Developmental patterning relies on morphogen gradients, which generally involve feedback loops to buffer against perturbations caused by fluctuations in gene dosage and expression. Although many gene components involved in such feedback loops have been identified, how they work together to generate a robust pattern remains unclear. Here we study the network of extracellular proteins that patterns the dorsal region of the Drosophila embryo by establishing a graded activation of the bone morphogenic protein (BMP) pathway. We find that the BMP activation gradient itself is robust to changes in gene dosage. Computational search for networks that support robustness shows that transport of the BMP class ligands (Scw and Dpp) into the dorsal midline by the BMP inhibitor Sog is the key event in this patterning process. The mechanism underlying robustness relies on the ability to store an excess of signalling molecules in a restricted spatial domain where Sog is largely absent. It requires extensive diffusion of the BMP-Sog complexes, coupled with restricted diffusion of the free ligands. We show experimentally that Dpp is widely diffusible in the presence of Sog but tightly localized in its absence, thus validating a central prediction of our theoretical study.
PurposeTo compare the performance of various commercially available stethoscopes using standard acoustic engineering criteria, under recording studio conditions.Materials and methodsEighteen stethoscopes (11 acoustic, 7 electronic) were analyzed using standard acoustic analysis techniques under professional recording studio conditions. An organic phantom that accurately simulated chest cavity acoustics was developed. Test sounds were played via a microphone embedded within it and auscultated at its surface by the stethoscopes. Recordings were made through each stethoscope’s binaurals and/or downloaded (electronic models). Recordings were analyzed using standard studio techniques and software, including assessing ambient noise (AMB) rejection. Frequency ranges were divided into those corresponding to various standard biological sounds (cardiac, respiratory, and gastrointestinal).ResultsLoudness and AMB rejection: Overall, electronic stethoscopes, when set to a maximum volume, exhibited greater values of perceived loudness compared to acoustic stethoscopes. Significant variation was seen in AMB rejection capability. Frequency detection: Marked variation was also seen, with some stethoscopes performing better for different ranges (eg, cardiac) vs others (eg, gastrointestinal).ConclusionThe acoustic properties of stethoscopes varied considerably in loudness, AMB rejection, and frequency response. Stethoscope choice should take into account clinical conditions to be auscultated and the noise level of the environment.
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