Engineering Papers⌕ Search

SEARCH · Engineering Papers

Results for “Mechanisms of action”

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.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 records
All sourcesNASA NTRSDOE OSTI
DOE OSTI2022

Characterization of Recovery Human Action Mechanisms in Nuclear Power Plants

Recovery human action is defined as the action that prevents deviant conditions from producing unwanted effects. Analyzing recovery actions has been a critical part in human reliability analysis (HRA). However, there are a couple of limitations to treat recovery actions only depending on the current HRA methods. Representatively, the existing recovery analysis does not specifically consider recovery actions as are occurred in actual nuclear power plants (NPPs). The overall goal of this study aims to develop a novel recovery analysis method to account for human action recoveries in context of scenarios as well as complement the limitations of existing recovery analysis. In this paper, the recovery analysis in current HRA methods and their challenges are introduced. A strategy to achieve the goal is introduced with a modified recovery definition. Then, how we have researched the approach will be introduced in the paper.

99 GENERAL AND MISCELLANEOUS↗
NASA NTRS1982

Microscopic contour changes of tribological surfaces by chemical and mechanical action

An electronic optical laser interferometer capable of resolving depth differences of as low as 30 A and planar displacements of 6000 A was constructed for the examination of surface profiles of bearing surfaces without physical contact. This instrument was used to determine topological chemical reactivity by applying a drop of dilute alcoholic hydrochloric acid and measuring the profile of the solid surface before and after application of this probe. It was found that scuffed bearing surfaces reacted much faster than virgin ones but that bearing surfaces exposed to lubricants containing an organic chloride reacted much more slowly. In a separate series of experiments, a number of stainless steel plates were heated in a nitrogen atmosphere to different temperatures and their reactivity examined later at ambient temperature. The change of surface contour as a result of the probe reaction was found to follow an Arrhenius-type relation with respect to heat treatment temperature. This result could have implications on the scuffing mechanism.

Lauer, J. L.↗
NASA NTRS2001

Proton Pumps: Mechanism of Action and Applications

Recent progress in understanding molecular structures and mechanisms of action of proton pumps has paved the way to their novel applications in biotechnology. Proton pumps, in particular bacteriorhodopsin and ATP synthases, are capable of continuous, renewable conversion of light to chemical, mechanical or electrical energy, which can be used in macro- or nano-scale devices. The capability of protein systems incorporated into liposomes to generate ATP, which can be further used to drive chemical reactions, and to act as molecular motors has been already demonstrated. Other possible applications of such biochemical devices include targeted drug delivery and biocatalytic re actors. All these devices might prove superior to their inorganic alternatives.

Lanyi, Janos K.↗
NASA NTRS2003

Structure-Derived Proton-Transfer Mechanism of Action Human Pyruvate Dehydrogenase

The derivative of vitamin B1 thiamin pyrophosphate (TPP) is a cofactor of pyruvate dehydrogenase (E1p) that is involved in decarboxylation of pyruvate followed by reductive acetylation of lipoic acid covalently bound to a lysine residue of dihydrolipoamide acetyltransferase. The structure of E1p recently determined in our laboratory revealed patterns of association of foul subunits and specifics of two TPP binding sites. The mechanism of action in part includes a conserved hydrogen bond between the N1' atom of the aminopyrimidine ring of the cofactor and the carboxylate group of Glu59 from the beta subunits, and a V-conformation of the cofactor that brings the N4' atom of the aminopyrimidine ring to the distance of the intramolecular hydrogen bond formed with the C2-atom of the thiazolium moiety. The carboxylate group of Glu59 is the local proton acceptor that enables proton translocation within the aminopyrimidine ring and stabilization of the rare N4' - iminopyrimidine tautomer. Based on the analysis of E1p structure, we postulate that the protein environment drives N4' - amino/N4' - imino dynamics resulting in a concerted shuttle-like movement of the subunits. We also propose that this movement of the subunits is strictly coordinated with the two enzymatic reactions carried out in E1p by each of the two cofactor sites. It is proposed that these reactions are in alternating phases such that when one active site is involved in decarboxylation, the other is involved in acetylation of lipoyl noiety.

