bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of MTH1-Binding Nucleotide Analogs Based on 7,8-Dihalogenated 7-Deaza-dG Derivatives
Authors: Shi Hui , Ishikawa Ren , Heh Choon Han , Sasaki Shigeki , Taniguchi Yosuke
Published: January 2021

MTH1 is an enzyme that hydrolyzes 8-oxo-dGTP, which is an oxidatively damaged nucleobase, into 8-oxo-dGMP in nucleotide pools to prevent its mis-incorporation into genomic DNA. Selective and potent MTH1-binding molecules have potential as biological tools and drug candidates. We recently developed 8-halogenated 7-deaza-dGTP as an 8-oxo-dGTP mimic and found that it was not hydrolyzed, but inhibited enzyme activity. To further increase MTH1 binding, we herein designed and synthesized 7,8-dihalogenated 7-deaza-dG derivatives. We successfully synthesized multiple derivatives, including substituted nucleosides and nucleotides, using 7-deaza-dG as a starting material. Evaluations of the inhibition of MTH1 activity revealed the strong inhibitory effects on enzyme activity of the 7,8-dihalogenated 7-deaza-dG derivatives, particularly 7,8-dibromo 7-daza-dGTP. Based on the results obtained on kinetic parameters and from computational docking simulating studies, these nucleotide analogs interacted with the active site of MTH1 and competitively inhibited the substrate 8-oxodGTP. Therefore, novel properties of repair enzymes in cells may be elucidated using new compounds.
Anti-Inflammatory Effects of Ellagic Acid on Keratinocytes via MAPK and STAT Pathways
Authors: Gil Tae-Young , Hong Chul-Hee , An Hyo-Jin
Published: January 2021

Atopic dermatitis (AD) is a chronic inflammatory skin disease that is characterized by an impaired skin barrier and intense itchiness, which decreases the individual’s quality of life. No fully effective therapeutic agents have prevailed for AD due to an insufficient grasp of the complex etiology. Ellagic acid (EA), a natural compound, has anti-inflammatory properties in chronic diseases. The effects of EA on AD have not yet been explored. The present study investigated the effects of EA on TNF-α/IFN-γ-stimulated HaCaT keratinocytes and house dust mite-induced AD-like skin lesions in NC/Nga mice. Treatment with EA suppressed inflammatory responses in keratinocytes by regulating critical inflammatory signaling pathways, such as mitogen-activated protein kinases and signal transducers and activators of transcription. In vivo studies using a DfE-induced AD mouse model showed the effects of EA administration through ameliorated skin lesions via decremented histological inflammatory reactions. These results suggest that EA could be a potential therapeutic alternative for the treatment of AD by inhibiting inflammatory signaling pathways.
Role of Sphingosine 1-Phosphate Signalling Axis in Muscle Atrophy Induced by TNFα in C2C12 Myotubes
Authors: Bernacchioni Caterina , Ghini Veronica , Squecco Roberta , Idrizaj Eglantina , Garella Rachele , Puliti Elisa , Cencetti Francesca , Bruni Paola , Donati Chiara
Published: January 2021

Skeletal muscle atrophy is characterized by a decrease in muscle mass causing reduced agility, increased fatigability and higher risk of bone fractures. Inflammatory cytokines, such as tumor necrosis factor-alpha (TNFα), are strong inducers of skeletal muscle atrophy. The bioactive sphingolipid sphingosine 1-phoshate (S1P) plays an important role in skeletal muscle biology. S1P, generated by the phosphorylation of sphingosine catalyzed by sphingosine kinase (SK1/2), exerts most of its actions through its specific receptors, S1P1–5. Here, we provide experimental evidence that TNFα induces atrophy and autophagy in skeletal muscle C2C12 myotubes, modulating the expression of specific markers and both active and passive membrane electrophysiological properties. NMR-metabolomics provided a clear picture of the deep remodelling of skeletal muscle fibre metabolism induced by TNFα challenge. The cytokine is responsible for the modulation of S1P signalling axis, upregulating mRNA levels of S1P2 and S1P3 and downregulating those of SK2. TNFα increases the phosphorylated form of SK1, readout of its activation. Interestingly, pharmacological inhibition of SK1 and specific antagonism of S1P3 prevented the increase in autophagy markers and the changes in the electrophysiological properties of C2C12 myotubes without affecting metabolic remodelling induced by the cytokine, highlighting the involvement of S1P signalling axis on TNFα-induced atrophy in skeletal muscle.
The Pharmacology of Xenobiotics after Intracerebro Spinal Fluid Administration: Implications for the Treatment of Brain Tumors
Authors: Paris Justine , Angeli Eurydice , Bousquet Guilhem
Published: January 2021

The incidence of brain metastasis has been increasing for 10 years, with poor prognosis, unlike the improvement in survival for extracranial tumor localizations. Since recent advances in molecular biology and the development of specific molecular targets, knowledge of the brain distribution of drugs has become a pharmaceutical challenge. Most anticancer drugs fail to cross the blood–brain barrier. In order to get around this problem and penetrate the brain parenchyma, the use of intrathecal administration has been developed, but the mechanisms governing drug distribution from the cerebrospinal fluid to the brain parenchyma are poorly understood. Thus, in this review we discuss the pharmacokinetics of drugs after intrathecal administration, their penetration of the brain parenchyma and the different systems causing their efflux from the brain to the blood.
The Central Role of Fibrinolytic Response in COVID-19—A Hematologist’s Perspective
Authors: Kwaan Hau C. , Lindholm Paul F.
Published: January 2021

