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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 973 records · Page 54
All sourcesNASA NTRSDOE OSTI
DOE OSTI2017

Distance Determination by Gated Viewing Systems Taking into Account the Illuminating Pulse Shape

For gated viewing systems with triangular and trapezoidal illuminating pulses, we have obtained the range-intensity profiles (RIPs) of the signal as the time delay was varied between the leading edges of the gate pulse and the illuminating pulse. We have established that if the duration of the illuminating pulse Δt{sub las} is less than or equal to the duration of the gate pulse Δt{sub IC}, then the expressions for the characteristic distances are the same as for rectangular pulses and they can be used to determine the distance to objects. When Δt{sub las} > Δt{sub IC}, in the case of triangular illuminating pulses the RIP is bell-shaped. For trapezoidal pulses, the RIP is bell-shaped with or without a plateau section. We propose an empirical method for determining the characteristic distances to the RIP maximum and the boundary points for the plateau section, which we then use to calculate the distance to the object. Using calibration constants, we propose a method for determining the distance to an object and we have experimentally confirmed the feasibility of this method.

42 ENGINEERING↗
DOE OSTI2018

Synthesis and structures of Cu{sup I,II} complexes with a 2,2´-bipyridine derivative bearing a (+)-3-carene moiety

The complex salt {[CuL_2][Cu_4I_6]•MeCN}{sub n} (1) and the compound [Cu{sub 4}L{sub 3}I{sub 4}]•3 MeCN (2) (L is a chiral ligand bearing a natural monoterpene (+)-3-carene moiety) were synthesized. The crystal structures of compounds 1 and 2 were determined by X-ray diffraction. The structure of compound 1 consists of complex cations [CuL{sub 2}]{sup 2+} (N{sub 3}O{sub 2} polyhedron is a trigonal bipyramid) and Cu{sup I} coordination polymers (CuI{sub 4} polyhedron is a tetrahedron) as anions. The experimental magnetic moment μ{sub eff} at 300 K is 1.90 μ{sub B}, which is consistent with the X-ray diffraction data and the assumption that compound 1 is mixed-valence. The structure of compound 2 comprises a tetranuclear Cu{sup I} complex, in which three Cu atoms are coordinated by two N atoms of the ligand L and two I atoms, and the fourth Cu atom is coordinated by four I atoms (coordination polyhedra are distorted tetrahedra). Compounds L and 2 were found to influence the viability of human laryngeal carcinoma cells (Hep2). The IC{sub 50} value for complex 2 (13.0±1.7 μM) is substantially smaller than IC{sub 50} for compound L (30.5±0.5 μM).

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2019

Polymer nanoparticles of N-vinylpyrrolidone loaded with an organic aminonitroxyl platinum (IV) complex. Characterization and investigation of their in vitro cytotoxicity

The conditions for obtaining stable aqueous solutions of a lipophilic aminonitroxyl platinum complex, namely, e-amine-d-(4-amino-2,2,6,6-tetramethylpiperidine 1-oxyl)-a, f-bis(octanoato)-b, c-dichloroplatinum(IV), by means of its encapsulation into nanoparticles of copolymers of N-vinylpyrrolidone with triethylene glycol dimethacrylate with various monomer compositions and topologies were found. Aqueous solutions of the complex encapsulated into polymer particles were investigated by dynamic light scattering, the temperature dependence of nanostructure sizes was studied. Transmission electron microscopy established that the hybrid nanostructures are core—shell particles, in which the platinum complex forms small clusters (∼4 nm). The parameters of ESR spectra of aqueous dispersions indicate a high mobility of nitroxyl contained in hybrid nanostructures. Voltammetric measurements demonstrate a similarity of the redox reactions related to the free radical fragment of the aminonitroxyl Pt{sup IV} complex and of the 4-acetylamino-2,2,6,6-tetramethylpiperidine 1-oxyl radical. Polymer products containing the platinum complex were studied by IR spectroscopy, TGA, and DSC. The cytotoxicity index (IC{sub 50}) of the free and the encapsulated complex was determined for HeLa tumor cells. The cytotoxicity of the latter (IC{sub 50} 47–205 nmol L{sup −1}) depends on the monomeric composition of the nanoparticles and the incubation time.

