bluuebunny/crossref_metadata_2025 huggingface dataset:
Possibility of a Solution of the Sustainability of Transport and Mobility with the Application of Discrete Computer Simulation—A Case Study
Authors: Mikušová Nikoleta , Fedorko Gabriel , Molnár Vieroslav , Hlatká Martina , Kampf Rudolf , Sirková Veronika
Published: September 2021

The paper is focused on an example of a solution for the sustainability of transport and mobility with the application of discrete computer simulation. The obtained results from the realized simulation were complemented with the selected multi-criteria decision-making method, namely the analytic hierarchy process (AHP) method. The paper describes the use of the simulation model for obtaining characteristics of alternative solutions that were designed for the needs of transport sustainability. The aim is to address the problem of traffic congestion in urban agglomerations. The simulation model serves as a means to provide information for the needs of their analysis by multi-criteria evaluation by the AHP. The methodology is based on a combination of computer simulation and multi-criteria decision-making and presents a useful tool that can be used in the field of transport sustainability. The paper notes methods to implement analysis of alternative solutions in transport. However, this procedure can also be used to solve other problems in the field of logistics systems. The paper compares five possible solutions for the organization of transport at intersections. Multi-criteria decision-making was realized based on 12 criteria. The result was the solution that reduced the length of congestion in almost all directions, with a maximum shortening of 69 m and a shortening of the average delay by 26 s compared to the current state.
Innovative Design Concept of Cooling Water Tanks/Basins in Geothermal Power Plants Using Ultra-High-Performance Fiber-Reinforced Concrete with Enhanced Durability
Authors: Al-Obaidi Salam , Bamonte Patrick , Animato Francesco , Lo Monte Francesco , Mazzantini Iacopo , Luchini Massimo , Scalari Sandra , Ferrara Liberato
Published: September 2021

The structure presented in this paper is intended to be used as a prototype reservoir for collecting water coming from the cooling tower of a geothermal plant, and is primarily designed to compare the performance of different materials (traditional reinforced concrete and Ultra-High-Performance Fiber-Reinforced Concrete (UHPFRC)) as well to assess the performance of different structural solutions (wall with constant thickness versus wall provided with stiffening buttresses). In the absence of specific code provisions, given the novelty of the UHPFRC used, the main properties used for the design were determined through a dedicated experimental campaign (tensile/flexural properties and shrinkage). The main focus of the design was on the Serviceability Limit States, more specifically the requirements regarding water tightness. Given the rather simple structural layout, especially in the compartments where no stiffening buttresses are present, linear elastic analysis was used to determine the internal actions. The nonlinear behavior ensuing from the peculiar tensile constitutive response of the material was taken into account locally, in order to determine the stress level, the depth of the compression zone and the crack width. The performance was finally compared with the reference compartment (made with ordinary reinforced concrete), through on-site observations and measurements.
Categorical Nonstandard Analysis
Authors: Saigo Hayato , Nohmi Juzo
Published: September 2021

In the present paper, we propose a new axiomatic approach to nonstandard analysis and its application to the general theory of spatial structures in terms of category theory. Our framework is based on the idea of internal set theory, while we make use of an endofunctor U on a topos of sets S together with a natural transformation υ, instead of the terms as “standard”, “internal”, or “external”. Moreover, we propose a general notion of a space called U-space, and the category USpace whose objects are U-spaces and morphisms are functions called U-spatial morphisms. The category USpace, which is shown to be Cartesian closed, gives a unified viewpoint toward topological and coarse geometric structure. It will also be useful to further study symmetries/asymmetries of the systems with infinite degrees of freedom, such as quantum fields.
Parallel Locally Strictly Convex Surfaces in Four-Dimensional Affine Space Contained in Hyperquadrics
Authors: Witowicz Paweł
Published: September 2021

Locally strictly convex surfaces in four-dimensional affine space are studied from a perspective of the affine structure invented by Nuño-Ballesteros and Sánchez, which is especially suitable in convex geometry. The surfaces that are embedded in locally strictly convex hyperquadrics are classified under assumptions that the second fundamental form is parallel with respect to the induced connection and the normal connection is compatible with a metric on the transversal bundle. Both connections are induced by a canonical transversal plane bundle, which is defined by certain symmetry conditions. The obtained surfaces are always products of an ellipse and a conical planar curve.
Existence Theory for Positive Iterative Solutions to a Type of Boundary Value Problem
Authors: Sun Bo
Published: September 2021

We introduce some research results on a type of third-order boundary value problem for positive iterative solutions. The existence of solutions to these problems was proved using the monotone iterative technique. As an examination of the proposed method, an example to illustrate the effectiveness of our results was presented.
A Weight Assignment Algorithm for Incomplete Traffic Information Road Based on Fuzzy Random Forest Method
Authors: Wang Longhao , Wu Jing , Li Rui , Song Yanjiao , Zhou Jiayue , Rui Xiaoping , Xu Hanwei
Published: September 2021

