bluuebunny/crossref_metadata_2025 huggingface dataset:
Teleworking and Online Shopping: Socio-Economic Factors Affecting Their Impact on Transport Demand
Authors: López Soler Juan , Christidis Panayotis , Vassallo José
Published: June 2021

Teleworking and online shopping became commonplace during the COVID-19 pandemic and can be expected to maintain a strong presence in the foreseeable future. They can lead to significant changes in mobility patterns and transport demand. It is still unclear, however, how extensive their adoption can be, since each individual has different preferences or constraints. The overall impact on transport depends on which segments of the population will modify their behaviour and on what the substitutes to the current patterns will be. The purpose of this work is to identify the user profiles and spatial aspects that affect the adoption of teleworking and online shopping, and to explore the potential impact on transport demand. To that end, data from an EU-wide survey on mobility were analysed using a Machine Learning methodology. The results suggest that while the take up of the new work and consumption patterns is high on average, there are significant differences among countries and across different socio-economic profiles. Teleworking appears to have a high potential mainly in certain services sectors, affecting commuting patterns predominantly in large urban areas. Online shopping activity is more uniform across the population, although differences among countries and age groups may still be relevant. The findings of this work can be useful for the analysis of policies to encourage the uptake of new technologies in transport and mobility. They can be also a good reference point for future studies on the ex-post analysis of the impacts of the pandemic on mobility.
Implementing Cancer Care in Rwanda: Capacity Building for Treatment and Scale-Up
Authors: Park Paul H. , Shyirambere Cyprien , Kateera Fred , Gupta Neil , Rusangwa Christian , Mukherjee Joia , Coutinho Alex , Lehmann Leslie , Buswell Lori , Shulman Lawrence N. , Mubiligi Joel M. , Uwinkindi Francois , Hirschhorn Lisa R.
Published: June 2021

Background: The majority of countries in sub-Saharan Africa are ill-prepared to address the rising burden of cancer. While some have been able to establish a single cancer referral center, few have been able to scale-up services nationally towards universal health coverage. The literature lacks a step-wise implementation approach for resource-limited countries to move beyond a single-facility implementation strategy and implement a national cancer strategy to expand effective coverage. Methods: We applied an implementation science framework, which describes a four-phase approach: Exploration, Preparation, Implementation, and Sustainment (EPIS). Through this framework, we describe Rwanda’s approach to establish not just a single cancer center, but a national cancer program. Results: By applying EPIS to Rwanda’s implementation approach, we analyzed and identified the implementation strategies and factors, which informed processes of each phase to establish foundational cancer delivery components, including trained staff, diagnostic technology, essential medicines, and medical informatics. These cancer delivery components allowed for the implementation of Rwanda’s first cancer center, while simultaneously serving as the nidus for capacity building of foundational components for future cancer centers. Conclusion: This “progressive scaling” approach ensured that initial investments in the country’s first cancer center was a step toward establishing future cancer centers in the country.
Examining Cross-Border Cultural Tourism as an Indicator of Territorial Integration across the Slovak–Hungarian Border
Authors: Hardi Tamás , Kupi Marcell , Ocskay Gyula , Szemerédi Eszter
Published: June 2021

There are numerous examples of cross-border regions in Europe, which are regions not properly demarcated by national borders. One of the main driving forces of the European Union is to turn the dividing borders into connecting borders by strengthening the cohesion between states and regions, thus, encouraging regions to remedy the existing ethnic and cultural fragmentation by increasing the intensity and number of cross-border contacts. Our research focuses on proving that, in symbolic places, such as the cross-border area of Komárom and Komárno, the cultural values, monuments, and heritage sites are the strongest attraction factors for nationality-based cultural tourism. To support our hypothesis, we conducted an empirical survey within the framework of the H2020 SPOT (Social and Innovative Platform on Cultural Tourism and its potential towards deepening Europeanisation) in the cross-border region of Komárom and Komárno. The evaluation concentrated on four aspects of cultural tourism: the nature of cultural tourism in the area, the resident and visitor perceptions of the cultural tourism offerings, opportunities to increase cross-border collaboration, and options to improve the cultural tourism offerings of the area. Our results show that, although there is a great potential in the cross-border tourist destination of Komárom–Komárno, the integration of the (once united) two towns is advancing very slowly, which can be witnessed in the weaknesses of tourism integration as well.
“A Very Noble Crop”: Financial Stability, Agronomic Expertise, and Personal Values Support Conservation in Shade-Grown Coffee Farms
Authors: Richards Jeannine H. , Torrez Luna Ingrid M. , Vargas Alberto
Published: June 2021

Shade-grown coffee is an important reservoir for tropical biodiversity, but habitat quality hinges on decisions made by farmers. Our research aims to investigate the link between coffee producers’ decisions and outcomes for biodiversity, using epiphytes as our focal group. Using qualitative methods, we interviewed 33 producers in northern Nicaragua to understand how they connect trees and epiphytes on their farms to ecosystem services and how personal values, access to agronomic expertise, labor supply, and financial stability influence decision-making. We used interview responses to construct six producer typologies. Most producers had strong positive attitudes toward trees and associated them with a variety of important ecosystem services. Smallholders were more likely to connect trees with provisioning services, while producers on larger farms and with greater agronomic knowledge emphasized regulating services. Most producers connected epiphytes primarily with aesthetic values. Across demographics, producers emphasized the restorative potential for shade coffee in repairing damage to soil, water, and nutrient cycles caused by other forms of agriculture. The conservation significance and sustainability of this social-ecological system can be maintained and expanded through economic and capacity-building conservation interventions, especially when those can be connected to values already held by farmers.
Syrian Refugees’ Integration Policies in Jordanian Labor Market
Authors: AlShwawra Ahmad
Published: June 2021

