Towards intelligent drug design system: Application of artificial dipeptide receptor library in QSAR-oriented studies

The pharmacophore properties of a new series of potential purinoreceptor (P2X) inhibitors determined using a coupled neural network and the partial least squares method with iterative variable elimination (IVE-PLS) are presented in a ligand-based comparative study of the molecular surface by comparative molecular surface analysis (CoMSA). Moreover, we focused on the interpretation of noticeable variations in the potential selectiveness of interactions of individual inhibitor-receptors due to their physicochemical properties; therefore, the library of artificial dipeptide receptors (ADP) was designed and examined. The resulting library response to individual inhibitors was arranged in the array, preprocessed and transformed by the principal component analysis (PCA) and PLS procedures. A dominant absolute contribution to PC1 of the Glu attached to heptanoic gating acid and Phe bonded to the linker m-phenylenediamine/triazine scaffold was revealed by the PCA. The IVE-PLS procedure indicated the receptor systems with predominant Pro bonded to the linker and Glu, Gln, Cys and Val directly attached to the gating acid. The proposed comprehensive ligand-based and simplified structure-based methodology allows the in-depth study of the performance of peptide receptors against the tested set of compounds.NC

The digital library management on the example of Krakow's digital libraries

Celem pracy było zbadanie i zaprezentowanie źródeł oraz sposobów finansowania bibliotek cyfrowych w Polsce, w tym procesu digitalizacji, a także analiza organizacji pracy bibliotek cyfrowych, na podstawie badań przeprowadzonych w siedmiu krakowskich bibliotekach cyfrowych. Zarysowano charakterystykę każdej z badanych bibliotek cyfrowych, w tym ich krótką historię oraz informacje o typie zasobów i ich ilości. Po przeanalizowaniu wyników badań stwierdzono, że większość bibliotek cyfrowych nie posiada własnego budżetu, finansowane są jedynie przez organizatora. Tylko biblioteki cyfrowe dużych instytucji mają potencjał niezbędny do uzyskania funduszy z programów Unii Europejskiej. Pracownicy zatrudnieni przy digitalizowaniu zasobów pełnią wiele funkcji równocześnie, często nie są to ich jedyne obowiązki pracownicze.The aim of this thesis was to examine and to present the sources and means of digital libraries’ financing in Poland, including the process of digitization, and to analyse digital libraries’ work organization, on the basis of research conducted in seven Krakow’s digital libraries. The characteristic of each researched digital libraries, including their short history and information containing type and amount of resources, was depicted. It was stated, after the analyse of the research results, that the most digital libraries don’t have their own budget, but only funding from their organiser. Only digital libraries maintained by large institution have the potential necessary to obtain European Union funds. The workers, employed in digitization of resources, fulfil at the same time many functions, which often aren’t their only duties

Jagiellonian Digital Library – the concept and problems of its creation

The aim of this master's thesis is the presentation of the idea of Jagiellonian Digital Library (JDL) and the problems, that are appearing in process of its creation. JDL is a result of two projects: “Jagiellonian Digital Library” and “Safe and complex accessibility of Jagiellonian University digital resources in the Internet. Stage I”, that are co-financed by European Union and emphasize the protection of antique library collections and the development of information society. The concept of JDL and the stages of its creation was presented in detail, and potential and real problems were taken under consideration. The picture of JDL, its collections and popularity were shown using statistics of dLibra program. The conclusion of this research was a statement, that the most popular publication type is a periodical in Polish, in DjVu format and it is already in public domain.Celem pracy było przedstawienie koncepcji Jagiellońskiej Biblioteki Cyfrowej (JBC) oraz problemów w procesie jej tworzenia. JBC to rezultat projektów „Jagiellońska Biblioteka Cyfrowa” oraz „ Bezpieczne i kompleksowe udostępnianie zasobów cyfrowych Uniwersytetu Jagiellońskiego w sieci Internet. Etap I”, dofinansowanych przez Unię Europejską i kładących nacisk na ochronę zabytkowych zbiorów bibliotecznych oraz rozwój społeczeństwa informacyjnego. Szczegółowo zaprezentowano koncepcję JBC oraz etapy jej powstawania, z uwzględnieniem potencjalnych i rzeczywiście występujących problemów. Wykorzystując statystki programu dLibra zarysowano obraz JBC, jej zbiorów i popularności. Wnioskiem z badań było stwierdzenie, że najbardziej popularnym typem publikacji jest czasopismo w języku polskim, w formacie DjVu, znajdujące się w domenie publicznej

