A convenient synthesis of new pyrido[3,2-e][1,4]diazepine-2,5-diones and pyrido[2,3-e][1,4]diazepine-2,5-diones

A convenient synthesis of a series of pyrido[3,2-e][1,4]-diazepine-2,5-diones 8 and pyrido[2,3-e][1,4]diazepine-2,5-diones 9, is reported using the condensation of α-amino acid methyl ester derivatives with 1H-pyrido[3,2-d][1,3]oxazine-2,4-dione and 1H-pyrido[2,3-d][1,3]oxazine-2,4-dione. Compounds 8 and 9 were also synthesized by peptide coupling of α-amino acid methyl ester derivatives with β-amino acids (2 or 3) followed by the cyclisation in tetrahydrofuran with sodium hydride (NaH).     

Convenient synthesis of 2,4-disubstituted pyrido[2,3-d]pyrimidines via regioselective palladium-catalyzed reactions

A novel and effective route for the synthesis of 2,4-disubstituted pyrido[2,3-d]pyrimidines III is reported starting from the corresponding 2,4-dichloropyridopyrimidine 1 through regioselective functionalization palladium-catalyzed C–C coupling reactions, by two successive palladium-catalyzed reactions involving an original regioselective chlorine discrimination. Alternatively, type III compounds were elaborated from 2 by C-2 chlorine further displacement of the C-4 isopropylsulfanyl group, which acted as a temporary C-4 protecting group. Further Suzuki–Miyaura cross-coupling reactions led to C-2 and C-4 disubstituted compounds.     

Study of the thermal stability of Zerodur glass ceramics suitable for a scanning probe microscope frame

The work presents measurements of the length stability of Zerodur glass ceramic with temperature change. Measurement of this thermal characteristic is necessary for determination of the optimal temperature at which the Zerodur glass ceramic has a coefficient of thermal expansion close to zero. The principle of the measurement is to monitor the length changes using an optical resonator with a cavity mirror spacer made from the Zerodur material to be studied. The resonator is placed inside a vacuum chamber with a temperature control. A tunable laser diode is locked to a certain optical mode of the resonator to monitor the optical frequency of this mode. A beat-note signal from optical mixing between the laser and a stabilized femtosecond frequency comb is detected and processed. The temperature dependence of the glass ceramics was determined and analyzed. The resolution of the length measurement of the experimental set-up is on the order of 0.1 nm.     

On the voxel size and magnetic field strength dependence of spectral resolution in magnetic resonance spectroscopy

While the inherent low sensitivity of in vivo MR spectroscopy motivated a trend towards higher magnetic fields, B(0), it has since become apparent that this increase does not seem to translate into the anticipated improvement in spectral resolution. This is attributed to the decrease of the transverse relaxation time, T(2)*, in vivo due to macro- and mesoscopic tissue susceptibility. Using spectral contrast-to-noise ratio (SCNR) arguments, we show that if in biological systems the linewidth (on the frequency scale) increases linearly with the field, the spectral resolution (in parts per million) improves approximately as the fifth-root of B(0) for chemically shifted lines and decreases as about B(0)(4/5) (in hertz) for a structure of J-coupled multiplets. It is also shown that for any given B(0) there is a unique voxel size that is optimal in spectral resolution, linking the spectral and spatial resolutions. Since in practical applications the spatial resolution may be dictated by the target anatomy, nomograms to determine the B(0) required to achieve the desired spectral resolution at that voxel size are presented. More generally, the scaling of the nomograms to determine the achievable spectral and spatial resolutions at any given field is described.     

Cartan’s Spiral Staircase in Physics and, in Particular, in the Gauge Theory of Dislocations

In 1922, Cartan introduced in differential geometry, besides the Riemannian curvature, the new concept of torsion. He visualized a homogeneous and isotropic distribution of torsion in three dimensions (3d) by the “helical staircase”, which he constructed by starting from a 3d Euclidean space and by defining a new connection via helical motions. We describe this geometric procedure in detail and define the corresponding connection and the torsion. The interdisciplinary nature of this subject is already evident from Cartan’s discussion, since he argued—but never proved—that the helical staircase should correspond to a continuum with constant pressure and constant internal torque. We discuss where in physics the helical staircase is realized: (i) In the continuum mechanics of Cosserat media, (ii) in (fairly speculative) 3d theories of gravity, namely (a) in 3d Einstein-Cartan gravity—this is Cartan’s case of constant pressure and constant intrinsic torque—and (b) in 3d Poincaré gauge theory with the Mielke-Baekler Lagrangian, and, eventually, (iii) in the gauge field theory of dislocations of Lazar et al., as we prove for the first time by arranging a suitable distribution of screw dislocations. Our main emphasis is on the discussion of dislocation field theory.     

Extreme boundaries of convex bodies inl 2

Every uncountable complete separable metric space is homomorphic to the set of extreme points (in the weak topology) of a bounded closed convex body inl ₂.     

Matrix-assisted laser desorption/ionization mass spectrometry for the evaluation of the C-terminal lysine distribution of a recombinant monoclonal antibody

Recombinant monoclonal antibodies produced using mammalian cell lines contain multiple chemical modifications. One specific modification resides on the C-terminus of the heavy chain. Enzymes inside the cell can cleave the C-terminal lysine from the heavy-chain molecules, and variants with and without C-terminal lysine can be produced. In order to fully characterize the protein, there is a need for analytical methods that are able to account for the different product variants. Conventional analytical methods used for the measurement of the distribution of the two different variants are based on chemical or enzymatic degradation of the protein followed by chromatographic separation of the degradation products. Chromatographic separations with gradient elution have long run times, and analyses of multiple samples are time-consuming. This paper reports development of a novel method for the determination of the relative amounts of the two C-terminal heavy-chain variants based on matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS) measurements of the cyanogen bromide degraded recombinant monoclonal antibody products. The distribution of the variants is determined from the MALDI-TOF mass spectra by measuring the peak areas of the two C-terminal peptides. The assay was used for the assessment of the C-terminal lysine distribution in different development lots. The method was able to differentiate between the products obtained using the same cell line as well as between products obtained from different cell lines.