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Lam, Doris

Publications and source records attributed to Lam, Doris.

7 records
All sourcesNASA NTRSDOE OSTI
DOE OSTI2024

Evaluation of Subetadex-α-methyl, a Polyanionic Cyclodextrin Scaffold, as a Medical Countermeasure against Fentanyl and Related Opioids

Subetadex-α-methyl (SBX-Me), a modified, polyanionic cyclodextrin scaffold, has been evaluated for its utilization as a medical countermeasure (MCM) to neutralize the effects of fentanyl and related opioids. Initial in vitro toxicity assays demonstrate that SBX-Me has a nontoxic profile, comparable to the FDA-approved cyclodextrin-based drug Sugammadex. Pharmacokinetic analysis showed rapid clearance of SBX-Me with an elimination half-life of ~7.4 h and little accumulation in major organs. SBX-Me was also evaluated for its ability to counteract the effects of fentanyl, carfentanil, and remifentanil in rats. Recovery times in rats exposed to sublethal fentanyl doses were found to be shorter when treated with SBX-Me after opioid exposure. The recovery times were reduced from ~35 to ~17 min for fentanyl, ~172 to ~59 min for carfentanil, and ~18 to ~12 min for remifentanil. SBX-Me increased the elimination half-life for fentanyl and remifentanil from 5.37 to 6.42 h and 8.24 to 9.74 h, respectively. These data support SBX-Me as a solid platform from which further research can be launched for the development of a MCM against the effects of fentanyl and its analogs. Furthermore, the data suggests that SBX-Me and other analogs are attractive candidates as broad spectrum opioids targeting MCMs.

Chemistry↗
DOE OSTI2024

Biphasic response of human iPSC-derived neural network activity following exposure to a sarin-surrogate nerve agent

Organophosphorus nerve agents (OPNA) are hazardous environmental exposures to the civilian population and have been historically weaponized as chemical warfare agents (CWA). OPNA exposure can lead to several neurological, sensory, and motor symptoms that can manifest into chronic neurological illnesses later in life. There is still a large need for technological advancement to better understand changes in brain function following OPNA exposure. The human-relevant in vitro multi-electrode array (MEA) system, which combines the MEA technology with human stem cell technology, has the potential to monitor the acute, sub-chronic, and chronic consequences of OPNA exposure on brain activity. However, the application of this system to assess OPNA hazards and risks to human brain function remains to be investigated. In a concentration-response study, we have employed a human-relevant MEA system to monitor and detect changes in the electrical activity of engineered neural networks to increasing concentrations of the sarin surrogate 4-nitrophenyl isopropyl methylphosphonate (NIMP). We report a biphasic response in the spiking (but not bursting) activity of neurons exposed to low (i.e., 0.4 and 4 μM) versus high concentrations (i.e., 40 and 100 μM) of NIMP, which was monitored during the exposure period and up to 6 days post-exposure. Regardless of the NIMP concentration, at a network level, communication or coordination of neuronal activity decreased as early as 60 min and persisted at 24 h of NIMP exposure. Once NIMP was removed, coordinated activity was no different than control (0 μM of NIMP). Interestingly, only in the high concentration of NIMP did coordination of activity at a network level begin to decrease again at 2 days post-exposure and persisted on day 6 post-exposure. Notably, cell viability was not affected during or after NIMP exposure. Also, while the catalytic activity of AChE decreased during NIMP exposure, its activity recovered once NIMP was removed. Gene expression analysis suggests that human iPSC-derived neurons and primary human astrocytes resulted in altered genes related to the cell’s interaction with the extracellular environment, its intracellular calcium signaling pathways, and inflammation, which could have contributed to how neurons communicated at a network level.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS2013

Model Based Document and Report Generation for Systems Engineering

As Model Based Systems Engineering (MBSE) practices gain adoption, various approaches have been developed in order to simplify and automate the process of generating documents from models. Essentially, all of these techniques can be unified around the concept of producing different views of the model according to the needs of the intended audience. In this paper, we will describe a technique developed at JPL of applying SysML Viewpoints and Views to generate documents and reports. An architecture of model-based view and document generation will be presented, and the necessary extensions to SysML with associated rationale will be explained. A survey of examples will highlight a variety of views that can be generated, and will provide some insight into how collaboration and integration is enabled. We will also describe the basic architecture for the enterprise applications that support this approach.

