Human hemoglobin (Hb) is the preferred iron source of Staphylococcus aureus. This pathogenic bacterium exploits a sophisticated protein machinery called Iron-regulated surface determinant (Isd) system to bind Hb, extract and internalize heme and finally degrade it to complete iron acquisition. IsdB, the surface exposed Hb receptor, is a proven virulence factor of S. aureus and the inhibition of its interaction with Hb can be pursued as a strategy to develop new classes of antimicrobials. To identify small molecules able to disrupt IsdB:Hb protein-protein interactions (PPIs), we carried out a structure-based virtual screening campaign and developed an ad-hoc immunoassay to screen the retrieved set of commercially available compounds. Saturation-transfer difference (STD) NMR was applied to verify specific interactions of a sub-set of molecules, chosen based on their efficacy in reducing the amount of Hb bound to IsdB. Among molecules for which direct binding was verified, the best hit was submitted to ITC analysis to measure the binding affinity to Hb, which was found to be in the sub-micromolar range. The results demonstrate the viability of the proposed in silico/in vitro experimental pipeline to discover and test IsdB:Hb PPI inhibitors. The identified lead compound will be the starting point for future SAR and molecule optimization campaigns.
Rad istražuje momentum i contrarian strategije na hrvatskom dioničkom tržištu u razdoblju od 2000. do 2022. te nekoliko podrazdoblja unutar tog perioda. U cjelokupnom analiziranom razdoblju rezultati potvrđuju contarian efekt u kratkom, srednjem i dugom ulagačkom roku, dok su momentum i contrarian efekti potvrđeni u kratkom i srednjem ulagačkom roku u nekoliko podrazdoblja, pri čemu je contrarian efekt potvrđen u znatno većem broju slučajeva. Analiza ukazuje na varijabilnost veličine te značajnost momentum i contrarian efekta ovisno o periodu formiranja i periodu držanja portfelja te tržišnom režimu. Contrarian efekt potvrđen je u većem broju slučajeva i karakterizira ga općenito viša profitabilnost. Rezultati istraživanja u skladu su s nalazima literature koja je analizirala ove fenomene na razvijenim tržištima i tržištima u razvoju te upućuju na zaključak da hrvatsko tržište ima određenu vrstu memorije koja može biti podloga za generiranje dugoročnih ulagačkih profita.
CO-CREATION OF A VIRTUAL INTERACTIVE TEACHING PACKAGE FOR AUDITORS OF HEALTHCARE PLACEMENTS – TOWARDS ASSURANCE OF QUALITY OF HEALTH CARE TRAINEESHIPS
Actor network theory is a prominent theory on establishing connection between actors in a whole process. In this study, the application of the theory examines and establishes the connection between six actors that consist of human and nonhuman actors. Human actors are mainly the customers and wholesale operators, while nonhuman actors consist of digital platform, software, and application that are used to automate the process. This study is using a qualitative approach where researchers use an ethnographic case study approach. The researcher stays in the business-to-business procurement business for about 6 months and makes a series of observations on the process and network that connect one actor to another. The observation data is organized into several themes and presented in this chapter. The study contributes to the application of ANT in business-to-business procurement, especially wholesale procurement.