The novel coronavirus disease (COVID-19) has many characteristics common to those in two other coronavirus acute respiratory diseases, severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). They are all highly contagious and have severe pulmonary complications. Clinically, patients with COVID-19 run a rapidly progressive course of an acute respiratory tract infection with fever, sore throat, cough, headache and fatigue, complicated by severe pneumonia often leading to acute respiratory distress syndrome (ARDS). The infection also involves other organs throughout the body. In all three viral illnesses, the fibrinolytic system plays an active role in each phase of the pathogenesis. During transmission, the renin-aldosterone-angiotensin-system (RAAS) is involved with the spike protein of SARS-CoV-2, attaching to its natural receptor angiotensin-converting enzyme 2 (ACE 2) in host cells. Both tissue plasminogen activator (tPA) and plasminogen activator inhibitor 1 (PAI-1) are closely linked to the RAAS. In lesions in the lung, kidney and other organs, the two plasminogen activators urokinase-type plasminogen activator (uPA) and tissue plasminogen activator (tPA), along with their inhibitor, plasminogen activator 1 (PAI-1), are involved. The altered fibrinolytic balance enables the development of a hypercoagulable state. In this article, evidence for the central role of fibrinolysis is reviewed, and the possible drug targets at multiple sites in the fibrinolytic pathways are discussed.
Angiogenin (ANG)—Ribonuclease Inhibitor (RNH1) System in Protein Synthesis and Disease
Authors: Sarangdhar Mayuresh Anant , Allam Ramanjaneyulu
Published: January 2021

Protein synthesis is a highly complex process executed by well-organized translation machinery. Ribosomes, tRNAs and mRNAs are the principal components of this machinery whereas RNA binding proteins and ribosome interacting partners act as accessory factors. Angiogenin (ANG)—Ribonuclease inhibitor (RNH1) system is one such accessory part of the translation machinery that came into focus afresh due to its unconventional role in the translation. ANG is conventionally known for its ability to induce blood vessel formation and RNH1 as a “sentry” to protect RNAs from extracellular RNases. However, recent studies suggest them to be important in translation regulation. During cell homeostasis, ANG in the nucleus promotes rRNA transcription. While under stress, ANG translocates to the cytosol and cleaves tRNA into fragments which inhibit ribosome biogenesis and protein synthesis. RNH1, which intimately interacts with ANG to inhibit its ribonucleolytic activity, can also bind to the 40S ribosomes and control translation by yet to be known mechanisms. Here, we review recent advancement in the knowledge of translation regulation by the ANG-RNH1 system. We also gather information about this system in cell homeostasis as well as in pathological conditions such as cancer and ribosomopathies. Additionally, we discuss the future research directions and therapeutic potential of this system.
Overexpression of PtoCYCD3;3 Promotes Growth and Causes Leaf Wrinkle and Branch Appearance in Populus
Authors: Guan Chaonan , Xue Yuan , Jiang Pengfei , He Chengcheng , Zhuge Xianglin , Lan Ting , Yang Hailing
Published: January 2021

D-type cyclin (cyclin D, CYCD), combined with cyclin-dependent kinases (CDKs), participates in the regulation of cell cycle G1/S transition and plays an important role in cell division and proliferation. CYCD could affect the growth and development of herbaceous plants, such as Arabidopsis thaliana, by regulating the cell cycle process. However, its research in wood plants (e.g., poplar) is poor. Phylogenetic analysis showed that in Populus trichocarpa, CYCD3 genes expanded to six members, namely PtCYCD3;1–6. P. tomentosa CYCD3 genes were amplified based on the CDS region of P. trichocarpa CYCD3 genes. PtoCYCD3;3 showed the highest expression in the shoot tip, and the higher expression in young leaves among all members. Therefore, this gene was selected for further study. The overexpression of PtoCYCD3;3 in plants demonstrated obvious morphological changes during the observation period. The leaves became enlarged and wrinkled, the stems thickened and elongated, and multiple branches were formed by the plants. Anatomical study showed that in addition to promoting the differentiation of cambium tissues and the expansion of stem vessel cells, PtoCYCD3;3 facilitated the division of leaf adaxial epidermal cells and palisade tissue cells. Yeast two-hybrid experiment exhibited that 12 PtoCDK proteins could interact with PtoCYCD3;3, of which the strongest interaction strength was PtoCDKE;2, whereas the weakest was PtoCDKG;3. Molecular docking experiments further verified the force strength of PtoCDKE;2 and PtoCDKG;3 with PtoCYCD3;3. In summary, these results indicated that the overexpression of PtoCYCD3;3 significantly promoted the vegetative growth of Populus, and PtoCYCD3;3 may interact with different types of CDK proteins to regulate cell cycle processes.
Metabolic Transition of Milk Triacylglycerol Synthesis in Response to Varying Levels of Three 18-Carbon Fatty Acids in Porcine Mammary Epithelial Cells
Authors: Lv Yantao , Chen Fang , Zhang Shihai , Chen Jun , Zhang Yinzhi , Tian Min , Guan Wutai
Published: January 2021

