The significance of halogen bonding in ligand-receptor interactions : the lesson learned from molecular dynamic simulations of the D4D_{4} receptor

Recently, a computational approach combining a structure–activity relationship library containing pairs of halogenated ligands and their corresponding unsubstituted ligands (called XSAR) with QM-based molecular docking and binding free energy calculations was developed and used to search for amino acids frequently targeted by halogen bonding, also known as XB hot spots. However, the analysis of ligand–receptor complexes with halogen bonds obtained by molecular docking provides a limited ability to study the role and significance of halogen bonding in biological systems. Thus, a set of molecular dynamics simulations for the dopamine D4 receptor, recently crystallized with the antipsychotic drug nemonapride (5WIU), and the five XSAR sets were performed to verify the identified hot spots for halogen bonding, in other words, primary (V5x40), and secondary (S5x43, S5x461 and H6x55). The simulations confirmed the key role of halogen bonding with V5x40 and H6x55 and supported S5x43 and S5x461. The results showed that steric restrictions and the topology of the molecular core have a crucial impact on the stabilization of the ligand–receptor complex by halogen bonding

Social activation of local communities in Poland from the perspective of 25 years of self-government

Odrodzenie samorządu terytorialnego w 1990 r. stanowiło zasadniczą zmianę ustrojową. Niedawno minęło 25 lat od tego wydarzenia, ale obraz rozwoju samorządności w Polsce trudno jednoznacznie ocenić. Celem niniejszego artykułu jest zarysowanie odpowiedzi na pytanie, w jakim stopniu oczekiwania związane z rewitalizacją społeczności lokalnych poprzez odrodzenie samorządu terytorialnego zostały spełnione, a więc w jakim stopniu realizację znalazła idea pomocniczości. Kwestia ta jest analizowana na przykładzie kilku obszarów życia społecznego: a) aktywności tzw. trzeciego sektora i współpracy organizacji pozarządowych z jednostkami samorządu terytorialnego (pomocniczość pozioma); b) stosowania procedur i technik partycypacji (włączania obywateli do procesu podejmowaniu decyzji publicznych); c) działania jednostek pomocniczych (rad osiedli i sołectw ‒ pomocniczość pionowa); d) aktywności obywatelskiej w postaci ruchów i inicjatyw społecznych (zwłaszcza tzw. ruchów miejskich); e) regionalizmu.Jeśli uznać, że celem reformy samorządowej było praktyczne zrealizowanie idei pomocniczości, to cel ten został osiągnięty. Jednak niewątpliwy sukces polskiej samorządności, który zmienił Polskę na lepsze, nie przełożył się na sukces polskiej samorządności rozumianej jako sfera harmonijnej współpracy wybieralnych władz lokalnych odpowiedzialnych wobec aktywnych społeczności. Struktury samorządu zdominowały życie lokalne, w wielu przypadkach urzędy stanowią największego pracodawcę, co ma negatywne oddziaływanie zarówno w sferze ekonomicznej, jak i społecznej. W tym sensie więc można mówić o częściowej porażce samorządności, która jest dzieckiem sukcesu reformy samorządowej.The revival of local government in 1990 constituted a fundamental change in the Polish political regime. However, on the twenty-fifth anniversary of this event the picture of local government in Poland is still unclear. The article offers answers to questions about how the expectations related to the revitalisation of local communities through the revival of local government have been met and about the scope of the idea of subsidiarity implementation. The following areas of social life are analysed: (i) the activity of what are known as third sector organisations and their cooperation with local government (horizontal subsidiarity); (ii) the use of procedures and techniques of participation by local government; (iii) the functioning of local government auxiliary units (district councils and village councils – vertical subsidiarity); (iv) activities of urban social movementsand initiatives; (v) regionalism. Considering the practical implementation of the idea of subsidiarity as the main purpose of the local government reform, the objective has been achieved. However, the unquestionable success of the Polish self-government which have changed Poland for the better does not entail the revival of Polish local communities. The harmonious  cooperation of elected local authorities accountable to an active community is still missing. Local government structures have dominated local life, being in many places the largest employer, with all negative consequences of this in terms of both economic and social life. In this sense, it can be argued that a partial failure of self-government is a side effect of the success of the self-government reform

Samorząd terytorialny w oczach socjologów – dyskusja

The last elections in Poland have substantially changed the political discourse. The new government has started to implement numerous reforms. Many of them aroused great controversy, including the one introducing changes in the local government system. This discussion can be considered as an invitation to broader considerations on the future of local government in Poland. It contains statements of six sociologists who are professionally interested in local government issues. They were inspired by three questions (asked by the editors of the text) about: (i) the possible outcome of the reform of the territorial self-government (ii) the functioning of the territorial self-government (iii) the evaluation of the discussion on the announced changes. The answers to these questions were based on the research knowledge and research experiences of the respondents and are therefore more science-based that general opinions typical for a public discussion which often manifest the worldview (or political attitudes) of the debating parties.Ostatnie wybory w Polsce mocno zmieniły sytuację polityczną. Nowe władze przystąpiły do realizacji licznych reform. Wiele z nich wzbudziło duże kontrowersje. Dotyczy to także zapowiedzi związanych ze zmianami w systemie samorządu terytorialnego. Artykuł można potraktować jako zaproszenie do dyskusji na temat przyszłości samorządności terytorialnej w Polsce. Zawiera wypowiedzi sześciu socjologów zajmujących się problematyką samorządową. Były one inspirowane trzema pytaniami, które dotyczyły: (1) bilansu polskiej reformy samorządowej, (2) problemów funkcjonowania samorządów, (3) oceny przebiegu dyskusji poświęconej zapowiedzianym zmianom. Wypowiedzi (odpowiedzi na pytania) opierają się na kompetencjach badaczy i ich doświadczeniu badawczym, są zatem w większym stopniu odwzorowaniem wiedzy naukowej i doświadczeń badawczych niż opinii, czy światopoglądu, które właściwe są dyskursowi publicznemu

