bluuebunny/crossref_metadata_2025 huggingface dataset:
Proteogenomic Characterization of the Cement and Adhesive Gland of the Pelagic Gooseneck Barnacle Lepas anatifera
Authors: Domínguez-Pérez Dany , Almeida Daniela , Wissing Josef , Machado André M. , Jänsch Lothar , Antunes Agostinho , Castro Luís Filipe , Vasconcelos Vitor , Campos Alexandre , Cunha Isabel
Published: March 2021

We focus on the stalked goose barnacle L. anatifera adhesive system, an opportunistic less selective species for the substrate, found attached to a variety of floating objects at seas. Adhesion is an adaptative character in barnacles, ensuring adequate positioning in the habitat for feeding and reproduction. The protein composition of the cement multicomplex and adhesive gland was quantitatively studied using shotgun proteomic analysis. Overall, 11,795 peptide sequences were identified in the gland and 2206 in the cement, clustered in 1689 and 217 proteinGroups, respectively. Cement specific adhesive proteins (CPs), proteases, protease inhibitors, cuticular and structural proteins, chemical cues, and many unannotated proteins were found, among others. In the cement, CPs were the most abundant (80.5%), being the bulk proteins CP100k and -52k the most expressed of all, and CP43k-like the most expressed interfacial protein. Unannotated proteins comprised 4.7% of the cement proteome, ranking several of them among the most highly expressed. Eight of these proteins showed similar physicochemical properties and amino acid composition to known CPs and classified through Principal Components Analysis (PCA) as new CPs. The importance of PCA on the identification of unannotated non-conserved adhesive proteins, whose selective pressure is on their relative amino acid abundance, was demonstrated.
The Contemporary Approach to CALR-Positive Myeloproliferative Neoplasms
Authors: Belčič Mikič Tanja , Pajič Tadej , Zver Samo , Sever Matjaž
Published: March 2021

CALR mutations are a revolutionary discovery and represent an important hallmark of myeloproliferative neoplasms (MPN), especially essential thrombocythemia and primary myelofibrosis. To date, several CALR mutations were identified, with only frameshift mutations linked to the diseased phenotype. It is of diagnostic and prognostic importance to properly define the type of CALR mutation and subclassify it according to its structural similarities to the classical mutations, a 52-bp deletion (type 1 mutation) and a 5-bp insertion (type 2 mutation), using a statistical approximation algorithm (AGADIR). Today, the knowledge on the pathogenesis of CALR-positive MPN is expanding and several cellular mechanisms have been recognized that finally cause a clonal hematopoietic expansion. In this review, we discuss the current basis of the cellular effects of CALR mutants and the understanding of its implementation in the current diagnostic laboratorial and medical practice. Different methods of CALR detection are explained and a diagnostic algorithm is shown that aids in the approach to CALR-positive MPN. Finally, contemporary methods joining artificial intelligence in accordance with molecular-genetic biomarkers in the approach to MPN are presented.
Extracellular Vesicles and Their Role in the Spatial and Temporal Expansion of Tumor–Immune Interactions
Authors: Lipinski Simone , Tiemann Katharina
Published: March 2021

Extracellular vesicles (EVs) serve as trafficking vehicles and intercellular communication tools. Their cargo molecules directly reflect characteristics of their parental cell. This includes information on cell identity and specific cellular conditions, ranging from normal to pathological states. In cancer, the content of EVs derived from tumor cells is altered and can induce oncogenic reprogramming of target cells. As a result, tumor-derived EVs compromise antitumor immunity and promote cancer progression and spreading. However, this pro-oncogenic phenotype is constantly being challenged by EVs derived from the local tumor microenvironment and from remote sources. Here, we summarize the role of EVs in the tumor–immune cross-talk that includes, but is not limited to, immune cells in the tumor microenvironment. We discuss the potential of remotely released EVs from the microbiome and during physical activity to shape the tumor–immune cross-talk, directly or indirectly, and confer antitumor activity. We further discuss the role of proinflammatory EVs in the temporal development of the tumor–immune interactions and their potential use for cancer diagnostics.
Quantitative Proteomic Approach Reveals Altered Metabolic Pathways in Response to the Inhibition of Lysine Deacetylases in A549 Cells under Normoxia and Hypoxia
Authors: Martín-Bernabé Alfonso , Tarragó-Celada Josep , Cunin Valérie , Michelland Sylvie , Cortés Roldán , Poignant Johann , Boyault Cyril , Rachidi Walid , Bourgoin-Voillard Sandrine , Cascante Marta , Seve Michel
Published: March 2021

Growing evidence is showing that acetylation plays an essential role in cancer, but studies on the impact of KDAC inhibition (KDACi) on the metabolic profile are still in their infancy. Here, we analyzed, by using an iTRAQ-based quantitative proteomics approach, the changes in the proteome of KRAS-mutated non-small cell lung cancer (NSCLC) A549 cells in response to trichostatin-A (TSA) and nicotinamide (NAM) under normoxia and hypoxia. Part of this response was further validated by molecular and biochemical analyses and correlated with the proliferation rates, apoptotic cell death, and activation of ROS scavenging mechanisms in opposition to the ROS production. Despite the differences among the KDAC inhibitors, up-regulation of glycolysis, TCA cycle, oxidative phosphorylation and fatty acid synthesis emerged as a common metabolic response underlying KDACi. We also observed that some of the KDACi effects at metabolic levels are enhanced under hypoxia. Furthermore, we used a drug repositioning machine learning approach to list candidate metabolic therapeutic agents for KRAS mutated NSCLC. Together, these results allow us to better understand the metabolic regulations underlying KDACi in NSCLC, taking into account the microenvironment of tumors related to hypoxia, and bring new insights for the future rational design of new therapies.
Early-Life Development of the Bifidobacterial Community in the Infant Gut
Authors: Saturio Silvia , Nogacka Alicja M. , Suárez Marta , Fernández Nuria , Mantecón Laura , Mancabelli Leonardo , Milani Christian , Ventura Marco , de los Reyes-Gavilán Clara G. , Solís Gonzalo , Arboleya Silvia , Gueimonde Miguel
Published: March 2021