77 NANOSCIENCE AND NANOTECHNOLOGY↗
DOE OSTI2019

Study of the Electrical and Diffusion Barrier Properties in Ultrathin Carbon Film-Coated Copper Microwires for Interconnects

Four specimen patterns with the microstructure of a microcopper wire are deposited on the Si-wafer substrate plus thermal oxide (SiO{sub 2}) film as the top layer. Each pattern was prepared to have two kinds of specimens, including with and without ultrathin carbon film between the copper wire and the top layer (SiO{sub 2}). The effect of carbon film on electrical properties is evaluated via the measurements of the I (current)–V (voltage) curve, sheet electrical resistance, current leakage, and its ratio and effective permittivity. A rapid thermal annealing (RTA) technique is provided as an economic and efficient method to grow the ultrathin carbon film rapidly as the interlayer. Appropriate choices of 900 °C and 3 min as the annealing temperature and time can produce ultrathin carbon film with nearly 100% coverage of the copper surface. The sheet resistance of specimen demonstrates the behavior exactly opposite to that of the carbon film coverage of wire surface. The combined effect of elevating the voltage and annealing temperature of the specimen with carbon film on the current leakage is much lower than that arising in the specimen without carbon film, so long as the carbon films operating at that temperature (between 350 and 500 °C) are still sustainable. The differences in current leakage and effective permittivity between these two kinds of specimen are significantly increased by raising the temperature. The intensity (IC) of copper diffusions into the SiO{sub 2} layer in the specimens with the carbon film demonstrates behavior similar to that of current leakage (CL). The IC and CL values for the temperatures ≦ 350 °C are much lower than those obtained at 500 °C.

36 MATERIALS SCIENCE↗
DOE OSTI2019

Biological Activities Evaluation of Enantiopure Isoxazolidine Derivatives: In Vitro, In Vivo and In Silico Studies

A series of enantiopure isoxazolidines (3a–c) were synthesized by 1,3-dipolar cycloaddition between a (−)-menthone-derived nitrone and various terminal alkenes. The screened compounds were evaluated for their antioxidant activity by two in vitro antioxidant assays, including β-carotene/linoleic acid bleaching, and inhibition of lipid peroxidation (thiobarbituric acid reactive species, TBARS). The results revealed that compound 3b (EC{sub 50} = 0.55 ± 0.09 mM) was the most potent antioxidant as compared to the standard drug (EC{sub 50} = 2.73 ± 0.07 mM) using the TBARS assay. Furthermore, the antimicrobial activity was assessed using disc diffusion and microdilution methods. Among the synthesized compounds, 3c was found to be the most potent antimicrobial agent as compared to the standard drug. Subsequently, the acute toxicity study has also been carried out for the newly synthesized compounds and the experimental studies revealed that all compounds were safe up to 500 mg/kg and no death of animals were recorded. The cytotoxicity of these compounds was assessed by the MTT cell proliferation assay against the continuous human cell lines HeLa and compound 3c (GI{sub 50} = 46.2 ± 1.2 μM) appeared to be more active than compound 3a (GI{sub 50} = 200 ± 2.8 μM) and 3b (GI{sub 50} = 1400 ± 7.8 μM). Interestingly, all tested compounds displayed a good α-amylase inhibitory activity in competitive manner with IC{sub 50} values ranging between 23.7 and 64.35 μM when compared to the standard drug acarbose (IC{sub 50} = 282.12 μM). In addition, molecular docking studies were performed to understand the possible binding and the interaction of the most active compounds to the α-amylase pocket.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2019

Evaluation of the Structure and Biological Activities of Condensed Tannins from Acanthus ilicifolius Linn and Their Effect on Fresh-Cut Fuji Apples

