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Natural infections and vaccination with a pathogen typically stimulate the production of potent antibodies specific for the pathogen through a Darwinian evolutionary process known as affinity maturation. Such antibodies provide protection against reinfection by the same strain of a pathogen. A highly mutable virus, like HIV or influenza, evades recognition by these strain-specific antibodies via the emergence of new mutant strains. A vaccine that elicits antibodies that can bind to many diverse strains of the virus-known as broadly neutralizing antibodies (bnAbs)-could protect against highly mutable pathogens. Despite much work, the mechanisms by which bnAbs emerge remain uncertain. Using a computational model of affinity maturation, we studied a wide variety of vaccination strategies. Our results suggest that an effective strategy to maximize bnAb evolution is through a sequential immunization protocol, wherein each new immunization optimally increases the pressure on the immune system to target conserved antigenic sites, thus conferring breadth. We describe the mechanisms underlying why sequentially driving the immune system increasingly further from steady state, in an optimal fashion, is effective. The optimal protocol allows many evolving B cells to become bnAbs via diverse evolutionary paths.

We present an analytical model of the drift in the resonant fiber optic gyroscope (RFOG) caused by thermally induced changes in the fiber beat length ${\rm L_{B}(T)}$ and find that the relevant metric for thermal-drift performance is not ${\rm dL_{B}/dT}$ but rather ${\rm(1/L_{B}^{2})dL_{B}/dT}$ . This disfavors conventional solid-core PM fibers for which ${\rm L_{B}}$ is very short and ${\rm dL_{B}/dT}$ is large. Because the air core of hollow-core fibers does not support the strains associated with differential thermal expansion in conventional PM fibers, the birefringence of hollow-core fibers should be more thermally stable than conventional fibers with a correspondingly smaller ${\rm (1/L_{B}^{2})dL_{B}/dT}$ . To identify the relative merits of different types of fibers in the RFOG, we measure ${\rm (1/L_{B}^{2})dL_{B}/dT}$ for a variety of air-core and solid-core fibers by recording the shift in the resonance frequencies of an all-fiber ring resonator when its temperature is changed. We find that the PM air-core fiber offers a 270-fold improvement in ${\rm (1/L_{B}^{2})dL_{B}/dT}$ coefficient compared to a Panda fiber.