This study aimed to examine the effects of increasing levels of three 18-carbon fatty acids (stearate, oleate and linoleate) on mammary lipogenesis, and to evaluate their effects on the milk lipogenic pathway in porcine mammary epithelial cells (pMECs). We found that increasing the three of 18-carbon fatty acids enhanced the cellular lipid synthesis in a dose-dependent manner, as reflected by the increased (triacylglycerol) TAG content and cytosolic lipid droplets in pMECs. The increased lipid synthesis by the three 18-carbon fatty acids was probably caused by the up-regulated expression of major genes associated with milk fat biosynthesis, including CD36 (long chain fatty acid uptake); GPAM, AGPAT6, DGAT1 (TAG synthesis); PLIN2 (lipid droplet formation); and PPARγ (regulation of transcription). Western blot analysis of CD36, DGAT1 and PPARγ proteins confirmed this increase with the increasing incubation of 18-carbon fatty acids. Interestingly, the mRNA expressions of ACSL3 and FABP3 (fatty acids intracellular activation and transport) were differentially affected by the three 18-carbon fatty acids. The cellular mRNA expressions of ACSL3 and FABP3 were increased by stearate, but were decreased by oleate or linoleate. However, the genes involved in fatty acid de novo synthesis (ACACA and FASN) and the regulation of transcription (SREBP1) were decreased by incubation with increasing concentrations of 18-carbon fatty acids. In conclusion, our findings provided evidence that 18-carbon fatty acids (stearate, oleate and linoleate) significantly increased cytosolic TAG accumulation in a dose-dependent manner, probably by promoting lipogenic genes and proteins that regulate the channeling of fatty acids towards milk TAG synthesis in pMECs.
New Highlights of Resveratrol: A Review of Properties against Ocular Diseases
Authors: Delmas Dominique , Cornebise Clarisse , Courtaut Flavie , Xiao Jianbo , Aires Virginie
Published: January 2021

Eye diseases are currently a major public health concern due to the growing number of cases resulting from both an aging of populations and exogenous factors linked to our lifestyles. Thus, many treatments including surgical pharmacological approaches have emerged, and special attention has been paid to prevention, where diet plays a preponderant role. Recently, potential antioxidants such as resveratrol have received much attention as potential tools against various ocular diseases. In this review, we focus on the mechanisms of resveratrol against ocular diseases, in particular age-related macular degeneration, glaucoma, cataract, diabetic retinopathy, and vitreoretinopathy. We analyze, in relation to the different steps of each disease, the resveratrol properties at multiple levels, such as cellular and molecular signaling as well as physiological effects. We show and discuss the relationship to reactive oxygen species, the regulation of inflammatory process, and how resveratrol can prevent ocular diseases through a potential epigenetic action by the activation of sirtuin-1. Lastly, various new forms of resveratrol delivery are emerging at the same time as some clinical trials are raising more questions about the future of resveratrol as a potential tool for prevention or in therapeutic strategies against ocular diseases. More preclinical studies are required to provide further insights into RSV’s potential adjuvant activity.
Role of NLRs in the Regulation of Type I Interferon Signaling, Host Defense and Tolerance to Inflammation
Authors: Kienes Ioannis , Weidl Tanja , Mirza Nora , Chamaillard Mathias , Kufer Thomas A.
Published: January 2021

Type I interferon signaling contributes to the development of innate and adaptive immune responses to either viruses, fungi, or bacteria. However, amplitude and timing of the interferon response is of utmost importance for preventing an underwhelming outcome, or tissue damage. While several pathogens evolved strategies for disturbing the quality of interferon signaling, there is growing evidence that this pathway can be regulated by several members of the Nod-like receptor (NLR) family, although the precise mechanism for most of these remains elusive. NLRs consist of a family of about 20 proteins in mammals, which are capable of sensing microbial products as well as endogenous signals related to tissue injury. Here we provide an overview of our current understanding of the function of those NLRs in type I interferon responses with a focus on viral infections. We discuss how NLR-mediated type I interferon regulation can influence the development of auto-immunity and the immune response to infection.
The rDNA Loci—Intersections of Replication, Transcription, and Repair Pathways
Authors: Goffová Ivana , Fajkus Jiří
Published: January 2021

Genes encoding ribosomal RNA (rDNA) are essential for cell survival and are particularly sensitive to factors leading to genomic instability. Their repetitive character makes them prone to inappropriate recombinational events arising from collision of transcriptional and replication machineries, resulting in unstable rDNA copy numbers. In this review, we summarize current knowledge on the structure and organization of rDNA, its role in sensing changes in the genome, and its linkage to aging. We also review recent findings on the main factors involved in chromatin assembly and DNA repair in the maintenance of rDNA stability in the model plants Arabidopsis thaliana and the moss Physcomitrella patens, providing a view across the plant evolutionary tree.
Effect of Increased IL-1β on Expression of HK in Alzheimer’s Disease
Authors: Han Shuangxue , He Zhijun , Jacob Cornelius , Hu Xia , Liang Xiao , Xiao Wenchang , Wan Lu , Xiao Peng , D’Ascenzo Nicola , Ni Jiazuan , Liu Qiong , Xie Qingguo
Published: January 2021

