Background & Aims: Androgen effects on hepatocellular carcinoma (HCC) remain controversial and androgen ablation therapy to treat HCC also leads to inconsistent results. Here we examine androgen ...receptor (AR) roles in hepatocarcinogenesis using mice lacking AR in hepatocytes. Methods: By using the Cre-Lox conditional knockout mice model injected with carcinogen, we examined the AR roles in hepatocarcinogenesis. We also tested the possible roles of AR in cellular oxidative stress and DNA damage sensing/repairing systems. By using AR degrading compound, ASC-J9, or AR-small interference RNA, we also examined the therapeutic potentials of targeting AR in HCC. Results: We found AR expression was increased in human HCC compared with normal livers. We also found mice lacking hepatic AR developed later and less HCC than their wild-type littermates with comparable serum testosterone in both male and female mice. Addition of functional AR in human HCC cells also resulted in the promotion of cell growth in the absence or presence of 5α-dihydrotestosterone. Mechanistic dissection suggests that AR may promote hepatocarcinogenesis via increased cellular oxidative stress and DNA damage, as well as suppression of p53-mediated DNA damage sensing/repairing system and cell apoptosis. Targeting AR directly via either AR-small interference RNA or ASC-J9 resulted in suppression of HCC in both ex vivo cell lines and in vivo mice models. Conclusions: Our data point to AR, but not androgens, as a potential new and better therapeutic target for the battle of HCC.
Route development programs have become popular with airports worldwide to enhance air connectivity. Enhanced air connectivity of an airport has been found to have a positive and significant impact on ...the competitiveness and attractiveness of the airport and the regional economy in which the airport is located. However, the drivers behind route development programs and their performance are not always clear; this has been less explored in the literature. In this paper, a dynamic performance management approach is taken to build a modeling framework in which key drivers affecting route development performance and strategic resources affecting key drivers are identified. Route-level planning is used in an empirical study to demonstrate the dynamic mechanism of airport route development initiatives and performance measurements. The proposed framework can not only provide performance monitoring, but also suggest suitable indicators to evaluate the performance for policymakers in future airport route development.
•Bayesian network in a delay-tree framework (DPT-BN model) is developed.•DPT-BN model accounts for multiple connecting sources of an airline network.•Results showed that this model can identify weak ...links in a flight network.•DTP-BN model can model heterogeneous delay propagation in a network.•New delay multiplier metrics could better account for past flight delay profiles.
We developed an airline network delay propagation model using a Bayesian Network in a delay-tree framework, accounting for multiple connecting sources of an airline including aircraft, crew connections, and passenger connections. A case study was conducted to examine the heterogeneous delay propagation effects in a flight network. Results showed that the model was able to identify weak links in a flight network based on past operational data. Two new delay multiplier metrics were developed and test results showed that the Expected Delay Multiplier could better account for historical flight delay profiles by inferring posterior probability distributions based on new observations.
In this work, a high thermoelectric figure of merit, zT of 1.9 at 740 K is achieved in Ge
Bi
Te crystals through the concurrent of Seebeck coefficient enhancement and thermal conductivity reduction ...with Bi dopants. The substitution of Bi for Ge not only compensates the superfluous hole carriers in pristine GeTe but also shifts the Fermi level (E
) to an eligible region. Experimentally, with moderate 6-10% Bi dopants, the carrier concentration is drastically decreased from 8.7 × 10
cm
to 3-5 × 10
cm
and the Seebeck coefficient is boosted three times to 75 μVK
. In the meantime, based on the density functional theory (DFT) calculation, the Fermi level E
starts to intersect with the pudding mold band at L point, where the band effective mass is enhanced. The enhanced Seebeck coefficient effectively compensates the decrease of electrical conductivity and thus successfully maintain the power factor as large as or even superior than that of the pristine GeTe. In addition, the Bi doping significantly reduces both thermal conductivities of carriers and lattices to an extremely low limit of 1.57 W m
K
at 740 K with 10% Bi dopants, which is an about 63% reduction as compared with that of pristine GeTe. The elevated figure of merit observed in Ge
Bi
Te specimens is therefore realized by synergistically optimizing the power factor and downgrading the thermal conductivity of alloying effect and lattice anharmonicity caused by Bi doping.
This article reports the results of a holiday destination choice model of domestic travelers in Australia. Although destination choices have been studied before, travelers’ behavior when choosing an ...airline ticket is less well investigated, in particular the effect of the choice of airline ticket and tourism features on each other and on the final destination choice. Multinomial logit (MNL) models were estimated using data from a Stated Preference (SP) choice experiment based on a D-Efficient design. Following the leader-driven primacy phenomenon, the article also tests whether destination choices are influenced by sequentially receiving information about airline tickets and tourism features. Results show that when airline ticket information is presented first, the destination choice behavior could be affected. In this context, the information sequencing effect is clear. However, the influence of tourism features is not as clear on the final choice when travelers are first exposed to tourism features and then airline tickets.