One of the keys in time-dependent routing is determining the weight for each road network link based on symmetrical and complete traffic information. To facilitate travel planning considering traffic situations based on historical global position system (GPS) trajectory data which uncover the whole road network, this paper proposes a fuzzy random forest-based road section data estimation method, which uses the third law of geography as the core idea. For different time periods, road grade, tidal lane, proximity to infrastructure (main places that affect traffic, such as schools, hospitals), and accident road sections were selected as indicators that influence the traffic. The random forest algorithm is used to build the mapping relationship between attribute data with average traffic which is obtained based on GPS data. Subsequently, the fuzzy reasoning method is used to obtain the weight of road links missing traffic information by calculating their similarities with typical road section samples. Using the road network of Suzhou City as an example, the proposed method was used to analyze estimate the average driving speeds of road sections with missing traffic information for different time periods. Experimental results show that this method can effectively avoid congested road sections and obtain high-speed travel routes.
On PID Design Constraints in Relation to Control of Strictly Metzler Linear MIMO Systems
Authors: Krokavec Dušan , Filasová Anna
Published: September 2021

For time-invariant Metzler linear MIMO systems, this paper proposes an original approach reflecting necessary matching conditions, specifically structural system constraints and necessary positiveness in solving the problem of MIMO PID control. Covering the matching conditions by the supporting structure of measurement, refining the controller and system parameter constraints and introducing enhanced equivalent system descriptions, the reformulated design task is consistent with PID control law parameter representation and is formulated as a linear matrix inequality feasibility problem. Characterization of the PID control law parameters is permitted to highlight dynamical properties of the closed-loop system and the structural influence of the control derivative gain value in the design step. For the first time, the paper comprehensively sets the synthesis standard for PID control of MIMO Metzler systems because others for the given task have not been created at present.
On Some New Trapezoidal Type Inequalities for Twice (p, q) Differentiable Convex Functions in Post-Quantum Calculus
Authors: Sitthiwirattham Thanin , Murtaza Ghulam , Ali Muhammad Aamir , Ntouyas Sotiris K. , Adeel Muhammad , Soontharanon Jarunee
Published: September 2021

Quantum information theory, an interdisciplinary field that includes computer science, information theory, philosophy, cryptography, and symmetry, has various applications for quantum calculus. Inequalities has a strong association with convex and symmetric convex functions. In this study, first we establish a p,q-integral identity involving the second p,q-derivative and then we used this result to prove some new trapezoidal type inequalities for twice p,q-differentiable convex functions. It is also shown that the newly established results are the refinements of some existing results in the field of integral inequalities. Analytic inequalities of this nature and especially the techniques involved have applications in various areas in which symmetry plays a prominent role.
λ-Interval of Triple Positive Solutions for the Perturbed Gelfand Problem
Authors: Kang Shugui , Lu Youmin , Feng Wenying
Published: September 2021

We study a two-point Boundary Value Problem depending on two parameters that represents a mathematical model arising from the combustion theory. Applying fixed point theorems for concave operators, we prove uniqueness, existence, upper, and lower bounds of positive solutions. In addition, we give an estimation for the value of λ* such that, for the parameter λ∈[λ*,λ*], there exist exactly three positive solutions. Numerical examples are presented to illustrate various cases. The results complement previous work on this problem.
Modelling the Enablers for Branded Content as a Strategic Marketing Tool in the COVID-19 Era
Authors: Sindhu Shilpa , Mor Rahul S
Published: September 2021

This study aims towards identifying and modelling the significant factors which act as enablers for the branded content to be used strategically by marketers as a marketing tool in the COVID-19 era. A qualitative approach was adopted for this study, and significant factors associated with branded content were identified from the literature review and primary survey. The factors were then verified by the experts in the area of branding and digital marketing. Total interpretive structural modelling (TISM) and Decision-making Trial and Evaluation Laboratory (DEMATEL) techniques were used to model the factors as per their contextual relationships. As per the model outcomes from TISM and DEMATEL approaches, branded content is an efficient marketing tool that promises value delivery to stakeholders. This, in turn, depends on the authenticity and transparency in content development and distribution. The most significant driving enablers for the system suggest efficient measurement and evaluation strategies and the customer as co-creator for the branded content.
N-Acetylcysteine Inhibits Patulin-Induced Apoptosis by Affecting ROS-Mediated Oxidative Damage Pathway
Authors: Liu Jiayu , Liu Qi , Han Jiahui , Feng Jiayu , Guo Tianmin , Li Zhiman , Min Fenyi , Jin Ruyi , Peng Xiaoli
Published: September 2021

Patulin (PAT) belongs to the family of food-borne mycotoxins. Our previous studies revealed that PAT caused cytotoxicity in human embryonic kidney cells (HEK293). In the present research, we systematically explored the detailed mechanism of ROS production and ROS clearance in PAT-induced HEK293 cell apoptosis. Results showed that PAT treatment (2.5, 5, 7.5, 10 μM) for 10 h could regulate the expression of genes and proteins involved in the mitochondrial respiratory chain complex, resulting in dysfunction of mitochondrial oxidative phosphorylation and induction of ROS overproduction. We further investigated the role of N-acetylcysteine (NAC), an ROS scavenger, in promoting the survival of PAT-treated HEK293 cells. NAC improves PAT-induced apoptosis of HEK293 cells by clearing excess ROS, modulating the expression of mitochondrial respiratory chain complex genes and proteins, and maintaining normal mitochondrial function. In addition, NAC protects the activity of antioxidant enzymes, maintains normal GSH content, and relieves oxidative damage. Additionally, 4 mM NAC alleviated 7.5 μM PAT-mediated apoptosis through the caspase pathway in HEK293 cells. In summary, our study demonstrated that ROS is significant in PAT-mediated cytotoxicity, which provides valuable insight into the management of PAT-associated health issues.
Efficient Degradation of Zearalenone by Dye-Decolorizing Peroxidase from Streptomyces thermocarboxydus Combining Catalytic Properties of Manganese Peroxidase and Laccase
Authors: Qin Xing , Xin Yanzhe , Su Xiaoyun , Wang Xiaolu , Wang Yaru , Zhang Jie , Tu Tao , Yao Bin , Luo Huiying , Huang Huoqing
Published: September 2021

