Plant-based indole alkaloids are very rich in pharmacological activities, and the indole nucleus is considered to contribute greatly to these activities. This review’s fundamental objective is to summarize the pharmacological potential of indole alkaloids that have been derived from plants and provide a detailed evaluation of their established pharmacological activities, which may contribute to identifying new lead compounds. The study was performed by searching various scientific databases, including Springer, Elsevier, ACS Publications, Taylor and Francis, Thieme, Wiley Online Library, ProQuest, MDPI, and online scientific books. A total of 100 indole compounds were identified and reviewed. The most active compounds possessed a variety of pharmacological activities, including anticancer, antibacterial, antiviral, antimalarial, antifungal, anti-inflammatory, antidepressant, analgesic, hypotensive, anticholinesterase, antiplatelet, antidiarrheal, spasmolytic, antileishmanial, lipid-lowering, antimycobacterial, and antidiabetic activities. Although some compounds have potent activity, some only have mild-to-moderate activity. The pharmacokinetic profiles of some of the identified compounds, such as brucine, mitragynine, 7-hydroxymitragynine, vindoline, and harmane, were also reviewed. Most of these compounds showed promising pharmacological activity. An in-depth pharmacological evaluation of these compounds should be performed to determine whether any of these indoles may serve as new leads.

In recent years, NASA has initiated the development of a focused near-to mid-term concept called "Integrated Demand Management" (IDM) under the Airspace Operations and Safety Program (AOSP). The focus of the research has been to develop more powerful, integrated operations and tools for managing trajectory constraints, leveraging existing systems and adding new automation tools and methods where needed. The IDM concept is predicated on the idea that in situations where the capacity of critical resources (such as airspace or airports) is insufficient to meet demand, a better match between available capacity and the predicted demand would significantly benefit the operations, with potential improvements in throughput, delays, and efficient flight trajectories. In current operations the reasons for the capacity/demand mismatches can vary, and range from problems due to structural limitations (e.g., surface capacity at high-volume airports, high-complexity en route or arrival airspace); to wind-related capacity changes; to the more severe, unstable and dynamic mismatches that occur with convective weather. The IDM solution proposes to address the demand / capacity mismatches by using the strategic flow management capabilities within the traffic flow management system (TFMS) toolset to "pre-condition" demand into the more tactical time-based flow management (TBFM) system, which should enable TBFM to better manage delivery to the capacity-constrained resource(s). The intent of IDM is to leverage the strengths of each of these systems to produce an integrated solution that is more powerful and robust than either could provide alone, or than the two would provide today as uncoordinated systems.Newark Liberty International Airport (EWR) was chosen to be the focus of our initial design problem for several reasons. EWR routinely sees scheduled demand at or near airport capacity through much of the day with a varying mix of short-haul and long-haul flights. Although this is usually managed effectively using miles-in-trail and TBFM metering, close-in departures can experience excessive and unpredictable ground delay if the overhead flow is saturated. In the initial development of IDM concept, an alternative solution to this volume problem was proposed that integrates 3 key capabilities: 1) Collaborative Trajectory Options Program (CTOP) capability within TFMS to issue traffic management initiatives that can "strategically" manage demand into the TBFM system; 2) TBFM capability closer to the destination airport to "tactically" manage delivery to the capacity-constrained destination; and 3) required-time-of-arrival (RTA) capability on the flight deck to provide a more controlled traffic demand using the CTOP derived schedule into the TBFM domain.The IDM concept development is ongoing and iterative, based on inputs from the FAA and airline stakeholders, as well as on insights gained from a series of human-in-the-loop

Air traffic management in the New York (NY) metropolitan area presents significant challenges including excess demand, chronic delays, and inefficient routes. At NASA, a new research effort has been initiated to explore Next Generation Air Transportation System (NextGen) Trajectory Based Operations (TBO) solutions to address lingering problems in the NY metroplex. One of the larger problems in NY is departure delays at LaGuardia airport (LGA). Constant traffic demand and physical limitations in the number of taxiways and runways cause LGA to often end up with excessive departure queues that can persist throughout the day. At the Airspace Operations Laboratory (AOL) located at NASA Ames Research Center, a TBO solution for "Departure-Sensitive Arrival Spacing" (DSAS) was developed. DSAS allows for maximum departure throughput without adversely impacting the arrival traffic during the peak demand period. The concept uses Terminal Sequencing and Spacing (TSS) operations to manage the actual runway threshold times for arrivals. An interface enhancement to the traffic manager's timeline was also added, providing the ability to manually adjust inter-arrival spacing to build precise gaps for two or even three departures between arrivals. With this set of capabilities, inter-arrival spacing could be controlled for optimal departure throughput. The concept was prototyped in a human-in-the-loop (HITL) simulation environment to determine operational requirements such as coordination procedures, timing and magnitude of TSS schedule adjustments, and display features for the tower, Terminal Radar Approach Control (TRACON), and Traffic Management Unit (TMU). A HITL simulation was conducted in August, 2014, to evaluate the concept in terms of feasibility, impact on controller workload, and potential benefits. Three conditions were compared: (1) a baseline condition using new RNAV/RNP procedures (no TSS); (2) the new procedures + TSS; and (3) new procedures + TSS + DSAS schedule adjustments. Results showed that with a maximum arrival demand (40-41 arrivals per hour), departure throughput could be increased from 38 / hour (baseline condition), to 44 / hour (TSS condition), to 47 / hour (TSS + DSAS). The results suggest that DSAS operations have the potential to increase departure throughput at LGA by up to 9 a/c per hour with little or no impact on arrivals during peak traffic demand period.

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