TWEAK is a member of the TNF ligand family that induces angiogenesis in vivo. We report cloning of a receptor for TWEAK (TweakR) from a human umbilical vein endothelial cell (HUVEC) library. The mature form of TweakR has only one hundred and two amino acids and six cysteine residues in its extracellular region. Five different assays demonstrate TWEAK-TweakR binding, and the interaction affinity constant (Kd) is within a physiologically relevant range of 2.3 +/- 0.1 nM. The TweakR cytoplasmic domain binds TRAFs 1, 2, and 3. Cross-linking of TweakR induces HUVEC growth, and mRNA levels are upregulated in vitro by a variety of agents and in vivo following arterial injury. Soluble TweakR inhibits endothelial cell migration in vitro and corneal angiogenesis in vivo.
Mechanical properties of layered silicates on the nanometer scale have been associated with large uncertainty. We attempt to clarify the linear elastic properties including tensile moduli, shear moduli, and potential failure mechanisms for the minerals pyrophyllite, montmorillonite, and mica in the order of increasing cation exchange capacity (CEC) under a broad range of stress using electronic structure calculations, semiempirical classical molecular dynamics simulation, and the comparison to available macroscopic experimental data. In-plane tensile moduli (xx and yy) are ∼160 GPa independent of CEC and stress, whereas perpendicular tensile moduli (zz) range from 5 to 60 GPa as a function of CEC at low stress (0.01 to 1 GPa) and approach in-plane values at high stress. In-plane shear moduli (xy) are ∼70 GPa independent of CEC and the shear strength increases from ∼1 to ∼3 GPa with increasing cation density. Shear moduli parallel to the layers (xz and yz) are between 2 and 20 GPa as a function of CEC, with a shear strength of 0.2 to 1 GPa beyond which the layers exhibit lateral shear flow. Tensile zz moduli, shear moduli, and shear strength in the xz and yz direction reach a local minimum at a cation density of 0.3 relative to mica. The simulation suggests sliding of the layers, in-plane kinks, and cation intrusion into the layers as potential failure mechanisms equal to amorphization on the macroscale. The anisotropy and stress-dependence of the mechanical properties is determined by the presence of rigid layers and flexible interlayer spaces of variable cation density. Current classical simulation models tend to overestimate in-plane moduli (xx, yy, xy) in a systematic way relative to electronic structure (DFT) and experimental results.
Abdominal acupuncture and metformin improved the endocrine and metabolic function of patients with obesity-type PCOS. Abdominal acupuncture may be more effective in improving menstrual frequency, BMI, and WHR, with few adverse effects.
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