bluuebunny/crossref_metadata_2025 huggingface dataset:
A Universal Design of FPGA-Based Real-Time Simulator for Active Distribution Networks Based on Reconfigurable Computing
Authors: Jin Shuo , Yu Hao , Fu Xiaopeng , Wang Zhiying , Yuan Kai , Li Peng
Published: May 2019

Reconfigurable computing is that the logical resources in the system can be reconfigured according to the real-time changing data flow to achieve different calculation functions. The reconfigurable computing system has both high efficiency on hardware and universality of software. The field programmable gate array (FPGA)-based real-time simulator for active distribution networks (ADNs) requires a long compilation time for case modification, with low efficiency and low versatility, making it inconvenient and difficult for users. To solve the problem of long compile time with a new case, a universal design of the FPGA-based real-time simulator for ADNs based on reconfigurable computing is proposed in this paper. It includes the universal design of the simulation parameter configuration, the simulation initial value setting, the linear equations solving module and the simulation result output module. The proposed universal design of the simulator makes the modification and change of the cases and parameters without recompiling and further improves the simulation efficiency. Simulation results are conducted and compared with PSCAD/EMTDC to validate the correctness and effectiveness of the universal design.
A Practical Method for Speeding up the Cavitation Prediction in an Industrial Double-Suction Centrifugal Pump
Authors: Pei Ji , Osman Majeed Koranteng , Wang Wenjie , Appiah Desmond , Yin Tingyun , Deng Qifan
Published: May 2019

Researches have over the past few years have been applying optimization algorithms to quickly find optimum parameter combinations during cavitation optimization design. This method, although better than the traditional trial-and-error design method, consumes lots of computational resources, since it involves several numerical simulations to determine the critical cavitation point for each test case. As such, the Traditional method for NPSHr prediction was compared to a novel and alternative approach in an axially-split double-suction centrifugal pump. The independent and dependent variables are interchanged at the inlet and outlet boundary conditions, and an algorithm adapted to estimate the static pressure at the pump outlet. Experiments were conducted on an original size pump, and the two numerical procedures agreed very well with the hydraulic and cavitation results. For every flow condition, the time used by the computational resource to calculate the NPSHr for each method was recorded and compared. The total number of hours used by the new and alternative approach to estimate the NPSHr was reduced by 54.55% at 0.6 Qd, 45.45% at 0.8 Qd, 50% at 1.0 Qd, and 44.44% at 1.2 Qd respectively. This new method was demonstrated to be very efficient and robust for real engineering applications and can, therefore, be applied to reduce the computation time during the application of intelligent cavitation optimization methods in pump design.
Planning of High Renewable-Penetrated Distribution Systems Considering Complementarity and Cluster Partitioning
Authors: Hu Di , Ding Ming , Sun Lei , Zhang Jingjing
Published: May 2019

Photovoltaic (PV) and wind power (WT) resources can influence each other in some scenarios, and this influence tends to show that the rise of PV resources may indicate the drop of WT resources, and vice versa. This pattern of PV and WT resources influencing each other is called the complementary characteristics of PV and WT power. The complementary characteristics of the power outputs of different kinds of distributed renewable energy resources (DRERs) and the correlation between DRERs outputs and loads can impact the consumption of DRERs by the loads within the grid, which represents the rate of DRER outputs consumed by loads instead of being reduced. In this regard, this paper investigates a planning strategy for DRERs considering these two factors. An improved co-variance matrix method is applied to generate complementary samples of DRERs and correlated samples of DRERs and loads. The samples generated are used to study the impacts of the degree of correlation between DRERs and loads on the consumption ability of DRERs. The concept of the cluster is introduced as a region including DRERs with complementary characteristics. Based on the cluster partition method and the samples generated, the DRERs planning model is proposed to maximize the profits of different DRER stakeholders. The planning model is transformed into a single objective model through the ideal point method. A Benders decomposition-based method is developed to efficiently solve the proposed model, and an actual network in China is used to illustrate its performance. The results show DRER consumption can be significantly improved by the proposed planning model.
A Modified Blasingame Production Analysis Method for Vertical Wells Considering the Quadratic Gradient Term
Authors: Ren Junjie , Zheng Qiao , Zhao Chunlan
Published: May 2019

Fluid flow in actual oil reservoirs is consistent with material balance, which should be described by the nonlinear governing equation, including the quadratic gradient term (QGT). Nonetheless, the widely-used Blasingame production decline analysis (BPDA) is established based on the conventional governing equation neglecting the QGT, which leads to some errors in the interpretation of production data under some conditions, such as wells producing at a large drawdown pressure. This work extends BPDA to incorporate the effect of the QGT by modifying material balance time and normalized rate functions. The step-by-step procedure for the proposed production decline analysis (PPDA) is presented and compared with that for BPDA. The simulated cases for various production scenarios are used to validate PPDA. A field case is employed to show the applicability of PPDA in practice. Comparisons between the results obtained by BPDA and PPDA are analyzed in detail. It is found that BPDA overestimates the permeability and original oil-in-place, while PPDA works well. Compared with BPDA, PPDA can be employed to obtain more accurate original oil-in-place and reservoir properties, especially when wells produce at a large drawdown pressure.
Numerical Simulation Investigation on the Windage Power Loss of a High-Speed Face Gear Drive
Authors: Dai Yu , Ma Feiyue , Zhu Xiang , Jia Jifu
Published: May 2019

