The moderate band gap of black phosphorus (BP) in the range of 0.3-2 eV, along a high mobility of a few hundred cm(2) V(-1) s(-1) provides a bridge between the gapless graphene and relatively low-mobility transition metal dichalcogenides. Here, we study the mechanism of electrical and thermoelectric transport in 10-30 nm thick BP devices by measurements of electrical conductance and thermopower (S) with various temperatures (T) and gate-electric fields. The T dependences of S and the sheet conductance (σ□) of the BP devices show behaviors of T(1/3) and exp[-(1/T)(1/3)], respectively, where S reaches ∼0.4 mV/K near room T. This result indicates that two-dimensional (2D) Mott's variable range hopping (VRH) is a dominant mechanism in the thermoelectric and electrical transport in our examined thin BP devices. We consider the origin of the 2D Mott's VRH transport in our BPs as trapped charges at the surface of the underlying SiO2 based on the analysis with observed multiple quantum dots.
Background
Factor VIII (FVIII) pharmacokinetics (PK) in adult hemophilia A populations are highly variable and have been previously determined to be influenced by von Willebrand factor:antigen (VWF:Ag), ABO blood group, and age. However, additional genetic determinants of FVIII PK are largely unknown.
Objectives
The contribution of VWF clearance, VWF‐FVIII‐binding activity, and genetic variants in VWF clearance receptors to FVIII PK in adult patients were assessed.
Methods
FVIII PK assessment was performed in 44 adult subjects (age 18‐61 years) with moderate or severe hemophilia A. VWF:Ag, VWF propeptide (VWFpp), VWFpp/VWF:Ag, and VWF:FVIII binding activity were measured. The VWF modifying loci CLEC4M, SCARA5, STAB2, and ABO, and the D′D3 FVIII‐binding region of the VWF gene were genotyped.
Results
VWF:Ag, VWFpp, and VWF:FVIIIB positively correlated with FVIII half‐life and negatively correlated with FVIII clearance. VWFpp/VWF:Ag negatively correlated with FVIII half‐life and positively correlated with FVIII clearance. The correlation between VWFpp/VWF:Ag and FVIII half‐life was stronger for type non‐O patients than for type O patients, suggesting that slower VWF clearance increases FVIII half‐life. Patients heterozygous for the CLEC4M rs868875 variant had increased FVIII clearance when compared with individuals homozygous for the reference allele. The CLEC4M variable number of tandem repeat (VNTR) alleles were also associated with the rate of FVIII clearance. When compared with the quartile of patients with the fastest FVIII clearance, the quartile of patients with the slowest FVIII clearance had a decreased frequency of the CLEC4M 5‐VNTR.
Conclusions
VWF‐FVIII binding activity and genetic determinants of VWF clearance are important contributors to FVIII pharmacokinetics in adult patients.
Von Willebrand factor (VWF) is a critical component of the hemostatic system. Basal secretion of VWF from endothelial cells is the principal determinant of an individual's baseline plasma VWF levels, while endothelial VWF release can also be induced by several biochemical agonists and biomechanical forces such as increased shear stress. However, the mechanotransduction machinery responsible for this latter response is unclear. Here we propose that the endothelial glycocalyx (EGC), a dynamic layer of proteins and carbohydrates that covers the surface of the vascular endothelium, may play a key role in mediating this response. The EGC has previously been implicated in mediating the mechanotransduction of shear stress in other shear‐responsive endothelial processes, such as nitric oxide production and stem cell differentiation. Here, we hypothesize that a similar mechanism may be responsible for the basal secretion of endothelial VWF, whereby the EGC mediates the mechanotransduction of physiological shear stress generated by flowing blood, that in turn contributes to the maintenance of physiological plasma VWF levels.
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