bluuebunny/crossref_metadata_2025 huggingface dataset:
A New Method of GPS Water Vapor Tomography for Maximizing the Use of Signal Rays
Authors: Yang Fei , Guo Jiming , Shi Junbo , Zhao Yinzhi , Zhou Lv , Song Shengdeng
Published: April 2019

The spatio-temporal distribution of atmospheric water vapor information can be obtained by global positioning system (GPS) water vapor tomography. GPS signal rays pass through the tomographic area from different boundaries because the scope of the research region (latitude, longitude, and altitude) is designated in the process of tomographic modeling, the influence of the geographic distribution of receivers, and the geometric location of satellite constellations. Traditionally, only signal rays penetrating the entire tomographic area are considered in the computation of water vapor information, whereas those passing through the sides are neglected. Therefore, the accuracy of the tomographic result, especially at the bottom of the area, does not reach its full potential. To solve this problem, this paper proposes a new method that simultaneously considers the discretized tomographic voxels and the troposphere outside the research area as unknown parameters. This method can effectively improve the utilization of existing GPS observations and increase the number of voxels crossed by satellite signals, especially by increasing the proportion of voxels penetrated. A tomographic experiment is implemented using GPS data from the Hong Kong Satellite Positioning Reference Station Network. Compared to the traditional method, the proposed method increases the number of voxels crossed by signal rays and the utilization of the observed data by 15.14% and 19.68% on average, respectively. Numerical results, including comparisons of slant water vapor (SWV), precipitable water vapor (PWV), and water vapor density profile, show that the proposed method is better than traditional methods. In comparison to the water vapor density profile, the root-mean-square error (RMS), mean absolute error (MAE), standard deviation (SD), and bias of the proposed method are 1.39, 1.07, 1.30, and −0.21 gm−3, respectively. For the SWV and PWV comparison, the RMS/MAE of the proposed method are 10.46/8.17 mm and 4.00/3.39 mm, respectively.
Preparation and Characterization of Ultra-Lightweight Foamed Concrete Incorporating Lightweight Aggregates
Authors: Abd Elrahman Mohamed , El Madawy Mohamed E. , Chung Sang-Yeop , Sikora Pawel , Stephan Dietmar
Published: April 2019

Increasing interest is nowadays being paid to improving the thermal insulation of buildings in order to save energy and reduce ecological problems. Foamed concrete has unique characteristics and considerable potential as a promising material in construction applications. It is produced with a wide range of dry densities, between 600 and 1600 kg/m3. However, at a low density below 500 kg/m3, it tends to be unstable in its fresh state while exhibiting high drying shrinkage in its hardened state. In this study, lightweight aggregate-foamed concrete mixtures were prepared by the addition of preformed foam to a cement paste and aggregate. The focus of the research is the influence of fly ash, as well as fine lightweight aggregate addition, on the properties of foamed concrete with a density lower than 500 kg/m3. Concrete properties, including stability and consistency in the fresh state as well as thermal conductivity and mechanical properties in the hardened state, were evaluated in this study. Scanning electron microscopy (SEM) was used to study the microstructure of the foamed concrete. Several mixes with the same density were prepared and tested. The experimental results showed that under the same bulk density, incorporation of fine lightweight aggregate has a significant role on compressive strength development, depending on the characteristics of the lightweight aggregate. However, thermal conductivity is primarily related to the dry density of foamed concrete and only secondarily related to the aggregate content. In addition, the use of fine lightweight aggregate significantly reduces the drying shrinkage of foamed concrete. The results achieved in this work indicate the important role of lightweight aggregate on the stability of low-density foamed concrete, in both fresh and hardened states.
Practical Design of a High-Voltage Pulsed Power Supply Implementing SiC Technology for Atmospheric Pressure Plasma Reactors
Authors: Kołek Jacek , Hołub Marcin
Published: April 2019

Non-thermal plasma reactors offer numerous advantages and are used in a wide variety of applications. Exemplary fields of use include exhaust gas or water quality improvement, surface processing, agriculture, or medical processes. Two of the most popular discharge chamber constructions are dielectric barrier discharge (DBD) and pulsed corona discharge (PCD, barrierless) plasma reactors. Various power supply constructions are presented in the literature with varying complexity and operating principles. A simple, power electronic, pulsed power supply construction is presented in this work, implementing resonant power switch operation, modern silicon carbide (SiC) power semiconductors and a Tesla coil-like transformer design. The power supply construction is immune to short circuits in the reactor and can be used for both types of reactor constructions. The principles of operation, simulation results, and prototype test verifications are presented with main power supply characteristics.
A Novel Dual Authenticated Encryption Scheme Suitable for Social Networking Services
Authors: Lin Han-Yu
Published: April 2019

Nowadays there are many social networking services supporting three-party communication such as Skype, Line, and Facebook Messenger. To ensure the message security, a cryptographic encryption scheme is a commonly adopted measure. However, the traditional asymmetric encryption only allows one designated recipient to decrypt the ciphertext with his/her private key. It is thus difficult for two parties to share the same ciphertext without exposing their private keys. In this paper, the author comes up with a novel dual authenticated encryption (DAE) scheme designed for three-party communication environments. Specifically, a DAE scheme enables a party to generate a single ciphertext that could be solely decrypted by the other two participants without sharing their private keys. It is also formally shown that the proposed scheme achieves the crucial security properties using the random oracle proof model.
Trajectory Tracking Control of a Hydraulic System Using TSMCSPO based on Sliding Perturbation Observer
Authors: Wang Jie , Lee Min Cheol , Kallu Karam Dad , Abbasi Saad Jamshed , Ahn Seokyoung
Published: April 2019