Antibacterial and Antifungal Properties of Modified Chitosan Nonwovens

Chitosan acquires bacteriostatic properties via protonation of its amino groups. However, much of the literature assumes that chitosan itself inhibits the growth of bacteria. This article presents a comparative study of chitosan nonwovens modified with various acids, including acetic, propionic, butyric, and valeric organic acids, as well as hydrochloric acid. The aim was to determine which acid salts influence the antibacterial and antifungal activity of chitosan-based materials. Two methods were used to modify (formation of ammonium salts) the chitosan nonwovens: First, acid vapors (gassing process) were used to find which salt of chitosan had the best antibacterial properties. Based on the results, the most effective acid was prepared in a solution in ethanol. The influence of the acid concentration in ethanol, the time of treatment of chitosan materials with acid solution, and the rinsing process of modified nonwovens on the antimicrobial activity of the modified materials was investigated. The modified materials were subjected to microbiological tests. Each of the modified materials was placed in bacterial inoculum. The cultures were tested on agar to observe their microbial activity. Toxicity to human red blood cells was also investigated. A reduction in the number of bacterial cells was observed for the S. aureus strain with chitosan salt modified with 10% acetic acid in ethanol. The antibacterial activity of the chitosan salts increased with the percentage of acid salts formed on the surface of the solid material (decreasing numbers of bacterial colonies or no growth). No reduction in growth was observed for the E. coli strain. The chitosan samples were either inactive or completely eliminated the bacterial cells. Antimicrobial activity was observed for chitosan salts with hydrochloric acid and acetic acid. Finally, 1H-NMR spectroscopy and FTIR spectroscopy were used to confirm the incorporation of the acid groups to the amino groups of chitosan

1,3,5-Triazine Nitrogen Mustards with Different Peptide Group as Innovative Candidates for AChE and BACE1 Inhibitors

A series of new analogs of nitrogen mustards (4a–4h) containing the 1,3,5-triazine ring substituted with dipeptide residue were synthesized and evaluated for the inhibition of both acetylcholinesterase (AChE) and β-secretase (BACE1) enzymes. The AChE inhibitory activity studies were carried out using Ellman’s colorimetric method, and the BACE1 inhibitory activity studies were carried out using fluorescence resonance energy transfer (FRET). All compounds displayed considerable AChE and BACE1 inhibition. The most active against both AChE and BACE1 enzymes were compounds A and 4a, with an inhibitory concentration of AChE IC50 = 0.051 µM; 0.055 µM and BACE1 IC50 = 9.00 µM; 11.09 µM, respectively

Revised Coordination Model and Stability Constants of Cu(II) Complexes of Tris Buffer

2-Amino-2-hydroxymethyl-propane-1,3-diol, or tris(hydroxymethyl)aminomethane (Tris), is probably the most common biochemical buffer used alone or in combination with other buffers because it is stable, unreactive, and compatible with most proteins and other biomolecules. Being nontoxic, it has even found applications in medicine. Tris is known, however, to coordinate transition metal ions, Cu(II) among them. Although often ignored, this feature affects interactions of Cu(II) ions with biomolecules, as Tris is usually used in high molar excess. Therefore, it is important to have precise knowledge on the stoichiometry, stability, and reactivity of cupric Tris complexes. The literature data are incoherent in this respect. We reinvestigated the complex formation in the Tris-Cu(II) system by potentiometry, UV-vis, ESI-MS, and EPR at a broad range of concentrations and ratios. We found, contrary to several previous papers, that the maximum stoichiometry of Tris to Cu(II) is 2 and at neutral pH, dimeric complexes are formed. The apparent affinity of Tris buffer for Cu(II), determined by the competitivity index (CI) approach [Krężel, A.; Wójcik, J.; Maciejczyk, M.; Bal, W. Chem. Commun. 2003, 6, 704-705] at pH 7.4 varies between 2 × 10(6) and 4 × 10(4) M(-1), depending on the Tris and Cu(II) concentrations and molar ratio

Chemical Modification as a Method of Improving Biocompatibility of Carbon Nonwovens

It was shown that carbon nonwoven fabrics obtained from polyacrylonitrile fibers (PAN) by thermal conversion may be modified on the surface in order to improve their biological compatibility and cellular response, which is particularly important in the regeneration of bone or cartilage tissue. Surface functionalization of carbon nonwovens containing C–C double bonds was carried out using in situ generated diazonium salts derived from aromatic amines containing both electron-acceptor and electron-donor substituents. It was shown that the modification method characteristic for materials containing aromatic structures may be successfully applied to the functionalization of carbon materials. The effectiveness of the surface modification of carbon nonwoven fabrics was confirmed by the FTIR method using an ATR device. The proposed approach allows the incorporation of various functional groups on the nonwovens’ surface, which affects the morphology of fibers as well as their physicochemical properties (wettability). The introduction of a carboxyl group on the surface of nonwoven fabrics, in a reaction with 4-aminobenzoic acid, became a starting point for further modifications necessary for the attachment of RGD-type peptides facilitating cell adhesion to the surface of materials. The surface modification reduced the wettability (θ) of the carbon nonwoven by about 50%. The surface free energy (SFE) in the chemically modified and reference nonwovens remained similar, with the surface modification causing an increase in the polar component (ɣp). The modification of the fiber surface was heterogeneous in nature; however, it provided an attractive site of cell–materials interaction by contacting them to the fiber surface, which supports the adhesion process