1. Identification of triazolopyrimidinyl scaffold SARS-CoV-2 papain-like protease (PLpro) inhibitorSebastjan Kralj, Marko Jukič, Miha Bahun, Luka Kranjc, Anja Kolarič, Milan Hodošček, Nataša Poklar Ulrih, Urban Bren, 2024, original scientific article Abstract: The global impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its companion disease, COVID-19, has reminded us of the importance of basic coronaviral research. In this study, a comprehensive approach using molecular docking, in vitro assays, and molecular dynamics simulations was applied to identify potential inhibitors for SARS-CoV-2 papain-like protease (PLpro), a key and underexplored viral enzyme target. A focused protease inhibitor library was initially created and molecular docking was performed using CmDock software (v0.2.0), resulting in the selection of hit compounds for in vitro testing on the isolated enzyme. Among them, compound 372 exhibited promising inhibitory properties against PLpro, with an IC50 value of 82 ± 34 μM. The compound also displayed a new triazolopyrimidinyl scaffold not yet represented within protease inhibitors. Molecular dynamics simulations demonstrated the favorable binding properties of compound 372. Structural analysis highlighted its key interactions with PLpro, and we stress its potential for further optimization. Moreover, besides compound 372 as a candidate for PLpro inhibitor development, this study elaborates on the PLpro binding site dynamics and provides a valuable contribution for further efforts in pan-coronaviral PLpro inhibitor development.
Keywords: drug design, protease inhibitor, SARS-CoV-2, papain-like protease, PLpro, antiviral design, in silico drug design, CADD, virtual screening, HTVS, structure-based design
Published in DiRROS: 07.08.2024; Views: 81; Downloads: 90
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2. Harmonizing microstructures and enhancing mechanical resilience : novel powder metallurgy approach for Zn–Mg alloysAnna Boukalová, Jiří Kubásek, David Nečas, Peter Minárik, Črtomir Donik, Drahomír Dvorský, Dalibor Vojtěch, Alena Michalcová, Matjaž Godec, Irena Paulin, 2024, original scientific article Abstract: Zinc alloys are recognised for their excellent biocompatibility and favourable corrosion rates, making them suitable for bioabsorbable implants. However, their mechanical properties necessitate improvement to fulfil the rigorous requirements of biomedical applications. This research focuses on engineering pseudo-harmonic structures within zinc alloys through a comprehensive method combining mechanical alloying, spark plasma sintering, and hot extrusion techniques. This fabrication process results in a composite material characterised by a soft core surrounded by a continuous, three-dimensional, ultrafine-grained hard shell. The experiment involved blending pure zinc with Zn–1Mg alloy powder, leading to the formation of both ductile zinc and fine-grained Zn–1Mg regions. While the Mg2Zn11 intermetallic phase was found to enhance the alloy's mechanical strength, the presence of oxide shells adversely affected the material's properties. The elimination of these shells via hot extrusion markedly improved the alloy's tensile strength, reaching an average value of tensile strength of 333 ± 7 MPa. This study provides significant insights into the material engineering of zinc-based alloys for biodegradable implant applications, demonstrating a viable approach to optimising their mechanical performance.
Keywords: zinc, magnesium, biodegradable, powder metallurgy, harmonic structure
Published in DiRROS: 23.07.2024; Views: 128; Downloads: 129
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3. Why are the Early Gothic murals in St. Jacob’s Church in Ormož, Slovenia, almost entirely black?Anabelle Križnar, Katja Kavkler, Sabina Dolenec, 2024, original scientific article Abstract: In St. Jacob’s parish church in Ormož, Slovenia, mural paintings from around 1350–1370 are partially conserved in the northeastern corner of the main nave. They are almost completely black, indicating a large-scale pigment degradation. They were studied as a part of a larger research project aiming to identify materials applied and their possible degradation. First, they were studied in situ, and next, extracted samples of plaster, pigments, and colour layers were analysed by optical microscopy, Raman spectroscopy, FTIR spectroscopy, SEM-EDS, and XRD. Haematite, green earth, malachite, azurite, and tenorite were identified, showing that azurite and perhaps also malachite degraded to black tenorite, probably due to their fine grinding and their application directly on the fresh plaster. The plaster is made with small and large amounts of aggregate with mostly quartz with some impurities, which makes it fragile. The original appearance of these murals was of bright blue and green colours.