Alzheimer’s disease (AD) is a neurodegenerative disease characterized by decreased glucose metabolism and increased neuroinflammation. Hexokinase (HK) is the key enzyme of glucose metabolism and is associated with mitochondria to exert its function. Recent studies have demonstrated that the dissociation of HK from mitochondria is enough to activate the NOD-like receptor protein 3 (NLRP3) inflammasome and leads to the release of interleukin-1β (IL-1β). However, the effect of increased IL-1β on the expression of HK is still unclear in AD. In this paper, we used positron emission tomography (PET), Western blotting and immunofluorescence to study the glucose metabolism, and the expression and distribution of HK in AD. Furthermore, we used lipopolysaccharide (LPS), nigericin (Nig), CY-09 and lonidamine (LND) to treat N2a and N2a-sw cells to investigate the link between IL-1β and HK in AD. The results show decreased expression of HK and the dissociation of HK from mitochondria in AD. Furthermore, a reduction of the expression of IL-1β could increase the expression of HK in AD. These results suggest that inhibiting inflammation may help to restore glucose metabolism in AD.
High-Temperature Conditions Promote Soybean Flowering through the Transcriptional Reprograming of Flowering Genes in the Photoperiod Pathway
Authors: No Dong Hyeon , Baek Dongwon , Lee Su Hyeon , Cheong Mi Sun , Chun Hyun Jin , Park Mi Suk , Cho Hyun Min , Jin Byung Jun , Lim Lack Hyeon , Lee Yong Bok , Shim Sang In , Chung Jong-Il , Kim Min Chul
Published: January 2021

Global warming has an impact on crop growth and development. Flowering time is particularly sensitive to environmental factors such as day length and temperature. In this study, we investigated the effects of global warming on flowering using an open-top Climatron chamber, which has a higher temperature and CO2 concentration than in the field. Two different soybean cultivars, Williams 82 and IT153414, which exhibited different flowering times, were promoted flowering in the open-top Climatron chamber than in the field. We more specifically examined the expression patterns of soybean flowering genes on the molecular level under high-temperature conditions. The elevated temperature induced the expression of soybean floral activators, GmFT2a and GmFT5a as well as a set of GmCOL genes. In contrast, it suppressed floral repressors, E1 and E2 homologs. Moreover, high-temperature conditions affected the expression of these flowering genes in a day length-independent manner. Taken together, our data suggest that soybean plants properly respond and adapt to changing environments by modulating the expression of a set of flowering genes in the photoperiod pathway for the successful production of seeds and offspring.
The Special Developmental Biology of Craniofacial Tissues Enables the Understanding of Oral and Maxillofacial Physiology and Diseases
Authors: Weber Manuel , Wehrhan Falk , Deschner James , Sander Janina , Ries Jutta , Möst Tobias , Bozec Aline , Gölz Lina , Kesting Marco , Lutz Rainer
Published: January 2021

Maxillofacial hard tissues have several differences compared to bones of other localizations of the human body. These could be due to the different embryological development of the jaw bones compared to the extracranial skeleton. In particular, the immigration of neuroectodermally differentiated cells of the cranial neural crest (CNC) plays an important role. These cells differ from the mesenchymal structures of the extracranial skeleton. In the ontogenesis of the jaw bones, the development via the intermediate stage of the pharyngeal arches is another special developmental feature. The aim of this review was to illustrate how the development of maxillofacial hard tissues occurs via the cranial neural crest and pharyngeal arches, and what significance this could have for relevant pathologies in maxillofacial surgery, dentistry and orthodontic therapy. The pathogenesis of various growth anomalies and certain syndromes will also be discussed.
Acknowledgment to Reviewers of Inventions in 2020
Authors:   Inventions Editorial Office
Published: January 2021

Peer review is the driving force of journal development, and reviewers are gatekeepers who ensure that Inventions maintains its standards for the high quality of its published papers [...]
Genome Editing for β-Hemoglobinopathies: Advances and Challenges
Authors: Frati Giacomo , Miccio Annarita
Published: January 2021

β-hemoglobinopathies are the most common genetic disorders worldwide and are caused by mutations affecting the production or the structure of adult hemoglobin. Patients affected by these diseases suffer from anemia, impaired oxygen delivery to tissues, and multi-organ damage. In the absence of a compatible donor for allogeneic bone marrow transplantation, the lifelong therapeutic options are symptomatic care, red blood cell transfusions and pharmacological treatments. The last decades of research established lentiviral-mediated gene therapy as an efficacious therapeutic strategy. However, this approach is highly expensive and associated with a variable outcome depending on the effectiveness of the viral vector and the quality of the cell product. In the last years, genome editing emerged as a valuable tool for the development of curative strategies for β-hemoglobinopathies. Moreover, due to the wide range of its applications, genome editing has been extensively used to study regulatory mechanisms underlying globin gene regulation allowing the identification of novel genetic and pharmacological targets. In this work, we review the current advances and challenges of genome editing approaches to β-hemoglobinopathies. Special focus has been directed towards strategies aimed at correcting the defective β-globin gene or at inducing fetal hemoglobin (HbF), which are in an advanced state of clinical development.
Model Calibration and Data Set Determination Considering the Local Micro-Structure for Short Fiber Reinforced Polymers
Authors: Primetzhofer Andreas , Stadler Gabriel , Pinter Gerald , Grün Florian
Published: January 2021

