26 research outputs found
Comb-Based Radio-Frequency Photonic Filters with Rapid Tunability and High Selectivity
Photonic technologies have received considerable attention for enhancement of
radio-frequency (RF) electrical systems, including high-frequency analog signal
transmission, control of phased arrays, analog-to-digital conversion, and
signal processing. Although the potential of radio-frequency photonics for
implementation of tunable electrical filters over broad RF bandwidths has been
much discussed, realization of programmable filters with highly selective
filter lineshapes and rapid reconfigurability has faced significant challenges.
A new approach for RF photonic filters based on frequency combs offers a
potential route to simultaneous high stopband attenuation, fast tunability, and
bandwidth reconfiguration. In one configuration tuning of the RF passband
frequency is demonstrated with unprecedented (~40 ns) speed by controlling the
optical delay between combs. In a second, fixed filter configuration, cascaded
four-wave mixing simultaneously broadens and smoothes comb spectra, resulting
in Gaussian RF filter lineshapes exhibiting extremely high (>60 dB) main lobe
to sidelobe suppression ratio and (>70 dB) stopband attenuation.Comment: Updated the submission with the most recent version of the pape
Modulation of 11β-hydroxysteroid dehydrogenase as a strategy to reduce vascular inflammation
Atherosclerosis is a chronic inflammatory disease in which initial vascular damage leads to extensive macrophage and lymphocyte infiltration. Although acutely glucocorticoids suppress inflammation, chronic glucocorticoid excess worsens atherosclerosis, possibly by exacerbating systemic cardiovascular risk factors. However, glucocorticoid action within the lesion may reduce neointimal proliferation and inflammation. Glucocorticoid levels within cells do not necessarily reflect circulating levels due to pre-receptor metabolism by 11β-hydroxysteroid dehydrogenases (11β-HSDs). 11β-HSD2 converts active glucocorticoids into inert 11-keto forms. 11β-HSD1 catalyses the reverse reaction, regenerating active glucocorticoids. 11β-HSD2-deficiency/ inhibition causes hypertension, whereas deficiency/ inhibition of 11β-HSD1 generates a cardioprotective lipid profile and improves glycemic control. Importantly, 11β-HSD1-deficiency/ inhibition is atheroprotective, whereas 11β-HSD2-deficiency accelerates atherosclerosis. These effects are largely independent of systemic risk factors, reflecting modulation of glucocorticoid action and inflammation within the vasculature. Here, we consider whether evidence linking the 11β-HSDs to vascular inflammation suggests these isozymes are potential therapeutic targets in vascular injury and atherosclerosis
Receptor concentration and diffusivity control multivalent binding of Sv40 to membrane bilayers
Incoming Simian Virus 40 particles bind to their cellular receptor, the glycolipid GM1, in the plasma membrane and thereby induce membrane deformation beneath the virion leading to endocytosis and infection. Efficient membrane deformation depends on receptor lipid structure and the organization of binding sites on the internalizing particle. To determine the role of receptor diffusion, concentration and the number of receptors required for stable binding in this interaction, we analyze the binding of SV40 to GM1 in supported membrane bilayers by computational modeling based on experimental data. We measure the diffusion rates of SV40 virions in solution by fluorescence correlation spectroscopy and of the receptor in bilayers by single molecule tracking. Quartz-crystal microbalance with dissipation (QCM-D) is used to measure binding of SV40 virus-like particles to bilayers containing the viral receptor GM1. We develop a phenomenological stochastic dynamics model calibrated against this data, and use it to investigate the early events of virus attachment to lipid membranes. Our results indicate that SV40 requires at least 4 attached receptors to achieve stable binding. We moreover find that receptor diffusion is essential for the establishment of stable binding over the physiological range of receptor concentrations and that receptor concentration controls the mode of viral motion on the target membrane. Our results provide quantitative insight into the initial events of virus-host interaction at the nanoscopic level