Ligninolytic enzymes, including laccase, manganese peroxidase, and dye-decolorizing peroxidase (DyP), have attracted much attention in the degradation of mycotoxins. Among these enzymes, the possible degradation pathway of mycotoxins catalyzed by DyP is not yet clear. Herein, a DyP-encoding gene, StDyP, from Streptomyces thermocarboxydus 41291 was identified, cloned, and expressed in Escherichia coli BL21/pG-Tf2. The recombinant StDyP was capable of catalyzing the oxidation of the peroxidase substrate 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid), phenolic lignin compounds 2,6-dimethylphenol, and guaiacol, non-phenolic lignin compound veratryl alcohol, Mn2+, as well as anthraquinone dye reactive blue 19. Moreover, StDyP was able to slightly degrade zearalenone (ZEN). Most importantly, we found that StDyP combined the catalytic properties of manganese peroxidase and laccase, and could significantly accelerate the enzymatic degradation of ZEN in the presence of their corresponding substrates Mn2+ and 1-hydroxybenzotriazole. Furthermore, the biological toxicities of the main degradation products 15-OH-ZEN and 13-OH-ZEN-quinone might be remarkably removed. These findings suggested that DyP might be a promising candidate for the efficient degradation of mycotoxins in food and feed.
BmK86-P1, a New Degradation Peptide with Desirable Thermostability and Kv1.2 Channel-Specific Activity from Traditional Chinese Scorpion Medicinal Material
Authors: Qin Chenhu , Yang Xuhua , Zuo Zheng , Yang Liuting , Yang Fan , Cao Zhijian , Chen Zongyun , Wu Yingliang
Published: September 2021

Thermally processed Buthus martensii Karsch scorpions are a traditional Chinese medical material for treating various diseases. However, their pharmacological foundation remains unclear. Here, a new degraded peptide of scorpion toxin was identified in Chinese scorpion medicinal material by proteomics. It was named BmK86-P1 and has six conserved cysteine residues. Homology modeling and circular dichroism spectra experiments revealed that BmK86-P1 not only contained representative disulfide bond-stabilized α-helical and β-sheet motifs but also showed remarkable stability at test temperatures from 20–95 °C. Electrophysiology experiments indicated that BmK86-P1 was a highly potent and selective inhibitor of the hKv1.2 channel with IC50 values of 28.5 ± 6.3 nM. Structural and functional dissection revealed that two residues of BmK86-P1 (i.e., Lys19 and Ile21) were the key residues that interacted with the hKv1.2 channel. In addition, channel chimeras and mutagenesis experiments revealed that three amino acids (i.e., Gln357, Val381 and Thr383) of the hKv1.2 channel were responsible for BmK86-P1 selectivity. This research uncovered a new bioactive peptide from traditional Chinese scorpion medicinal material that has desirable thermostability and Kv1.2 channel-specific activity, which strongly suggests that thermally processed scorpions are novel peptide resources for new drug discovery for the Kv1.2 channel-related ataxia and epilepsy diseases.
Modification Strategy of D-leucine Residue Addition on a Novel Peptide from Odorrana schmackeri, with Enhanced Bioactivity and In Vivo Efficacy
Authors: Yao Aifang , Ma Yingxue , Chen Xiaoling , Zhou Mei , Xi Xinping , Ma Chengbang , Ren Shen , Chen Tianbao , Shaw Chris , Wang Lei
Published: September 2021

Brevinins are a well-characterised, frog-skin-derived, antimicrobial peptide (AMP) family, but their applications are limited by high cytotoxicity. In this study, a wild-type des-Leu2 brevinin peptide, named brevinin-1OS (B1OS), was identified from Odorrana schmackeri. To explore the significant role of the leucine residue at the second position, two variants, B1OS-L and B1OS-D-L, were designed by adding L-leucine and D-leucine residues at this site, respectively. The antibacterial and anticancer activities of B1OS-L and B1OS-D-L were around ten times stronger than the parent peptide. The activity of B1OS against the growth of Gram-positive bacteria was markedly enhanced after modification. Moreover, the leucine-modified products exerted in vivo therapeutic potential in an methicillin-resistant Staphylococcus aureus (MRSA)-infected waxworm model. Notably, the single substitution of D-leucine significantly increased the killing speed on lung cancer cells, where no viable H838 cells survived after 2 h of treatment with B1OS-D-L at 10 μM with low cytotoxicity on normal cells. Overall, our study suggested that the conserved leucine residue at the second position from the N-terminus is vital for optimising the dual antibacterial and anticancer activities of B1OS and proposed B1OS-D-L as an appealing therapeutic candidate for development.
Evaluation of Signaling Pathways Profiling in Human Dermal Endothelial Cells Treated by Snake Venom Cysteine-Rich Secretory Proteins (svCRiSPs) from North American Snakes Using Reverse Phase Protein Array (RPPA)
Authors: Suntravat Montamas , Sanchez Oscar , Reyes Armando , Cirilo Abcde , Ocheltree Jack S. , Galan Jacob A. , Salazar Emelyn , Davies Peter , Sanchez Elda E.
Published: September 2021

