bluuebunny/crossref_metadata_2025 huggingface dataset:
Several Problems with Froude-Number Based Scale Modeling of Fires in Small Compartments
Authors: Zimny Mateusz , Antosiewicz Piotr , Krajewski Grzegorz , Burdzy Tomasz , Krasuski Adam , Węgrzyński Wojciech
Published: September 2019

The Froude-number based reduced-scale modeling is a technique commonly used to investigate the flow of heat and mass in building fires. The root of the method is the thermodynamic model of a flow in a compartment and several non-dimensional flow numbers based on the proportionalities of the Navier-Stokes and heat transfer equations. The ratio of inertial forces to the buoyancy forces, known as the Froude-number, plays a pivotal role within these proportionalities. This paper is an attempt to define the range of credible scale modeling using the Froude-number. We verify the credibility of the modeling by small fire (approximately 150 kW) in a small compartment, comparing data from a physical test (scale 1:1 and 1:4) and the numerical model’s data (Fire Dynamics Simulator, scales 1:1, 1:2, 1:4, 1:10, 1:20, and 1:50). The scope of the research covers a wide range of fires, with observed change of the flow from turbulent to laminar. The results show that the applicability of Froude-number reduced-scale modeling has limitations related to the scale. Therefore, it should be applied with care following sensibility analysis. We propose a method for sensibility analysis using Computational Fluid Dynamics (CFD) modeling.
A Review on Transformerless Step-Up Single-Phase Inverters with Different DC-Link Voltage for Photovoltaic Applications
Authors: Liu Wenjie , Niazi Kamran Ali Khan , Kerekes Tamas , Yang Yongheng
Published: September 2019

Photovoltaic (PV) energy has been competitive in power generation as an alternative to fossil energy resources over the past decades. The installation of grid-connected solar energy systems is expected to increase rapidly with the fast development of the power electronics technology. As the key to the interface of the PV energy and the grid, power converters should be reliable, efficient and comply with the grid requirements. Considering the nature of PV energy, the power conversion should be flexible (e.g., high step-up DC-DC conversion and harmonic-free DC-AC conversion). Accordingly, many power electronic converters have been reported in literature. Compared with isolated inverters, transformerless inverters show great advantages. This paper thus presents an overview of the transformerless step-up single-phase inverters for PV applications based on the dc-link configurations. Grid-connected PV inverters are classified as constant dc-link voltage structures, pseudo-dc-link voltage structures, pulsating dc-link voltage structures and integrated dc-link voltage structures. The discussion on the composition of different dc-link structures is presented, which provides guidance to select appropriate transformerless inverter topologies for PV applications.
Application of Least-Cost Movement Modeling in Planning Wildlife Mitigation Measures along Transport Corridors: Case Study of Forests and Moose in Lithuania
Authors: Wierzchowski Jack , Kučas Andrius , Balčiauskas Linas
Published: September 2019

The present work presents the development of a moose movement model to explore the value of wildlife mitigation structures and examine how hypothetical changes in land use patterns could alter wildlife habitats at landscape scales. Collisions between vehicles and animals pose a threat to humans and wildlife populations, the most dangerous collisions being with moose. Migrations of moose are generally predictable and habitat-dependent. Here, we use GIS-based simulations of moose movements to examine road-related habitat fragmentation around the main highways A1 and A2 in Lithuania. From forest data, we develop a moose habitat suitability map. Then, by running multiple simulation iterations, we generate potential moose pathways and statistically describe the most efficient potential long-range movement routes that are based on the principles of habitat utilization. Reflecting the probabilities of cross-highway moose movement, ranks are assigned to all 1 km highway segments, characterizing them in terms of their likelihood of moose movement, and thus identifying discrete migration corridors and highway crossing zones. Bottlenecks are identified through simulation, such as where sections of wildlife fencing end without highway crossing structures, thereby creating a ‘spillover’ effect, i.e., moose moving parallel to the highway, then crossing. The tested model has proven the prognostic capacity of the tool to foresee locations of moose-vehicle collisions with high accuracy, thus allowing it to be a valuable addition to the toolbox of highway planners.
Estimating the Sustainability of Managed Natural Forests in Costa Rica—A Hybrid Delphi & Choice Experiment Approach
Authors: Salas-Garita Cynthia , Soliño Mario
Published: September 2019

Management of natural forests in Costa Rica allows timber extraction in so far as it is guaranteed that the logging activities comply with diverse Sustainability Principles, Criteria and Indicators (PCIs). These are hierarchical and complex systems used, ex-ante in the formulation and approval of the Management Plan but have not been used for ex-post evaluation of managed forests. Development of sustainability evaluation systems that include few criteria is highly recommended. In that sense, the choice experiments contribute to simplification of the initial system of decision making, complementing a complex system of PCIs that permits detailed analysis of the management units. In this study, a choice experiment was included in a Delphi application and 5 key variables were identified to evaluate the sustainability of managed natural forests. These variables are, in order of importance—technical, legal and administrative conditions; external financing conditions; production performance; costs of preparing the Management Plan; and payment mechanisms for environmental services. The definition of these variables confirms not only that the technical, legal and administrative conditions are critical for sustainability but also that they could reflect the type of governance involved in sustainability forest management.
Climate Changes and Food Quality: The Potential of Microbial Activities as Mitigating Strategies in the Wine Sector
Authors: Berbegal Carmen , Fragasso Mariagiovanna , Russo Pasquale , Bimbo Francesco , Grieco Francesco , Spano Giuseppe , Capozzi Vittorio
Published: September 2019