The latest advances in wireless communication in aviation, wind turbines and bridges

Present-day technologies used in SHM (Structural Health Monitoring) systems in many implementations are based on wireless sensor networks (WSN). In the context of the continuous development of these systems, the costs of the elements that form the monitoring system are decreasing. In this situation, the challenge is to select the optimal number of sensors and the network architecture, depending on the wireless system’s other parameters and requirements. It is a challenging task for WSN to provide scalability to cover a large area, fault tolerance, transmission reliability, and energy efficiency when no events are detected. In this article, fundamental issues concerning wireless communication in structural health monitoring systems (SHM) in the context of non-destructive testing sensors (NDT) were presented. Wireless technology developments in several crucial areas were also presented, and these include engineering facilities such as aviation and wind turbine systems as well as bridges and associated engineering facilities

FACTORS OF MANAGING EFFECTIVENESS AND SOLVING CONFLICTS IN TERRITORIAL SELF-GOVERNMENTS

One can observe existence of significant differentiation in the situation of Polish territorial self-governments when it is examined from the perspective of the year 2000, i.e. 10 years after restitution of territorial self government system and one year since a reform o f administration by the Government of the Republic o f Poland which was supposed to grant the subjectivity to regional and subregional collectivities. On one hand - the differences observed concern a level of wealth of particular collectivities and a level of their respective economic advancement. On the other - the situation of particular self-governments is differentiated also in relation with adapting to new mechanisms of power performance and, as well, in what concerns adapting of all participants in collective life to new conditions under system transformation being still continued. The Author has discussed the above mentioned factors in macro-, mezo- and micro-scales and he concludes that there is no way to consider them separately. For instance - it won’t help to enjoy a good economic conjuncture of a State in such cases when local power occurs to be abortive and corrupt and some larger regional community does not show any activity of its own, any resourcefulness or economical sense on its own territory. The Author mentions also the destructive (but sometimes positive, too) role of a local conflict (e.g. increased activity and solidarity among members of local society

Influence of Terpene Type on the Release from an O/W Nanoemulsion: Experimental and Theoretical Studies

The interaction between a drug molecule and its carrier’s components is an important factor which influences the drug release profile. For this purpose, molecular dynamics (MD) may be the in silico tool which can help to understand the mechanism of drug loading/release. The aim of this work is to explain the effect of interactions between different types of terpenes, namely perillyl alcohol, forskolin, ursolic acid, and the nanoemulsion droplet core, on the release by means of experimental and theoretical studies. The basic nanoemulsion was composed of caprylic/capric triglyceride as the oil phase, polysorbate 80 as the emulsifier, and water. The in vitro release tests from a terpene-loaded nanoemulsion were carried out to determine the release profiles. The behavior of terpenoids in the nanoemulsion was also theoretically investigated using the molecular dynamics method. The forskolin-loaded nanoemulsion showed the highest percentage of drug release (almost 80% w/w) in contrast to ursolic acid and perillyl alcohol-loaded nanoemulsions (about 53% w/w and 19% w/w, respectively). The results confirmed that the kinetic model of release was terpene-type dependent. The zero-order model was the best to describe the ursolic acid release profile, while the forskolin and the perillyl alcohol followed a first-order and Higuchi model, respectively. Molecular dynamics simulations, especially energetical analysis, confirmed that the driving force of terpenes diffusion from nanoemulsion interior was their interaction energy with a surfactant

Application of Fragment Molecular Orbital Method to investigate dopamine receptors

GPCRs are a vast family of seven-domain transmembrane proteins. This family includes dopamine receptors (D1, D2, D3, D4, and D5), which mediate the variety of dopamine-controlled physiological functions in the brain and periphery. Ligands of dopamine receptors are used for managing several neuropsychiatric disorders, including bipolar disorder, schizophrenia, anxiety, and Parkinson’s disease. Recent studies have revealed that dopamine receptors could be part of multiple signaling cascades, rather than of a single signaling pathway. For these targets, a variety of experimental and computational drug design techniques are utilized. In this work, dopamine receptors D2, D3, and D4 were investigated using molecular dynamic method as well as computational ab initio Fragment Molecular Orbital method (FMO), which can reveal atomistic details about ligand binding. The results provided useful insights into the significances of amino acid residues in ligand binding sites. Moreover, similarities and differences between active-sites of three studied types of receptors were examined