The establishment of the gut microbiota poses implications for short and long-term health. Bifidobacterium is an important taxon in early life, being one of the most abundant genera in the infant intestinal microbiota and carrying out key functions for maintaining host-homeostasis. Recent metagenomic studies have shown that different factors, such as gestational age, delivery mode, or feeding habits, affect the gut microbiota establishment at high phylogenetic levels. However, their impact on the specific bifidobacterial populations is not yet well understood. Here we studied the impact of these factors on the different Bifidobacterium species and subspecies at both the quantitative and qualitative levels. Fecal samples were taken from 85 neonates at 2, 10, 30, 90 days of life, and the relative proportions of the different bifidobacterial populations were assessed by 16S rRNA–23S rRNA internal transcribed spacer (ITS) region sequencing. Absolute levels of the main species were determined by q-PCR. Our results showed that the bifidobacterial population establishment is affected by gestational age, delivery mode, and infant feeding, as it is evidenced by qualitative and quantitative changes. These data underline the need for understanding the impact of perinatal factors on the gut microbiota also at low taxonomic levels, especially in the case of relevant microbial populations such as Bifidobacterium. The data obtained provide indications for the selection of the species best suited for the development of bifidobacteria-based products for different groups of neonates and will help to develop rational strategies for favoring a healthy early microbiota development when this process is challenged.
Evodiamine Inhibits Helicobacter pylori Growth and Helicobacter pylori-Induced Inflammation
Authors: Yang Ji Yeong , Kim Jong-Bae , Lee Pyeongjae , Kim Sa-Hyun
Published: March 2021

Helicobacter pylori (H. pylori) classified as a class I carcinogen by the World Health Organization (WHO) plays an important role in the progression of chronic gastritis and the development of gastric cancer. A major bioactive component of Evodia rutaecarpa, evodiamine, has been known for its anti-bacterial effect and anti-cancer effects. However, the inhibitory effect of evodiamine against H. pylori is not yet known and the inhibitory mechanisms of evodiamine against gastric cancer cells are yet to be elucidated concretely. In this study, therefore, anti-bacterial effect of evodiamine on H. pylori growth and its inhibitory mechanisms as well as anti-inflammatory effects and its mechanisms of evodiamine on H. pylori-induced inflammation were investigated in vitr. Results of this study showed the growth of the H. pylori reference strains and clinical isolates were inhibited by evodiamine. It was considered one of the inhibitory mechanisms that evodiamine downregulated both gene expressions of replication and transcription machineries of H. pylori. Treatment of evodiamine also induced downregulation of urease and diminished translocation of cytotoxin-associated antigen A (CagA) and vacuolating cytotoxin A (VacA) proteins into gastric adenocarcinoma (AGS) cells. This may be resulted from the reduction of CagA and VacA expressions as well as the type IV secretion system (T4SS) components and secretion system subunit protein A (SecA) protein which are involved in translocation of CagA and VacA into host cells, respectively. In particular, evodiamine inhibited the activation of signaling proteins such as the nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) and the mitogen-activated protein kinase (MAPK) pathway induced by H. pylori infection. It consequently might contribute to reduction of interleukin (IL)-8 production in AGS cells. Collectively, these results suggest anti-bacterial and anti-inflammatory effects of evodiamine against H. pylori.
Is Dialdehyde Chitosan a Good Substance to Modify Physicochemical Properties of Biopolymeric Materials?
Authors: Grabska-Zielińska Sylwia , Sionkowska Alina , Olewnik-Kruszkowska Ewa , Reczyńska Katarzyna , Pamuła Elżbieta
Published: March 2021

