Enantiomeric Cyclic Peptides with Different Caco‐2 Permeability Suggest Carrier‐Mediated Transport

Recently, oral absorption of cyclic hexapeptides was improved by N‐methylation of their backbone amides. However, the number and position of N‐methylations or of solvent exposed NHs did not correlate to intestinal permeability, measured in a Caco‐2 model. In this study, we investigate enantiomeric pairs of three polar and two lipophilic peptides to demonstrate the participation of carrier‐mediated transporters. As expected, all the enantiomeric peptides exhibited identical lipophilicity (logD_7.4) and passive transcellular permeability determined by the parallel artificial membrane permeability assay (PAMPA). However, the enantiomeric polar peptides exhibited different Caco‐2 permeability (P_app) in both directions a–b and b–a. The same trend was observed for one of the lipophilic peptide, whereas the second lipophilic enantiomer pair showed identical Caco‐2 permeability (within the errors). These findings provide the first evidence for the involvement of carrier‐mediated transport for peptides, especially for those of polar nature.     

On the Effect of Secondary Nucleation on Deracemization through Temperature Cycles

Herein, the pivotal role of secondary nucleation in a crystallization-enhanced deracemization process is reported. During this process, complete and rapid deracemization of chiral conglomerate crystals of an isoindolinone is attained through fast microwave-assisted temperature cycling. A parametric study of the main factors that affect the occurrence of secondary nucleation in this process, namely agitation rate, suspension density, and solute supersaturation, confirms that an enhanced stereoselective secondary nucleation rate maximizes the deracemization rate. Analysis of the system during a single temperature cycle showed that, although stereoselective particle production during the crystallization stage leads to enantiomeric enrichment, undesired kinetic dissolution of smaller particles of the preferred enantiomer occurs during the dissolution step. Therefore, secondary nucleation is crucial for the enhancement of deracemization through temperature cycles and as such should be considered in further design and optimization of this process, as well as in other temperature cycling processes commonly applied in particle engineering.     

A Convergent Lagrangian Discretization for a Nonlinear Fourth-Order Equation

A fully discrete Lagrangian scheme for numerical solution of the nonlinear fourth-order DLSS equation in one space dimension is analyzed. The discretization is based on the equation’s gradient flow structure in the \(L^2\)-Wasserstein metric. By construction, the discrete solutions are strictly positive and mass conserving. A further key property is that they dissipate both the Fisher information and the logarithmic entropy. Our main result is a proof of convergence of fully discrete to weak solutions in the limit of vanishing mesh size. Convergence is obtained for arbitrary nonnegative, possibly discontinuous initial data with finite entropy, without any CFL-type condition. The key estimates in the proof are derived from the dissipations of the two Lyapunov functionals. Numerical experiments illustrate the practicability of the scheme.     

m‐Xylylene bismaleimide: a versatile building block for high‐performance thermosets

m‐Xylylene bismaleimide, Compimide ? ? Compimide® is a registered trademark.
MXBI (hereafter MXBI), was developed as a building block for formulating bismaleimide resins with improved processability. MXBI on its own, or in combination with 4,4′‐bismaleimidodiphenylmethane (Compimide MDAB, hereafter MDAB) and with 2,2′‐diallylbisphenol‐A as a co‐monomer, provides very low‐melting resin blends, which can be processed at temperatures around 60–80°C via RTM (Resin Transfer Moulding), VARIM (Vacuum Assisted Resin Infusion Moulding), prepregging, and wet filament winding (FW). Uncured and cured resin properties were evaluated. The mechanical property spectrum of the MXBI/MDAB/diallylbisphenol‐A system with varying MXBI/MDAB ratio shows almost equivalent contributions of MXBI and MDAB to the mechanical properties of a system. Higher MXBI proportions are responsible for lower resin viscosities and hence superior processability. Copyright © 2015 John Wiley & Sons, Ltd.     

