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At least 37 records · Page 2
All sourcesNASA NTRSDOE OSTI
DOE OSTI2020

Structural integrity of additively manufactured stainless steel with cold sprayed barrier coating under combined cyclic loading

Integration of metal additive manufacturing (AM) and cold spray (CS) technologies provide an unprecedented opportunity to manufacture coated material systems with complex geometrical features. The application of these material systems in functionally critical components requires adequate structural integrity, particularly in the presence of cyclic loading. This article researches the multiaxial fatigue (axial-torsional cyclic loading) behavior of a coated material system consisting of 15Cr-5Ni precipitation-hardening stainless steel (15-5 PH SS) substrate additively manufactured by direct metal laser sintering with a layer of chromium carbide nickel (CrC-Ni) barrier coating deposited by CS. The influence of AM and CS-induced residual stresses on fatigue performance of test specimens was thoroughly studied. Additionally, the effect of surface roughness and processes induced defects were considered to explain the crack growth mechanism. Stresses assessed by synchrotron X-ray diffraction indicated a substantial accumulation of residual stresses, particularly in the outer surface of the as-fabricated 155 PH SS specimens. The state of residual stress was changed notably following the deposition of CrC-Ni coating in the axial, hoop, and radial directions of the fatigue test specimen. Also, CS deposition of CrC-Ni coating caused significant improvement in the surface quality of the additively manufactured components. Fatigue test results indicated, CS deposition of CrC-Ni substantially enhances the fatigue life of the AM-produced 15-5 PH SS substrate in all loading conditions, particularly in the high cycle fatigue regime. The improvement in the fatigue life of the specimens with coating was associated with a reduction in equivalent residual stress at the substrate surface and improvement in the specimens' surface condition (i.e., reduced surface roughness). The fractographic analysis of the specimen indicated the cracks tend to initiate in the surface of both as-fabricated and cold-sprayed specimens. However, the mechanism of crack growth changed notably following the deposition of CrC-Ni coating. The cracks tended to propagate in the planes parallel or with a small deviation from the build layers of the AM-produced specimens. On the other hand, deposition of CrC-Ni coating increased the deviation of crack growth plane from the build layers of the substrate.

36 MATERIALS SCIENCE↗
DOE OSTI2026

Effects of gas purity on backgrounds of collision reaction cell-equipped MC-ICP-MS

The advent of multi-collector inductively coupled plasma mass spectrometry (MC-ICP-MS) instruments equipped with collision reaction cells (CRCs) facilitates interference removal/mitigation via online gas phase separations. This approach has proven effective for high intensity ion beams measured on Faraday collectors; however, it has been observed that introduction of gas in the CRC can result in significant background signals relative to the more sensitive ion counters. These backgrounds hinder use of these instruments for low level concentration and isotopic ratio measurements when employing a reaction gas. Here, this work directly evaluates the effect of gas purity on backgrounds of CRC-MC-ICP-MS instruments. Introducing high-purity research grade O 2 (99.999%) into the CRC produces complex background spectra with intensities >10 4 cps observed at most masses across the measured mass range (7-300 m / z ). Some features of the observed spectra (i.e., positive mass defects) can be attributed to molecular compounds comprised of significant hydrogen. Additionally, some specific molecular species can be identified (i.e., MoO x H y + ) and appear to be derived from molybdenum rods comprising the CRC. Further purifying the gas reduces the intensity of these backgrounds by several orders of magnitude, to <10 2 cps in many cases, and reduces complexity of the resulting spectra. This reduction in background appears to be in part driven by removal of impurities (i.e., H 2 O) from the gas. This work demonstrates that additional purification of reaction gases prior to introduction into the CRC significantly reduces backgrounds detected, potentially expanding the utility of CRC-MC-ICP-MS for making low level measurements using inline gas phase ion separations.