Reducing the energy consumption and improving the efficiency of high-speed transmission systems are increasingly common goals; the windage power loss is not negligible in these methods. In this work, the multi-reference frame (MRF) and periodic boundary conditions (PBC) based on the computational fluid dynamics (CFD) method were adopted to investigate the windage phenomena of a single face gear with and without a shroud, and the impact of the gear speed on the windage power loss was analyzed. Furthermore, the effects on the distribution of static pressure due to the distances between the shroud and the gear body in different directions, including the outer radius direction, the inner radius direction, and the addendum direction were investigated. The results indicate that the gear speed significantly affected the windage loss, as the higher the gear speed was, the greater the windage power loss. Additionally, the shroud could effectively reduce the windage power loss, where the optimal distance from the addendum to the shroud was not the minimum distance; however, for the distances from the shroud to the inner radius and the outer radius, the smaller the distance was, the smaller the windage loss. The results can provide a theoretical basis and technical reference for reducing the windage power loss of various face gear drives.
Land Use Change Impacts on Hydrology in the Nenjiang River Basin, Northeast China
Authors: Li Fengping , Zhang Guangxin , Li Hongyan , Lu Wenxi
Published: May 2019

The objectives of this study were to assess land use changes and their hydrological impacts in the Nenjiang River Basin (NRB). The Soil and Water Assessment Tool (SWAT) model was employed to evaluate the impacts of land use changes. The Cellular Automata-Markov model was used to predict a land use map in 2038. Streamflow under each land use state was simulated by the SWAT model. The results showed that there was a significant expansion of agriculture area at the expense of large areas of grassland, wetland, and forest during 1975–2000. The land use changes during the period of 1975 to 2000 had decreased the water yield (3.5%), surface runoff (1.7%), and baseflow (19%) while they increased the annual evapotranspiration (2.1%). For impacts of individual land use type, the forest proved to have reduced streamflow in the flood season (10%–28%) and increased surface runoff in the drought season (20%–38%). Conversely, grassland, dry land, and paddy land scenarios resulted in increase of streamflow during summer months by 7%–37% and a decrease of streamflow in the cold seasons by 11.7%–59.7%. When the entire basin was changed to wetland, streamflow reduced over the whole year, with the largest reduction during January to March. The 2038 land use condition is expected to increase the annual water yield, surface runoff and wet season flow, and reduce evapotranspiration and baseflow. These results could help to improve sustainable land use management and water utilization in the NRB.
Current and Emerging Technologies for the Detection of Norovirus from Shellfish
Authors: Gyawali Pradip , KC Sanjaya , Beale David J. , Hewitt Joanne
Published: May 2019

Reports of norovirus infections associated with the consumption of contaminated bivalve molluscan shellfish negatively impact both consumers and commercial shellfish operators. Current virus recovery and PCR detection methods can be expensive and time consuming. Due to the lack of rapid, user-friendly and onsite/infield methods, it has been difficult to establish an effective virus monitoring regime that is able to identify contamination points across the production line (i.e., farm-to-plate) to ensure shellfish quality. The focus of this review is to evaluate current norovirus detection methods and discuss emerging approaches. Recent advances in omics-based detection approaches have the potential to identify novel biomarkers that can be incorporated into rapid detection kits for onsite use. Furthermore, some omics techniques have the potential to simultaneously detect multiple enteric viruses that cause human disease. Other emerging technologies discussed include microfluidic, aptamer and biosensor-based detection methods developed to detect norovirus with high sensitivity from a simple matrix. Many of these approaches have the potential to be developed as user-friendly onsite detection kits with minimal costs. However, more collaborative efforts on research and development will be required to commercialize such products. Once developed, these emerging technologies could provide a way forward that minimizes public health risks associated with shellfish consumption.
Relativistic Aspects of Accreting Supermassive Black Hole Binaries in Their Natural Habitat: A Review
Authors: Gold Roman
Published: May 2019

In this review a summary is given on recent theoretical work, on understanding accreting supermassive black hole binaries in the gravitational wave (GW)-driven regime. A particular focus is given to theoretical predictions of properties of disks and jets in these systems during the gravitational wave driven phase. Since a previous review by Schnittman 2013, which focussed on Newtonian aspects of the problem, various relativistic aspects have been studied. In this review we provide an update on these relativistic aspects. Further, a perspective is given on recent observational developments that have seen a surge in the number of proposed supermassive black hole binary candidates. The prospect of bringing theoretical and observational efforts closer together makes this an exciting field of research for years to come.
Use of Paleoflood Deposits to Determine the Contribution of Anthropogenic Trace Metals to Alluvial Sediments in the Hyperarid Rio Loa Basin, Chile
Authors: Miller Jerry R. , Walsh Danvey , Villarroel Lionel F.
Published: May 2019

