
Source Apportionment and Health Risk Assessment of Heavy Metals in Eastern Guangdong Municipal Solid Waste
Authors: Tang Zhihua , Liu Minru , Yi Linzi , Guo Huafang , Ouyang Tingping , Yin Hua , Li Mingkun
Published: November 2019

This research focused on the contents of the five most bio-toxic heavy metals, As, Cd, Hg, Cr, and Pb of 26 municipal solid waste (MSW) samples from the Eastern Guangdong Area. To investigate the apportion of the heavy metal source, Pearson correlation and principal component analysis (PCA) were introduced as major approaches. The health risks posed to MSW workers exposed to heavy metals in MSW were assessed using a Monte Carlo simulation combined with the US Environmental Protection Agency Health Risk Assessment Model. The As, Cd, Hg, Cr, and Pb contents of the east Guangdong MSW were (0.76 ± 0.75), (2.14 ± 4.44), (0.11 ± 0.14), (55.42 ± 31.88), and (30.67 ± 20.58) mg/kg, respectively. Hg, Cr, and Pb were potentially derived from glass, textile, food waste, and white plastic, while As and Cd were mainly derived from soil and food waste in the MSW. The non-carcinogenic risks of heavy metal in MSW exposure to MSW workers could be ignored. However, the heavy metals in MSW might pose carcinogenic risks, with the probabilities for male and female workers being 35% and 45%, respectively. The non-carcinogenic and carcinogenic risk indices were slightly higher for female workers under the same exposure situations.
Mixed-Mode Delamination Growth Prediction in Stiffened CFRP Panels by Means of a Novel Fast Procedure
Authors: Sellitto Andrea , Saputo Salvatore , Damiano Michele , Russo Angela , Riccio Aniello
Published: November 2019

Carbon fiber reinforced plastic (CFRP) structures are highly sensitive to delaminations, resulting from low energy impacts or manufacturing defects. Non-linear numerical algorithms are mandatory to investigate the complex mechanisms governing the delamination growth phenomena. Although the high computational costs associated to the non-linear algorithms are acceptable in a detail verification design stage, less expensive procedures are desired in a preliminary design stage or during optimization procedure. In this work, a fast numerical procedure, able to determine the delamination growth initiation in composite structures in the framework of a damage tolerant design approach when mixed mode I and II growth is expected, is introduced. The state of the art of the fast delamination growth procedures is critically discussed and improvements to the existing approaches are proposed to extend their applicability and to increase their accuracy. Comparisons with the standard non-linear delamination growth approaches are presented to assess the effectiveness of the proposed novel Fast approach. The results of the proposed fast approach are comparable with the ones obtained by means of standard numerical non-linear technique, allowing up to 95% computational cost saving.
Assessing the Impact of Ozone and Particulate Matter on Mortality Rate from Respiratory Disease in Seoul, Korea
Authors: Park Sun Kyoung
Published: November 2019

The evidence linking ozone and particulate matter with adverse health impacts is increasing. The goal of this study was to assess the impact of air pollution on the mortality rate from respiratory disease in Seoul, Korea, between 2008 and 2017. The analysis was conducted using a decision tree model in two ways: using 24-h average concentrations and using 1-h maximum values to compare any health impacts from the different times of exposure to pollution. Results show that in spring an elevated level of ozone is one of the most important factors, but in summer temperature has a greater impact than air pollution. Nitrogen dioxide is one of the most important factors in fall, while high levels of particles less than 2.5 μm (PM2.5) and 10 μm in size (PM10) and cooler temperatures are key factors in winter. We checked the accuracy of our results through a 10-fold cross validation method. Error rates using 24-h average and 1-h maximum concentrations were in the ranges of 24.9–42% and 27.6–42%, respectively, indicating that 24-h average concentrations are slightly more directly related with mortality rate. These results could be useful for policy makers in determining the temporal scale of predicted pollutant concentrations for an air quality warning system to help minimize the adverse impacts of air pollution.
Parameterization of Wave Boundary Layer
Authors: Chalikov Dmitry , Babanin Alexander V.
Published: November 2019