Schlieder, Tyler D. [Pacific Northwest National La↗
DOE OSTI2023

Formin‐like 2 promotes angiogenesis and metastasis of colorectal cancer by regulating the EGFL6 / CKAP4 / ERK axis

Abstract Increasing evidence indicates that angiogenesis plays a pivotal role in tumor progression. Formin‐like 2 (FMNL2) is well‐known for promoting metastasis; however, the molecular mechanisms by which FMNL2 promotes angiogenesis in colorectal cancer (CRC) remain unclear. Here, we found that FMNL2 promotes angiogenesis and metastasis of CRC in vitro and in vivo. The GDB/FH3 domain of FMNL2 directly interacts with epidermal growth factor‐like protein 6 (EGFL6). Formin‐like 2 promotes EGFL6 paracrine signaling by exosomes to regulate angiogenesis in CRC. Cytoskeleton associated protein 4 (CKAP4) is a downstream target of EGFL6 and is involved in CRC angiogenesis. Epidermal growth factor‐like protein 6 binds to the N‐terminus of CKAP4 to promote the migration of HUVECs by activating the ERK/MMP pathway. These findings suggest that FMNL2 promotes the migration of HUVECs and enhances angiogenesis and tumorigenesis in CRC by regulating the EGFL6/CKAP4/ERK axis. Therefore, the EGFL6/CKAP4/ERK axis could be a candidate therapeutic target for CRC treatment.

He, Guoyang↗
DOE OSTI2021

HIF1α promotes tumor chemoresistance via recruiting GDF15-producing TAMs in colorectal cancer

Chemoresistance is a tremendous challenge to efficacy of systemic chemotherapy which is the preferred treatment for the advanced CRC patients. More tumor-associated macrophages (TAMs) are recruited into the CRC tumor under chemotherapy, which are highly implicated in the chemoresistance development, but the underlying molecular mechanism is unclear. Here, we present that activated HIF1α signaling in CRC cells under chemotherapy drives the expression of HMGB1to promotes macrophage infiltration and in turn chemoresistance development. Chemotherapeutic treatment with 5-FU leads to increased recruitment of macrophages into tumors, which display tumor-protective alternative activation. Mechanistically, tumor HIF1α signaling activated by chemo-induced ROS drives the transcription of HMGB1 to promote more macrophage infiltration into CRC tumor. Furthermore, high levels of GDF15 produced by TAMs impair the chemosensitity of tumor cells via enhancing fatty acids β-oxidation. Together, our current study reveals a new insight into the cross-talking between tumor cells and immune cells, and provides novel drug targets for clinic treatments for CRC.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2025

Enhancing cold spray coatings: Microstructural dynamics and performance attributes of Inconel 625 with chromium carbide incorporation for hydropower applications

The incorporation of chromium carbide (CrC) particles into the cold spray (CS) process is known to mitigate nozzle clogging, although at the expense of deposition efficiency. This study explores the intricate microstructural changes induced by varying amounts of CrC powder (12.5 % and 6 %) in conjunction with Inconel-625 (Inc-625) powder. The deposition was carried out onto A27 cast steel under different CS parameters. Microstructural characterization, including detailed electron microscopy studies, reveals a complex yet structurally stable coating. Noteworthy features include grain fragmentation and a cellular structure enriched with Nb and Mo, with minimal plastic deformation of CrC in the matrix. The cold-sprayed coatings exhibit a significant (~4 times) increase in microhardness compared to the A27 substrate. Mechanical and cavitation erosion properties were systematically investigated. Coatings subjected to higher particle energy conditions with a gas pressure of 600 psi and gas temperature of 650 °C, demonstrated superior resistance to cavitation erosion. This resistance is attributed to a combination of factors, including microstructural characteristics and porosity. Altogether, the study provides valuable insights into the structural dynamics and performance of CS coatings enriched with CrC particles.

A27 cast steel↗
DOE OSTI2020

Complex radius in the R-matrix algorithm for inclusion of direct capture component [Slides]

In the low-energy range there are two possible physical mechanisms for γ-ray emissions. While both mechanisms emit γ-rays, the compound radiative capture (CRC) process is generated by the formation of a compound nucleus state before γ-emission. CRC has a characteristic resonance structure in the cross section, The direct radiative capture (DRC) process goes to the final state by the electromagnetic radiation of the incident neutron. DRC has a smooth behavior in the cross section. For light nuclei, a non-negligible component of the neutron capture process can be often associated to DRC process. Although these two mechanisms should be described by a unified theoretical formalism, in the nuclear data libraries, the CRC and DRC components are evaluated and reported separately. The updated R-matrix algorithm will allow the ability to implicitly include correlations between CRC and DRC mechanisms, to improve the quality of nuclear data evaluations, and to facilitate simple large-scale applicability to current nuclear data evaluations.

