bluuebunny/crossref_metadata_2025 huggingface dataset:
Natural History of NAFLD
Authors: Pais Raluca , Maurel Thomas
Published: March 2021

The epidemiology and the current burden of chronic liver disease are changing globally, with non-alcoholic fatty liver disease (NAFLD) becoming the most frequent cause of liver disease in close relationship with the global epidemics of obesity, type 2 diabetes and metabolic syndrome. The clinical phenotypes of NAFLD are very heterogeneous in relationship with multiple pathways involved in the disease progression. In the absence of a specific treatment for non-alcoholic steatohepatitis (NASH), it is important to understand the natural history of the disease, to identify and to optimize the control of factors that are involved in disease progression. In this paper we propose a critical analysis of factors that are involved in the progression of the liver damage and the occurrence of extra-hepatic complications (cardiovascular diseases, extra hepatic cancer) in patients with NAFLD. We also briefly discuss the impact of the heterogeneity of the clinical phenotype of NAFLD on the clinical practice globally and at the individual level.
Perception of Citizens Regarding Marine Litter Impacts: Collaborative Methodologies in Island Fishing Communities of Cape Verde
Authors: Ferreira José C. , Monteiro Renato , Vasconcelos Lia , Duarte Cláudio M. , Ferreira Filipa , Santos Euclides
Published: March 2021

Marine litter has been considered one of the most serious global challenges, requiring urgent action by governmental bodies, especially in African Small Island Developing States (SIDS), where resources and research are limited. In addition to this, waste management and environmental education and ocean literacy programs in schools are scarce, with islands suffering more seriously from these problems. Despite the amount of literature regarding causes and impacts of marine litter, there is still not enough research conducted concerning the public perceptions on both the problem and the potential solutions. This is even more noticeable in African developing countries, where resources and research are scarce. Perception plays a key role for ecosystem management and conservation policies. This study intends to explore the perceptions of local island fishing communities in Cape Verde regarding marine litter, in order to contribute for an improvement of marine ecosystem management and development of conservation policies. To achieve that, two participatory sessions were conducted in two communities in the island of Santiago—Porto Mosquito and Porto Gouveia—where brainstorming and active listening were used to create shared and authentic spaces for dialogue between the members of the community. Results show that the population of both communities were very aware of the marine litter problem. They were able to identify the lack of a proper waste management system in the island and the inappropriate behaviours of the population as the main causes of this problem. Equipment damages and the presence of plastic inside the fish were the most relevant impacts identified by the participants. These findings reinforce previous research on the importance of public engagement and environmental education to contribute to the conservation of marine ecosystems and to build a strong collaborative ocean governance.
3-Dimensional Modeling and Attitude Control of Multi-Joint Autonomous Underwater Vehicles
Authors: Yu Lin , Meng Qinghao , Zhang Hongwei
Published: March 2021

To achieve rapid and flexible vertical profile exploration of deep-sea hybrid structures, a multi-joint autonomous underwater vehicle (MJ-AUV) with orthogonal joints was designed. This paper focuses on the 3-dimensional (3D) modeling and attitude control of the designed vehicle. Considering the situation of gravity and buoyancy imbalance, a 3D model of the MJ-AUV was established according to Newton’s second law and torque balance principle. And then the numerical simulation was carried out to verify the credibility of the model. To solve the problems that the pitch and yaw attitude of the MJ-AUV are coupled and the disturbance is unknown, a linear quadratic regulator (LQR) decoupling control method based on a linear extended state observer (LESO) was proposed. The system was decoupled into pitch and yaw subsystems, treated the internal forces and external disturbances of each subsystem as total disturbances, and estimated the total disturbances with LESO. The control law was divided into two parts. The first part was the total disturbance compensator, while the second part was the linear state feedback controller. The simulation results show that the overshoot of the controlled system in the dynamic process is nearly 0 rad, reaching the design value very smoothly. Moreover, when the controlled system is in a stable state, the control precision is within 0.005%.
Inocybe brijunica sp. nov., a New Ectomycorrhizal Fungus from Mediterranean Croatia Revealed by Morphology and Multilocus Phylogenetic Analysis
Authors: Mešić Armin , Haelewaters Danny , Tkalčec Zdenko , Liu Jingyu , Kušan Ivana , Aime M. Catherine , Pošta Ana
Published: March 2021

A new ectomycorrhizal species was discovered during the first survey of fungal diversity at Brijuni National Park (Croatia), which consists of 14 islands and islets. The National Park is located in the Mediterranean Biogeographical Region, a prominent climate change hot-spot. Inocybe brijunica sp. nov., from sect. Hysterices (Agaricales, Inocybaceae), is described based on morphology and multilocus phylogenetic data. The holotype collection was found at the edge between grassland and Quercus ilex forest with a few planted Pinus pinea trees, on Veli Brijun Island, the largest island of the archipelago. It is easily recognized by a conspicuous orange to orange–red–brown membranaceous surface layer located at or just above the basal part of the stipe. Other distinctive features of I. brijunica are the medium brown, radially fibrillose to rimose pileus; pale to medium brown stipe with fugacious cortina; relatively small, amygdaliform to phaseoliform, and smooth basidiospores, measuring ca. 6.5–9 × 4–5.5 µm; thick-walled, utriform, lageniform or fusiform pleurocystidia (lamprocystidia) with crystals and mostly not yellowing in alkaline solutions; cheilocystidia of two types (lamprocystidia and leptocystidia); and the presence of abundant caulocystidia only in the upper 2–3 mm of the stipe. Phylogenetic reconstruction of a concatenated dataset of the internal transcribed spacer region (ITS), the nuclear 28S rRNA gene (nrLSU), and the second largest subunit of RNA polymerase II (rpb2) resolved I. brijunica and I. glabripes as sister species.
Monocyte-Derived Dendritic Cells Can Revert In Vitro Antigen-Specific Cellular Anergy in Active Human Paracoccidioidomycosis
Authors: Sato Paula Keiko , Oshiro Telma Miyuki , Passos Érika Cano , Miranda Tatiana Giselle Rodrigues , Diogo Constância Lima , Fonseca Claudia de Abreu , Sadahiro Aya , de Almeida Sandro Rogério , Shikanai-Yasuda Maria Aparecida
Published: March 2021