The aim of this work was to compare physicochemical properties of three dimensional scaffolds based on silk fibroin, collagen and chitosan blends, cross-linked with dialdehyde starch (DAS) and dialdehyde chitosan (DAC). DAS was commercially available, while DAC was obtained by one-step synthesis. Structure and physicochemical properties of the materials were characterized using Fourier transfer infrared spectroscopy with attenuated total reflectance device (FTIR-ATR), swelling behavior and water content measurements, porosity and density observations, scanning electron microscopy imaging (SEM), mechanical properties evaluation and thermogravimetric analysis. Metabolic activity with AlamarBlue assay and live/dead fluorescence staining were performed to evaluate the cytocompatibility of the obtained materials with MG-63 osteoblast-like cells. The results showed that the properties of the scaffolds based on silk fibroin, collagen and chitosan can be modified by chemical cross-linking with DAS and DAC. It was found that DAS and DAC have different influence on the properties of biopolymeric scaffolds. Materials cross-linked with DAS were characterized by higher swelling ability (~4000% for DAS cross-linked materials; ~2500% for DAC cross-linked materials), they had lower density (Coll/CTS/30SF scaffold cross-linked with DAS: 21.8 ± 2.4 g/cm3; cross-linked with DAC: 14.6 ± 0.7 g/cm3) and lower mechanical properties (maximum deformation for DAC cross-linked scaffolds was about 69%; for DAS cross-linked scaffolds it was in the range of 12.67 ± 1.51% and 19.83 ± 1.30%) in comparison to materials cross-linked with DAC. Additionally, scaffolds cross-linked with DAS exhibited higher biocompatibility than those cross-linked with DAC. However, the obtained results showed that both types of scaffolds can provide the support required in regenerative medicine and tissue engineering. The scaffolds presented in the present work can be potentially used in bone tissue engineering to facilitate healing of small bone defects.
Helicobacter pylori Infection Acts Synergistically with a High-Fat Diet in the Development of a Proinflammatory and Potentially Proatherogenic Endothelial Cell Environment in an Experimental Model
Authors: Krupa Agnieszka , Gonciarz Weronika , Rusek-Wala Paulina , Rechciński Tomasz , Gajewski Adrian , Samsel Zuzanna , Dziuba Anna , Śmiech Agnieszka , Chmiela Magdalena
Published: March 2021

Classic atherosclerosis risk factors do not explain all cases of chronic heart disease. There is significant evidence that gut microbiota may influence the development of atherosclerosis. The widespread prevalence of chronic Helicobacter pylori (H. pylori, HP) infections suggests that HP can be the source of components that stimulate local and systemic inflammatory responses. Elevated production of reactive oxygen species during HP infection leads to cholesterol oxidation, which drives atherogenesis. The aim of this study is to explore the link between persistent HP infection and a high-fat diet in the development of proinflammatory conditions that are potentially proatherogenic. An in vivo model of Caviae porcellus infected with HP and exposed to an experimental diet was investigated for the occurrence of a proinflammatory and proatherogenic endothelial environment. Vascular endothelial primary cells exposed to HP components were tested in vitro for oxidative stress, cell activation and apoptosis. The infiltration of inflammatory cells into the vascular endothelium of animals infected with HP and exposed to a high-fat diet was observed in conjunction with an increased level of inflammatory markers systemically. The arteries of such animals were the least elastic, suggesting the role of HP in arterial stiffness. Soluble HP components induced transformation of macrophages to foam cells in vitro and influenced the endothelial life span, which was correlated with Collagen I upregulation. These preliminary results support the hypothesis that HP antigens act synergistically with a high-fat diet in the development of proatherogenic conditions.
Exploring the Continuous Usage Intention of Online Learning Platforms from the Perspective of Social Capital
Authors: Huang Chun-Hsiung
Published: March 2021

This research explores the factors that influence students’ continuous usage intention regarding online learning platforms from the perspectives of social capital, perceived usefulness, and perceived ease of use. The questionnaire survey method was used in the research to analyze the relationship between the research variables and verify the hypothesis based on data from 248 collected valid questionnaire responses. The following results were obtained: (1) “Social interaction ties” positively affect students’ continuous usage intention. (2) “Shared language” negatively affects students’ continuous usage intention. (3) “Shared vision” positively affects students’ continuous usage intention. (4) “Perceived usefulness” positively affects students’ continuous usage intention. (5) “Perceived ease of use” positively affects students’ continuous usage intention. According to the results, students believe in useful teaching that promotes knowledge and skills. The ease of use of learning tools is key to whether they can learn successfully. Paying attention to the interaction and communication between students, so that students have a shared goal and participate in teamwork, is something that teachers must pay attention to in the course of operation. The professional vocabulary of the teaching content and the way of announcing information should avoid using difficult terminology, which is also a point to which teachers need to pay attention.
Increased Oxidative Stress in Acute Myeloid Leukemia Patients after Red Blood Cell Transfusion, but Not Platelet Transfusion, Results Mainly from the Oxidative/Nitrative Protein Damage: An Exploratory Study
Authors: Czubak-Prowizor Kamila , Trelinski Jacek , Stelmach Paulina , Stelmach Piotr , Madon Agnieszka , Zbikowska Halina Malgorzata
Published: March 2021

Chronic oxidative stress (OS) can be an important factor of acute myeloid leukemia (AML) progression; however, there are no data on the extent/consequence of OS after transfusion of packed red blood cells (pRBCs) and platelet concentrates (PCs), which are commonly used in the treatment of leukemia-associated anemia and thrombocytopenia. We aimed to investigate the effects of pRBC/PC transfusion on the OS markers, i.e., thiol and carbonyl (CO) groups, 3-nitrotyrosine (3-NT), thiobarbituric acid reactive substances (TBARS), advanced glycation end products (AGE), total antioxidant capacity (TAC), SOD, GST, and LDH, in the blood plasma of AML patients, before and 24 h post-transfusion. In this exploratory study, 52 patients were examined, of which 27 were transfused with pRBCs and 25 with PCs. Age-matched healthy subjects were also enrolled as controls. Our results showed the oxidation of thiols, increased 3-NT, AGE levels, and decreased TAC in AML groups versus controls. After pRBC transfusion, CO groups, AGE, and 3-NT significantly increased (by approximately 30, 23, and 35%; p < 0.05, p < 0.05, and p < 0.01, respectively) while thiols reduced (by 18%; p < 0.05). The PC transfusion resulted in the raise of TBARS and AGE (by 45%; p < 0.01 and 31%; p < 0.001), respectively). Other variables showed no significant post-transfusion changes. In conclusion, transfusion of both pRBCs and PCs was associated with an increased OS; however, transfusing the former may have more severe consequences, since it is associated with the irreversible oxidative/nitrative modifications of plasma proteins.
The GERtality Score: The Development of a Simple Tool to Help Predict in-Hospital Mortality in Geriatric Trauma Patients
Authors: Scherer Julian , Kalbas Yannik , Ziegenhain Franziska , Neuhaus Valentin , Lefering Rolf , Teuben Michel , Sprengel Kai , Pape Hans-Christoph , Jensen Kai Oliver
Published: March 2021