Stage-I fatigue crack studies in order to validate the dislocation-free zone model of fracture for bulk materials

Stage-I fatigue cracks are commonly described by the model of Bilby, Cottrell and Swinden (BCS model). However, since several experimental investigations have shown a dislocation-free zone (DFZ) in front of crack-tips, it is necessary to validate the new DFZ model and to examine the deviations to the BCS model. Therefore, the dislocation density distribution is derived from height profiles of slip lines in front of stage-I fatigue cracks in CMSX4® single crystals measured by contact-mode atomic force microscopy. This is possible, because the cracks are initiated at notches milled by focused ion beam technique directly on slip planes with a high Schmid factor. Consequently, the directions of the Burgers vectors are well known; it is possible to calculate the dislocation density distributions from the height profiles. The measured distributions are compared to the calculated distribution function of the DFZ model proposed by Chang et al. The additionally measured microscopic friction stress of the dislocations is then used to calculate the influence of grain boundaries on the dislocation density distribution in front of stage-I cracks. The calculation is done by the extended DFZ model of Shiue et al. and compared with the measured distribution function in polycrystalline specimens. Finally, the crack-tip sliding displacement as a measure for the crack propagation rate is compared for the DFZ model and the BCS model with the experimentally revealed values. The important result: the often used BCS model does not reflect the experimental measurements. On the contrary, the DFZ model reflects the measurements at stage-I cracks qualitatively and quantitatively.     

Turbulence structure of dilute polymer and surfactant solutions in artificially roughened pipes

Pressure drop and velocity profile measurements are presented for turbulent flows of drag reducing fluids. The investigation was done in two rough pipes, known as k- and d-type rough pipes. The results are compared with those obtained in hydraulically smooth pipe of identical diameter. The spatial arrangement of the roughness elements in the pipe determines the parallel shift in the elastic sublayer and in the core region of the dimensionless turbulent velocity profile. The slopes of the velocity profiles in these regions remain unaffected by the arrangement which is an indication that the hydrodynamic influence of the roughness is restricted to the near-wall region. The drag reducing surfactant solution exhibited a drag reduction in the smooth as well as in the rough pipes which was higher than that given by Virk's maximum drag reduction asymptote. For this solution no influence of the roughness on the turbulence was detected when the dimensionless roughness height in viscous units was less than 12.     

Helical flow of molten polymers in a cylindrical annulus

Summary The paper is concerned with an analytical investigation of helical flow of a non-Newtonian fluid through an annulus with a rotating inner cylinder. The shear dependence of viscosity is described by a power law and the temperature dependence by an exponential function.Velocity and temperature profiles, energy input and shear along the stream lines, pressure drop, and torque are presented for the range of input parameters encountered in polymer extrusion.The results of the study can be applied to a mixing element in a screw extruder and for a device to control extrudate temperature and output.Nomenclature a thermal diffusivity [m²/s] - b temperature coefficient [K^–1], see eq. [4] - c heat capacity [J/kg K] - h slot width [m] - I ₁,I ₂,I ₃ invariants of the rate of deformation tensor, see eq. [5] - k thermal conductivity [J/m s K] - l, L = 1/h length of the slot - l _T ,l _K thermal and kinematic entrance length - m power law exponent, see eq. [3] - M torque [m N] - p pressure [N/m²] - P dimensionless pressure gradient, see eq. [24] - P _R,P _RZ dimensionless components of the shear stress tensor, see eq. [25] and eq. [26] - r, R = r/r _wa radial coordinate - r _wa, r_wi outer and inner radius of annulus [m] - t time [s]; dwell time in the annulus - T temperature [K] - v , v_r, V_z velocity components [m/s] - v ₀ angular velocity at inner wall [m/s] - average velocity inz-direction [m/s] - V , V_R, V_Z dimensionless velocity components,v /v₀, v_r/v₀, v_z/v₀ - V _z velocity ratio, helical parameter - Y coordinate inr-direction, see eq. [20] - z, Z = z/h Pe axial coordinate - deformation - rate of deformation tensor [s^–1] - apparent viscosity [N s/m²], see eq. [3] - dimensionless temperature,b (T – T ₀) - azimuth coordinate - ratio of radii,r _wi/r_wa - density [kg/m³] - , kl shear stress tensor [N/m²] - fluidity [m²w/Nw s], see eq. [4] - Gf Griffith number, see eq. [12] - Pe Péclet number, see eq. [13] - Re Reynolds number, - 0 initial state, reference state - equilibrium state - e entrance - wi, wa at surface of inner or outer wall - r, R, z, Z, coordinates - i, j radial and axial position of nodal point in the grid - k, l tensor components Presented at Euromech 37, Napoli 6. 20–23. 1972.With 15 figuresDedicated to Prof. Dr.-Ing. G. Schenkel on his 60th birthday