We investigated the in vitro effects of two Paracoccidioides brasiliensis antigens on monocyte-derived dendritic cells (moDCs) from patients with paracoccidioidomycosis (PCM). MoDCs from patients with active or treated PCM and non-PCM subjects were generated, stimulated with TNF-α, and P. brasiliensis antigens, 43 kDa glycoprotein (gp43) and cell-free antigen (CFA), and analyzed by flow cytometry and enzyme-linked immunosorbent assays (ELISA). Our data revealed that patients with PCM had a high frequency of HLA-DR+ cells, but the treated group had more CD86+ cells with increased IL-12p40. Patients with active PCM had more CD80+ moDCs, and as a novel finding, large amounts of chemokine (C-C motif) ligand 18 (CCL18) in the supernatants from their in vitro moDC cultures. Both gp43- and CFA-stimulated moDCs from the patients with PCM successfully reverted the in vitro antigen-specific anergy, inducing a proliferative response. However, CFA-stimulated moDCs led to higher lymphoproliferation, with increased IFN-γ and TNF-α in the cells from the patients with active PCM compared with gp43. These original results combined with constant IL-10 and increased IL-12p40 levels suggest that a more complex antigen, such as CFA, may be a better inducer of the protective Th1 immune response than purified gp43 is, and a suitable target for future studies on anti-P. brasiliensis dendritic cell (DC)-based vaccines.
The Role of Fungi in the Cocoa Production Chain and the Challenge of Climate Change
Authors: Delgado-Ospina Johannes , Molina-Hernández Junior Bernardo , Chaves-López Clemencia , Romanazzi Gianfranco , Paparella Antonello
Published: March 2021

Background: The role of fungi in cocoa crops is mainly associated with plant diseases and contamination of harvest with unwanted metabolites such as mycotoxins that can reach the final consumer. However, in recent years there has been interest in discovering other existing interactions in the environment that may be beneficial, such as antagonism, commensalism, and the production of specific enzymes, among others. Scope and approach: This review summarizes the different fungi species involved in cocoa production and the cocoa supply chain. In particular, it examines the presence of fungal species during cultivation, harvest, fermentation, drying, and storage, emphasizing the factors that possibly influence their prevalence in the different stages of production and the health risks associated with the production of mycotoxins in the light of recent literature. Key findings and conclusion: Fungi associated with the cocoa production chain have many different roles. They have evolved in a varied range of ecosystems in close association with plants and various habitats, affecting nearly all the cocoa chain steps. Reports of the isolation of 60 genera of fungi were found, of which only 19 were involved in several stages. Although endophytic fungi can help control some diseases caused by pathogenic fungi, climate change, with increased rain and temperatures, together with intensified exchanges, can favour most of these fungal infections, and the presence of highly aggressive new fungal genotypes increasing the concern of mycotoxin production. For this reason, mitigation strategies need to be determined to prevent the spread of disease-causing fungi and preserve beneficial ones.
Exploring the Sensitivity of Recurrent Neural Network Models for Forecasting Land Cover Change
Authors: van Duynhoven Alysha , Dragićević Suzana
Published: March 2021

Recurrent Neural Networks (RNNs), including Long Short-Term Memory (LSTM) architectures, have obtained successful outcomes in timeseries analysis tasks. While RNNs demonstrated favourable performance for Land Cover (LC) change analyses, few studies have explored or quantified the geospatial data characteristics required to utilize this method. Likewise, many studies utilize overall measures of accuracy rather than metrics accounting for the slow or sparse changes of LC that are typically observed. Therefore, the main objective of this study is to evaluate the performance of LSTM models for forecasting LC changes by conducting a sensitivity analysis involving hypothetical and real-world datasets. The intent of this assessment is to explore the implications of varying temporal resolutions and LC classes. Additionally, changing these input data characteristics impacts the number of timesteps and LC change rates provided to the respective models. Kappa variants are selected to explore the capacity of LSTM models for forecasting transitions or persistence of LC. Results demonstrate the adverse effects of coarser temporal resolutions and high LC class cardinality on method performance, despite method optimization techniques applied. This study suggests various characteristics of geospatial datasets that should be present before considering LSTM methods for LC change forecasting.
Editorial for Special Issue: “Collaboration and Multi-Stakeholder Engagement in Landscape Governance and Management in Africa: Lessons from Practice”
Authors: Favretto Nicola , Shackleton Sheona , Sallu Susannah M. , Hoffman Tali
Published: March 2021

