Electrochemiluminescence Bioassays with a Water‐Soluble Luminol Derivative Can Outperform Fluorescence Assays

The most efficient and commonly used electrochemiluminescence (ECL) emitters are luminol, [Ru(bpy)₃]²⁺, and derivatives thereof. Luminol stands out due to its low excitation potential, but applications are limited by its insolubility under physiological conditions. The water‐soluble m‐carboxy luminol was synthesized in 15 % yield and exhibited high solubility under physiological conditions and afforded a four‐fold ECL signal increase (vs. luminol). Entrapment in DNA‐tagged liposomes enabled a DNA assay with a detection limit of 3.2 pmol L^?1, which is 150 times lower than the corresponding fluorescence approach. This remarkable sensitivity gain and the low excitation potential establish m‐carboxy luminol as a superior ECL probe with direct relevance to chemiluminescence and enzymatic bioanalytical approaches.     

A note on the central limit theorem for bipower variation of general functions

In this paper we present a central limit theorem for general functions of the increments of Brownian semimartingales. This provides a natural extension of the results derived in [O.E. Barndorff-Nielsen, S.E. Graversen, J. Jacod, M. Podolskij, N. Shephard, A central limit theorem for realised power and bipower variations of continuous semimartingales, in: From Stochastic Analysis to Mathematical Finance, Festschrift for Albert Shiryaev, Springer, 2006], where the central limit theorem was shown for even functions. We prove an infeasible central limit theorem for general functions and state some assumptions under which a feasible version of our results can be obtained. Finally, we present some examples from the literature to which our theory can be applied.     

Fragment‐Based De Novo Design Reveals a Small‐Molecule Inhibitor of Helicobacter Pylori HtrA

Sustained identification of innovative chemical entities is key for the success of chemical biology and drug discovery. We report the fragment‐based, computer‐assisted de novo design of a small molecule inhibiting Helicobacter pylori HtrA protease. Molecular binding of the designed compound to HtrA was confirmed through biophysical methods, supporting its functional activity in vitro. Hit expansion led to the identification of the currently best‐in‐class HtrA inhibitor. The results obtained reinforce the validity of ligand‐based de novo design and binding‐kinetics‐guided optimization for the efficient discovery of pioneering lead structures and prototyping drug‐like chemical probes with tailored bioactivity.     

Context-based identification of protein-protein interfaces and "hot-spot" residues

Reliable determination of protein-protein interaction sites is of critical importance for structure-based design of small molecules modulating protein function through macromolecular interfaces. We present an alignment-free computational method for prediction of protein-protein interface residues. The method ("iPred") is based on a knowledge-based scoring function adapted from the field of protein folding and small molecule docking. Based on a training set of 394 hetero-dimeric proteins iPred achieves sustained accuracy on an external unbound test set. Prediction robustness was assessed from more than 1500 diverse complexes containing homo- and hetero-dimers. The technique does not rely on sequence conservation, so that rapid interface identification is possible even for proteins for which homologs are unknown or lack conserved residue patterns in interface region. Functional "hot-spot" residues are enriched among the predicted interface residues, rendering the method predestined for macromolecular binding site identification and drug design studies aiming at modulating protein-protein interaction that might influence protein function. For a comparative structural model of peptidase HtrA from Helicobacter pylori, we performed mutation studies for predicted hot-spot residues, which were confirmed as functionally relevant for HtrA activity or oligomerization.     

A characterization of bounded convex approximation properties

The characterization of bounded approximation properties defined by arbitrary operator ideals due to Oja is extended to bounded convex approximation properties. As an application, it is shown that the unique extension property of a Banach space X enables to lift the metric convex approximation property from a Banach space X to its dual space X*.     

