bluuebunny/crossref_metadata_2025 huggingface dataset:
Wnt10b Participates in Regulating Fatty Acid Synthesis in the Muscle of Zebrafish
Authors: Liu Dongwu , Pang Qiuxiang , Han Qiang , Shi Qilong , Zhang Qin , Yu Hairui
Published: August 2019

There are 19 Wnt genes in mammals that belong to 12 subfamilies. Wnt signaling pathways participate in regulating numerous homeostatic and developmental processes in animals. However, the function of Wnt10b in fatty acid synthesis remains unclear in fish species. In the present study, we uncovered the role of the Wnt10b signaling pathway in the regulation of fatty acid synthesis in the muscle of zebrafish. The gene of Wnt10b was overexpressed in the muscle of zebrafish using pEGFP-N1-Wnt10b vector injection, which significantly decreased the expression of glycogen synthase kinase 3β (GSK-3β), but increased the expression of β-catenin, peroxisome proliferators-activated receptor γ (PPARγ), and CCAAT/enhancer binding protein α (C/EBPα). Moreover, the activity and mRNA expression of key lipogenic enzymes ATP-citrate lyase (ACL), acetyl-CoA carboxylase (ACC) and fatty acid synthetase (FAS), and the content of non-esterified fatty acids (NEFA), total cholesterol (TC), and triglyceride (TG) were also significantly decreased. Furthermore, interference of the Wnt10b gene significantly inhibited the expression of β-catenin, PPARγ, and C/EBPα, but significantly induced the expression of GSK-3β, FAS, ACC, and ACL. The content of NEFA, TC, and TG as well as the activity of FAS, ACC, and ACL significantly increased. Thus, our results showed that Wnt10b participates in regulating fatty acid synthesis via β-catenin, C/EBPα and PPARγ in the muscle of zebrafish.
Graph Convolutional Network and Convolutional Neural Network Based Method for Predicting lncRNA-Disease Associations
Authors: Xuan Ping , Pan Shuxiang , Zhang Tiangang , Liu Yong , Sun Hao
Published: August 2019

Aberrant expressions of long non-coding RNAs (lncRNAs) are often associated with diseases and identification of disease-related lncRNAs is helpful for elucidating complex pathogenesis. Recent methods for predicting associations between lncRNAs and diseases integrate their pertinent heterogeneous data. However, they failed to deeply integrate topological information of heterogeneous network comprising lncRNAs, diseases, and miRNAs. We proposed a novel method based on the graph convolutional network and convolutional neural network, referred to as GCNLDA, to infer disease-related lncRNA candidates. The heterogeneous network containing the lncRNA, disease, and miRNA nodes, is constructed firstly. The embedding matrix of a lncRNA-disease node pair was constructed according to various biological premises about lncRNAs, diseases, and miRNAs. A new framework based on a graph convolutional network and a convolutional neural network was developed to learn network and local representations of the lncRNA-disease pair. On the left side of the framework, the autoencoder based on graph convolution deeply integrated topological information within the heterogeneous lncRNA-disease-miRNA network. Moreover, as different node features have discriminative contributions to the association prediction, an attention mechanism at node feature level is constructed. The left side learnt the network representation of the lncRNA-disease pair. The convolutional neural networks on the right side of the framework learnt the local representation of the lncRNA-disease pair by focusing on the similarities, associations, and interactions that are only related to the pair. Compared to several state-of-the-art prediction methods, GCNLDA had superior performance. Case studies on stomach cancer, osteosarcoma, and lung cancer confirmed that GCNLDA effectively discovers the potential lncRNA-disease associations.
Multi-Wavelength Filters of Templated Blue Phase Liquid Crystal
Authors: Zha Shenghao , Zhang Hongzhou , Sun Changli , Feng Yifan , Lu Jiangang
Published: August 2019

The multi-wavelength filters in the visible light band using the blue phase liquid crystal (BPLC) template was investigated. A multi-layer templated BPLC (T-BPLC) filter without intermediate dielectric layers was fabricated, which may reflect multi-wavelength in one filter. Compared with the cholesteric liquid crystal (CLC) filter, the T-BPLC filter may get a much narrower reflection bandwidth (<15 nm), show better angular stability of incident light, and have a more stable wavelength and bandwidth with a temperature shift. Furthermore, the central wavelength and bandwidth can be easily controlled by the fabrication process and the optimization of the material concentration. When the incident angle varies, the shift of the center wavelength of the T-BPLC filter is much smaller than that of the CLC filter. The multi-wavelength filter shows a potential application in color filters and high-density wavelength division multiplexed networks.
Modelling of Optical Damage in Nanorippled ZnO Produced by Ion Irradiation
Authors: Redondo-Cubero Andrés , Vázquez Luis , Jalabert Denis , Lorenz Katharina , Ben Sedrine Nebiha
Published: August 2019

Here, we report on the production of nanoripples on the surface of ZnO bulk substrates by ion beam erosion with 20 keV Ar+ ions at an oblique incidence (60°). The ripple patterns, analyzed by atomic force microscopy, follow a power law dependence for both the roughness and the wavelength. At high fluences these ripples show coarsening and asymmetric shapes, which become independent of the beam direction and evidence additional mechanisms for the pattern development. The shallow damaged layer is not fully amorphized by this process, as confirmed by medium energy ion scattering. A detailed study of the damage-induced changes on the optical properties was carried out by means of spectroscopic ellipsometry. Using a 3-layer model based on Tauc-Lorenz and critical point parameter band oscillators, the optical constants of the damaged layer were determined. The results showed a progressive reduction in the refractive index and enhanced absorption below the bandgap with the fluence.
Photometric Long-Range Positioning of LED Targets for Cooperative Navigation in UAVs
Authors: Jospin Laurent , Stoven-Dubois Alexis , Cucci Davide Antonio
Published: August 2019