Keywords: mural painting, medieval painting, Gothic art, St. Jacob's Church, Ormož, Slovenia, pigments, chemical structure, colour degradation, optical microscopy, Raman microspectroscopy, FTIR, XRD
Published in DiRROS: 17.04.2024; Views: 265; Downloads: 261
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4. Effect of post-treated low-temperature plasma nitriding on the wear and corrosion resistance of 316L stainless steel manufactured by laser powder-bed fusionMatjaž Godec, Črtomir Donik, Aleksandra Kocijan, Bojan Podgornik, Danijela Anica Skobir Balantič, 2020, original scientific article Keywords: austenitic stainless steel, powder bed fusion, low-temperature plasma nitriding, wear and corrosion behaviour, dislocation cell structure
Published in DiRROS: 25.03.2024; Views: 306; Downloads: 187
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5. Geological-genetic structure of Irpin city, the role of lithological factors during engineering-geological zoning and construction assessmentPavlo Zhyrnov, Iryna Solomakha, 2023, original scientific article Abstract: The scheme of engineering-construction assessment created based on engineering-geological zoning of the city’s territory is desirable among additional graphic materials in the design of master plans projects as determined by building regulations. Engineering-geological zoning provides for different ranks’ selection of engineering-geological units (EG units), which have a particular range of common engineering-geological conditions that ultimately determine the construction sites’ affiliation to a specific suitability category. Geological-genetic structure of Irpin city of Kyiv region (Ukraine) is explored in this article. A variant of the creation of a large-scale engineering-geological map and corresponding geological-lithological sections by supporting boreholes in the borders of the city based on the engineering-geological survey conducted is presented. The obtained result allowed the selection of engineering geological zoning units – engineering geological districts by general conditions of geological development and subdistricts by engineering-geological complexes of Quaternary rocks’ thickness. The analysis of soils’ geomechanical properties (engineering-geological elements) lays the foundations for the selection of engineering-geological sites based on the comparison of this information with geomorphological, hydrogeological and geodynamic data. Accounting of geological-lithological factors in the preparation of the construction assessment scheme in the project of Irpin city’s master plan has become the ultimate result.
Keywords: engineering-geological zoning, engineering-geological units, geological-genetic structure, engineering-geological map, construction assessment
Published in DiRROS: 15.01.2024; Views: 449; Downloads: 193
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6. Transverse Dinaric zone of increased compression between the Kraški rob and Hrušica Regions, NE MicroadriaLadislav Placer, Igor Rižnar, Ana Novak, 2023, original scientific article Abstract: The Kvarner fault divides the Microadria (Adria microplate, the Adria stable core) into the Po and Adria segments. The Istra block, which is sandwiched between the right-lateral Kvarner Fault and the left-lateral Sistiana Fault lies at the extreme eastern edge of the Po segment. Both faults run transversely to the Dinarides and reach their thrust boundary in the east. The Microadria has been moving towards the Dinarides since the Middle Miocene. The movement of the Istra block is exposed in relation to the neighbouring blocks, so an extensive pushed area (the Istra Pushed Area) was formed in the External Dinarides, which is bent towards the northeast. It is defined by two flexural zones, one lying in the extension of the Sistiana Fault and the other in the extension of the Kvarner Fault. The structure of the Dinaric thrust border on the north-eastern side of the Istra block is complex. Its prominent structural element is the Črni Kal Anomaly, due to which a zone of increased compression developed within the Istra Pushed Area and transversely to the Dinarides (Kraški rob – Hrušica Traverse), which lies between the Sistiana and Kvarner Flexural Zones. In terms of kinematics, it differs greatly from these two, and various geomorphologically responsive deformations have occurred within it. Mt. Vremščica (1027 m), which represents a transpressive anticline within the wider zone of the Raša Fault is the most prominent. In order to understand the genesis of the Classical Karst relief, it is important to know that the Mt. Vremščica ridge rose from the levelled karst surface.
