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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 613 records · Page 34
All sourcesNASA NTRSDOE OSTI
DOE OSTI2015

Complement activation as a bioequivalence issue relevant to the development of generic liposomes and other nanoparticulate drugs

Liposomes are known to activate the complement (C) system, which can lead in vivo to a hypersensitivity syndrome called C activation-related pseudoallergy (CARPA). CARPA has been getting increasing attention as a safety risk of i.v. therapy with liposomes, whose testing is now recommended in bioequivalence evaluations of generic liposomal drug candidates. This review highlights the adverse consequences of C activation, the unique symptoms of CARPA triggered by essentially all i.v. administered liposomal drugs, and the various features of vesicles influencing this adverse immune effect. For the case of Doxil, we also address the mechanism of C activation and the opsonization vs. long circulation (stealth) paradox. In reviewing the methods of assessing C activation and CARPA, we delineate the most sensitive porcine model and an algorithm for stepwise evaluation of the CARPA risk of i.v. liposomes, which are proposed for standardization for preclinical toxicology evaluation of liposomal and other nanoparticulate drug candidates. - Highlights: • Outlining of difficulties in generic development of liposomal drugs. • New regulatory requirements to evaluate CARPA in preclinical studies. • Review of complement activation by liposomes and its adverse consequences (CARPA). • Assays of C activation in vitro and CARPA in vivo, with the porcine test in focus. • Decision tree how to handle the risk of CARPA assessed by a battery of tests.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Insect taste receptors relevant to host identification by recognition of secondary metabolite patterns of non-host plants

Highlights: • Three putative bitter gustatory receptor of silkworm respond to several secondary metabolites in non-host plants. • Secondary metabolites responsive to the gustatory receptor are representative feeding-deterrents in non-host plants. • One feeding-deterrent gustatory receptor respond to multiple feeding deterrents. • Feeding deterrent receptors are expressed in silkworm mouthparts. • Representative secondary metabolite of a non-host plant, coumarin exactly had a suppressive effect on food intake of silkworm. The taste sensing system is crucial for food recognition in insects and other animals. It is commonly believed that insect gustatory receptors (Grs) expressed in gustatory organs are indispensable for host plant selection. Many behavioral studies have shown that mono- or oligo-phagous lepidopteran insects use the balance between feeding attractants and feeding deterrents in host plants and that these are sensed by taste organs for host plant recognition. However, the molecular mechanism underlying taste recognition, especially of feeding deterrents, remains to be elucidated. To better understand this mechanism, we studied orphan Grs, including Bombyx mori Gr (BmGr) 16, BmGr18, and BmGr53, from the mono-phagous insect, Bombyx mori. Using Calcium imaging in mammalian cells, we first confirmed in lepidoptera insects that three of the putative bitter Grs widely responded to structurally different feeding deterrents. Although the phylogenetic distance of these Grs was considerable, they responded to partially overlapping deterrents of plant secondary metabolites. These findings suggest that not only these three Grs but also most of the Grs that have been assigned to putative bitter Grs are feeding-deterrent receptors that play a role in host plant recognition.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Aβ1-40 mediated aggregation of proteins and metabolites unveils the relevance of amyloid cross-seeding in amyloidogenesis

The multicomponent nature of neuronal plaques in Alzheimer's disease signifies the possible recruitment of non-Aβ candidates during the amyloid growth of Aβ peptides. Here, we show that amyloid fibrils of Aβ{sub 1-40} peptide can effectively initiate amyloid formation in different globular proteins and metabolites, converting native structures into β-sheet rich assemblies. Structural and biophysical properties of the resultant protein fibrils display amyloid like characteristic features. Viable contacts between Aβ peptide's cross-β architecture and the native structure of proteins, mediated through H-bonds and hydrophobic interactions seem crucial for the onset of amyloid cross-seeding. Results reveal the inherent cross-seeding potential of Aβ amyloids to initiate amyloid formation process in proteins and metabolites and revelation of such a property may further our mechanistic understanding of amyloid pathologies.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

IFN-γ, IL-17A, or zonulin rapidly increase the permeability of the blood-brain and small intestinal epithelial barriers: Relevance for neuro-inflammatory diseases