Climate change threatens food systems, with huge repercussions on food security and on the safety and quality of final products. We reviewed the potential of food microbiology as a source of biotechnological solutions to design climate-smart food systems, using wine as a model productive sector. Climate change entails considerable problems for the sustainability of oenology in several geographical regions, also placing at risk the wine typicity. The main weaknesses identified are: (i) The increased undesired microbial proliferation; (ii) the improved sugars and, consequently, ethanol content; (iii) the reduced acidity and increased pH; (iv) the imbalanced perceived sensory properties (e.g., colour, flavour); and (v) the intensified safety issues (e.g., mycotoxins, biogenic amines). In this paper, we offer an overview of the potential microbial-based strategies suitable to cope with the five challenges listed above. In terms of microbial diversity, our principal focus was on microorganisms isolated from grapes/musts/wines and on microbes belonging to the main categories with a recognized positive role in oenological processes, namely Saccharomyces spp. (e.g., Saccharomyces cerevisiae), non-Saccharomyces yeasts (e.g., Metschnikowia pulcherrima, Torulaspora delbrueckii, Lachancea thermotolerans, and Starmerella bacillaris), and malolactic bacteria (e.g., Oenococcus oeni, Lactobacillus plantarum).
Century-Scale Fire Dynamics in a Savanna Ecosystem
Authors: Leys Bérangère A. , Griffin Daniel , Larson Evan R. , McLauchlan Kendra K.
Published: September 2019

(1) Background: Frequent fire, climate variability, and human activities collectively influence savanna ecosystems. The relative role of these three factors likely varies on interannual, decadal, and centennial timescales. Here, we tested if Euro-American activities uncoupled drought and fire frequencies relative to previous centuries in a temperate savanna site. (2) Methods: We combined records of fire frequency from tree ring fire scars and sediment charcoal abundance, and a record of fuel type based on charcoal particle morphometry to reconstruct centennial scale shifts in fire frequency and fuel sources in a savanna ecosystem. We also tested the climate influence on fire occurrence with an independently derived tree-ring reconstruction of drought. We contextualized these data with historical records of human activity. (3) Results: Tree fire scars revealed eight fire events from 1822–1924 CE, followed by localized suppression. Charcoal signals highlight 13 fire episodes from 1696–2001. Fire–climate coupling was not clearly evident both before and after Euro American settlement The dominant fuel source shifted from herbaceous to woody fuel during the early-mid 20th century. (4) Conclusions: Euro-American settlement and landscape fragmentation disrupted the pre-settlement fire regime (fire frequency and fuel sources). Our results highlight the potential for improved insight by synthesizing interpretation of multiple paleofire proxies, especially in fire regimes with mixed fuel sources.
In Vitro Effects of Bisphenol A and Tetrabromobisphenol A on Cell Viability and Reproduction-Related Gene Expression in Pituitaries from Sexually Maturing Atlantic Cod (Gadus morhua L.)
Authors: von Krogh Kristine , Ropstad Erik , Nourizadeh-Lillabadi Rasoul , Haug Trude Marie , Weltzien Finn-Arne
Published: September 2019

Bisphenol A (BPA) and tetrabromobisphenol A (TBBPA) are widely used industrial chemicals, ubiquitously present in the environment. While BPA is a well-known endocrine disruptor and able to affect all levels of the teleost reproductive axis, information regarding TBBPA on this subject is very limited. Using primary cultures from Atlantic cod (Gadus morhua), the present study was aimed at investigating potential direct effects of acute (72 h) BPA and TBBPA exposure on cell viability and the expression of reproductive-relevant genes in the pituitary. The results revealed that both bisphenols stimulate cell viability in terms of metabolic activity and membrane integrity at environmentally relevant concentrations. BPA had no direct effects on gonadotropin gene expression, but enhanced the expression of gonadotropin-releasing hormone (GnRH) receptor 2a, the main gonadotropin modulator in Atlantic cod. In contrast, TBBPA increased gonadotropin transcript levels but had no effect on GnRH receptor mRNA. In conclusion, both anthropogenic compounds display endocrine disruptive properties and are able to directly interfere with gene expression related to reproductive function in cod pituitary cells at environmentally relevant concentrations in vitro.
Lactic Acid Fermentation as a Pre-Treatment Process for Faba Bean Flour and Its Effect on Textural, Structural and Nutritional Properties of Protein-Enriched Gluten-Free Faba Bean Breads
Authors: Sozer Nesli , Melama Leena , Silbir Selim , Rizzello Carlo G. , Flander Laura , Poutanen Kaisa
Published: September 2019

