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Mueller, Stephen

Publications and source records attributed to Mueller, Stephen.

13 records
All sourcesNASA NTRSDOE OSTI
DOE OSTI2023

Deoptimization of FMDV P1 Region Results in Robust Serotype-Independent Viral Attenuation

Foot-and-mouth disease (FMD), caused by the FMD virus (FMDV), is a highly contagious disease of cloven-hoofed livestock that can have severe economic impacts. Control and prevention strategies, including the development of improved vaccines, are urgently needed to effectively control FMD outbreaks in endemic settings. Previously, we employed two distinct strategies (codon pair bias deoptimization (CPD) and codon bias deoptimization (CD)) to deoptimize various regions of the FMDV serotype A subtype A12 genome, which resulted in the development of an attenuated virus in vitro and in vivo, inducing varying levels of humoral responses. In the current study, we examined the versatility of the system by using CPD applied to the P1 capsid coding region of FMDV serotype A subtype, A24, and another serotype, Asia1. Viruses carrying recoded P1 (A24-P1Deopt or Asia1-P1Deopt) exhibited different degrees of attenuation (i.e., delayed viral growth kinetics and replication) in cultured cells. Studies in vivo using a mouse model of FMD demonstrated that inoculation with the A24-P1Deopt and Asia1-P1Deopt strains elicited a strong humoral immune response capable of offering protection against challenge with homologous wildtype (WT) viruses. However, different results were obtained in pigs. While clear attenuation was detected for both the A24-P1Deopt and Asia1-P1Deopt strains, only a limited induction of adaptive immunity and protection against challenge was detected, depending on the inoculated dose and serotype deoptimized. Our work demonstrates that while CPD of the P1 coding region attenuates viral strains of multiple FMDV serotypes/subtypes, a thorough assessment of virulence and induction of adaptive immunity in the natural host is required in each case in order to finely adjust the degree of deoptimization required for attenuation without affecting the induction of protective adaptive immune responses.

60 APPLIED LIFE SCIENCES↗
NASA NTRS2011

The Planning Execution Monitoring Architecture

The Planning Execution Monitoring (PEM) architecture is a design concept for developing autonomous cockpit command and control software. The PEM architecture is designed to reduce the operations costs in the space transportation system through the use of automation while improving safety and operability of the system. Specifically, the PEM autonomous framework enables automatic performance of many vehicle operations that would typically be performed by a human. Also, this framework supports varying levels of autonomous control, ranging from fully automatic to fully manual control. The PEM autonomous framework interfaces with the core flight software to perform flight procedures. It can either assist human operators in performing procedures or autonomously execute routine cockpit procedures based on the operational context. Most importantly, the PEM autonomous framework promotes and simplifies the capture, verification, and validation of the flight operations knowledge. Through a hierarchical decomposition of the domain knowledge, the vehicle command and control capabilities are divided into manageable functional "chunks" that can be captured and verified separately. These functional units, each of which has the responsibility to manage part of the vehicle command and control, are modular, re-usable, and extensible. Also, the functional units are self-contained and have the ability to plan and execute the necessary steps for accomplishing a task based upon the current mission state and available resources. The PEM architecture has potential for application outside the realm of spaceflight, including management of complex industrial processes, nuclear control, and control of complex vehicles such as submarines or unmanned air vehicles.

Wang, Lui↗