It is known that drag coefficient varies in broad limits depending on wind velocity and wave age as well as on wave spectrum and some other parameters. All those effects produce large scatter of the drag coefficient, so, the data is plotted as a function of wind velocity forming a cloud of points with no distinct regularities. Such uncertainty can be overcome by the implementation of the WBL model instead of the calculations of drag with different formulas. The paper is devoted to the formulation of the Wave Boundary Layer (WBL) model for the parameterization of the ocean-atmosphere interactions in coupled ocean-atmosphere models and wave prediction models. The equations explicitly take into account the vertical flux of momentum generated by the wave-produced fluctuations of pressure, velocity and stresses (WPMF). Their surface values are calculated with the use of the spectral beta-functions whose expression was obtained by means of the 2-D simulation of the WBL. Hence, the model directly connects the properties of the WBL with an arbitrary wave spectrum. The spectral and direct wave modeling should also take into account the momentum flux to a subgrid part of the spectrum. The parameterization of this effect in the present paper is formulated in terms of wind and cut-off frequency of the spectrum.
Fractional Whitham–Broer–Kaup Equations within Modified Analytical Approaches
Authors: Shah Rasool , Khan Hassan , Baleanu Dumitru
Published: November 2019

The fractional traveling wave solution of important Whitham–Broer–Kaup equations was investigated by using the q-homotopy analysis transform method and natural decomposition method. The Caputo definition of fractional derivatives is used to describe the fractional operator. The obtained results, using the suggested methods are compared with each other as well as with the exact results of the problems. The comparison shows the best agreement of solutions with each other and with the exact solution as well. Moreover, the proposed methods are found to be accurate, effective, and straightforward while dealing with the fractional-order system of partial differential equations and therefore can be generalized to other fractional order complex problems from engineering and science.
Informal Complete Metric Space and Fixed Point Theorems
Authors: Wu Hsien-Chung
Published: November 2019

The concept of informal vector space is introduced in this paper. In informal vector space, the additive inverse element does not necessarily exist. The reason is that an element in informal vector space which subtracts itself cannot be a zero element. An informal vector space can also be endowed with a metric to define a so-called informal metric space. The completeness of informal metric space can be defined according to the similar concept of a Cauchy sequence. A new concept of fixed point and the related results are studied in informal complete metric space.
Organs-On-Chip Models of the Female Reproductive System
Authors: Mancini Vanessa , Pensabene Virginia
Published: November 2019

Microfluidic-based technology attracts great interest in cell biology and medicine, in virtue of the ability to better mimic the in vivo cell microenvironment compared to conventional macroscale cell culture platforms. Recent Organs-on-chip (OoC) models allow to reproduce in vitro tissue and organ-level functions of living organs and systems. These models have been applied for the study of specific functions of the female reproductive tract, which is composed of several organs interconnected through intricate endocrine pathways and communication mechanisms. To date, a disease and toxicology study of this system has been difficult to perform. Thus, there is a compelling need to develop innovative platforms for the generation of disease model and for performing drug toxicity/screening in vitro studies. This review is focused on the analysis of recently published OoC models that recreate pathological and physiological characteristics of the female reproductive organs and tissues. These models aim to be used to assess changes in metabolic activity of the specific cell types and the effect of exposure to hormonal treatment or chemical substances on some aspects of reproduction and fertility. We examined these models in terms of device specifications, operating procedures, accuracy for studying the biochemical and functional activity of living tissues and the paracrine signalling that occurs within the different tissues. These models represent a powerful tool for understanding important diseases and syndromes affecting women all around the world. Immediate adoption of these models will allow to clarify diseases, causes and adverse events occurring during pregnancy such as pre-eclampsia, infertility or preterm birth, endometriosis and infertility.
Uncoupling of Carbonic Anhydrase from Na-H exchanger-1 in Experimental Colitis: A Possible Mechanistic Link with Na-H Exchanger
Authors: Khan Islam , Khan Khalid
Published: November 2019

