An online nano‐LC‐ESI‐FTICR‐MS method for comprehensive characterization of endogenous fragments from amyloid β and amyloid precursor protein in human and cat cerebrospinal fluid

Amyloid precursor protein (APP) is the precursor protein to amyloid β (Aβ), the main constituent of senile plaques in Alzheimer's disease (AD). Endogenous Aβ peptides reflect the APP processing, and greater knowledge of different APP degradation pathways is important to understand the mechanism underlying AD pathology. When one analyzes longer Aβ peptides by low‐energy collision‐induced dissociation tandem mass spectrometry (MS/MS), mainly long b‐fragments are observed, limiting the possibility to determine variations such as amino acid variants or post‐translational modifications (PTMs) within the N‐terminal half of the peptide. However, by using electron capture dissociation (ECD), we obtained a more comprehensive sequence coverage for several APP/Aβ peptide species, thus enabling a deeper characterization of possible variants and PTMs. Abnormal APP/Aβ processing has also been described in the lysosomal storage disease Niemann–Pick type C and the major large animal used for studying this disease is cat. By ECD MS/MS, a substitution of Asp7 → Glu in cat Aβ was identified. Further, sialylated core 1 like O‐glycans at Tyr10, recently discovered in human Aβ (a previously unknown glycosylation type), were identified also in cat cerebrospinal fluid (CSF). It is therefore likely that this unusual type of glycosylation is common for (at least) species belonging to the magnorder Boreoeutheria. We here describe a detailed characterization of endogenous APP/Aβ peptide species in CSF by using an online top‐down MS‐based method. Copyright © 2012 John Wiley & Sons, Ltd.     

A numerical algorithm for nonlinear parabolic equations with highly oscillating coefficients

A numerical algorithm is constructed for the solution to a class of nonlinear parabolic operators in the case of homogenization. We consider parabolic operators of the form d/dt + A_ϵ, where A_ϵ is monotone. More precisely, we consider the case when A_ϵu=−div (a(x/ϵ, e/ϵ^k) |Du|^p−2Du), where p≥2 and k>0. © 1996 John Wiley & Sons, Inc.     

Homogeneous Reforming of Aqueous Ethylene Glycol to Glycolic Acid and Pure Hydrogen Catalyzed by Pincer-Ruthenium Complexes Capable of Metal–Ligand Cooperation

Glycolic acid is a useful and important α-hydroxy acid that has broad applications. Herein, the homogeneous ruthenium catalyzed reforming of aqueous ethylene glycol to generate glycolic acid as well as pure hydrogen gas, without concomitant CO₂ emission, is reported. This approach provides a clean and sustainable direction to glycolic acid and hydrogen, based on inexpensive, readily available, and renewable ethylene glycol using 0.5 mol % of catalyst. In-depth mechanistic experimental and computational studies highlight key aspects of the PNNH-ligand framework involved in this transformation.     

A Simple Nickel Catalyst Enabling an E-Selective Alkyne Semihydrogenation

Stereoselective alkyne semihydrogenations are attractive approaches to alkenes, which are key building blocks for synthesis. With regards to the most atom-economic reducing agent dihydrogen (H₂), only few catalysts for the challenging E-selective alkyne semihydrogenation have been disclosed, each with a unique substrate scope profile. Here, we show that a commercially available nickel catalyst facilitates the E-selective alkyne semihydrogenation of a wide variety of substituted internal alkynes. This results in a simple and broadly applicable overall protocol to stereoselectively access E-alkenes employing H₂, which could serve as a general method for synthesis.     

On two-scale convergence and related sequential compactness topics

A general concept of two-scale convergence is introduced and two-scale compactness theorems are stated and proved for some classes of sequences of bounded functions in L ²(Ω) involving no periodicity assumptions. Further, the relation to the classical notion of compensated compactness and the recent concepts of two-scale compensated compactness and unfolding is discussed and a defect measure for two-scale convergence is introduced.     

