Intact and middle-down CIEF of commercial therapeutic monoclonal antibody products under non-denaturing conditions

A two-step CIEF with chemical mobilization was developed for charge profiling of the therapeutic mAb rituximab under non-denaturing separation conditions. CIEF of the intact mAb was combined with a middle-down approach analyzing Fc/2 and F(ab´)₂ fragments after digest with a commercial cysteine protease (IdeS). CIEF methods were optimized separately for the intact mAb and its fragments due to their divergent pIs. Best resolution was achieved by combining Pharmalyte (PL) 8–10.5 with PL 3–10 for variants of intact rituximab and of F(ab´)₂ fragments, respectively, whereas PL 6.7–7.7 in combination with PL 3–10 was used for Fc/2 variants. Charge heterogeneity in Fc/2 dominates over F(ab´)₂. In addition, a copy product of rituximab, and adalimumab were analyzed. Both mAbs contain additional alkaline C-terminal lysine variants as confirmed by digest with carboxypeptidase B. The optimized CIEF methods for intact mAb and Fc/2 were tested for their potential as platform approaches for these mAbs. The CIEF method for Fc/2 was slightly adapted in this process. The pI values for major intact mAb variants were determined by adjacent pI markers resulting in 9.29 (rituximab) and 8.42 (adalimumab). In total, seven to eight charge variants could be distinguished for intact adalimumab and rituximab, respectively.     

Linear magnetization dependence of the intrinsic anomalous Hall effect

The anomalous Hall effect is investigated experimentally and theoretically for ferromagnetic thin films of Mn5Ge3. We have separated the intrinsic and extrinsic contributions to the experimental anomalous Hall effect and calculated the intrinsic anomalous Hall conductivity from the Berry curvature of the Bloch states using first-principles methods. The intrinsic anomalous Hall conductivity depends linearly on the magnetization, which can be understood from the long-wavelength fluctuations of the spin orientation at finite temperatures. The quantitative agreement between theory and experiment is remarkably good, not only near 0 K but also at finite temperatures, up to about approximately 240 K (0.8TC).     

Hydrolysis of Cellobiose in Dilute Sulpuric Acid and Under Hydrothermal Conditions

The sulfuric acid hydrolysis rate of cellobiose between pH 2 and 3 is directly proportional to the acid concentration. In good agreement with other authors, an activation energy of 133 kJ/Mol was found under these acidic conditions. The relation of the reaction rate constants for the glucose formation and glucose degradation (k₁/k₂) shows, in contrast to the hydrolysis of cellulose, little dependence on the temperature. Hydroxymethylfurfural, and to a lesser extent furfural, are glucose degradation products, which are also consumed but at a lower reaction rate than glucose. At pH values between 3 and 4.7 (pure water) strong deviations of the hydrolysis rates were observed. The formation of organic acids decreases the pH but has no influence on the reaction rate. This fact indicates that hydrothermolysis follows a reaction mechanism different from that of acidic hydrolysis.     

Plasmon response of a quantum-confined electron gas probed by core-level photoemission

We demonstrate the existence of quantized "bulk" plasmons in ultrathin magnesium films on Si(111) by analyzing plasmon-loss satellites in core-level photoemission spectra, recorded as a function of the film thickness d. Remarkably, the plasmon energy is shown to vary as 1/d2 all the way down to three atomic layers. The loss spectra are dominated by the n=1 and n=2 normal modes, consistent with the excitation of plasmons involving quantized electronic subbands. With decreasing film thickness, spectral weight is gradually transferred from the plasmon modes to the low-energy single-particle excitations. These results represent striking manifestations of the role of quantum confinement on plasmon resonances in precisely controlled nanostructures.     

Distributions of Points in <Emphasis Type="Italic">d</Emphasis> Dimensions and Large <Emphasis Type="Italic">k</Emphasis>-Point Simplices

We consider a variant of Heilbronn’s triangle problem by investigating for a fixed dimension d≥2 and for integers k≥2 with k≤d distributions of n points in the d-dimensional unit cube [0,1] ^d , such that the minimum volume of the simplices, which are determined by (k+1) of these n points is as large as possible. Denoting by Δ _k,d (n), the supremum of this minimum volume over all distributions of n points in [0,1] ^d , we show that c _k,d ⋅(log n)^1/(d−k+1)/n ^k/(d−k+1)≤Δ _k,d (n)≤c _k,d ′/n ^k/d for fixed 2≤k≤d, and, moreover, for odd integers k≥1, we show the upper bound Δ _k,d (n)≤c _k,d ″/n ^{k/d+(k−1)/(2d(d−1))}, where c _k,d ,c _k,d ′,c _k,d ″>0 are constants. A preliminary version of this paper appeared in COCOON ’05.     

General relativity as a conformally invariant scalar gauge field theory

The global symmetry implied by the fact that one can multiply all masses with a common constant is made into a local, gauge symmetry. The matter action then becomes Conformally invariant and it seems natural to choose for the corresponding scalar gauge field the action for a conformally invariant (massless) scalar field. The resulting conformally invariant theory turns out to be equivalent to general relativity. Since this means that the usual Einstein-Hilbert action is not, in fact, a true gauge action for the space-time geometry, the full theory ought to be supplied with such a term. Gauge-theoretic arguments and conformal invariance requirements dictate its form.     

Invariance identities associated with finite gauge transformations and the uniqueness of the equations of motion of a particle in a classical gauge field

A certain class of geometric objects is considered against the background of a classical gauge field associated with an arbitrary structural Lie group. It is assumed that the components of these objects depend on the gauge potentials and their first derivatives, and also on certain gauge-dependent parameters whose properties are suggested by the interaction of an isotopic spin particle with a classical Yang-Mills field. It is shown that the necessary and sufficient conditions for the invariance of the given objects under a finite gauge transformation are embodied in a set of three relations involving the derivatives of their components. As a special case these so-called invariance identities indicate that there cannot exist a gauge-invariant Lagrangian that depends on the gauge potentials, the interaction parameters, and the4-velocity components of a test particle. However, the requirement that the equations of motion that result from such a Lagrangian be gauge-invariant, uniquely determines the structure of these equations.