Cysteine-Rich Secretory Proteins (CRiSPs) are typically found in many snake venoms; however, the role that these toxins play in the pathophysiology of snakebites is still unclear. Herein, we compared the effects of snake venom CRiSPs (svCRiSPs) from the most medically important species of North American snakes on endothelial cell permeability and vascular permeability. We used reverse phase protein array (RPPA) to identify key signaling molecules on human dermal lymphatic (HDLECs) and blood (HDBECs) endothelial cells treated with svCRiSPs. The results showed that Css-CRiSP isolated from Crotalus scutulatus scutulatus and App-CRiSP from Agkistrodon piscivorus piscivorus are the most potent causes of increase vascular and endothelial permeability in comparison with other svCRiSPs used in this study. We examined the protein expression levels and their activated phosphorylation states in HDLECs and HDBECs induced by App-CRiSP and Css-CRiSP using RPPA. Interestingly, both App-CRiSP and Css-CRiSP induced caveolin-1 expression in HDBECs. We also found that stimulating HDBECs with Css-CRiSP and App-CRiSP significantly induced the phosphorylation of mTOR and Src, respectively. In HDLECs, Css-CRiSP significantly downregulated the expression of N-Cadherin and phospholipase C-gamma, while App-CRiSP significantly enhanced Akt and JNK phosphorylation. These results suggest that the increased endothelial permeability in HDLECs and HDBECs by Css-CRiSP and App-CRiSP may occur through different pathways.
Macroscopic Limit of Quantum Systems
Authors: Polonyi Janos
Published: September 2021

Classical physics is approached from quantum mechanics in the macroscopic limit. The technical device to achieve this goal is the quantum version of the central limit theorem, derived for an observable at a given time and for the time-dependent expectation value of the coordinate. The emergence of the classical trajectory can be followed for the average of an observable over a large set of independent microscopical systems, and the deterministic classical laws can be recovered in all practical purposes, owing to the largeness of Avogadro’s number. This result refers to the observed system without considering the measuring apparatus. The emergence of a classical trajectory is followed qualitatively in Wilson’s cloud chamber.
FLRW Cosmological Models with Dynamic Cosmological Term in Modified Gravity
Authors: Tiwari Rishi Kumar , Beesham Aroonkumar , Shukla Bhupendra Kumar
Published: September 2021

Although the standard lambda cold dark matter cosmological model is quite successful in describing the universe, there are still several issues that are still not resolved. Some of these are the cosmological constant problem, certain anomalies in the cosmic microwave background radiation and whether general relativity is valid on large scales. Therefore, it is interesting to examine modified theories in an attempt to solve these problems, and to examine the entire range of possibilities that are allowed. In this work, we examine one of these modified theories, viz., f(R,T) gravity. We study the homogeneous and isotropic models in this theory, which have some pleasing features, such as no initial singularity, a dynamic cosmological term, and a transition from early deceleration to late-time acceleration as intimated by observations. The physical parameters of the model, as well as the energy conditions, are discussed and a viable cosmological model can be constructed.
New Anisotropic Exact Solution in Multifield Cosmology
Authors: Paliathanasis Andronikos
Published: September 2021

In the case of two-scalar field cosmology, and specifically for the Chiral model, we determine an exact solution for the field equations with an anisotropic background space. The exact solution can describe anisotropic inflation with a Kantowski–Sachs geometry and can be seen as the anisotropic analogue of the hyperbolic inflation. Finally, we investigate the stability conditions for the exact solution.
The Hunt for Pevatrons: The Case of Supernova Remnants
Authors: Cristofari Pierre
Published: September 2021

The search for Galactic pevatrons is now a well-identified key science project of all instruments operating in the very-high-energy domain. Indeed, in this energy range, the detection of gamma rays clearly indicates that efficient particle acceleration is taking place, and observations can thus help identify which astrophysical sources can energize particles up to the ~PeV range, thus being pevatrons. In the search for the origin of Galactic cosmic rays (CRs), the PeV range is an important milestone, since the sources of Galactic CRs are expected to accelerate PeV particles. This is how the central scientific goal that is ’solving the mystery of the origin of CRs’ has often been distorted into ’finding (a) pevatron(s)’. Since supernova remnants (SNRs) are often cited as the most likely candidates for the origin of CRs, ’finding (a) pevatron(s)’ has often become ’confirming that SNRs are pevatrons’. Pleasingly, the first detection(s) of pevatron(s) were not associated to SNRs. Moreover, all clearly detected SNRs have yet revealed to not be pevatrons, and the detection from VHE gamma rays from regions unassociated with SNRs, are reminding us that other astrophysical sites might well be pevatrons. This short review aims at highlighting a few important results on the search for Galactic pevatrons.
Novel Acinetobacter baumannii Bacteriophage Aristophanes Encoding Structural Polysaccharide Deacetylase
Authors: Timoshina Olga Yu. , Shneider Mikhail M. , Evseev Peter V. , Shchurova Anastasia S. , Shelenkov Andrey A. , Mikhaylova Yulia V. , Sokolova Olga S. , Kasimova Anastasia A. , Arbatsky Nikolay P. , Dmitrenok Andrey S. , Knirel Yuriy A. , Miroshnikov Konstantin A. , Popova Anastasia V.
Published: September 2021