This paper proposes a new designed trajectory tracking method for a hydraulic manipulator, which is the terminal sliding mode control with sliding perturbation observer (TSMCSPO). The dynamics of the hydraulic system are complex and uncertain, it also generates a large reaction force when working as an excavator or a dismantling robot. In this paper, the new control law is designed to force the trajectory of the hydraulic system to follow the reference despite complex dynamics, modeling error, the huge reaction force, and dynamic uncertainties. The sliding perturbation observer (SPO) in TSMCSPO estimates all disturbances from the outside environment, dynamic uncertainties, and modeling errors in real time. We included a simulation and an experiment to verify the approach, and to demonstrate the performance compared with other controllers (SMCSPO, SMC, and TSMC). Stabilities of SPO and TSMCSPO were analyzed based on the Lyapunov stability theory.
Evidence-Theory-Based Robust Optimization and Its Application in Micro-Electromechanical Systems
Authors: Huang Zhiliang , Xu Jiaqi , Yang Tongguang , Li Fangyi , Deng Shuguang
Published: April 2019

The conventional engineering robustness optimization approach considering uncertainties is generally based on a probabilistic model. However, a probabilistic model faces obstacles when handling problems with epistemic uncertainty. This paper presents an evidence-theory-based robustness optimization (EBRO) model and a corresponding algorithm, which provide a potential computational tool for engineering problems with multi-source uncertainty. An EBRO model with the twin objectives of performance and robustness is formulated by introducing the performance threshold. After providing multiple target belief measures (Bel), the original model is transformed into a series of sub-problems, which are solved by the proposed iterative strategy driving the robustness analysis and the deterministic optimization alternately. The proposed method is applied to three problems of micro-electromechanical systems (MEMS), including a micro-force sensor, an image sensor, and a capacitive accelerometer. In the applications, finite element simulation models and surrogate models are both given. Numerical results show that the proposed method has good engineering practicality due to comprehensive performance in terms of efficiency, accuracy, and convergence.
Comparison of Machine Learning Regression Algorithms for Cotton Leaf Area Index Retrieval Using Sentinel-2 Spectral Bands
Authors: Mao Huihui , Meng Jihua , Ji Fujiang , Zhang Qiankun , Fang Huiting
Published: April 2019

Leaf area index (LAI) is a crucial crop biophysical parameter that has been widely used in a variety of fields. Five state-of-the-art machine learning regression algorithms (MLRAs), namely, artificial neural network (ANN), support vector regression (SVR), Gaussian process regression (GPR), random forest (RF) and gradient boosting regression tree (GBRT), have been used in the retrieval of cotton LAI with Sentinel-2 spectral bands. The performances of the five machine learning models are compared for better applications of MLRAs in remote sensing, since challenging problems remain in the selection of MLRAs for crop LAI retrieval, as well as the decision as to the optimal number for the training sample size and spectral bands to different MLRAs. A comprehensive evaluation was employed with respect to model accuracy, computational efficiency, sensitivity to training sample size and sensitivity to spectral bands. We conducted the comparison of five MLRAs in an agricultural area of Northwest China over three cotton seasons with the corresponding field campaigns for modeling and validation. Results show that the GBRT model outperforms the other models with respect to model accuracy in average ( R 2 ¯ = 0.854, R M S E ¯ = 0.674 and M A E ¯ = 0.456). SVR achieves the best performance in computational efficiency, which means it is fast to train, and to validate that it has great potentials to deliver near-real-time operational products for crop management. As for sensitivity to training sample size, GBRT behaves as the most robust model, and provides the best model accuracy on the average among the variations of training sample size, compared with other models ( R 2 ¯ = 0.884, R M S E ¯ = 0.615 and M A E ¯ = 0.452). Spectral bands sensitivity analysis with dCor (distance correlation), combined with the backward elimination approach, indicates that SVR, GPR and RF provide relatively robust performance to the spectral bands, while ANN outperforms the other models in terms of model accuracy on the average among the reduction of spectral bands ( R 2 ¯ = 0.881, R M S E ¯ = 0.625 and M A E ¯ = 0.480). A comprehensive evaluation indicates that GBRT is an appealing alternative for cotton LAI retrieval, except for its computational efficiency. Despite the different performance of the ML models, all models exhibited considerable potential for cotton LAI retrieval, which could offer accurate crop parameters information timely and accurately for crop fields management and agricultural production decisions.
Performance Evaluation of Reinforced Recycled Aggregate Concrete Columns under Cyclic Loadings
Authors: Wang Fan , Yu Yong , Zhao Xin-Yu , Xu Jin-Jun , Xie Tian-Yu , Deresa Simret Tesfaye
Published: April 2019