73 NUCLEAR PHYSICS AND RADIATION PHYSICS↗
DOE OSTI2021

INTS6 promotes colorectal cancer progression by activating of AKT and ERK signaling

Highlights: • INTS6 is upregulated in colorectal cancer and correlated with poor prognosis. • INTS6 promotes the growth of colorectal cancer cells in vitro and in vivo. • INTS6 affects the cell cycle distribution of colorectal cancer cells. • INTS6 activates the AKT and ERK signaling in colorectal cancer. INTS6 (integrator complex subunit 6) has been reported as a tumor suppressor in many cancers. However, the expression and biological function of INTS6 in colorectal cancer (CRC) has not been investigated yet. In this study, we found that INTS6 expression was significantly increased in CRC tissues when compared with normal tissues and was associated with poor prognosis. Downregulation of INTS6 induced G1/S-phase cell cycle arrest, and markedly suppressed the growth of CRC cells and the derived tumors, while overexpression of INTS6 showed opposite effect. Mechanism study revealed that INTS6 increased the levels of phosphorylated AKT (p-AKT) and ERK (p-ERK), and the growth-promoting effect of INTS6 was inhibited by AKT and ERK inhibitors. Besides, INTS6 also affected the expression of two targets of PI3K/AKT and MAPK signaling, c-Myc and CDK2, which contributed to cell cycle alteration. Altogether, the present study has revealed the oncogenic role of INTS6 in CRC, providing a novel therapeutic target for this malignant cancer.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

PDRG1 predicts a poor prognosis and facilitates the proliferation and metastasis of colorectal cancer

Highlights: • PDRG1 is overexpressed in colorectal cancer tissues and is associated with poor prognosis of colorectal cancer patients. • PDRG1 regulates the proliferation, apoptosis, cell cycle progression and metastasis of colorectal cancer cells. • PDRG1 promotes the proliferation, migration and invasion of colorectal cancer via p21-mediated cell cycle progression. The incidence and mortality of colorectal cancer (CRC) is increasing yearly and CRC patients are becoming younger in global. Evidences have revealed the carcinogenic effect of p53 and DNA damage-regulated gene 1 (PDRG1) in several types of tumors. However, its biological function is yet to be investigated in CRC. This study aimed to unveil the prooncogenic role of PDRG1 in CRC.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2024

Characteristics of a cost-effective blood test for colorectal cancer screening

Background: Blood-based biomarker tests can potentially change the landscape of colorectal cancer (CRC) screening. We characterize the conditions under which blood test screening would be as effective and cost-effective as annual fecal immunochemical testing or decennial colonoscopy. Methods: We used the 3 Cancer Information and Surveillance Modeling Network–Colon models to compare scenarios of no screening, annual fecal immunochemical testing, decennial colonoscopy, and a blood test meeting Centers for Medicare & Medicaid (CMS) coverage criteria (74% CRC sensitivity and 90% specificity). We varied the sensitivity to detect CRC (74%-92%), advanced adenomas (10%-50%), screening interval (1-3 years), and test cost ($25-$500). Primary outcomes included quality-adjusted life-years (QALY) gained from screening and costs for a US average-risk cohort of individuals aged 45 years. Results: Annual fecal immunochemical testing yielded 125-163 QALY gained per 1000 at a cost of 3811-5384 dollars per person, whereas colonoscopy yielded 132-177 QALY gained at a cost of 5375-7031 dollars per person. A blood test with 92% CRC sensitivity and 50% advanced adenoma sensitivity yielded 117-162 QALY gained if used every 3 years and 133-173 QALY gained if used every year but would not be cost-effective if priced above $$125 per test. If used every 3 years, a $500 blood test only meeting CMS coverage criteria yielded 83-116 QALY gained at a cost of $8559-$9413 per person. Conclusion: Blood tests that only meet CMS coverage requirements should not be recommended to patients who would otherwise undergo screening by colonoscopy or fecal immunochemical testing because of lower benefit. Blood tests need higher advanced adenoma sensitivity (above 40%) and lower costs (below $125) to be cost-effective.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2020