In this study, we investigated a mechanistic link between Na–H exchanger-1 (NHE-1) and carbonic anhydrase (CA) in experimental colitis induced in the rats by intrarectal administration of trinitrobenzenesulphonic acid (TNBS). Western blot analysis showed CA-I and CA-II as the major isoforms and CA-IV as a minor one in the colon, and they all are expressed as minor isoforms in the ileum. Co-immunoprecipitation and confocal immunofluorescence microscopy showed colocalization of NHE-1 with CA-I and CA-II, but not with CA-IV. TNBS significantly reduced the levels of NHE-1 and CA protein isoforms in the colon, but not in the uninflamed ileum. A similar reduction profile of the expression of CA isozymes was also obtained in ex vivo treatment of normal colon strips with TNF-α. The level of uncoupling as detected by co-immunoprecipitation was significantly more pronounced. A peptide (83 aa) from the NHE-1 C-terminus demonstrated binding of CA-II only, but not of the CA-I or CA-IV isoform. Furthermore, the profile of inflammatory test markers confirmed inflammation in the tissue used. These findings taken together suggest an inflammation-induced uncoupling of CA and NHE-1, which might be a putative mechanism for reducing the activity of NHE-1 in experimental colitis. This uncoupling might lead to an intracellular accumulation of H+, resulting in acidosis and necrosis in the inflamed colon.
Cytokinin Detection during the Dictyostelium discoideum Life Cycle: Profiles Are Dynamic and Affect Cell Growth and Spore Germination
Authors: Aoki Megan , Kisiala Anna , Li Shaojun , Stock Naomi , Brunetti Craig , Huber Robert , Emery R.
Published: November 2019

Cytokinins (CKs) are a family of evolutionarily conserved growth regulating hormones. While CKs are well-characterized in plant systems, these N6-substituted adenine derivatives are found in a variety of organisms beyond plants, including bacteria, fungi, mammals, and the social amoeba, Dictyostelium discoideum. Within Dictyostelium, CKs have only been studied in the late developmental stages of the life cycle, where they promote spore encapsulation and dormancy. In this study, we used ultra high-performance liquid chromatography-positive electrospray ionization-high resolution tandem mass spectrometry (UHPLC-(ESI+)-HRMS/MS) to profile CKs during the Dictyostelium life cycle: growth, aggregation, mound, slug, fruiting body, and germination. Comprehensive profiling revealed that Dictyostelium produces 6 CK forms (cis-Zeatin (cZ), discadenine (DA), N6-isopentenyladenine (iP), N6-isopentenyladenine-9-riboside (iPR), N6-isopentenyladenine-9-riboside-5′ phosphate (iPRP), and 2-methylthio-N6-isopentenyladenine (2MeSiP)) in varying abundance across the sampled life cycle stages, thus laying the foundation for the CK biosynthesis pathway to be defined in this organism. Interestingly, iP-type CKs were the most dominant CK analytes detected during growth and aggregation. Exogenous treatment of AX3 cells with various CK types revealed that iP was the only CK to promote the proliferation of cells in culture. In support of previous studies, metabolomics data revealed that DA is one of the most significantly upregulated small molecules during Dictyostelium development, and our data indicates that total CK levels are highest during germination. While much remains to be explored in Dictyostelium, this research offers new insight into the nature of CK biosynthesis, secretion, and function during Dictyostelium growth, development, and spore germination.
Curcumin Ameliorates Lead-Induced Hepatotoxicity by Suppressing Oxidative Stress and Inflammation, and Modulating Akt/GSK-3β Signaling Pathway
Authors: Alhusaini Ahlam , Fadda Laila , Hasan Iman H. , Zakaria Enas , Alenazi Abeer M. , Mahmoud Ayman M.
Published: November 2019

Lead (Pb) is a toxic heavy metal pollutant with adverse effects on the liver and other body organs. Curcumin (CUR) is the principal curcuminoid of turmeric and possesses strong antioxidant and anti-inflammatory activities. This study explored the protective effect of CUR on Pb hepatotoxicity with an emphasis on oxidative stress, inflammation and Akt/GSK-3β signaling. Rats received lead acetate and CUR and/or ascorbic acid (AA) for seven days and samples were collected for analyses. Pb(II) induced liver injury manifested by elevated serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH), as well as histopathological alterations, including massive hepatocyte degeneration and increased collagen deposition. Lipid peroxidation, nitric oxide, TNF-α and DNA fragmentation were increased, whereas antioxidant defenses were diminished in the liver of Pb(II)-intoxicated rats. Pb(II) increased hepatic NF-κB and JNK phosphorylation and caspase-3 cleavage, whereas Akt and GSK-3β phosphorylation was decreased. CUR and/or AA ameliorated liver function, prevented tissue injury, and suppressed oxidative stress, DNA damage, NF-κB, JNK and caspase-3. In addition, CUR and/or AA activated Akt and inhibited GSK-3β in Pb(II)-induced rats. In conclusion, CUR prevents Pb(II) hepatotoxicity via attenuation of oxidative injury and inflammation, activation of Akt and inhibition of GSK-3β. However, further studies scrutinizing the exact role of Akt/GSK-3β signaling are recommended.
Dynamical Rearrangement of Human Epidermal Growth Factor Receptor 2 upon Antibody Binding: Effects on the Dimerization
Authors: R. Magalhães Pedro , Machuqueiro Miguel , G. Almeida José , Melo André , D. S. Cordeiro M. Natália , Cabo Verde Sandra , H. Gümüş Zeynep , S. Moreira Irina , D. G. Correia João , Melo Rita
Published: November 2019