The Government of Jordan declared that there are more than one million Syrian refugees in Jordan while UNHCR statistics show that the number is about 700,000. Nonetheless, it is still a large problem for Jordan, especially since there is no real solution that seems to be looming on the horizon for the Syrian crisis. Consequently, that means that those refugees’ stay in Jordan is indefinite. This fact requires Jordan to work towards solutions to avoid the warehousing of those refugees in camps and to integrate them in Jordanian community to ease their stay in Jordan. To achieve that integration, Jordan must facilitate the Syrians’ access to the Jordanian labor market so they can achieve self-reliance. In February 2016, donors gathered in London for the ‘Supporting Syria and the Region’ conference, known as the London Conference, to mobilize funding for the needs of the people affected by the Syrian crisis. In that conference, Jordan pledged to facilitate Syrian refugees’ access to the labor market. This paper will study the process of Syrian integration in Jordanian society by discussing the policies and the procedures that Jordan has developed to facilitate the Syrians’ access to the labor market. The event study method combined with interviews and desk research were used to evaluate the new policies and procedures developed to facilitate this access. It was found that Jordan succeeded in creating a legal and procedural environment that facilitates Syrians’ access to formal jobs, and the Syrians went a long way toward integration in Jordan. Nonetheless, they are still not fully integrated.
Outflow FDI and Domestic Investment: Aggregated and Disaggregated Analysis
Authors: Ameer Waqar , Xu Helian , Sohag Kazi , Shah Syed Hasanat
Published: June 2021

Recently, the Gulf Cooperation Council (GCC) member countries increased their foreign investment outflows (OFDI), underpinning domestic investment (DCF) and diversifying their economies to reduce the reliance on hydrocarbon economies and augmenting green investments. Thus, our research study examines the effects of OFDI on aggregate capital formation and the decomposing effects of capital formation in to private as well as public investment by applying the common correlation effects (CS-ARDL) panel data methodology in the GCC countries. Our empirical result findings show that OFDI do not significantly spur domestic investment in the GCC countries. However, our disaggregated analysis shows that OFDI significantly contributes to private capital formation only while its contribution to public capital formation remains inconclusive. The extensive public involvement in the economies causes a crowding-out effect, eventually impedes the economic diversification, competitiveness and green activities. Our empirical evidence provides a few policy implications.
The Web-GIS TRIG Eau Platform to Assess Urban Flood Mitigation by Domestic Rainwater Harvesting Systems in Two Residential Settlements in Italy
Authors: Palla Anna , Gnecco Ilaria
Published: June 2021

Urban flooding has become one of the most frequent natural disasters in recent years, and the low-impact development (LID) approach is currently recognised as an alternative to traditional grey infrastructure to mitigate the negative impact of urbanisation on hydrological processes. The main objective of the present research was to develop a web-GIS platform in order to assess the impact of LID systems on mitigating urban flooding and to support their implementation at the urban catchment scale. The TRIG Eau platform, developed in the framework of the homonymous INTERREG MARITTIMO IT-FR project, is configured as a web-GIS application of the stormwater management model (SWMM). Urban flood conditions were examined for two case studies in Liguria and Tuscany (IT), where DRWH systems are proposed as a mitigation strategy. The presented results and their visualisation showcase the potential of the TRIG Eau platform to better support the implementation of LIDs. Findings from the flood analysis confirm that even for the 10-year return period event, DRWHs are effective in reducing network stress by more than 70% in cases of empty tanks, thus underlining the need for RTC technology to pre-empty the system.
Price and Income Elasticities of Residential Heat Demand from District Heating System: A Price Sensitivity Measurement Experiment in South Korea
Authors: Lim Seul-Ye , Min Jeoung-Sik , Yoo Seung-Hoon
Published: June 2021

Since the price for residential heat (RH) from district heating system in South Korea is regulated by the government rather than being freely determined in the market, it is difficult to estimate the demand function for RH properly using the distorted market data. Thus, undistorted data on price and demand are required in obtaining the demand function. This article tries to estimate the demand function for RH by applying the price sensitivity measurement (PSM) technique, with some variation, and then use this to obtain information about the price and income elasticities. To this end, in the PSM survey 1000 households were first asked about their consumption of RH and their expenditure on that consumption and then asked about how much they would lower their demand for RH in response to four hypothetical increases in the price for RH (10%, 20%, 50%, and 100%). Thus, five sets of price and consumption of RH were available for each household. The demand function for RH was estimated using a total of 5000 observations. The price and income elasticities were estimated with statistical significance to be about −0.478 and 0.033, respectively. These values can be utilized in decision-making and/or policy-making related to RH management.
Pseudo-Laminarization of Mixed Microbubble Water and Complex Fluids in Capillary Flows
Authors: Kobayashi Takaki , Ushida Akiomi , Sato Taisuke
Published: June 2021