Oxaliplatin–DNA Adducts as Predictive Biomarkers of FOLFOX Response in Colorectal Cancer: A Potential Treatment Optimization Strategy

FOLFOX is one of the most effective treatments for advanced colorectal cancer (CRC). However, cumulative oxaliplatin neurotoxicity often results in halting the therapy. Oxaliplatin functions predominantly via the formation of toxic covalent drug-DNA adducts. We hypothesize that oxaliplatin-DNA adduct levels formed in vivo in peripheral blood mononuclear cells (PBMC) are proportional to tumor shrinkage caused by FOLFOX therapy. We further hypothesize that adducts induced by sub-therapeutic "diagnostic microdoses" are proportional to those induced by therapeutic doses and are also predictive of response to FOLFOX therapy. These hypotheses were tested in CRC cell lines and a pilot clinical study. Four CRC cell lines were cultured with therapeutically relevant (100 µM) or diagnostic microdose (1 µM) concentrations of [ 14 C]oxaliplatin. The C-14 label enabled quantification of oxaliplatin-DNA adduct level with accelerator mass spectrometry (AMS). Oxaliplatin-DNA adduct formation was correlated with oxaliplatin cytotoxicity for each cell line as measured by the MTT viability assay. Six CRC patients received by IV a diagnostic microdose containing [ 14 C]oxaliplatin prior to treatment, as well as a second [ 14 C]oxaliplatin dose during FOLFOX chemotherapy, termed a "therapeutic dose." Oxaliplatin-DNA adduct levels from PBMC correlated significantly to mean tumor volume change of evaluable target lesions (5 of the 6 patients had measurable disease). Finally, oxaliplatin-DNA adduct levels were linearly proportional between microdose and therapeutically relevant concentrations in cell culture experiments and patient samples, as was plasma pharmacokinetics, indicating potential utility of diagnostic microdosing.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2022

An Evolutionary Algorithm to Personalize Stool-Based Colorectal Cancer Screening

Fecal immunochemical testing (FIT) is an established method for colorectal cancer (CRC) screening. Measured FIT-concentrations are associated with both present and future risk of CRC, and may be used for personalized screening. However, evaluation of personalized screening is computationally challenging. In this study, a broadly applicable algorithm is presented to efficiently optimize personalized screening policies that prescribe screening intervals and FIT-cutoffs, based on age and FIT-history. We present a mathematical framework for personalized screening policies and a bi-objective evolutionary algorithm that identifies policies with minimal costs and maximal health benefits. The algorithm is combined with an established microsimulation model (MISCAN-Colon), to accurately estimate the costs and benefits of generated policies, without restrictive Markov assumptions. The performance of the algorithm is demonstrated in three experiments. In Experiment 1, a relatively small benchmark problem, the optimal policies were known. The algorithm approached the maximum feasible benefits with a relative difference of 0.007%. Experiment 2 optimized both intervals and cutoffs, Experiment 3 optimized cutoffs only. Optimal policies in both experiments are unknown. Compared to policies recently evaluated for the USPSTF, personalized screening increased health benefits up to 14 and 4.3%, for Experiments 2 and 3, respectively, without adding costs. Generated policies have several features concordant with current screening recommendations. The method presented in this paper is flexible and capable of optimizing personalized screening policies evaluated with computationally-intensive but established simulation models. It can be used to inform screening policies for CRC or other diseases. For CRC, more debate is needed on what features a policy needs to exhibit to make it suitable for implementation in practice.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2022

Front-End Engineering Design Study for Retrofit Post-Combustion Carbon Capture on a Natural Gas Combined Cycle Power Plant

