Iskanje po katalogu digitalne knjižnice

Opis: Abstract Peptides, or short chains of amino-acid residues, are becoming increasingly important as active ingredients of drugs and as crucial probes and/or tools in medical, biotechnological, and pharmaceutical research. Situated at the interface between small molecules and larger macromolecular systems, they pose a difficult challenge for computational methods. We report an in silico peptide library generation and prioritization workflow using CmDock for identifying tetrapeptide ligands that bind to Fc regions of antibodies that is analogous to known in vitro recombinant peptide libraries’ display and expression systems. The results of our in silico study are in accordance with existing scientific literature on in vitro peptides that bind to antibody Fc regions. In addition, we postulate an evolving in silico library design workflow that will help circumvent the combinatorial problem of in vitro comprehensive peptide libraries by focusing on peptide subunits that exhibit favorable interaction profiles in initial in silico peptide generation and testing.
Ključne besede: peptide design, in silico combinatorial library, peptide combinatorial library, peptide library design, high-throughput virtual screening, peptide molecular docking, antibody purification, peptide drug design, recombinant peptide libraries
Objavljeno v DKUM: 01.12.2023; Ogledov: 8; Prenosov: 0
Celotno besedilo (8,11 MB)
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Opis: The heterogeneity of welded joints’ microstructure affects their mechanical properties, which can vary significantly in relation to specific weld zones. Given the dimensional limitations of the available test volumes of such material zones, the determination of mechanical properties presents a certain challenge. The paper investigates X welded joint of S690QL1 grade high strength steel (HSS), welded with slightly overmatching filler metal. The experimental work is focused on tensile testing to obtain stress-strain properties, as well as fracture mechanics testing. Considering the aforementioned limitations of the material test volume, tensile testing is carried out with mini tensile specimens (MTS), determining stress-strain curves for each characteristic weld zone. Fracture mechanical testing is carried out to determine the fracture toughness using the characteristic parameters. The experimental investigation is carried out using the single edge notch bend (SENB) specimens located in several characteristic welded joint zones: base metal (BM), heat affected zone (HAZ), and weld metal (WM). Fractographic analysis provides deeper insight into crack behavior in relation to specific weld zones. The numerical simulations are carried out in order to describe the fracture behavior of SENB specimens. Damage initiation and evolution is simulated using the ductile damage material behavior. This paper demonstrates the possibility of experimental and numerical determination of fracture mechanics behavior of characteristic heterogeneous welded joint zones and their influence on crack path growth.
Ključne besede: heterogeneous welded joint, high strength steel, mechanical testing, damage, fracture, mechanical properties, finite element analysis
Objavljeno v DKUM: 30.11.2023; Ogledov: 35; Prenosov: 0
Celotno besedilo (11,25 MB)
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Opis: High-throughput virtual screening (HTVS) is, in conjunction with rapid advances in computer hardware, becoming a staple in drug design research campaigns and cheminformatics. In this context, virtual compound library design becomes crucial as it generally constitutes the first step where quality filtered databases are essential for the efficient downstream research. Therefore, multiple filters for compound library design were devised and reported in the scientific literature. We collected the most common filters in medicinal chemistry (PAINS, REOS, Aggregators, van de Waterbeemd, Oprea, Fichert, Ghose, Mozzicconacci, Muegge, Egan, Murcko, Veber, Ro3, Ro4, and Ro5) to facilitate their open access use and compared them. Then, we implemented these filters in the open platform Konstanz Information Miner (KNIME) as a freely accessible and simple workflow compatible with small or large compound databases for the benefit of the readers and for the help in the early drug design steps.
