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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 1,477 records · Page 82
All sourcesNASA NTRSDOE OSTI
DOE OSTI2024

Activation of polycystin-1 signaling by binding of stalk-derived peptide agonists

Polycystin-1 (PC1) is the protein product of thePKD1gene whose mutation causes autosomal dominant Polycystic Kidney Disease (ADPKD). PC1 is an atypical G protein-coupled receptor (GPCR) with an autocatalytic GAIN domain that cleaves PC1 into extracellular N-terminal and membrane-embedded C-terminal (CTF) fragments. Recently, activation of PC1 CTF signaling was shown to be regulated by a stalk tethered agonist (TA), resembling the mechanism observed for adhesion GPCRs. Here, synthetic peptides of the first 9- (p9), 17- (p17), and 21-residues (p21) of the PC1 stalk TA were shown to re-activate signaling by a stalkless CTF mutant in human cell culture assays. Novel Peptide Gaussian accelerated molecular dynamics (Pep-GaMD) simulations elucidated binding conformations of p9, p17, and p21 and revealed multiple specific binding regions to the stalkless CTF. Peptide agonists binding to the TOP domain of PC1 induced close TOP-putative pore loop interactions, a characteristic feature of stalk TA-mediated PC1 CTF activation. Additional sequence coevolution analyses showed the peptide binding regions were consistent with covarying residue pairs identified between the TOP domain and the stalk TA. These insights into the structural dynamic mechanism of PC1 activation by TA peptide agonists provide an in-depth understanding that will facilitate the development of therapeutics targeting PC1 for ADPKD treatment.

Life Sciences & Biomedicine - Other Topics↗
DOE OSTI2025

Testing convolutional neural network based deep learning systems: a statistical metamorphic approach

Machine learning technology spans many areas and today plays a significant role in addressing a wide range of problems in critical domains,i.e., healthcare, autonomous driving, finance, manufacturing, cybersecurity,etc. Metamorphic testing (MT) is considered a simple but very powerful approach in testing such computationally complex systems for which either an oracle is not available or is available but difficult to apply. Conventional metamorphic testing techniques have certain limitations in verifying deep learning-based models (i.e., convolutional neural networks (CNNs)) that have a stochastic nature (because of randomly initializing the network weights) in their training. In this article, we attempt to address this problem by using a statistical metamorphic testing (SMT) technique that does not require software testers to worry about fixing the random seeds (to get deterministic results) to verify the metamorphic relations (MRs). We propose seven MRs combined with different statistical methods to statistically verify whether the program under test adheres to the relation(s) specified in the MR(s). We further use mutation testing techniques to show the usefulness of the proposed approach in the healthcare space and test two CNN-based deep learning models (used for pneumonia detection among patients). The empirical results show that our proposed approach uncovers 85.71% of the implementation faults in the classifiers under test (CUT). Furthermore, we also propose an MRs minimization algorithm for the CUT, thus saving computational costs and organizational testing resources.

Computer Science↗
DOE OSTI2023

The Genetics of Aerotolerant Growth in Zymomonas mobilis

Reduced genome bacteria are genetically simplified systems that facilitate biological study and industrial use. The free-living Alphaproteobacterium, Zymomonas mobilis, has a naturally reduced genome containing fewer than 2000 protein coding genes. Despite its small genome, Z. mobilis thrives in diverse conditions including the presence or absence of atmospheric oxygen. However, insufficient characterization of essential and conditionally essential genes has limited broader adoption of Z. mobilis as a model Alphaproteobacterium. Here, we use genome-scale CRISPRi-seq to systematically identify and characterize Z. mobilis genes that are conditionally essential for aerotolerant or anaerobic growth, or are generally essential across both conditions. Comparative genomics revealed that the essentiality of most "generally essential" genes was shared between Z. mobilis and other Alphaproteobacteria, validating Z. mobilis as reduced genome model. Among conditionally essential genes, we found that the DNA repair gene, recJ, was critical only for aerobic growth but reduced the mutation rate under both conditions. Further, we show that genes encoding the F1FO ATP synthase and Rnf respiratory complex are required for anaerobic growth of Z. mobilis. Combining CRISPRi partial knockdowns with metabolomics and membrane potential measurements, we determined that the ATP synthase generates membrane potential that is consumed by Rnf to power downstream processes. Rnf knockdown strains accumulated isoprenoid biosynthesis intermediates, suggesting a key role for Rnf in powering essential biosynthetic reactions. Our work establishes Z. mobilis as a streamlined model for alphaproteobacterial genetics, has broad implications in bacterial energy coupling, and informs Z. mobilis genome manipulation for optimized production of valuable isoprenoid-based bioproducts

Alphaproteobacteria↗
NASA NTRS1966

Molecules and Evolution

Biochemical basis of evolution - evolution and DNA, genetic code, microbiology and heredity, mutations, and evolution and hemoglobins