Symmetry in fluid flow is determined by external factors such as magnetic or electric fields. Owing to the electrical properties of fluids, liquids containing fine bubble or ionic surfactant molecules differ from the normal fluid flow. Therefore, the pressure drop and frictional coefficient in a pipe are measured and estimated for water alone, for mixed microbubble water (MB), and for complex fluids (anionic surfactant solution and polymer solution) in capillary flow with constant flow rate. For water alone, good agreement is obtained between the experimental and theoretical values for laminar Hagen–Poiseuille flow and the Blasius expression in turbulent flow. For the MB, pseudo-laminarization is suggested up to a Reynolds number of 4.2×103. Both the anionic surfactant solution and the polymer solution exhibit the same tendency as that of the MB. In explaining these behaviors, elasticity and electrical interaction are discussed, and electrical interaction on the capillary wall is strongly suggested to be a contributing factor. Additionally, surface tension is investigated and supports the discussion.
Get a Grip: Variation in Human Hand Grip Strength and Implications for Human Evolution
Authors: Bardo Ameline , Kivell Tracy L. , Town Katie , Donati Georgina , Ballieux Haiko , Stamate Cosmin , Edginton Trudi , Forrester Gillian S.
Published: June 2021

Although hand grip strength is critical to the daily lives of humans and our arboreal great ape relatives, the human hand has changed in form and function throughout our evolution due to terrestrial bipedalism, tool use, and directional asymmetry (DA) such as handedness. Here we investigate how hand form and function interact in modern humans to gain an insight into our evolutionary past. We measured grip strength in a heterogeneous, cross-sectional sample of human participants (n = 662, 17 to 83 years old) to test the potential effects of age, sex, asymmetry (hand dominance and handedness), hand shape, occupation, and practice of sports and musical instruments that involve the hand(s). We found a significant effect of sex and hand dominance on grip strength, but not of handedness, while hand shape and age had a greater influence on female grip strength. Females were significantly weaker with age, but grip strength in females with large hands was less affected than those with long hands. Frequent engagement in hand sports significantly increased grip strength in the non-dominant hand in both sexes, while only males showed a significant effect of occupation, indicating different patterns of hand dominance asymmetries and hand function. These results improve our understanding of the link between form and function in both hands and offer an insight into the evolution of human laterality and dexterity.
Synthesis, Optical and DFT Characterizations of Laterally Fluorinated Phenyl Cinnamate Liquid Crystal Non-Symmetric System
Authors: Al-Mutabagani Laila A. , Alshabanah Latifah A. , Ahmed Hoda A. , El-Atawy Mohamed A.
Published: June 2021

A new laterally fluorinated unsymmetric liquid crystalline homologous series, based on cinnamate linkage, named 2-fluoro-4-(4-(alkoxy)phenyl)diazenyl)phenyl cinnamate (In), was synthesized and evaluated via different experimental and computational tools. The series had different terminal alkoxy-chain lengths with a lateral F atom in the meta position with respect to the azo moiety. The experimental mesomorphic and optical investigations were carried out using differential scanning calorimetry (DSC) and polarized optical microscopy (POM). Theoretical calculations and geometrical parameter predictions were conducted using the DFT program method at B3LYP/6-311G** level of theory. The results revealed that all the designed compounds exhibited the nematic (N) mesophase enantiotropically. The nematic stability and temperature range were impacted by the terminal alkoxy chain length. Compounds with the shortest chains (I6 and I8) showed a monotropic smectic A (SmA) phase, while the longest chain derivative, I16, possessed enantiotropic Sm A phase. Theoretical density functional theory (DFT) predictions were correlated with the practically observed data from the mesomorphic investigations. Data revealed that the terminal alkoxy and lateral F groups had an essential impact on the total energy of possible geometrical structures and their physical and thermal parameters.
Quantum Information in the Protein Codes, 3-Manifolds and the Kummer Surface
Authors: Planat Michel , Aschheim Raymond , Amaral Marcelo M. , Fang Fang , Irwin Klee
Published: June 2021

Every protein consists of a linear sequence over an alphabet of 20 letters/amino acids. The sequence unfolds in the 3-dimensional space through secondary (local foldings), tertiary (bonds) and quaternary (disjoint multiple) structures. The mere existence of the genetic code for the 20 letters of the linear chain could be predicted with the (informationally complete) irreducible characters of the finite group Gn:=Zn⋊2O (with n=5 or 7 and 2O the binary octahedral group) in our previous two papers. It turns out that some quaternary structures of protein complexes display n-fold symmetries. We propose an approach of secondary structures based on free group theory. Our results are compared to other approaches of predicting secondary structures of proteins in terms of α helices, β sheets and coils, or more refined techniques. It is shown that the secondary structure of proteins shows similarities to the structure of some hyperbolic 3-manifolds. The hyperbolic 3-manifold of smallest volume—Gieseking manifold—some other 3 manifolds and the oriented hypercartographic group are singled out as tentative models of such secondary structures. For the quaternary structure, there are links to the Kummer surface.
Monitoring Spin-Crossover Properties by Diffused Reflectivity
Authors: Rotaru Gelu-Marius , Codjovi Epiphane , Dahoo Pierre-Richard , Maurin Isabelle , Linares Jorge , Rotaru Aurelian
Published: June 2021