To ensure the usability of parts made of fiber-reinforced polymers, a lifetime assessment has to be made in an early stage of the development process. To describe the whole life cycle of these parts, continuous simulation chains can be used. From production to the end of the service life, all influences are mapped virtually. The later material strength is already given after the manufacturing process due to the process dependent fiber alignment. To be able to describe this fiber orientation within the lifetime assessment, this paper presents an approach for model calibration and data set determination to consider the local micro-structure. Therefore, quasi-static and cyclic tests were performed on specimens with longitudinal and transversal fiber orientation. A supplementary failure analysis provides additional information about the local micro-structure. The local fiber orientation is determined with µCT (micro computer tomography)-measurements, correlated to the extraction positions of the specimen, and implemented in a dataset. With an attached lifetime calculation on a demonstrator, a major influence of the local micro-structure on the calculation results can be shown. Therefore, it is indispensable to consider the local fiber orientation in the data set determination of short fiber reinforced polymers.
Diagnosing Marine Piston Engines Driving Generators at Different Operational Loads
Authors: Monieta Jan
Published: January 2021

Loads at which diagnostic research should be carried out were selected of operational investigation and preliminary diagnostic tests. It is difficult to keep the load constant during operational tests, so there is a need to apply the theory of the experiment. Operational investigation determined, the average and representative loads of tested engines driving generators. In preliminary diagnostic tests, the effects of loading on values of diagnostic parameters in various domains of signals analysis were checked and used to reduce the range the diagnostic research. Besides, the most useful symptoms were selected based on the correlation with the load. The diagnostic of pressure in the injection subsystem and in-cylinder pressure signals were subjected to time frequency analysis. In the principal studies, attempts were made to investigate the value of diagnostic symptoms while maintaining a constant load. For operating marine combustion engines, it is difficult to obtain repeatable test conditions because it is dependent on the principles of engine control and consumption of electricity by shipboard receivers. In operational tests on sea-going vessels, a wireless load measurement system and a system for processing and analyzing the parameters of working and residual processes were used. The wireless simultaneous load measurement system was effective in cases where load indicators and meters were away from the diagnosed objects. A wireless load and selected signals transmission system was used in tests on the ship. The aim of the article is to develop diagnostic models for bringing different test conditions to the common representative and reliable diagnostic decision. The article presents how to adjust diagnostic parameters of the working process, recorded at slightly different loads, to the value of common and equal load. This was done based on the best-fitted approximation model.
The Future of Energy and the Case of the Arctic Offshore: The Role of Strategic Management
Authors: Carayannis Elias G. , Ilinova Alina , Cherepovitsyn Alexey
Published: January 2021

As risk and uncertainty factors have become more prominent in the already volatile energy market because of the COVID-19 pandemic, the development of Arctic hydrocarbon resources has become a debatable issue. At any rate, oil and gas companies need to improve their strategic management systems (along with the development of technologies) for the successful implementation of such complex projects. The purpose of this study was to propose the conceptual basis for transforming strategic management and planning systems of oil and gas companies so that they can successfully face global challenges when implementing offshore oil and gas projects in the Arctic as well as provide more sustainable energy sources. The article discusses the current situation with Arctic initiatives and the results of an analysis of price instability in the energy sector, along with an analysis of several megatrends affecting oil and gas companies. All this allows for presenting a conceptual vision of how a strategic management system should be transformed in order to become able to meet the requirements for implementing Arctic projects, with the emphasis being placed on sustainability, management requirements, and the key principles. The research is based on the fundamentals of strategic management and strategic planning and relies on methods such as desk study, content analysis, event analysis, comparative analysis, and factor analysis.
Integrating Different Lines of Evidence to Establish a Novel Ascomycete Genus and Family (Anastomitrabeculia, Anastomitrabeculiaceae) in Pleosporales
Authors: Bhunjun Chitrabhanu S. , Phukhamsakda Chayanard , Jeewon Rajesh , Promputtha Itthayakorn , Hyde Kevin D.
Published: January 2021

A novel genus, Anastomitrabeculia, is introduced herein for a distinct species, Anastomitrabeculia didymospora, collected as a saprobe on dead bamboo culms from a freshwater stream in Thailand. Anastomitrabeculia is distinct in its trabeculate pseudoparaphyses and ascospores with longitudinally striate wall ornamentation. A new family, Anastomitrabeculiaceae, is introduced to accommodate Anastomitrabeculia. Anastomitrabeculiaceae forms an independent lineage basal to Halojulellaceae in Pleosporales and it is closely related to Neohendersoniaceae based on phylogenetic analyses of a combined LSU, SSU and TEF1α dataset. In addition, divergence time estimates provide further support for the establishment of Anastomitrabeculiaceae. The family diverged around 84 million years ago (MYA) during the Cretaceous period, which supports the establishment of the new family. The crown and stem age of Anastomitrabeculiaceae was also compared to morphologically similar pleosporalean families.
Digital Media Production of Refugee-Background Youth: A Scoping Review
Authors: Michalovich Amir
Published: January 2021