Autonomous flight with unmanned aerial vehicles (UAVs) nowadays depends on the availability and reliability of Global Navigation Satellites Systems (GNSS). In cluttered outdoor scenarios, such as narrow gorges, or near tall artificial structures, such as bridges or dams, reduced sky visibility and multipath effects compromise the quality and the trustworthiness of the GNSS position fixes, making autonomous, or even manual, flight difficult and dangerous. To overcome this problem, cooperative navigation has been proposed: a second UAV flies away from any occluding objects and in line of sight from the first and provides the latter with positioning information, removing the need for full and reliable GNSS coverage in the area of interest. In this work we use high-power light-emitting diodes (LEDs) to signalize the second drone and we present a computer vision pipeline that allows to track the second drone in real-time from a distance up to 100 m and to compute its relative position with decimeter accuracy. This is based on an extension to the classical iterative algorithm for the Perspective-n-Points problem in which the photometric error is minimized according to a image formation model. This extension allow to substantially increase the accuracy of point-feature measurements in image space (up to 0.05 pixels), which directly translates into higher positioning accuracy with respect to conventional methods.
Design of a Network Permutation Entropy and Its Applications for Chaotic Time Series and EEG Signals
Authors: Yan Bo , He Shaobo , Sun Kehui
Published: August 2019

Measuring the complexity of time series provides an important indicator for characteristic analysis of nonlinear systems. The permutation entropy (PE) is widely used, but it still needs to be modified. In this paper, the PE algorithm is improved by introducing the concept of the network, and the network PE (NPE) is proposed. The connections are established based on both the patterns and weights of the reconstructed vectors. The complexity of different chaotic systems is analyzed. As with the PE algorithm, the NPE algorithm-based analysis results are also reliable for chaotic systems. Finally, the NPE is applied to estimate the complexity of EEG signals of normal healthy persons and epileptic patients. It is shown that the normal healthy persons have the largest NPE values, while the EEG signals of epileptic patients are lower during both seizure-free intervals and seizure activity. Hence, NPE could be used as an alternative to PE for the nonlinear characteristics of chaotic systems and EEG signal-based physiological and biomedical analysis.
Design of an Electrically Powered Rickshaw, for Use in India
Authors: Cochrane Colin , Muneer Tariq , Fraser Bashabi
Published: August 2019

The main aim of this article is to present research findings related to the design of an electric rickshaw for use in Kolkata, India, identifying weaknesses in the current cycle rickshaw, developing a design solution to address problems found, and exploring the possibility of utilising solar power. Through research and testing it was found there were many design issues, concerns with health and safety, comfort, and ergonomics. All problems found were addressed by implementing design upgrades. The testing of the current cycle rickshaw identified the power and energy required to implement an electric drive system, where a 500 W 24 V DC motor and a battery capacity of 220 ampere hours was used in conjunction with a pedal assist system to provide a range of up to 52 km. A conceptual prototype was developed to prove the successful application of a pedal assist system, which was established as a viable option for design. The design has been critically evaluated and the relevant issues discussed.
Mitigation of Common Mode Voltage Issues in Electric Vehicle Drive Systems by Means of an Alternative AC-Decoupling Power Converter Topology
Authors: Robles Endika , Fernandez Markel , Ibarra Edorta , Andreu Jon , Kortabarria Iñigo
Published: August 2019

Electric vehicles (EV) are gaining popularity due to current environmental concerns. The electric drive, which is constituted by a power converter and an electric machine, is one of the main elements of the EV. Such machines suffer from common mode voltage (CMV) effects. The CMV introduces leakage currents through the bearings, leading to premature failures and reducing the propulsion system life cycles. As future EV power converters will rely on wide bandgap semiconductors with high switching frequency operation, CMV problems will become more prevalent, making the research on CMV mitigation strategies more relevant. A variety of CMV reduction methods can be found in the scientific literature, such as the inclusion of dedicated filters and the implementation of specific modulation techniques. However, alternative power converter topologies can also be introduced for CMV mitigation. The majority of such power converters for CMV mitigation are single-phase topologies intended for photovoltaic applications; thus, solutions in the form of three-phase topologies that could be applied to EVs are very limited. Considering all these, this paper proposes alternative three-phase topologies that could be exploited in EV applications. Their performance is compared with other existing proposals, providing a clear picture of the available alternatives, emphasizing their merits and drawbacks. From this comprehensive study, the benefits of a novel AC-decoupling topology is demonstrated. Moreover, an adequate modulation technique is also investigated in order to exploit the benefits of this topology while considering a trade-off between CMV mitigation, efficiency, and total harmonic distortion (THD). In order to extend the results of the study close to the real application, the performance of the proposed AC-decoupling topology is simulated using a complete and accurate EV model (including vehicle dynamics and a detailed propulsion system model) by means of state-of-the-art digital real-time simulation.
Hydrogen Photo-Production from Glycerol Using Nickel-Doped TiO2 Catalysts: Effect of Catalyst Pre-Treatment
Authors: Hidalgo-Carrillo Jesús , Martín-Gómez Juan , Morales Julia , Espejo Juan Carlos , Urbano Francisco José , Marinas Alberto
Published: August 2019

