Characterization of cetuximab Fc/2 dimers by off-line CZE-MS

Monoclonal antibody (mAb) therapeutics attract the largest concern due to their strong therapeutic potency and specificity. The Fc region of mAbs is common to many new biotherapeutics as biosimilar, antibody drug conjugate or fusion protein. Fc region has consequences for Fc-mediated effector functions that might be desirable for therapeutic applications. As a consequence, there is a continuous need for improvement of analytical methods to enable fast and accurate characterization of biotherapeutics. Capillary zone electrophoresis-Mass spectrometry couplings (CZE-MS) appear really attractive methods for the characterization of biological samples. In this report, we used CZE-MS systems developed in house and native MS infusion to allow precise middle-up characterization of F_c/2 variant of cetuximab. Molecular weights were measured for three F_c/2 charge variants detected in the CZE separation of cetuximab subunits. Two F_c/2 C-terminal lysine variants were identified and separated. As the aim is to understand the presence of three peaks in the CZE separation for two F_c/2 subunits, we developed a strategy using CZE-UV/MALDI-MS and CZE-UV/ESI-MS to evaluate the role of N-glycosylation and C-terminal lysine truncation on the CZE separation. The chemical structure of N-glycosylation expressed on the Fc region of cetuximab does not influence CZE separation while C-terminal lysine is significantly influencing separation. In addition, native MS infusion demonstrated the characterization of F_c/2 dimers at pH 5.7 and 6.8 and the first separation of these dimers using CZE-MS.     

Hydrogen production on iron–magnesium oxide in the high-temperature water-gas shift reaction

The effect of the structure of the achiral primary amine additive on the enantioselective heterogeneous catalytic hydrogenation of (E)-2-methyl-2-butenoic acid over cinchonidine modified Pd/Al₂O₃ was studied. It was found that a variety of amines increase the enantioselectivity, which was always accompanied by decrease in the initial rate of the hydrogenations. Based on these results, the participation of the amine additive in the formation of the intermediate complex responsible for enantioselection was suggested. A decrease in the reaction temperature resulted in further increase in the optical purity of the product up to 67%, the highest value reported in the hydrogenation of unsaturated aliphatic acids in this heterogeneous catalytic system so far.     

Structural phase transition and elastic properties of Curium and Uranium monobismuthides under pressure effect

A density functional (DFT) calculations of the structural, elastic and high pressure properties of the cubic XBi (X=U,Cm) compounds, has been reported using the full potential linear muffin-tin orbital (FP-LMTO) method. In this approach the local density approximation (LDA) is used for the exchange-correlation (XC) potential. Results are given for lattice constant, bulk modulus and its pressure derivatives. The pressure transitions at which these compounds undergo structural phase transition from NaCl-type (B1) to CsCl-type (B2) phase were found to be in good agreement with the available theoretical results. We have determined the elastic constants C₁₁, C₁₂, C₄₄ and their pressure dependence which have not been established experimentally or theoretically.     

Symmetric versus asymmetric equilibria in symmetric supermodular games

This paper investigates the general properties of symmetric n-player supermodular games with complete-lattice action spaces. In particular, we examine the extent to which all pure strategy Nash equilibria tend to be symmetric for the general case of multi-dimensional strategy spaces. As asymmetric equilibria are possible even for strictly supermodular games, we investigate whether some symmetric equilibrium would always Pareto dominate all asymmetric equilibria. While this need not hold in general, we identify different sufficient conditions, each of which guarantees that such dominance holds: 2-player games with scalar action sets, uni-signed externalities, identical interests, and superjoin payoffs. Various illustrative examples are provided. Finally, some economic applications are discussed. The first version of this paper was completed while M. Jakubczyk and M. Knauff were visiting junior scholars at CORE, Louvain-la-Neuve, Belgium, financed through the Marie-Curie Early Stage Training program of the European Union (under contract no HPMT-CT-2001-00327), which is hereby gratefully acknowledged. The presentation of the revised version of this paper has benefitted from detailed and careful suggestions by two anonymous referees and William Thomson (as editor) of this Journal.     

Eigenvalues and eigenvectors assignment for neutral type systems

For a class of linear neutral type systems, the problem of eigenvalues and eigenvectors assignment is investigated, i.e. the system that has the given spectrum and almost all, in some sense, eigenvectors is investigated. The result is used for the analysis of the critical number of solvability of a vector moment problem.     

Surface-assisted laser desorption-ionization mass spectrometry on titanium dioxide (TiO2) nanotube layers

The paper reports on the use of a titanium oxide (TiO(2)) nanotube layer as a sensitive substrate for surface-assisted laser desorption-ionization mass spectrometry (SALDI-MS) of peptides and small molecules. The nanotube layers were prepared by electrochemical anodization of titanium foil. The optimized TiO(2) nanotubes morphology coupled to a controlled surface chemistry allowed desorption-ionization (D/I) of a peptide mixture (Mix1) with a detection limit of 10 femtomoles for the neurotensin peptide. The performance of the TiO(2) nanotubes for the D/I of small molecules was also tested for the detection of sutent, a small tyrosine kinase inhibitor, and verapamil. A detection limit of 50 fmol was obtained for these molecules, as compared to 500 fmol using classical matrix-assisted laser desorption-ionization mass spectrometry (MALDI-MS). Both amorphous and anatase TiO(2) layers displayed a comparable performance for D/I of analyte molecules. In a control experiment, we have performed D/I of analyte molecules on a flat TiO(2) layer. The absence of signal emphasizes the role of the nanostructured substrate in the D/I process.     

Singularities of the solution of a mixed problem for a general second order elliptic equation and boundary stabilizationof the wave equation

We deal here with a second order elliptic mixed problem which is posed in a regular open bounded domain of . We study the regularity of its solution. We apply our results to the boundary stabilization of the wave equation.     

A simple and efficient hydrogenation of benzyl alcohols to methylene compounds using triethylsilane and a palladium catalyst

Hydrogenolysis of benzyl alcohols using triethylsilane (Et₃SiH) and a catalytic amount of palladium(II) chloride (PdCl₂) is described. The reaction takes place under mild conditions affording high yields of the corresponding methylene compounds in short reaction times.