In this work we present a detailed study showing the importance of the Kubelka-Munk (KM) correction in the analysis of diffuse reflectivity measurements to characterize spin crossover compounds. Combined reflectance and magnetic susceptibility measurements are carried out as a function of temperature or time to highlight the conditions under which this correction becomes critical. In particular, we investigate the influence of the color contrast between the two spin states on the reflectance measurements. Interestingly, the samples’ contrast seems to play an important role on the spin-like domain structure as suggested by the symmetry of the FORC diagrams. These latest results are discussed within the framework of Classical Preisach model (CPM).
Numerical Stability Investigations of the Method of Fundamental Solutions Applied to Wave-Current Interactions Using Generating-Absorbing Boundary Conditions
Authors: Loukili Mohammed , Dutykh Denys , Kotrasova Kamila , Ning Dezhi
Published: June 2021

In this paper, the goal is to revolve around discussing the stability of the Method of Fundamental Solutions (MFS) for the use case of wave-current interactions. Further, the reliability of Generating-Absorbing Boundary Conditions (GABCs) applied to the wave-current interactions is investigated using the Method of Fundamental Solutions (MFS), in a Numerical Wave Tank (NWT) within the potential theory where the main regular manifestations are the periodicity, and symmetry of traveling waves. Besides, the investigations cover different aspects of currents (coplanar current, without current, and opposing current), and also different water depths. Furthermore, the accuracy and stability of the numerical method (MFS) used in this work is evaluated for different locations and numbers of source points.
Application of Anti-Diagonal Averaging in Response Reconstruction
Authors: Collins Bradley Dean , Heyns Stephan , Kok Schalk , Wilke Daniel Nico
Published: June 2021

Response reconstruction is used to obtain accurate replication of vehicle structural responses of field recorded measurements in a laboratory environment, a crucial step in the process of Accelerated Destructive Testing (ADA). Response Reconstruction is cast as an inverse problem whereby an input signal is inferred to generate the desired outputs of a system. By casting the problem as an inverse problem we veer away from the familiarity of symmetry in physical systems since multiple inputs may generate the same output. We differ in our approach from standard force reconstruction problems in that the optimisation goal is the recreated output of the system. This alleviates the need for highly accurate inputs. We focus on offline non-causal linear regression methods to obtain input signals. A new windowing method called AntiDiagonal Averaging (ADA) is proposed to improve the regression techniques’ performance. ADA introduces overlaps within the predicted time signal windows and averages them. The newly proposed method is tested on a numerical quarter car model and shown to accurately reproduce the system’s outputs, which outperform related Finite Impulse Response (FIR) methods. In the nonlinear configuration of the numerical quarter car, ADA achieved a recreated output Mean Fit Function Error (MFFE) score of 0.40% compared to the next best performing FIR method, which generated a score of 4.89%. Similar performance was shown for the linear case.
Coordinated SSM: An Adaptation of the SSM Learning Cycle
Authors: Salavati Sadaf , Mirijamdotter Anita , Elm Patrik , Perez Miguel
Published: June 2021

This paper discusses the coordinated use of the Soft Systems Methodology (SSM) learning cycle with additional bodies of knowledge. This approach furthers focused understanding and appreciation for taking action within social systems. Adapting the SSM learning cycle extends the richness of the real-world situation understood from an analytic soft systems perspective to encompass the appreciation of a problematical situation using additional bodies of knowledge to explain and explore. Examples illustrate using SSM to foster learning and improve teaching in a research education practice, in a national level research project and, further, in professional in-service at advanced level education.
Phytobiotics with Adsorbent to Mitigate Toxicity of Multiple Mycotoxins on Health and Growth of Pigs
Authors: Holanda Debora Muratori , Kim Young Ihn , Parnsen Wanpuech , Kim Sung Woo
Published: June 2021

Phytobiotics with a mycotoxin adsorbent were used to mitigate negative effects of multiple mycotoxins in diets fed to pigs. In experiment 1, 120 pigs (11.6 kg body weight; BW) were assigned to five treatments (three pigs/pen) and fed for 28 days. Treatments were CON (control), MTD (CON + 2.5 mg/kg of deoxynivalenol), DP (MTD + phytobiotics at 0.1%), and DPA1 and DPA2 (MTD + phytobiotics and adsorbent at 0.1% and 0.2%, respectively). In experiment 2, 96 pigs (28.5 kg BW) were assigned to four treatments (three pigs/pen) and fed for 26 days. Treatments were CON, MTAF (CON + 0.19 mg/kg of aflatoxin and 8 mg/kg of fumonisins), AFP (MTAF + phytobiotics at 0.1%), and AFPA (MTAF + phytobiotics and adsorbent at 0.1%). Growth performance was measured weekly, and blood was sampled at the end of study to measure hepatic function and inflammatory status (TNF-α). Data were analyzed using the MIXED procedure. In experiment 1, pigs fed MTD, DP, DPA1, and DPA2 had smaller (p < 0.05) BW than CON. Pigs fed DPA2 had greater (p < 0.05) BW than MTD. Pigs fed DP and DPA2 tended to have lower (p < 0.1) serum total protein than CON. Pigs fed MTD and DPA2 tended to have higher (p < 0.1) alanine aminotransferase than CON. Similarly, pigs fed MTD, DP, and DPA2 tended to have higher (p < 0.1) urea nitrogen/creatinine than CON. In experiment 2, pigs fed MTAF, AFP, and AFPA had smaller (p < 0.05) BW than CON. Pigs fed MTAF, AFP, and AFPA had smaller (p < 0.05) ADFI than CON. Pigs fed AFPA had higher (p < 0.05) aspartate aminotransferase than CON and MTAF. Pigs fed AFP and AFPA had higher (p < 0.05) alanine aminotransferase than CON. Pigs fed MTAF, AFP, and AFPA had lower (p < 0.05) urea nitrogen/creatinine than CON. Pigs fed AFPA had higher (p < 0.05) TNF-α than CON and MTAF. In conclusion, feeding an additional 2.5 mg/kg of deoxynivalenol or 0.19 mg/kg of aflatoxin with 8 mg/kg of fumonisins reduced the growth of pigs. Deoxynivalenol compromised the hepatic function of pigs. Phytobiotics with adsorbent could partly overcome the detrimental effects of mycotoxins.
The Effects of Mixed Fusarium Mycotoxins at EU-Permitted Feed Levels on Weaned Piglets’ Tissue Lipids
Authors: Ali Omeralfaroug , Mézes Miklós , Balogh Krisztián , Kovács Melinda , Szabó András
Published: June 2021