In the present piece of research, hydrogen production via the photo-reforming of glycerol (a byproduct from biodiesel generation) is studied. Catalysts consisted of titania modified by Ni (0.5% by weight) obtained through deposition–precipitation or impregnation synthetic methods (labelled as Ni-0.5-DP and Ni-0.5-IMP, respectively). Reactions were performed both under UV and solar irradiation. Activity significantly improved in the presence of Ni, especially under solar irradiation. Moreover, pre-reduced solids exhibited higher catalytic activities than untreated solids, despite the “in-situ” reduction of nickel species and the elimination of surface chlorides under reaction conditions (as evidenced by XPS). It is possible that the catalyst pretreatment at 400 °C under hydrogen resulted in some strong metal–support interactions. In summary, the highest hydrogen production value (ca. 2600 micromole H2·g−1) was achieved with pre-reduced Ni-0.5-DP solid using UV light for an irradiation time of 6 h. This value represents a 15.7-fold increase as compared to Evonik P25.
Gen-Set Control in Stand-Alone/RES Integrated Power Systems
Authors: Corsini Alessandro , Cedola Luca , Lucchetta Francesca , Tortora Eileen
Published: August 2019

Power supply in stand-alone power systems, such those in non-grid connected islands, represents an important area of study in investigating smart energy concepts. In particular, the discontinuity in renewable energy availability and the mismatch with power demand are likely to hinder grid stability and overall system efficiency. Typically, the load-levelling relies on diesel engine gen-sets which suffer the modulation of power output resulting in increased operation costs and life time reduction. Although energy storage can complement power fluxes balance, a proper dispatch strategy is needed in order to improve diesel engine operations in Renewable Energy Source (RES) integrated systems. The present study investigates the merit of a dispatch strategy aiming at improving gen-set performance in a hybrid RES/storage/Diesel Engine Generator set (DEGS) power configuration. The proposed dispatch strategy is modelled in a transient simulation software, with hourly based analysis over a year period and is applied to a small island case study.
SEO Practices: A Study about the Way News Websites Allow the Users to Comment on Their News Articles
Authors: Karyotakis Minos-Athanasios , Lamprou Evangelos , Kiourexidou Matina , Antonopoulos Nikos
Published: August 2019

In the current media world, there is a huge debate about the importance of the visibility of a news website in order to secure its existence. Thus, search engine optimization (SEO) practices have emerged in the news media systems around the world. This study aimed to expand the current literature about the SEO practices by focusing on examining, via the walkthrough method, the ways that news companies allow the users to comment on their online news articles. The comments on the news websites are related to the notions of social influence, information diffusion, and play an essential role as a SEO practice, for instance, by providing content and engagement. The examined sample was collected by the most visited news websites’ rankings of alexa.com for a global scale and for the countries Greece and Cyprus. The findings reveal that the news websites throughout the globe use similar features and ways to support the comments of the users. In the meantime, though, a high number of the news websites did not allow the users to use their social media accounts in order to comment the provided news articles, or provided multiple comment platforms. This trend goes against the SEO practices. It is believed that this finding is associated with the difficulty of the news organizations to regulate and protect themselves by the users’ comments that promote, in some case harmful rhetoric and polarization.
A Super-Clustering Approach for Fully Automated Single Particle Picking in Cryo-EM
Authors: Al-Azzawi Adil , Ouadou Anes , Tanner John J. , Cheng Jianlin
Published: August 2019

Structure determination of proteins and macromolecular complexes by single-particle cryo-electron microscopy (cryo-EM) is poised to revolutionize structural biology. An early challenging step in the cryo-EM pipeline is the detection and selection of particles from two-dimensional micrographs (particle picking). Most existing particle-picking methods require human intervention to deal with complex (irregular) particle shapes and extremely low signal-to-noise ratio (SNR) in cryo-EM images. Here, we design a fully automated super-clustering approach for single particle picking (SuperCryoEMPicker) in cryo-EM micrographs, which focuses on identifying, detecting, and picking particles of the complex and irregular shapes in micrographs with extremely low signal-to-noise ratio (SNR). Our method first applies advanced image processing procedures to improve the quality of the cryo-EM images. The binary mask image-highlighting protein particles are then generated from each individual cryo-EM image using the super-clustering (SP) method, which improves upon base clustering methods (i.e., k-means, fuzzy c-means (FCM), and intensity-based cluster (IBC) algorithm) via a super-pixel algorithm. SuperCryoEMPicker is tested and evaluated on micrographs of β-galactosidase and 80S ribosomes, which are examples of cryo-EM data exhibiting complex and irregular particle shapes. The results show that the super-particle clustering method provides a more robust detection of particles than the base clustering methods, such as k-means, FCM, and IBC. SuperCryoEMPicker automatically and effectively identifies very complex particles from cryo-EM images of extremely low SNR. As a fully automated particle detection method, it has the potential to relieve researchers from laborious, manual particle-labeling work and therefore is a useful tool for cryo-EM protein structure determination.
Vine Waste Valorisation: Integrated Approach for the Prospection of Bioactive Lipophilic Phytochemicals
Authors: Salvador Ângelo C. , Simões Mário M. Q. , Silva Artur M. S. , Santos Sónia A. O. , Rocha Sílvia M. , Silvestre Armando J. D.
Published: August 2019