Architecture↗
NASA NTRS2012

Model-Based Systems Engineering Approach to Managing Mass Margin

When designing a flight system from concept through implementation, one of the fundamental systems engineering tasks ismanaging the mass margin and a mass equipment list (MEL) of the flight system. While generating a MEL and computing a mass margin is conceptually a trivial task, maintaining consistent and correct MELs and mass margins can be challenging due to the current practices of maintaining duplicate information in various forms, such as diagrams and tables, and in various media, such as files and emails. We have overcome this challenge through a model-based systems engineering (MBSE) approach within which we allow only a single-source-of-truth. In this paper we describe the modeling patternsused to capture the single-source-of-truth and the views that have been developed for the Europa Habitability Mission (EHM) project, a mission concept study, at the Jet Propulsion Laboratory (JPL).

cloud comu↗
NASA NTRS2011

MOS 2.0: Modeling the Next Revolutionary Mission Operations System

Designed and implemented in the 1980's, the Advanced Multi-Mission Operations System (AMMOS) was a breakthrough for deep-space NASA missions, enabling significant reductions in the cost and risk of implementing ground systems. By designing a framework for use across multiple missions and adaptability to specific mission needs, AMMOS developers created a set of applications that have operated dozens of deep-space robotic missions over the past 30 years. We seek to leverage advances in technology and practice of architecting and systems engineering, using model-based approaches to update the AMMOS. We therefore revisit fundamental aspects of the AMMOS, resulting in a major update to the Mission Operations System (MOS): MOS 2.0. This update will ensure that the MOS can support an increasing range of mission types, (such as orbiters, landers, rovers, penetrators and balloons), and that the operations systems for deep-space robotic missions can reap the benefits of an iterative multi-mission framework.12 This paper reports on the first phase of this major update. Here we describe the methods and formal semantics used to address MOS 2.0 architecture and some early results. Early benefits of this approach include improved stakeholder input and buy-in, the ability to articulate and focus effort on key, system-wide principles, and efficiency gains obtained by use of well-architected design patterns and the use of models to improve the quality of documentation and decrease the effort required to produce and maintain it. We find that such methods facilitate reasoning, simulation, analysis on the system design in terms of design impacts, generation of products (e.g., project-review and software-delivery products), and use of formal process descriptions to enable goal-based operations. This initial phase yields a forward-looking and principled MOS 2.0 architectural vision, which considers both the mission-specific context and long-term system sustainability.

ground support systems↗
NASA NTRS2011

Dynamic Gate Product and Artifact Generation from System Models

Model Based Systems Engineering (MBSE) is gaining acceptance as a way to formalize systems engineering practice through the use of models. The traditional method of producing and managing a plethora of disjointed documents and presentations ("Power-Point Engineering") has proven both costly and limiting as a means to manage the complex and sophisticated specifications of modern space systems. We have developed a tool and method to produce sophisticated artifacts as views and by-products of integrated models, allowing us to minimize the practice of "Power-Point Engineering" from model-based projects and demonstrate the ability of MBSE to work within and supersede traditional engineering practices. This paper describes how we have created and successfully used model-based document generation techniques to extract paper artifacts from complex SysML and UML models in support of successful project reviews. Use of formal SysML and UML models for architecture and system design enables production of review documents, textual artifacts, and analyses that are consistent with one-another and require virtually no labor-intensive maintenance across small-scale design changes and multiple authors. This effort thus enables approaches that focus more on rigorous engineering work and less on "PowerPoint engineering" and production of paper-based documents or their "office-productivity" file equivalents.

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