Recycled concrete aggregates (RCAs) generated from construction and demolition activities have been recognized as a feasible alternative to natural aggregates (NAs). Naturally, the columns fabricated with reinforced recycled concrete (RRC) have been proposed and investigated to promote the structural use of recycled aggregate concrete (RAC). There is still, however, very limited modeling research available to reproduce, accurately and efficiently, the seismic response of RRC columns under lateral cyclic loading; proper evaluations are also lacking on addressing the columns’ seismic behaviors. To fill some of those research gaps, a fiber-based numerical model is developed in this study and then validated with the experimental results published in the literature. Subsequently, the numerical model justified is applied to carry out a comprehensive parametric study to examine the effects of a range of variables on the hysteretic characteristics of RRC columns. Furthermore, a grey relational analysis is conducted to establish quantifiable evidence of key variable sensitivities. The evaluation results imply that the use of the additional water method (AWM) for manufacturing RAC is likely to reduce the lateral load-carrying capacity of the RRC columns (up to 10%), whereas the opposite would occur if a conventional mixing procedure is adopted. Moreover, compared with other factors such as steel area ratio, the content of RCA replacement has a less remarkable effect on the seismic performance of the RRC columns. In general, the RRC columns possess acceptable seismic-resistant properties, and they can be used in earthquake-prone regions with confidence.
Wing Load and Angle of Attack Identification by Integrating Optical Fiber Sensing and Neural Network Approach in Wind Tunnel Test
Authors: Wada Daichi , Tamayama Masato
Published: April 2019

The load and angle of attack (AoA) for wing structures are critical parameters to be monitored for efficient operation of an aircraft. This study presents wing load and AoA identification techniques by integrating an optical fiber sensing technique and a neural network approach. We developed a 3.6-m semi-spanned wing model with eight flaps and bonded two optical fibers with 30 fiber Bragg gratings (FBGs) each along the main and aft spars. Using this model in a wind tunnel test, we demonstrate load and AoA identification through a neural network approach. We input the FBG data and the eight flap angles to a neural network and output estimated load distributions on the eight wing segments. Thereafter, we identify the AoA by using the estimated load distributions and the flap angles through another neural network. This multi-neural-network process requires only the FBG and flap angle data to be measured. We successfully identified the load distributions with an error range of −1.5–1.4 N and a standard deviation of 0.57 N. The AoA was also successfully identified with error ranges of −1.03–0.46° and a standard deviation of 0.38°.
Combined MvdXML and Semantic Technologies for Green Construction Code Checking
Authors: Jiang Shaohua , Wu Zheng , Zhang Bo , Cha Hee Sung
Published: April 2019

The construction process plays a key role in sustainable development of the environment. With the concept of sustainable construction being put forward in the world, some countries released green construction standards to strengthen the requirements in the construction phase. Green construction code checking needs to integrate semantic information embedded in green construction standards and model information involved in Industry Foundation Classes (IFC) and/or Model View Definition (MVD), which are generated separately and lead to difficulty in information integration for green construction code checking. At present, the existing code-checking methods cannot be directly used for green construction. Related practitioners need an efficient and convenient method for green construction code checking urgently. To ameliorate this situation, this research proposes an innovative approach to organize, store, and re-use green construction knowledge by combining mvdXML and semantic technologies. The code checking of green construction is classified into four types based on the difficulty level to meet the requirements of the clauses in green construction standard. Depending on the characteristics of each inspection type, mvdXML or semantic technology is adopted for the appropriate inspection type. This paper demonstrates the deployment and validation of such automated checking procedures in a case study. Based on these experiences, a detailed discussion about the identified issues is provided as the starting point for future research.
A Tabu List-Based Algorithm for Capacitated Multilevel Lot-Sizing with Alternate Bills of Materials and Co-Production Environments
Authors: Romero-Conrado Alfonso R. , Coronado-Hernandez Jairo R. , Rius-Sorolla Gregorio , García-Sabater José P.
Published: April 2019

The definition of lot sizes represents one of the most important decisions in production planning. Lot-sizing turns into an increasingly complex set of decisions that requires efficient solution approaches, in response to the time-consuming exact methods (LP, MIP). This paper aims to propose a Tabu list-based algorithm (TLBA) as an alternative to the Generic Materials and Operations Planning (GMOP) model. The algorithm considers a multi-level, multi-item planning structure. It is initialized using a lot-for-lot (LxL) method and candidate solutions are evaluated through an iterative Material Requirements Planning (MRP) procedure. Three different sizes of test instances are defined and better results are obtained in the large and medium-size problems, with minimum average gaps close to 10.5%.
Influence of Nitrogen Source and Growth Phase on Extracellular Biosynthesis of Silver Nanoparticles Using Cultural Filtrates of Scenedesmus obliquus
Authors: Darwesh Osama M. , Matter Ibrahim A. , Eida Mohamed F. , Moawad Hassan , Oh You-Kwan
Published: April 2019