Lactic acid fermentation could be used as a potential modification tool for faba bean flour to enable its incorporation in boosting the nutritional profile of gluten-free breads. Gluten-free breads made with fermented or unfermented faba bean flours were compared with commercial soy flour. The amounts of faba- and soy-bean flours were adjusted to obtain the same protein content in bread (16%). Both fermented and unfermented faba bean flour resulted in larger bread volume (2.1 mL/g and 2.4 mL/g, respectively) compared to bread made with soybean flour (1.5 mL/g). Breads made with unfermented and fermented faba flour had higher porosity (82% and 72%, respectively) than bread with soy flour (61%). The faba breads also were softer than the soy bread. Fermentation of faba flour prior to bread making significantly increased crumb hardness (584 vs. 817 g). Fermentation increased in vitro protein digestibility (72.3% vs. 64.8%). Essential Amino Acid and Biological Value indexes were significantly higher for breads containing fermented faba flour compared to breads made with unfermented faba and soy flour. The Protein Efficiency Ratio and Nutritional Index increased by fermentation from 33 to 36 and 1.6 to 2.7, respectively. Pre-fermentation of faba bean flour improved the nutritional properties of high-protein, gluten-free faba bread. A sensory panel indicated that fermentation did not affect the crumbliness, evenness of pore size and springiness of breadcrumb.
Phenolic Compounds from Sesame Cake and Antioxidant Activity: A New Insight for Agri-Food Residues’ Significance for Sustainable Development
Authors: Mekky Reham Hassan , Abdel-Sattar Essam , Segura-Carretero Antonio , Contreras María del Mar
Published: September 2019

Agri-food residues represent a rich source of nutrients and bioactive secondary metabolites, including phenolic compounds. The effective utilization of these by-products in food supplements and the nutraceuticals industry could provide a way of valorization in the transition to becoming more sustainable. In this context, the present study describes the phenolic profiling of sesame (Sesamum indicum L.) cake using reversed-phase high-performance liquid chromatography coupled to diode array detection and quadrupole-time-of-flight-mass spectrometry. Compounds were characterized based on their retention time, UV spectra, accurate mass spectrometry (MS) and MS/MS data along with comparison with standards, whenever possible, and the relevant literature. The characterized compounds (112 metabolites) belong to several classes, namely, phenolic acids (hydroxybenzoic acids and hydroxycinnamic acids), flavonoids, and lignans. Moreover, organic acids and some nitrogenous compounds were characterized. The total phenol content and the antioxidant activity of the cake extract were determined. This study provides useful information for the valorization of by-products from the sesame oil industry.
Acceptance of a New Food Enriched in β-Glucans among Adolescents: Effects of Food Technology Neophobia and Healthy Food Habits
Authors: Proserpio Cristina , Pagliarini Ella , Laureati Monica , Frigerio Beatrice , Lavelli Vera
Published: September 2019

The aim of the present study was to evaluate adolescents’ acceptability of a novel flat bread modified by substituting a part of the wheat flour content with a Pleurotus ostreatus powder rich in β-glucans, which can potentially provide health benefits. The effects of food technology neophobia and adolescents’ food habits on hedonic perception of the developed product was also investigated. Two hundred and two adolescents (age range: 13–18 years; girls: 49.5%; boys: 50.5%) evaluated their liking of two flat breads, one with mushroom powder added and one control sample with only wheat flour. Sample acceptance was studied in relation to age, gender, neophobic traits and healthy food habits. The results showed that, even if the sample with mushroom powder added was generally well accepted, there were different hedonic responses among adolescents according to their food technology neophobia level and healthy habits. In particular, adolescents with a low food technology neophobia level and healthy eating behavior mostly appreciated the sample with mushroom powder added, whereas subjects with neophobic and unhealthy eating behavior gave comparable hedonic scores to the two samples. Moreover, a negative correlation was found between food technology neophobia level and healthy food habits. In conclusion, it is possible to develop a β-glucan-enriched product appreciated by adolescents using a sustainable ingredient. The developed product may be used to achieve the daily recommended intake of β-glucans by adolescents.
Overview of Foodborne Disease Outbreaks in Brazil from 2000 to 2018
Authors: Finger Jéssica A. F. F. , Baroni Wilma S. G. V. , Maffei Daniele F. , Bastos Deborah H. M. , Pinto Uelinton M.
Published: September 2019

This study aimed to assess the foodborne diseases (FBD) outbreaks reported in Brazil between 2000 and 2018, based on data from the Brazilian Ministry of Health (official data) and from scientific literature. According to official data, 13,163 FBD outbreaks were reported in the country during this period, involving 247,570 cases and 195 deaths. The largest prevalence of FBD outbreaks was observed in the Southeast region of Brazil (45.6%). In most outbreaks it was not possible to determine the food implicated (45.9%) but among those identified, water was the most frequently associated (12.0%). The etiological agent was not identified in most outbreaks (38.0%), while Salmonella (14.4%) was the most frequently reported among those identified. Homes were the main site of FBD occurrence (12.5%). Regarding data obtained from the scientific literature, 57 articles dealing with FBD in the country throughout the same period were selected and analyzed. Based on these articles, mixed foods were the most prevalent in the outbreaks (31.6%), Salmonella spp. was the pathogen most frequently reported (22.8%) and homes were also the main site of FBD occurrence (45.6%). Despite under-notification, the records of FBD outbreaks that have occurred in Brazil in the past recent years show alarming data, requiring attention from health authorities. The notification of outbreaks is essential to facilitate public health actions.
Allele-Specific Expression of CD4+ T Cells in Response to Marek’s Disease Virus Infection
Authors: Bai Hao , He Yanghua , Ding Yi , Carrillo José A. , Selvaraj Ramesh K. , Zhang Huanmin , Chen Jilan , Song Jiuzhou
Published: September 2019