Feasible and predictive scoring systems for severely injured geriatric patients are lacking. Therefore, the aim of this study was to develop a scoring system for the prediction of in-hospital mortality in severely injured geriatric trauma patients. The TraumaRegister DGU® (TR-DGU) was utilized. European geriatric patients (≥65 years) admitted between 2008 and 2017 were included. Relevant patient variables were implemented in the GERtality score. By conducting a receiver operating characteristic (ROC) analysis, a comparison with the Geriatric Trauma Outcome Score (GTOS) and the Revised Injury Severity Classification II (RISC-II) Score was performed. A total of 58,055 geriatric trauma patients (mean age: 77 years) were included. Univariable analysis led to the following variables: age ≥ 80 years, need for packed red blood cells (PRBC) transfusion prior to intensive care unit (ICU), American Society of Anesthesiologists (ASA) score ≥ 3, Glasgow Coma Scale (GCS) ≤ 13, Abbreviated Injury Scale (AIS) in any body region ≥ 4. The maximum GERtality score was 5 points. A mortality rate of 72.4% was calculated in patients with the maximum GERtality score. Mortality rates of 65.1 and 47.5% were encountered in patients with GERtality scores of 4 and 3 points, respectively. The area under the curve (AUC) of the novel GERtality score was 0.803 (GTOS: 0.784; RISC-II: 0.879). The novel GERtality score is a simple and feasible score that enables an adequate prediction of the probability of mortality in polytraumatized geriatric patients by using only five specific parameters.
Fundamental Investigations in Tool Wear and Characteristics of Surface Microstructure for Ultrasonic Vibration Superimposed Machining of Heat-Treated X46Cr13 Steel Using Different Cutting Materials
Authors: Börner Richard , Landgraf Pierre , Kimme Simon , Titsch Christian , Lampke Thomas , Schubert Andreas
Published: March 2021

The importance of functional surfaces is continuously growing in the context of increasing demands on the sustainability of performance, resource efficiency and manufacturing costs of technical systems. For example, microstructured substrate surfaces can contribute to enhance the adhesion of layers, which in turn ensure the wear protection of a highly loaded component. Many microstructuring processes require a system change, entailing high costs. However, the ultrasonic vibration superimposed machining (UVSM) can be implemented as a finishing process. Due to its defined cutting-edge geometry and kinematics, UVSM represents a suitable method for a reliable generation of predefined surface microstructures. In order to optimize the process regarding the tool wear behavior and thus the geometrical characteristics of the surface microstructure, experimental investigations are carried out to find the most suitable combination of heat treatment condition of the martensitic stainless-steel X46Cr13 and various cutting materials. A vibration system for workpiece-side excitation is used for the experimental cutting tests. The most promising results were obtained within the combination of cemented carbide as a cutting tool and soft annealing as a heat treatment condition. They serve as a base for extensive investigations on the effects of substrate microstructuring to the adhesion of chemical vapor deposition (CVD) diamond layers to steel.
Region-Searching of Multiple Autonomous Underwater Vehicles: A Distributed Cooperative Path-Maneuvering Control Approach
Authors: Chen Tao , Qu Xingru , Zhang Zhao , Liang Xiao
Published: March 2021

In this article, a distributed cooperative path-maneuvering control approach is developed for the region-searching of multiple autonomous underwater vehicles under both dynamic uncertainties and ocean currents. Salient contributions are as follows: (1) by virtue of boustrophedon motions and trigonometric functions, the coverage path-planning design is first proposed to generate multiple parameterized paths, which can guarantee that the region-searching is successfully completed by one trial; (2) combining with sliding mode and adaptive technique, distributed maneuvering control laws for surge and yaw motions are employed to drive vehicles to track the assigned paths, thereby contributing to the cooperative maneuvering performance with high accuracy; (3) by the aid of graph theory, the distributed signal observer-based consensus protocols are developed for path parameter synchronization, and successfully apply to maintain the desired formation configuration. The globally asymptotical stability of the closed-loop signals is analyzed via the direct Lyapunov approach, and simulation studies on WL-II are conducted to illustrate the remarkable performance of the proposed path-maneuvering control approach.
Ocean Thermal Energy Conversion and Other Uses of Deep Sea Water: A Review
Authors: Herrera Jorge , Sierra Santiago , Ibeas Asier
Published: March 2021