In this study, silver nanoparticles (AgNPs) were green-synthesized extracellularly by the action of bioactive compounds in cultural filtrates of green microalga Scenedesmus obliquus (KY621475). The influences of six different nitrogen sources (i.e., NaNO3, CO(NH4)2, (NH4)2CO3, KNO3, NH4NO3, and (NH4)2SO4) on extracellular biosynthesis of AgNPs were observed by UV–Visible spectroscopy (380–425 nm) and confirmed using high-resolution transmission electron microscopy (HRTEM). The highest biomass production was observed in the case of urea and ammonium carbonate treatments, which, surprisingly, showed negative activity for AgNPs biosynthesis. Considering their coupling and compatible presence in cultural filtrates, reductases (especially nitrate reductase) as reduction agents are assumed to play a key role in the extracellular biosynthesis of AgNPs. The cultural filtrates of the potassium and sodium nitrate treatments produce AgNPs of relatively small size (5–10 and 4–10 nm, respectively), smaller than those produced by filtrate of ammonium nitrate treatment. The antimicrobial activity of produced AgNPs was a function mainly of particle size, which was influenced by the nitrogen source of the microalgal culture. The AgNPs produced from the KNO3 and NaNO3 cultural filtrates performed the best as antimicrobial agents.
Effects of Magnetic Fields on Quench Characteristics of Superconducting Tape for Superconducting Fault Current Limiter
Authors: Xiang Bin , Gao Lei , Junaid Muhammad , Liu Zhiyuan , Geng Yingsan , Wang Jianhua , Yanabu Satoru
Published: April 2019

In DC systems, DC resistive type superconducting fault current limiters (R-SFCLs) can respond within a few hundred milliseconds and limit the fault current to a very low level to protect the power equipment in DC systems. The main part of R-SFCLs are superconducting tapes. When short-circuit faults occur in the system, the superconducting tapes will quench and become a large quenched resistor to limit the fault current. The surrounding magnetic fields and the magnetic fields caused by the superconducting tapes itself influence the quench characteristics of the superconducting tapes of R-SFCLs. Thus, the current limiting characteristics of R-SFCLs will also be affected. Until present, very few studies have investigated the effects of magnetic fields on quench characteristics of superconducting tapes for DC R-SFCL. The objective of this paper is to obtain the effects of magnetic fields on quench characteristics of superconducting tapes for DC R-SFCL. Two different kinds of YBa2Cu3O7-δ (YBCO) tapes are studied under a permanent magnetic field of 0, 42.4, 75.9, 122.9 mT, respectively. One is from Shanghai Superconductor Technology Co., Ltd., Shanghai, China, type ST-12-L (named SC_SH) and the other is from American Superconductor Inc. Boston, MA, USA, type 8602 (named SC_8602). The research results show that the magnetic fields influence both the amplitude and the rising rate of the quenched resistance of an SC_SH tape. Under the same magnetic field, both the speed of quenching and the quenching resistance of SC_SH tape are larger than them of SC_8602 when the prospective current exceeds 800 A. Thus SC_SH tape can limit the fault current faster and to a lower level.
Topological Photonic Media and the Possibility of Toroidal Electromagnetic Wavepackets
Authors: Onoda Masaru
Published: April 2019

This study aims to present a theoretical investigation of a feasible electromagnetic wavepacket with toroidal-type dual vortices. The paper begins with a discussion on geometric phases and angular momenta of electromagnetic vortices in free space and periodic structures, and introduces topological photonic media with a review on topological phenomena of electron systems in solids, such as quantum Hall systems and topological insulators. Representative simulations demonstrate both the characteristics of electromagnetic vortices in a periodic structure and of exotic boundary modes of a topological photonic crystal, on a Y-shaped waveguide configuration. Those boundary modes stem from photonic helical surface modes, i.e., a photonic analog of electronic helical surface states of topological insulators. Then, we discuss the possibility of toroidal electromagnetic wavepackets via topological photonic media, based on the dynamics of an electronic wavepacket around the boundary of a topological insulator and a correspondence relation between electronic helical surface states and photonic helical surface modes. Finally, after introducing a simple algorithm for the construction of wavepacket solutions to Maxwell’s equations with multiple types of vortices, we examine the stability of a toroidal electromagnetic wavepacket against reflection and refraction, and further discuss the transformation laws of its topological properties in the corresponding processes.
A New Coverage Flight Path Planning Algorithm Based on Footprint Sweep Fitting for Unmanned Aerial Vehicle Navigation in Urban Environments
Authors: Majeed Abdul , Lee Sungchang
Published: April 2019

This paper presents a new coverage flight path planning algorithm that finds collision-free, minimum length and flyable paths for unmanned aerial vehicle (UAV) navigation in three-dimensional (3D) urban environments with fixed obstacles for coverage missions. The proposed algorithm significantly reduces computational time, number of turns, and path overlapping while finding a path that passes over all reachable points of an area or volume of interest by using sensor footprints’ sweeps fitting and a sparse waypoint graph in the pathfinding process. We devise a novel footprints’ sweep fitting method considering UAV sensor footprint as coverage unit in the free spaces to achieve maximal coverage with fewer and longer footprints’ sweeps. After footprints’ sweeps fitting, the proposed algorithm determines the visiting sequence of footprints’ sweeps by formulating it as travelling salesman problem (TSP), and ant colony optimization (ACO) algorithm is employed to solve the TSP. Furthermore, we generate a sparse waypoint graph by connecting footprints’ sweeps’ endpoints to obtain a complete coverage flight path. The simulation results obtained from various scenarios fortify the effectiveness of the proposed algorithm and verify the aforementioned claims.
The Enigma of the Muon and Tau Solved by Emergent Quantum Mechanics?
Authors: van Holten Theo
Published: April 2019