Marek’s disease (MD) is a T cell lymphoma disease induced by Marek’s disease virus (MDV), a highly oncogenic α herpesvirus primarily affecting chickens. MD is a chronic infectious disease that threatens the poultry industry. However, the mechanisms of genetic resistance for MD are complex and not completely understood. In this study, to identify high-confidence candidate genes of MD genetic resistance, high throughput sequencing (RNA-seq) was used to obtain transcriptomic data of CD4+ T cells isolated from MDV-infected and non-infected groups of two reciprocal crosses of individuals mating by two highly inbred chicken lines (63 MD-resistant and 72 MD-susceptible). After RNA-seq analysis with two biological replicates in each group, we identified 61 and 123 single nucleotide polymorphisms (SNPs) (false discovery rate (FDR) < 0.05) annotated in 39 and 132 genes in intercrosses 63 × 72 and 72 × 63, respectively, which exhibited allele-specific expression (ASE) in response to MDV infection. Similarly, we identified 62 and 79 SNPs annotated in 66 and 96 genes in infected and non-infected groups, respectively. We identified 534 and 1543 differentially expressed genes (DEGs) (FDR < 0.05) related to MDV infection in intercrosses 63 × 72 and 72 × 63, respectively. We also identified 328 and 20 DEGs in infected and non-infected groups, respectively. The qRT-PCR using seven DEGs further verified our results of RNA-seq analysis. The qRT-PCR of 11 important ASE genes was performed for gene functional validation in CD4+ T cells and tumors. Combining the analyses, six genes (MCL1, SLC43A2, PDE3B, ADAM33, BLB1, and DMB2), especially MCL1, were highlighted as the candidate genes with the potential to be involved in MDV infection. Gene-set enrichment analysis revealed that many ASE genes are linked to T cell activation, T cell receptor (TCR), B cell receptor (BCR), ERK/MAPK, and PI3K/AKT-mTOR signaling pathways, which play potentially important roles in MDV infection. Our approach underlines the importance of comprehensive functional studies for gaining valuable biological insight into the genetic factors behind MD and other complex traits, and our findings provide additional insights into the mechanisms of MD and disease resistance breeding in poultry.
The Role of Molecular Testing for the Indeterminate Thyroid FNA
Authors: Rossi Esther Diana , Pantanowitz Liron , Faquin William C.
Published: September 2019

Thyroid nodules are common in the adult population where a majority are benign and only 4.0% to 6.5% are malignant. Fine needle aspiration (FNA) is a key method used in the early stages to evaluate and triage patients with thyroid nodules. While a definitive cytological diagnosis is provided in more than 70–75% of all thyroid FNA cases, the group of indeterminate lesions offers a challenge in terms of interpretation and clinical management. Molecular testing platforms have been developed, are recognized as an option by the 2015 American Thyroid Association Guidelines, and are frequently used in conjunction with FNA as an integral part of the cytologic evaluation. In this review, the utility of molecular testing options for nodules assigned to the group of indeterminate thyroid FNAs is described.
The Rhetoric of Krishna versus the Counter-Rhetoric of Vyas: The Place of Commiseration in the Mahabharat
Authors: Aryal Bhushan
Published: September 2019

In the context of the mixed perception among scholars whether the Mahabharat is a pacifist or a militant text, this paper analyzes the rhetorical project of the epic to examine its position on violence. Highlighting the existence of two main arguments in the Mahabharat, this paper argues that the author has crafted a grand rhetorical project to question the dominant war ideology of the time that Krishna presents as the divine necessity. Historically, the emergence of Krishna—one of the major characters of the epic—as an incarnation of Lord Vishnu in Hindu tradition and the extraction and elevation of the Bhagavad Gita from the epic as an independent text have undermined the complexity of Vyas’ rhetoric. This paper places Krishna’s argument within the broad rhetorical scheme of the epic and demonstrates how Vyas has represented Krishna’s rhetoric of ‘just war’ only to illustrate its pitfalls. By directing his narrative lens to the devastating consequences of the war in the later parts of the epic, Vyas problematizes Krishna’s insistence on the need to suppress human emotions to attain a higher cognitive and ontological condition. What emerges is the difference between how Vyas and Krishna view the status of feeling: the scientist Krishna thinks that human emotions and individual lives are trivial, incidental instances in the cosmic game—something not worthy of a warrior’s concern; Vyas’ rhetoric, this paper argues, restores the significance of ordinary human emotions. It is a war—not human life and feeling—that arises as a futile enterprise in Vyas’ rhetoric.
Immunotherapy for Uterine Cervical Cancer
Authors: Kagabu Masahiro , Nagasawa Takayuki , Fukagawa Daisuke , Tomabechi Hidetoshi , Sato Saiya , Shoji Tadahiro , Baba Tsukasa
Published: September 2019

Cervical cancer is a malignant neoplastic disease that is the fourth most commonly occurring cancer in women worldwide. Since the introduction of angiogenesis inhibitors, treatments for recurrent and advanced cervical cancers have improved significantly in the past five years. However, the median overall survival in advanced cervical cancer is 16.8 months, with a 5-year overall survival rate of 68% for all stages, indicating that the effects of the treatment are still unsatisfactory. The development of a new treatment method is therefore imperative. Recently, in the clinical oncology field, remarkable progress has been made in immunotherapy. Immunotherapy is already established as standard therapy in some fields and in some types of cancers, and its clinical role in all areas, including the gynecology field, will change further based on the outcomes of currently ongoing clinical trials. This manuscript summarizes the results from previous clinical trials in cervical cancer and describes the ongoing clinical trials, as well as future directions.
Evolution of Acid Mine Drainage from a Coal Waste Rock Pile Reclaimed with a Simple Soil Cover
Authors: Ramasamy Murugan , Power Christopher
Published: September 2019