Research into renewable energy is an active field of research, with photovoltaic and wind being the most representative technologies. A promising renewable energy source is Ocean Thermal Energy Conversion (OTEC), based on the temperature gradient of seawater. This technology has two contradictory features, as its efficiency is relatively low while, on the other hand, its energy source is almost unlimited. OTEC research has focused on optimizing energy extraction, with different techniques having been used for this purpose. This article presents a review of the advances and applications of OTEC technology around the world. Throughout the document, the different uses of deep seawater are analyzed; further, the current systems which generate energy through the marine temperature gradient are reviewed, and the main advantages and disadvantages of each method are highlighted. The technical operations, construction variations, and the projects that have been developed around the world and those which are in the planning phase are also detailed. The two main conclusions are that this technology is still under development, but it is quite promising, especially for regions with little access to drinking water. Second, given the high implementation costs and low conversion efficiency, the development of this technology must be sponsored by governments.
Skin Wound-Healing Potential of Polysaccharides from Medicinal Mushroom Auricularia auricula-judae (Bull.)
Authors: Mapoung Sariya , Umsumarng Sonthaya , Semmarath Warathit , Arjsri Punnida , Thippraphan Pilaiporn , Yodkeeree Supachai , Limtrakul (Dejkriengkraikul) Pornngarm
Published: March 2021

Auricularia auricula-judae, a nutrient-rich mushroom used in traditional medicine, is a macrofungi that exhibits various biological properties. In this study, we have reported on the mechanisms that promote the wound-healing effects of a water-soluble polysaccharide-rich extract obtained from A. auricula-judae (AAP). AAP contained high amounts of polysaccharides (349.83 ± 5.00 mg/g extract) with a molecular weight of 158 kDa. The main sugar composition of AAP includes mannose, galactose, and glucose. AAP displayed antioxidant activity in vitro and was able to abort UVB-induced intracellular ROS production in human fibroblasts in cellulo. AAP significantly promoted both fibroblast and keratinocyte proliferation, migration, and invasion, along with augmentation of the wound-healing process by increasing collagen synthesis and decreasing E-cadherin expression (All p < 0.05). Specifically, the AAP significantly accelerated the wound closure in a mice skin wound-healing model on day 9 (2.5%AAP, p = 0.031 vs. control) and day 12 (1% and 2.5%AAP with p = 0.009 and p < 0.001 vs. control, respectively). Overall, our results indicate that the wound-healing activities of AAP can be applied in an AAP-based product for wound management.
Volatile Organic Compound Chamber: A Novel Technology for Microbiological Volatile Interaction Assays
Authors: Álvarez-García Samuel , Mayo-Prieto Sara , Carro-Huerga Guzmán , Rodríguez-González Álvaro , González-López Óscar , Gutiérrez Santiago , Casquero Pedro A.
Published: March 2021

The interest in the study of microbiological interactions mediated by volatile organic compounds (VOCs) has steadily increased in the last few years. Nevertheless, most assays still rely on the use of non-specific materials. We present a new tool, the volatile organic compound chamber (VOC chamber), specifically designed to perform these experiments. The novel devices were tested using four Trichoderma strains against Fusarium oxysporum and Rhizoctonia solani. We demonstrate that VOC chambers provide higher sensitivity and selectivity between treatments and higher homogeneity of results than the traditional method. VOC chambers are also able to test both vented and non-vented conditions. We prove that ventilation plays a very important role regarding volatile interactions, up to the point that some growth-inhibitory effects observed in closed environments switch to promoting ones when tested in vented conditions. This promoting activity seems to be related to the accumulation of squalene by T. harzianum. The VOC chambers proved to be an easy, homogeneous, flexible, and repeatable method, able to better select microorganisms with high biocontrol activity and to guide the future identification of new bioactive VOCs and their role in microbial interactions.
Systems Approaches to Treatment Response to Imatinib in Severe Asthma: A Pilot Study
Authors: Baek Seung Han , Foer Dinah , Cahill Katherine N. , Israel Elliot , Maiorino Enrico , Röhl Annika , Boyce Joshua A. , Weiss Scott T.
Published: March 2021

There is an acute need for advances in pharmacologic therapies and a better understanding of novel drug targets for severe asthma. Imatinib, a tyrosine kinase inhibitor, has been shown to improve forced expiratory volume in 1 s (FEV1) in a clinical trial of patients with severe asthma. In a pilot study, we applied systems biology approaches to epithelium gene expression from these clinical trial patients treated with imatinib to better understand lung function response with imatinib treatment. Bronchial brushings from ten imatinib-treated patient samples and 14 placebo-treated patient samples were analyzed. We used personalized perturbation profiles (PEEPs) to characterize gene expression patterns at the individual patient level. We found that strong responders—patients with greater than 20% increase in FEV1—uniquely shared multiple downregulated mitochondrial-related pathways. In comparison, weak responders (5–10% FEV1 increase), and non-responders to imatinib shared none of these pathways. The use of PEEP highlights its potential for application as a systems biology tool to develop individual-level approaches to predicting disease phenotypes and response to treatment in populations needing innovative therapies. These results support a role for mitochondrial pathways in airflow limitation in severe asthma and as potential therapeutic targets in larger clinical trials.
Ecosystem Services Provisioning, Urban Growth and the Rural–Urban Interface: A Case Study from China
Authors: Feng Haiying , Squires Victor R. , Wu Jingji
Published: March 2021