Ciszak, Ewa↗
DOE OSTI2024

Mechanisms of Action of Dorsal Root Ganglion Stimulation

The dorsal root ganglion (DRG) serves as a pivotal site for managing chronic pain through dorsal root ganglion stimulation (DRG-S). In recent years, the DRG-S has emerged as an attractive modality in the armamentarium of neuromodulation therapy due to its accessibility and efficacy in alleviating chronic pain refractory to conventional treatments. Despite its therapeutic advantages, the precise mechanisms underlying DRG-S-induced analgesia remain elusive, attributed in part to the diverse sensory neuron population within the DRG and its modulation of both peripheral and central sensory processing pathways. Emerging evidence suggests that DRG-S may alleviate pain by several mechanisms, including the reduction of nociceptive signals at the T-junction of sensory neurons, modulation of pain gating pathways within the dorsal horn, and regulation of neuronal excitability within the DRG itself. However, elucidating the full extent of DRG-S mechanisms necessitates further exploration, particularly regarding its supraspinal effects and its interactions with cognitive and affective networks. Understanding these mechanisms is crucial for optimizing neurostimulation technologies and improving clinical outcomes of DRG-S for chronic pain management. This review provides a comprehensive overview of the DRG anatomy, mechanisms of action of the DRG-S, and its significance in neuromodulation therapy for chronic pain.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2023

On the correlation between the stress exponent for creep determined by nanoindentation and the mechanism of action enabling stress relief in indium

Instrumented indentation performed at room temperature with a Berkovich and 10 μm radius sphere has been used to measure the stress exponent for creep before and after the strain burst observed in well-annealed, high-purity indium. Before the strain burst, the measured values are successfully rationalized using a new model based on stress directed diffusional flow along the interface between the indenter tip and test specimen. After the strain burst, the measured stress exponents are found to be representative of dislocation glide and climb assisted glide. Here these results are compared and contrasted to the previous experimental investigations and modeling efforts of Feng et al., Lucas et al., and Li et al. Collectively, the experimental observations and rationalization presented here provide significant new insight into the mechanisms of action that control the competition for stress relief in small, constrained volumes of crystalline metals subjected to high homologous temperatures.

36 MATERIALS SCIENCE↗
DOE OSTI2024

Revealing the mechanism of action of a first-in-class covalent inhibitor of $\mathrm{KRASG12C}$ $\mathrm{(ON)}$ and other functional properties of oncogenic $\text{KRAS}$ by 31 P $\mathrm{NMR}$

Individual oncogenic KRAS mutants confer distinct differences in biochemical properties and signaling for reasons that are not well understood. KRAS activity is closely coupled to protein dynamics and is regulated through two interconverting conformations: state 1 (inactive, effector binding deficient) and state 2 (active, effector binding enabled). Here, we use 31 P NMR to delineate the differences in state 1 and state 2 populations present in WT and common KRAS oncogenic mutants (G12C, G12D, G12V, G13D, and Q61L) bound to its natural substrate GTP or a commonly used nonhydrolyzable analog GppNHp (guanosine-5'-[(β,γ)-imido] triphosphate). Our results show that GppNHp-bound proteins exhibit significant state 1 population, whereas GTP-bound KRAS is primarily (90% or more) in state 2 conformation. This observation suggests that the predominance of state 1 shown here and in other studies is related to GppNHp and is most likely nonexistent in cells. We characterize the impact of this differential conformational equilibrium of oncogenic KRAS on RAF1 kinase effector RAS-binding domain and intrinsic hydrolysis. Through a KRAS G12C drug discovery, we have identified a novel small-molecule inhibitor, BBO-8956, which is effective against both GDP- and GTP-bound KRAS G12C. We show that binding of this inhibitor significantly perturbs state 1–state 2 equilibrium and induces an inactive state 1 conformation in GTP-bound KRAS G12C. In the presence of BBO-8956, RAF1–RAS-binding domain is unable to induce a signaling competent state 2 conformation within the ternary complex, demonstrating the mechanism of action for this novel and active-conformation inhibitor.