Acinetobacter baumannii appears to be one of the most crucial nosocomial pathogens. A possible component of antimicrobial therapy for infections caused by extremely drug-resistant A. baumannii strains may be specific lytic bacteriophages or phage-derived enzymes. In the present study, we observe the biological features, genomic organization, and phage–host interaction strategy of novel virulent bacteriophage Aristophanes isolated on A. baumannii strain having K26 capsular polysaccharide structure. According to phylogenetic analysis phage Aristophanes can be classified as a representative of a new distinct genus of the subfamily Beijerinckvirinae of the family Autographiviridae. This is the first reported A. baumannii phage carrying tailspike deacetylase, which caused O-acetylation of one of the K26 sugar residues.
Chronic Hepatitis B Treatment Strategies Using Polymerase Inhibitor-Based Combination Therapy
Authors: Ohsaki Eriko , Suwanmanee Yadarat , Ueda Keiji
Published: September 2021

Viral polymerase is an essential enzyme for the amplification of the viral genome and is one of the major targets of antiviral therapies. However, a serious concern to be solved in hepatitis B virus (HBV) infection is the difficulty of eliminating covalently closed circular (ccc) DNA. More recently, therapeutic strategies targeting various stages of the HBV lifecycle have been attempted. Although cccDNA-targeted therapies are attractive, there are still many problems to be overcome, and the development of novel polymerase inhibitors remains an important issue. Interferons and nucleos(t)ide reverse transcriptase inhibitors (NRTIs) are the only therapeutic options currently available for HBV infection. Many studies have reported that the combination of interferons and NRTI causes the loss of hepatitis B surface antigen (HBsAg), which is suggestive of seroconversion. Although NRTIs do not directly target cccDNA, they can strongly reduce the serum viral DNA load and could suppress the recycling step of cccDNA formation, improve liver fibrosis/cirrhosis, and reduce the risk of hepatocellular carcinoma. Here, we review recent studies on combination therapies using polymerase inhibitors and discuss the future directions of therapeutic strategies for HBV infection.
Serological, Molecular and Culture-Based Diagnosis of Lentiviral Infections in Small Ruminants
Authors: Kalogianni Aphrodite I. , Stavropoulos Ioannis , Chaintoutis Serafeim C. , Bossis Ioannis , Gelasakis Athanasios I.
Published: September 2021

Small ruminant lentiviruses (SRLVs) infections lead to chronic diseases and remarkable economic losses undermining health and welfare of animals and the sustainability of farms. Early and definite diagnosis of SRLVs infections is the cornerstone for any control and eradication efforts; however, a “gold standard” test and/or diagnostic protocols with extensive applicability have yet to be developed. The main challenges preventing the development of a universally accepted diagnostic tool with sufficient sensitivity, specificity, and accuracy to be integrated in SRLVs control programs are the genetic variability of SRLVs associated with mutations, recombination, and cross-species transmission and the peculiarities of small ruminants’ humoral immune response regarding late seroconversion, as well as intermittent and epitope-specific antibody production. The objectives of this review paper were to summarize the available serological and molecular assays for the diagnosis of SRLVs, to highlight their diagnostic performance emphasizing on advantages and drawbacks of their application, and to discuss current and future perspectives, challenges, limitations and impacts regarding the development of reliable and efficient tools for the diagnosis of SRLVs infections.
Processing Hundreds of SARS-CoV-2 Samples with an In-House PCR-Based Method without Robotics
Authors: Mair Theresa , Ivankovic Maja , Paar Christian , Salzer Helmut , Heissl Angelika , Lamprecht Bernd , Schreier-Lechner Elisabeth , Tiemann-Boege Irene
Published: September 2021

The SARS-CoV-2 pandemic has required the development of multiple testing systems to monitor and control the viral infection. Here, we developed a PCR test to screen COVID-19 infections that can process up to ~180 samples per day without the requirement of robotics. For this purpose, we implemented the use of multichannel pipettes and plate magnetics for the RNA extraction step and combined the reverse transcription with the qPCR within one step. We tested the performance of two RT-qPCR kits as well as different sampling buffers and showed that samples taken in NaCl or PBS are stable and compatible with different COVID-19 testing systems. Finally, we designed a new internal control based on the human RNase P gene that does not require a DNA digestion step. Our protocol is easy to handle and reaches the sensitivity and accuracy of the standardized diagnostic protocols used in the clinic to detect COVID-19 infections.
African Swine Fever in Wild Boar in Europe—A Review
Authors: Sauter-Louis Carola , Conraths Franz J. , Probst Carolina , Blohm Ulrike , Schulz Katja , Sehl Julia , Fischer Melina , Forth Jan Hendrik , Zani Laura , Depner Klaus , Mettenleiter Thomas C. , Beer Martin , Blome Sandra
Published: September 2021