Condensed tannins (CT{sub S}) have been isolated and purified from leaves of Acanthus ilicifolius Linn. And their structures were investigated by three methods: {sup 13}C nuclear magnetic resonance ({sup 13}C NMR), reversed-phase high-performance liquid chromatography (RP-HPLC), and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). The results showed that the CT{sub S} were a mixture of catechin/epicatechin, galatechin/epicatechin, and amphicin/epigalin, and that the polymer chain lengths were 3-mers to 14-mers. Antityrosinase activities and antioxidant activities of the CT{sub S} from A. ilicifolius leaves were further studied. The IC{sub 50} of the CT{sub S} on mushroom tyrosinase activity was determined to be 19.7 ± 0.13 μg/mL, and inhibition type analyses indicated that the CT{sub S} were mixed type inhibitors and their inhibition CT{sub S} was reversible. The CT{sub S} from A. ilicifolius leaves also exhibited potential antioxidant activity. The IC{sub 50} of DPPH and ABTS scavenging activities were 104 ± 0.894 μg/mL and 86 ± 0.616 μg/mL, respectively. And the FRAP value was 758.28 ± 2.42 mg AAE/g. In addition, we found that the CT{sub S} from A. ilicifolius leaves had an excellent effect on preserving the quality of fresh-cut apples by preventing apples from browning through reducing polyphenol oxidase activities in apples.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2019

Core polarization effects: Oscillator strengths, transition probabilities and radiative lifetimes of levels in Bi IV

In this work a systematic analysis of Bi IV atomic properties is presented. Ab initio relativistic Hartree–Fock calculations in an intermediate coupling (IC) formalism and taking into account Core Polarization Effects (CPE) are used. We use for the IC calculations the standard method of least square fitting of experimental energy levels by means of computer codes from Cowan which was modified in order to include CPE. Our calculations have been made from 17 configurations of Bi IV: 5d{sup 10}6s{sup 2}, 5d{sup 10}6p{sup 2}, 5d{sup 10}6sns (n= 7–10) and 5d{sup 10}6snd (n= 6–9) for even parity and 5d{sup 10}6snp (n=6,7), 5d{sup 10}6snf (n=5,6), 5d{sup 9}6s{sup 2}6p and 5d{sup 9}6s{sup 2}nf (n=5,6) for odd parity. Transition probabilities and oscillator strengths for 100 lines and some radiative lifetimes of Bi IV have been calculated. Besides a comparison of our results with the scarce experimental values available in the bibliography are presented. The presence of spectral lines of bismuth in stellar atmospheres has been reported in different stars. This is the motivation by this work can be very interest in astrophysical area. Recently the Bi IV is taking importance because it is considered as the main dopant in the prospective used for the design and synthesis of new scintillators.

74 ATOMIC AND MOLECULAR PHYSICS↗
DOE OSTI2013

Inhibition by TRPA1 agonists of compound action potentials in the frog sciatic nerve

Highlights: •TRPA1 agonists inhibited compound action potentials in frog sciatic nerves. •This inhibition was not mediated by TRPA1 channels. •This efficacy was comparable to those of lidocaine and cocaine. •We found for the first time an ability of TRPA1 agonists to inhibit nerve conduction. -- Abstract: Although TRPV1 and TRPM8 agonists (vanilloid capsaicin and menthol, respectively) at high concentrations inhibit action potential conduction, it remains to be unknown whether TRPA1 agonists have a similar action. The present study examined the actions of TRPA1 agonists, cinnamaldehyde (CA) and allyl isothiocyanate (AITC), which differ in chemical structure from each other, on compound action potentials (CAPs) recorded from the frog sciatic nerve by using the air-gap method. CA and AITC concentration-dependently reduced the peak amplitude of the CAP with the IC{sub 50} values of 1.2 and 1.5 mM, respectively; these activities were resistant to a non-selective TRP antagonist ruthenium red or a selective TRPA1 antagonist HC-030031. The CA and AITC actions were distinct in property; the latter but not former action was delayed in onset and partially reversible, and CA but not AITC increased thresholds to elicit CAPs. A CAP inhibition was seen by hydroxy-α-sanshool (by 60% at 0.05 mM), which activates both TRPA1 and TRPV1 channels, a non-vanilloid TRPV1 agonist piperine (by 20% at 0.07 mM) and tetrahydrolavandulol (where the six-membered ring of menthol is opened; IC{sub 50} = 0.38 mM). It is suggested that TRPA1 agonists as well as TRPV1 and TRPM8 agonists have an ability to inhibit nerve conduction without TRP activation, although their agonists are quite different in chemical structure from each other.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2013