Ključne besede: high-throughput virtual screening, virtual screening, compound libraries, library design, compound filtering
Objavljeno v DKUM: 25.07.2023; Ogledov: 200; Prenosov: 9
Celotno besedilo (4,19 MB)
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Opis: The present thesis is devoted to the immunity of Heads of State and high-ranking State officials, generally meaning the Heads of Government, and the Foreign Ministers, before the national and international courts, for international crimes as codified in the Rome Statute of the International Criminal Court (ICC), namely the crime of genocide, crimes against humanity, war crimes and the crime of aggression, with partial touch upon the crime of torture as well. The introductory part lays out the prosecution of State officials throughout the history all the way to the World War II, the Nuremberg and Tokyo Trials, and the developments in the decades post-World War II, with the eventual establishment of the ICC. Afterwards, the definitions and list of international crimes are discussed. Following the arguments for the rationale behind immunity and the correlation between immunity and jurisdiction, I elaborate on the various types of immunity, such as State immunity – and its subcategories personal and functional immunities – and diplomatic immunity. Thereby, I discuss at length the range of seemingly outstanding questions relating to, e.g., the scope of State officials entitled to immunity ratione personae, whether the commission of international crimes constitute officials acts, whether the immunity of State precludes a lawsuit towards State for breaches of jus cogens norms by acts that qualify as acta jure imperii, whether the diplomatic immunity pertains to high-ranking State officials other than ambassadors and diplomatic agents, etc. The explanations of other, less debatable questions, such as the distinction between personal and functional immunities for international crimes before national courts, is also provided. In the following part, I analyse the immunity of the incumbent high-ranking State officials before international courts, with a particular focus set on the ICC and Article 27 of the Rome Statute. Emphasizing provisions concerning international cooperation and judicial assistance to the ICC, I bring up Article 98 of the Rome Statute as a counterweight to the rejection of immunity before the ICC, and consider the interplay between both, Articles 27 and 98. Another point of divergence here is the question of which States fall under the scope of the term ‘third State’ in Article 98 of the Rome Statute. Furthermore, the analysis of the Al-Bashir case is provided through the application of the United Nations (UN) Security Council Resolution 1593 (2005), as well as Articles 25 and 103 of the UN Charter. Additionally, I intend to provide a method of resolving some of the ambiguities stemming out of the seemingly contradicting Rome Statute provisions by applying the rules of treaty interpretation, in particular its subsidiary means, discerning the object and purpose of the Rome Statute through the lenses of its Preamble. In the final part, I have sought out various other concepts that could supersede the immunity of high-ranking State officials for international crimes, including the jus cogens international crime exception to immunity, the obligation aut dedere aut judicare, and the universal jurisdiction.
Ključne besede: State immunity, immunity ratione personae, immunity ratione materiae, Heads of State, high-ranking State officials, international crimes, international courts, International Criminal Court (ICC), Rome Statute, Al-Bashir case, UN Security Council
Objavljeno v DKUM: 23.07.2021; Ogledov: 1010; Prenosov: 108
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Opis: The aim of this doctoral research was to develop and optimize parenteral nanoemulsions as well as the total parenteral nutrition (TPN) admixture containing a nanoemulsion obtained in the course of the optimization process (hereinafter referred to as optimal nanoemulsion), and to examine their physicochemical and biological quality as well. In addition, the quality of the prepared nanoemulsions was compared with the quality of the industrial nanoemulsion (Lipofundin® MCT/LCT 20%), and, in the end, the TPN admixture initially prepared was also compared with the admixture into which the industrial emulsion was incorporated. Parenteral nanoemulsions that were considered in this dissertation were prepared by the high-pressure homogenization method. This method is the most widely applied method for the production of nanoemulsions due to the shortest length of homogenization time, the best-obtained homogeneity of the product and the smallest droplet diameter. For the nanoemulsion formulation, preparation and optimization purposes, by using, firstly, the concept of the computer-generated fractional design, and, after that, the full experimental design, the assessment of both direct effects of different formulation and process parameters (the oil phase type, the emulsifier type and concentration, a number of homogenization cycles and the pressure under which homogenization was carried out) as well as the effects of their interactions on the characteristics of prepared nanoemulsions was performed. Monitoring the nanoemulsion physical and chemical stability parameters was carried out immediately after their preparation, and then after 10, 30 and 60 days. It included the visual inspection, the measurement of the droplet diameter (the mean and volume droplet diameter), the polydispersity index, the ζ-potential, the pH value, the electrical conductivity, and the peroxide number. After the preparation and after 60 days, the biological evaluation (the sterility test and the endotoxic test) of the prepared nanoemulsions was carried out. As far as the characterization of the TPN admixture is concerned, it included practically the same parameters. The dynamics of monitoring the characteristics of the TPN admixture was determined on the basis of practical needs of hospitalized patients (0h, 24h and 72h). The scope and comprehensiveness of this issue indicated the need to divide the doctoral dissertation into three basic stages. The first stage was preliminary. Using the 24-1 fractional factorial design, nanoemulsions for the parenteral nutrition were prepared. They contained either a combination of soybean and fish oil, or a combination of medium chain triglycerides and fish oil. In addition, the type and the amount of an emulsifier used, a number of high-pressure homogenization cycles, and the homogenization pressure, were also varied. The measurement of the above-mentioned parameters for the industrial nanoemulsion was parallely carried out (Lipofundin® MCT/LCT 20%). The objective of this part of the research was to identify critical numerical factors having the most significant effect on the characteristics that define the prepared parenteral nanoemulsions. Parameters that were singled out as the result of this stage of the research (the emulsifier concentration and a number of homogenization cycles) were used as independent variables in the second stage of the research.
Ključne besede: nanoemulsions, total parenteral nutrition admixtures, high pressure homogenization, design of experiments, optimization, analysis of variance, artificial neural networks
Objavljeno v DKUM: 07.06.2019; Ogledov: 11670; Prenosov: 17
Celotno besedilo (2,82 MB)