Toxic trace metals are a common and significant contaminant in riverine ecosystems, and are derived from both natural and anthropogenic sources. Determining the contributions of metals from these sources has proven difficult, in part, because physical and biogeochemical processes alter the nature (e.g., grain size, mineral composition, organic matter content) of the source materials as they are transported through the drainage network. This study examined the use of paleoflood deposits located along the hyperarid Rio Salado, a tributary to the Rio Loa of northern Chile, to construct local background functions and enrichment factors (LEFs) to differentiate between natural and anthropogenic metal sources. Significant variations in metal content occurred between river reaches and flood deposits of a given reach; these variations were primarily related to changes in sediment source that may reflect differences in El Niño and La Niña precipitation patterns. Three conservative elements (Al, Fe, Co) were examined to construct background functions for seven trace metals. Cobalt yielded the most effective background functions for As, Cd, Ni, Pb, and Zn; Fe was selected for Cr, and Al for Cu. The resulting LEFs approximated 1, illustrating that paleoflood deposits produced effective background functions, and could be applied to downstream sites contaminated by mining activity.
Chemistry for Audio Heritage Preservation: A Review of Analytical Techniques for Audio Magnetic Tapes
Authors: Bressan Federica , Hess Richard L. , Sgarbossa Paolo , Bertani Roberta
Published: May 2019

Vast and important cultural resources are entrusted to magnetic tape around the world, but they are susceptible to degradation, which may lead to severe replay problems. Audio magnetic tapes are complex and multicomponent devices containing organic compounds and metal systems, which can be potential catalysts for many degradative reactions in the presence of water, light, or heating. The aim of this review is to collect the literature concerning the analytical determinations and instrumental approaches that can achieve the chemical identification of the components in the tape and the degradation state. Thus, a combination of destructive (such as acetone extraction) and non-destructive techniques (such as ATR FTIR spectroscopy) have been proposed, together with SEM, ESEM, XRD and TGA analyses to assess the chemical and physical characterization of the tape with the purpose to individualize restoration treatments and optimize conditions for preservation. The impact of the studies reviewed in this paper may go beyond audio, being potentially relevant to video, data, instrumentation, and logging tapes.
Analysis of Global Research on Malaria and Plasmodium vivax
Authors: Garrido-Cardenas José Antonio , Cebrián-Carmona José , González-Cerón Lilia , Manzano-Agugliaro Francisco , Mesa-Valle Concepción
Published: May 2019

Background: Malaria is one of the infectious diseases of greatest interest to the scientific community and of greatest concern to international health authorities. Traditionally, the focus has been on Plasmodium falciparum, the parasite that causes the most severe form of the disease in Africa. However, in the last twenty years, the Plasmodium vivax parasite, responsible for a large number of cases in Latin America, the Middle East, South and Southeast Asia, the Horn of Africa, and Oceania, has also generated enormous interest due, among other things, to the published evidence that it can cause severe malaria. Methods: In this paper, the international scientific publication on malaria and P. vivax has been analyzed using the Scopus database to try to define global trends in this field of study. Results: It has been shown that events such as the emergence of resistance to certain drugs can break a trend. The important role of non-malaria-endemic countries such as the USA or Switzerland in malaria research is also evident. Conclusions: International cooperation will be essential for the eradication of the disease. Moreover, in this sense, the general vision given by the bibliometric analysis of malaria caused by P. vivax is fundamental to paint the picture regarding the current situation and encourage international cooperation and control efforts.
Horsepower of Doctors’ Cars Correlates with Cardiovascular Risk and Sedentary Lifestyle but Not with Sexual Dysfunction or Sexual Satisfaction
Authors: Niederseer David , Gilhofer Thomas , Schmied Christian , Steger Bernhard , Dankl Christian , Colvin Hans Peter , Rieder Josef , Neunhäuserer Daniel , Niebauer Josef , Datz Christian
Published: May 2019

Background: The horsepower not only of doctors’ cars correlates with personal income and social status. However, no clear relationship has previously been described between the horsepower of doctors’ cars and cardiovascular health or sexual dysfunction and/or satisfaction. Objective: Cross-sectional online survey to evaluate associations between self-reported horsepower of physicians’ cars and health aspects. Methods: Of 1877 physicians from the two University-Hospitals in Austria that were asked to participate in the study, 363 (37.7 ± 8.0 years, 208 (57.3%) men) were included into the final analysis. Results: Physicians that own a car with a stronger engine were significantly older, were more often male, had more often a leading position, had a higher monthly income (all p < 0.001), had a higher scientific output (p = 0.030), and had hypercholesteremia more often (p = 0.009). They also tended to have a higher body mass index (p = 0.088), reported a higher maximum weight in previous years (p = 0.004) and less often reported regular healthy commuting to and from work (p = 0.010). No significant associations were found for self-reported physical fitness, smoking status, and arterial hypertension. In addition, sexual satisfaction and sexual dysfunction were also not related to horsepower in the whole population and the male subgroup. The findings essentially persisted after controlling for age. Conclusion: The horsepower of Austrian physicians’ cars correlates with senior position and increased cardiovascular risk. However, our data shows no relationship between sexual dysfunction or lack of sexual satisfaction and the horsepower of doctors’ cars.
How Personal Perspectives Shape Health Professionals’ Perceptions of Fetal Alcohol Spectrum Disorder and Risk
Authors: Bagley Kerryn , Badry Dorothy
Published: May 2019

This article examines how health, allied health and social service professionals’ personal perspectives about alcohol and the risks associated with alcohol consumption become non-clinical factors that may influence their professional practice responses in relation to fetal alcohol spectrum disorder (FASD). It presents findings derived from a qualitative, interview-based study of professionals from a range of health, allied health and social service professions in New Zealand. The data derived from these interviews revealed four frames of reference that practitioners use when thinking about alcohol and risk: reflection on personal experience; experiences of friends, relatives and colleagues; social constructions of alcohol use and misuse; and comparisons to other types of drug use. The article concludes that these non-clinical factors are important considerations in professional decision making about FASD.
Phenotypic Stability of Staphylococcus aureus Small Colony Variants (SCV) Isolates from Cystic Fibrosis (CF) Patients
Authors: Kittinger Clemens , Toplitsch Daniela , Folli Bettina , Masoud Landgraf Lilian , Zarfel Gernot
Published: May 2019