This paper addresses the long-standing question of how it may be explained that the three charged leptons (the electron, muon and tau particle) have different masses, despite their conformity in other respects. In the field of Emergent Quantum Mechanics non-singular electron models are being revisited, and from this exploration has come a possible answer. In this paper a deformable droplet model is considered. It is shown how the model can be made self-consistent, whilst obeying the laws of momentum and energy conservation as well as Larmor’s radiation law. The droplet appears to have three different static equilibrium configurations, each with a different mass. Tentatively, these three equilibrium masses were assumed to correspond with the measured masses of the charged leptons. The droplet model was tuned accordingly, and was thereby completely quantified. The dynamics of the droplet then showed a “De Broglie-like” relation p = K / λ . Beat patterns in the vibrations of the droplet play the role of the matter waves of usual quantum mechanics. The value of K , calculated by the droplet theory, practically equals Planck’s constant: K ≅ h . This fact seems to confirm the correctness of identifying the three types of charged leptons with the equilibria of a droplet of charge.
The 3D Navier–Stokes Equations: Invariants, Local and Global Solutions
Authors: Semenov Vladimir I.
Published: April 2019

In this article, I consider local solutions of the 3D Navier–Stokes equations and its properties such as an existence of global and smooth solution, uniform boundedness. The basic role is assigned to a special invariant class of solenoidal vector fields and three parameters that are invariant with respect to the scaling procedure. Since in spaces of even dimensions the scaling procedure is a conformal mapping on the Heisenberg group, then an application of invariant parameters can be considered as the application of conformal invariants. It gives the possibility to prove the sufficient and necessary conditions for existence of a global regular solution. This is the main result and one among some new statements. With some compliments, the rest improves well-known classical results.
3D Encapsulation Made Easy: A Coaxial-Flow Circuit for the Fabrication of Hydrogel Microfibers Patches
Authors: Campiglio Chiara Emma , Ceriani Francesca , Draghi Lorenza
Published: April 2019

To fully exploit the potential of hydrogel micro-fibers in the design of regenerative medicinal materials, we designed a simple, easy to replicate system for cell embedding in degradable fibrous scaffolds, and validated its effectiveness using alginate-based materials. For scaffold fabrication, cells are suspended in a hydrogel-precursor and injected in a closed-loop circuit, where a pump circulates the ionic cross-linking solution. The flow of the cross-linking solution stretches and solidifies a continuous micro-scaled, cell-loaded hydrogel fiber that whips, bends, and spontaneously assembles in a self-standing, spaghetti-like patch. After investigation and tuning of process- and solution-related parameters, homogeneous microfibers with controlled diameters and consistent scaffolds were obtained from different alginate concentrations and blends with biologically favorable macromolecules (i.e., gelatin or hyaluronic acid). Despite its simplicity, this coaxial-flow encapsulation system allows for the rapid and effortless fabrication of thick, well-defined scaffolds, with viable cells being homogeneously distributed within the fibers. The reduced fiber diameter and the inherent macro-porous structure that is created from the random winding of fibers can sustain mass transport, and support encapsulated cell survival. As different materials and formulations can be processed to easily create homogeneously cell-populated structures, this system appears as a valuable platform, not only for regenerative medicine, but also, more in general, for 3D cell culturing in vitro.
The Impact of a New “Inverted Arch” Prosthetic Annuloplasty Ring on the Mitral Valve’s 3-D Motion: An Experimental Ex-Vivo Study
Authors: Caimmi Philippe , Kapetanakis Emmanouil , Beggino Carla , Vacca Giovanni , Grossini Elena , Stratica Florian , Sacco Roberto , Capponi Andrea
Published: April 2019

This experimental study aimed to evaluate the ex-vivo three-dimensional (3-D) motion of the Inverted Arch Ring (IAR), an innovative new design concept for a flexible incomplete annuloplasty prosthesis with an incorporated stabilizing rigid arch that can be used in correcting mitral valve regurgitation. Twenty explanted porcine hearts were placed in a circulation simulation system. Ultrasonometry transducers implanted in the mitral annulus were used to measure the 3-D valvular motion during a simulated cardiac cycle. Annular distance measurements were recorded and compared in each heart before and after the implantation of the IAR prosthesis at pressures corresponding to mid-systole and mid-diastole. Distances measured in mid-systole and mid-diastole demonstrated no significant differences in annular motion or in valve areas either prior to or after IAR implantation. Therefore, the results of this study confirm the minimal effects exerted by the IAR prosthesis on the mitral valve’s 3-D motion during a simulated cardiac cycle.
Freeze Tolerance in Sculpins (Pisces; Cottoidea) Inhabiting North Pacific and Arctic Oceans: Antifreeze Activity and Gene Sequences of the Antifreeze Protein
Authors: Yamazaki Aya , Nishimiya Yoshiyuki , Tsuda Sakae , Togashi Koji , Munehara Hiroyuki
Published: April 2019

