The consequences of cavity creation on the folding landscape of a repeat protein depend upon context.

The effect of introducing internal cavities on protein native structure and global stability has been well documented, but the consequences of these packing defects on folding free-energy landscapes have received less attention. We investigated the effects of cavity creation on the folding landscape of the leucine-rich repeat protein pp32 by high-pressure (HP) and urea-dependent NMR and high-pressure small-angle X-ray scattering (HPSAXS). Despite a modest global energetic perturbation, cavity creation in the N-terminal capping motif (N-cap) resulted in very strong deviation from two-state unfolding behavior. In contrast, introduction of a cavity in the most stable, C-terminal half of pp32 led to highly concerted unfolding, presumably because the decrease in stability by the mutations attenuated the N- to C-terminal stability gradient present in WT pp32. Interestingly, enlarging the central cavity of the protein led to the population under pressure of a distinct intermediate in which the N-cap and repeats 1-4 were nearly completely unfolded, while the fifth repeat and the C-terminal capping motif remained fully folded. Thus, despite modest effects on global stability, introducing internal cavities can have starkly distinct repercussions on the conformational landscape of a protein, depending on their structural and energetic context.

Bone Conduction as a Viable Alternative to Current Communications Systems in Fighter Cockpits.

INTRODUCTION: Effective voice communication is essential when operating aircraft. Because of the loud operating environment in fighter cockpits, it has been a challenge to provide effective communication while simultaneously protecting the hearing sense. The objective of this study was to determine the feasibility of using bone conducting transducers (BCT) in place of legacy communications systems in fighter cockpits. METHODS: A military flight helmet was modified and outfitted with BCT and air-conducting speakers. BCT were independently tested against air-conducting speakers using a clinical audiometer under three conditions: without earplugs, with earplugs, and with earplugs in the presence of 100-dB broad-spectrum noise. Three test subjects were given an audiological examination using tones of varying intensity ranging from 100 Hz to 8000 Hz. The lowest hearable intensity indicated by button press was recorded for each frequency. RESULTS: In the presence of 100-dB ambient noise, bone conducting transducers performed better than air-conducting speakers at all frequencies. Hearability of BCT by audiogram was, on average, 10-20% lower intensity (dB) than air-conducting speakers. DISCUSSION: Currently, USAF pilots wear two layers of hearing protection; i.e., the helmet's integrated earcup and some form of ear plug (e.g., foam earplug or custom-molded earbud). Our results suggest that bone conducting audio transducers may be better for layered hearing protection than air-conducting speakers when used with foam earplugs. Given the cost, complexity, and non-interoperability of custom-molded earphones, helmet-integrated bone conducting transducers and foam earplugs may be a better option for sustained airborne operations.Bradke BS, White Z, Poston J. Bone conduction as a viable alternative to current communications systems in fighter cockpits. Aerosp Med Hum Perform. 2018; 89(10):927-930.