One of the most interesting features of Staphylococcus aureus is its ability to switch to a small colony variant (SCV). This switch allows the pathogen to survive periods of antibiotic treatment or pressure from the immune system of the host and further enables it to start the infection once again after the environmental stress declines. However, so far only little is known about this reversion back to the more virulent wild type phenotype. Therefore, this study aimed to analyze the frequency of reversion to the wild type phenotype of thymidine auxotroph S. aureus SCV isolates (TD-SCVs) obtained from patients with cystic fibrosis (CF). With the use of single cell starting cultures, the occurrence of the thymidine prototroph revertants was monitored. The underlying mutational cause of the SCVs and subsequent revertants were analyzed by sequencing the gene coding for thymidylate synthase (ThyA), whose mutations are known to produce thymidine auxotroph S. aureus SCV. In our study, the underlying mutational cause for the switch to the TD-SCV phenotype was primarily point mutations. Out of twelve isolates, seven isolates showed an occurrence of revertants with a frequency ranging from 90.06% to 0.16%. This high variability in the frequency of reversion to the wild type was not expected. However, this variability in the frequency of reversion may also be the key to successful re-infection of the host. Sometimes quick reversion to the wild type proves necessary for survival, whereas other times, staying hidden for a bit longer leads to success in re-colonization of the host.
Linking a History of Childhood Abuse to Adult Health among Canadians: A Structural Equation Modelling Analysis
Authors: Cameranesi Margherita , Lix Lisa M. , Piotrowski Caroline C.
Published: May 2019

A history of childhood abuse has been linked to serious and long-lasting problems in adulthood. We developed two theoretical models concerning how early adverse experiences affect health in adulthood, and we tested the empirical fit of the two models in a population-based representative sample of Canadian adults (N = 25,113) using a structural equation modelling (SEM) technique, path analysis. The first model included direct pathways by which a history of three types of childhood abuse—exposure to intimate partner violence, physical abuse, and sexual abuse—affected adult physical and mental health, as well as indirect pathways by which perceived social support and everyday life stress acted as mediators of these associations. The second model included only indirect pathways and tested mediating effects. Global statistics indicated that both models were a good fit to the data, and local statistics supported the hypothesized associations between independent, dependent, and mediator variables.
Learning Cartographic Building Generalization with Deep Convolutional Neural Networks
Authors: Feng Yu , Thiemann Frank , Sester Monika
Published: May 2019

Cartographic generalization is a problem, which poses interesting challenges to automation. Whereas plenty of algorithms have been developed for the different sub-problems of generalization (e.g., simplification, displacement, aggregation), there are still cases, which are not generalized adequately or in a satisfactory way. The main problem is the interplay between different operators. In those cases the human operator is the benchmark, who is able to design an aesthetic and correct representation of the physical reality. Deep learning methods have shown tremendous success for interpretation problems for which algorithmic methods have deficits. A prominent example is the classification and interpretation of images, where deep learning approaches outperform traditional computer vision methods. In both domains-computer vision and cartography-humans are able to produce good solutions. A prerequisite for the application of deep learning is the availability of many representative training examples for the situation to be learned. As this is given in cartography (there are many existing map series), the idea in this paper is to employ deep convolutional neural networks (DCNNs) for cartographic generalizations tasks, especially for the task of building generalization. Three network architectures, namely U-net, residual U-net and generative adversarial network (GAN), are evaluated both quantitatively and qualitatively in this paper. They are compared based on their performance on this task at target map scales 1:10,000, 1:15,000 and 1:25,000, respectively. The results indicate that deep learning models can successfully learn cartographic generalization operations in one single model in an implicit way. The residual U-net outperforms the others and achieved the best generalization performance.
Speed Estimation of Multiple Moving Objects from a Moving UAV Platform
Authors: Biswas Debojit , Su Hongbo , Wang Chengyi , Stevanovic Aleksandar
Published: May 2019

Speed detection of a moving object using an optical camera has always been an important subject to study in computer vision. This is one of the key components to address in many application areas, such as transportation systems, military and naval applications, and robotics. In this study, we implemented a speed detection system for multiple moving objects on the ground from a moving platform in the air. A detect-and-track approach is used for primary tracking of the objects. Faster R-CNN (region-based convolutional neural network) is applied to detect the objects, and a discriminative correlation filter with CSRT (channel and spatial reliability tracking) is used for tracking. Feature-based image alignment (FBIA) is done for each frame to get the proper object location. In addition, SSIM (structural similarity index measurement) is performed to check how similar the current frame is with respect to the object detection frame. This measurement is necessary because the platform is moving, and new objects may be captured in a new frame. We achieved a speed accuracy of 96.80% with our framework with respect to the real speed of the objects.
Role of Hyaluronan in Human Adipogenesis: Evidence from in-Vitro and in-Vivo Studies
Authors: Wilson Nicholas , Steadman Robert , Muller Ilaria , Draman Mohd , Rees D. Aled , Taylor Peter , Dayan Colin M. , Ludgate Marian , Zhang Lei
Published: May 2019