A multitude of interconnected socio-economic and environmental impacts are emerging across Africa as a result of escalating anthropogenic drivers of global and local change [...]
SARS-CoV-2 Molecular Transmission Clusters and Containment Measures in Ten European Regions during the First Pandemic Wave
Authors: Bousali Maria , Dimadi Aristea , Kostaki Evangelia-Georgia , Tsiodras Sotirios , Nikolopoulos Georgios K. , Sgouras Dionyssios N. , Magiorkinis Gkikas , Papatheodoridis George , Pogka Vasiliki , Lourida Giota , Argyraki Aikaterini , Angelakis Emmanouil , Sourvinos George , Beloukas Apostolos , Paraskevis Dimitrios , Karamitros Timokratis
Published: March 2021

Background: The spatiotemporal profiling of molecular transmission clusters (MTCs) using viral genomic data can effectively identify transmission networks in order to inform public health actions targeting SARS-CoV-2 spread. Methods: We used whole genome SARS-CoV-2 sequences derived from ten European regions belonging to eight countries to perform phylogenetic and phylodynamic analysis. We developed dedicated bioinformatics pipelines to identify regional MTCs and to assess demographic factors potentially associated with their formation. Results: The total number and the scale of MTCs varied from small household clusters identified in all regions, to a super-spreading event found in Uusimaa-FI. Specific age groups were more likely to belong to MTCs in different regions. The clustered sequences referring to the age groups 50–100 years old (y.o.) were increased in all regions two weeks after the establishment of the lockdown, while those referring to the age group 0–19 y.o. decreased only in those regions where schools’ closure was combined with a lockdown. Conclusions: The spatiotemporal profiling of the SARS-CoV-2 MTCs can be a useful tool to monitor the effectiveness of the interventions and to reveal cryptic transmissions that have not been identified through contact tracing.
Implications of COVID-19 Pandemic on the Emergence of Antimicrobial Resistance: Adjusting the Response to Future Outbreaks
Authors: Rusic Doris , Vilovic Marino , Bukic Josipa , Leskur Dario , Seselja Perisin Ana , Kumric Marko , Martinovic Dinko , Petric Ana , Modun Darko , Bozic Josko
Published: March 2021

The net effect of the coronavirus disease 2019 (COVID-19) pandemic and the response to it on the emergence of antimicrobial resistance is yet unknown. Positive impacts on the spread of multiresistant pathogens and infections in general may be observed with the implementation of general preventative measures for the spread of infectious disease such as social distancing, reduced travel and increased personal hygiene. This pandemic has accelerated the development of novel technologies, such as mRNA vaccines, that may be used to fight other diseases. These should be capitalized upon to manage the ongoing antimicrobial resistance pandemic in the background. However, it is likely that the COVID-19 pandemic is fueling the emergence of antimicrobial resistance due to high rates of inappropriate antimicrobial prescribing, the high use of biocides and the interruption of treatment for other conditions. Clinical uncertainty driven by the lack of effective diagnostics and practice of telemedicine may have driven the inappropriate use of antimicrobials. As pathogens know no borders, increased focus is needed for infectious diseases still threatening low- and middle-income countries such as tuberculosis. Stewardship measures for future outbreaks should stress the importance of social distancing and hand washing but discourage the overuse of disinfectants and antimicrobials that are not proven effective.
The Multifaceted Regulation of Mitochondria in Ferroptosis
Authors: Wu Hao , Wang Fengli , Ta Na , Zhang Ting , Gao Weihua
Published: March 2021

Ferroptosis is characterized as a novel form of regulated cell death, which is initiated by the lethal accumulation of lipid peroxidation catalyzed by cellular labile free iron. This iron driven cell death sharply differs from other well characterized forms of regulated cell death at morphological, genetic and biochemical levels. Increasing research has elaborated a high relevance between dysregulated ferroptosis and the pathogenesis of degenerative diseases and organs injury in human patients. Additionally, targeted induction of ferroptosis is considered as a potentially therapeutic design for the clinical intervention of other therapy-resistant cancers. It is well understood that mitochondria, the cellular powerhouse, determine several types of regulated cell death. Recently, compromised mitochondrial morphology and functionalities have been primarily formulated in ferroptosis. Several mitochondria associated proteins and metabolic processes have been elaborated to fine-tune ferroptotic program. Herein, we critically review the recent advances in this booming field, with focus on summarizing the multifaceted mitochondrial regulation of ferroptosis and providing a perspective on the potential biochemical basis. Finally, we are attempting to shed light on an integrative view on the possibility of mitochondria- and ferroptosis-targeting therapeutics as novel treatment designs for the intervention of ferroptosis related diseases.
Recent Progress Using De Novo Design to Study Protein Structure, Design and Binding Interactions
Authors: Ferrando Juan , Solomon Lee A.
Published: March 2021

