TRPC1 regulates calcium-activated chloride channels in salivary gland cells

Calcium-activated chloride channel (CaCC) plays an important role in modulating epithelial secretion. It has been suggested that in salivary tissues, sustained fluid secretion is dependent on Ca2+ influx that activates ion channels such as CaCC to initiate Cl- efflux. However direct evidence as well as the molecular identity of the Ca2+ channel responsible for activating CaCC in salivary tissues is not yet identified. Here we provide evidence that in human salivary cells, an outward rectifying Cl- current was activated by increasing [Ca2+]i, which was inhibited by the addition of pharmacological agents niflumic acid (NFA), an antagonist of CaCC, or T16Ainh-A01, a specific TMEM16a inhibitor. Addition of thapsigargin (Tg), that induces store-depletion and activates TRPC1-mediated Ca2+ entry, potentiated the Cl- current, which was inhibited by the addition of a non-specific TRPC channel blocker SKF96365 or removal of external Ca2+. Stimulation with Tg also increased plasma membrane expression of TMEM16a protein, which was also dependent on Ca2+ entry. Importantly, in salivary cells, TRPC1 silencing, but not that of TRPC3, inhibited CaCC especially upon store depletion. Moreover, primary acinar cells isolated from submandibular gland also showed outward rectifying Cl- currents upon increasing [Ca2+]i. These Cl- currents were again potentiated with the addition of Tg, but inhibited in the presence of T16Ainh-A01. Finally, acinar cells isolated from the submandibular glands of TRPC1 knockout mice showed significant inhibition of the outward Cl- currents without decreasing TMEM16a expression. Together the data suggests that Ca2+ entry via the TRPC1 channels is essential for the activation of CaCC.Fil: Sun, Yuyang. University Of North Dakota; Estados UnidosFil: Birnbaumer, Lutz. National Institutes of Health; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Singh, Brij B.. University Of North Dakota; Estados Unido

Assessing the effectiveness of managed lane strategies for the rapid deployment of cooperative adaptive cruise control technology

Connected and Automated Vehicle (C/AV) technologies are fast expanding in the transportation and automotive markets. One of the highly researched examples of C/AV technologies is the Cooperative Adaptive Cruise Control (CACC) system, which exploits various vehicular sensors and vehicle-to-vehicle communication to automate vehicular longitudinal control. The operational strategies and network-level impacts of CACC have not been thoroughly discussed, especially in near-term deployment scenarios where Market Penetration Rate (MPR) is relatively low. Therefore, this study aims to assess CACC\u27s impacts with a combination of managed lane strategies to provide insights for CACC deployment. The proposed simulation framework incorporates 1) the Enhanced Intelligent Driver Model; 2) Nakagami-based radio propagation model; and 3) a multi-objective optimization (MOOP)-based CACC control algorithm. The operational impacts of CACC are assessed under four managed lane strategies (i.e., mixed traffic (UML), HOV (High Occupancy Vehicle)-CACC lane (MML), CACC dedicated lane (DL), and CACC dedicated lane with access control (DLA)). Simulation results show that the introduction of CACC, even with 10% MPR, is able to improve the network throughput by 7% in the absence of any managed lane strategies. The segment travel times for both CACC and non-CACC vehicles are reduced. The break-even point for implementing dedicated CACC lane is 30% MPR, below which the priority usage of the current HOV lane for CACC traffic is found to be more appropriate. It is also observed that DLA strategy is able to consistently increase the percentage of platooned CACC vehicles as MPR grows. The percentage of CACC vehicles within a platoon reaches 52% and 46% for DL and DLA, respectively. When it comes to the impact of vehicle-to-vehicle (V2V), it is found that DLA strategy provides more consistent transmission density in terms of median and variance when MPR reaches 20% or above. Moreover, the performance of the MOOP-based cooperative driving is examined. With average 75% likelihood of obtaining a feasible solution, the MOOP outperforms its counterpart which aims to minimize the headway objective solely. In UML, MML, and DL strategy, the proposed control algorithm achieves a balance spread among four objectives for each CACC vehicle. In the DLA strategy, however, the probability of obtaining feasible solution falls to 60% due to increasing size of platoon owing to DLA that constraints the feasible region by introduction more dimensions in the search space. In summary, UML or MML is the preferred managed lane strategy for improving traffic performance when MPR is less than 30%. When MRP reaches 30% or above, DL and DLA could improve the CACC performance by facilitating platoon formation. If available, priority access to an existing HOV lane can be adopted to encourage adaptation of CACC when CACC technology becomes publically available

Analyzing Attacks on Cooperative Adaptive Cruise Control (CACC)

Cooperative Adaptive Cruise Control (CACC) is one of the driving applications of vehicular ad-hoc networks (VANETs) and promises to bring more efficient and faster transportation through cooperative behavior between vehicles. In CACC, vehicles exchange information, which is relied on to partially automate driving; however, this reliance on cooperation requires resilience against attacks and other forms of misbehavior. In this paper, we propose a rigorous attacker model and an evaluation framework for this resilience by quantifying the attack impact, providing the necessary tools to compare controller resilience and attack effectiveness simultaneously. Although there are significant differences between the resilience of the three analyzed controllers, we show that each can be attacked effectively and easily through either jamming or data injection. Our results suggest a combination of misbehavior detection and resilient control algorithms with graceful degradation are necessary ingredients for secure and safe platoons.Comment: 8 pages (author version), 5 Figures, Accepted at 2017 IEEE Vehicular Networking Conference (VNC

Automated Merging in a Cooperative Adaptive Cruise Control (CACC) System

Cooperative Adaptive Cruise Control (CACC) is a form of cruise control in which a vehicle maintains a constant headway to its preceding vehicle using radar and vehicle-to-vehicle (V2V) communication. Within the Connect & Drive1 project we have implemented and tested a prototype of such a system, with IEEE 802.11p as the enabling communication technology. In this paper we present an extension of our CACC system that allows vehicles to merge inside a platoon of vehicles at a junction, i.e., at a pre-defined location. Initially the merging vehicle and the platoon are outside each other’s communication range and are unaware of each other. Our merging algorithm is fully distributed and uses asynchronous multi-hop communication. Practical testing of our algorithm is planned for May 2011