Thermoluminescence of YAG:Nd crystals coloured with x-rays

The spectral distribution of the thermoluminescence (TL) of YAG:Nd crystals coloured by x-ray irradiation at room temperature (RT) and at 80 K has been investigated. The spectral distribution of TL in the uv-, visible and near ir ranges shows that the energy transfer by bound exciton states (BES) to the RE³⁺ ions (Nd³⁺ and Tb³⁺) decreases with increasing temperature. The TL spectrum in the uv range is ascribed to the hole defect centers. Diminution of the energy transferred by the BES to the Nd³⁺ and Tb³⁺ ions is the direct cause for the occurrence of the group of lines ascribed to the Nd³⁺ ions in TL observed at LT, whereas at RT and higher only the groups of Tb lines are observed.     

Fission reactions of 469-MeV56Fe+238U: Detection of4He/1H emission from pre- and post-fission sources

The emission of⁴He and¹H has been measured in coincidence with fission for reactions of 469-MeV⁵⁶Fe+²³⁸U. By using a gas-ionization telescope in kinematic coincidence with a position-sensitive avalanche detector, the folding angle between two fission fragments was determined in order to distinguish fusion reactions from fission following smaller-momentum-transfer collisions. In both fusion fission and sequential fission reactions, the⁴He/¹H energy spectra are relatively narrow with relatively flat angular distributions at backward angles and become broader in energy with enhanced cross-sections at forward angles. The extent of forward peaking is significantly greater for peripheral collisions than for central collisions. The light-charged-particle multiplicities are quite similar for⁴He and¹H, being much larger for fusion fission than for sequential fission. Detailed comparisons of the spectral shapes with Monte Carlo simulations of reaction kinematics impose strong constraints on the participation of different emission sources. We find important contributions to the observed⁴He/¹H emission both from accelerated fragments (FE) and from the composite system prior to fission (CE). For⁴He emission, the multiplicity of CE is much larger for fusion fission than for sequential fission, possibly as a consequence of the higher spins and shorter reaction times associated with deeply inelastic and quasi-elastic processes. For¹H emission, a corresponding but somewhat smaller difference is observed for the CE multiplicities. An excess of⁴He/¹H particles, found at forward angles in both fusion and sequential fission processes, cannot be attributed to evaporative emission from any fragments and therefore must originate in pre-thermalization emission.     

Radionuclides in produced water from Norwegian oil and gas installations — concentrations and bioavailability

Substantial amounts of produced water, containing elevated levels of radionuclides (mainly ²²⁶Ra and ²²⁸Ra) are discharged to the sea as a result of oil and gas production on the Norwegian Continental Shelf. So far no study has assessed the potential radiological effects on marine biota in connection with radionuclide discharges to the North Sea. The main objective of the project is to establish radiological safe discharge limits for radium, lead and polonium associated with other components in produced water from oil and gas installations on the Norwegian continental shelf.This study reports results indicating that the presence of added chemicals such as scale inhibitors in produced water has a marked influence on the formation of radium and barium sulphates when produced water is mixed with sea water. Thus, the mobility and bioavailability of radium (and barium) will be larger than anticipated. Also, the bioavailability of food-borne radium is shown to increase due to presence of such chemicals.     

Synthetic applications of 3‐(cyanoacetyl)indoles and related compounds

Various synthetic applications of 3‐(cyanoacetyl)indoles, as well as syntheses of some related indoles, have been investigated. Diethyl 2‐(1H‐indol‐3‐yl)‐2‐oxoethylphosphonate and a methyl derivative thereof have been prepared in one step from indole. Moreover, it was demonstrated that 3‐(cyanoacetyl)indoles are useful starting materials for the preparation of for example 3‐(1H‐indol‐3‐yl)‐3‐oxopropanamides, 3‐heteroarylindoles or 3‐heteroaroylindoles.     

Production of milligram quantities of affinity tagged-proteins using automated multistep chromatographic purification

A new chromatography system, AKTAxpress (GE Healthcare, Amersham Biosciences, Uppsala, Sweden) has been designed to meet the demand for high-throughput purification of proteins in structural genomics and drug discovery. The system offers a number of automated multistep purification protocols for affinity-tagged proteins. All protocols start with affinity chromatography followed by combinations of desalting, ion exchange chromatography and gel filtration. As an option, tag removal can be included in the purification protocols. Up to 16 proteins can be purified per day and the yield can be as high as 50 mg of each protein at > 90% purity. To highlight the versatility of the system, this paper presents several case studies; purifications of hexahistidine- and glutathione S-transferase-tagged proteins using different protocols, automated on-column tag cleavage and optimization studies for a hexahistidine-tagged kinase.