The introduction of genotype II African swine fever (ASF) virus, presumably from Africa into Georgia in 2007, and its continuous spread through Europe and Asia as a panzootic disease of suids, continues to have a huge socio-economic impact. ASF is characterized by hemorrhagic fever leading to a high case/fatality ratio in pigs. In Europe, wild boar are especially affected. This review summarizes the currently available knowledge on ASF in wild boar in Europe. The current ASF panzootic is characterized by self-sustaining cycles of infection in the wild boar population. Spill-over and spill-back events occur from wild boar to domestic pigs and vice versa. The social structure of wild boar populations and the spatial behavior of the animals, a variety of ASF virus (ASFV) transmission mechanisms and persistence in the environment complicate the modeling of the disease. Control measures focus on the detection and removal of wild boar carcasses, in which ASFV can remain infectious for months. Further measures include the reduction in wild boar density and the limitation of wild boar movements through fences. Using these measures, the Czech Republic and Belgium succeeded in eliminating ASF in their territories, while the disease spread in others. So far, no vaccine is available to protect wild boar or domestic pigs reliably against ASF.
Further Characterization of Rio Grande Virus and Potential for Cross Reactivity with Rift Valley Fever Virus Assays
Authors: Szymczak Mitchell S. , Reeves Will K. , Miller Myrna M.
Published: September 2021

Phleboviruses (genus Phlebovirus, family Phenuiviridae) are emerging pathogens of humans and animals. Sand-fly-transmitted phleboviruses are found in Europe, Africa, the Middle East, and the Americas, and are responsible for febrile illness and nervous system infections in humans. Rio Grande virus (RGV) is the only reported phlebovirus in the United States. Isolated in Texas from southern plains woodrats, RGV is not known to be pathogenic to humans or domestic animals, but serologic evidence suggests that sheep (Ovis aries) and horses (Equus caballus) in this region have been infected. Rift Valley fever virus (RVFV), a phlebovirus of Africa, is an important pathogen of wild and domestic ruminants, and can also infect humans with the potential to cause severe disease. The introduction of RVFV into North America could greatly impact U.S. livestock and human health, and the development of vaccines and countermeasures is a focus of both the CDC and USDA. We investigated the potential for serologic reagents used in RVFV diagnostic assays to also detect cells infected with RGV. Western blots and immunocytochemistry assays were used to compare the antibody detection of RGV, RVFV, and two other New World phlebovirus, Punta Toro virus (South and Central America) and Anhanga virus (Brazil). Antigenic cross-reactions were found using published RVFV diagnostic reagents. These findings will help to inform test interpretation to avoid false positive RVFV diagnoses that could lead to public health concerns and economically costly agriculture regulatory responses, including quarantine and trade restrictions.
Dual Promoters Improve the Rescue of Recombinant Measles Virus in Human Cells
Authors: Chey Soroth , Palmer Juliane Maria , Doerr Laura , Liebert Uwe Gerd
Published: September 2021

Reverse genetics is a technology that allows the production of a virus from its complementary DNA (cDNA). It is a powerful tool for analyzing viral genes, the development of novel vaccines, and gene delivery vectors. The standard reverse genetics protocols are laborious, time-consuming, and inefficient for negative-strand RNA viruses. A new reverse genetics platform was established, which increases the recovery efficiency of the measles virus (MV) in human 293-3-46 cells. The novel features compared with the standard system involving 293-3-46 cells comprise (a) dual promoters containing the RNA polymerase II promoter (CMV) and the bacteriophage T7 promoter placed in uni-direction on the same plasmid to enhance RNA transcription; (b) three G nucleotides added just after the T7 promoter to increase the T7 RNA polymerase activity; and (c) two ribozymes, the hairpin hammerhead ribozyme (HHRz), and the hepatitis delta virus ribozyme (HDVrz), were used to cleavage the exact termini of the antigenome RNA. Full-length antigenome cDNA of MV of the wild type IC323 strain or the vaccine AIK-C strain was inserted into the plasmid backbone. Both virus strains were easily rescued from their respective cloned cDNA. The rescue efficiency increased up to 80% compared with the use of the standard T7 rescue system. We assume that this system might be helpful in the rescue of other human mononegavirales.
Intracellular Life Cycle Kinetics of SARS-CoV-2 Predicted Using Mathematical Modelling
Authors: Grebennikov Dmitry , Kholodareva Ekaterina , Sazonov Igor , Karsonova Antonina , Meyerhans Andreas , Bocharov Gennady
Published: September 2021

SARS-CoV-2 infection represents a global threat to human health. Various approaches were employed to reveal the pathogenetic mechanisms of COVID-19. Mathematical and computational modelling is a powerful tool to describe and analyze the infection dynamics in relation to a plethora of processes contributing to the observed disease phenotypes. In our study here, we formulate and calibrate a deterministic model of the SARS-CoV-2 life cycle. It provides a kinetic description of the major replication stages of SARS-CoV-2. Sensitivity analysis of the net viral progeny with respect to model parameters enables the identification of the life cycle stages that have the strongest impact on viral replication. These three most influential parameters are (i) degradation rate of positive sense vRNAs in cytoplasm (negative effect), (ii) threshold number of non-structural proteins enhancing vRNA transcription (negative effect), and (iii) translation rate of non-structural proteins (positive effect). The results of our analysis could be used for guiding the search for antiviral drug targets to combat SARS-CoV-2 infection.
COVID-19 Vaccine Intention among Rural Residents in Mexico: Validation of a Questionnaire
Authors: Alvarez-Manzo Hector S. , Badillo-Davila Rafael , Olaya-Gomez Alejandro , Gonzalez-de-Cossio-Tello Barbara , Cardoso-Arias Rafael , Gamboa-Balzaretti Emilio S. , Baranzini-Rogel Carlos D. , Garcia-Garnica Gabriel , Hernandez-Corrales Luis E. , Linares-Koloffon Carlos A.
Published: September 2021