Human epidermal growth factor 2 (HER2) is a ligand-free tyrosine kinase receptor of the HER family that is overexpressed in some of the most aggressive tumours. Although it is known that HER2 dimerization involves a specific region of its extracellular domain, the so-called “dimerization arm”, the mechanism of dimerization inhibition remains uncertain. However, uncovering how antibody interactions lead to inhibition of HER2 dimerization is of key importance in understanding its role in tumour progression and therapy. Herein, we employed several computational modelling techniques for a molecular-level understanding of the interactions between HER and specific anti-HER2 antibodies, namely an antigen-binding (Fab) fragment (F0178) and a single-chain variable fragment from Trastuzumab (scFv). Specifically, we investigated the effects of antibody-HER2 interactions on the key residues of “dimerization arm” from molecular dynamics (MD) simulations of unbound HER (in a total of 1 µs), as well as ScFv:HER2 and F0178:HER2 complexes (for a total of 2.5 µs). A deep surface analysis of HER receptor revealed that the binding of specific anti-HER2 antibodies induced conformational changes both in the interfacial residues, which was expected, and in the ECDII (extracellular domain), in particular at the “dimerization arm”, which is critical in establishing protein–protein interface (PPI) interactions. Our results support and advance the knowledge on the already described trastuzumab effect on blocking HER2 dimerization through synergistic inhibition and/or steric hindrance. Furthermore, our approach offers a new strategy for fine-tuning target activity through allosteric ligands.
Amazon Fruits Inhibit Growth and Promote Pro-apoptotic Effects on Human Ovarian Carcinoma Cell Lines
Authors: de Souza Vanessa Rosse , Brum Mariana Concentino Menezes , Guimarães Isabella dos Santos , dos Santos Paula de Freitas , do Amaral Thuane Oliveira , Abreu Joel Pimentel , Passos Thuane , Freitas-Silva Otniel , Gimba Etel Rodrigues Pereira , Teodoro Anderson Junger
Published: November 2019

Murici (Byrsonima crassifolia (L.) Kunth and B. verbascifolia (L.) DC.) and tapereba (Spondias mombin) are Amazonian fruits that contain bioactive compounds. Biochemical and molecular characterization of these fruits can reveal their potential use in preventing diseases, including cancer. The extracts were characterized regarding the presence and profile of carotenoids by high-performance liquid chromatography (HPLC), total phenolic content by the Folin–Ciocalteu assay, and antioxidant activity by antioxidant value 2,2-diphenyl-1-picrylhydrazyl (DPPH) content analysis, 22,20-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) content analysis, Ferric-Reducing Ability of Plasma (FRAP), and Oxygen Radical Absorbance Capacity (ORAC) analysis. The extracts of tapereba and murici studied were important sources of total carotenoids and lutein, respectively. The extracts were then tested for their effect on the viability of the A2780 ovarian cancer (OC) cell line and its cisplatin (CDDP)-resistant derived cell line, called ACRP, by using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assays. Their influence on cell cycle and apoptosis were analyzed by using flow cytometry. Murici and tapereba cell extracts exhibited a strong bioactivity by inhibiting A2780 and ACRP cell viability by 76.37% and 78.37%, respectively, besides modulating the cell cycle and inducing apoptotic cell death. Our results open new perspectives for the development of innovative therapeutic strategies using these Amazon fruit extracts to sensitize ovarian cancer cells to current chemotherapeutic options.
Dynamic DNA Energy Landscapes and Substrate Complexity in Triplet Repeat Expansion and DNA Repair
Authors: Völker Jens , Plum G. Eric , Gindikin Vera , Breslauer Kenneth J.
Published: November 2019

