Ionotróp receptorok allosztérikus modulációja = Allosteric modulation of ionotropic receptors

A pentamer szerkezetű ionofór neurotranszmitter ?-aminovajsav, szerotonin és glicin receptorok (GABAAR, 5-HT3R, GlyR) szerkezetét és allosztérikus szabályozását vizsgáltuk meg. Az 5-HT3AR-ok pontmutációi és számítógépes modellezése antagonistáik kétféle kötődésmódját igazolták. Két fő neuroszteroidnak (allopregnanolon és THDOC) a GABAAR kötődésre és ionofór funkciója potencírozására kifejtett eltérő hatásai alapján a nanomoláris allopregnanolon az α6ßδ GABAAR-ok fiziológiás modulátora. Au allopregnanolon 17ß-származékát az első nanomólos affinitású, α6ßδ receptor- és sztereoszelektív neuroszteroid antagonistaként jellemeztük. Bifenil származékok gyulladásgátló és GABAAR-kötődési hatásainak szerkezeti kritériumait megkülönböztettük. 5-HT3 R antagonistákból kifejlesztettünk GlyR-okra és hiperekplexia mutánsukra szelektív potenciáló (nor)tropeineket. A heteroaromás tropein észterek heterogén GlyR-kötődésének nanomólos fázisát potenciáláshoz, a µmólost gátláshoz rendeltük. Az α1 GlyR pontmutációi és molekuladinamikai szimulációja alátámasztja az Arg-119 rotamerek és nortropeinek kötődésmódjai eltérő szerepét a GlyR-t gátló és potenciáló hatásokban. | The structures and allosteric modulation of pentameric ionotropic neurotransmitter receptors of ?-aminobutyric acid, serotonin and glycine (GABAAR, 5-HT3R, GlyR) were examined. Point mutations and computer modeling of 5-HT3ARs supported dual binding modes of antagonists. Based on different effects of two major neurosteroids, allopregnanolone and THDOC, on GABAAR binding and ionophore potentiation, nanomolar allopregnanolone is the physiologic modulator of α6ßδ GABAARs. Structural requirements of the anti-inflammatory and GABAAR-binding effects of biphenyl derivatives were distinguished. From 5-HT3 R antagonists (nor)tropeines were developed to selective potentiators of GlyRs and their hyperekplexia mutants. Nanomolar and micromolar phases of GlyR binding of heteroaromatic tropeine esters were attributed to potentiation and inhibition of GlyRs respectively. Point mutations of α1 GlyRs and molecular dynamic simulations supported the differential roles of Arg-119 rotamers and dual binding modes of nortropeines to block versus potentiate GlyRs

Bimetallic cast iron rolls – Some approaches to assure the exploitation properties

U ovom se radu detaljno razmatra utjecaj nekih tehnoloških faktora na trajnost valjaoničkih željeznih valjaka i predlažu rješenja za povećanje izdržljivosti u uporabi. Istraživanjem se pokušavaju dati odgovori na najvažnije probleme u vezi povećanja tvrdoće valjaka. Dobiveni rezultati su od neposredne praktične koristi kako za proizvođačku industriju valjaoničkih valjaka od lijevanog željeza tako i za valjaoničke odjele. U tom se smislu ovi rezultati mogu koristiti u ljevaonicama i valjaonicama za osiguranje kvalitete valjaka sve od faze proizvodnje pa do uporabe, što neizbježno vodi do osiguranja kvalitete proizvedenih laminata. Analiziraju se stvarni tehnički uvjeti lijevanja kako bi se povećala otpornost valjaka na trošenje, smanjili troškovi konverzije i reducirao otpad, smanjili radni troškovi smanjivanjem bogato legiranog željeza s potrošnjom nikla, kroma i molibdena. Korištenjem nove metode istraživanja – numeričke simulacije – obradili su se statistički i matematički podaci zabilježeni kada se elaborirao željezni lijev tipa FDId2 namijenjen lijevanju tvrde kore bimetalnih valjaka velikog promjera. Svrha je optimizirati kemijski sastav kao faktor od utjecaja na tvrdoću valjaka, a tako implicitno i na njihova uporabna svojstva. Postizanje optimalnog kemijskog sastava može predstavljati tehnički efikasan način za osiguranje uporabnih svojstava budući da materijal valjaka ima u tom smislu važnu ulogu. Primijenjena je matematička metoda počevši od diferenciranja sastavnih dijelova valjaka, uzimajući u obzir industrijske podatke dobivene u ljevaonici valjaka, kao i specifikacije nacionalnog standarda koji preporučuje tvrdoću kod različitih kemijskih sastava. U tom smislu ovo istraživanje može pridonijeti optimiziranju industrijskih tehnologija analizom i matematičkim eksperimentom.The study represents a detailed approach of the influence of some technological factors on durability in exploitation of rolling mill iron rolls and suggests solutions meant to increase the durability of the rolls in exploitation. These researches are trying to give answers to most of the actual problems related to the increase of hardness of rolling mill rolls. These results are of immediate practical utility both for the cast-iron rolling mills roll manufacturing industry and the rolling sectors. In this sense, these research results can be used in the collective framework of the foundries and the rolling mills sectors for quality assurance of rolls as far back as the phase of production to their exploitation, what leads to, inevitably, the quality assurance of produced laminates. Genuine casting technical conditions are analyzed in order to increase the rolls\u27 resistance to wearing, decrease the conversion costs and reduce the waste, decrease the labor costs by lowering the richly alloyed iron with nickel, chromium and molybdenum consumption. Using the new research technique – the numerical simulation – statistical and mathematical data, registered when elaborating the cast iron type FDId2 destined to cast the hard crust of the large-diameter bimetallic rolls, were processed within the present research. The purpose is the optimization of the chemical composition as an influential factor on the rolls hardness, thus, implicitly, on their exploiting qualities. The realization of an optimal chemical composition can constitute a technically efficient mode to assure the exploitation properties, the rolling mills rolls material having an important role in this sense. From this point of view the mathematical modeling is applied, starting from the differentiation on rolls component parts, taking into consideration the industrial data obtained in rolls-foundry, as well as the national standard specifications, which recommend the hardness for different chemical compositions. From this point of view the research is inscribed in the context of scientific capitalization of the process and the industrial technologies optimization, in the way of the analysis and the mathematical experiment