The COVID-19 pandemic forced the scientific community and the pharmaceutical industry to develop new vaccines, in an attempt to reach herd immunity and stop the SARS-CoV-2 from spreading. However, to ensure vaccination among the general population, COVID-19 vaccine intention must be measured. So far, no studies have focused on rural residents in Latin America, which represent approximately 20% of the population of this geographical region. In this study, we present the validation of a self-developed questionnaire, which was validated in a pilot study with 40 Spanish-speaking Mexican rural residents in the state of Guerrero, Mexico. In this study, we describe the chronological validation of the questionnaire, including the assessment of its internal consistency and temporal reliability, which we measured with the Cronbach’s alpha and Spearman’s rank correlation coefficient, respectively. After the psychometrical analysis, we were able to validate a 20-item questionnaire, which intends to assess vaccine intention among the rural population. Aiming to develop a comprehensive policy and vaccination strategies, we hope this instrument provides valuable insight regarding COVID-19 vaccination willingness across rural communities in Mexico and Latin America. Finally, if we want to reach worldwide herd immunity, it is important to understand rural residents’ position towards COVID-19 vaccination.
Predictors of Willingness to Receive COVID-19 Vaccine: Cross-Sectional Study of Palestinian Dental Students
Authors: Kateeb Elham , Danadneh Mayar , Pokorná Andrea , Klugarová Jitka , Abdulqader Huthaifa , Klugar Miloslav , Riad Abanoub
Published: September 2021

The overarching aim of this study was to assess the predictors related to the willingness of Palestinian dental students to receive the COVID-19 vaccine when it becomes available. A cross-sectional study was conducted among a universal sample of dental students in the Palestinian territories. Willingness to get the COVID-19 vaccine was related to the following factors: Demographic characteristics, COVID-19-related experiences, beliefs and knowledge about the vaccine, attitudes toward vaccinations in general, and other factors outlined by the WHO SAGE Vaccination Hesitancy Questionnaire. Four hundred and seventeen students completed the questionnaire (response rate = 41.7%). In general, 57.8% (n = 241) were willing to take the COVID-19 vaccine when it became available to them, 27% (n = 114) were hesitant, and 14.9% (n = 62) were not willing to get vaccinated. The final regression model explained 46% of the variation in the willingness to receive the COVID-19 vaccine as follows: Attitudes towards new vaccines (β = 6.23, p < 0.001), believing in a favorable risk–benefit ratio (β = 5.64, p < 0.001), trust in the pharmaceutical industry (β = 5.92, p = 0.001), believing that natural immunity is better than being vaccinated (β = −4.24, p < 0.001), and having enough information about the vaccine (β = 4.12, p < 0.001). Adequate information about vaccines, their risk–benefit ratios, and natural and acquired immunity are important to build trust and favorable attitudes towards vaccines among future dentists.
Interests of the Non-Human Primate Models for HIV Cure Research
Authors: Terrade Gauthier , Huot Nicolas , Petitdemange Caroline , Lazzerini Marie , Orta Resendiz Aurelio , Jacquelin Beatrice , Müller-Trutwin Michaela
Published: September 2021

Non-human primate (NHP) models are important for vaccine development and also contribute to HIV cure research. Although none of the animal models are perfect, NHPs enable the exploration of important questions about tissue viral reservoirs and the development of intervention strategies. In this review, we describe recent advances in the use of these models for HIV cure research and highlight the progress that has been made as well as limitations using these models. The main NHP models used are (i) the macaque, in which simian immunodeficiency virus (SIVmac) infection displays similar replication profiles as to HIV in humans, and (ii) the macaque infected by a recombinant virus (SHIV) consisting of SIVmac expressing the HIV envelope gene serving for studies analyzing the impact of anti-HIV Env broadly neutralizing antibodies. Lessons for HIV cure that can be learned from studying the natural host of SIV are also presented here. An overview of the most promising and less well explored HIV cure strategies tested in NHP models will be given.
An Update on mRNA-Based Viral Vaccines
Authors: Jeeva Subbiah , Kim Ki-Hye , Shin Chong Hyun , Wang Bao-Zhong , Kang Sang-Moo
Published: September 2021

With the success of COVID-19 vaccines, newly created mRNA vaccines against other infectious diseases are beginning to emerge. Here, we review the structural elements required for designing mRNA vaccine constructs for effective in vitro synthetic transcription reactions. The unprecedently speedy development of mRNA vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was enabled with previous innovations in nucleoside modifications during in vitro transcription and lipid nanoparticle delivery materials of mRNA. Recent updates are briefly described in the status of mRNA vaccines against SARS-CoV-2, influenza virus, and other viral pathogens. Unique features of mRNA vaccine platforms and future perspectives are discussed.
Influenza Vaccination Strategies in Healthcare Workers: A Cohort Study (2018–2021) in an Italian University Hospital
Authors: Dettori Marco , Arghittu Antonella , Deiana Giovanna , Azara Antonio , Masia Maria Dolores , Palmieri Alessandra , Spano Antonio Lorenzo , Serra Antonello , Castiglia Paolo
Published: September 2021