Reviews of research have provided insights into the digital media production practices of youth in and out of school. Although such practices hold promise for the language and literacy education of refugee-background youth, no review has yet integrated findings across studies and different digital media production practices to explore this promise. This scoping review summarizes and discusses the key findings from research on varied types of digital media produced specifically by refugee-background youth in and out of school. It situates digital media production practices in the context of this diverse population, which experiences forced migration, and highlights 5 main themes from findings in 42 reviewed articles. Digital media production afforded refugee-background youth: (1) Ownership of representations across time and space; (2) opportunity to expand, strengthen, or maintain social networks; (3) identity work; (4) visibility and engagement with audiences; and (5) communication and embodied learning through multimodal literacies.
Serum microRNAs as Tool to Predict Early Response to Benralizumab in Severe Eosinophilic Asthma
Authors: Cañas José A. , Valverde-Monge Marcela , Rodrigo-Muñoz José M. , Sastre Beatriz , Gil-Martínez Marta , García-Latorre Raquel , Rial Manuel J. , Gómez-Cardeñosa Aida , Fernández-Nieto Mar , Pinillos-Robles Erwin J. , Rodríguez-Nieto María J. , González-Mangado Nicolás , Sastre Joaquín , del Pozo Victoria
Published: January 2021

Severe eosinophilic asthma poses a serious health and economic problem, so new therapy approaches have been developed to control it, including biological drugs such as benralizumab, which is a monoclonal antibody that binds to IL-5 receptor alpha subunit and depletes peripheral blood eosinophils rapidly. Biomarkers that predict the response to this drug are needed so that microRNAs (miRNAs) can be useful tools. This study was performed with fifteen severe eosinophilic asthmatic patients treated with benralizumab, and serum miRNAs were evaluated before and after treatment by semi-quantitative PCR (qPCR). Patients showed a clinical improvement after benralizumab administration. Additionally, deregulation of miR-1246, miR-5100 and miR-338-3p was observed in severe asthmatic patients after eight weeks of therapy, and a correlation was found between miR-1246 and eosinophil counts, including a number of exacerbations per year in these severe asthmatics. In silico pathway analysis revealed that these three miRNAs are regulators of the MAPK signaling pathway, regulating target genes implicated in asthma such as NFKB2, NFATC3, DUSP1, DUSP2, DUSP5 and DUSP16. In this study, we observed an altered expression of miR-1246, miR-5100 and miR-338-3p after eight weeks of benralizumab administration, which could be used as early response markers.
MANET Performance Optimization Using Network-Based Criteria and Unmanned Aerial Vehicles
Authors: Gromova Ekaterina V. , Kireev Sergei , Lazareva Alina , Kirpichnikova Anna , Gromov Dmitry
Published: January 2021

In this contribution we consider the problem of optimal drone positioning for improving the operation of a mobile ad hoc network. We build upon our previous results devoted to the application of game-theoretic methods for computing optimal strategies. One specific problem that arises in this context is that the optimal solution cannot be uniquely determined. In this case, one has to use some other criteria to choose the best (in some sense) of all optimal solutions. It is argued that centrality measures as well as node ranking can provide a good criterion for the selection of a unique solution. We showed that for two specific networks most criteria yielded the same solution, thus demonstrating good coherence in their predictions.
Toward a New Urban Cycle? A Closer Look to Sprawl, Demographic Transitions and the Environment in Europe
Authors: Smiraglia Daniela , Salvati Luca , Egidi Gianluca , Salvia Rosanna , Giménez-Morera Antonio , Halbac-Cotoara-Zamfir Rares
Published: January 2021

Urban growth is a largely debated issue in social science. Specific forms of metropolitan expansion—including sprawl—involve multiple and fascinating research dimensions, making mixed (quali-quantitative) analysis of this phenomenon particularly complex and challenging at the same time. Urban sprawl has attracting the attention of multidisciplinary studies defining nature, dynamics, and consequences that dispersed low-density settlements are having on biophysical and socioeconomic contexts worldwide. The present commentary provides a brief overview on nature and implications of the latent relationship between sprawl, demographic dynamics, and background socio-environmental contexts with special focus on Europe. Empirical evidence supports the idea that spatial planning should cope more effectively with the increasing environmental and socioeconomic exposure of European regions to sprawl and demographic transitions, being progressively far away from a traditional urban cycle with sequential waves of urbanization, suburbanization, counter-urbanization, and re-urbanization. Growing socio-ecological vulnerability of metropolitan regions was evaluated based on a literature review demonstrating how a better comprehension of the intimate linkage between long-term demographic dynamics and urban cycles is necessary to inform fine-tuned policies controlling sprawl and promoting a sustainable management of peri-urban land.
Introducing the Special Issue: Interdisciplinary Perspectives on Code-Switching
Authors: Kašćelan Draško , Deuchar Margaret
Published: January 2021

Research on code-switching was the province of specialists in linguistics alone in the latter part of the twentieth century and is still a valuable source of insights into the human language faculty [...]
The Aging Bowel Dysfunction and Elderly Vulnerability towards COVID-19 Infection
Authors: Lerner Aaron , McCarty Mark F.
Published: January 2021