Many marine species inhabiting icy seawater produce antifreeze proteins (AFPs) to prevent their body fluids from freezing. The sculpin species of the superfamily Cottoidea are widely found from the Arctic to southern hemisphere, some of which are known to express AFP. Here we clarified DNA sequence encoding type I AFP for 3 species of 2 families (Cottidae and Agonidae) belonging to Cottoidea. We also examined antifreeze activity for 3 families and 32 species of Cottoidea (Cottidae, Agonidae, and Rhamphocottidae). These fishes were collected in 2013–2015 from the Arctic Ocean, Alaska, Japan. We could identify 8 distinct DNA sequences exhibiting a high similarity to those reported for Myoxocephalus species, suggesting that Cottidae and Agonidae share the same DNA sequence encoding type I AFP. Among the 3 families, Rhamphocottidae that experience a warm current did not show antifreeze activity. The species inhabiting the Arctic Ocean and Northern Japan that often covered with ice floe showed high activity, while those inhabiting Alaska, Southern Japan with a warm current showed low/no activity. These results suggest that Cottoidea acquires type I AFP gene before dividing into Cottidae and Agonidae, and have adapted to each location with optimal antifreeze activity level.
Organellar DNA Polymerases in Complex Plastid-Bearing Algae
Authors: Hirakawa Yoshihisa , Watanabe Arisa
Published: April 2019

DNA replication in plastids and mitochondria is generally regulated by nucleus-encoded proteins. In plants and red algae, a nucleus-encoded enzyme called POP (plant and protist organellar DNA polymerase) is involved in DNA replication in both organelles by virtue of its dual localization. POPs are family A DNA polymerases, which include bacterial DNA polymerase I (PolI). POP homologs have been found in a wide range of eukaryotes, including plants, algae, and non-photosynthetic protists. However, the phylogeny and subcellular localizations of POPs remain unclear in many algae, especially in secondary and tertiary plastid-bearing groups. In this study, we report that chlorarachniophytes possess two evolutionarily distinct POPs, and fluorescent protein-tagging experiments demonstrate that they are targeted to the secondary plastids and mitochondria, respectively. The timing of DNA replication is different between the two organelles in the chlorarachniophyte Bigelowiella natans, and this seems to be correlated to the transcription of respective POP genes. Dinoflagellates also carry two distinct POP genes, possibly for their plastids and mitochondria, whereas haptophytes and ochrophytes have only one. Therefore, unlike plants, some algal groups are likely to have evolved multiple DNA polymerases for various organelles. This study provides a new insight into the evolution of organellar DNA replication in complex plastid-bearing organisms.
Improving Payload Capacity and Anti-Tumor Efficacy of Mesenchymal Stem Cells Using TAT Peptide Functionalized Polymeric Nanoparticles
Authors: Moku Gopikrishna , Layek Buddhadev , Trautman Lana , Putnam Samuel , Panyam Jayanth , Prabha Swayam
Published: April 2019

Mesenchymal stem cells (MSCs) accumulate specifically in both primary tumors and metastases following systemic administration. However, the poor payload capacity of MSCs limits their use in small molecule drug delivery. To improve drug payload in MSCs, we explored polymeric nanoparticles that were functionalized with transactivator of transcription (TAT) peptide. Paclitaxel loaded poly(DL-lactide-co-glycolide) (PLGA) nanoparticles (15–16% w/w paclitaxel; diameter of 225 ± 7 nm; and zeta potential of −15 ± 4 mV) were fabricated by emulsion-solvent evaporation method, followed by TAT-conjugation to the surface of nanoparticles via maleimide-thiol chemistry. Our studies demonstrated that TAT functionalization improved the intracellular accumulation and retention of nanoparticles in MSCs. Further, nano-engineering of MSCs did not alter the migration and differentiation potential of MSCs. Treatment with nano-engineered MSCs resulted in significant (p < 0.05) inhibition of tumor growth and improved survival (p < 0.0001) in a mouse orthotopic model of lung cancer compared to that with free or nanoparticle encapsulated drug. In summary, our results demonstrated that MSCs engineered using TAT functionalized nanoparticles serve as an efficient carrier for tumor specific delivery of anticancer drugs, resulting in greatly improved therapeutic efficacy.
Annexin A2 Regulates AKT Upon H2O2-Dependent Signaling Activation in Cancer Cells
Authors: Castaldo Stéphanie Anais , Ajime Tom , Serrão Gisela , Anastácio Fábio , Rosa Joana Teixeira , Giacomantonio Carman Anthony , Howarth Alison , Hill Richard , Madureira Patrícia Alexandra
Published: April 2019

Hydrogen peroxide (H2O2) is a main second messenger in oncogenic signaling networks including the Ras and the growth factor receptor pathways. This is achieved predominantly through the oxidation of redox-sensitive cysteine (Cys) residues in proteins resulting in changes to their structure and function. We previously identified annexin A2 (ANXA2) as a redox regulatory protein that plays an important cellular role during oxidative stress and also promoting tumorigenesis. Here we investigated the role of ANXA2 in the regulation of H2O2-dependent signaling that drives tumor progression. We show that depletion of ANXA2 leads to the enhanced activation of AKT following either EGF/EGFR stimulation or oncogenic Ras transformation. The phosphatase and tensin homologue (PTEN) protein negatively regulates the PI3K/AKT pathway. We demonstrate that ANXA2 via its reactive Cys-8 residue, binds to PTEN and that the co-expression of PTEN and ANXA2, but not ANXA2 Cys-8-Ala mutant, inhibits AKT phosphorylation on Ser 473. These results indicate that ANXA2 is important for PTEN regulation within the PI3K/AKT signaling cascade. Furthermore, we also reveal that ANXA2 inversely regulates the expression of the peroxidase, peroxiredoxin 2, in a reactive oxygen species dependent manner.
Association Analysis of Deep Genomic Features Extracted by Denoising Autoencoders in Breast Cancer
Authors: Liu Qian , Hu Pingzhao
Published: April 2019

