Immunostimulatory effects of three classes of CpG oligodeoxynucleotides on PBMC from HCV chronic carriers

Background  

Chronic hepatitis C virus (HCV) infection results from weak or absent T cell responses. Pegylated-interferon-alpha (IFN-α) and ribavirin, the standard of care for chronic HCV, have numerous immune effects but are not potent T cell activators. A potent immune activator such as TLR9 agonist CpG oligodeoxynucleotide (CpG) may complement current treatment approaches.     

The elementary divisor theory over the Hurwitz order of integral quaternions

There exists a diagonal form with certain divisibility conditions for matrices over the Hurwitz order of integral quaternions under unimodular equivalence. The diagonal entries are uniquely determined up to similarity. Given two such diagonal forms, where the diagonal entries are similar by pairs, the matrices prove to be ummodularly equivalent, whenever the rank of the matrices is creater than one.     

Coupled problems in transient fluid and structural dynamics in nuclear engineering: Part 1: Safety problems solved by flow singularity methods

Some important problems in coupled fluid-structural dynamics which occur in safety investigations of liquid metal fast breeder reactors (LMFBR), light water reactors and nuclear reprocessing plants are discussed and a classification of solution methods is introduced. A distinction is made between the step by step solution procedure, where available computer codes in fluid and structural dynamics are coupled, and advanced simultaneous solution methods, where the coupling is carried out at the level of the fundamental equations. Results presented include the transient deformation of a two-row pin bundle surrounded by an infinite fluid field, vapour explosions in a fluid container and containment distortions due to bubble collapse in the pressure suppression system of a boiling water reactor. A recently developed simultaneous solution method is presented in detail. Here the fluid dynamics (inviscid, incompressible fluid) is described by a singularity method which reduces the three-dimensional fluid dynamics problem to a two-dimensional formulation. In this way the three-dimensional fluid dynamics as well as the structural (shell) dynamics can be described essentially by common unknowns at the fluid-structural interface. The resulting equations for the coupled fluid-structural dynamics are analogous to the equations of motion of the structural dynamics alone.     

Non-Heme-Iron-Mediated Selective Halogenation of Unactivated Carbon−Hydrogen Bonds

Oxidation of the iron(II) precursor [(L¹)Fe^IICl₂], where L¹ is a tetradentate bispidine, with soluble iodosylbenzene (^sPhIO) leads to the extremely reactive ferryl oxidant [(L¹)(Cl)Fe^IV=O]⁺ with a cis disposition of the chlorido and oxido coligands, as observed in non-heme halogenase enzymes. Experimental data indicate that, with cyclohexane as substrate, there is selective formation of chlorocyclohexane, the halogenation being initiated by C−H abstraction and the result of a rebound of the ensuing radical to an iron-bound Cl⁻. The time-resolved formation of the halogenation product indicates that this primarily results from ^sPhIO oxidation of an initially formed oxido-bridged diiron(III) resting state. The high yield of up to >70 % (stoichiometric reaction) as well as the differing reactivities of free Fe²⁺ and Fe³⁺ in comparison with [(L¹)Fe^IICl₂] indicate a high complex stability of the bispidine-iron complexes. DFT analysis shows that, due to a large driving force and small triplet-quintet gap, [(L¹)(Cl)Fe^IV=O]⁺ is the most reactive small-molecule halogenase model, that the Fe^III/radical rebound intermediate has a relatively long lifetime (as supported by experimentally observed cage escape), and that this intermediate has, as observed experimentally, a lower energy barrier to the halogenation than the hydroxylation product; this is shown to primarily be due to steric effects.     

Sensitive determination of hydrazine using poly(phenolphthalein), Au nanoparticles and multiwalled carbon nanotubes modified glassy carbon electrode

