Engineering topics

Schmidt, Tim

Publications and source records attributed to Schmidt, Tim.

3 records

DOE OSTI2023

Targeting Enterococcus faecalis HMG-CoA reductase with a non-statin inhibitor

HMG-CoA reductase (HMGR), a rate-limiting enzyme of the mevalonate pathway in Gram-positive pathogenic bacteria, is an attractive target for development of novel antibiotics. In this study, we report the crystal structures of HMGR from Enterococcus faecalis (efHMGR) in the apo and liganded forms, highlighting several unique features of this enzyme. Statins, which inhibit the human enzyme with nanomolar affinity, perform poorly against the bacterial HMGR homologs. We also report a potent competitive inhibitor (Chembridge2 ID 7828315 or compound 315) of the efHMGR enzyme identified by a high-throughput, in-vitro screening. The X-ray crystal structure of efHMGR in complex with 315 was determined to 1.27 Å resolution revealing that the inhibitor occupies the mevalonate-binding site and interacts with several key active site residues conserved among bacterial homologs. Importantly, 315 does not inhibit the human HMGR. Our identification of a selective, non-statin inhibitor of bacterial HMG-CoA reductases will be instrumental in lead optimization and development of novel antibacterial drug candidates.

59 BASIC BIOLOGICAL SCIENCES↗

NASA NTRS2016

Application of High Speed Digital Image Correlation in Rocket Engine Hot Fire Testing

Hot fire testing of rocket engine components and rocket engine systems is a critical aspect of the development process to understand performance, reliability and system interactions. Ground testing provides the opportunity for highly instrumented development testing to validate analytical model predictions and determine necessary design changes and process improvements. To properly obtain discrete measurements for model validation, instrumentation must survive in the highly dynamic and extreme temperature application of hot fire testing. Digital Image Correlation has been investigated and being evaluated as a technique to augment traditional instrumentation during component and engine testing providing further data for additional performance improvements and cost savings. The feasibility of digital image correlation techniques were demonstrated in subscale and full scale hotfire testing. This incorporated a pair of high speed cameras to measure three-dimensional, real-time displacements and strains installed and operated under the extreme environments present on the test stand. The development process, setup and calibrations, data collection, hotfire test data collection and post-test analysis and results are presented in this paper.

Gradl, Paul R.↗

NASA NTRS2012

Photogrammetry Measurements During a Tanking Test on the Space Shuttle External Tank, ET-137

On November 5, 2010, a significant foam liberation threat was observed as the Space Shuttle STS-133 launch effort was scrubbed because of a hydrogen leak at the ground umbilical carrier plate. Further investigation revealed the presence of multiple cracks at the tops of stringers in the intertank region of the Space Shuttle External Tank. As part of an instrumented tanking test conducted on December 17, 2010, a three dimensional digital image correlation photogrammetry system was used to measure radial deflections and overall deformations of a section of the intertank region. This paper will describe the experimental challenges that were overcome in order to implement the photogrammetry measurements for the tanking test in support of STS-133. The technique consisted of configuring and installing two pairs of custom stereo camera bars containing calibrated cameras on the 215-ft level of the fixed service structure of Launch Pad 39-A. The cameras were remotely operated from the Launch Control Center 3.5 miles away during the 8 hour duration test, which began before sunrise and lasted through sunset. The complete deformation time history was successfully computed from the acquired images and would prove to play a crucial role in the computer modeling validation efforts supporting the successful completion of the root cause analysis of the cracked stringer problem by the Space Shuttle Program. The resulting data generated included full field fringe plots, data extraction time history analysis, section line spatial analyses and differential stringer peak ]valley motion. Some of the sample results are included with discussion. The resulting data showed that new stringer crack formation did not occur for the panel examined, and that large amounts of displacement in the external tank occurred because of the loads derived from its filling. The measurements acquired were also used to validate computer modeling efforts completed by NASA Marshall Space Flight Center (MSFC).

Littell, Justin D.↗