At exactly the individual permitted EU-tolerance dietary limits, fumonisins (FB: 5 mg/kg diet) and mixed fusariotoxins (DZ: 0.9 mg deoxynivalenol + 0.1 mg zearalenone/kg diet, and FDZ: 5 mg fumonisins + 0.9 mg deoxynivalenol + 0.1 mg zearalenone/kg diet) were administered to piglets (n = 6/group) for three weeks. Bodyweights of intoxicated piglets increased, while feed conversion ratios decreased. In FDZ, both the absolute and relative weight of the liver decreased. In the renal-cellular membrane, the most pronounced alterations were in FDZ treatment, followed by individual FB exposure. In both treatments, high proportions of C20:0 and C22:0 with low fatty acid (FA) unsaturation were found. In hepatocyte phospholipids, FDZ toxins exerted antagonistic interactions, and FB had the strongest increasing effect on FA monounsaturation. Among all investigated organs, the spleen lipids were the least responsive, in which FDZ expressed synergistic reactions on C20:0 (↑ FDZ vs. FB) and C22:0 (↓ FDZ vs. DZ). The antioxidant defense of the kidney was depleted (↓ glutathione concentration by FB-exposure). Blood plasma indicated renal injury (profound increase of urea and creatinine in FB vs. DZ and FDZ). FB strongly increased total-cholesterol and low density lipoprotein concentrations, whereas FDZ synergistically increased gamma-glutamyltransferase, alkaline-phosphatase, calcium and phosphorus levels. Summarized, individual and combined multiple fusariotoxins modified the membrane lipid profile and antioxidant defense of splanchnic organs, and serum biochemicals, without retarding growth in piglets.
Botulinum Toxin Injection for Medically Refractory Neurogenic Bladder in Children: A Systematic Review
Authors: Wu Shu-Yu , Chang Shang-Jen , Yang Stephen Shei-Dei , Hsu Chun-Kai
Published: June 2021

The objective was to evaluate the use of botulinum toxin A (BTX-A) injection in children with medically refractory neurogenic bladder. A systematic review of the literature was conducted using three databases (Medline via PubMed, Cochrane, and EMBASE). Articles evaluating BTX-A in children with neurogenic bladder were collected. The clinical and urodynamic parameters were reviewed for the safety and efficacy evaluation. Sixteen studies were selected into this study and a total of 455 children with medical refractory neurogenic bladder were evaluated. All of the patients had received traditional conservative medications such as antimuscarinics and intermittent catheterization as previous treatment. The duration of treatments ranged from 2 months to 5.7 years. Improvements in incontinence and vesicoureteral reflux were the most common clinical outcomes. The detrusor pressure, bladder capacity and bladder compliance improvement were the most common urodynamic parameters which had been reported. However, patient satisfaction with the procedure remained controversial. There was only a minimal risk of minor adverse effects. In all of the studies, BTX-A injection was well tolerated. In conclusion, BTX-A injection appears to be a safe and effective treatment in the management of medically unresponsive neurogenic bladder in children. There is currently no evidence that the use of BTX-A injection could be used as a first-line therapy for neurogenic bladder in children.
Computational Approaches to Explore Bacterial Toxin Entry into the Host Cell
Authors: Pezeshkian Weria , Shillcock Julian C. , Ipsen John H.
Published: June 2021

Many bacteria secrete toxic protein complexes that modify and disrupt essential processes in the infected cell that can lead to cell death. To conduct their action, these toxins often need to cross the cell membrane and reach a specific substrate inside the cell. The investigation of these protein complexes is essential not only for understanding their biological functions but also for the rational design of targeted drug delivery vehicles that must navigate across the cell membrane to deliver their therapeutic payload. Despite the immense advances in experimental techniques, the investigations of the toxin entry mechanism have remained challenging. Computer simulations are robust complementary tools that allow for the exploration of biological processes in exceptional detail. In this review, we first highlight the strength of computational methods, with a special focus on all-atom molecular dynamics, coarse-grained, and mesoscopic models, for exploring different stages of the toxin protein entry mechanism. We then summarize recent developments that are significantly advancing our understanding, notably of the glycolipid–lectin (GL-Lect) endocytosis of bacterial Shiga and cholera toxins. The methods discussed here are also applicable to the design of membrane-penetrating nanoparticles and the study of the phenomenon of protein phase separation at the surface of the membrane. Finally, we discuss other likely routes for future development.
PhaLP: A Database for the Study of Phage Lytic Proteins and Their Evolution
Authors: Criel Bjorn , Taelman Steff , Van Criekinge Wim , Stock Michiel , Briers Yves
Published: June 2021

