Structure-activity-based design of a synthetic malaria peptide eliciting sporozoite inhibitory antibodies in a virosomal formulation

The circumsporozoite protein (CSP) of Plasmodium falciparum is a leading candidate antigen for inclusion in a malaria subunit vaccine. We describe here the design of a conformationally constrained synthetic peptide, designated UK-39, which has structural and antigenic similarity to the NPNA-repeat region of native CSP. NMR studies on the antigen support the presence of helical turn-like structures within consecutive NPNA motifs in aqueous solution. Intramuscular delivery of UK-39 to mice and rabbits on the surface of reconstituted influenza virosomes elicited high titers of sporozoite crossreactive antibodies. Influenza virus proteins were crucially important for the immunostimulatory activity of the virosome-based antigen delivery system, as a liposomal formulation of UK-39 was not immunogenic. IgG antibodies elicited by UK-39 inhibited invasion of hepatocytes by P. falciparum sporozoites, but not by antigenically distinct P. yoelii sporozoites. Our approach to optimized virosome-formulated synthetic peptide vaccines should be generally applicable for other infectious and noninfectious diseases.     

Synthesis and characterization of immobilized PAMAM dendrons

This communication describes the synthesis and characterization of immobilized PAMAM dendrons onto a surface modified silicon wafer substrate (functionalized using plasma polymerized PAA) using a "growing from" strategy.     

Synthesis,Structure, and Electrochemical Properties of Sterically Protected Molybdenum Trihydride Redox Pairs: A Paramagnetic “Stretched” Dihydrogen Complex?

Complexes [MoCp(#)(PMe(3))(2)H(3)] (Cp(#)=1,2,4-C(5)H(2)tBu(3), 2 a; C(5)HiPr(4), 2 b) have been synthesized from the corresponding compounds [MoCp(#)Cl(4)] (1 a, 1 b) and fully characterized, including by X-ray crystallography and by a neutron diffraction study for 2 a. Protonation of 2 a led to complex [Mo(1,2,4-C(5)H(2)tBu(3))(PMe(3))(2)H(4)](+) (3 a) in THF and to [Mo(1,2,4-C(5)H(2)tBu(3))(PMe(3))(2)(MeCN)H(2)](+) (4 a) in MeCN. Complex 4 b analogously derives from protonation of 2 b in MeCN, whereas the tetrahydride complex 3 b is unstable. One-electron oxidation of 2 a and 2 b by [FeCp(2)]PF(6) produces the EPR-active 17-electron complexes 2 a(+) and 2 b(+). The former is thermally more stable than the latter and could be crystallographically characterized as the PF(6) (-) salt by X-ray diffraction, providing evidence for the presence of a stretched dihydrogen ligand (H...H=1.36(6) angstroms). Controlled thermal decomposition of 2 a(+) yielded the product of H(2) elimination, the 15-electron monohydride complex [Mo(1,2,4-C(5)H(2)tBu(3))(PMe(3))(2)H]PF(6) (5 a), which was characterized by X-ray crystallography and by EPR spectroscopy at liquid He temperature. The compound establishes an equilibrium with the solvent adduct in THF. An electrochemical study by cyclic voltammetry provides further evidence for a rapid H(2) elimination process from the 17-electron complexes. In contrast to the previously investigated [MoCp*(dppe)H(3)](+) system (dppe=1,2-bis(diphenylphosphino)ethane; Cp*=pentamethylcyclopentadienyl), the decomposition of 2 a(+) by H(2) substitution with a solvent molecule appears to follow a dissociative pathway in MeCN.     

Wurster's crowns: a comparative study of ortho- and para-phenylenediamine-containing macrocyclic receptors

Two series of isomeric, redox-responsive azacrown ethers based on ortho- and para-phenylenediamine (Wurster's crowns) have been synthesized and their properties explored through 13C NMR spectroscopy, electrospray ionization mass spectrometry, cyclic voltammetry, and X-ray crystallography. These crowns display strong affinity for alkali metal cations while maintaining comparable selectivity profiles to the parent crown ethers from which they are derived. Like Wurster's reagent (N,N,N',N'-tetramethyl-p-phenylenediamine or para-TMPD), the para-Wurster's crowns undergo two reversible one-electron oxidations. The integrity of the alkali metal ion complexes is maintained in the neutral and singly oxidized ligand states but not after removal of two electrons. In contrast, the oxidation of ortho-Wurster's crowns is scan rate dependent, occurring at potentials substantially higher than their para counterparts, with their complexes oxidizing irreversibly. X-ray crystal structures of representative complexes show, in all cases, participation of the redox-active phenylenediamine subunits in complex formation via direct bonding to the guest cation.     