De novo protein design is a powerful methodology used to study natural functions in an artificial-protein context. Since its inception, it has been used to reproduce a plethora of reactions and uncover biophysical principles that are often difficult to extract from direct studies of natural proteins. Natural proteins are capable of assuming a variety of different structures and subsequently binding ligands at impressively high levels of both specificity and affinity. Here, we will review recent examples of de novo design studies on binding reactions for small molecules, nucleic acids, and the formation of protein-protein interactions. We will then discuss some new structural advances in the field. Finally, we will discuss some advancements in computational modeling and design approaches and provide an overview of some modern algorithmic tools being used to design these proteins.
Analysis of Brain Functions in Men with Prostate Cancer under Androgen Deprivation Therapy: A One-Year Longitudinal Study
Authors: Sánchez-Martínez Vanessa , Buigues Cristina , Navarro-Martínez Rut , García-Villodre Laura , Jeghalef Noura , Serrano-Carrascosa María , Rubio-Briones José , Cauli Omar
Published: March 2021

The relationship between cognitive decline and androgen deprivation therapy (ADT) under luteinizing hormone-releasing hormone (LHRH) analogues is unclear, and there is a scarcity of longitudinal studies considering the interaction between cognition, depressive symptoms and sleep quality in men with prostate cancer (PCa) treated with ADT. This study aimed to determine if there were differences in the scores obtained in cognitive assessment, depressive symptoms, and sleep quality after one year of ADT and determine the interrelations between sleep, mood, and cognitive status. A prospective longitudinal observational study was designed, in which a cohort of men (mean age was 70.8 years) newly treated with androgen-deprivation therapy was assessed in the first six months of treatment and 12 months later. Analysis of cognitive function by the Mini-Mental State Examination (MMSE) scores indicated a significant (p < 0.05) increase after one year of treatment and by the Brief Scale for Cognitive Evaluation (BCog) scores indicated no changes in the scores before and after one year of treatment. Analysis of depressive symptoms with the Geriatric Depression Scale and sleep quality with the Athens Insomnia Scale (AIS) scores showed significant (p < 0.05) changes after one year of treatment with ADT, with men describing more depressive symptoms and more sleep disturbances. No statistically significant differences were found in the cognitive performance between men with impaired sleep or depression results and those without them. Our study showed no clinical evidence of the relationship between ADT under luteinizing hormone-releasing hormone (LHRH) analogues and cognitive deterioration in 1-year follow-up, but there are impairments in the sleep quality in men with PCa undergoing ADT and an increase in depressive symptoms which has important implications for clinicians as they would impair quality of life and adherence to treatment.
Warpage Optimisation on the Moulded Part with Straight Drilled and Conformal Cooling Channels Using Response Surface Methodology (RSM), Glowworm Swarm Optimisation (GSO) and Genetic Algorithm (GA) Optimisation Approaches
Authors: Mohd Hanid Mohd Hazwan , Abd Rahim Shayfull Zamree , Gondro Joanna , Sharif Safian , Al Bakri Abdullah Mohd Mustafa , Zain Azlan Mohd , El-hadj Abdellah Abdellah , Mat Saad Mohd Nasir , Wysłocki Jerzy J. , Nabiałek Marcin
Published: March 2021

It is quite challenging to control both quality and productivity of products produced using injection molding process. Although many previous researchers have used different types of optimisation approaches to obtain the best configuration of parameters setting to control the quality of the molded part, optimisation approaches in maximising the performance of cooling channels to enhance the process productivity by decreasing the mould cycle time remain lacking. In this study, optimisation approaches namely Response Surface Methodology (RSM), Genetic Algorithm (GA) and Glowworm Swarm Optimisation (GSO) were employed on front panel housing moulded using Acrylonitrile Butadiene Styrene (ABS). Each optimisation method was analysed for both straight drilled and Milled Groove Square Shape (MGSS) conformal cooling channel moulds. Results from experimental works showed that, the performance of MGSS conformal cooling channels could be enhanced by employing the optimisation approach. Therefore, this research provides useful scientific knowledge and an alternative solution for the plastic injection moulding industry to improve the quality of moulded parts in terms of deformation using the proposed optimisation approaches in the used of conformal cooling channels mould.
A New Approach to Obtaining Nano-Sized Graphene Oxide for Biomedical Applications
Authors: Bolibok Paulina , Szymczak Bartosz , Roszek Katarzyna , Terzyk Artur P. , Wiśniewski Marek
Published: March 2021

Graphene oxide (GO) is one of the most exciting and widely used materials. A new method of nanographene oxide (n-GO) formation is presented. The described unique sequence of ultrasonication in dimethyl sulfoxide solution allows us to obtain different sizes of n-GO sheets by controlling the timing of the cutting and re-aggregation processes. The obtained n-GO exhibits only minor spectral changes, mainly due to the formation of S-containing surface groups; thus, it can be concluded that the material is not reduced during the process. Maintaining the initial oxygen functionalities together with the required nano-size (down to 200 nm) and high homogeneity are beneficial for extensive applications of n-GO. Moreover, we prove that the obtained material is evidently biocompatible. The calculated half-maximal effective concentration (EC50) increases by 5-fold, i.e., from 50 to 250 µg/mL, when GO is converted to n-GO. As a consequence, the new n-GO neither disturbs blood flow even in the narrowest capillaries nor triggers a toxic influence in surrounding cells. Thus, it can be a serious candidate for drugs and biomolecule carriers administered systemically.
Evaluation of the Hydration Characteristics and Anti-Washout Resistance of Non-Dispersible Underwater Concrete with Nano-SiO2 and MgO
Authors: Jeon In Kyu , Woo Byeong Hun , Yoo Dong Ho , Ryou Jae Suk , Kim Hong Gi
Published: March 2021