The rural-urban (peri-urban) interface zones are important places that generate demands for ecosystem goods and services (EG & S). Urban regions face transitions in land use that affect ecosystem services (EG & S) and thus human wellbeing. Especially in urban areas with high population densities (as in most of China) and high demand for EG & S, the future availability of such services must be considered in order to promote effective and sustainable decision making and prevent further ecosystem degradation. The challenge for local government planners and land managers is to find tools that allow relevant data to be collected and analyzed. Ideally, such tools should be able to give a rapid assessment, and not involve large teams of highly trained personnel or incur high costs. The paper reports on the development and trial of such a tool. The paper has three main parts. First, we present a brief overview of the current and developing situation in China, in relation to urbanization, population shifts and the creation of peri-urban areas (PUAs). Next, we build on insights from the literature and from discussions with village heads and county- and prefecture-level officials to develop an understanding of their needs for tools to help planning and land management within the constraints of the national policy. Lastly, a “template” was derived from our multi-method approach that provided a new technical tool for the rapid assessment of the value of EG & S in each of five land use categories. The tool embodies a way to address trade-offs between environmental, social and economic values in the transition zone between rural and urban areas. The tool was trialed in QinBei District in Guangxi Autonomous Region in south China and judged to be useful and adaptable to other rural–urban regions.
Impact of Road Fencing on Ungulate–Vehicle Collisions and Hotspot Patterns
Authors: Kučas Andrius , Balčiauskas Linas
Published: March 2021

The number of road traffic accidents decreased in Lithuania from 2002 to 2017, while the ungulate–vehicle collision (UVC) number increased and accounted for approximately 69% of all wildlife–vehicle collisions (WVC) in the country. Understanding the relationship between UVCs, traffic intensity, and implemented mitigation measures is important for the assessment of UVC mitigation measure efficiency. We assessed the effect of annual average daily traffic (AADT) and wildlife fencing on UVCs using regression analysis of changes in annual UVCs and UVC hotspots on different categories of roads. At the highest rates, annual UVC numbers and UVC hotspots increased on lower category (national and regional) roads, forming a denser network. Lower rates of UVC increase occurred on higher category (main) roads, forming sparser road networks and characterized by the highest AADT. Before 2011, both UVC occurrence and fenced road sections were most common on higher-category roads. However, as of 2011, the majority of UVCs occurred on lower-category roads where AADT and fencing had no impact on UVCs. We conclude that wildlife fencing on roads characterized by higher speed and traffic intensity may decrease UVC numbers and at the same time shifting UVC occurrence towards roads characterized by lower speed and traffic intensity. Wildlife fencing re-allocates wildlife movement pathways toward roads with insufficient or no mitigation measures.
Hidden Blemish in European Law: Judgements on Unconventional Monetary Programmes
Authors: Herzog Bodo
Published: March 2021

This article studies the hidden blemishes of two benchmark rulings of the European Court of Justice (ECJ). In 2015 and 2018, the ECJ approved two unconventional monetary instruments, among others ‘Outright Monetary Transactions’ and the ‘Public Sector Purchase Program’. Yet, there is a vigorous debate about both monetary operations in law and economics. In this interdisciplinary article, we address law and economic arguments in order to elucidate insights to the legal community. In particular, we elaborate on the legal implications of a variety of concerning issues such as public policy interference, effect on wealth redistribution, erosion of democratic legitimacy and lack of effectiveness of monetary policy. These topics remain disregarded in the ECJ rulings. Consequently, the verdicts do not identify the economic boundaries of the European Central Bank’s mandate appropriately.
Machine-Learning-Based Atomistic Model Analysis on High-Temperature Compressive Creep Properties of Amorphous Silicon Carbide
Authors: Kubo Atsushi , Umeno Yoshitaka
Published: March 2021

Ceramic matrix composites (CMCs) based on silicon carbide (SiC) are used for high-temperature applications such as the hot section in turbines. For such applications, the mechanical properties at a high temperature are essential for lifetime prediction and reliability design of SiC-based CMC components. We developed an interatomic potential function based on the artificial neural network (ANN) model for silicon-carbon systems aiming at investigation of high-temperature mechanical properties of SiC materials. We confirmed that the developed ANN potential function reproduces typical material properties of the single crystals of SiC, Si, and C consistent with first-principles calculations. We also validated applicability of the developed ANN potential to a simulation of an amorphous SiC through the analysis of the radial distribution function. The developed ANN potential was applied to a series of creep test for an amorphous SiC model, focusing on the amorphous phase, which is expected to be formed in the SiC-based composites. As a result, we observed two types of creep behavior due to different atomistic mechanisms depending on the strain rate. The evaluated activation energies are lower than the experimental values in literature. This result indicates that an amorphous region can play an important role in the creep process in SiC composites.
Construction of TiO2-Eggshell for Efficient Degradation of Tetracycline Hydrochloride: Sunlight Induced In-Situ Formation of Carbonate Radical
Authors: Huang Zhuquan , Wang Jiaqi , Yang Min-Quan , Qian Qingrong , Liu Xin-Ping , Xiao Liren , Xue Hun
Published: March 2021