Artificial intelligence-based unsupervised deep learning (DL) is widely used to mine multimodal big data. However, there are few applications of this technology to cancer genomics. We aim to develop DL models to extract deep features from the breast cancer gene expression data and copy number alteration (CNA) data separately and jointly. We hypothesize that the deep features are associated with patients’ clinical characteristics and outcomes. Two unsupervised denoising autoencoders (DAs) were developed to extract deep features from TCGA (The Cancer Genome Atlas) breast cancer gene expression and CNA data separately and jointly. A heat map was used to view and cluster patients into subgroups based on these DL features. Fisher’s exact test and Pearson’ Chi-square test were applied to test the associations of patients’ groups and clinical information. Survival differences between the groups were evaluated by Kaplan–Meier (KM) curves. Associations between each of the features and patient’s overall survival were assessed using Cox’s proportional hazards (COX-PH) model and a risk score for each feature set from the different omics data sets was generated from the survival regression coefficients. The risk scores for each feature set were binarized into high- and low-risk patient groups to evaluate survival differences using KM curves. Furthermore, the risk scores were traced back to their gene level DAs weights so that the three gene lists for each of the genomic data points were generated to perform gene set enrichment analysis. Patients were clustered into two groups based on concatenated features from the gene expression and CNA data and these two groups showed different overall survival rates (p-value = 0.049) and different ER (Estrogen receptor) statuses (p-value = 0.002, OR (odds ratio) = 0.626). All the risk scores from the gene expression and CNA data and their concatenated one were significantly associated with breast cancer survival. The patients with the high-risk group were significantly associated with patients’ worse outcomes (p-values ≤ 0.0023). The concatenated risk score was enriched by the AMP-activated protein kinase (AMPK) signaling pathway, the regulation of DNA-templated transcription, the regulation of nucleic acid-templated transcription, the regulation of apoptotic process, the positive regulation of gene expression, the positive regulation of cell proliferation, heart morphogenesis, the regulation of cellular macromolecule biosynthetic process, with FDR (false discovery rate) less than 0.05. We confirmed DAs can effectively extract meaningful genomic features from genomic data and concatenating multiple data sources can improve the significance of the features associated with breast cancer patients’ clinical characteristics and outcomes.
A Therapeutic Strategy for Chemotherapy-Resistant Gastric Cancer via Destabilization of Both β-Catenin and RAS
Authors: Ryu Won-Ji , Lee Jae Eun , Cho Yong-Hee , Lee Gunho , Seo Mi-kyoung , Lee Sang-Kyu , Hwang Jeong-Ha , Min Do Sik , Noh Sung Hoon , Paik Soonmyung , Kim Sangwoo , Cheong Jae-Ho , Choi Kang-Yell
Published: April 2019

Treatment of advanced gastric cancer patients with current standard chemotherapeutic agents frequently results in resistance, leading to poor overall survival. However, there has been no success in developing strategies to overcome it. We showed the expression levels of both β-catenin and RAS were significantly increased and correlated in tissues of 756 gastric cancer (GC) patients and tissues of primary- and acquired-resistance patient-derived xenograft tumors treated with 5-fluorouracil and oxaliplatin modulated with leucovorin (FOLFOX). On the basis of our previous studies, where small molecules to suppress colorectal cancer (CRC) via degrading both β-catenin and RAS were developed, we tested the effectiveness of KYA1797K, a representative compound functioning by binding axin, in the growth of GC cells. The efficacy test of the drugs using gastric tumor organoids of Apc1638N mice showed that the CD44 and ALDH1A3 cancer stem cell markers were induced by FOLFOX, but not by KYA1797K. KYA1797K also efficiently suppressed tumors generated by re-engrafting the FOLFOX-resistant patient-derived xenograft (PDX) tumors, which also showed resistance to paclitaxel. Overall, the small-molecule approach degrading both β-catenin and RAS has potential as a therapeutic strategy for treating GC patients resistant to current standard chemotherapies.
Head and Body/Tail Pancreatic Carcinomas Are Not the Same Tumors
Authors: Birnbaum David , Bertucci François , Finetti Pascal , Birnbaum Daniel , Mamessier Emilie
Published: April 2019

The association between pancreatic ductal adenocarcinoma (PDAC) location (head vs. Body/Tail (B/T)) and clinical outcome remains controversial. We collected clinicopathological and gene expression data from 249 resected PDAC samples from public data sets, and we compared data between 208 head and 41 B/T samples. The 2-year overall survival (OS) was better for the head than for the B/T PDACs (44 vs. 27%, p = 0.043), especially when comparing tumors with similar TNM classification (T3/4N0M0: 67% vs. 17%, p = 0.002) or from the same molecular class (squamous subtype: 31% vs. 0%, p < 0.0001). Bailey’s molecular subtypes were differentially distributed within the two groups, with the immunogenic subtype being underrepresented in the “B/T” group (p = 0.005). Uni- and multivariate analyses indicated that PDAC anatomic location was an independent prognostic factor. Finally, the supervised analysis identified 334 genes differentially expressed. Genes upregulated in the “head” group suggested lymphocyte activation and pancreas exocrine functions. Genes upregulated in the “B/T” group were related to keratinocyte differentiation, in line with the enrichment for squamous phenotype. We identified a robust gene expression signature (GES) associated with B/T PDAC location, suggesting that head and B/T PDAC are different. This GES could serve as an indicator for differential therapeutic management based on PDAC location.
DNA Repair Gene Expression Adjusted by the PCNA Metagene Predicts Survival in Multiple Cancers
Authors: Peterson Leif E. , Kovyrshina Tatiana
Published: April 2019

