The patterning of many developing tissues is orchestrated by gradients of morphogens through a variety of elaborate regulatory interactions. Such interactions are thought to make gradients robust, that is, resistant to changes induced by genetic or environmental perturbations; but just how this might be done is a major unanswered question. Recently extensive numerical simulations suggest that robustness of signaling gradients cannot be attained by negative feedback (of the Hill’s function type) on signaling receptors but can be achieved through binding with nonsignaling receptors (or nonreceptors for short) such as heparan sulfate proteoglycans with the resulting complexes degrading after endocytosis. These were followed by a number of analytical and numerical studies in support of the aforementioned observations. However, evidence of feedback regulating signaling gradients has been reported in literature. The present paper undertakes a different approach to the role of feedback in robust signaling gradients. The overall goal of the project is to investigate the effectiveness of feedback mechanisms on ligand synthesis, receptor synthesis, nonreceptor synthesis, and other regulatory processes in the morphogen gradient system. As a first step, we embark herein a proof-of-concept examination of a new spatially uniform feedback process that is distinctly different from the conventional spatially nonuniform Hill function approach.
Continuous glucose monitors (CGM) display real-time glucose values enabling greater glycemic awareness with reduced management burden. Factory-calibrated CGM systems allow for glycemic assessment without the pain and inconvenience of fingerstick glucose testing. Advances in sensor chemistry and CGM algorithms have enabled factory-calibrated systems to have greater accuracy than previous generations of CGM technology. Despite these advances many patients and providers are hesitant about the idea of removing fingerstick testing from their diabetes care. In this commentary, we aim to review the clinical trials on factory-calibrated CGM systems, present the algorithms which facilitate factory-calibrated CGMs to improve accuracy, discuss clinical use of factory-calibrated CGMs, and finally present two cases demonstrating the dangers of utilizing exploits in commercial systems to prolong sensor life.
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