Photocatalytic degradation of an antibiotic by utilizing inexhaustible solar energy represents an ideal solution for tackling global environment issues. The target generation of active oxidative species is highly desirable for the photocatalytic pollutants degradation. Herein, aiming at the molecular structure of tetracycline hydrochloride (TC), we construct sunlight-activated high-efficient catalysts of TiO2-eggshell (TE). The composite ingeniously utilizes the photoactive function of TiO2 and the composition of eggshell, which can produce oxidative ·CO3− species that are especially active for the degradation of aromatic compounds containing phenol or aniline structures. Through the synergistic oxidation of the··CO3− with the traditional holes (h+), superoxide radicals (·O2−) and hydroxyl radicals (·OH) involved in the photocatalytic process, the optimal TE photocatalyst degrades 92.0% TC in 30 min under solar light, which is higher than TiO2 and eggshell. The photocatalytic degradation pathway of TC over TE has been proposed. The response surface methodology is processed by varying four independent parameters (TC concentration, pH, catalyst dosage and reaction time) on a Box–Behnken design (BBD) to optimize the experimental conditions. It is anticipated that the present work can facilitate the development of novel photocatalysts for selective oxidation based on ·CO3−.
MAPLE Coatings Embedded with Essential Oil-Conjugated Magnetite for Anti-Biofilm Applications
Authors: Gherasim Oana , Popescu Roxana Cristina , Grumezescu Valentina , Mogoșanu George Dan , Mogoantă Laurențiu , Iordache Florin , Holban Alina Maria , Vasile Bogdan Ștefan , Bîrcă Alexandra Cătălina , Oprea Ovidiu-Cristian , Grumezescu Alexandru Mihai , Andronescu Ecaterina
Published: March 2021

The present study reports on the development and evaluation of nanostructured composite coatings of polylactic acid (PLA) embedded with iron oxide nanoparticles (Fe3O4) modified with Eucalyptus (Eucalyptus globulus) essential oil. The co-precipitation method was employed to synthesize the magnetite particles conjugated with Eucalyptus natural antibiotic (Fe3O4@EG), while their composition and microstructure were investigated using grazing incidence X-ray diffraction (GIXRD), Fourier transform infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA), transmission electron microscopy (TEM) and dynamic light scattering (DLS). The matrix-assisted pulsed laser evaporation (MAPLE) technique was further employed to obtain PLA/Fe3O4@EG thin films. Optimal experimental conditions for laser processing were established by complementary infrared microscopy (IRM) and scanning electron microscopy (SEM) investigations. The in vitro biocompatibility with eukaryote cells was proven using mesenchymal stem cells, while the anti-biofilm efficiency of composite PLA/Fe3O4@EG coatings was assessed against Gram-negative and Gram-positive pathogens.
Modelling of Fuel- and Energy-Switching Prices by Mean-Reverting Processes and Their Applications to Alberta Energy Markets
Authors: Lu Weiliang , Arrigoni Alexis , Swishchuk Anatoliy , Goutte Stéphane
Published: March 2021

This paper introduces a fuel-switching price to the Alberta market, which is designed for encouraging power plant companies to switch from coal to natural gas when they produce electricity; this has been successfully applied to the European market. Moreover, we consider an energy-switching price which considers power switch from natural gas to wind. We modeled these two prices using five mean reverting processes including a Regime-switching processes, Lévy-driven Ornstein–Uhlenbeck process and Inhomogeneous Geometric Brownian Motion, and estimate them based on multiple procedures such as Maximum likelihood estimation and Expectation-Maximization algorithm. Finally, this paper proves previous results applied to the Albertan Market where the jump modeling technique is needed when modeling fuel-switching data. In addition, it not only gives promising conclusions on the necessity of introducing Regime-switching models to the fuel-switching data, but also shows that the Regime-switching model is better fitted to the data.
Multivariate Multifractal Detrending Moving Average Analysis of Air Pollutants
Authors: Kojić Milena , Mitić Petar , Dimovski Marko , Minović Jelena
Published: March 2021

One of the most challenging endeavors of contemporary research is to describe and analyze the dynamic behavior of time series arising from real-world systems. To address the need for analyzing long-range correlations and multifractal properties of multivariate time series, we generalize the multifractal detrended moving average algorithm (MFDMA) to the multivariate case and propose a multivariate MFDMA algorithm (MV-MFDMA). The validity and performance of the proposed algorithm are tested by conducting numerical simulations on synthetic multivariate monofractal and multifractal time series. The MV-MFDMA algorithm is then utilized to analyze raw, seasonally adjusted, and remainder components of five air pollutant time series. Results from all three cases reveal multifractal properties with persistent long-range correlations.
Hybrid Gravitational–Firefly Algorithm-Based Load Frequency Control for Hydrothermal Two-Area System
Authors: Gupta Deepak Kumar , Soni Ankit Kumar , Jha Amitkumar V. , Mishra Sunil Kumar , Appasani Bhargav , Srinivasulu Avireni , Bizon Nicu , Thounthong Phatiphat
Published: March 2021

The load frequency control (LFC) and tie-line power are the key deciding factors to evaluate the performance of a multiarea power system. In this paper, the performance analysis of a two-area power system is presented. This analysis is based on two performance metrics: LFC and tie-line power. The power system consists of a thermal plant generation system and a hydro plant generation system. The performance is evaluated by designing a proportional plus integral (PI) controller. The hybrid gravitational search with firefly algorithm (hGFA) has been devised to achieve proper tuning of the controller parameter. The designed algorithm involves integral time absolute error (ITAE) as an objective function. For two-area hydrothermal power systems, the load frequency and tie-line power are correlated with the system generation capacity and the load. Any deviation in the generation and in the load capacity causes variations in the load frequencies, as well as in the tie-line power. Variations from the nominal value may hamper the operation of the power system with adverse consequences. Hence, performance of the hydrothermal power system is analyzed using the simulations based on the step load change. To elucidate the efficacy of the hGFA, the performance is compared with some of the well-known optimization techniques, namely, particle swarm optimization (PSO), genetic algorithm (GA), gravitational search algorithm (GSA) and the firefly algorithm (FA).
Oscillatory Solutions to Neutral Delay Differential Equations
Authors: Alsharari Fahad , Bazighifan Omar , Nofal Taher A. , Khedher Khaled Mohamed , Raffoul Youssef N.
Published: March 2021

