Physics-Informed Modeling and Control of Multi-Actuator Soft Catheter Robots

Catheter-based endovascular interventional procedures have become increasingly popular in recent years as they are less invasive and patients spend less time in the hospital with less recovery time and less pain. These advantages have led to a significant growth in the number of procedures that are performed annually. However, it is still challenging to position a catheter in a target vessel branch within the highly complicated and delicate vascular structure. In fact, vessel tortuosity and angulation, which cause difficulties in catheterization and reaching the target site, have been reported as the main causes of failure in endovascular procedures. Maneuverability of a catheter for intravascular navigation is a key to reaching the target area; ability of a catheter to move within the target vessel during trajectory tracking thus affects to a great extent the length and success of the procedure. To address this issue, this paper models soft catheter robots with multiple actuators and provides a time-dependent model for characterizing the dynamics of multi-actuator soft catheter robots. Built on this model, an efficient and scalable optimization-based framework is developed for guiding the catheter to pass through arteries and reach the target where an aneurysm is located. The proposed framework models the deflection of the multi-actuator soft catheter robot and develops a control strategy for movement of catheter along a desired trajectory. This provides a simulation-based framework for selection of catheters prior to endovascular catheterization procedures, assuring that given a fixed design, the catheter is able to reach the target location. The results demonstrate the benefits that can be achieved by design and control of catheters with multiple number of actuators for navigation into small vessels.

p53-mediated AKT and mTOR inhibition requires RFX7 and DDIT4 and depends on nutrient abundance

In recent years the tumor suppressor p53 has been increasingly recognized as a potent regulator of the cell metabolism and for its ability to inhibit the critical pro-survival kinases AKT and mTOR. The mechanisms through which p53 controls AKT and mTOR, however, are largely unclear. Here, we demonstrate that p53 activates the metabolic regulator DDIT4 indirectly through the regulatory factor X 7 (RFX7). We provide evidence that DDIT4 is required for p53 to inhibit mTOR complex 2 (mTORC2)-dependent AKT activation. Most strikingly, we also find that the DDIT4 regulator RFX7 is required for p53-mediated inhibition of mTORC1 and AKT. Our results suggest that AMPK activation plays no role and p53-mediated AKT inhibition is not critical for p53-mediated mTORC1 inhibition. Moreover, using recently developed physiological cell culture media we uncover that basal p53 and RFX7 activity can play a critical role in restricting mTORC1 activity under physiological nutrient conditions, and we propose a nutrient-dependent model for p53-RFX7-mediated mTORC1 inhibition. These results establish RFX7 and its downstream target DDIT4 as essential effectors in metabolic control elicited by p53.

Studying the Influence of External Photon Fields on Blazar Spectra Using a One-Zone Hadro-Leptonic Time-Dependent Model

The recent associations of neutrinos with blazars require the efficient interaction of relativistic protons with ambient soft photon fields. However, along side the neutrinos, γ-ray photons are produced, which interact with the same soft photon fields producing electron-positron pairs. The strength of this cascade has significant consequences on the photon spectrum in various energy bands and puts severe constraints on the pion and neutrino production. In this study, we discuss the influence of the external thermal photon fields (accretion disk, broad-line region, and dusty torus) on the proton-photon interactions, employing a newly developed time-dependent one-zone hadro-leptonic code OneHaLe. We present steady-state cases, as well as a time-dependent case, where the emission region moves through the jet. Within the limits of this toy study, the external fields can disrupt the “usual” double-humped blazar spectrum. Similarly, a moving region would cross significant portions of the jet without reaching the previously-found steady states.