NFkappaB inhibition mitigates serum amyloid a-induced pro-atherogenic responses in endothelial cells and leukocyte adhesion and adverse changes to endothelium function in isolated aorta

The acute phase protein serum amyloid A (SAA) is associated with endothelial dysfunction and early-stage atherogenesis. Stimulation of vascular cells with SAA increases gene expression of pro-inflammation cytokines and tissue factor (TF). Activation of the transcription factor, nuclear factor kappa-B (NFκB), may be central to SAA-mediated endothelial cell inflammation, dysfunction and pro-thrombotic responses, while targeting NFκB with a pharmacologic inhibitor, BAY11-7082, may mitigate SAA activity. Human carotid artery endothelial cells (HCtAEC) were pre-incubated (1.5 h) with 10 μM BAY11-7082 or vehicle (control) followed by SAA (10 μg/mL; 4.5 h). Under these conditions gene expression for TF and Tumor Necrosis Factor (TNF) increased in SAA-treated HCtAEC and pre-treatment with BAY11-7082 significantly (TNF) and marginally (TF) reduced mRNA expression. Intracellular TNF and interleukin 6 (IL-6) protein also increased in HCtAEC supplemented with SAA and this expression was inhibited by BAY11-7082. Supplemented BAY11-7082 also significantly decreased SAA-mediated leukocyte adhesion to apolipoprotein E-deficient mouse aorta in ex vivo vascular flow studies. In vascular function studies, isolated aortic rings pre-treated with BAY11-7082 prior to incubation with SAA showed improved endothelium-dependent vasorelaxation and increased vascular cyclic guanosine monophosphate (cGMP) content. Together these data suggest that inhibition of NFκB activation may protect endothelial function by inhibiting the pro-inflammatory and pro-thrombotic activities of SAA.Abigail Vallejo, Belal Chami, Joanne M. Dennis, Martin Simone, Gulfam Ahmad, Adrian I. Abdo ... et al

Frequency Tunable Attosecond Apparatus

The development of attosecond technology is one of the most significant recent achievements in the field of ultrafast optics; it opens up new frontiers in atomic and molecular spectroscopy and dynamics. A unique attosecond pumpprobe apparatus using a compact Mach-Zehnder interferometer is developed. The interferometer system is compact (∼290 cm2) and completely located outside of the vacuum chamber. The location reduces the mechanical vibration from vacuum components such as turbopumps and roughing pumps. The stability of the interferometer is ∼50 as RMS over 24 hours, stabilized with an active feedback loop. The pump and probe fields can be easily altered to incorporate multiple colors. In the interferometer, double optical gating optics are arranged to generate isolated attosecond pulses with a supercontinuum spectrum. The frequencies of the attosecond pulses can be selected to be in the extreme ultraviolet (XUV) region (25–55 eV, 140 as) or the vacuum ultraviolet (VUV) region (15–24 eV, ∼400 as) by metal filters. Furthermore, the near infrared probe field (1.65 eV) can be upconverted to the ultraviolet (3.1 eV). The frequency tunability in the XUV and VUV is critical for selecting excited states of target atoms and molecules