Hyaluronan (HA), an extra-cellular matrix glycosaminoglycan, may play a role in mesenchymal stem cell differentiation to fat but results using murine models and cell lines are conflicting. Our previous data, illustrating decreased HA production during human adipogenesis, suggested an inhibitory role. We have investigated the role of HA in adipogenesis and fat accumulation using human primary subcutaneous preadipocyte/fibroblasts (PFs, n = 12) and subjects of varying body mass index (BMI). The impact of HA on peroxisome proliferator-activated receptor gamma (PPARγ) expression was analysed following siRNA knockdown or HA synthase (HAS)1 and HAS2 overexpression. PFs were cultured in complete or adipogenic medium (ADM) with/without 4-methylumbelliferone (4-MU = HA synthesis inhibitor). Adipogenesis was evaluated using oil red O (ORO), counting adipogenic foci, and measurement of a terminal differentiation marker. Modulating HA production by HAS2 knockdown or overexpression increased (16%, p < 0.04) or decreased (30%, p = 0.01) PPARγ transcripts respectively. The inhibition of HA by 4-MU significantly enhanced ADM-induced adipogenesis with 1.52 ± 0.18- (ORO), 4.09 ± 0.63- (foci) and 2.6 ± 0.21-(marker)-fold increases compared with the controls, also increased PPARγ protein expression (40%, (p < 0.04)). In human subjects, circulating HA correlated negatively with BMI and triglycerides (r = −0.396 (p = 0.002), r = −0.269 (p = 0.038), respectively), confirming an inhibitory role of HA in human adipogenesis. Thus, enhancing HA action may provide a therapeutic target in obesity.
Targeting Angiogenesis in Prostate Cancer
Authors: Melegh Zsombor , Oltean Sebastian
Published: May 2019

Prostate cancer is the most commonly diagnosed cancer among men in the Western world. Although localized disease can be effectively treated with established surgical and radiopharmaceutical treatments options, the prognosis of castration-resistant advanced prostate cancer is still disappointing. The objective of this study was to review the role of angiogenesis in prostate cancer and to investigate the effectiveness of anti-angiogenic therapies. A literature search of clinical trials testing the efficacy of anti-angiogenic therapy in prostate cancer was performed using Pubmed. Surrogate markers of angiogenic activity (microvessel density and vascular endothelial growth factor A (VEGF-A) expression) were found to be associated with tumor grade, metastasis, and prognosis. Six randomizedstudies were included in this review: two phase II trials on localized and hormone-sensitive disease (n = 60 and 99 patients) and four phase III trials on castration-resistant refractory disease (n = 873 to 1224 patients). Although the phase II trials showed improved relapse-free survival and stabilisation of the disease, the phase III trials found increased toxicity and no significant improvement in overall survival. Although angiogenesis appears to have an important role in prostate cancer, the results of anti-angiogenic therapy in castration-resistant refractory disease have hitherto been disappointing. There are various possible explanations for this lack of efficacy in castration-resistant refractory disease: redundancy of angiogenic pathways, molecular heterogeneity of the disease, loss of tumor suppressor protein phosphatase and tensin homolog (PTEN) expression as well as various VEGF-A splicing isoforms with pro- and anti-angiogenic activity. A better understanding of the molecular mechanisms of angiogenesis may help to develop effective anti-angiogenic therapy in prostate cancer.
MiR-150-5p May Contribute to Pathogenesis of Human Leiomyoma via Regulation of the Akt/p27Kip1 Pathway In Vitro
Authors: Lee Jae Hoon , Choi Young Sik , Park Ji Hyun , Kim Heeyon , Lee Inha , Won Young Bin , Yun Bo Hyon , Park Joo Hyun , Seo Seok Kyo , Lee Byung Seok , Cho SiHyun
Published: May 2019

Uterine leiomyoma is found in ~50–80% of women of a reproductive age and is the most common reason for hysterectomy. Recently, posttranscriptional gene silencing by microRNAs (miRs) has been reported as a mechanism for regulating gene expression stability in the pathogenesis of uterine leiomyomas. In this study, miR microarray analysis of leiomyomas and paired myometrial tissue revealed numerous aberrantly expressed miRs, including miR-150. In functional assays, transfection with miR-150 mimic resulted in decreased migration and fibrosis, implying an inhibition of leiomyoma growth. To identify the target genes of miR-150 in leiomyoma, gene set analysis and network analysis were performed. To overcome the limitations of in silico analysis, changes in expression levels of hallmark genes in leiomyoma after transfection with a miR-150 mimic were also evaluated using qRT-PCR. As a result, the Akt/p27Kip1 pathway was presumed to be one of the target pathways of miR-150. After transfecting cultured leiomyoma cells with the miR-150 mimic, expression levels of its target gene Akt decreased, whereas those of p27Kip1 increased significantly. Our results suggest that miR-150 affects the cell cycle regulation in uterine leiomyoma through the Akt/p27Kip1 pathway.
Identification and Characterization of Approved Drugs and Drug-Like Compounds as Covalent Escherichia coli ClpP Inhibitors
Authors: Sassetti Elisa , Durante Cruz Cristina , Tammela Päivi , Winterhalter Mathias , Augustyns Koen , Gribbon Philip , Windshügel Björn
Published: May 2019

