Subunit rotation models activation of serotonin 5-HT<Subscript>3AB</Subscript> receptors by agonists

The N-terminal extracellular regions of heterooligomeric 3AB-type human 5-hydroxytryptamine receptors (5-HT3ABR) were modelled based on the crystal structure of snail acetylcholine binding protein AChBP. Stepwise rotation of subunit A by 5 degrees was performed between -10 degrees and 15 degrees to mimic agonist binding and receptor activation. Anticlockwise rotation reduced the size of the binding cavity in interface AB and reorganised the network of hydrogen bonds along the interface. AB subunit dimers with different rotations were applied for docking of ligands with different efficacies: 5-HT, m-chlorophenylbiguanide, SR 57227, quinolinyl piperazine and lerisetron derivatives. All ligands were docked into the dimer with -10 degrees rotation representing ligand-free, open binding cavities similarly, without pharmacological discrimination. Their ammonium ions were in hydrogen bonding distance to the backbone carbonyl of W183. Anticlockwise rotation and contraction of the binding cavity led to distinctive docking interactions of agonists with E129 and cation-pi interactions of their ammonium ions. Side chains of several further amino acids participating in docking (Y143, Y153, Y234 and E236) are in agreement with the effects of point mutations in the binding loops. Our model postulates that 5-HT binds to W183 in a hydrophobic cleft as well as to E236 in a hydrophilic vestibule. Then it elicits anticlockwise rotation to draw in loop C via pi-cation-pi interactions of its ammonium ion with W183 and Y234. Finally, closure of the binding cavity might end in rebinding of 5-HT to E129 in the hydrophilic vestibule.     

Characterisation of a hydraulic high-pressure sample introduction assisted flow injection-inductively coupled plasma time-of-flight mass spectrometry system and its application to the analysis of biological samples

A flow injection (FI) method was developed using hydraulic high-pressure nebulization as a sample introduction system, coupled to inductively coupled plasma time-of-flight mass spectrometer (ICP-TOFMS) for rapid and simultaneous determination of 19 elements. The operating conditions of the system (analyte flow rate, heating and cooling temperatures of the desolvation module, carrier gas flow rate) for the simultaneous determination of 19 analytes were optimised. The optimum parameters of the sample introduction system were found to be 1.4 ml min⁻¹ and 1.35 l min⁻¹ for the analyte solution and nebulizer flow rates, respectively. A compromised condition for heating and cooling stage temperatures of 170 and −5 °C was chosen. The detection limits were compared to those obtained by using ICP-TOFMS with alternative sample introduction techniques e.g. conventional nebulization, flow injection chemical hydride generation (FI-CHG) and the obtained results were comparable or better than those resulting from alternative sample introduction. Applying the optimised conditions the simultaneous determination of Ag, As, Ba, Cd, Co, Cu, Ga, In, Li, Mn, Mo, Pb, Sb, Se, Sn, Sr, Tl, V and Zn was carried out. Absolute detection limits (3σ) in the range of 2-750 pg and precision between 0.5 and 9.6% from five replicate measurements of 10 ng ml⁻¹ multielemental sample solutions were achieved by using a 200 μl sample loop. The developed method was applied for the analysis of certified reference materials of biological origin (TORT-2 “Lobster Hepatopancrease”, BCR-422 “Cod Muscle” and IAEA MA-B-3/TM “Fish Homogenate”), and the results showed good agreement with the certified values.     

On approximately convex functions

A real valued function defined on a real interval is called -convex if it satisfies

The main results of the paper offer various characterizations for -convexity. One of the main results states that is -convex for some positive and if and only if can be decomposed into the sum of a convex function, a function with bounded supremum norm, and a function with bounded Lipschitz-modulus. In the special case , the results reduce to that of Hyers, Ulam, and Green obtained in 1952 concerning the so-called -convexity.