This article aims to mark out new conditions for oscillation of the even-order Emden–Fowler neutral delay differential equations with neutral term β1ıΦα[ζr−1ı]′+β3ıΦα[ςξı]=0. The obtained results extend, and simplify known conditions in the literature. The results are illustrated with examples.
Antiplasmodial Compounds from Deep-Water Marine Invertebrates
Authors: Wright Amy E. , Collins Jennifer E. , Roberts Bracken , Roberts Jill C. , Winder Priscilla L. , Reed John K. , Diaz Maria Cristina , Pomponi Shirley A. , Chakrabarti Debopam
Published: March 2021

Novel drug leads for malaria therapy are urgently needed because of the widespread emergence of resistance to all available drugs. Screening of the Harbor Branch enriched fraction library against the Plasmodium falciparum chloroquine-resistant strain (Dd2) followed by bioassay-guided fractionation led to the identification of two potent antiplasmodials; a novel diterpene designated as bebrycin A (1) and the known C21 degraded terpene nitenin (2). A SYBR Green I assay was used to establish a Dd2 EC50 of 1.08 ± 0.21 and 0.29 ± 0.02 µM for bebrycin A and nitenin, respectively. Further analysis was then performed to assess the stage specificity of the inhibitors antiplasmodial effects on the Dd2 intraerythrocytic life cycle. Exposure to bebrycin A was found to block parasite maturation at the schizont stage if added any time prior to late schizogony at 42 hours post invasion, (HPI). In contrast, early life cycle exposure to nitenin (prior to 18 HPI) was identified as crucial to parasite inhibition, suggesting nitenin may target the maturation of the parasite during the transition from ring to early trophozoite (6–18 HPI), a novel property among known antimalarials.
Actuating a Magnetic Shape Memory Element Locally with a Set of Coils
Authors: Armstrong Andrew , Müllner Peter
Published: March 2021

The local actuation of a magnetic shape memory (MSM) element as used in an MSM micropump is considered. This paper presents the difference between an electromagnetic driver and a driver that uses a rotating permanent magnet. For the magnetic field energy of the permanent magnetic drive, the element takes in a significant stray field. In a particular case, energy reduction was 12.7 mJ. For an electromagnetic drive with an identical size of the MSM element, the total magnetic field energy created by the system was 2.28 mJ. Attempts to experimentally nucleate twins in an MSM element by energizing an electromagnetic drive failed even though the local magnetic field exceeded the magnetic switching field. The energy variation is an order of magnitude smaller for the electromagnetic drive, and it does not generate the necessary driving force. It was assumed in previous work that the so-called magnetic switching field presents a sufficient requirement to nucleate a twin and, thus, to locally actuate an MSM element. Here, we show that the total magnetic field energy available to the MSM element presents another requirement.
Oversizing Thread Diagnosis in Tapping Operation
Authors: Gil Del Val Alain , Veiga Fernando , Penalva Mariluz , Arizmendi Miguel
Published: March 2021

Automotive, railway and aerospace sectors require a high level of quality on the thread profiles in their manufacturing systems knowing that the tapping process is a complex manufacturing process and the last operation in a manufacturing cell. Therefore, a multivariate statistical process control chart, for each tap, is presented based on the principal components of the torque signal directly measured from spindle motor drive to diagnosis the thread profile quality. This on-line multivariate control chart has implemented an alarm to avoid defected screw threads (oversized). Therefore, it could work automatically without any operator intervention assessing the thread quality and the safety is guaranteed during the tapping process.
Metabolic Signature of Arrhythmogenic Cardiomyopathy
Authors: Volani Chiara , Rainer Johannes , Hernandes Vinicius Veri , Meraviglia Viviana , Pramstaller Peter Paul , Smárason Sigurður Vidir , Pompilio Giulio , Casella Michela , Sommariva Elena , Paglia Giuseppe , Rossini Alessandra
Published: March 2021

Arrhythmogenic cardiomyopathy (ACM) is a genetic-based cardiac disease accompanied by severe ventricular arrhythmias and a progressive substitution of the myocardium with fibro-fatty tissue. ACM is often associated with sudden cardiac death. Due to the reduced penetrance and variable expressivity, the presence of a genetic defect is not conclusive, thus complicating the diagnosis of ACM. Recent studies on human induced pluripotent stem cells-derived cardiomyocytes (hiPSC-CMs) obtained from ACM individuals showed a dysregulated metabolic status, leading to the hypothesis that ACM pathology is characterized by an impairment in the energy metabolism. However, despite efforts having been made for the identification of ACM specific biomarkers, there is still a substantial lack of information regarding the whole metabolomic profile of ACM patients. The aim of the present study was to investigate the metabolic profiles of ACM patients compared to healthy controls (CTRLs). The targeted Biocrates AbsoluteIDQ® p180 assay was used on plasma samples. Our analysis showed that ACM patients have a different metabolome compared to CTRLs, and that the pathways mainly affected include tryptophan metabolism, arginine and proline metabolism and beta oxidation of fatty acids. Altogether, our data indicated that the plasma metabolomes of arrhythmogenic cardiomyopathy patients show signs of endothelium damage and impaired nitric oxide (NO), fat, and energy metabolism.