Purification of deoxynivalenol from Fusarium graminearum rice culture and mouldy corn by high-speed counter-current chromatography

Deoxynivalenol (DON) is a mycotoxin produced by several Fusarium species and is toxic to a wide range of organisms, including human beings and livestock. To produce large amounts of pure DON for research purposes, a novel method using high-speed counter-current chromatography (HSCCC) was developed. Rice cultured with Fusarium graminearum and field mouldy corn infected by F. graminearum were extracted with methanol and found to contain 1.16 and 1.30 mg DON/g, respectively. The extracts were concentrated and then separated using a biphasic solvent system consisting of ethyl acetate-water (1:1, v/v). Collected fractions were analyzed by high-performance liquid chromatography (HPLC) and identified by congruent retention time and UV/vis spectrum and mass spectrometric data. Fractions containing DON were combined and freeze-dried. This method produced 116 mg and 65 mg DON with a purity of greater than 94.9% from 200 g of the rice culture and the mouldy corn, respectively. The HSCCC method had a recovery rate of DON at 88% from the crude extracts of both samples. This one-step purification method provided a simple and effective tool for obtaining a large amount of DON, an essential material for studies related to toxicology and detoxification of this mycotoxin.     

Reaction of Aplysia limacina metmyoglobin with hydrogen peroxide

Myoglobin (Mb) from gastropod mollusc Aplysia limacina shows only 20% sequence homology to the 'prototype' sperm whale Mb but exhibits a typical Mb fold and can reversibly bind oxygen. An intriguing feature of aplysia Mb is that it lacks the distal histidine and displays a ligand stabilisation based on an arginine. Here we report the reaction of aplysia metMb with hydrogen peroxide studied by optical and electron paramagnetic resonance (EPR) spectroscopies. Two electron oxidation of the protein by H2O2 results in formation of two intermediates typical for this class of reactions, the oxoferryl haem state and a globin-bound free radical. An unusual characteristic of the aplysia Mb reaction is formation, prior to haem oxidation, of an optically distinct compound with an EPR spectrum typical of the low spin Fe3+ haem state. This compound is interpreted as the complex between H2O2 and the ferric haem state (Compound), formed prior to cleavage of the dioxygen bond. We conclude that H2O2 is singly deprotonated in Compound which can thus be notated as [Fe3+--OOH]. A new low spin ferric haem state has been observed over the period of Compound decay, and hypotheses have been formulated as to its identity and role. The location of the protein bound radical observed in aplysia Mb is discussed in light of the fact that the protein does not have any tyrosine residues, the most common site of free radical formation in the haem protein/peroxide systems. All intermediates of the reaction are kinetically characterised.     

Anomaly detection in a mobile communication network

Mobile communication networks produce massive amounts of data which may be useful in identifying the location of an emergency situation and the area it affects. We propose a one pass clustering algorithm for quickly identifying anomalous data points. We evaluate this algorithm’s ability to detect outliers in a data set and describe how such an algorithm may be used as a component of an emergency response management system.

Increasing the Weight of Minimum Spanning Trees

The problems of computing the maximum increase in the weight of the minimum spanning trees of a graph caused by the removal of a given number of edges, or by finite increases in the weights of the edges, are investigated. For the case of edge removals, the problem is shown to be NP-hard and an Ω(1/log k)-approximation algorithm is presented for it, where (input parameter) k > 1 is the number of edges to be removed. The second problem is studied, assuming that the increase in the weight of an edge has an associated cost proportional to the magnitude of the change. An O(n³m² log(n²/m)) time algorithm is presented to solve it.     

Novel europium and osmium complexes for pure red light emitting diode applications

Pure and efficient red light-emitting diodes based on novel europium (Eu) and osmium (Os) complexes were demonstrated. The Eu complex, with dendron substituted diketone ligands, exhibits high photoluminescence efficiency of 45%. When a copolymer containing carbazole and 1,3,4-oxadiazole groups was used as the host, narrow electroluminescence at 617 nm was achieved, with a full width at half maximum of 4 nm and a maximum external quantum efficiency (η) of 0.80%. The Os complex shows pure red emission peaking at 650 nm. The Commission Internationale de l'Eclairage (CIE) chromaticity coordinates (x, y) are (0.65, 0.33). Maximum η and brightness achieved were 0.82% and 590 cd/m², respectively.     

Nanoindentation of polymers: an overview

In this paper, the application of instrumented indentation devices to the measurement of the elastic modulus of polymeric materials is reviewed. This review includes a summary of traditional analyses of load‐penetration data and a discussion of associated uncertainties. Also, the use of scanning probe microscopes to measure the nanoscale mechanical response of polymers is discussed, particularly with regard to the associated limitations. The application of these methods to polymers often leads to measurements of elastic modulus that are somewhat high relative to bulk measurements with potentially artificial trends in modulus as a function of penetration depth. Also, power law fits to indentation unloading curves are often a poor representation of the actual data, and the power law exponents tend to fall outside the theoretical range. These problems are likely caused by viscoelasticity, the effects of which have only been studied recently. Advancement of nanoindentation testing toward quantitative characterization of polymer properties will require material‐independent calibration procedures, polymer reference materials, advances in instrumentation, and new testing and analysis procedures that account for viscoelastic and viscoplastic polymer behavior.