Simulating Depth Perception in Virtual Microscopy

Abstract

3D datasets production capacity in bioimaging has widely evolved in recent years. This trend also results in a growing demand of more suitable display procedures. In this paper, we propose a new virtual microscopy approach aiming at recovering the third dimension, in order to get closer to analogue microscopes. For this purpose, we rely on multi-view autosteroscopic display with off-centered parallel virtual cameras to ensure 3D perception for a more realistic user experience. Also, this approach handles very large volume data size thanks to an out-of-core data management structure which offers interactive navigation by using complete GPU algorithms.

Mechanisms of Specific versus Nonspecific Interactions of Aggregation-Prone Inhibitors and Attenuators

“…To investigate the types of interactions between EPAC and the ESIs that could occur both below and above their CACs, we monitored the ESI titrations through chemical shift changes and intensity losses in the NH-HSQC spectra of the uniformly 15 N-labeled cAMPbinding domain (residues 149-318) of EPAC1 (EPAC1 CBD ). CE3F4R, a unique uncompetitive inhibitor, 31,33,34 binds to the cAMP-bound state of EPAC1 CBD resulting initially in significant chemical shift changes (Figure 2A,B). The chemical shift changes are both residue dependent and multidirectional within the ( 1 H, 15 N) plane, as typically expected for specific interactions (Figure 2A,B).…”

“…To address the open questions about the ABI mechanism as well as ABI detection and attenuation, here we focus on two prototypical hydrophobic inhibitors that target the exchange protein directly activated by cAMP (EPAC), i.e., CE3F4R and ESI-09 ( Figure 1A,D). Both EPAC-selective inhibitors (ESIs) inhibit EPAC effectively and specifically at low micromolar concentrations [31][32][33][34][35][36] and are promising pharmacological leads for treating EPAC-associated diseases, such as pancreatic cancer and cardiac hypertrophy. [33][34][35][36] However, at higher concentrations ESIs exhibit multiple hallmarks of aggregation-based inhibition.…”

“…Both EPAC-selective inhibitors (ESIs) inhibit EPAC effectively and specifically at low micromolar concentrations [31][32][33][34][35][36] and are promising pharmacological leads for treating EPAC-associated diseases, such as pancreatic cancer and cardiac hypertrophy. [33][34][35][36] However, at higher concentrations ESIs exhibit multiple hallmarks of aggregation-based inhibition. 37 Herein, we investigate the aggregation equilibria of CE3F4R and ESI-09, and we examine how the resulting aggregates interact nonspecifically with EPAC and interfere with specific binding.…”