In this paper, the effect of nano-SiO2 (NS) and MgO on the hydration characteristics and anti-washout resistance of non-dispersible underwater concrete (UWC) was evaluated. A slump flow test, a viscosity test, and setting time measurement were conducted to identify the impacts of NS and MgO on the rheological properties of UWC. The pH and turbidity were measured to investigate the anti-washout performance of UWC mixes. To analyze the hydration characteristics and mechanical properties, hydration heat analysis, a compressive strength test, and thermogravimetric analyses were conducted. The experimental results showed that the fine particles of NS and MgO reduced slump flow, increased viscosity, and enhanced the anti-washout resistance of UWC. In addition, both NS and MgO shortened the initial and final setting times, and the replacement of MgO specimens slightly prolonged the setting time. NS accelerated the peak time and increased the peak temperature, and MgO delayed the hydration process and reduced the temperature due to the formation of brucite. The compressive results showed that NS improved the compressive strength of the UWC, and MgO slightly decreased the strength. The addition of NS also resulted in the formation of extra C–S–H, and the replacement of MgO caused the generation of a hydrotalcite phase.
Effect of Solution Annealing on Fatigue Crack Propagation in the AISI 304L TRIP Steel
Authors: Jambor Michal , Vojtek Tomáš , Pokorný Pavel , Šmíd Miroslav
Published: March 2021

Fatigue crack propagation in near-threshold regime was studied in the 304L austenitic stainless steel in two microstructural states: as-received (AR) with finer microstructure and low susceptibility to the transformation-induced plasticity (TRIP) effect, and solution-annealed (SA) with coarser microstructure and higher susceptibility to TRIP. At the load ratio R = 0.1 the threshold was higher in the SA state than in the AR state due to coarser grains and possibly the TRIP effect. In order to clarify the role of crack closure, experiments at R = 0.7 were done. The threshold in the SA state was still higher by 1 MPa·m0.5. This effect was identified as crack tip shielding induced by phase transformation, an example of a non-closure shielding effect. Higher resistance to crack growth in the SA state was attributed to promoted martensitic transformation in non-favorable oriented grain families rather than thicker martensite layers in the crack path area. The conclusions were verified by experiments at R = 0.7 and temperature 150 °C > Ms which did not reveal any notable difference in thresholds. However, the threshold values were affected by the load-shedding gradient C = −dΔK/da, which had to be equalized in both experimental setups inside and outside the furnace.
Effect of Fine Size-Fractionated Sunflower Husk Biochar on Water Retention Properties of Arable Sandy Soil
Authors: Gluba Łukasz , Rafalska-Przysucha Anna , Szewczak Kamil , Łukowski Mateusz , Szlązak Radosław , Vitková Justína , Kobyłecki Rafał , Bis Zbigniew , Wichliński Michał , Zarzycki Robert , Kacprzak Andrzej , Usowicz Bogusław
Published: March 2021

Biochar application has been reported to improve the physical, chemical, and hydrological properties of soil. However, the information about the size fraction composition of the applied biochar as a factor that may have an impact on the properties of soil-biochar mixtures is often underappreciated. Our research shows how sunflower husk biochar (pyrolyzed at 650 °C) can modify the water retention characteristics of arable sandy soil depending on the biochar dose (up to 9.52 wt.%) and particle size (<50 µm, 50–100 µm, 100–250 µm). For comparison, we used soil samples mixed with biochar passed through 2 mm sieve and an unamended reference. The addition of sieved biochar to the soil caused a 30% increase in the available water content (AWC) in comparing to the soil without biochar. However, the most notable improvement (doubling the reference AWC value from 0.078 m3 m−3 to 0.157 m3 m−3) was observed at the lowest doses of biochar (0.95 and 2.24 wt.%) and for the finest size fractions (below 100 µm). The water retention effects on sandy soil are explained as the interplay between the dose, the size of biochar particles, and the porous properties of biochar fractions.
Charge Injection and Dielectric Characteristics of Polyethylene Terephthalate Based on Semiconductor Electrodes
Authors: Liu Guan-Yu , Sun Wei-Feng , Lei Qing-Quan
Published: March 2021

Employing a novel semiconductor electrode in comparison with the traditional semiconductor electrode made of polyethylene/ethylene-vinyl-acetate copolymer/carbon-black (PE/EVA/CB) composite, characteristic charge carriers are injected into polyethylene terephthalate (PET) as a polymer dielectric paradigm, which will be captured by specific deep traps of electrons and holes. Combined with thermal stimulation current (TSC) experiments and first-principles electronic-state calculations, the injected charges from the novel electrode are characterized, and the corresponding dielectric behavior is elucidated through DC conductance, electrical breakdown and dielectric spectrum tests. TSC experiments with novel and traditional semiconductor electrodes can distinguish the trapping characteristics between hole and electron traps in polymer dielectrics. The observable discrepancy in space charge-limited conductance and the stable dielectric breakdown strength demonstrate that the electron injection into PET film specimen is restricted by using the novel semiconductor electrode. Attributed to the favorable suppression on the inevitable electron injections from metal electrodes, adopting novel i-electrode can avoid the evident abatement of dipole orientation polarization caused by space charge clamp, but will engender the accessional high-frequency dielectric loss from dielectric relaxations of interface charges at i-electrodes.
A Mathematical Analysis of RNA Structural Motifs in Viruses
Authors: Churkin Alexander , Totzeck Franziska , Zakh Rami , Parr Marina , Tuller Tamir , Frishman Dmitrij , Barash Danny
Published: March 2021