Waste rock piles (WRPs) are commonly remediated with cover systems to limit water and oxygen influx and mitigate the impacts of acid mine drainage (AMD) on the environment. While numerous types of cover systems exist, simple, single-layer soil covers remain an attractive option due to their low cost and simplicity of installation. Since knowledge of their long-term performance in humid climates is limited, this study was undertaken to assess and predict a single-layer cover system at a WRP in Nova Scotia, Canada. A two-dimensional finite element model was developed to simulate variably saturated flow and solute transport at the WRP and surrounding area. Key parameters collected during five years of field monitoring, including moisture contents, groundwater levels and dissolved metal concentrations, were used to produce a well-calibrated and verified model. Early results confirm that the cover system has already decreased AMD into both groundwater (reduced water infiltration/seepage in the WRP) and surface water (eliminated contaminated surface water runoff). Long-term acidity depletion rates indicate that all sulphidic minerals within the pile will be oxidized within 34 years, but due to the slow leaching rates into water, it will take over 9000 years to deplete all acidity. Numerical simulations predict the evolution of groundwater and surface water quality over time until full acidity depletion. Current work involves kinetic tests on waste rock samples to more accurately access the annual generation and release of AMD.
Rubella Virus Infection, the Congenital Rubella Syndrome, and the Link to Autism
Authors: Mawson Anthony R. , Croft Ashley M.
Published: September 2019

Rubella is a systemic virus infection that is usually mild. It can, however, cause severe birth defects known as the congenital rubella syndrome (CRS) when infection occurs early in pregnancy. As many as 8%–13% of children with CRS developed autism during the rubella epidemic of the 1960s compared to the background rate of about 1 new case per 5000 children. Rubella infection and CRS are now rare in the U.S. and in Europe due to widespread vaccination. However, autism rates have risen dramatically in recent decades to about 3% of children today, with many cases appearing after a period of normal development (‘regressive autism’). Evidence is reviewed here suggesting that the signs and symptoms of rubella may be due to alterations in the hepatic metabolism of vitamin A (retinoids), precipitated by the acute phase of the infection. The infection causes mild liver dysfunction and the spillage of stored vitamin A compounds into the circulation, resulting in an endogenous form of hypervitaminosis A. Given that vitamin A is a known teratogen, it is suggested that rubella infection occurring in the early weeks of pregnancy causes CRS through maternal liver dysfunction and exposure of the developing fetus to excessive vitamin A. On this view, the multiple manifestations of CRS and associated autism represent endogenous forms of hypervitaminosis A. It is further proposed that regressive autism results primarily from post-natal influences of a liver-damaging nature and exposure to excess vitamin A, inducing CRS-like features as a function of vitamin A toxicity, but without the associated dysmorphogenesis. A number of environmental factors are discussed that may plausibly be candidates for this role, and suggestions are offered for testing the model. The model also suggests a number of measures that may be effective both in reducing the risk of fetal CRS in women who acquire rubella in their first trimester and in reversing or minimizing regressive autism among children in whom the diagnosis is suspected or confirmed.
Multi-Scale Remote Sensing Semantic Analysis Based on a Global Perspective
Authors: Cui Wei , Zhang Dongyou , He Xin , Yao Meng , Wang Ziwei , Hao Yuanjie , Li Jie , Wu Weijie , Cui Wenqi , Huang Jiejun
Published: September 2019

Remote sensing image captioning involves remote sensing objects and their spatial relationships. However, it is still difficult to determine the spatial extent of a remote sensing object and the size of a sample patch. If the patch size is too large, it will include too many remote sensing objects and their complex spatial relationships. This will increase the computational burden of the image captioning network and reduce its precision. If the patch size is too small, it often fails to provide enough environmental and contextual information, which makes the remote sensing object difficult to describe. To address this problem, we propose a multi-scale semantic long short-term memory network (MS-LSTM). The remote sensing images are paired into image patches with different spatial scales. First, the large-scale patches have larger sizes. We use a Visual Geometry Group (VGG) network to extract the features from the large-scale patches and input them into the improved MS-LSTM network as the semantic information, which provides a larger receptive field and more contextual semantic information for small-scale image caption so as to play the role of global perspective, thereby enabling the accurate identification of small-scale samples with the same features. Second, a small-scale patch is used to highlight remote sensing objects and simplify their spatial relations. In addition, the multi-receptive field provides perspectives from local to global. The experimental results demonstrated that compared with the original long short-term memory network (LSTM), the MS-LSTM’s Bilingual Evaluation Understudy (BLEU) has been increased by 5.6% to 0.859, thereby reflecting that the MS-LSTM has a more comprehensive receptive field, which provides more abundant semantic information and enhances the remote sensing image captions.
Smad7 Binds Differently to Individual and Tandem WW3 and WW4 Domains of WWP2 Ubiquitin Ligase Isoforms
Authors: Wahl Lloyd C. , Watt Jessica E. , Yim Hiu T. T. , De Bourcier Danielle , Tolchard James , Soond Surinder M. , Blumenschein Tharin M. A. , Chantry Andrew
Published: September 2019