Highlights: • Zonulin rapidly (within 60 min) increases the permeability of the IEB and BBB in vitro. • Both IL-17A and IFN-γ enhance the permeability of the BBB and IEB within 1 h. • All three pro-inflammatory mediators rapidly modify IEB TJs, by causing mislocalization of ZO-1, claudin-5, and occludin. • Rapid TJ disassembly by all mediators was accompanied by dramatic depolymerization of the peri-junctional actin cytoskeleton. Breakdown of the blood-brain barrier (BBB) precedes lesion formation in the brains of multiple sclerosis (MS) patients. Since recent data implicate disruption of the small intestinal epithelial barrier (IEB) in the pathogenesis of MS, we hypothesized that the increased permeability of the BBB and IEB are mechanistically linked. Zonulin, a protein produced by small intestine epithelium, can rapidly increase small intestinal permeability. Zonulin blood levels are elevated in MS, but it is unknown whether zonulin can also disrupt the BBB. Increased production of IL-17A and IFN-γ has been implicated in the pathogenesis of MS, epilepsy, and stroke, and these cytokines impact BBB integrity after 24 h. We here report that primary human brain microvascular endothelial cells expressed the EGFR and PAR2 receptors necessary to respond to zonulin, and that zonulin increased BBB permeability to a 40 kDa dextran tracer within 1 h. Moreover, both IL-17A and IFN-γ also rapidly increased BBB and IEB permeability. By using confocal microscopy, we found that exposure of the IEB to zonulin, IFN-γ, or IL-17A in vitro rapidly modified the localization of the TJ proteins, ZO-1, claudin-5, and occludin. TJ disassembly was accompanied by marked depolymerization of the peri-junctional F-actin cytoskeleton. Our data indicate that IFN-γ, IL-17A, or zonulin can increase the permeability of the IEB and BBB rapidly in vitro, by modifying TJs and the underlying actin cytoskeleton. These observations may help clarify how the gut-brain axis mediates the pathogenesis of neuro-inflammatory diseases.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2013

On the relevance of volume increase for the length changes of mortar bars in sulfate solutions

The ingress of sulfate ions into cementitious materials leads to the formation of ettringite, gypsum and other phases. The increase in solid volume through the formation of these phases is often assumed to be the only reason for expansion. In this paper we systematically compare the volume increase predicted by thermodynamic modeling to macroscopic expansion for mortars made with CEM I in different sulfate solutions and for mortars made with a range of blended cements in sodium sulfate solution. It is shown that the length changes cannot be explained by simple volume increase alone. A more plausible explanation of expansion lies in the theory of crystallization pressure, in which crystals forming from a supersaturated solution may exert pressure on their surroundings. It is observed that expansion occurs in systems where thermodynamic modeling predicts the co-existence of ettringite with gypsum. In such a case, if monosulfate and gypsum are both present locally, the solution can be highly supersaturated with respect to ettringite, whose formation in confined conditions (such as within C–S–H) can then exert expansive forces.

36 MATERIALS SCIENCE↗
DOE OSTI2023

Thermal energy storage in concrete: Review, testing, and simulation of thermal properties at relevant ranges of elevated temperature

This study examines the thermal performance of concrete used for thermal energy storage (TES) applications. The influence of concrete constituents (aggregates, cementitious materials, and fibers) on the thermal conductivity and specific heat are summarized based on literature and via experimentation at elevated temperatures. It is indicated that concrete with siliceous aggregate, low water/cement ratios, and steel fibers produces better overall thermal properties. The results of literature review and laboratory testing are used for numerical simulation to evaluate the impact of concrete thermal property variability on TES capabilities. The TES module consists of the heat exchanger and surrounding concrete as the storage media. Both idealized cases without heat loss and realistic cases with insulation and heat losses are considered. Furthermore, the result shows that conventional concrete mixes can be tailored to decrease the module charge/discharge durations and increase the amount of thermal energy storage.

25 ENERGY STORAGE↗
DOE OSTI2018

Response of bentonite microbial communities to stresses relevant to geodisposal of radioactive waste

Microbes have been isolated previously from bentonite materials that may be used as barriers for the disposal of radioactive waste. Actively respiring microbes in such barrier materials, within a repository environment, have the potential to adversely affect waste container corrosion rates. Additionally, they could potentially alter the properties of the bentonite barrier itself. This is of significance, since the integrity of the waste container and properties of the bentonite barrier are required to fulfil defined safety functions. Furthermore to help identify the critical factors that affect microbial activity in bentonite materials, this study examines the impact of a range of parameters that could affect microbial metabolism in a geodisposal environment. Several bentonites from different sources (bentonite mined from locations in Spain and the USA, along with commercially-sourced bentonite) were subjected to increased pressure (74 MPa, 30 s), heat (90 °C, 24 h), and irradiation (1000 Gy, 24.17 Gy min –1 ), before incubation in growth media selective for sulfate-reducing bacteria (SRB) or iron-reducing bacteria (IRB).

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2021

Autoignition and preliminary heat release of gasoline surrogates and their blends with ethanol at engine-relevant conditions: Experiments and comprehensive kinetic modeling

This work utilizes a rapid compression machine (RCM) to experimentally quantify autoignition and preliminary heat release characteristics for blends of 0 to 30% ethanol by volume into two surrogates (FGF-LLNL and FGF-KAUST) that represent a full boiling range gasoline (FACE-F). Experimental conditions cover pressures from 15 to 100 bar, temperatures from 700 to 1000 K, and diluted/stoichiometric and undiluted/lean fuel loading conditions representative of boosted spark-ignition and advanced compression ignition engines, respectively. Direct comparison is made with previously reported results for FACE-F/E0–E30 blends. Here, a detailed gasoline surrogate chemistry model is also proposed, and chemical kinetic modeling is undertaken using the proposed model to generate chemical insights into the compositional effects and ethanol blending effects.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