Substantial amounts of vine wastes are produced during vineyard management, and the chemical profiling of high-value lipophilic phytochemicals is becoming crucial in order to find a complementary route towards their integrated valorisation. The prospection of bioactive phytochemicals from unripe grape, vine shoot, vine cane, stalk and leaf dichloromethane extracts was carried out by gas chromatography–mass spectrometry (GC–MS), analysing samples from a mixture of four red Vitis vinifera L. varieties (Baga, Aragonez, Água Santa and Shiraz), collected at Bairrada Appellation, as a representative case study of typical multi-variety Portuguese vineyards. Vine wastes showed distinct amounts of lipophilic extract, ranging from 0.68% (vine canes) to 13.35% (vine leaves) at dry weight (dw). Thirty-three components were identified, including fatty acids and alcohols, sterols and triterpenoids accounting for amounts from 118.9 mg/100 g dw to 1512.0 mg/100 g dw. The integrated study revealed that unripe grape, stalk and leaf dichloromethane extracts stood out as possible sources of triterpenic compounds (103.2 to 653.5 mg/100 g dw), with lupeol, ursolic and oleanolic acids prevailing. Leaf extract is also reported as an undervalued source of α-tocopherol, as the major component detected in this matrix (300.5 mg/100 g dw). These exploratory results are a relevant contribution for the exploitation of undervalued vine residues as a source of health-promoting components with the potential to be used as supplements or nutraceutical ingredients.
Wnt/β-Catenin Signaling: The Culprit in Pancreatic Carcinogenesis and Therapeutic Resistance
Authors: Ram Makena Monish , Gatla Himavanth , Verlekar Dattesh , Sukhavasi Sahithi , K. Pandey Manoj , C. Pramanik Kartick
Published: August 2019

Pancreatic ductal adenocarcinoma (PDAC) is responsible for 7.3% of all cancer deaths. Even though there is a steady increase in patient survival for most cancers over the decades, the patient survival rate for pancreatic cancer remains low with current therapeutic strategies. The Wnt/β-catenin pathway controls the maintenance of somatic stem cells in many tissues and organs and is implicated in pancreatic carcinogenesis by regulating cell cycle progression, apoptosis, epithelial-mesenchymal transition (EMT), angiogenesis, stemness, tumor immune microenvironment, etc. Further, dysregulated Wnt has been shown to cause drug resistance in pancreatic cancer. Although different Wnt antagonists are effective in pancreatic patients, limitations remain that must be overcome to increase the survival benefits associated with this emerging therapy. In this review, we have summarized the role of Wnt signaling in pancreatic cancer and suggested future directions to enhance the survival of pancreatic cancer patients.
Surfactant Protein B Deficiency Induced High Surface Tension: Relationship between Alveolar Micromechanics, Alveolar Fluid Properties and Alveolar Epithelial Cell Injury
Authors: Rühl Nina , Lopez-Rodriguez Elena , Albert Karolin , Smith Bradford J , Weaver Timothy E , Ochs Matthias , Knudsen Lars
Published: August 2019

High surface tension at the alveolar air-liquid interface is a typical feature of acute and chronic lung injury. However, the manner in which high surface tension contributes to lung injury is not well understood. This study investigated the relationship between abnormal alveolar micromechanics, alveolar epithelial injury, intra-alveolar fluid properties and remodeling in the conditional surfactant protein B (SP-B) knockout mouse model. Measurements of pulmonary mechanics, broncho-alveolar lavage fluid (BAL), and design-based stereology were performed as a function of time of SP-B deficiency. After one day of SP-B deficiency the volume of alveolar fluid V(alvfluid,par) as well as BAL protein and albumin levels were normal while the surface area of injured alveolar epithelium S(AEinjure,sep) was significantly increased. Alveoli and alveolar surface area could be recruited by increasing the air inflation pressure. Quasi-static pressure-volume loops were characterized by an increased hysteresis while the inspiratory capacity was reduced. After 3 days, an increase in V(alvfluid,par) as well as BAL protein and albumin levels were linked with a failure of both alveolar recruitment and airway pressure-dependent redistribution of alveolar fluid. Over time, V(alvfluid,par) increased exponentially with S(AEinjure,sep). In conclusion, high surface tension induces alveolar epithelial injury prior to edema formation. After passing a threshold, epithelial injury results in vascular leakage and exponential accumulation of alveolar fluid critically hampering alveolar recruitability.
Karyotypes and Sex Chromosomes in Two Australian Native Freshwater Fishes, Golden Perch (Macquaria ambigua) and Murray Cod (Maccullochella peelii) (Percichthyidae)
Authors: Shams Foyez , Dyer Fiona , Thompson Ross , Duncan Richard P. , Thiem Jason D. , Majtánová Zuzana , Ezaz Tariq
Published: August 2019