Efficient aircraft turnaround operations at airports are vital to ensure overall air traffic network performance. After the outbreak of COVID-19, the traditional aircraft ground handling process has ...changed significantly due to new requirements put forward by the pandemic prevention and control policy. To better understand how COVID-19 has affected ground handling operations, a discrete-event simulation model of turnaround is established to analyze the change in the whole turnaround process before and after the pandemic. The critical path of turnaround operations was used to identify the significantly affected subprocesses to which airports should pay attention. For a case study on the two busiest airports in China, the aircraft turnaround time increased by about 18% after COVID-19. Cabin cleaning, catering, and passenger embarking were the main processes in causing this increase. By evaluating the impact mechanism of COVID-19 on turnaround operations, the study sheds light on strategic, tactical, and operational approaches for relevant authorities.
This study proposes a novel framework to investigate the interdependence and determinants of tourism participation, expenditure, and duration related to tourism behavior. A discrete–continuous model ...was constructed to jointly estimate the participation and expenditure decisions. Then, a structural equation model was used to explore the corresponding influential determinants of tourism expenditure and trip duration. An empirical study was conducted using historical travel data collected from Taiwanese citizens traveling abroad. Results revealed a significant relationship between participation and expenditure as well as between expenditure and duration. Furthermore, package and frequent travelers were willing to spend more on trips of shorter duration, but individual and independent travelers were more cost-conscious and travel for longer periods. Overall, time constraints were found to take priority over personal income when making tourism decisions. These findings help travel agents and policymakers to better understand travelers’ needs and develop tourism policies.
For reasons of tractability, the airline scheduling problem has traditionally been sequentially decomposed into various stages (e.g. schedule generation, fleet assignment, aircraft routing, and crew ...pairing), with the decisions from one stage imposed upon the decision-making process in subsequent stages. Whilst this approach greatly simplifies the solution process, it unfortunately fails to capture many dependencies between the various stages, most notably between those of aircraft routing and crew pairing, and how these dependencies affect the propagation of delays through the flight network. In Dunbar et al. (2012) 9 we introduced a new algorithm to accurately calculate and minimize the cost of propagated delay, in a framework that integrates aircraft routing and crew pairing. In this paper we extend the approach of Dunbar et al. (2012) 9 by proposing two new algorithms that achieve further improvements in delay propagation reduction via the incorporation of stochastic delay information. We additionally propose a heuristic, used in conjunction with these two approaches, capable of re-timing an incumbent aircraft and crew schedule to further minimize the cost of delay propagation. These algorithms provide promising results when applied to a real-world airline network and motivate our final integrated aircraft routing, crew pairing and re-timing approach which provides a substantially significant reduction in delay propagation.
Air Transportation is a major contributor to international mobility and has high requirements to ensure safe and secure operations. Aircraft ground operations are impacted significantly by the ...current pandemic situation so that standard operating procedures need a redesign to incorporate the upcoming sanitation requirements. In particular, the passenger boarding process is challenged with requirements for physical distances between passengers, while in addition to standard cleaning, the cabin has to be disinfected after each flight. We evaluate potential alterations of these two aircraft cabin processes with respect to a pre-pandemic reference aircraft turnaround. The implementation of microscopic approaches allows to consider individual interactions and a step-wise process adaptation aiming for an efficient operational design. We find a significant extension of boarding times (more than doubled) if the physical distance rule is applied. The new disinfection process further extends the critical path of the turnaround, so we see a high impact on airport and airline operations. To compensate for the increased workload and process times, we provide an integrated cleaning and disinfection procedure with additional personnel. Our results indicate that the pre-pandemic turnaround times cannot be maintained for the same seat load, even if the process adaptations are being implemented. However, a seat allocation scheme with empty middle-seats (seat load of 67%) and the use of an apron position (additional use of rear aircraft door for boarding) enable pre-pandemic turnaround times without additional cleaning personnel. Aircraft turnarounds at terminal positions require between 10% (with additional personnel) and 20% (without additional personnel) more ground time.
This paper proposes a new localization method for mobile robots based on received signal strength (RSS) in indoor wireless local area networks (WLANs). In indoor wireless networks, propagation ...conditions are very difficult to predict due to interference, reflection, and fading effects. As a result, an explicit measurement equation is not available. In this paper, an observation likelihood model is accomplished using kernel density estimation to characterize the dependence of location and RSS. Based on the measured RSS, the robot's location is dynamically estimated using the proposed adaptive local search particle filter (ALSPF), which adopts the covariance adaptation for correcting the system states and updating the motion uncertainty. To deal with low sensor density in large-space environments, we present a strategy based on the strongest signal with minimum variance to choose a subset of detectable access points (APs) for enhancing robot localization and reducing the computational burden. The proposed approaches are verified by realistic low-density WLAN APs to demonstrate the feasibility and suitability. Experimental results indicate that the proposed ALSPF provides approximately 1-m error and significant improvements over particle filtering.
PDF