RNA stem-loop structures play an important role in almost every step of the viral replication cycle. In this contribution, a mathematical analysis is performed on a large dataset of RNA secondary structure elements in the coding regions of viruses by using topological indices that capture the Laplacian eigenvalues of the associated RNA graph representations and thereby enable structural classification, supplemented by folding energy and mutational robustness. The application of such an analysis for viral RNA structural motifs is described, being able to extract structural categories such as stem-loop structures of different sizes according to the tree-graph representation of the RNA structure, in our attempt to find novel functional motifs. While the analysis is carried on a large dataset of viral RNA structures, it can be applied more generally to other data that involve RNA secondary structures in biological agents.
Constructing C0-Semigroups via Picard Iterations and Generating Functions: An Application to a Black–Scholes Integro-Differential Operator
Authors: Rodrigo Marianito R.
Published: March 2021

An alternative approach is proposed for constructing a strongly continuous semigroup based on the classical method of successive approximations, or Picard iterations, together with generating functions. An application to a Black–Scholes integro-differential operator which arises in the pricing of European options under jump-diffusion dynamics is provided. The semigroup is expressed as the Mellin convolution of time-inhomogeneous jump and Black–Scholes kernel functions. Other applications to the heat and transport equations are also given. The connection of the proposed approach to the Adomian decomposition method is explored.
Bayesian Inference for Finite Mixture Regression Model Based on Non-Iterative Algorithm
Authors: Shan Ang , Yang Fengkai
Published: March 2021

Finite mixtures normal regression (FMNR) models are widely used to investigate the relationship between a response variable and a set of explanatory variables from several unknown latent homogeneous groups. However, the classical EM algorithm and Gibbs sampling to deal with this model have several weak points. In this paper, a non-iterative sampling algorithm for fitting FMNR model is proposed from a Bayesian perspective. The procedure can generate independently and identically distributed samples from the posterior distributions of the parameters and produce more reliable estimations than the EM algorithm and Gibbs sampling. Simulation studies are conducted to illustrate the performance of the algorithm with supporting results. Finally, a real data is analyzed to show the usefulness of the methodology.
Four-Quadrant Riemann Problem for a 2×2 System II
Authors: Hwang Jinah , Shin Suyeon , Shin Myoungin , Hwang Woonjae
Published: March 2021

In previous work, we considered a four-quadrant Riemann problem for a 2×2 hyperbolic system in which delta shock appears at the initial discontinuity without assuming that each jump of the initial data projects exactly one plane elementary wave. In this paper, we consider the case that does not involve a delta shock at the initial discontinuity. We classified 18 topologically distinct solutions and constructed analytic and numerical solutions for each case. The constructed analytic solutions show the rich structure of wave interactions in the Riemann problem, which coincide with the computed numerical solutions.
The Effect of Flow Lines on the Mechanical Properties in Hot-Rolled Bearing Steel
Authors: Qian Dongsheng , Ma Chengfei , Wang Feng
Published: March 2021

Hot rolling is an essential process for the shape-forming of bearing steel. It plays a significant role in the formation and distribution of flow lines. In this work, the effect of flow lines is investigated by analyzing the microstructure and mechanical anisotropy of hot-rolled bearing steel. It was found that carbides rich with Cr and Mn elements are distributed unevenly along the flow-line direction of the hot-rolled bearing steel. Moreover, the mechanical characterization indicates that ultimate tensile strength and yield strength do not have any significant difference in two directions. Nevertheless, an ultrahigh section shrinkage of 57.51% is obtained in the 0° sample that has parallel flow lines, while 90° sample shows poor section shrinkage. The uneven distributed carbides will affect the direction and speed of crack propagation during tensile deformation. Therefore, the 0° and 90° samples exhibit great difference in plastic property. Meanwhile, after tensile deformation, a delaminated texture is observed in the flow lines, which may be caused by different degrees of deformation of grains due to the uneven distribution of carbides. The results of this work may provide guidance for controlling and optimizing flow lines in the manufacturing of bearing rings.
Numerical and Experimental Analysis of Hardening Distortions of Drawpieces Produced in Hot Stamping Process
Authors: Wróbel Ireneusz
Published: March 2021

The paper presents the results of a numerical simulation of the distortions in drawpieces, generated during the production of the drawpieces using the hot stamping method. A division of the distortions is proposed depending on their shape and based on the industrial experience of the author of this publication, i.e., concerning flexure and torsion (skewing). Numerical simulations of the hot stamping process were performed for the representative drawpieces, in which the hardening distortions can be assigned to the above specified forms. A numerical compensation of the hardening distortions was proposed to obtain, after the compensation process, a drawpiece complying with the requirements concerning shape and dimensional tolerances. The results of the simulations have been confirmed in the course of the experimental studies. Conclusions and recommendations for the analysis of the process were also elaborated.
Benchmarking Non-Targeted Metabolomics Using Yeast-Derived Libraries
Authors: Rampler Evelyn , Hermann Gerrit , Grabmann Gerlinde , El Abiead Yasin , Schoeny Harald , Baumgartinger Christoph , Köcher Thomas , Koellensperger Gunda
Published: March 2021