31P NMR↗
NASA NTRS2006

Mechanism of Action for Anti-Radiation Vaccine in Reducing the Biological Impact of High-Dose Irradiation

Ionizing radiation is a major health risk of long-term space travel, the biological consequences of which include genetic and oxidative damage. In this study, we propose an original mechanism by which high doses of ionizing radiation induce acute toxicity. We identified biological components that appear in the lymphatic vessels shortly after gamma irradiation. These radiation-induced toxins, which we have named specific radiation determinants (SRD), were generated in the irradiated tissues and then collected and circulated throughout the body via the lymph circulation and bloodstream. Depending on the type of SRD elicited, different syndromes of acute radiation sickness (ARS) were expressed. The SRDs were developed into a vaccine used to confer active immunity against acute radiation toxicity in immunologically naive animals. Animals that were pretreated with SRDs exhibited resistance to lethal doses of gamma radiation, as measured by increased survival times and survival rates. In comparison, untreated animals that were exposed to similar large doses of gamma radiation developed acute radiation sickness and died within days. This phenomenon was observed in a number of mammalian species. We partially analyzed the biochemical characteristics of the SRDs. The SRDs were large molecular weight (200-250 kDa) molecules that were comprised of a mixture of protein, lipid, carbohydrate, and mineral. Further analysis is required to further identify the SRD molecules and the biological mechanism by which the mediate the toxicity associated with acute radiation sickness. By doing so, we may develop an effective specific immunoprophylaxis as a countermeasure against the acute effects of ionizing radiation.

Maliev, Vladislav↗
NASA NTRS2007

Mechanism of Action for Anti-radiation Vaccine in Reducing the Biological Impact of High-dose Gamma Irradiation

Ionizing radiation is a major health risk of long-term space travel, the biological consequences of which include genetic and oxidative damage. In this study, we propose an original mechanism by which high doses of ionizing radiation induce acute toxicity. We identified biological components that appear in the lymphatic vessels shortly after gamma irradiation. These radiation-induced toxins, which we have named specific radiation determinants (SRD), were generated in the irradiated tissues and then collected and circulated throughout the body via the lymph circulation and bloodstream. Depending on the type of SRD elicited, different syndromes of acute radiation sickness (ARS) were expressed. The SRDs were developed into a vaccine used to confer active immunity against acute radiation toxicity in immunologically naive animals. Animals that were pretreated with SRDs exhibited resistance to lethal doses of gamma radiation, as measured by increased survival times and survival rates. In comparison, untreated animals that were exposed to similar large doses of gamma radiation developed acute radiation sickness and died within days. This phenomenon was observed in a number of mammalian species. Initial analysis of the biochemical characteristics indicated that the SRDs were large molecular weight (200-250 kDa) molecules that were comprised of a mixture of protein, lipid, carbohydrate, and mineral. Further analysis is required to further identify the SRD molecules and the biological mechanism by which the mediate the toxicity associated with acute radiation sickness. By doing so, we may develop an effective specific immunoprophylaxis as a countermeasure against the acute effects of ionizing radiation.

Maliev, Vladislav↗
NASA NTRS1970

Mechanisms of action of light on circadian rhythms in the monkey

Light is considered by many investigators to be the primary Zeitgeber for most physiologic rhythms. In order to study the effects on biorhythms of changing photoperiods and to provide information on the nature of the wave forms and the mechanisms of entrainment, unrestrained male monkeys (Cebus albifrons, Macaca nemestrina) were maintained in a sound-proofed environmental chamber. The Cebus was initially maintained on a 12L:12D schedule; it was subjected to a 180 degrees phase shift for 14 days, then returned to the original photoperiod. In two experiments (24 days; 27 days each) the same monkey was again maintained on a 12L:12D schedule which was gradually altered to a constant light environment. Deep body temperature (DBT) data were obtained with miniature radiotransmitters. Locomotor activity (LMA) was measured by strain gauges. Under the 12L:12D regimens the Macaca DBT cycles were uniform as to phase and wave form for over 60 weeks. These wave forms were analyzed by the use of periodogram and correlogram analyses and by fitting to the Volterra Integro-Differential Equation. Phase angle relationships between Zeitgeber and physiologic parameters were characterized. After the photoperiod phase shift the DBT cycle rephased in about 9 days. During the rephasing process the wave form changed. The shapes of the wave forms of DBT and activity were maintained with increasing light until an 18L:6D photoperiod was reached. The rhythms were entrained to the onset of darkness rather than lights on. Major and minor periods of LMA were detected. Hysteresis diagrams showed that DBT led the onset of major LA by 6 hr and the end of major activity by 2 hr.

