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In the future, there will be a growing need for more flexible but efficient utilization of radio resources. Increased flexibility in radio transmission, however, yields a higher likelihood of interference owing to limited coordination among users. In this paper, we address the problem of flexible spectrum sharing where a wideband single carrier modulated signal is spectrally overlapped by unknown narrowband interference (NBI) and where a cyclic Wiener filter is utilized for nonparametric NBI suppression at the receiver. The pulse shape design for the wideband signal is investigated to improve the NBI suppression capability of cyclic Wiener filtering. Specifically, two pulse shaping schemes, which outperform existing raised cosine pulse shaping schemes even for the same amount of excess bandwidth, are proposed. Based on computer simulation, the interference suppression capability of cyclic Wiener filtering is evaluated for both the proposed and existing pulse shaping schemes under several interference conditions and over both AWGN and Rayleigh fading channels.

Glucagon-like peptide-1 receptor (GLP-1R) agonists are efficacious antidiabetic medications that work by enhancing glucose-dependent insulin secretion and improving energy balance. Currently approved GLP-1R agonists are peptide based, and it has proven difficult to obtain small-molecule activators possessing optimal pharmaceutical properties. We report the discovery and mechanism of action of LY3502970 (OWL833), a nonpeptide GLP-1R agonist. LY3502970 is a partial agonist, biased toward G protein activation over ß-arrestin recruitment at the GLP-1R. The molecule is highly potent and selective against other class B G protein-coupled receptors (GPCRs) with a pharmacokinetic profile favorable for oral administration. A highresolution structure of LY3502970 in complex with active-state GLP- 1R revealed a unique binding pocket in the upper helical bundle where the compound is bound by the extracellular domain (ECD), extracellular loop 2, and transmembrane helices 1, 2, 3, and 7. This mechanism creates a distinct receptor conformation that may explain the partial agonism and biased signaling of the compound. Further, interaction between LY3502970 and the primate-specific Trp33 of the ECD informs species selective activity for the molecule. In efficacy studies, oral administration of LY3502970 resulted in glucose lowering in humanized GLP-1R transgenic mice and insulinotropic and hypophagic effects in nonhuman primates, demonstrating an effect size in both models comparable to injectable exenatide. Together, this work determined the molecular basis for the activity of an oral agent being developed for the treatment of type 2 diabetesmellitus, offering insights into the activation of class B GPCRs by nonpeptide ligands. [ABSTRACT FROM AUTHOR]