Tehnološke korelacije između tvrdoće i glavnih legirnih elemenata kod valjaka od polutvrdog lijevanog željeza

The technical conditions, which are imposed on the cast iron rolls in the exploitation period, are very different and often contradictory. The obtaining of various physical and mechanical properties at the different points of the same foundry product meets difficult technological problems in the industrial conditions. One of the parameters, which determine the structure of the irons destined for rolls casting, is the chemical composition. If we do not respect this composition, which guarantees the exploitation properties of each roll in the stand of rolling mill, it will lead to rejection. Alloying elements have in principle the same influence on structure and properties. This paper suggests a mathematical interpretation of the influence of the main alloying elements on the mechanical characteristics (the hardness on the crust of the rolls) of this nodular irons, resulting in the average values and average square aberration of the variables HB, and the main alloying elements (Cr, Ni, Mo), the equations of the hyper surface in the four dimensional space. For the statistical and mathematical analysis, there were used some industrial cases. The resulted surfaces, belonging to the three-dimensional space, can be represented and, therefore, interpreted by technologists. Knowing these level curves allows the correlation of the values of two independent variables so that HB can be obtained within the requested limits.Tehnički uvjeti koji djeluju na valjke od lijevanog željeza tijekom upotrebe su jako različiti i često kontradiktorni. Tijekom dobivanja različitih fizičkih i mehaničkih svojstava u različitim fazama istog proizvoda susrećemo se s teškim tehnološkim problemima u industrijskim uvjetima. Kemijski sastav je jedan od parametara koji određuje strukturu željeza predodređenih za lijevanje valjaka. Ako ne poštujemo ovaj sastav, koji garantira dobra svojstva svakog valjka u valjaonici, to će dovesti do pojave škarta. Legirni elementi imaju u principu isti utjecaj na strukturu i svojstva. Ovaj rad predlaže matematički model utjecaja glavnih legirnih elemenata na mehanička svojstva (tvrdoća površine valjka) ovih nodularnih lijevova, što rezultira srednjim vrijednostima i srednjim kvadratnim odstupanjem varijabli HB, i glavnih legirnih elemenata (Cr, Ni, Mo), jednadžbe hiper-površine u četverodimenzionalnom prostoru. Za statističku i matematičku analizu korišteni su neki industrijski slučajevi. Tehnolozi mogu prikazati i interpretirati dobivene površine koje pripadaju trodimenzionalnom prostoru. Poznavanje tih krivulja nivoa omogućuje korelaciju vrijednosti dvije neovisne varijable tako da se HB može dobiti unutar traženih granica

A turizmus fejlesztési lehetőségei a Kadarkúti - Nagybajomi kistérségben

The main objective of the research is to examine the tourist characteristic of Kadarkút micro-region and explore potential development areas, break out and possible forms of cooperation points in the region. After reviewing the attractive tourist places, and the available services we identified, that the tourism supply factors are distributed unequally, in a mosaic form. The main tourist products (eco, rural, active, cultural and heritage tourism) and the connected services do not appear as relevant economic factors, because the demand is mainly local or regional. The national and even international demand appear as well, but only in modest level. Probably the increase tourism would accelerate if such cooperation between municipalities and the tourist service providers, which would ensure a reliable, continuous supply and provide high-quality image in the region

State-Dependent Network Connectivity Determines Gating in a K+ Channel

YesX-ray crystallography has provided tremendous insight into the different structural states of membrane proteins and, in particular, of ion channels. However, the molecular forces that determine the thermodynamic stability of a particular state are poorly understood. Here we analyze the different X-ray structures of an inwardly rectifying potassium channel (Kir1.1) in relation to functional data we obtained for over 190 mutants in Kir1.1. This mutagenic perturbation analysis uncovered an extensive, state-dependent network of physically interacting residues that stabilizes the pre-open and open states of the channel, but fragments upon channel closure. We demonstrate that this gating network is an important structural determinant of the thermodynamic stability of these different gating states and determines the impact of individual mutations on channel function. These results have important implications for our understanding of not only K+ channel gating but also the more general nature of conformational transitions that occur in other allosteric proteins.Wellcome Trus