WWP2 is an E3 ubiquitin ligase that differentially regulates the contextual tumour suppressor/progressor TGFβ signalling pathway by alternate isoform expression. WWP2 isoforms select signal transducer Smad2/3 or inhibitor Smad7 substrates for degradation through different compositions of protein–protein interaction WW domains. The WW4 domain-containing WWP2-C induces Smad7 turnover in vivo and positively regulates the metastatic epithelial–mesenchymal transition programme. This activity and the overexpression of these isoforms in human cancers make them candidates for therapeutic intervention. Here, we use NMR spectroscopy to solve the solution structure of the WWP2 WW4 domain and observe the binding characteristics of Smad7 substrate peptide. We also reveal that WW4 has an enhanced affinity for a Smad7 peptide phosphorylated at serine 206 adjacent to the PPxY motif. Using the same approach, we show that the WW3 domain also binds Smad7 and has significantly enhanced Smad7 binding affinity when expressed in tandem with the WW4 domain. Furthermore, and relevant to these biophysical findings, we present evidence for a novel WWP2 isoform (WWP2C-ΔHECT) comprising WW3–WW4 tandem domains and a truncated HECT domain that can inhibit TGFβ signalling pathway activity, providing a further layer of complexity and feedback to the WWP2 regulatory apparatus. Collectively, our data reveal a structural platform for Smad substrate selection by WWP2 isoform WW domains that may be significant in the context of WWP2 isoform switching linked to tumorigenesis.
Challenges in Exosome Isolation and Analysis in Health and Disease
Authors: Ludwig Nils , Whiteside Theresa L. , Reichert Torsten E.
Published: September 2019

A growing body of evidence emphasizes the important role exosomes in different physiological and pathological conditions. Exosomes, virus-size extracellular vesicles (EVs), carry a complex molecular cargo, which is actively processed in the endocytic compartment of parental cells. Exosomes carry and deliver this cargo to recipient cells, serving as an intercellular communication system. The methods for recovery of exosomes from supernatants of cell lines or body fluids are not uniformly established. Yet, studies of the quality and quantity of exosome cargos underlie the concept of “liquid biopsy.” Exosomes are emerging as a potentially useful diagnostic tool and a predictor of disease progression, response to therapy and overall survival. Although many novel approaches to exosome isolation and analysis of their cargos have been introduced, the role of exosomes as diagnostic or prognostic biomarkers of disease remains unconfirmed. This review considers existing challenges to exosome validation as disease biomarkers. Focusing on advantages and limitations of methods for exosome isolation and characterization, approaches are proposed to facilitate further progress in the development of exosomes as biomarkers in human disease.
Nickel Carcinogenesis Mechanism: DNA Damage
Authors: Guo Hongrui , Liu Huan , Wu Hongbin , Cui Hengmin , Fang Jing , Zuo Zhicai , Deng Junliang , Li Yinglun , Wang Xun , Zhao Ling
Published: September 2019

Nickel (Ni) is known to be a major carcinogenic heavy metal. Occupational and environmental exposure to Ni has been implicated in human lung and nasal cancers. Currently, the molecular mechanisms of Ni carcinogenicity remain unclear, but studies have shown that Ni-caused DNA damage is an important carcinogenic mechanism. Therefore, we conducted a literature search of DNA damage associated with Ni exposure and summarized known Ni-caused DNA damage effects. In vitro and vivo studies demonstrated that Ni can induce DNA damage through direct DNA binding and reactive oxygen species (ROS) stimulation. Ni can also repress the DNA damage repair systems, including direct reversal, nucleotide repair (NER), base excision repair (BER), mismatch repair (MMR), homologous-recombination repair (HR), and nonhomologous end-joining (NHEJ) repair pathways. The repression of DNA repair is through direct enzyme inhibition and the downregulation of DNA repair molecule expression. Up to now, the exact mechanisms of DNA damage caused by Ni and Ni compounds remain unclear. Revealing the mechanisms of DNA damage from Ni exposure may contribute to the development of preventive strategies in Ni carcinogenicity.
Silver Nanoparticles Addition in Poly(Methyl Methacrylate) Dental Matrix: Topographic and Antimycotic Studies
Authors: De Matteis Valeria , Cascione Mariafrancesca , Toma Chiara Cristina , Albanese Giovanni , De Giorgi Maria Luisa , Corsalini Massimo , Rinaldi Rosaria
Published: September 2019

The widespread use of nanoparticles (NPs) in medical devices has opened a new scenario in the treatment and prevention of many diseases and infections owing to unique physico-chemical properties of NPs. In this way, silver nanoparticles (AgNPs) are known to have a strong antimicrobial activity, even at low concentrations, due to their ability to selectively destroy cellular membranes. In particular, in the field of dental medicine, the use of AgNPs in different kinds of dental prosthesis matrixes could be a fundamental tool in immunodepressed patients that suffer of different oral infections. Candida albicans (C. albicans), an opportunistic pathogenic yeast with high colonization ability, is one of the causative agents of oral cavity infection. In our work, we added monodispersed citrate-capping AgNPs with a size of 20 nm at two concentrations (3 wt% and 3.5 wt%) in poly(methyl methacrylate) (PMMA), the common resin used to develop dental prostheses. After AgNPs characterization, we evaluated the topographical modification of PMMA and PMMA with the addition of AgNPs by means of atomic force microscopy (AFM), showing the reduction of surface roughness. The C. albicans colonization on PMMA surfaces was assessed by the Miles and Misra technique as well as by scanning electron microscopy (SEM) at 24 h and 48 h with encouraging results on the reduction of yeast viability after AgNPs exposure.
EGFR-Specific Tyrosine Kinase Inhibitor Modifies NK Cell-Mediated Antitumoral Activity against Ovarian Cancer Cells
Authors: Mallmann-Gottschalk Nina , Sax Yvonne , Kimmig Rainer , Lang Stephan , Brandau Sven
Published: September 2019