Severe acute respiratory syndrome coronavirus 2, primarily a respiratory tract virus, also affects the enteric organs. The most affected sector of the community are the retirement and nursing home elderly residents. Along their life the senescent gastrointestinal functions are deteriorating and failing to fully execute their digestive, absorptive, mucosal barriers, and immune protective duties. Adding the decreased motility, increased intestinal permeability, dysbiosis, morbid chronic disease background, the consumed polypharmacy enteric adverse effects to the presence of the SARS-CoV-2 host receptor along the intestinal tracts put the basis for the current hypothesis. It is hypothesized that the disadvantages and failures of the aging enteric tract contribute to the elderly morbidity and mortality during the current new coronavirus pandemic. In a more optimistic look, several nutraceuticals can prevent or restore the dysfunctional intestinal barrier functions, mainly in the elderly and potentially in those who are SARS-CoV-2 infected.
The Influence of Cement Layer Thickness on the Stress State of Metal Inlay Restorations—Photoelastic Analysis
Authors: Sokolowski Grzegorz , Krasowski Michal , Szczesio-Wlodarczyk Agata , Konieczny Bartlomiej , Sokolowski Jerzy , Bociong Kinga
Published: January 2021

The successful restoration of teeth requires a good connection between the inlay and natural tissue. A strong bond may improve retention and reinforce tooth structure. The purpose of this study was to evaluate the influence of cement layer thickness on contraction stress generated during photopolymerization, and to determine the changes in stress state of the cement occurring during aging in water (over 84 days). Two cements were used: resin composite cement (NX3) and self-adhesive resin cement (Maxcem Elite Chroma). A cylindrical sample made of CuZn alloy was used to imitate the inlay. The stress state was measured by photoelastic analysis. The contraction stress of the inlay restoration was calculated for cement layer thicknesses of 25 µm, 100 µm, 200 µm, and 400 µm. For both tested materials, the lowest contraction stress was observed for the thinnest layer (25 µm), and this increased with thickness. Following water immersion, a significant reduction in contraction stress was observed due to hygroscopic expansion. Applying a thin layer (approximately 25 µm) of composite and self-adhesive resin cements resulted in high levels of expansion stresses (over −6 MPa) after water aging.
Combining Thermal Loading System with Acoustic Emission Technology to Acquire the Complete Stress-Deformation Response of Plain Concrete in Direct Tension
Authors: Zhang Rui , Guo Li , Li Wanjin
Published: January 2021

The tensile properties of plain concrete are very important for the concrete structural design, and the complete tensile stress-strain curve is essential for creating accurate and reliable designs, especially when considering special load cases such as earthquakes and impacts. To study the complete tensile stress-deformation response of plain concrete, the direct tension tests were conducted on a novel thermal tensile testing machine (TTTM), which was reformed from a hydraulic universal testing machine (UTM). Acoustic emission (AE) technology was applied to monitor the damage process of plain concrete in tests. The TTTM was powered by the thermal expansion of loading columns, and had a stiffness similar to the specimen, thus eliminating the potential AE noises in the UTM, and simulating the rapid fracture process in real concrete structures. A static-dynamic acquisition system was established to obtain the complete tensile stress-strain curves, of which the data before and at the fracture moment were respectively acquired by the static acquisition system and the dynamic acquisition system. The AE technology is a useful approach to analyze the damage process of concrete, and makes it feasible to determine the damage state and the fracture location of the specimen in real time.
First-Principles Studies for Electronic Structure and Optical Properties of p-Type Calcium Doped α-Ga2O3
Authors: Mondal Abhay Kumar , Mohamed Mohd Ambri , Ping Loh Kean , Mohamad Taib Mohamad Fariz , Samat Mohd Hazrie , Mohammad Haniff Muhammad Aniq Shazni , Bahru Raihana
Published: January 2021

Gallium oxide (Ga2O3) is a promising wide-band-gap semiconductor material for UV optical detectors and high-power transistor applications. The fabrication of p-type Ga2O3 is a key problem that hinders its potential for realistic power applications. In this paper, pure α-Ga2O3 and Ca-doped α-Ga2O3 band structure, the density of states, charge density distribution, and optical properties were determined by a first-principles generalized gradient approximation plane-wave pseudopotential method based on density functional theory. It was found that calcium (Ca) doping decreases the bandgap by introducing deep acceptor energy levels as the intermediate band above the valence band maximum. This intermediate valence band mainly consists of Ca 3p and O 2p orbitals and is adequately high in energy to provide an opportunity for p-type conductivity. Moreover, Ca doping enhances the absorptivity and reflectivity become low in the visible region. Aside, transparency decreases compared to the pure material. The optical properties were studied and clarified by electrons-photons interband transitions along with the complex dielectric function’s imaginary function.
(Ti,Sn) Solid Solution Based Gas Sensors for New Monitoring of Hydraulic Oil Degradation
Authors: Fioravanti Ambra , Marani Pietro , Massarotti Giorgio Paolo , Lettieri Stefano , Morandi Sara , Carotta Maria Cristina
Published: January 2021

The proper operation of a fluid power system in terms of efficiency and reliability is directly related to the fluid state; therefore, the monitoring of fluid ageing in real time is fundamental to prevent machine failures. For this aim, an innovative methodology based on fluid vapor analysis through metal oxide (shortened: MOX) gas sensors has been developed. Two apparatuses were designed and realized: (i) a dedicated test bench to fast-age the fluid under controlled conditions; (ii) a laboratory MOX sensor system to test the headspace of the aged fluid samples. To prepare the set of MOX gas sensors suitable to detect the analytes’ concentrations in the fluid headspace, different functional materials were synthesized in the form of nanopowders, characterizing them by electron microscopy and X-ray diffraction. The powders were deposited through screen-printing technology, realizing thick-film gas sensors on which dynamical responses in the presence of the fluid headspace were obtained. It resulted that gas sensors based on solid solution TixSn1–xO2 with x = 0.9 and 0.5 offered the best responses toward the fluid headspace with lower response and recovery times. Furthermore, a decrease in the responses (for all sensors) with fluid ageing was observed.
Claude Mydorge Reader and Interpreter of Apollonius’ Conics
Authors: Florio Emilia
Published: January 2021