Vaccinating healthcare workers (HCWs) is the most effective intervention for preventing nosocomial influenza infection. However, influenza vaccination coverage (VC%) among HCWs remains low. The aim of the study was to analyse the trend of VC% among healthcare workers in an Italian hospital through a three-year vaccination project covering three influenza seasons (2018–2019, 2019–2020, and 2020–2021). A gap analysis was performed at the case base (2018–2019), on-site vaccination was trialled in the 2019–2020 season, and an integrated vaccination offer (on-site vaccination and the classic offer at a vaccination clinic) was implemented for the 2020–2021 season. For each unit of vaccinated HCWs, the following variables were recorded: main demographic details, area of affiliation (medical/surgical/services), and professional category. Logistic regression analyses were performed to assess the relationship between outcome (undergoing vaccination in 2020–2021) and other variables related to the healthcare workers’ characteristics. In the three seasons, VC% values of 13.2%. 27.7%, and 58.9% were recorded, respectively (p < 0.005). The highest VC% was recorded among physicians (94.93%), in the medical area (63.27%), and males (62.59%) and in general among the youngest HCWs. Comparison of the coverage values recorded in the three seasons showed that in the last season considered (2020–2021) about 80% of health workers preferred to be vaccinated in the workplace instead of using the standard vaccination delivery method (invitation to attend the vaccination clinic). Our study suggests that the integrated vaccination offer may lead to an increase in VC% among HCWs compared to the classical offer modalities.
Occurrence of BNT162b2 Vaccine Adverse Reactions Is Associated with Enhanced SARS-CoV-2 IgG Antibody Response
Authors: Rechavi Yoav , Shashar Moshe , Lellouche Jonathan , Yana Moshe , Yakubovich Daniel , Sharon Nechama
Published: September 2021

Promoting SARS-CoV-2 vaccination has been a global mission since the first vaccines were approved for emergency use. Alongside the excitement following the possibility of eradicating SARS-CoV-2 and ending the COVID-19 pandemic, there has been ample vaccine hesitancy, some due to the abundant reporting of adverse reactions. We report here that the occurrence of BNT162b2 vaccine adverse reactions is associated with enhanced antibody response. We found a statistically significant correlation between having an adverse reaction, whether local or systemic, and higher antibody levels. No sex difference was observed in antibody levels. However, as was recently reported, the antibody response was found to be lower among older vaccinees. The demonstration of a clear correlation between adverse reactions and antibody levels may help reduce vaccination hesitancy by reassuring that the presence of such reactions is an indication of a well-functioning immune system.
Social Learning: Methods Matter but Facilitation and Supportive Context Are Key—Insights from Water Governance in Sweden
Authors: Prutzer Madeleine , Morf Andrea , Nolbrant Peter
Published: September 2021

This paper analyses and discusses how and to what extent social learning (SL), as a means to address complex adaptive problems in water governance, can be enabled in local and regional multi-stakeholder collaborations. Using a multi-method, qualitative, collaborative, and self-reflective case study design, the conditions, challenges, and enablers for SL were studied, comparing three complementary cases of voluntary multi-actor platforms (water councils) to improve water quality in West Sweden. These councils were established to foster the implementation of the Water Frame Directive and—on a voluntary basis without a formal decision mandate or responsibility—to implement measures or act. Using participant observation, evaluation workshops, and a survey, the methods employed by the councils, which were founded on trust-based approaches, were assessed based on how they contributed to trust and social learning. Observed outcomes included an increased number of participants, sub-projects, local water groups, and measures. Respondents mentioned better dialogue, higher commitment, and broader knowledge as positive outcomes. Based on this, we conclude that there is a need for neutral spaces for meetings led by process facilitators, enabling cross-sectorial and cross-level exchanges, a process which is not common in Swedish water management.
Application of Internal Carbon Source from Sewage Sludge: A Vital Measure to Improve Nitrogen Removal Efficiency of Low C/N Wastewater
Authors: Wang Huacai , Jiang Cancan , Wang Xu , Xu Shengjun , Zhuang Xuliang
Published: September 2021

Biological nitrogen removal from wastewater is widely used all over the world on account of high efficiency and relatively low cost. However, nitrogen removal efficiency is not optimized when the organic matter has inadequate effect for the lack of a sufficient carbon source in influent. Although addition of an external carbon source (e.g., methanol and acetic acid) could solve the insufficient carbon source problem, it raises the operating cost of wastewater treatment plants (WWTPs). On the other hand, large amounts of sludge are produced during biological sewage treatment, which contain high concentrations of organic matter. This paper reviews the emerging technologies to obtain an internal organic carbon resource from sewage sludge and their application on improving nitrogen removal of low carbon/nitrogen wastewater of WWTPs. These are methods that could solve the insufficient carbon problem and excess sludge crisis simultaneously. The recovery of nitrogen and phosphorus from treated sludge before recycling as an internal carbon source should also be emphasized, and the energy and time consumed to treat sludge should be reduced in practical application.