The serine protease Caseinolytic protease subunit P (ClpP) plays an important role for protein homeostasis in bacteria and contributes to various developmental processes, as well as virulence. Therefore, ClpP is considered as a potential drug target in Gram-positive and Gram-negative bacteria. In this study, we utilized a biochemical assay to screen several small molecule libraries of approved and investigational drugs for Escherichia coli ClpP inhibitors. The approved drugs bortezomib, cefmetazole, cisplatin, as well as the investigational drug cDPCP, and the protease inhibitor 3,4-dichloroisocoumarin (3,4-DIC) emerged as ClpP inhibitors with IC50 values ranging between 0.04 and 31 µM. Compound profiling of the inhibitors revealed cefmetazole and cisplatin not to inhibit the serine protease bovine α-chymotrypsin, and for cefmetazole no cytotoxicity against three human cell lines was detected. Surface plasmon resonance studies demonstrated all novel ClpP inhibitors to bind covalently to ClpP. Investigation of the potential binding mode for cefmetazole using molecular docking suggested a dual covalent binding to Ser97 and Thr168. While only the antibiotic cefmetazole demonstrated an intrinsic antibacterial effect, cDPCP clearly delayed the bacterial growth recovery time upon chemically induced nitric oxide stress in a ClpP-dependent manner.
6-SFT, a Protein from Leymus mollis, Positively Regulates Salinity Tolerance and Enhances Fructan Levels in Arabidopsis thaliana
Authors: Li Mao , He Xiaolan , Hao Dongdong , Wu Jun , Zhao Jixin , Yang Qunhui , Chen Xinhong
Published: May 2019

Fructans play vital roles in abiotic stress tolerance in plants. In this study, we isolated the sucrose:6-fructosyltransferase gene, which is involved in the synthesis of fructans, from Leymus mollis by rapid amplification of cDNA ends. The Lm-6-SFT gene was introduced into Arabidopsis thaliana cv. Columbia by Agrobacterium-mediated transformation. The transgenic plants were evaluated under salt stress conditions. The results showed that the expression of Lm-6-SFT was significantly induced by light, abscisic acid (ABA), salicylic acid (SA), and salt treatment in L. mollis plants. Overexpression of Lm-6-SFT in Arabidopsis promoted seed germination and primary root growth during the early vegetative growth stage under salt stress. We also found that the transgenic plants expressing Lm-6-SFT had increased proline and fructan levels. β-Glucuronidase staining and promoter analysis indicated that the promoter of Lm-6-SFT was regulated by light, ABA, and salt stress. Quantitative PCR suggested that overexpression of Lm-6-SFT could improve salt tolerance by interacting with the expression of some salt stress tolerance genes. Thus, we demonstrated that the Lm-6-SFT gene is a candidate gene that potentially confers salt stress tolerance to plants. Our study will aid the elucidation of the regulatory mechanism of 6-SFT genes in herb plants.
Synaptic Vesicles Having Large Contact Areas with the Presynaptic Membrane are Preferentially Hemifused at Active Zones of Frog Neuromuscular Junctions Fixed during Synaptic Activity
Authors: Jung Jae Hoon
Published: May 2019

Synaptic vesicles dock on the presynaptic plasma membrane of axon terminals and become ready to fuse with the presynaptic membrane or primed. Fusion of the vesicle membrane and presynaptic membrane results in the formation of a pore between the membranes, through which the vesicle’s neurotransmitter is released into the synaptic cleft. A recent electron tomography study on frog neuromuscular junctions fixed at rest showed that there is no discernible gap between or merging of the membrane of docked synaptic vesicles with the presynaptic membrane, however, the extent of the contact area between the membrane of docked synaptic vesicles and the presynaptic membrane varies 10-fold with a normal distribution. The study also showed that when the neuromuscular junctions are fixed during repetitive electrical nerve stimulation, the portion of large contact areas in the distribution is reduced compared to the portion of small contact areas, suggesting that docked synaptic vesicles with the largest contact areas are greatly primed to fuse with the membrane. Furthermore, the finding of several hemifused synaptic vesicles among the docked vesicles was briefly reported. Here, the spatial relationship of 81 synaptic vesicles with the presynaptic membrane at active zones of the neuromuscular junctions fixed during stimulation is described in detail. For the most of the vesicles, the combined thickness of each of their contact sites was not different from the sum of the membrane thicknesses of the vesicle membrane and presynaptic membrane, similar to the docked vesicles at active zones of the resting neuromuscular junctions. However, the combined membrane thickness of a small portion of the vesicles was considerably less than the sum of the membrane thicknesses, indicating that the membranes at their contact sites were fixed in a state of hemifusion. Moreover, the hemifused vesicles were found to have large contact areas with the presynaptic membrane. These findings support the recently proposed hypothesis that, at frog neuromuscular junctions, docked synaptic vesicles with the largest contact areas are most primed for fusion with the presynaptic membrane, and that hemifusion is a fusion intermediate step of the vesicle membrane with the presynaptic membrane for synaptic transmission.
Safety Evaluation of Oral Care Probiotics Weissella cibaria CMU and CMS1 by Phenotypic and Genotypic Analysis
Authors: Kang Mi-Sun , Yeu Ji-Eun , Hong Sang-Phil
Published: May 2019