The objective of the project is to conduct a Front-End Engineering Design (FEED) study to determine the technical and economic feasibility of installing a retrofit, post-combustion, carbon capture facility on a commercially operating, natural gas-fired, combined cycle (NGCC) power plant. The Electric Power Research Institute (EPRI), California Resources Corporation (CRC), and Fluor Corporation used Fluor's Econamine FG Plus SM (EFG+) conducted the FEED study for capturing CO 2 produced by CRC's 550 MWe Elk Hills Power Plant (EHPP), located in the Elk Hills Oil Field near Tupman, Kern County, California. The EHPP was commissioned in 2003 and is powered by two General Electric 7FA gas turbines, with two heat recovery steam generators (HRSGs) providing steam to a General Electric D11 steam turbine. The target capture amount is 4,000 tonnes CO 2 /day for use in either enhanced oil recovery or dedicated geological saline storage located on CRC property at or nearby EHPP. This CO 2 is captured from a combination of the CO 2 emitted from the flue gas from EHPP and the flue gas generated from a natural gas-fired auxiliary boiler that supplies steam to the EFG+ process.

03 NATURAL GAS↗
DOE OSTI2020

Microstructure, hardness and cavitation erosion resistance of different cold spray coatings on stainless steel 316 for hydropower applications

There is an urgent need for repair of hydropower components that have undergone damage due to cavitation. Conventional repair methods involve melting of materials and can deteriorate material properties and cause distortion. This study investigated the relevant properties of different materials using solid phase processing—cold spray technology. Stainless steel (SS) 316, Inconel 625 and CrC-NiCr materials were cold spray deposited onto base metal SS 316, respectively. Cold spray achieved dense uniform deposits with low level porosity, and intimate contact between the deposit and the base metal was observed. Severe plastic deformation imparted during the cold spray process resulted in significant grain size refinement, nanostructured regions were observed in the deposits across the interfacial area. Cold sprayed deposits exhibited elevated hardness in contrast to that of the base metal SS 316. The cavitation erosion resistance of the deposits was evaluated with a cavitation erosion jet adhering to ASTM G134. Both SS 316 and Inconel 625 achieved better cavitation erosion resistance when compared to that of the SS 316 base metal, with the former exhibiting close to a 4 times improvement.

Jiang, Xiujuan↗
DOE OSTI2023

Simultaneous carbon catabolite repression governs sugar and aromatic co-utilization in Pseudomonas putida M2

ABSTRACT Pseudomonas putida have emerged as promising biocatalysts for the conversion of sugars and aromatic compounds obtained from lignocellulosic biomass. Understanding the role of carbon catabolite repression (CCR) in these strains is critical to optimize biomass conversion to fuels and chemicals. The CCR functioning in P. putida M2, a strain capable of consuming both hexose and pentose sugars as well as aromatic compounds, was investigated by cultivation experiments, proteomics, and CRISPRi-based gene repression. Strain M2 co-utilized sugars and aromatic compounds simultaneously; however, during cultivation with glucose and aromatic compounds ( p- coumarate and ferulate) mixture, intermediates (4-hydroxybenzoate and vanillate) accumulated, and substrate consumption was incomplete. In contrast, xylose-aromatic consumption resulted in transient intermediate accumulation and complete aromatic consumption, while xylose was incompletely consumed. Proteomics analysis revealed that glucose exerted stronger repression than xylose on the aromatic catabolic proteins. Key glucose (Eda) and xylose (XylX) catabolic proteins were also identified at lower abundance during cultivation with aromatic compounds implying simultaneous catabolite repression by sugars and aromatic compounds. Reduction of crc expression via CRISPRi led to faster growth and glucose and p -coumarate uptake in the CRISPRi strains compared to the control, while no difference was observed on xylose+ p -coumarate. The increased abundances of Eda and amino acid biosynthesis proteins in the CRISPRi strain further supported these observations. Lastly, small RNAs (sRNAs) sequencing results showed that CrcY and CrcZ homologues levels in M2, previously identified in P. putida strains, were lower under strong CCR (glucose+ p -coumarate) condition compared to when repression was absent ( p -coumarate or glucose only). IMPORTANCE A newly isolated Pseudomonas putida strain, P. putida M2, can utilize both hexose and pentose sugars as well as aromatic compounds making it a promising host for the valorization of lignocellulosic biomass. Pseudomonads have developed a regulatory strategy, carbon catabolite repression, to control the assimilation of carbon sources in the environment. Carbon catabolite repression may impede the simultaneous and complete metabolism of sugars and aromatic compounds present in lignocellulosic biomass and hinder the development of an efficient industrial biocatalyst. This study provides insight into the cellular physiology and proteome during mixed-substrate utilization in P. putida M2. The phenotypic and proteomics results demonstrated simultaneous catabolite repression in the sugar-aromatic mixtures, while the CRISPRi and sRNA sequencing demonstrated the potential role of the crc gene and small RNAs in carbon catabolite repression.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