The adverse prognosis of most patients with ovarian cancer is related to recurrent disease caused by resistance to chemotherapeutic and targeted therapeutics. Besides their direct activity against tumor cells, monoclonal antibodies and tyrosine kinase inhibitors (TKIs) also influence the antitumoral activity of immune cells, which has important implications for the design of immunotherapies. In this preclinical study, we treated different ovarian cancer cell lines with anti-epidermal growth factor receptor (EGFR) TKIs and co-incubated them with natural killer (NK) cells. We studied treatment-related structural and functional changes on tumor and immune cells in the presence of the anti-EGFR antibody cetuximab and investigated NK-mediated antitumoral activity. We show that long-term exposure of ovarian cancer cells to TKIs leads to reduced responsiveness of intrinsically sensitive cancer cells over time. Inversely, neither long-term treatment with TKIs nor cetuximab could overcome the intrinsic resistance of certain ovarian cancer cells to anti-EGFR agents. Remarkably, tumor cells pretreated with anti-EGFR TKIs showed increased sensitivity towards NK cell-mediated antibody-dependent cellular cytotoxicity (ADCC). In contrast, the cytokine secretion of NK cells was reduced by TKI sensitization. Our data suggest that sensitization of tumor cells by anti-EGFR TKIs differentially modulates interactions with NK cells. These data have important implications for the design of chemo-immuno combination therapies in this tumor entity.
Development of Teleost Intermuscular Bones Undergoing Intramembranous Ossification Based on Histological-Transcriptomic-Proteomic Data
Authors: Nie Chun-Hong , Wan Shi-Ming , Liu Yu-Long , Liu Han , Wang Wei-Min , Gao Ze-Xia
Published: September 2019

Intermuscular bones (IBs) specially exist in lower teleost fish and the molecular mechanism for its development remains to be clarified. In this study, different staining methods and comparative proteomics were conducted to investigate the histological structure and proteome of IB development in Megalobrama amblycephala, including four key IB developmental stages (S1—IBs have not emerged in the tail part; S2—several small IBs started to ossify in the tail part; S3—IBs appeared rapidly; S4—all the IBs appeared with mature morphology). Alcian blue and alizarin red S stained results indicated that IBs were gradually formed from S2 to S4, undergoing intramembranous ossification without a cartilaginous phase. A total of 3368 proteins were identified by using the isobaric tags for relative and absolute quantitation (iTRAQ) approach. Functional annotation showed that proteins which were differentially expressed among stages were involved in calcium, MAPK, Wnt, TGF-β, and osteoclast pathways which played a critical role in bone formation and differentiation. Three proteins (collagen9α1, stat1, tnc) associated with chondrocytes did not exhibit significant changes through S2 to S4; however, proteins (entpd5, casq1a, pvalb, anxa2a, anxa5) which associated with osteoblasts and bone formation and differentiation showed significantly a higher expression level from S1 to S2, as well as to S3 and S4. These further demonstrated that development of IBs did not go through a cartilaginous phase. The inhibitors of TGF-β and Wnt pathways were tested on zebrafish (sp7/eGFP) and the results indicated that both inhibitors significantly delayed IB development. This study provides a comprehensive understanding of the IB ossification pattern, which will help further elucidate the molecular mechanisms for IB development in teleosts.
CRISPR/Cas9-Based Mutagenesis of Starch Biosynthetic Genes in Sweet Potato (Ipomoea Batatas) for the Improvement of Starch Quality
Authors: Wang Hongxia , Wu Yinliang , Zhang Yandi , Yang Jun , Fan Weijuan , Zhang Hui , Zhao Shanshan , Yuan Ling , Zhang Peng
Published: September 2019

CRISPR/Cas9-mediated genome editing is a powerful technology that has been used for the genetic modification of a number of crop species. In order to evaluate the efficacy of CRISPR/Cas9 technology in the root crop, sweet potato (Ipomoea batatas), two starch biosynthetic pathway genes, IbGBSSI (encoding granule-bound starch synthase I), and IbSBEII (encoding starch branching enzyme II), were targeted in the starch-type cultivar Xushu22 and carotenoid-rich cultivar Taizhong6. I. batatas was transformed using a binary vector, in which the Cas9 gene is driven by the Arabidopsis AtUBQ promoter and the guide RNA is controlled by the Arabidopsis AtU6 promoter. A total of 72 Xushu22 and 35 Taizhong6 transgenic lines were generated and analyzed for mutations. The mutation efficiency was 62–92% with multi-allelic mutations in both cultivars. Most of the mutations were nucleotide substitutions that lead to amino acid changes and, less frequently, stop codons. In addition, short nucleotide insertions or deletions were also found in both IbGBSSI and IbSBEII. Furthermore, a 2658 bp deletion was found in one IbSBEII transgenic line. The total starch contents were not significantly changed in IbGBSSI- and IbSBEII-knockout transgenic lines compared to the wild-type control. However, in the allopolyploid sweet potato, the IbGBSSI-knockout reduced, while the IbSBEII-knockout increased, the amylose percentage. Our results demonstrate that CRISPR/Cas9 technology is an effective tool for the improvement of starch qualities in sweet potato and breeding of polyploid root crops.
Microbiome Influence in the Pathogenesis of Prion and Alzheimer’s Diseases
Authors: D’Argenio Valeria , Sarnataro Daniela
Published: September 2019