Design, synthesis and evaluation of a potent substrate analog inhibitor identified by scanning Ala/Phe mutagenesis, mimicking substrate co-evolution, against multidrug-resistant HIV-1 protease

Highlights: •Inhibitors against MDR HIV-1 protease were designed, synthesized and evaluated. •Lead peptide (6a) showed potent inhibition (IC{sub 50}: 4.4 nM) of MDR HIV-1 protease. •(6a) Showed favorable binding isotherms against NL4-3 and MDR proteases. •(6a) Induced perturbations in the {sup 15}N-HSQC spectrum of MDR HIV-1 protease. •Molecular modeling suggested that (6a) may induce total flap closure inMDR protease. -- Abstract: Multidrug-resistant (MDR) clinical isolate-769, human immunodeficiency virus type-1 (HIV-1) protease (PDB ID: (1TW7)), was shown to exhibit wide-open flaps and an expanded active site cavity, causing loss of contacts with protease inhibitors. In the current study, the expanded active site cavity of MDR769 HIV-1 protease was screened with a series of peptide-inhibitors that were designed to mimic the natural substrate cleavage site, capsid/p2. Scanning Ala/Phe chemical mutagenesis approach was incorporated into the design of the peptide series to mimic the substrate co-evolution. Among the peptides synthesized and evaluated, a lead peptide (6a) with potent activity (IC{sub 50}: 4.4 nM) was identified against the MDR769 HIV-1 protease. Isothermal titration calorimetry data showed favorable binding profile for 6aagainst both wild type and MDR769 HIV-1 protease variants. Nuclear magnetic resonance spectrum of {sup 15}N-labeled MDR769 HIV-1 protease in complex with 6a showed some major perturbations in chemical shift, supporting the peptide induced conformational changes in protease. Modeling analysis revealed multiple contacts between 6a and MDR769 HIV-1 protease. The lead peptide-inhibitor, 6a, with high potency and good binding profile can be used as the basis for developing potent small molecule inhibitors against MDR variants of HIV.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2013

FGF7 supports hematopoietic stem and progenitor cells and niche-dependent myeloblastoma cells via autocrine action on bone marrow stromal cells in vitro

Highlights: •FGF7 is downregulated in MED1-deficient mesenchymal cells. •FGF7 produced by mesenchymal stromal cells is a novel hematopoietic niche molecule. •FGF7 supports hematopoietic progenitor cells and niche-dependent leukemia cells. •FGF7 activates FGFR2IIIb of bone marrow stromal cells in an autocrine manner. •FGF7 indirectly acts on hematopoietic cells lacking FGFR2IIIb via stromal cells. -- Abstract: FGF1 and FGF2 support hematopoietic stem and progenitor cells (HSPCs) under stress conditions. In this study, we show that fibroblast growth factor (FGF7) may be a novel niche factor for HSPC support and leukemic growth. FGF7 expression was attenuated in mouse embryonic fibroblasts (MEFs) deficient for the MED1 subunit of the Mediator transcriptional coregulator complex. When normal mouse bone marrow (BM) cells were cocultured with Med1{sup +/+} MEFs or BM stromal cells in the presence of anti-FGF7 antibody, the growth of BM cells and the number of long-time culture-initiating cells (LTC-ICs) decreased significantly. Anti-FGF7 antibody also attenuated the proliferation and cobblestone formation of MB1 stromal cell-dependent myeloblastoma cells. The addition of recombinant FGF7 to the coculture of BM cells and Med1{sup −/−} MEFs increased BM cells and LTC-ICs. FGF7 and its cognate receptor, FGFR2IIIb, were undetectable in BM cells, but MEFs and BM stromal cells expressed both. FGF7 activated downstream targets of FGFR2IIIb in Med1{sup +/+} and Med1{sup −/−} MEFs and BM stromal cells. Taken together, we propose that FGF7 supports HSPCs and leukemia-initiating cells indirectly via FGFR2IIIb expressed on stromal cells.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

Derivatives of Dictyostelium differentiation-inducing factors inhibit lysophosphatidic acid–stimulated migration of murine osteosarcoma LM8 cells