Removal of the proliferation component of gene expression by proliferating cell nuclear antigen (PCNA) adjustment via statistical methods has been addressed in numerous survival prediction studies for breast cancer and all cancers in the Cancer Genome Atlas (TCGA). These studies indicate that the removal of proliferation in gene expression by PCNA adjustment removes the statistical significance for predicting overall survival (OS) when gene selection is performed on a genome-wide basis. Since cancers become addicted to DNA repair as a result of forced cellular replication, increased oxidation, and repair deficiencies from oncogenic loss or genetic polymorphisms, we hypothesized that PCNA adjustment of DNA repair gene expression does not remove statistical significance for OS prediction. The rationale and importance of this translational hypothesis is that new lists of repair genes which are predictive of OS can be identified to establish new targets for inhibition therapy. A candidate gene approach was employed using TCGA RNA-Seq data for 121 DNA repair genes in 8 molecular pathways to predict OS for 18 cancers. Statistical randomization test results indicate that after PCNA adjustment, OS could be predicted significantly by sets of DNA repair genes for 61% (11/18) of the cancers. These findings suggest that removal of the proliferation signal in expression by PCNA adjustment does not remove statistical significance for predicting OS. In conclusion, it is likely that previous studies on PCNA adjustment and survival were biased because genes identified through a genome-wide approach are strongly co-regulated by proliferation.
Perovskite-type LaFeO3: Photoelectrochemical Properties and Photocatalytic Degradation of Organic Pollutants Under Visible Light Irradiation
Authors: Ismael Mohammed , Wark Michael
Published: April 2019

Perovskite-type oxides lanthanum ferrite (LaFeO3) photocatalysts were successfully prepared by a facile and cost-effective sol-gel method using La(NO)3 and Fe(NO)3 as metal ion precursors and citric acid as a complexing agent at different calcination temperatures. The properties of the resulting LaFeO3 samples were characterized by powder X-ray diffraction (XRD), energy dispersive X-ray spectroscopy (EDXS), UV-Vis diffuse reflectance spectroscopy (DRS), X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectra (IR), transmission electron microscopy (TEM), N2 adsorption/desorption and photoelectrochemical tests. The photoactivity of the LaFeO3 samples was tested by monitoring the photocatalytic degradation of Rhodamine B (RhB) and 4-chlorophenol (4-CP) under visible light irradiation, the highest photocatalytic activity was found for LaFeO3 calcined at 700 °C, which attributed to the relatively highest surface area (10.6 m2/g). In addition, it was found from trapping experiments that the reactive species for degradation were superoxide radical ions (O2−) and holes (h+). Photocurrent measurements and electrochemical impedance spectroscopy (EIS) proved the higher photo-induced charge carrier transfer and separation efficiency of the LaFeO3 sample calcined at 700 °C compared to that that calcined at 900 °C. Band positions of LaFeO3 were estimated using the Mott-Schottky plots, which showed that H2 evolution was not likely.
Updates on the CDK4/6 Inhibitory Strategy and Combinations in Breast Cancer
Authors: Sobhani Navid , D’Angelo Alberto , Pittacolo Matteo , Roviello Giandomenico , Miccoli Anna , Corona Silvia Paola , Bernocchi Ottavia , Generali Daniele , Otto Tobias
Published: April 2019

Breast Cancer (BC) is the second most common type of cancer worldwide and displays the highest cancer-related mortality among women worldwide. Targeted therapies have revolutionized the way BC has been treated in recent decades, improving the life expectancies of millions of women. Among the different molecular pathways that have been of interest for the development of targeted therapies are the Cyclin-Dependent Kinases (CDK). CDK inhibitors are a class of molecules that already exist in nature and those belonging to the Cyclin dependent kinase inhibitors family INK4 that specifically inhibit CDK4/6 proteins. CDK4/6 inhibitors specifically block the transition from the G1 to the S phase of the cell cycle by dephosphorylation of the retinoblastoma tumor suppressor protein. In the past four years, the CDK4/6 inhibitors, palbociclib, ribociclib, and abemaciclib, received their first FDA approval for the treatment of Hormone Receptor (HR)-positive and Human Epidermal growth factor Receptor 2 (HER2)-negative breast cancer after showing significant improvements in progression-free survival in the PALOMA-1, MONALEESA-2 and the MONARCH-2 randomized clinical trials, respectively. After the encouraging results from these clinical trials, CDK4/6 inhibitors have also been investigated in other BC subtypes. In HER2-positive BC, a combination of CDK4/6 inhibitors with HER2-targeted therapies showed promise in preclinical studies and their clinical evaluation is ongoing. Moreover, in triple-negative BC, the efficacy of CDK4/6 inhibitors has been investigated in combination with other targeted therapies or immunotherapies. This review summarizes the molecular background and clinical efficacy of CDK4/6 inhibitors as single agents or in combination with other targeted therapies for the treatment of BC. Future directions for ongoing clinical trials and predictive biomarkers will be further debated.