Phage lytic proteins are a clinically advanced class of novel enzyme-based antibiotics, so-called enzybiotics. A growing community of researchers develops phage lytic proteins with the perspective of their use as enzybiotics. A successful translation of enzybiotics to the market requires well-considered selections of phage lytic proteins in early research stages. Here, we introduce PhaLP, a database of phage lytic proteins, which serves as an open portal to facilitate the development of phage lytic proteins. PhaLP is a comprehensive, easily accessible and automatically updated database (currently 16,095 entries). Capitalizing on the rich content of PhaLP, we have mapped the high diversity of natural phage lytic proteins and conducted analyses at three levels to gain insight in their host-specific evolution. First, we provide an overview of the modular diversity. Secondly, datamining and interpretable machine learning approaches were adopted to reveal host-specific design rules for domain architectures in endolysins. Lastly, the evolution of phage lytic proteins on the protein sequence level was explored, revealing host-specific clusters. In sum, PhaLP can act as a starting point for the broad community of enzybiotic researchers, while the steadily improving evolutionary insights will serve as a natural inspiration for protein engineers.
Emodin from Aloe Inhibits Porcine Reproductive and Respiratory Syndrome Virus via Toll-Like Receptor 3 Activation
Authors: Xu Zhichao , Huang Meiyan , Xia Yongbo , Peng Peng , Zhang Yun , Zheng Shumei , Wang Xiaowei , Xue Chunyi , Cao Yongchang
Published: June 2021

Porcine reproductive and respiratory syndrome virus (PRRSV) causes severe reproductive failure in sows and respiratory diseases in growing and finishing pigs and results in great economic losses to the swine industry. Although vaccines are available, PRRSV remains a major threat to the pig farms. Thus, there is an urgent need to develop antiviral drugs to compensate for vaccines. In this study, we report that Aloe extract (Ae) can strongly inhibit PRRSV in Marc-145 cells and porcine alveolar macrophages lines (iPAMs) in vitro. Furthermore, we identified a novel anti-PRRSV molecule, Emodin, from Ae by high-performance liquid chromatography (HPLC). Emodin exerted its inhibitory effect through targeting the whole stages of PRRSV infectious cycle. Moreover, we also found that Emodin can inactivate PRRSV particles directly. Notably, we confirmed that Emodin was able to significantly induce Toll-like receptor 3 (TLR3) (p < 0.01), IFN-α (p < 0.05) and IFN-β expression in iPAMs, indicating that induction of antiviral agents via TLR3 activation by Emodin might contribute to its anti-PRRSV effect. These findings imply that the Emodin from Aloe could hamper the proliferation of PRRSV in vitro and might constitute a new approach for treating PRRSV infection.
Histopathological Analysis of Adrenal Glands after Simian Varicella Virus Infection
Authors: Niemeyer Christy S. , Mescher Teresa , Griggs Rocio , Orlicky David J. , Wilkerson Gregory K. , Bubak Andrew N. , Hassell James E. , Feia Brittany , Mahalingam Ravi , Traina-Dorge Vicki , Nagel Maria A.
Published: June 2021

Latent varicella zoster virus (VZV) has been detected in human adrenal glands, raising the possibility of virus-induced adrenal damage and dysfunction during primary infection or reactivation. Rare cases of bilateral adrenal hemorrhage and insufficiency associated with VZV reactivation have been reported. Since there is no animal model for VZV infection of adrenal glands, we obtained adrenal glands from two non-human primates (NHPs) that spontaneously developed varicella from primary simian varicella virus (SVV) infection, the NHP VZV homolog. Histological and immunohistochemical analysis revealed SVV antigen and DNA in the adrenal medulla and cortex of both animals. Adrenal glands were observed to have Cowdry A inclusion bodies, cellular necrosis, multiple areas of hemorrhage, and varying amounts of polymorphonuclear cells. No specific association of SVV antigen with βIII-tubulin-positive nerve fibers was found. Overall, we found that SVV can productively infect NHP adrenal glands, and is associated with inflammation, hemorrhage, and cell death. These findings suggest that further studies are warranted to examine the contribution of VZV infection to human adrenal disease. This study also suggests that VZV infection may present itself as acute adrenal dysfunction with “long-hauler” symptoms of fatigue, weakness, myalgias/arthralgias, and hypotension.
Effect of Aprotinin and Avifavir® Combination Therapy for Moderate COVID-19 Patients
Authors: Ivashchenko Andrey A. , Azarova Valeria N. , Egorova Alina N. , Karapetian Ruben N. , Kravchenko Dmitry V. , Krivonos Natalia V. , Loginov Vladimir G. , Poyarkov Stanislav V. , Merkulova Elena A. , Rosinkova Olga S. , Savchuk Nikolay P. , Topr Mikhail A. , Simakina Elena N. , Yakubova Elena V. , Ivachtchenko Alexandre V.
Published: June 2021