This study reports a detailed analysis of an electrode material containing poly(phenolphthalein), carbon nanotubes and gold nanoparticles which shows superior catalytic effect towards to hydrazine oxidation in Britton–Robinson buffer (pH 10.0). Glassy carbon electrode was modified by electropolymerization of phenolphthalein (PP) monomer (poly(PP)/GCE) and the multiwalled carbon nanotubes (MWCNTs) was dropped on the surface. This modified surface was electrodeposited with gold nanoparticles (AuNPs/CNT/poly(PP)/GCE). The fabricated electrode was analysed the determination of hydrazine using cyclic voltammetry, linear sweep voltammetry and amperometry. The peak potential of hydrazine oxidation on bare GCE, poly(PP)/GCE, CNT/GCE, CNT/poly(PP)/GCE, and AuNPs/CNT/poly(PP)/GCE were observed at 596 mV, 342 mV, 320 mV, 313 mV, and 27 mV, respectively. A shift in the overpotential to more negative direction and an enhancement in the peak current indicated that the AuNPs/CNT/poly(PP)/GC electrode presented an efficient electrocatalytic activity toward oxidation of hydrazine. Modified electrodes were characterized with High-resolution transmission electron microscopy (HRTEM), scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS) and electrochemical impedance spectroscopy (EIS). Amperometric current responses in the low hydrazine concentration range of 0.25–13 µM at the AuNPs/CNT/poly(PP)/GCE. The limit of detection (LOD) value was obtained to be 0.083 µM. A modified electrode was applied to naturel samples for hydrazine determination.     

Pathways of the Extremely Reactive Iron(IV)-oxido complexes with Tetradentate Bispidine Ligands

The nonheme iron(IV)-oxido complex trans-N3-[(L¹)Fe^IV=O(Cl)]⁺, where L¹ is a derivative of the tetradentate bispidine 2,4-di(pyridine-2-yl)-3,7-diazabicyclo[3.3.1]nonane-1-one, is known to have an S=1 electronic ground state and to be an extremely reactive oxidant for oxygen atom transfer (OAT) and hydrogen atom abstraction (HAA) processes. Here we show that, in spite of this ferryl oxidant having the “wrong” spin ground state, it is the most reactive nonheme iron model system known so far and of a similar order of reactivity as nonheme iron enzymes (C−H abstraction of cyclohexane, −90 °C (propionitrile), t_1/2=3.5 sec). Discussed are spectroscopic and kinetic data, supported by a DFT-based theoretical analysis, which indicate that substrate oxidation is significantly faster than self-decay processes due to an intramolecular demethylation pathway and formation of an oxido-bridged diiron(III) intermediate. It is also shown that the iron(III)-chlorido-hydroxido/cyclohexyl radical intermediate, resulting from C−H abstraction, selectively produces chlorocyclohexane in a rebound process. However, the life-time of the intermediate is so long that other reaction channels (known as cage escape) become important, and much of the C−H abstraction therefore is unproductive. In bulk reactions at ambient temperature and at longer time scales, there is formation of significant amounts of oxidation product – selectively of chlorocyclohexane – and it is shown that this originates from oxidation of the oxido-bridged diiron(III) resting state.     

Construction of an Internally B3N3‐Doped Nanographene Molecule

The synthesis of a hexa‐peri‐hexabenzocoronene (HBC) with a central borazine core is described. The solid‐state structure of this BN‐doped HBC (BN‐HBC) is isotypic with that of the parent HBC. Scanning tunneling microscopy shows that BN‐HBC lies flat on Au(111) in a two‐dimensional pattern.     

The effects of 5-aminolevulinic acid esters on protoporphyrin IX production in human adenocarcinoma cell lines.

Photodynamic diagnosis (PDD) and photodynamic therapy (PDT) using 5-aminolevulinic acid (ALA)-induced protoporphyrin IX (PPIX) is an interesting approach to detect and treat dysplasia and early cancers in the gastrointestinal tract. Because of low lipophilicity resulting in poor penetration across cell membranes, high doses of ALA should be administered in order to reach clinically relevant levels of PPIX. One way of increasing PPIX accumulation is derivatization of ALA into a more lipophilic molecule. In our in vitro study, different esterifications of ALA were investigated to analyze the effects on PPIX accumulation in human adenocarcinoma cell lines. For systematic analysis of cell type-specific PPIX accumulation, three human adenocarcinoma cell lines (SW480, HT29 and CaCo2) and a fibroblast cell line (CCD18) were tested. 3-(4,5-Dimethylthiazole-2-yl)-2,5-biphenyl tetrazolium bromide (MTT) assays were performed to ensure that the ALA esters showed no cellular dark toxicity. Different concentrations (ranging from 0.012 to 0.6 mmol/L, 3 h) and incubation times (5, 10, 30, 180 min; 0.12 mmol/L) were examined. PPIX accumulation was measured using flow cytometry. ALA esters, especially ALA-hexylester and ALA-benzylester, induced significant higher PPIX levels in adenocarcinoma cell lines when compared with ALA and may be promising candidates for PDT and PDD.