Misfolded and abnormal β-sheets forms of wild-type proteins, such as cellular prion protein (PrPC) and amyloid beta (Aβ), are believed to be the vectors of neurodegenerative diseases, prion and Alzheimer’s disease (AD), respectively. Increasing evidence highlights the “prion-like” seeding of protein aggregates as a mechanism for pathological spread in AD, tauopathy, as well as in other neurodegenerative diseases, such as Parkinson’s. Mutations in both PrPC and Aβ precursor protein (APP), have been associated with the pathogenesis of these fatal disorders with clear evidence for their pathogenic significance. In addition, a critical role for the gut microbiota is emerging; indeed, as a consequence of gut–brain axis alterations, the gut microbiota has been involved in the regulation of Aβ production in AD and, through the microglial inflammation, in the amyloid fibril formation, in prion diseases. Here, we aim to review the role of microbiome (“the other human genome”) alterations in AD and prion disease pathogenesis.
Current Possibilities of Gynecologic Cancer Treatment with the Use of Immune Checkpoint Inhibitors
Authors: Grywalska Ewelina , Sobstyl Małgorzata , Putowski Lechosław , Roliński Jacek
Published: September 2019

Despite the ongoing progress in cancer research, the global cancer burden has increased to 18.1 million new cases and 9.6 million deaths in 2018. Gynecological cancers, such as ovarian, endometrial, and cervical cancers, considerably contribute to global cancer burden, leading to $5,862.6, $2,945.7, and $1,543.9 million of annual costs of cancer care, respectively. Thus, the development of effective therapies against gynecological cancers is still a largely unmet medical need. One of the novel therapeutic approaches is to induce anti-cancer immunity by the inhibition of the immune checkpoint pathways using monoclonal antibodies. The molecular targets for monoclonal antibodies are cytotoxic T lymphocyte-associated protein-4 (CTLA-4), programmed cell death protein-1 (PD-1), and programmed death-ligand 1 (PD-L1). The rationale for the use of immune checkpoint inhibitors in patients with gynecological cancers was based on the immunohistological studies showing high expression levels of PD-1 and PD-L1 in those cancers. Currently available immune checkpoint inhibitors include nivolumab, pembrolizumab, atezolizumab, avelumab, durvalumab, and ipilimumab. The efficacy and safety of these inhibitors, used as monotherapy and with combination with chemotherapy, is being currently evaluated in several clinical studies. As the results are promising, more clinical trials are being planned, which may lead to the development of efficient therapies for gynecological cancer patients.
Soy Lecithin-Derived Liposomal Delivery Systems: Surface Modification and Current Applications
Authors: Le Ngoc Thuy Trang , Cao Van Du , Nguyen Thi Nhu Quynh , Le Thi Thu Hong , Tran Thach Thao , Hoang Thi Thai Thanh
Published: September 2019

The development of natural phospholipids for nanostructured drug delivery systems has attracted much attention in the past decades. Lecithin that was derived from naturally occurring in soybeans (SL) has introduced some auspicious accomplishments to the drug carrying aspect, like effectual encapsulation, controlled release, and successful delivery of the curative factors to intracellular regions in which they procure these properties from their flexible physicochemical and biophysical properties, such as large aqueous center and biocompatible lipid, self-assembly, tunable properties, and high loading capacity. Despite the almost perfect properties as a drug carrier, liposome is known to be quite quickly eliminated from the body systems. The surface modification of liposomes has been investigated in many studies to overcome this drawback. In this review, we intensively discussed the surface-modified liposomes that enhancing the targeting, cellular uptake, and therapeutic response. Moreover, the recent applications of soy lecithin-derived liposome, focusing on cancer treatment, brain targeting, and vaccinology, are also summarized.
MicroRNAs in Cardiac Hypertrophy
Authors: Wehbe Nadine , Nasser Suzanne , Pintus Gianfranco , Badran Adnan , Eid Ali , Baydoun Elias
Published: September 2019

Like other organs, the heart undergoes normal adaptive remodeling, such as cardiac hypertrophy, with age. This remodeling, however, is intensified under stress and pathological conditions. Cardiac remodeling could be beneficial for a short period of time, to maintain a normal cardiac output in times of need; however, chronic cardiac hypertrophy may lead to heart failure and death. MicroRNAs (miRNAs) are known to have a role in the regulation of cardiac hypertrophy. This paper reviews recent advances in the field of miRNAs and cardiac hypertrophy, highlighting the latest findings for targeted genes and involved signaling pathways. By targeting pro-hypertrophic genes and signaling pathways, some of these miRNAs alleviate cardiac hypertrophy, while others enhance it. Therefore, miRNAs represent very promising potential pharmacotherapeutic targets for the management and treatment of cardiac hypertrophy.