DNA repeat domains implicated in DNA expansion diseases exhibit complex conformational and energy landscapes that impact biological outcomes. These landscapes include ensembles of entropically driven positional interchanges between isoenergetic, isomeric looped states referred to as rollamers. Here, we present evidence for the position-dependent impact on repeat DNA energy landscapes of an oxidative lesion (8oxodG) and of an abasic site analogue (tetrahydrofuran, F), the universal intermediate in base excision repair (BER). We demonstrate that these lesions modulate repeat bulge loop distributions within the wider dynamic rollamer triplet repeat landscapes. We showed that the presence of a lesion disrupts the energy degeneracy of the rollameric positional isomers. This lesion-induced disruption leads to the redistribution of loop isomers within the repeat loop rollamer ensemble, favoring those rollameric isomers where the lesion is positioned to be energetically least disruptive. These dynamic ensembles create a highly complex energy/conformational landscape of potential BER enzyme substrates to select for processing or to inhibit processing. We discuss the implications of such lesion-induced alterations in repeat DNA energy landscapes in the context of potential BER repair outcomes, thereby providing a biophysical basis for the intriguing in vivo observation of a linkage between pathogenic triplet repeat expansion and DNA repair.
Zika and Flavivirus Shell Disorder: Virulence and Fetal Morbidity
Authors: Goh Gerard , Dunker A. , Foster James , Uversky Vladimir
Published: November 2019

Zika virus (ZIKV) was first discovered in 1947 in Africa. Since then, sporadic ZIKV infections of humans have been reported in Africa and Asia. For a long time, this virus was mostly unnoticed due to its mild symptoms and low fatality rates. However, during the 2015–2016 epidemic in Central and South America, when millions of people were infected, it was discovered that ZIKV causes microcephaly in the babies of mothers infected during pregnancy. An examination of the M and C proteins of the ZIKV shell using the disorder predictor PONDR VLXT revealed that the M protein contains relatively high disorder levels comparable only to those of the yellow fever virus (YFV). On the other hand, the disorder levels in the C protein are relatively low, which can account for the low case fatality rate (CFR) of this virus in contrast to the more virulent YFV, which is characterized by high disorder in its C protein. A larger variation was found in the percentage of intrinsic disorder (PID) in the C protein of various ZIKV strains. Strains of African lineage are characterized by higher PIDs. Using both in vivo and in vitro experiments, laboratories have also previously shown that strains of African origin have a greater potential to inflict higher fetal morbidity than do strains of Asian lineage, with dengue-2 virus (DENV-2) having the least potential. Strong correlations were found between the potential to inflict fetal morbidity and shell disorder in ZIKV (r2 = 0.9) and DENV-2 (DENV-2 + ZIKV, r2 = 0.8). A strong correlation between CFR and PID was also observed when ZIKV was included in an analysis of sets of shell proteins from a variety of flaviviruses (r2 = 0.8). These observations have potential implications for antiviral vaccine development and for the design of cancer therapeutics in terms of developing therapeutic viruses that penetrate hard-to-reach organs.
The Mechanisms Underlying PTEN Loss in Human Tumors Suggest Potential Therapeutic Opportunities
Authors: Chang Hyeyoun , Cai Zhenying , Roberts Thomas M.
Published: November 2019

In this review, we will first briefly describe the diverse molecular mechanisms associated with PTEN loss of function in cancer. We will then proceed to discuss the molecular mechanisms linking PTEN loss to PI3K activation and demonstrate how these mechanisms suggest possible therapeutic approaches for patients with PTEN-null tumors.
CDK5: Key Regulator of Apoptosis and Cell Survival
Authors: Roufayel Rabih , Murshid Nimer
Published: November 2019

The atypical cyclin-dependent kinase 5 (CDK5) is considered as a neuron-specific kinase that plays important roles in many cellular functions including cell motility and survival. The activation of CDK5 is dependent on interaction with its activator p35, p39, or p25. These activators share a CDK5-binding domain and form a tertiary structure similar to that of cyclins. Upon activation, CDK5/p35 complexes localize primarily in the plasma membrane, cytosol, and perinuclear region. Although other CDKs are activated by cyclins, binding of cyclin D and E showed no effect on CDK5 activation. However, it has been shown that CDK5 can be activated by cyclin I, which results in anti-apoptotic functions due to the increased expression of Bcl-2 family proteins. Treatment with the CDK5 inhibitor roscovitine sensitizes cells to heat-induced apoptosis and its phosphorylation, which results in prevention of the apoptotic protein functions. Here, we highlight the regulatory mechanisms of CDK5 and its roles in cellular processes such as gene regulation, cell survival, and apoptosis.