Osteosarcoma is a common metastatic bone cancer that predominantly develops in children and adolescents. Metastatic osteosarcoma remains associated with a poor prognosis; therefore, more effective anti-metastatic drugs are needed. Differentiation-inducing factor-1 (DIF-1), −2, and −3 are novel lead anti-tumor agents that were originally isolated from the cellular slime mold Dictyostelium discoideum. Here we investigated the effects of a panel of DIF derivatives on lysophosphatidic acid (LPA)-induced migration of mouse osteosarcoma LM8 cells by using a Boyden chamber assay. Some DIF derivatives such as Br-DIF-1, DIF-3(+2), and Bu-DIF-3 (5–20 μM) dose-dependently suppressed LPA-induced cell migration with associated IC{sub 50} values of 5.5, 4.6, and 4.2 μM, respectively. On the other hand, the IC{sub 50} values of Br-DIF-1, DIF-3(+2), and Bu-DIF-3 versus cell proliferation were 18.5, 7.2, and 2.0 μM, respectively, in LM8 cells, and >20, 14.8, and 4.3 μM, respectively, in mouse 3T3-L1 fibroblasts (non-transformed). Together, our results demonstrate that Br-DIF-1 in particular may be a valuable tool for the analysis of cancer cell migration, and that DIF derivatives such as DIF-3(+2) and Bu-DIF-3 are promising lead anti-tumor agents for the development of therapies that suppress osteosarcoma cell proliferation, migration, and metastasis. - Highlights: • LPA induces cell migration (invasion) in murine osteosarcoma LM8 cells. • DIFs are novel lead anti-tumor agents found in Dictyostelium discoideum. • We examined the effects of DIF derivatives on LPA-induced LM8 cell migration in vitro. • Some of the DIF derivatives inhibited LPA-induced LM8 cell migration.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

Fatty acid transport protein-2 inhibitor Grassofermata/CB5 protects cells against lipid accumulation and toxicity

The inhibition of the fatty acid uptake into non-adipose tissues provides an attractive target for prevention of lipotoxicity leading to obesity-associated non-alcoholic fatty liver disease and type 2 diabetes. Fatty acid transport proteins (FATPs) are bifunctional proteins involved in the uptake and activation of fatty acids by esterification with coenzyme A. Here we characterize Grassofermata/CB5, previously identified as a fatty acid uptake inhibitor directed against HsFATP2. The compound was effective in inhibiting the uptake of fatty acids in the low micro-molar range (IC{sub 50} 8–11 μM) and prevented palmitate-mediated lipid accumulation and cell death in cell lines that are models for intestines, liver, muscle and pancreas. In adipocytes, uptake inhibition was less effective (IC{sub 50} 58 μM). Inhibition was specific for long chain fatty acids and was ineffective toward medium chain fatty acids, which are transported by diffusion. Kinetic analysis of Grassofermata-dependent FA transport inhibition verified a non-competitive mechanism. By comparison with Grassofermata, several atypical antipsychotic drugs previously implicated as inhibitors of FA uptake were ineffectual. In mice Grassofermata decreased absorption of {sup 13}C-oleate demonstrating its potential as a therapeutic agent. - Highlights: • Grassofermata is a small compound inhibitor of FATP2. • Uptake inhibition is specific for long chain fatty acids. • Uptake kinetics shows low specificity for adipocytes compared to other cell types. • Inhibition is by a non-competitive mechanism. • Atypical antipsychotics do not inhibit FA uptake by comparison with Grassofermata.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

Autophagy regulated by prolyl isomerase Pin1 and phospho-Ser-GSK3αβ involved in protection of oral squamous cell carcinoma against cadmium toxicity