COVID-19 is a contagious multisystem inflammatory disease caused by a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We studied the efficacy of Aprotinin (nonspecific serine proteases inhibitor) in combination with Avifavir® or Hydroxychloroquine (HCQ) drugs, which are recommended by the Russian Ministry of Health for the treatment therapy of moderate COVID-19 patients. This prospective single-center study included participants with moderate COVID-19-related pneumonia, laboratory-confirmed SARS-CoV-2, and admitted to the hospitals. Patients received combinations of intravenous (IV) Aprotinin (1,000,000 KIU daily, 3 days) and HCQ (cohort 1), inhalation (inh) treatment with Aprotinin (625 KIU four times per day, 5 days) and HCQ (cohort 2) or IV Aprotinin (1,000,000 KIU daily for 5 days) and Avifavir (cohort 3). In cohorts 1–3, the combination therapy showed 100% efficacy in preventing the transfer of patients (n = 30) to the intensive care unit (ICU). The effect of the combination therapy in cohort 3 was the most prominent, and the median time to SARS-CoV-2 elimination was 3.5 days (IQR 3.0–4.0), normalization of the CRP concentration was 3.5 days (IQR 3–5), of the D-dimer concentration was 5 days (IQR 4 to 5); body temperature was 1 day (IQR 1–3), improvement in clinical status or discharge from the hospital was 5 days (IQR 5–5), and improvement in lung lesions of patients on 14 day was 100%.
A Personal Tribute to Robert B. Sim with Reflections on Our Work Together on Factor H
Authors: Day Anthony J.
Published: June 2021

Robert (Bob) Sim had a profound effect on almost every aspect of my approach to scientific research, acting as a mentor and moral compass through the many different stages of my career [...]
Development of Broad-Spectrum Antiviral Agents—Inspiration from Immunomodulatory Natural Products
Authors: Zhang Mengxun , Zhong Jiaqing , Xiong Yongai , Song Xun , Li Chenyang , He Zhendan
Published: June 2021

Developing broad-spectrum antiviral drugs remains an important issue as viral infections continue to threaten public health. Host-directed therapy is a method that focuses on potential targets in host cells or the body, instead of viral proteins. Its antiviral effects are achieved by disturbing the life cycles of pathogens or modulating immunity. In this review, we focus on the development of broad-spectrum antiviral drugs that enhance the immune response. Some natural products present antiviral effects mediated by enhancing immunity, and their structures and mechanisms are summarized here. Natural products with immunomodulatory effects are also discussed, although their antiviral effects remain unknown. Given the power of immunity and the feasibility of host-directed therapy, we argue that both of these categories of natural products provide clues that may be beneficial for the discovery of broad-spectrum antiviral drugs.
Growth Kinetics and Protective Efficacy of Attenuated ASFV Strain Congo with Deletion of the EP402 Gene
Authors: Koltsova Galina , Koltsov Andrey , Krutko Sergey , Kholod Natalia , Tulman Edan R. , Kolbasov Denis
Published: June 2021

African swine fever (ASF) is an emerging disease threat to the swine industry worldwide. There is no vaccine against ASF, and progress is hindered by a lack of knowledge concerning the extent of ASFV strain diversity and the viral antigens conferring type-specific protective immunity in pigs. We have previously demonstrated that homologous ASFV serotype-specific proteins CD2v (EP402R) and/or C-type lectin are required for protection against challenge with the virulent ASFV strain Congo (Genotype I, Serogroup 2), and we have identified T-cell epitopes on CD2v which may be associated with serotype-specific protection. Here, using a cell-culture adapted derivative of the ASFV strain Congo (Congo-a) with specific deletion of the EP402R gene (ΔCongoCD2v) in swine vaccination/challenge experiments, we demonstrated that deletion of the EP402R gene results in the failure of ΔCongoCD2v to induce protection against challenge with the virulent strain Congo (Congo-v). While ΔCongoCD2v growth kinetics in COS-1 cells and primary swine macrophage culture were almost identical to parental Congo-a, replication of ΔCongoCD2v in vivo was significantly reduced compared with parental Congo-a. Our data support the idea that the CD2v protein is important for the ability of homologous live-attenuated vaccines to induce protective immunity against the ASFV strain Congo challenge in vivo.
Development of a Novel Live Attenuated Influenza A Virus Vaccine Encoding the IgA-Inducing Protein
Authors: Cáceres C. Joaquín , Cardenas-Garcia Stivalis , Jain Aarti , Gay L. Claire , Carnaccini Silvia , Seibert Brittany , Ferreri Lucas M. , Geiger Ginger , Jasinskas Algimantas , Nakajima Rie , Rajao Daniela S. , Isakova-Sivak Irina , Rudenko Larisa , Vincent Amy L. , Davies D. Huw , Perez Daniel R.
Published: June 2021

Live attenuated influenza virus (LAIV) vaccines elicit a combination of systemic and mucosal immunity by mimicking a natural infection. To further enhance protective mucosal responses, we incorporated the gene encoding the IgA-inducing protein (IGIP) into the LAIV genomes of the cold-adapted A/Leningrad/134/17/57 (H2N2) strain (caLen) and the experimental attenuated backbone A/turkey/Ohio/313053/04 (H3N2) (OH/04att). Incorporation of IGIP into the caLen background led to a virus that grew poorly in prototypical substrates. In contrast, IGIP in the OH/04att background (IGIP-H1att) virus grew to titers comparable to the isogenic backbone H1att (H1N1) without IGIP. IGIP-H1att- and H1caLen-vaccinated mice were protected against lethal challenge with a homologous virus. The IGIP-H1att vaccine generated robust serum HAI responses in naïve mice against the homologous virus, equal or better than those obtained with the H1caLen vaccine. Analyses of IgG and IgA responses using a protein microarray revealed qualitative differences in humoral and mucosal responses between vaccine groups. Overall, serum and bronchoalveolar lavage samples from the IGIP-H1att group showed trends towards increased stimulation of IgG and IgA responses compared to H1caLen samples. In summary, the introduction of genes encoding immunomodulatory functions into a candidate LAIV can serve as natural adjuvants to improve overall vaccine safety and efficacy.
Effects of Spatial Resolution on the Satellite Observation of Floating Macroalgae Blooms
Authors: Wang Xinhua , Xing Qianguo , An Deyu , Meng Ling , Zheng Xiangyang , Jiang Bo , Liu Hailong
Published: June 2021