     

Untersuchung von Mehl- und Backwaren

Ohne Zusammenfassung     

Synthesis of new sulfonic acid-containing oligosaccharide mimetics of sialyl Lewis A

Two trisaccharides as new sulfonic acid mimetics of the sialyl Lewis A tetrasaccharide were synthesized. The natural sialic acid residue is replaced by a C-sulfonic acid moiety attached to position C-3′ of the lactosamine unit of the mimetics. The l-fucose unit was also replaced by a d-arabinose ring in one of the analogues. Formation of the sulfonic acid moiety on the trisaccharide level could be successfully achieved by means of introduction of an acetylthio moiety into the galactose skeleton and subsequent oxidation. The equatorial arrangement of the acetylthio group linked to C-3 of the galactose ring could be achieved by double nucleophilic substitution; efficient formation of the gulo-triflate derivatives required low-power microwave activation. Oxidation of the acetylthio group was carried out using Oxone in acetic acid.     

Towards a superstatistical SU(2) Yang-Mills EoS

We study an SU(2) lattice gauge field system on a 10⁴ symmetric and on a 10³ × 2 asymmetric lattice in order to learn about the equation of state.     

Tree metrics and edge-disjoint S-paths

Given an undirected graph \(G=(V,E)\) with a terminal set \(S \subseteq V\) , a weight function on terminal pairs, and an edge-cost \(a: E \rightarrow \mathbf{Z}_+\) , the \(\mu \) -weighted minimum-cost edge-disjoint \(S\) -paths problem ( \(\mu \) -CEDP) is to maximize \(\sum \nolimits _{P \in \mathcal{P}} \mu (s_P,t_P) - a(P)\) over all edge-disjoint sets \(\mathcal{P}\) of \(S\) -paths, where \(s_P,t_P\) denote the ends of \(P\) and \(a(P)\) is the sum of edge-cost \(a(e)\) over edges \(e\) in \(P\) . Our main result is a complete characterization of terminal weights \(\mu \) for which \(\mu \) -CEDP is tractable and admits a combinatorial min–max theorem. We prove that if \(\mu \) is a tree metric, then \(\mu \) -CEDP is solvable in polynomial time and has a combinatorial min–max formula, which extends Mader’s edge-disjoint \(S\) -paths theorem and its minimum-cost generalization by Karzanov. Our min–max theorem includes the dual half-integrality, which was earlier conjectured by Karzanov for a special case. We also prove that \(\mu \) -EDP, which is \(\mu \) -CEDP with \(a = 0\) , is NP-hard if \(\mu \) is not a truncated tree metric, where a truncated tree metric is a weight function represented as pairwise distances between balls in a tree. On the other hand, \(\mu \) -CEDP for a truncated tree metric \(\mu \) reduces to \(\mu '\) -CEDP for a tree metric \(\mu '\) . Thus our result is best possible unless P = NP. As an application, we obtain a good approximation algorithm for \(\mu \) -EDP with “near” tree metric \(\mu \) by utilizing results from the theory of low-distortion embedding.     

On the volume of the convex hull of two convex bodies

In this note we examine the volume of the convex hull of two congruent copies of a convex body in Euclidean $n$ -space, under some subsets of the isometry group of the space. We prove inequalities for this volume if the two bodies are translates, or reflected copies of each other about a common point or a hyperplane containing it. In particular, we give a proof of a related conjecture of Rogers and Shephard.     

Discrete pseudo-integrals

Integration of simple functions is a corner stone of general integration theory and it covers integration over finite spaces discussed in this paper. Different kinds of decomposition and subdecomposition of simple functions into basic functions sums, as well as different kinds of pseudo-operations exploited for integration and sumation result into several types of integrals, including among others, Lebesgue, Choquet, Sugeno, pseudo-additive, Shilkret, PAN, Benvenuti and concave integrals. Some basic properties of introduced discrete pseudo-concave integrals are discussed, and several examples of new integrals are given.