Prolyl isomerase Pin1 plays an important role in cell proliferation and is overexpressed in many human tumors. However, its role in autophagy induction remains undefined. Here we show that Pin1 regulates cell survival via autophagy in cadmium (Cd)-exposed oral squamous cell carcinoma (OSCC). OSCC exposure to Cd induced autophagy, as demonstrated by the formation of green fluorescent punctae in transfected cells expressing GFP-conjugated microtubule-associated protein light chain 3 (LC3) and by LC3 flux in the presence of autophagy inhibitors. Suppression of Atg5 enhanced Cd-induced apoptosis, indicating that autophagy is involved in cell protection. In dose–response experiments, cleavage of procaspase-3, PARP-1, and LC3-II was induced by Cd with an IC{sub 50} of 45 μM. Expression of Pin1 was decreased at or above the Cd IC{sub 50} value and was inversely correlated with the level of phospho(p)-Ser-GSK3αβ. Genetic or pharmacologic inhibition of Pin1 suppressed Cd-induced autophagy, but increased p-Akt-mediated p-Ser-GSK3αβ; this was reversed by overexpression of Pin1. However, suppression of GSK3αβ inhibited Cd-induced autophagy and induced apoptosis, which could be reversed by overexpression of GSK3β. The PI3K inhibitor Ly294002 blocked p-Akt-mediated increases in p-Ser-GSK3αβ and autophagy and induced apoptosis. Therefore, p-Ser-GSK3αβ can directly regulate Cd-induced autophagy, although its function is suppressed by Pin1. Collectively, the present results indicate that targeting Pin1 and GSK3αβ at the same time could be an effective therapeutic tool for Cd-induced carcinogenesis. - Highlights: • Pin1 regulated autophagy to protect cells from cadmium toxicity. • Pin1 suppression inhibited cadmium-induced autophagy and induced apoptosis. • Pin1 inhibited the function of p-Ser-GSK3αβ in autophagy regulation. • p-Ser-GSK3αβ regulated autophagy independently of Pin1.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

K-Ras(G12D)-selective inhibitory peptides generated by random peptide T7 phage display technology

Amino-acid mutations of Gly{sup 12} (e.g. G12D, G12V, G12C) of V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (K-Ras), the most promising drug target in cancer therapy, are major growth drivers in various cancers. Although over 30 years have passed since the discovery of these mutations in most cancer patients, effective mutated K-Ras inhibitors have not been marketed. Here, we report novel and selective inhibitory peptides to K-Ras(G12D). We screened random peptide libraries displayed on T7 phage against purified recombinant K-Ras(G12D), with thorough subtraction of phages bound to wild-type K-Ras, and obtained KRpep-2 (Ac-RRCPLYISYDPVCRR-NH{sub 2}) as a consensus sequence. KRpep-2 showed more than 10-fold binding- and inhibition-selectivity to K-Ras(G12D), both in SPR analysis and GDP/GTP exchange enzyme assay. K{sub D} and IC{sub 50} values were 51 and 8.9 nM, respectively. After subsequent sequence optimization, we successfully generated KRpep-2d (Ac-RRRRCPLYISYDPVCRRRR-NH{sub 2}) that inhibited enzyme activity of K-Ras(G12D) with IC{sub 50} = 1.6 nM and significantly suppressed ERK-phosphorylation, downstream of K-Ras(G12D), along with A427 cancer cell proliferation at 30 μM peptide concentration. To our knowledge, this is the first report of a K-Ras(G12D)-selective inhibitor, contributing to the development and study of K-Ras(G12D)-targeting drugs. - Highlights: • The first K-Ras(G12D)-selective inhibitory peptides were generated. • These peptides showed more than 10-fold binding- and inhibition-selectivity to K-Ras(G12D) in compared to wild type K-Ras. • The peptide KRpep-2d suppressed downstream signal of K-Ras(G12D) and cell proliferations of cancer cell line A427.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Integrative analysis of rewired central metabolism in temozolomide resistant cells

Highlights: • Temozolomide (TMZ) resistant Neurospheroids (NSP) identified in U87MG cell line. • NSP shows varied dose response, two fold higher IC{sub 50} and 30% lower growth rate. • Altered Glucose and Glutamine uptake in U87MG and NSP shapes metabolic dynamics. • Differential mRNA levels of CAN genes & ABC transporters drive respiration/growth. • Integrative paradigm identifies potential metabolic drivers for TMZ resistance. An authenticated U87MG clonal glioblastoma cell line was investigated to identify a sub-population of neurospheroidal (NSP) cells within the main epithelial population (U87MG). The NSP cells sorted using Fluorescence Assisted Cell Sorting (FACS) showed varied morphology, 30% lower growth rates, 40% higher IC{sub 50} values for temozolomide drug and could differentiate into the glial cell type (NDx). Metabolite profiling using HR-LCMS identified glucose, glutamine and serine in both populations and tryptophan only in U87MG as growth limiting substrates. Glycine, alanine, glutamate and proline were secreted by U87MG, however proline and glycine were re-utilized in NSP. Exo-metabolite profiling and phenotypic microarrays identified differential metabolism of primary carbon sources glucose and derived pyruvate for U87MG; glutamine and derived glutamate metabolism in NSP. Differential mRNA abundance of AKT1, PTEN, PIK3CA controlling metabolism, drug efflux, nutrient transport and epigenetic control MDM2 are potentially critical in shaping DNA methylation effects of temozolomide. Our study provides a new insight into the combined effect of these factors leading to temozolomide resistance in NSP.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