Karyotypic data from Australian native freshwater fishes are scarce, having been described from relatively few species. Golden perch (Macquaria ambigua) and Murray cod (Maccullochella peelii) are two large-bodied freshwater fish species native to Australia with significant indigenous, cultural, recreational and commercial value. The arid landscape over much of these fishes’ range, coupled with the boom and bust hydrology of their habitat, means that these species have potential to provide useful evolutionary insights, such as karyotypes and sex chromosome evolution in vertebrates. Here we applied standard and molecular cytogenetic techniques to characterise karyotypes for golden perch and Murray cod. Both species have a diploid chromosome number 2n = 48 and a male heterogametic sex chromosome system (XX/XY). While the karyotype of golden perch is composed exclusively of acrocentric chromosomes, the karyotype of Murray cod consists of two submetacentric and 46 subtelocentric/acrocentric chromosomes. We have identified variable accumulation of repetitive sequences (AAT)10 and (CGG)10 along with diverse methylation patterns, especially on the sex chromosomes in both species. Our study provides a baseline for future cytogenetic analyses of other Australian freshwater fishes, especially species from the family Percichthyidae, to better understand their genome and sex chromosome evolution.
Preeclampsia: Maternal Systemic Vascular Disorder Caused by Generalized Endothelial Dysfunction Due to Placental Antiangiogenic Factors
Authors: Tomimatsu Takuji , Mimura Kazuya , Matsuzaki Shinya , Endo Masayuki , Kumasawa Keiichi , Kimura Tadashi
Published: August 2019

Preeclampsia, a systemic vascular disorder characterized by new-onset hypertension and proteinuria after 20 weeks of gestation, is the leading cause of maternal and perinatal morbidity and mortality. Maternal endothelial dysfunction caused by placental factors has long been accepted with respect to the pathophysiology of preeclampsia. Over the past decade, increased production of placental antiangiogenic factors has been identified as a placental factor leading to maternal endothelial dysfunction and systemic vascular dysfunction. This review summarizes the recent advances in understanding the molecular mechanisms of endothelial dysfunction caused by placental antiangiogenic factors, and the novel clinical strategies based on these discoveries.
Supplementation with 45S5 Bioactive Glass Reduces In Vivo Resorption of the β-Tricalcium-Phosphate-Based Bone Substitute Material Vitoss
Authors: Westhauser Fabian , Essers Christopher , Karadjian Maria , Reible Bruno , Schmidmaier Gerhard , Hagmann Sébastien , Moghaddam Arash
Published: August 2019

Compared to other materials such as 45S5 bioactive glass (BG), β-tricalcium phosphate (β-TCP)-based bone substitutes such as Vitoss show limited material-driven stimulation of osteogenesis and/or angiogenesis. The unfavorable degradation kinetics of β-TCP-based bone substitutes may result in an imbalance between resorption and osseous regeneration. Composite materials like Vitoss BA (Vitoss supplemented with 20 wt % 45S5-BG particles) might help to overcome these limitations. However, the influence of BG particles in Vitoss BA compared to unsupplemented Vitoss on osteogenesis, resorption behavior, and angiogenesis is not yet described. In this study, Vitoss and Vitoss BA scaffolds were seeded with human mesenchymal stromal cells before subcutaneous implantation in immunodeficient mice for 10 weeks. Scaffold resorption was monitored by micro-computed tomography, while osteoid formation and vascularization were assessed by histomorphometry and gene expression analysis. Whilst slightly more osteoid and improved angiogenesis were found in Vitoss BA, maturation of the osteoid was more advanced in Vitoss scaffolds. The volume of Vitoss implants decreased significantly, combined with a significantly increased presence of resorbing cells, whilst the volume remained stable in Vitoss BA scaffolds. Future studies should evaluate the interaction of 45S5-BG with resorbing cells and bone precursor cells in greater detail to improve the understanding and application of β-TCP/45S5-BG composite bone substitute materials.
Delivery of Mixed-Lineage Kinase Domain-Like Protein by Vapor Nanobubble Photoporation Induces Necroptotic-Like Cell Death in Tumor Cells
Authors: Van Hoecke Lien , Raes Laurens , Stremersch Stephan , Brans Toon , Fraire Juan C. , Roelandt Ria , Declercq Wim , Vandenabeele Peter , Raemdonck Koen , Braeckmans Kevin , Saelens Xavier
Published: August 2019

Modern molecular medicine demands techniques to efficiently deliver molecules directly into mammalian cells. As proteins are the final mediators of most cellular pathways, efficient intracellular protein delivery techniques are highly desired. In this respect, photoporation is a promising recent technique for the delivery of proteins directly into living cells. Here, we show the possibility to deliver a model saccharide (FD70) and a model protein (FITC-BSA) into murine B16 melanoma cells by using the vapor nanobubble photoporation technique with an efficiency of 62% and 38%, respectively. Next, we delivered the mixed-lineage kinase domain-like (MLKL) protein, the most terminal mediator of necroptosis currently known, and caspase-8 and -3 protein, which are important proteins in the initiation and execution of apoptosis. A significant drop in cell viability with 62%, 71% and 64% cell survival for MLKL, caspase-8 and caspase-3, respectively, was observed. Remarkably, maximal cell death induction was already observed within 1 h after protein delivery. Transduction of purified recombinant MLKL by photoporation resulted in rapid cell death characterized by cell swelling and cell membrane rupture, both hallmarks of necroptosis. As necroptosis has been identified as a type of cell death with immunogenic properties, this is of interest to anti-cancer immunotherapy. On the other hand, transduction of purified recombinant active caspase-3 or -8 into the tumor cells resulted in rapid cell death preceded by membrane blebbing, which is typical for apoptosis. Our results suggest that the type of cell death of tumor cells can be controlled by direct transduction of effector proteins that are involved in the executioner phase of apoptosis or necroptosis.
Highly Efficient and Heritable Targeted Mutagenesis in Wheat via the Agrobacterium tumefaciens-Mediated CRISPR/Cas9 System
Authors: Zhang Shujuan , Zhang Rongzhi , Gao Jie , Gu Tiantian , Song Guoqi , Li Wei , Li Dandan , Li Yulian , Li Genying
Published: August 2019

