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Povzetek: After three years of the SARS-CoV-2 pandemic, the search and availability of relatively low-cost benchtop therapeutics for people not at high risk for a severe disease are still ongoing. Although vaccines and new SARS-CoV-2 variants reduce the death toll, the long COVID-19 along with neurologic symptoms can develop and persist even after a mild initial infection. Reinfections, which further increase the risk of sequelae in multiple organ systems as well as the risk of death, continue to require caution. The spike protein of SARS-CoV-2 is an important target for both vaccines and therapeutics. The presence of disulfide bonds in the receptor binding domain (RBD) of the spike protein is essential for its binding to the human ACE2 receptor and cell entry. Here, we demonstrate that thiol-reducing peptides based on the active site of oxidoreductase thioredoxin 1, called thioredoxin mimetic (TXM) peptides, can prevent syncytia formation, SARS-CoV-2 entry into cells, and infection in a mouse model. We also show that TXM peptides inhibit the redox-sensitive HIV pseudotyped viral cell entry. These results support disulfide targeting as a common therapeutic strategy for treating infections caused by viruses using redox-sensitive fusion. Furthermore, TXM peptides exert anti-inflammatory properties by lowering the activation of NF-κB and IRF signaling pathways, mitogen-activated protein kinases (MAPKs) and lipopolysaccharide (LPS)-induced cytokines in mice. The antioxidant and anti-inflammatory effects of the TXM peptides, which also cross the blood-brain barrier, in combination with prevention of viral infections, may provide a beneficial clinical strategy to lower viral infections and mitigate severe consequences of COVID-19.
Ključne besede: SARS-CoV-2, Disulfides, Thiol-reacting compound, Spike, Anti-inflammatory activity
Objavljeno v DiRROS: 06.02.2024; Ogledov: 161; Prenosov: 71
Celotno besedilo (7,11 MB)
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Povzetek: Triassic strata in the Drežnica section, Bosnia and Herzegovina have been examined biostratigraphically. The limestone and dolostone strata were deposited in deep pelagic environment. The conodont faunas are marked by prevailing elements of the genus Pseudofurnishius including clusters that enabled to distinguish the huddlei (lower Longobardian) and murcianus (upper Longobardian–?Cordevolian) Zones, the later fauna is characterized by the presence of Budurovignathus with rare representation of Gladigondolella and Paragondolella. This is the first report on recovery of Pseudofurnishius in the region.
Ključne besede: Ladinian–?Carnian, conodonts, Pseudofurnishius, Budurovignathus, paleogeography, Dinarides
Objavljeno v DiRROS: 06.09.2023; Ogledov: 267; Prenosov: 118
Celotno besedilo (7,77 MB)

Povzetek: Debelost je kronična bolezen, za katero je značilno čezmerno kopičenje maščevja v telesu. Debeli bolniki imajo pogosto številne pridružene bolezni ter anatomske in presnovne spremembe, ki so povezane z večjim tveganjem za zaplete v perioperativnem obdobju. Debelost tako pomembno vpliva na izbiro anestezijske tehnike in zahteva multidisciplinarni pristop. V prispevku predstavljamo primer 60-letne bolnice z rakom na debelem črevesu in indeksom telesne mase (ITM) 48,1 kg/m2. Perioperativno smo jo obravnavali v skladu s protokolom za hitro okrevanje po kirurškem posegu (angl. Enhanced Recovery After Surgery, ERAS). Pred kirurškim posegom smo ocenili morebitna tveganja in jih upoštevali pri vodenju anestezije med kirurškim posegom. Po posegu smo bolnico obravnavali v enoti intenzivne terapije (EIT). V prispevku se osredotočamo na anesteziološke vidike perioperativnega vodenja. Čeprav je debelost nedvomno pomemben dejavnik tveganja kirurškega zdravljenja, pa v novejših raziskavah poročajo tudi o ugodnih vplivih debelosti z manjšo perioperativno obolevnostjo in smrtnostjo. Gre za t. i. paradoks debelosti, saj čezmerna telesna masa velja za zaščitni dejavnik, ki varuje pred zapleti kirurškega zdravljenja, kar smo potrdili tudi v našem primeru. Hkrati smo opredelili kritične točke pri anesteziji morbidno debelega bolnika in tista področja, na katerih lahko anesteziologi – ob upoštevanju protokola ERAS – pomembno prispevamo k bolnikovemu čim hitrejšemu okrevanju
Ključne besede: debelost, indeks telesne mase, kirurgija
Objavljeno v DiRROS: 27.07.2023; Ogledov: 277; Prenosov: 69
Celotno besedilo (173,51 KB)

Povzetek: The term Procedural Content Generation (PCG) refers to the (semi-)automatic generation of game content by algorithmic means, and its methods are becoming increasingly popular in game-oriented research and industry. A special class of these methods, which is commonly known as search-based PCG, treats the given task as an optimisation problem. Such problems are predominantly tackled by evolutionary algorithms. We will demonstrate in this paper that obtaining more information about the defined optimisation problem can substantially improve our understanding of how to approach the generation of content. To do so, we present and discuss three efficient analysis tools, namely diagonal walks, the estimation of high-level properties, as well as problem similarity measures. We discuss the purpose of each of the considered methods in the context of PCG and provide guidelines for the interpretation of the results received. This way we aim to provide methods for the comparison of PCG approaches and eventually, increase the quality and practicality of generated content in industry.
Ključne besede: optimization, search-based procedural content generation, exploratory landscape analysis, Mario level generation
Objavljeno v DiRROS: 24.02.2023; Ogledov: 410; Prenosov: 168
Celotno besedilo (745,09 KB)

Objavljeno v DiRROS: 24.01.2023; Ogledov: 441; Prenosov: 138
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