In 1639, the treatise Prodromi catoptricorum et dioptricorum sive Conicorum operis ad abdita radii reflexi et refracti mysteria praevij et facem praeferentis. Libri quatuor priores by Claude Mydorge was printed in Paris. This volume, which followed the printing of his first two books in 1631, has resonance especially in the writings of those who, after him, addressed the conics. This fact raises the question of who Mydorge was and what his knowledge of the “doctrine” of the conics was, what is the most appropriate cultural context in which to properly read this writing, and finally, what is the place of its content in the development of thought placed between the Veteres and the Recentiores. In this paper, I attempt to elaborate an answer to these different questions, with the aim of emphasizing how the author reads and interprets the first books of Apollonius’ Conics. Neither the treatise, nor the figure of Mydorge, have received much attention in the current literature, although he was estimated as a savant in Paris and he was believed by Descartes to be one of the greatest mathematicians of his time.
Permanence for Nonautonomous Differential Systems with Delays in the Linear and Nonlinear Terms
Authors: Faria Teresa
Published: January 2021

In this paper, we obtain sufficient conditions for the persistence and permanence of a family of nonautonomous systems of delay differential equations. This family includes structured models from mathematical biology, with either discrete or distributed delays in both the linear and nonlinear terms, and where typically the nonlinear terms are nonmonotone. Applications to systems inspired by mathematical biology models are given.
Molecular and Structural Characterizations of Lipases from Chlorella by Functional Genomics
Authors: Ben Hlima Hajer , Dammak Mouna , Karray Aida , Drira Maroua , Michaud Philippe , Fendri Imen , Abdelkafi Slim
Published: January 2021

Microalgae have been poorly investigated for new-lipolytic enzymes of biotechnological interest. In silico study combining analysis of sequences homologies and bioinformatic tools allowed the identification and preliminary characterization of 14 putative lipases expressed by Chlorella vulagaris. These proteins have different molecular weights, subcellular localizations, low instability index range and at least 40% of sequence identity with other microalgal lipases. Sequence comparison indicated that the catalytic triad corresponded to residues Ser, Asp and His, with the nucleophilic residue Ser positioned within the consensus GXSXG pentapeptide. 3D models were generated using different approaches and templates and demonstrated that these putative enzymes share a similar core with common α/β hydrolases fold belonging to family 3 lipases and class GX. Six lipases were predicted to have a transmembrane domain and a lysosomal acid lipase was identified. A similar mammalian enzyme plays an important role in breaking down cholesteryl esters and triglycerides and its deficiency causes serious digestive problems in human. More structural insight would provide important information on the enzyme characteristics.
Outcomes of Patients with Pulmonary Large Cell Neuroendocrine Carcinoma in I–IV Stage
Authors: Lowczak Anna , Kolasinska-Cwikla Agnieszka , Osowiecka Karolina , Glinka Lidia , Palucki Jakub , Rzepko Robert , Doboszynska Anna , Cwikla Jaroslaw B.
Published: January 2021

Background and Objectives: Large cell neuroendocrine cancer is characterised by poor prognosis. The standard of treatment is still not established. The aim of this study was to assess the predictive factors of overall survival (OS) and progression-free survival (PFS) of pulmonary large cell neuroendocrine carcinoma (LCNEC) and combined LCNEC. Materials and Methods: All patients had confirmed pathology stage I-IV disease recorded between period 2002–2018. Survival curves were estimated by Kaplan–Meier method. Uni- and multivariable analysis was conducted using Cox-regression analysis. Results: A total of 132 patients with LCNEC and combined LCNEC were included. Half of them had clinical stage IIIB/C-IV. Patients were treated with radical (n = 67, including surgery alone; resection with neo-adjuvant or adjuvant chemotherapy, radiochemotherapy, or adjuvant radiotherapy; patients treated with radiochemotherapy alone), palliative (n = 41) or symptomatic (n = 24) intention. Seventeen patients were treated with resection margin R1 or R2. Non-small cell carcinoma (NSCLC) chemotherapy (platinum-vinorelbine; PN schedule) and small-cell lung carcinoma (SCLC) chemotherapy approaches (platinum/carboplatinum-etoposide; PE/KE schedule) were administered in 20 and in 55 patients, respectively. The median (95% Confidence Interval (CI)) OS and PFS were 17 months (9.0–36.2 months) and 7 months (3.0–15.0 months), respectively. Patients treated with negative resection margin, with lower clinical stage, without lymph node metastasis, and with size of primary tumour ≤4 cm showed significantly better OS and PFS. The main risk factors with an adverse effect on survival were advanced CS and positive resection margin. Conclusions: Patients with LCNEC characterized poor prognosis. Independent prognostic factors influencing PFS were initial clinical stage and resection margin R0 vs. R1-2.