Non-targeted analysis by high-resolution mass spectrometry (HRMS) is an essential discovery tool in metabolomics. To date, standardization and validation remain a challenge. Community-wide accepted cost-effective benchmark materials are lacking. In this work, we propose yeast (Pichia pastoris) extracts derived from fully controlled fermentations for this purpose. We established an open-source metabolite library of >200 identified metabolites based on compound identification by accurate mass, matching retention times, and MS/MS, as well as a comprehensive literature search. The library includes metabolites from the classes of (1) organic acids and derivatives (2) nucleosides, nucleotides, and analogs, (3) lipids and lipid-like molecules, (4) organic oxygen compounds, (5) organoheterocyclic compounds, (6) organic nitrogen compounds, and (7) benzoids at expected concentrations ranges of sub-nM to µM. As yeast is a eukaryotic organism, key regulatory elements are highly conserved between yeast and all annotated metabolites were also reported in the human metabolome database (HMDB). Orthogonal state-of-the-art reversed-phase (RP-) and hydrophilic interaction chromatography mass spectrometry (HILIC-MS) non-targeted analysis and authentic standards revealed that 104 out of the 206 confirmed metabolites were reproducibly recovered and stable over the course of three years when stored at −80 °C. Overall, 67 out of these 104 metabolites were identified with comparably stable areas over all three yeast fermentation and are the ideal starting point for benchmarking experiments. The provided yeast benchmark material enabled not only to test for the chemical space and coverage upon method implementation and developments but also allowed in-house routines for instrumental performance tests. Transferring the quality control strategy of proteomics workflows based on the number of protein identification in HeLa extracts, metabolite IDs in the yeast benchmarking material can be used as metabolomics quality control. Finally, the benchmark material opens new avenues for batch-to-batch corrections in large-scale non-targeted metabolomics studies.
Formulation, Stability, Pharmacokinetic, and Modeling Studies for Tests of Synergistic Combinations of Orally Available Approved Drugs against Ebola Virus In Vivo
Authors: Finch Courtney L. , Dyall Julie , Xu Shuang , Nelson Elizabeth A. , Postnikova Elena , Liang Janie Y. , Zhou Huanying , DeWald Lisa Evans , Thomas Craig J. , Wang Amy , Xu Xin , Hughes Emma , Morris Patrick J. , Mirsalis Jon C. , Nguyen Linh H. , Arolfo Maria P. , Koci Bryan , Holbrook Michael R. , Hensley Lisa E. , Jahrling Peter B. , Schmaljohn Connie , Johansen Lisa M. , Olinger Gene G. , Schiffer Joshua T. , White Judith M.
Published: March 2021

Outbreaks of Ebola ebolavirus (EBOV) have been associated with high morbidity and mortality. Milestones have been reached recently in the management of EBOV disease (EVD) with licensure of an EBOV vaccine and two monoclonal antibody therapies. However, neither vaccines nor therapies are available for other disease-causing filoviruses. In preparation for such outbreaks, and for more facile and cost-effective management of EVD, we seek a cocktail containing orally available and room temperature stable drugs with strong activity against multiple filoviruses. We previously showed that (bepridil + sertraline) and (sertraline + toremifene) synergistically suppress EBOV in cell cultures. Here, we describe steps towards testing these combinations in a mouse model of EVD. We identified a vehicle suitable for oral delivery of the component drugs and determined that, thus formulated the drugs are equally active against EBOV as preparations in DMSO, and they maintain activity upon storage in solution for up to seven days. Pharmacokinetic (PK) studies indicated that the drugs in the oral delivery vehicle are well tolerated in mice at the highest doses tested. Collectively the data support advancement of these combinations to tests for synergy in a mouse model of EVD. Moreover, mathematical modeling based on human oral PK projects that the combinations would be more active in humans than their component single drugs.
Toxin-Activating Stapled Peptides Discovered by Structural Analysis Were Identified as New Therapeutic Candidates That Trigger Antibacterial Activity against Mycobacterium tuberculosis in the Mycobacterium smegmatis Model
Authors: Kang Sung-Min , Moon Heejo , Han Sang-Woo , Kim Byeong Wook , Kim Do-Hee , Kim Byeong Moon , Lee Bong-Jin
Published: March 2021

The structure-function relationships of toxin-antitoxin (TA) systems from Mycobacterium tuberculosis have prompted the development of novel and effective antimicrobial agents that selectively target this organism. The artificial activation of toxins by peptide inhibitors can lead to the growth arrest and eventual death of bacterial cells. Optimizing candidate peptides by hydrocarbon α-helix stapling based on structural information from the VapBC TA system and in vitro systematic validation led to V26-SP-8, a VapC26 activator of M. tuberculosis. This compound exhibited highly enhanced activity and cell permeability owing to the stabilizing helical propensity of the peptide. These characteristics will increase its efficacy against multidrug-resistant tuberculosis and extensively drug-resistant tuberculosis. Similar approaches utilizing structural and biochemical information for new antibiotic targets opens a new era for developing TB therapies.
Parallel Evolution of Enhanced Biofilm Formation and Phage-Resistance in Pseudomonas aeruginosa during Adaptation Process in Spatially Heterogeneous Environments
Authors: Yamamoto Kyosuke , Kusada Hiroyuki , Kamagata Yoichi , Tamaki Hideyuki
Published: March 2021