The CRISPR/Cas9 system has been successfully used in hexaploid wheat. Although it has been reported that the induced mutations can be passed to the next generation, gene editing and transmission patterns in later generations still need to be studied. In this study, we demonstrated that the CRISPR/Cas9 system could achieve efficient mutagenesis in five wheat genes via Agrobacterium-mediated transformation of an sgRNA targeting the D genome, an sgRNA targeting both the A and B homologues and three tri-genome guides targeting the editing of all three homologues. High mutation rates and putative homozygous or biallelic mutations were observed in the T0 plants. The targeted mutations could be stably inherited by the next generation, and the editing efficiency of each mutant line increased significantly across generations. The editing types and inheritance of targeted mutagenesis were similar, which were not related to the targeted subgenome number. The presence of Cas9/sgRNA could cause new mutations in subsequent generations, while mutated lines without Cas9/sgRNA could retain the mutation type. Additionally, off-target mutations were not found in sequences that were highly homologous to the selected sgRNA sequences. Overall, the results suggested that CRISPR/Cas9-induced gene editing via Agrobacterium-mediated transformation plays important roles in wheat genome engineering.
Cyclo-Oxygenase (COX) Inhibitors and Cardiovascular Risk: Are Non-Steroidal Anti-Inflammatory Drugs Really Anti-Inflammatory?
Authors: Khan Shanzana , Andrews Karen L. , Chin-Dusting Jaye P. F.
Published: August 2019

Cyclo-oxygenase (COX) inhibitors are among the most commonly used drugs in the western world for their anti-inflammatory and analgesic effects. However, they are also well-known to increase the risk of coronary events. This area is of renewed significance given alarming new evidence suggesting this effect can occur even with acute usage. This contrasts with the well-established usage of aspirin as a mainstay for cardiovascular prophylaxis, as well as overwhelming evidence that COX inhibition induces vasodilation and is protective for vascular function. Here, we present an updated review of the preclinical and clinical literature regarding the cardiotoxicity of COX inhibitors. While studies to date have focussed on the role of COX in influencing renal and vascular function, we suggest an interaction between prostanoids and T cells may be a novel factor, mediating elevated cardiovascular disease risk with NSAID use.
Value of Information of Structural Health Monitoring in Asset Management of Flood Defences
Authors: Klerk Wouter Jan , Schweckendiek Timo , den Heijer Frank , Kok Matthijs
Published: August 2019

One of the most rapidly emerging measures in infrastructure asset management is Structural Health Monitoring (SHM), which aims at reducing uncertainty in structural performance by using monitoring equipment. As earthen flood defence structures typically have large strength uncertainties, such techniques can be particularly promising. However, insight in the key characteristics for successful SHM for flood defences is lacking, which hampers the practical implementation. In this study, we explore the benefits of pore pressure monitoring, one of the most promising SHM techniques for earthen flood defences. The approach is based on a Bayesian pre-posterior analysis, and results are evaluated based on the Value of Information (VoI) obtained from different monitoring strategies. We specifically investigate the effect on long-term reinforcement decisions. The results show that, next to the relative magnitude of reducible uncertainty, the combination of the probability of having a useful observation and the duration of a SHM effort determine the VoI. As it is likely that increasing loads due to climate change will result in more frequent future reinforcements, the influence of scenarios of different rates of increase in future loads is also investigated. It was found that, in all considered possible scenarios, monitoring yields a positive Value of Information, hence it is an economically efficient measure for flood defence asset management both now and in the future.
A New Mechanism of Dynamic Phase Transformations in An Isothermal Forged Beta–Gamma Intermetallic Alloy
Authors: Zhang Zhengang , Qu Shoujiang , Cui Guorong , Feng Aihan , Shen Jun , Chen Daolun
Published: August 2019

A new mechanism of dynamic phase transformations of α2 ↔ γ in an isothermally forged γ-TiAl-based alloy that occur simultaneously during a short-term exposure at 1000 °C is identified in this study. In the heating process, γ phase significantly decreases through a phase transformation of γ → α2, while new γ lamellae are precipitated in the interior of equiaxed grains of α2 phase through a phase transformation of α2 → γ. The reasons for the presence of these two inverse phase transformations α2 ↔ γ occurring simultaneously are discussed.
TiN-Nanoparticulate-Reinforced ZrO2 for Electrical Discharge Machining
Authors: Lazar Ana , Kosmač Tomaž , Zavašnik Janez , Abram Anže , Kocjan Andraž
Published: August 2019