Keywords: NE Microadria (Adria Microplate), Istra peninsula, Istra Pushed Area, Črni Kal Anomaly, Kraški rob – Mt. Hrušica Traverse, stacked structure, envelope fault
Published in DiRROS: 15.01.2024; Views: 515; Downloads: 213
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7. Between but not within-species variation in the distribution of fitness effectsJennifer James, Chedly Kastallya, Katharina Budde, Santiago C. González-Martínez, Pascal Milesi, Tanja Pyhäjärvi, Martin Lascoux, 2023, original scientific article Abstract: New mutations provide the raw material for evolution and adaptation. The distribution of fitness effects (DFE) describes the spectrum of effects of new mutations that can occur along a genome, and is, therefore, of vital interest in evolutionary biology. Recent work has uncovered striking similarities in the DFE between closely related species, prompting us to ask whether there is variation in the DFE among populations of the same species, or among species with different degrees of divergence, that is whether there is variation in the DFE at different levels of evolution. Using exome capture data from six tree species sampled across Europe we characterized the DFE for multiple species, and for each species, multiple populations, and investigated the factors potentially influencing the DFE, such as demography, population divergence, and genetic background. We find statistical support for the presence of variation in the DFE at the species level, even among relatively closely related species. However, we find very little difference at the population level, suggesting that differences in the DFE are primarily driven by deep features of species biology, and those evolutionarily recent events, such as demographic changes and local adaptation, have little impact.
Keywords: DFE, deleterious mutations, population structure, forest trees
Published in DiRROS: 12.12.2023; Views: 528; Downloads: 196
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8. Rotational dynamics of a protein under shear flow studied by the eckart frame formalismPetra Papež, Franci Merzel, Matej Praprotnik, 2023, original scientific article Keywords: energy, kinetics, molecules, protein structure, rotational dynamics, molecules, protein structure, rotational dynamics
Published in DiRROS: 06.09.2023; Views: 488; Downloads: 256
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9. Valorized deinking paper residue as fill material for geotechnical structuresKarmen Fifer Bizjak, Barbara Likar, Ana Mladenovič, Vesna Zalar Serjun, 2021, original scientific article Abstract: This study introduces a novel geotechnical composite material comprising two types of fill material sourced from the paper industry-deinking paper sludge ash (DPSA) and deinking paper sludge (DPS). Five composites with different DPSA and DPS contents were investigated. Two composites were selected for further analyses. The technology and procedure for composite installation were implemented in field tests. The composites with 80% and 70% DPSA exhibited the elasticity required to withstand minor landslide slip deformations, in addition to achieving sufficiently high values of uniaxial compressive strength. The composites had a low maximum dry density value, which led to fewer settlements in the entire support structure. The enhanced shear characteristics can enable the construction of a thinner retaining wall. The delay between preparation and installation of the composites was further investigated. The field tests confirmed that the composites with 80% and 70% DPSA can be installed on the construction site 4 h and even 24 h after mixing. In 2018, a retaining wall structure with 70% DPSA and 30% DPS was successfully implemented near a railway line using conventional technology as followed-up research to the herein presented study. Results have been derived from work performed in the scope of the H2020 Paperchain project in which novel circular economy models centered on the valorization of the waste streams generated by the pulp and paper industry as secondary raw material for several resource-intensive sectors, including the construction sector, have been developed. Environmental benefits are savings in natural raw materials, reduction of landfill disposal as well as CO2 emission reduction.
Keywords: deinking paper sludge ash, deinking paper sludge, secondary resources, fill material, geotechnical structure, landslide, open access
Published in DiRROS: 04.07.2023; Views: 464; Downloads: 349
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10. 3D finite element analysis of a concrete dam behavior under changing hydrostatic load : a case studyPavel Žvanut, 2022, original scientific article Abstract: In this study, a large arch-gravity Moste Dam was analyzed, where an automated system for the measurements of horizontal displacements of the upper part of the dam was established. Two-dimensional (2D) and three-dimensional (3D) analyses of dam behavior, taking into account the earth pressures and the hydrostatic load, using the finite element method (FEM)-based computer program DIANA, were performed. The influence of lowering the water level of the reservoir by 6.2 m, on the horizontal displacements of the upper part of the dam, at stationary temperature conditions, was investigated. It was found that the results of the performed 2D and 3D FEM analyses fitted in very well with the result of experimentally determined measurement of horizontal displacements (which was 0.48 mm in the upstream direction) that was obtained using a hanging pendulum. An additional comparison of the results of 3D calculations showed that the finite element mesh density had a small effect on the calculated horizontal displacements.
Keywords: concrete dam, finite element method, material properties, structure behavior, measuring instruments, monitoring, ime series analysis, horizontal displacements, hydrostatic pressure
Published in DiRROS: 21.06.2023; Views: 558; Downloads: 301
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