Imiquimod enhances excitability of dorsal root ganglion neurons by inhibiting background (K2P) and voltage-gated (Kv1.1 and Kv1.2) potassium channels

<p>Abstract</p> <p>Background</p> <p>Imiquimod (IQ) is known as an agonist of Toll-like receptor 7 (TLR7) and is widely used to treat various infectious skin diseases. However, it causes severe itching sensation as its side effect. The precise mechanism of how IQ causes itching sensation is unknown. A recent report suggested a molecular target of IQ as TLR7 expressed in dorsal root ganglion (DRG) neurons. However, we recently proposed a TLR7-independent mechanism, in which the activation of TLR7 is not required for the action of IQ in DRG neurons. To resolve this controversy regarding the involvement of TLR7 and to address the exact molecular identity of itching sensation by IQ, we investigated the possible molecular target of IQ in DRG neurons.</p> <p>Findings</p> <p>When IQ was applied to DRG neurons, we observed an increase in action potential (AP) duration and membrane resistance both in wild type and TLR7-deficient mice. Based on these results, we tested whether the treatment of IQ has an effect on the activity of K⁺channels, K_v1.1 and K_v1.2 (voltage-gated K⁺channels) and TREK1 and TRAAK (K_2Pchannels). IQ effectively reduced the currents mediated by both K⁺channels in a dose-dependent manner, acting as an antagonist at TREK1 and TRAAK and as a partial antagonist at K_v1.1 and K_v1.2.</p> <p>Conclusions</p> <p>Our results demonstrate that IQ blocks the voltage-gated K⁺channels to increase AP duration and K_2Pchannels to increase membrane resistance, which are critical for the membrane excitability of DRG neurons. Therefore, we propose that IQ enhances the excitability of DRG neurons by blocking multiple potassium channels and causing pruritus.</p

Optimization of Airport Surface Traffic: A Case-Study of Incheon International Airport

This study aims to develop a controllers decision support tool for departure and surface management of ICN. Airport surface traffic optimization for Incheon International Airport (ICN) in South Korea was studied based on the operational characteristics of ICN and airspace of Korea. For surface traffic optimization, a multiple runway scheduling problem and a taxi scheduling problem were formulated into two Mixed Integer Linear Programming (MILP) optimization models. The Miles-In-Trail (MIT) separation constraint at the departure fix shared by the departure flights from multiple runways and the runway crossing constraints due to the taxi route configuration specific to ICN were incorporated into the runway scheduling and taxiway scheduling problems, respectively. Since the MILP-based optimization model for the multiple runway scheduling problem may be computationally intensive, computation times and delay costs of different solving methods were compared for a practical implementation. This research was a collaboration between Korea Aerospace Research Institute (KARI) and National Aeronautics and Space Administration (NASA)

Operational Characteristics Identification and Simulation Model Verification for Incheon International Airport

Incheon International Airport (ICN) is one of the hub airports in East Asia. Airport operations at ICN have been growing more than 5% per year in the past five years. According to the current airport expansion plan, a new passenger terminal will be added and the current cargo ramp will be expanded in 2018. This expansion project will bring 77 new stands without adding a new runway to the airport. Due to such continuous growth in airport operations and future expansion of the ramps, it will be highly likely that airport surface traffic will experience more congestion, and therefore, suffer from efficiency degradation. There is a growing awareness in aviation research community of need for strategic and tactical surface scheduling capabilities for efficient airport surface operations. Specific to ICN airport operations, a need for A-CDM (Airport - Collaborative Decision Making) or S-CDM(Surface - Collaborative Decision Making), and controller decision support tools for efficient air traffic management has arisen since several years ago. In the United States, there has been independent research efforts made by academia, industry, and government research organizations to enhance efficiency and predictability of surface operations at busy airports. Among these research activities, the Spot and Runway Departure Advisor (SARDA) developed and tested by National Aeronautics and Space Administration (NASA) is a decision support tool to provide tactical advisories to the controllers for efficient surface operations. The effectiveness of SARDA concept, was successfully verified through the human-in-the-loop (HITL) simulations for both spot release and runway operations advisories for ATC Tower controllers of Dallas/Fort Worth International Airport (DFW) in 2010 and 2012, and gate pushback advisories for the ramp controller of Charlotte/Douglas International Airport (CLT) in 2014. The SARDA concept for tactical surface scheduling is further enhanced and is being integrated into NASA's Airspace Technology Demonstration - 2 (ATD-2) project for technology demonstration of Integrated Arrival/Departure/Surface (ADS) operations at CLT. This study is a part of the international research collaboration between KAIA (Korea Agency for Infrastructure Technology Advancement)/KARI (Korea Aerospace Research Institute) and NASA, which is being conducted to validate the effectiveness of SARDA concept as a controller decision support tool for departure and surface management of ICN. This paper presents the preliminary results of the collaboration effort. It includes investigation of the operational environment of ICN, data analysis for identification of the operational characteristics of the airport, construction and verification of airport simulation model using Surface Operations Simulator and Scheduler (SOSS), NASA's fast-time simulation tool

Predicting microbial water quality with models: Over-arching questions for managing risk in agricultural catchments

The application of models to predict concentrations of faecal indicator organisms (FIOs) in environmental systems plays an important role for guiding decision-making associated with the management of microbial water quality. In recent years there has been an increasing demand by policy-makers for models to help inform FIO dynamics in order to prioritise efforts for environmental and human-health protection. However, given the limited evidence-base on which FIO models are built relative to other agricultural pollutants (e.g. nutrients) it is imperative that the end-user expectations of FIO models are appropriately managed. In response, this commentary highlights four over-arching questions associated with: (i) model purpose; (ii) modelling approach; (iii) data availability; and (iv) model application, that must be considered as part of good practice prior to the deployment of any modelling approach to predict FIO behaviour in catchment systems. A series of short and longer-term research priorities are proposed in response to these questions in order to promote better model deployment in the field of catchment microbial dynamics

How to Attract Talented Expatriates: The Key Role of Sustainable HRM

Retaining talented expatriates is important for multinational enterprises (MNEs) to maintain knowledge sustainability between their headquarters (HQ) and subsidiaries. However, depending on the host country image of a subsidiary, the attractiveness of the subsidiary may make it challenging to recruit prospective expatriates. Based on the sustainable human resource management (HRM) perspective, this study examines the direct effect of the host country image of a subsidiary and the moderating effect of family support policies on a subsidiary&rsquo;s attractiveness, by comparing subsidiaries in the US and Vietnam. The results are based on data from 434 Korean potential expatriate applicants and show that the host country image of a subsidiary has a direct effect on the subsidiary&rsquo;s attractiveness. Specifically, expatriate applicants are less attracted to a Vietnam-based subsidiary than to a US-based one. Further, the positive moderating effect of family support policies on subsidiary attractiveness is more relevant for the Vietnam-based subsidiary. This result suggests that family support policies can be a key strategy for overcoming the less preferred host country images of subsidiaries in emerging markets, thus improving subsidiary sustainability in the long term. The implications of these findings are provided in the context of sustainable HRM and the existing expatriate literature