This study presents a fabrication route for an electrically conductive ZrO2–TiN ceramic nanocomposite with a nanoscale TiN phase occupying ≤30 vol% to improve the mechanical reinforcement of the zirconia matrix, and at the same time provide electrical conductivity to facilitate electro-discharge machining (EDM). The TiN nanoparticles were incorporated into a 3 mol% yttria-stabilized tetragonal zirconia (Y-TZP) powder, either by admixing a TiN nanopowder (MCP) or by using in-situ synthesis (ISS) via the forced hydrolysis of a titanyl sulphate aqueous solution and the direct nitriding of as-synthesized titania nanoparticles, followed by consolidation and rapid sintering in a spark plasma sintering (SPS) system. The initial phase composition and crystal structure of the as-synthesized powders and the sintered samples were characterized by transmission electron microscopy (TEM) and X-ray difraction (XRD). The influence of the different fabrication routes on the microstructural evolution, electrical and mechanical properties, and affinity for EDM were assessed using TEM, focused ion beam scanning electron microscopy (FIB-SEM, Vickers indentation, electrical conductivity measurements, and profilometry. The MCP synthesis route resulted in finer microstructures that are less prone to microstructural inhomogeneities; however, using the ISS route, it was possible to fabricate electrically conductive Y-TZP nanocomposites containing only 15 vol% of the TiN nanoparticulate phase. Both synthesis routes resulted in an increase of the fracture toughness with an increase of the TiN phase due to the nanoparticulate TiN reinforcement of the Y-TZP ceramic matrix via crack-bridging toughening mechanisms. As both synthesis routes yielded Y-TZP nanocomposites capable of successful EDM machining at a TiN content of ≥30 vol% for the MCP and ≥ 15 vol% TiN for the ISS, a possible mechanism was developed based on the microstructure evolution and grain growth.
Gradient Microstructures and Mechanical Properties of Ti-6Al-4V/Zn Composite Prepared by Friction Stir Processing
Authors: Lv Yuting , Ding Zihao , Sun Xueyan , Li Lei , Sha Gang , Liu Rui , Wang Liqiang
Published: August 2019

In this work, a biomedical Ti-6Al-4V (TC4)/Zn composite with gradient microstructures was successfully prepared by friction stir processing (FSP). The microstructures and mechanical properties of the composite were systematically studied using scanning electron microscope (SEM), X-ray diffractometer (XRD), transmission electron microscope (TEM), atom probe tomography (APT), and microhardness test. The results show that TC4/Zn composite can be successfully prepared, and gradient microstructures varying from coarse grain to nanocrystalline is formed from the bottom to the upper surface. During FSP, adding Zn can accelerate the growth of β phase region, and the grain size significantly increases with the increasing rotation rate. The grain combination is the main mechanism for grain growth of β phase region. The deformation mechanisms gradually change from dislocation accumulations and rearrangement to dynamic recrystallization from the bottom to the upper surface (1.5 mm–150 μm from the upper surface). The composite exhibits slightly higher microhardness compared with the matrix. This paper provides a new method to obtain a TC4/Zn composite with gradient surface microstructures for potential applications in the biomedical field.
Effect of Silicone Rubber of a Waste Composite Insulator on Cement Mortar Properties
Authors: Qin Gang , Shen Zhongshuo , Yu Yongqiang , Fan Lidan , Cao Hongwei , Yin Chaowei
Published: August 2019

Due to the rapid growth of the electric power system, the silicone rubber composite insulator is so widely employed around the world. However, the aging damage and decommission of it inevitably generates plenty of waste silicone rubber. It takes up large amounts of land for non-degradation, which is becoming a serious environmental issue. In this paper, the effort has been made to reuse the silicone rubber of composite insulator by peeling, breaking and adding it into the cement mortar to partly replace river sand by 5%, 10%, 15%, 20% and 30% in volume. Moreover, the surface modification of silicone rubber particles with H2O2 and KOH is explored to improve hydrophilicity. The mechanical strength of silicone rubber mortar and modified silicone rubber mortar are measured in detail, and the effects of particle size, content and modification of silicone rubber on the properties of mortar are investigated. This study shows that at least a 5% addition of silicone rubber can reduce the strengths, while the 15% addition is obviously favorable for increasing the toughness. Furthermore, the mortar strength gets promoted due to the surface modification. Lastly, the superior thermal insulation and noise reduction of the mortar are obtained as the addition of silicone rubber particles, and an equation between dry apparent density and thermal conductivity of mortar has been developed.
Effects of Liner-Bonding of Implant-Supported Glass–Ceramic Crown to Zirconia Abutment on Bond Strength and Fracture Resistance
Authors: Jang Yong-Seok , Oh Sang-Hoon , Oh Won-Suck , Lee Min-Ho , Lee Jung-Jin , Bae Tae-Sung
Published: August 2019

This study was conducted to test the hypothesis that heat-bonding with a liner positively affects the bond strength and fracture resistance of an implant-supported glass–ceramic crown bonded to a zirconia abutment produced by a computer-aided design/computer-aided milling (CAD/CAM) procedure. Lithium disilicate-reinforced Amber Mill-Q glass ceramic blocks were bonded to 3 mol% yttria stabilized tetragonal zirconia polycrystal (3Y-TZP) blocks by heat-bonding with a liner or cementation with a dual-cure self-adhesive resin cement for a microtensile bond strength test. CAD/CAM implant-supported glass ceramic crowns were produced using Amber Mill-Q blocks and bonded to a milled 3Y-TZP zirconia abutments by heat-bonding or cementation for a fracture test. A statistical analysis was conducted to investigate the significant differences between the experimental results. The mode of failure was analyzed using high-resolution field emission scanning electron microscopy. Chemical bonding was identified at the interface between the zirconia ceramic and liner. The mean tensile bond strength of the liner-bonded group was significantly higher than that of the cement-bonded group. The initial chipping strength of the liner-bonded group was significantly higher than that of the cement-bonded group, although no statistically significant difference was found for the fracture strength. The mode of failure was mixed with cohesive fracture through the liner, whereas the cement-bonded group demonstrated adhesive failure at the interface of bonding.
Energy Coupling of Laser Radiation on AISI 304 Stainless Steel: Effect of High Temperatures and Surface Oxidation
Authors: Hipp Dominik , Mahrle Achim , Beyer Eckhard
Published: August 2019