PLEKHA7 signaling is necessary for the growth of mutant KRAS driven colorectal cancer

Plekha7 (Pleckstrin homology [PH] domain containing, family A member 7) regulates the assembly of proteins of the cytoplasmic apical zonula adherens junction (AJ), thus ensuring cell-cell adhesion and tight-junction barrier integrity. Little is known of Plekha7 function in cancer. In colorectal cancer (CRC) Plekha7 expression is elevated compared to adjacent normal tissue levels, increasing with clinical stage. Plekha7 was present at plasma membrane AJ with wild-type KRas (wt-KRas) but was dispersed in cells expressing mutant KRas (mut-KRas). Fluorescence lifetime imaging microscopy (FLIM) indicated a direct Plekha7 interaction with wt-KRas but scantily with mut-KRas. Inhibiting Plekha7 specifically decreased mut-KRas cell signaling, proliferation, attachment, migration, and retarded mut-KRAS CRC tumor growth. Binding of diC8-phosphoinositides (PI) to the PH domain of Plekha7 was relatively low affinity. This may be because a D175 amino acid residue plays a “sentry” role preventing PI(3,4)P{sub 2} and PI(3,4,5)P{sub 3} binding. Molecular or pharmacological inhibition of the Plekha7 PH domain prevented the growth of mut-KRas but not wt-KRas cells. Taken together the studies suggest that Plekha7, in addition to maintaining AJ structure plays a role in mut-KRas signaling and phenotype through interaction of its PH domain with membrane mut-KRas, but not wt-KRas, to increase the efficiency of mut-KRas downstream signaling.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2023

Combined First-Principles and Experimental Investigation into the Reactivity of Codeposited Chromium–Carbon under Pressure

High-pressure synthesis in the diamond anvil cell suffers from the lack of a general approach for the control of precursor stoichiometry and homogeneity. Here, we present results from a new method we have developed that uses magnetron cosputtering to prepare stoichiometrically precise and atomically mixed amorphous films of Cr:C. Laser-heated diamond anvil cell experiments carried out on a flake of this sample at pressures between 13.5 and 24.3 GPa lead to the observation of Cr 3 C (Pnma) over the entire pressure range–in good agreement with our in-house theoretical predictions–but also reveal two other metastable phases that were not expected: a novel monoclinic chromium carbide phase and the NaCl-type CrC (Fm3̅m) phase. The unexpected stability of CrC is investigated by using first-principles methods, revealing a large stabilizing effect tied to substoichiometry at the carbon site. These results offer an important case study into the current limitations of crystal structure prediction methods with regard to phase complexity and bolster the growing need for advanced theoretical approaches that can more completely survey experimentally unexplored phase space.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2022

A small molecule inhibitor prevents gut bacterial genotoxin production

Abstract The human gut bacterial genotoxin colibactin is a possible key driver of colorectal cancer (CRC) development. Understanding colibactin’s biological effects remains difficult owing to the instability of the proposed active species and the complexity of the gut microbiota. Here, we report small molecule boronic acid inhibitors of colibactin biosynthesis. Designed to mimic the biosynthetic precursor precolibactin, these compounds potently inhibit the colibactin-activating peptidase ClbP. Using biochemical assays and crystallography, we show that they engage the ClbP binding pocket, forming a covalent bond with the catalytic serine. These inhibitors reproduce the phenotypes observed in a clbP deletion mutant and block the genotoxic effects of colibactin on eukaryotic cells. The availability of ClbP inhibitors will allow precise, temporal control over colibactin production, enabling further study of its contributions to CRC. Finally, application of our inhibitors to related peptidase-encoding pathways highlights the power of chemical tools to probe natural product biosynthesis.

Biochemistry & Molecular Biology↗