Weissella cibaria CMU and CMS1 are known to exert beneficial effects on the oral cavity but have not yet been determined to be generally recognized as safe (GRAS), although they are used as commercial strains in Korea. We aimed to verify the safety of W. cibaria CMU and CMS1 strains through phenotypic and genotypic analyses. Their safety was evaluated by a minimum inhibitory concentration assay for 14 antibiotics, DNA analysis for 28 antibiotic resistance genes (ARGs) and one conjugative element, antibiotic resistance gene transferability, virulence gene analysis, hemolysis, mucin degradation, toxic metabolite production, and platelet aggregation reaction. W. cibaria CMU showed higher kanamycin resistance than the European Food Safety Authority (EFSA) cut-off, but this resistance was not transferred to the recipient strain. W. cibaria CMU and CMS1 lacked ARGs in chromosomes and plasmids, and genetic analysis confirmed that antibiotic resistance of kanamycin was an intrinsic characteristic of W. cibaria. Additionally, these strains did not harbor virulence genes associated with pathogenic bacteria and lacked toxic metabolite production, β-hemolysis, mucin degradation, bile salt deconjugation, β-glucuronidase, nitroreductase activity, gelatin liquefaction, phenylalanine degradation, and platelet aggregation. Our findings demonstrate that W. cibaria CMU and CMS1 can achieve the GRAS status in future.
Genome Editing to Integrate Seed Size and Abiotic Stress Tolerance Traits in Arabidopsis Reveals a Role for DPA4 and SOD7 in the Regulation of Inflorescence Architecture
Authors: Chen Siyu , Zhang Na , Zhang Qimeng , Zhou Ganghua , Tian Hainan , Hussain Saddam , Ahmed Sajjad , Wang Tianya , Wang Shucai
Published: May 2019

Both seed size and abiotic stress tolerance are important agronomic traits in crops. In Arabidopsis, two closely related transcription repressors DPA4 (Development-Related PcG Target in the APEX4)/NGAL3 and SOD7 (Suppressor of da1-1)/NGAL2 (NGATHA-like protein) function redundantly to regulate seed size, which was increased in the dpa4 sod7 double mutants. Whereas ABA-induced transcription repressors (AITRs) are involved in the regulation of ABA signaling and abiotic stress tolerance, Arabidopsis aitr2 aitr5 aitr6 (aitr256) triple mutant showed enhanced tolerance to drought and salt. Here we performed CRISPR/Cas9 genome editing to disrupt DPA4 and SOD7 in aitr256 mutant, trying to integrate seed size and abiotic stress tolerance traits in Arabidopsis, and also to examine whether DPA4 and SOD7 may regulate other aspects of plant growth and development. Indeed, seed size was increased in the dpa4 sod7 aitr256 quintuple mutants, and enhanced tolerance to drought was observed in the mutants. In addition, we found that shoot branching was affected in the dpa4 sod7 aitr256 mutants. The mutant plants failed to produce secondary branches, and flowers/siliques were distributed irregularly on the main stems of the plants. Floral organ number and fertility were also affected in the dpa4 sod7 aitr256 mutant plants. To examine if these phenotypes were dependent on loss-of-function of AITRs, dpa4 sod7 double mutants were generated in Col wild type background, and we found that the dpa4 sod7 mutant plants showed a phenotype similar to the dpa4 sod7 aitr256 quintuple mutants. Taken together, our results indicate that the integration of seed size and abiotic stress tolerance traits by CRISPR/Cas9 editing was successful, and our results also revealed a role of DPA4 and SOD7 in the regulation of inflorescence architecture in Arabidopsis.
Epac1 and Glycyrrhizin Both Inhibit HMGB1 Levels to Reduce Diabetes-Induced Neuronal and Vascular Damage in the Mouse Retina
Authors: Liu Li , Jiang Youde , Steinle Jena J.
Published: May 2019

The role of high mobility group box 1 (HMGB1) in acute diabetic retinal damage has been demonstrated. We recently reported that glycyrrhizin, a HMGB1 inhibitor, protected the diabetic retina against neuronal, vascular, and permeability changes. In this study, we wanted to investigate the role of exchange protein for cAMP 1 (Epac1) on HMGB1 and the actions of glycyrrhizin. Using endothelial cell specific knockout mice for Epac1, we made some mice diabetic using streptozotocin, and treated some with glycyrrhizin for up to 6 months. We measured permeability, neuronal, and vascular changes in the Epac1 floxed and knockout mice. We also investigated whether Epac1 and glycyrrhizin work synergistically to reduce the retinal inflammatory mediators, tumor necrosis factor alpha (TNFα) and interleukin-1-beta (IL1β), as well as sirtuin 1 (SIRT1) levels. Epac1 and glycyrrhizin reduced inflammatory mediators with synergistic actions. Glycyrrhizin also increased SIRT1 levels in the Epac1 mice. Overall, these studies demonstrate that glycyrrhizin and Epac1 can work together to protect the retina. Finally, glycyrrhizin may regulate HMGB1 through increased SIRT1 actions.
Ceftaroline Efficacy and Safety in Treatment of Complicated Skin and Soft Tissue Infection: A Systemic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Lan Shao-Huan , Chang Shen-Peng , Lai Chih-Cheng , Lu Li-Chin , Chao Chien-Ming
Published: May 2019