Gas-phase oxidation and reduction of some 1-(2-benzothiazolyl)-3,5-diphenyl formazans. Complex formation with transition metals under laser desorption ionization

Five differently substituted 1-(2-benzothiazolyl)-3,5-diphenyl formazans were studied by laser desorption ionization (LDI) and matrix assisted laser desorption/ionization (MALDI) mass spectrometry. The best explanation of the results is that the formazan molecules are photoionized to molecular radical ions, which then further react by ion-molecule reactions. Supporting this proposal was the abundant formation of [M − H]⁺ ions under LDI. These ions are not observed at all under either electron or chemical ionization. Under MALDI, the extent of the oxidation process is clearly dependent on the ability of the matrix to act as a reducing agent. With transition metals the formazans formed singly charged 1:2 metal:formazan complexes. The most stable electronic configuration of the complex determined the oxidation state of the metal regardless of its initial oxidation state. In some cases, this process also demanded a gas-phase reduction of the formazan. The ionization efficiency and affinity for complex formation depended on the substituent at the 3-phenyl group; both were increased by an electron donating substituent. The formazans were also tested as potential matrices for MALDI. Reasonable results were observed for several groups of compounds; however, only the piperazine ligands produced higher quality spectra with formazans than with common commercial matrices.     

Electric load forecasting methods: Tools for decision making

For decision makers in the electricity sector, the decision process is complex with several different levels that have to be taken into consideration. These comprise for instance the planning of facilities and an optimal day-to-day operation of the power plant. These decisions address widely different time-horizons and aspects of the system. For accomplishing these tasks load forecasts are very important. Therefore, finding an appropriate approach and model is at core of the decision process. Due to the deregulation of energy markets, load forecasting has gained even more importance. In this article, we give an overview over the various models and methods used to predict future load demands.     

Low-Valent MxAl3 Cluster Salts with Tetrahedral [SiAl3]+ and Trigonal-Bipyramidal [M2Al3]2+ Cores (M=Si/Ge)

Schnöckel's [(AlCp*)₄] and Jutzi's [SiCp*][B(C₆F₅)₄] (Cp*=C₅Me₅) are landmarks in modern main-group chemistry with diverse applications in synthesis and catalysis. Despite the isoelectronic relationship between the AlCp* and the [SiCp*]⁺ fragments, their mutual reactivity is hitherto unknown. Here, we report on their reaction giving the complex salts [Cp*Si(AlCp*)₃][WCA] ([WCA]⁻=[Al(OR^F)₄]⁻ and [F{Al(OR^F)₃}₂]⁻; R^F=C(CF₃)₃). The tetrahedral [SiAl₃]⁺ core not only represents a rare example of a low-valent silicon-doped aluminium-cluster, but also—due to its facile accessibility and high stability—provides a convenient preparative entry towards low-valent Si−Al clusters in general. For example, an elusive binuclear [Si₂(AlCp*)₅]²⁺ with extremely short Al−Si bonds and a high negative partial charge at the Si atoms was structurally characterised and its bonding situation analysed by DFT. Crystals of the isostructural [Ge₂(AlCp*)₅]²⁺ dication were also obtained and represent the first mixed Al−Ge cluster.     

Aerial Vehicle Search-Path Optimization: A Novel Method for Emergency Operations

This paper presents a novel search-path optimization method for moving target search by an aerial vehicle, applicable to realistically sized search areas. For such missions, long endurance vehicles are needed, which are usually fixed-winged. The proposed method accounts for flight kinematics of fixed-wing and rotary-wing aerial vehicles. It additionally accounts for movements of the target, considerably increasing complexity of search-path optimization, compared to a static target. The objective is to maximize the probability to detect a conditionally deterministic moving target within a given time period. We propose a first K-step-lookahead planning method that takes flight kinematic constraints into account and in which the target and platform state space are heterogeneous. It consists of a binary integer linear program that yields a physically feasible search-path, while maximizing the probability of detection. It is based on the Max-K-Coverage problem, as it selects K waypoints while maximizing the probability that a target is within the field of view of a platform at one of these waypoints. This K-step-lookahead planning method is embedded in an iterative framework, where the probability of overlooking a target is fed back to the controller after observations are made. Simulations show the applicability and effectiveness of this method.