An opportunistic pathogen Pseudomonas aeruginosa has a versatile phenotype and high evolutionary potential to adapt to various natural habitats. As the organism normally lives in spatially heterogeneous and polymicrobial environments from open fields to the inside of hosts, adaptation to abiotic (spatial heterogeneity) and biotic factors (interspecies interactions) is a key process to proliferate. However, our knowledge about the adaptation process of P. aeruginosa in spatially heterogeneous environments associated with other species is limited. We show herein that the evolutionary dynamics of P. aeruginosa PAO1 in spatially heterogeneous environments with Staphylococcus aureus known to coexist in vivo is dictated by two distinct core evolutionary trajectories: (i) the increase of biofilm formation and (ii) the resistance to infection by a filamentous phage which is retained in the PAO1 genome. Hyperbiofilm and/or pili-deficient phage-resistant variants were frequently selected in the laboratory evolution experiment, indicating that these are key adaptive traits under spatially structured conditions. On the other hand, the presence of S. aureus had only a marginal effect on the emergence and maintenance of these variants. These results show key adaptive traits of P. aeruginosa and indicate the strong selection pressure conferred by spatial heterogeneity, which might overwhelm the effect of interspecies interactions.
Role of Leishmania infantum in Meningoencephalitis of Unknown Origin in Dogs from a Canine Leishmaniosis Endemic Area
Authors: Portero Miriam , Miró Guadalupe , Checa Rocío , Martínez de Merlo Elena , Fragío Cristina , Benito Miguel , Sainz Ángel , Pérez Carmen
Published: March 2021

The main hypothesis for the aetiology of meningoencephalitis of unknown origin (MUO) in dogs is an autoimmune or genetic cause that is associated with a triggering event (environmental factors/infectious agents). The aim of this ambispective cohort study was to test for Leishmania infantum infection in the blood and cerebrospinal fluid (CSF) of dogs with MUO in an endemic area of canine leishmaniosis. Dogs with MUO were selected amongst all dogs undergoing blood anti-L. infantum antibody testing (control group). The blood plasma or serum samples from all dogs were analysed for anti- L. infantum antibodies by a quantitative indirect fluorescent assay (IFAT). In dogs with MUO, CSF samples were obtained for analysed by PCR detection of L. infantum DNA. Forty-four percent and 22% of the dogs in the MUO group featured magnetic resonance imaging (MRI) findings and CSF cytology respectively, consistent with L. infantum infection. IFAT, PCR, and histological findings were negative for L. infantum. A significant difference in L. infantum infection prevalence was found between the control and MUO group (p = 0.0022). While it seems unlikely that L. infantum plays a role in the aetiology of MUO, in endemic areas, this pathogen should be included in the differential diagnosis of this neurological disorder.
Application of SEM Imaging and MLA Mapping Method as a Tool for Wettability Restoration in Reservoir Core Samples for SCAL Experiments
Authors: Sripal Edison , Grant David , James Lesley
Published: March 2021

In reservoir engineering, special core analysis experiments (SCAL) are performed in the lab to evaluate the production capabilities of an oil reservoir. A critical component of SCAL experiments is core wettability restoration to its original wettability, i.e., oil wet condition. Typically, aging is performed by saturating the core with oil and aging at reservoir temperature where time is the variable in question dictating whether the resulting restored core is strongly or weakly oil-wet. In the lab, core wettability is often experimentally validated using contact angle measurements or USBM (United States Bureau of Mines) wettability tests, which are often time consuming, expensive and prone to error. In this study we developed a novel method by using Scanning Electron Microscope (SEM) and mineral liberation analysis (MLA) imaging (at low vacuum conditions) to determine the wettability of rocks saturated with reservoir fluids such as oil and brine. For this work a systematic approach was applied with comparing the SEM-MLA method against conventional methods to quantify the degree of uncertainty linked to a) wettability estimation and b) the aging time. We have used a comprehensive suite of core samples such as Berea, Silurian Dolomite and Chalk to represent the bulk of oil reservoirs in the world.
Identification and Sequence Analysis of a Novel Ilarvirus Infecting Sweet Cherry
Authors: Orfanidou Chrysoula G. , Xing Fei , Zhou Jun , Li Shifang , Katis Nikolaos I. , Maliogka Varvara I.
Published: March 2021

In the present study, we utilized high throughput and Sanger sequencing to determine the complete nucleotide sequence of a putative new ilarvirus species infecting sweet cherry, tentatively named prunus virus I (PrVI). The genome of PrVI is comprised of three RNA segments of 3474 nt (RNA1), 2911 nt (RNA2), and 2231 nt (RNA3) and features conserved motifs representative of the genus Ilarvirus. BlastN analysis revealed 68.1–71.9% nt identity of PrVI with strawberry necrotic shock virus (SNSV). In subsequent phylogenetic analysis, PrVI was grouped together with SNSV and blackberry chlorotic ringspot virus (BCRV), both members of subgroup 1 of ilarviruses. In addition, mini-scale surveys in stone fruit orchards revealed the presence of PrVI in a limited number of sweet cherries and in one peach tree. Overall, our data suggest that PrVI is a novel species of the genus Ilarvirus and it consists the fifth member of the genus that is currently known to infect Prunus spp.