Satellite images with different spatial resolutions are widely used in the observations of floating macroalgae booms in sea surface. In this study, semi-synchronous satellite images with different resolutions (10 m, 16 m, 30 m, 50 m, 100 m, 250 m and 500 m) acquired over the Yellow Sea, are used to quantitatively assess the effects of spatial resolution on the observation of floating macroalgae blooms of Ulva prolifera. Results indicate that the covering area of macroalgae-mixing pixels (MM-CA) detected from high resolution images is smaller than that from low resolution images; however, the area affected by macroalgae blooms (AA) is larger in high resolution images than in low resolution ones. The omission rates in the MM-CA and the AA increase with the decrease of spatial resolution. These results indicate that satellite remote sensing on the basis of low resolution images (especially, 100 m, 250 m, 500 m), would overestimate the covering area of macroalgae while omit the small patches in the affected zones. To reduce the impacts of overestimation and omission, high resolution satellite images are used to show the seasonal changes of macroalgae blooms in 2018 and 2019 in the Yellow Sea.
Hydroenergy Harvesting Assessment: The Case Study of Alviela River
Authors: Oliveira Pedro F. G. , Martins Nuno M. C. , Fontes Pedro , Covas Dídia
Published: June 2021

The current paper aims to develop and to apply a methodology for assessing the hydroenergy harvesting potential in water systems taking into account both technical and economic aspects. The methodology is a five-step procedure: (i) data collection and analysis; (ii) technology identification; (iii) energy harvesting assessment; (iv) economic analysis; and (v) final recommendation of the technological solution. The case study is located in the water source of the Alviela River, in Portugal. The energy harvesting potential is assessed for three turbine types, adequate for the 2.5 m available head: two propeller turbines, with and without adjustable blades, and the Archimedes screw turbine. Results show that the most feasible solution is the Archimedes screw turbine, with 3 m3/s rated discharge and 55 kW rated power, the capital cost of 160 k€, the internal rate of return above 10% and the payback period of eight years. This solution has the potential for harvesting energy in low-head sites with a wide range of flow rates.
Multivariate Analysis of Water Quality Data for Drinking Water Supply Systems
Authors: Maiolo Mario , Pantusa Daniela
Published: June 2021

Vulnerability of drinking water supply systems (DWSSs) depends on different factors such as failures, loss of security, man-made threats, and the change and deterioration of supply-water quality. Currently, the lifespan of several DWSSs worldwide has been exceeded, exasperating these issues. The monitoring activity and the transparency of information on water availability and quality are becoming increasingly important in accordance with the national regulations and standards, and with guidelines of the World Health Organization (WHO). These activities can be considered as support and guidance tools for identifying health-related risks, for building a safe management of drinking water supply systems, and for improved user confidence in the consumption of tap water. In this context, in the present work an analysis of the quality monitoring data of DWSSs was carried out using multivariate techniques. The analysis considered several chemical–physical parameters collected in the period 2013–2020 for some DWSSs in the Emilia-Romagna region, Italy. Principal component analysis (PCA) and cluster analysis (CA) methods were used to process and reduce the dimensionality of the data, to highlight the parameters that have the greatest influence on the qualitative state of the supplied water and to identify clusters.
Twenty-First Century Science Calls for Twenty-First Century Groundwater Use Law: A Retrospective Analysis of Transboundary Governance Weaknesses and Future Implications in the Laurentian Great Lakes Basin
Authors: Weekes Khafi , Krantzberg Gail
Published: June 2021

How has groundwater use been historically governed by the binational to municipal government levels across the Laurentian Great Lakes Basin (GLB)? To what extent have they contemplated the physical–environmental requirements to maintain aquifer storage in devising policies and making decisions governing groundwater use? Although it is amongst the largest freshwater stores in the globe, cases of groundwater shortages are increasingly being reported across GLB communities, raising questions on the fitness of governance approaches to maintain groundwater storage (GWS) with growing climate and human pressures. Applying retrospective analytical methods to assess the century-old collaboration of the United States and Canada to maintain GLB water quantities, we characterize long-term trends and undertake systematic diagnosis to gain insight into causal mechanisms that have persisted over the years resulting in current GWS governance gaps. We reveal the surprising prominence of policies originally intended to safeguard surface water quantities being used to govern groundwater use and thereby maintain GWS. We also connect these, based on sustainable aquifer yield theory, to growing groundwater insecurity in the Basin’s drought-prone and/or groundwater-dependent communities. Based on deep understanding of long-standing policy pathologies, findings inform transboundary GWS governance reform proposals that can be highly useful to multiple levels of government policymakers.