[Molecular mechanism of zoledronic acid inhibiting angiogenesis by semi flexible binding with vascular endothelial growth factor conformation].

Objective: To study the relationship between zoledronic acid (ZOL) and vascular endothelial growth factor (VEGF) conformation so as to reveal the mechanism of bisphosphonates inhibiting angiogenesis. Methods: The binding structures of ZOL and VEGF were preprocessed and the molecular dockings were simulated through AutoDockTools, Discovery studio4 and AutoDockVina. The best binding conformation was accurately screened. The effects of various concentrations of ZOL (group A was 0 µmol/L, groups B, C and D were 25, 50 and 100 µmol/L, respectively) on human umbilical vein endothelial cell (HUVEC) proliferation, angiogenesis and angiogenic molecules were detected by using cell counting kit-8 (CCK-8) in vivo and in vitro angiogenesis, immunofluorescence and Western blotting. Results: There was a ZOL binding site on the target protein VEGF conformation. The affinity was -5.2 kcal/mol. This binding site consisted of the hydrophobic region composed of amino acids Cys26, 51, 57, etc. and the hydrogen bond binding region of the A chain (ASP34, SER50) and B chain (CYS61, 68, LEU66, GLY59). The results of CCK-8 showed that the levels of value A in groups B, C and D were significantly lower than that in group A at each time point from 3 to 6 days (P<0.05). In vitro vascular experiments demonstrated that the numbers of budding in groups B, C and D [(208±28), (151±21) and (62±9), respectively] were significantly lower than that in group A (276±30) (P<0.05). In vivo vascular experiments displayed that the ratio of Matrigel gel/plasma fluorescence in group A (0.003 1±0.000 3) was significantly higher than those in group B (0.002 1±0.000 2), group C (0.001 6±0.000 2) and group D (0.000 6±0.000 1) (P<0.05). The results of Western blotting revealed that the expression of VEGF in groups B, C and D [(0.72±0.11), (0.41±0.07) and (0.24±0.04), respectively] were significantly lower than that in group A (1.01±0.02) (P<0.05), and the expression levels of hypoxia-inducible factor-1α (HIF-1α) in groups B, C and D [(0.68±0.09), (0.55±0.06) and (0.43±0.08), respectively] were significantly lower than that in group A (0.96±0.04) (P<0.05). Conclusions: ZOL could inhibit cell proliferation, in vivo and in vitro vascularization and expression of VEGF/HIF-1α. The binding site of ZOL with the conformation of VEGF was located in the hydrophobic region and hydrogen-bonding region of amino acids. Designing an antagonist targeting this site might potentially alleviate the effect of ZOL in inhibiting angiogenesis.

Correlation of Bandgap Reduction with Inversion Response in (Si)GeSn/High-k/Metal Stacks.

The bandgap tunability of (Si)GeSn group IV semiconductors opens a new era in Si-technology. Depending on the Si/Sn contents, direct and indirect bandgaps in the range of 0.4-0.8 eV can be obtained, offering a broad spectrum of both photonic and low power electronic applications. In this work, we systematically studied capacitance-voltage characteristics of high-k/metal gate stacks formed on GeSn and SiGeSn alloys with Sn-contents ranging from 0 to 14 at. % and Si-contents from 0 to 10 at. % particularly focusing on the minority carrier inversion response. A clear correlation between the Sn-induced shrinkage of the bandgap energy and enhanced minority carrier response was confirmed using temperature and frequency dependent capacitance voltage-measurements, in good agreement with k.p theory predictions and photoluminescence measurements of the analyzed epilayers as reported earlier. The enhanced minority generation rate for higher Sn-contents can be firmly linked to the bandgap reduction in the GeSn epilayer without significant influence of substrate/interface effects. It thus offers a unique possibility to analyze intrinsic defects in (Si)GeSn epilayers. The extracted dominant defect level for minority carrier inversion lies approximately 0.4 eV above the valence band edge in the studied Sn-content range (0-12.5 at. %). This finding is of critical importance since it shows that the presence of Sn by itself does not impair the minority carrier lifetime. Therefore, the continuous improvement of (Si)GeSn material quality should yield longer nonradiative recombination times which are required for the fabrication of efficient light detectors and to obtain room temperature lasing action.

Low Temperature Deposition of High-k/Metal Gate Stacks on High-Sn Content (Si)GeSn-Alloys.

(Si)GeSn is an emerging group IV alloy system offering new exciting properties, with great potential for low power electronics due to the fundamental direct band gap and prospects as high mobility material. In this Article, we present a systematic study of HfO2/TaN high-k/metal gate stacks on (Si)GeSn ternary alloys and low temperature processes for large scale integration of Sn based alloys. Our investigations indicate that SiGeSn ternaries show enhanced thermal stability compared to GeSn binaries, allowing the use of the existing Si technology. Despite the multielemental interface and large Sn content of up to 14 atom %, the HfO2/(Si)GeSn capacitors show small frequency dispersion and stretch-out. The formed TaN/HfO2/(Si)GeSn capacitors present a low leakage current of 2 × 10(-8) A/cm(2) at -1 V and a high breakdown field of ∼8 MV/cm. For large Sn content SiGeSn/GeSn direct band gap heterostructures, process temperatures below 350 °C are required for integration. We developed an atomic vapor deposition process for TaN metal gate on HfO2 high-k dielectric and validated it by resistivity as well as temperature and frequency dependent capacitance-voltage measurements of capacitors on SiGeSn and GeSn. The densities of interface traps are deduced to be in the low 10(12) cm(-2) eV(-1) range and do not depend on the Sn-concentration. The new processes developed here are compatible with (Si)GeSn integration in large scale applications.

Electrical characterization of strained and unstrained silicon nanowires with nickel silicide contacts.

We present electrical characterization of nickel monosilicide (NiSi) contacts formed on strained and unstrained silicon nanowires (NWs), which were fabricated by top-down processing of initially As(+) implanted and activated strained and unstrained silicon-on-insulator (SOI) substrates. The resistivity of doped Si NWs and the contact resistivity of the NiSi to Si NW contacts are studied as functions of the As(+) ion implantation dose and the cross-sectional area of the wires. Strained silicon NWs show lower resistivity for all doping concentrations due to their enhanced electron mobility compared to the unstrained case. An increase in resistivity with decreasing cross section of the NWs was observed for all implantation doses. This is ascribed to the occurrence of dopant deactivation. Comparing the silicidation of uniaxially tensile strained and unstrained Si NWs shows no difference in silicidation speed and in contact resistivity between NiSi/Si NW. Contact resistivities as low as 1.2 x 10(-8) Omega cm(-2) were obtained for NiSi contacts to both strained and unstrained Si NWs. Compared to planar contacts, the NiSi/Si NW contact resistivity is two orders of magnitude lower.