Design, synthesis, X-ray studies, and biological evaluation of novel macrocyclic HIV-1 protease inhibitors involving the P1'-P2' ligands

Design, synthesis, and evaluation of a new class of HIV-1 protease inhibitors containing diverse flexible macrocyclic P1'-P2' tethers are reported. Inhibitor 5a with a pyrrolidinone-derived macrocycle exhibited favorable enzyme inhibitory and antiviral activity (K i = 13.2 nM, IC 50 = 22 nM). Further incorporation of heteroatoms in the macrocyclic skeleton provided macrocyclic inhibitors 5m and 5o. Lastly, these compounds showed excellent HIV-1 protease inhibitory (K i = 62 pM and 14 pM, respectively) and antiviral activity (IC 50 = 5.3 nM and 2.0 nM, respectively). Inhibitor 5o also remained highly potent against a DRV-resistant HIV-1 variant.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Fracture properties and microstructure formation of hardened alkali-activated slag/fly ash pastes

This study presents a comprehensive experimental investigation on the fracture properties of hardened alkali-activated slag/fly ash (AASF) pastes in relation to the microstructure formation and reaction product composition. The main reaction product in AASF is C-(N-)A-S-H gel along with minor hydrotalcite phase, with the polymerization of C-(N-)A-S-H gel substantially governed by its Ca/Si ratio. Strong positive correlations are identified between the Ca/Si ratios of C-(N-)A-S-H gel and the fracture properties K{sub Ic} (J{sub tip}), whereas, the compressive strength of AASF pastes is primarily determined by its capillary porosity (>0.01 μm). The disagreements between the Ca/Si ratios and corresponding intrinsic mechanical properties of C-(N-)A-S-H gel as proof by contradiction indicate that the fracture properties K{sub Ic} (J{sub tip}) of AASF pastes could be dominated by a cohesion/adhesion-based mechanism. These findings provide promising guidance for fine-tuning the fracture properties of AASF and also advise on the tailoring strategies for high-performance composite such as strain-hardening geopolymer composite.

36 MATERIALS SCIENCE↗
DOE OSTI2022

Stannous chloride as a tool for mercury stripping in contaminated streams: Experimental assessment of toxicity in an invertebrate model species

In this work, the chronic toxicity of an innovative Hg water treatment system using tin (Sn) (II) chloride (SnCl 2 ) followed by air stripping was assessed through measurements of survival, growth, and reproduction rate in the freshwater cladoceran Ceriodaphnia dubia, a model species for toxicity testing. We first calculated the concentrations of Hg causing 25% reduction in survival and reproduction (Lethal or Inhibition Concentrations, or LC 25 and IC 25 , for survival and reproduction, respectively) through exposure to aqueous Hg at concentrations ranging from 0 to 25,000 ng L -1 . Then, we treated media (DMW and natural stream water) contaminated with Hg at LC 25 and IC 25 concentrations with SnCl 2 at a Sn:Hg stoichiometric ratio of 8:1 and air stripping and exposed C. dubia to this Sn-amended media. Our results showed that Hg significantly affected survival, reproduction rates and impaired growth. SnCl 2 -treatment removed 100% of the Hg from the media at all concentrations tested with no deleterious effects on survival, growth and reproduction. Our results confirmed the efficacy of SnCl 2 in removing aqueous Hg from stream water and showed that the added Sn did not impact C. dubia at the concentrations tested, supporting the suitability of SnCl 2 -based treatments in appropriate Hg-contaminated environments.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