The industrial application of laser materials processing methods is still far ahead of research into the physical phenomena occurring during these processes. In particular, the effect of high temperatures on the energy coupling of laser irradiation of metals is poorly understood. However, most processes in laser materials treatment involve temperatures above the melting point or even cause evaporation. This study therefore evaluates the effect of high temperatures on the energy coupling efficiency of stainless steel experimentally for three typical laser wavelengths (515 nm, 1.07 µm, 10.6 µm). As a result, it is shown that the effect of temperature on the energy coupling efficiency depends on the wavelength. In this context the relevance of the X-point phenomenon known from the emissivity theory could be demonstrated for laser material processing. Further, the effect of a process-induced surface oxidation is analyzed. At temperatures above 650 °C the energy coupling efficiency dramatically increases to around 65% at melting point and stays at this high level even in the liquid phase.
Temporal Acoustic Emission Index for Damage Monitoring of RC Structures Subjected to Bidirectional Seismic Loadings
Authors: Abarkane Chihab , Rescalvo Francisco J. , Donaire-Ávila Jesús , Galé-Lamuela David , Benavent-Climent Amadeo , Gallego Molina Antolino
Published: August 2019

This paper shows the acoustic emission (AE) analysis recorded during the loading process of reinforced concrete (RC) structures subjected to bidirectional seismic loadings. Two waffle plates (bidirectional) supported by isolated square columns were tested on a shaking table with a progressive and increasing ground acceleration until the final collapse. Each specimen was subjected to a different loading history. A relevant delay in the beginning of the significant AE energy is observed as the peak value of the ground acceleration increases. Based on this result, a new AE temporal damage index (TDI), defined as the time difference between the onset of the significant AE activity and the onset of the loading that causes this AE activity, is proposed and validated by comparing it with the plastic strain energy released by the concrete, typically used as a reliable damage level indicator. Good agreement was observed for both specimens and seismic inputs.
A Population-Based Analysis of Incidence, Mortality, and Survival in Testicular Cancer Patients in Lithuania
Authors: Drevinskaite Mingaile , Patasius Ausvydas , Kincius Marius , Jievaltas Mindaugas , Smailyte Giedre
Published: August 2019

Background and objectives: The aim of this study was to analyze trends in testicular cancer incidence, mortality, and survival in Lithuania during the period 1998–2013. Materials and Methods: The study was based on all cases of testicular cancer reported to the Lithuanian Cancer Registry between 1998 and 2013. Age group-specific rates and standardized rates were calculated using the direct method (European standard population). The Joinpoint regression model was used to provide the annual percentage change (APC). Five-year relative survival estimates were calculated using period analysis. Relative survival was calculated as the ratio of the observed survival of cancer patients and the expected survival of the underlying general population. Results: During the study period, the age-standardized incidence rate of testicular cancer increased from 1.97 to 3.45 per 100,000, with APC of 2.97% (95% CI 0.9 to 5.1). Incidence rate of seminomas changed from 0.71 to 1.54 per 100,000, with APC of 2.61% (95% CI −0.4 to 5.7), and the incidence rate of non-seminomas increased from 0.84 to 1.83 per 100,000, with APC of 4.16% (95% CI 1.6 to 6.8). The mortality rate of testicular cancer in Lithuania during this period declined from 0.78 to 0.51 per 100,000, with APC of −2.91% (95% CI −5.5 to −0.3). Relative five-year survival ratio for the period 2009–2013 was 89.39% (95% CI 82.2 to 94.4). In our study, the overall five-year relative survival increased slightly (10.1%) from 2004–2008 to 2009–2013 (from 79.3% to 89.4%). Conclusions: A moderate increase of testicular cancer incidence has been observed in Lithuania between the years 1998 and 2013, while the mortality rate decreased. The five-year relative survival increased according to different period estimates; however, the results could have been higher if a multidisciplinary approach to diagnostics and management in the concerned centers had been implemented in Lithuania as in other countries.
Influence of Burnout on Patient Safety: Systematic Review and Meta-Analysis
Authors: Garcia Cíntia , Abreu Luiz , Ramos José , Castro Caroline , Smiderle Fabiana , Santos Jaçamar , Bezerra Italla
Published: August 2019

Background and Objectives: Several factors can compromise patient safety, such as ineffective teamwork, failed organizational processes, and the physical and psychological overload of health professionals. Studies about associations between burn out and patient safety have shown different outcomes. Objective: To analyze the relationship between burnout and patient safety. Materials and Methods: A systematic review with a meta-analysis performed using PubMed and Web of Science databases during January 2018. Two searches were conducted with the following descriptors: (i) patient safety AND burnout professional safety AND organizational culture, and (ii) patient safety AND burnout professional safety AND safety management. Results: Twenty-one studies were analyzed, most of them demonstrating an association between the existence of burnout and the worsening of patient safety. High levels of burnout is more common among physicians and nurses, and it is associated with external factors such as: high workload, long journeys, and ineffective interpersonal relationships. Good patient safety practices are influenced by organized workflows that generate autonomy for health professionals. Through meta-analysis, we found a relationship between the development of burnout and patient safety actions with a probability of superiority of 66.4%. Conclusion: There is a relationship between high levels of burnout and worsening patient safety.