Light↗
DOE OSTI2020

PBT2 acts through a different mechanism of action than other 8-hydroxyquinolines: an X-ray fluorescence imaging study

8-Hydroxyquinolines (8HQs) comprise a family of metal-binding compounds that have been used or tested for use in numerous medicinal applications, including as treatments for bacterial infection, Alzheimer's disease, and cancer. Two key 8HQs, CQ (5-chloro-7-iodo-8-hydroxyquinoline) and PBT2 (2-(dimethylamino)methyl-5,7-dichloro-8-hydroxyquinoline), have drawn considerable interest and have been the focus of many studies investigating their in vivo properties. These drugs have been described as copper and zinc ionophores because they do not cause metal depletion, as would be expected for a chelation mechanism, but rather cellular accumulation of these ions. In studies of their anti-cancer properties, CQ has been proposed to elicit toxic intracellular copper accumulation and to trigger apoptotic cancer cell death through several possible pathways. In this study we used synchrotron X-ray fluorescence imaging, in combination with biochemical assays and light microscopy, to investigate 8HQ-induced alterations to metal ion homeostasis, as well as cytotoxicity and cell death. We used the bromine fluorescence from a bromine labelled CQ congener (5,7-dibromo-8-hydroxyquinoline; B2Q) to trace the intracellular localization of B2Q following treatment and found that B2Q crosses the cell membrane. We also found that 8HQ co-treatment with Cu(ii) results in significantly increased intracellular copper and significant cytotoxicity compared with 8HQ treatments alone. PBT2 was found to be more cytotoxic, but a weaker Cu(ii) ionophore than other 8HQs. Moreover, treatment of cells with copper in the presence of CQ or B2Q resulted in copper accumulation in the nuclei, while PBT2-guided copper was distributed near to the cell membrane. Furthermore, these results suggest that PBT2 may be acting through a different mechanism than that of other 8HQs to cause the observed cytotoxicity.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2020

Antifungal symbiotic peptide NCR044 exhibits unique structure and multifaceted mechanisms of action that confer plant protection

In the indeterminate nodules of a model legume Medicago truncatula, ~700 nodule-specific cysteine-rich (NCR) peptides with conserved cysteine signature are expressed. NCR peptides are highly diverse in sequence, and some of these cationic peptides exhibit antimicrobial activity in vitro and in vivo. However, there is a lack of knowledge regarding their structural architecture, antifungal activity, and modes of action against plant fungal pathogens. Here, the three-dimensional NMR structure of the 36-amino acid NCR044 peptide was solved. This unique structure was largely disordered and highly dynamic with one four-residue α-helix and one three-residue antiparallel β-sheet stabilized by two disulfide bonds. NCR044 peptide also exhibited potent fungicidal activity against multiple plant fungal pathogens, including Botrytis cinerea and three Fusarium spp. It inhibited germination in quiescent spores of B. cinerea. In germlings, it breached the fungal plasma membrane and induced reactive oxygen species. It bound to multiple bioactive phosphoinositides in vitro. Time-lapse confocal and superresolution microscopy revealed strong fungal cell wall binding, penetration of the cell membrane at discrete foci, followed by gradual loss of turgor, subsequent accumulation in the cytoplasm, and elevated levels in nucleoli of germlings. Spray-applied NCR044 significantly reduced gray mold disease symptoms caused by the fungal pathogen B. cinerea in tomato and tobacco plants, and postharvest products. Our work illustrates the antifungal activity of a structurally unique NCR peptide against plant fungal pathogens and paves the way for future development of this class of peptides as a spray-on fungistat/fungicide.

59 BASIC BIOLOGICAL SCIENCES↗