GENETIC CODE↗
NASA NTRS1971

Radiation and zero-gravity effects on human leukocytes and Neurospora crassa

The two parts of this experiment have resulted in proof that neither orbital space flight nor any of the stresses connected with it produced significant, unpredicted genetic damage, at least insofar as chromosomal-aberration production is a valid measure of this general type of effect. Furthermore, the Gemini 11 results lead to the conclusion that no synergistic effect exists between radiation and factors that are associated with space flight. No significant difference was found between dose-effect curves for survival or mutation induction of the inflight and ground-based samples irradiated on filters. Thus, like the blood experiment, this part of the experiment failed to result in data that were appropriate for confirmation of the apparent synergism that was observed in the Gemini 3 blood experiment. Also, the Nuerospora crassa experiment provided conclusive data that there is no difference in the genetic effects of irradiation during space flight and the genetic effects obtained in ground-based experiments. Both the Gemini 11 blood experiment and the Neurospora crassa experiment thus have failed to result in data confirmatory of the apparent synergism observed on the Gemini 3 mission.

Bender, M. A.↗
NASA NTRS1972

Theoretical foundations for a quantitative approach to paleogenetics. I, II.

It is shown that by neglecting the phenomena of multiple hits, back mutation, and chance coincidence errors larger than 100% can be introduced in the calculated value of the average number of nucleotide base differences to be expected between two homologous polynucleotides. Mathematical formulas are derived to correct quantitatively for these effects. It is pointed out that the effects change materially the quantitative aspects of phylogenics, such as the length of the legs of the trees. A number of problems are solved without approximation.-

Holmquist, R.↗
NASA NTRS1972

Genetic and metabolic variability in autotrophic and heterotrophic bacteria

The studies to evaluate an organism's ability to maintain normal physiological activities over a long period of time in a bioregenerative system are presented. Studies reviewed include: heat tolerant mutants of Pseudomonas fluoresceins, virulence factors of the Staphylococci, and the effect of mutations on the virulence for man in common and ubiquitous microorganisms.

Decicco, B. T.↗
NASA NTRS1972

Evolution of ribonuclease in relation to polypeptide folding mechanisms.

Comparisons of the N-terminal region of pancreatic RNAase in seven species are presented, taking into account cow, bison, deer, rat, pig, kangaroo, and turtle. The available limited evidence on hypervariable regions indicates that there is still an evolutionary constraint on them. It is proposed that there is a selection pressure acting on all regions of a protein sequence in evolution. Mutations that tend to obstruct the folding process can lead to various intensities of selection pressure.

Barnard, E. A.↗
NASA NTRS1972

Sequence data - Magnitude and implications of some ambiguities.

A stochastic model is applied to the divergence of the horse-pig lineage from a common ansestor in terms of the alpha and beta chains of hemoglobin and fibrinopeptides. The results are compared with those based on the minimum mutation distance model of Fitch (1972). Buckwheat and cauliflower cytochrome c sequences are analyzed to demonstrate their ambiguities. A comparative analysis of evolutionary rates for various proteins of horses and pigs shows that errors of considerable magnitude are introduced by Glx and Asx ambiguities into evolutionary conclusions drawn from sequences of incompletely analyzed proteins.

Holmquist, R.↗
NASA NTRS1975

Quarantine testing and biocharacterization of lunar materials

Quarantine testing was conducted to ensure the safety of all life on earth. The plants and animals which were exposed to lunar material were carefully observed for prolonged periods to determine if any mutation or changes in growing characteristics and behavior occurred. The quarantine testing was terminated after the Apollo 14 flight when it became apparent that previously returned lunar material contained no potentially harmful agents. Further biological experimentation with the lunar material was conducted to determine its chemical, physical, and nutritional qualities.

Gerald R. Taylor↗
NASA NTRS1976

The Identification of Scientific Programs to Utilize the Space Environment

A program to identify and develop ideas for scientific experimentation on the long duration exposure facility (LDEF) was completed. Four research proposals were developed: (1) Ultra pure germanium gamma ray radiation detectors in the space environment, intended to develop and demonstrate an X-ray and gamma-ray spectroscopy system incorporating a temperature cyclable high-purity germanium detector and diode heat pipe cryogenic system for cooling, (2) growth, morphogenesis and metabolism of plant embryos in the zero-gravity environment, to investigate if the space environment induces mutations in the embryogenic cells so that mutants of commercial significance with desirable attributes may be obtained, (3) effect of zero gravity on the growth and pathogenicity of selected zoopathic fungi. It is possible that new kinds of treatment for candidiasis, and tichophytosis could eventuate from the results of the proposed studies, and (4) importance of gravity to survival strategies of small animals. Gravitational effects may be direct or mediate the selection of genetic variants that are preadapted to weightlessness.

Kulacki, F. A.↗