This study aims to assess the clinical efficacy and safety of ceftaroline for the treatment of complicated skin and skin structure infections (cSSSIs) in adult patients through meta-analysis. PubMed, Embase, ClinicalTrials.gov, and Cochrane databases were searched up to April 2019. Only randomized controlled trials (RCTs) that evaluated ceftaroline and other comparators for treating cSSSIs in adult patients were included. The primary outcome was the clinical cure rate, whereas the secondary outcomes were clinical failure rate, microbiological eradication rate, relapse rate, and risk of an adverse event (AE). Five RCTs were included. Overall, ceftaroline had a clinical cure rate similar to comparators in the treatment of cSSSIs in the modified intent-to-treat population (risk ratio (RR), 1.00; 95% confidence interval (CI), 0.97–1.04; I2 = 0%) and in the clinically evaluable population (RR, 1.00; 95% CI, 0.97–1.03; I2 = 0%). In addition, no significant difference was observed between ceftaroline and comparators for the treatment of infection with Staphylococcus aureus (RR, 1.01; 95% CI, 0.98–1.05; I2 = 0%), methicillin-resistant S. aureus (RR, 0.99; 95% CI, 0.94–1.05; I2 = 0%), methicillin-susceptible S. aureus (RR, 1.01; 95% CI, 0.96–1.06; I2 = 26%), Streptococcus spp. (RR, 1.07; 95% CI, 0.92–1.24; I2 = 73%), and Gram-negative bacteria (RR, 0.94; 95% CI, 0.83–1.08; I2 = 0%). Furthermore, ceftaroline had a similar rate of microbiological eradication (92.2% vs. 92.6%, RR, 1.00; 95% CI, 0.97–1.03; I2 = 9%) and relapse (6.9% vs. 9.1%, RR, 0.48; 95% CI, 0.14–1.74; I2 = 0%) as comparators. Finally, the risks of treatment-emergent AEs (RR, 0.96; 95% CI, 0.88–1.05; I2 = 0%), serious AEs (RR, 1.03; 95% CI, 0.63–1.68; I2 = 0%), and discontinuation of study drug due to an AE (RR, 0.86; 95% CI, 0.50–1.49; I2 = 34%) did not differ significantly between ceftaroline and comparators. In conclusion, the clinical efficacy of ceftaroline is as high as that of comparators in the treatment of cSSSIs in adult patients, and this antibiotic is well tolerated like the comparators.
Wave Climate Change in the North Sea and Baltic Sea
Authors: Bonaduce Antonio , Staneva Joanna , Behrens Arno , Bidlot Jean-Raymond , Wilcke Renate Anna Irma
Published: May 2019

Wave climate change by the end of the 21st century (2075–2100) was investigated using a regional wave climate projection under the RCP 8.5 scenario. The performance of the historical run (1980–2005) in representing the present wave climate was assessed when compared with in situ (e.g., GTS) and remote sensing (i.e., Jason-1) observations and wave hindcasts (e.g., ERA5-hindcast). Compared with significant wave height observations in different subdomains, errors on the order of 20–30% were observed. A Principal Component (PC) analysis showed that the temporal leading modes obtained from in situ data were well correlated (0.9) with those from the historical run. Despite systematic differences (10%), the general features of the present wave climate were captured by the historical run. In the future climate projection, with respect to the historical run, similar wave climate change patterns were observed when considering both the mean and severe wave conditions, which were generally larger during summer. The range of variation in the projected extremes (±10%) was consistent with those observed in previous studies both at the global and regional spatial scales. The most interesting feature was the projected increase in extreme wind speed, surface Stokes drift speed and significant wave height in the Northeast Atlantic. On the other hand, a decrease was observed in the North Sea and the southern part of the Baltic Sea basin, while increased extreme values occurred in the Gulf of Bothnia during winter.
Genetic Algorithm-Based Design for Metal-Enhanced Fluorescent Nanostructures
Authors: Fixler Dror , Tzur Chen , Zalevsky Zeev
Published: May 2019

In this paper, we present our optimization tool for fluorophore-conjugated metal nanostructures for the purpose of designing novel contrast agents for multimodal bioimaging. Contrast agents are of great importance to biological imaging. They usually include nanoelements causing a reduction in the need for harmful materials and improvement in the quality of the captured images. Thus, smart design tools that are based on evolutionary algorithms and machine learning definitely provide a technological leap in the fluorescence bioimaging world. This article proposes the usage of properly designed metallic structures that change their fluorescence properties when the dye molecules and the plasmonic nanoparticles interact. The nanostructures design and evaluation processes are based upon genetic algorithms, and they result in an optimal separation distance, orientation angles, and aspect ratio of the metal nanostructure.
Research of Cu-Doped Hydroxyapatite Microbeads Fabricated by Pneumatic Extrusion Printing
Authors: Chi Wenchao , Zou Jiawei , Ai Fanrong , Lin Yanjun , Li Wenchao , Cao Chuanliang , Yang Kang , Zhou Kui
Published: May 2019

Copper is an indispensable micronutrient in human health, which has important effects on the promotion of angiogenesis and thus contributes to bone formation and antimicrobial activity. We used ion exchange and pneumatic printing methods to prepare hydroxyapatite (HA) microspheres with different copper content. The microspheres were characterized by scanning electron microscope (SEM), X-ray diffractometry (XRD) and X-Ray photoelectron spectroscopy (XPS). Considering the resistance of hydroxyapatite to biodegradation in vivo, the degradation rate of microspheres in modified simulated body fluids was studied. In addition, cell proliferation and antibacterial experiments were carried out to study the biological properties of microspheres. HA-1.5MCu microbeads treated by 1.5 mol/L CuSO4 curing solution have good performance on degradation, antibacterial properties and cell survival rate on day 7. The results showed that HA-1.5MCu microbeads may be used as a good repair material for bone defects.