The relationship between the radio and gamma-ray emission of blazars

Blazars are active galaxies with a jet closely oriented to our line of sight. They are powerful, variable emitters from radio to gamma-ray wavelengths. Although the general picture of synchrotron emission at low energies and inverse Compton at high energies is well established, important aspects of blazars are not well understood. In particular, the location of the gamma-ray emission region is not clearly established, with some theories favoring a location close to the central engine, while others place it at parsec scales in the radio jet.

We developed a program to locate the gamma-ray emission site in blazars, through the study of correlated variations between their gamma-ray and radio-wave emission. Correlated variations are expected when there is a relation between emission processes at both bands, while delays tell us about the relative location of their energy generation zones. Monitoring at 15 GHz using the Owens Valley Radio Observatory 40 meter telescope started in mid-2007. The program monitors 1593 blazars twice per week, including all blazars detected by the Fermi Gamma-ray Space Telescope (Fermi) north of -20 degrees declination. This program complements the continuous monitoring of gamma-rays by Fermi.

Three year long gamma-ray light curves for bright Fermi blazars are cross-correlated with four years of radio monitoring. The significance of cross-correlation peaks is investigated using simulations that account for the uneven sampling and noise properties of the light curves, which are modeled as red-noise processes with a simple power-law power spectral density. We found that out of 86 sources with high quality data, only three show significant correlations (AO 0235+164, B2 2308+34 and PKS 1502+106). Additionally, we find a significant correlation for Mrk 421 when including the strong gamma-ray/radio flare of late 2012. In all four cases radio variations lag gamma-ray variations, suggesting that the gamma-ray emission originates upstream of the radio emission. For PKS 1502+106 we locate the gamma-ray emission site parsecs away from the central engine, thus disfavoring the model of Blandford and Levinson (1995), while other cases are inconclusive. These findings show that continuous monitoring over long time periods is required to understand the cross-correlation between gamma-ray and radio-wave variability in most blazars.

MEMS for Diabetic Retinopathy

As the worldwide prevalence of diabetes mellitus continues to increase, diabetic retinopathy remains the leading cause of visual impairment and blindness in many developed countries. Between 32 to 40 percent of about 246 million people with diabetes develop diabetic retinopathy. Approximately 4.1 million American adults 40 years and older are affected by diabetic retinopathy. This glucose-induced microvascular disease progressively damages the tiny blood vessels that nourish the retina, the light-sensitive tissue at the back of the eye, leading to retinal ischemia (i.e., inadequate blood flow), retinal hypoxia (i.e., oxygen deprivation), and retinal nerve cell degeneration or death. It is a most serious sight-threatening complication of diabetes, resulting in significant irreversible vision loss, and even total blindness.

Unfortunately, although current treatments of diabetic retinopathy (i.e., laser therapy, vitrectomy surgery and anti-VEGF therapy) can reduce vision loss, they only slow down but cannot stop the degradation of the retina. Patients require repeated treatment to protect their sight. The current treatments also have significant drawbacks. Laser therapy is focused on preserving the macula, the area of the retina that is responsible for sharp, clear, central vision, by sacrificing the peripheral retina since there is only limited oxygen supply. Therefore, laser therapy results in a constricted peripheral visual field, reduced color vision, delayed dark adaptation, and weakened night vision. Vitrectomy surgery increases the risk of neovascular glaucoma, another devastating ocular disease, characterized by the proliferation of fibrovascular tissue in the anterior chamber angle. Anti-VEGF agents have potential adverse effects, and currently there is insufficient evidence to recommend their routine use.

In this work, for the first time, a paradigm shift in the treatment of diabetic retinopathy is proposed: providing localized, supplemental oxygen to the ischemic tissue via an implantable MEMS device. The retinal architecture (e.g., thickness, cell densities, layered structure, etc.) of the rabbit eye exposed to ischemic hypoxic injuries was well preserved after targeted oxygen delivery to the hypoxic tissue, showing that the use of an external source of oxygen could improve the retinal oxygenation and prevent the progression of the ischemic cascade.

The proposed MEMS device transports oxygen from an oxygen-rich space to the oxygen-deficient vitreous, the gel-like fluid that fills the inside of the eye, and then to the ischemic retina. This oxygen transport process is purely passive and completely driven by the gradient of oxygen partial pressure (pO₂). Two types of devices were designed. For the first type, the oxygen-rich space is underneath the conjunctiva, a membrane covering the sclera (white part of the eye), beneath the eyelids and highly permeable to oxygen in the atmosphere when the eye is open. Therefore, sub-conjunctival pO₂ is very high during the daytime. For the second type, the oxygen-rich space is inside the device since pure oxygen is needle-injected into the device on a regular basis.

To prevent too fast or too slow permeation of oxygen through the device that is made of parylene and silicone (two widely used biocompatible polymers in medical devices), the material properties of the hybrid parylene/silicone were investigated, including mechanical behaviors, permeation rates, and adhesive forces. Then the thicknesses of parylene and silicone became important design parameters that were fine-tuned to reach the optimal oxygen permeation rate.

The passive MEMS oxygen transporter devices were designed, built, and tested in both bench-top artificial eye models and in-vitro porcine cadaver eyes. The 3D unsteady saccade-induced laminar flow of water inside the eye model was modeled by computational fluid dynamics to study the convective transport of oxygen inside the eye induced by saccade (rapid eye movement). The saccade-enhanced transport effect was also demonstrated experimentally. Acute in-vivo animal experiments were performed in rabbits and dogs to verify the surgical procedure and the device functionality. Various hypotheses were confirmed both experimentally and computationally, suggesting that both the two types of devices are very promising to cure diabetic retinopathy. The chronic implantation of devices in ischemic dog eyes is still underway.

The proposed MEMS oxygen transporter devices can be also applied to treat other ocular and systemic diseases accompanied by retinal ischemia, such as central retinal artery occlusion, carotid artery disease, and some form of glaucoma.