Engineering Papers⌕ Search

SEARCH · Engineering Papers

Results for “TAN”

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 1,099 records · Page 61
All sourcesNASA NTRSDOE OSTI
DOE OSTI2023

A cryptic oxidoreductase safeguards oxidative protein folding in Corynebacterium diphtheriae

In many gram-positive Actinobacteria, including Actinomyces oris and Corynebacterium matruchotii , the conserved thiol-disulfide oxidoreductase MdbA that catalyzes oxidative folding of exported proteins is essential for bacterial viability by an unidentified mechanism. Intriguingly, in Corynebacterium diphtheriae , the deletion of mdbA blocks cell growth only at 37 °C but not at 30 °C, suggesting the presence of alternative oxidoreductase enzyme(s). By isolating spontaneous thermotolerant revertants of the mdbA mutant at 37 °C, we obtained genetic suppressors, all mapped to a single T-to-G mutation within the promoter region of tsdA , causing its elevated expression. Strikingly, increased expression of tsdA —via suppressor mutations or a constitutive promoter—rescues the pilus assembly and toxin production defects of this mutant, hence compensating for the loss of mdbA . Structural, genetic, and biochemical analyses demonstrated TsdA is a membrane-tethered thiol-disulfide oxidoreductase with a conserved CxxC motif that can substitute for MdbA in mediating oxidative folding of pilin and toxin substrates. Together with our observation that tsdA expression is upregulated at nonpermissive temperature (40 °C) in wild-type cells, we posit that TsdA has evolved as a compensatory thiol-disulfide oxidoreductase that safeguards oxidative protein folding in C. diphtheriae against thermal stress.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Large-scale analysis of structural brain asymmetries in schizophrenia via the ENIGMA consortium

Left–right asymmetry is an important organizing feature of the healthy brain that may be altered in schizophrenia, but most studies have used relatively small samples and heterogeneous approaches, resulting in equivocal findings. We carried out the largest case–control study of structural brain asymmetries in schizophrenia, with MRI data from 5,080 affected individuals and 6,015 controls across 46 datasets, using a single image analysis protocol. Asymmetry indexes were calculated for global and regional cortical thickness, surface area, and subcortical volume measures. Differences of asymmetry were calculated between affected individuals and controls per dataset, and effect sizes were meta-analyzed across datasets. Small average case–control differences were observed for thickness asymmetries of the rostral anterior cingulate and the middle temporal gyrus, both driven by thinner left-hemispheric cortices in schizophrenia. Analyses of these asymmetries with respect to the use of antipsychotic medication and other clinical variables did not show any significant associations. Assessment of age- and sex-specific effects revealed a stronger average leftward asymmetry of pallidum volume between older cases and controls. Case–control differences in a multivariate context were assessed in a subset of the data (N = 2,029), which revealed that 7% of the variance across all structural asymmetries was explained by case–control status. Subtle case–control differences of brain macrostructural asymmetry may reflect differences at the molecular, cytoarchitectonic, or circuit levels that have functional relevance for the disorder. Reduced left middle temporal cortical thickness is consistent with altered left-hemisphere language network organization in schizophrenia.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2023

Effect of local chemical order on the irradiation-induced defect evolution in CrCoNi medium-entropy alloy

High- (and medium-) entropy alloys have emerged as potentially suitable structural materials for nuclear applications, particularly as they appear to show promising irradiation resistance. Recent studies have provided evidence of the presence of local chemical order (LCO) as a salient feature of these complex concentrated solid-solution alloys. However, the influence of such LCO on their irradiation response has remained uncertain thus far. Here, in this work, we combine ion irradiation experiments with large-scale atomistic simulations to reveal that the presence of chemical short-range order, developed as an early stage of LCO, slows down the formation and evolution of point defects in the equiatomic medium-entropy alloy CrCoNi during irradiation. In particular, the irradiation-induced vacancies and interstitials exhibit a smaller difference in their mobility, arising from a stronger effect of LCO in localizing interstitial diffusion. This effect promotes their recombination as the LCO serves to tune the migration energy barriers of these point defects, thereby delaying the initiation of damage. These findings imply that local chemical ordering may provide a variable in the design space to enhance the resistance of multi-principal element alloys to irradiation damage.

36 MATERIALS SCIENCE↗
DOE OSTI2023

Lipid nanoparticle topology regulates endosomal escape and delivery of RNA to the cytoplasm

RNA therapeutics have the potential to resolve a myriad of genetic diseases. Lipid nanoparticles (LNPs) are among the most successful RNA delivery systems. Expanding their use for the treatment of more genetic diseases hinges on our ability to continuously evolve the design of LNPs with high potency, cellular-specific targeting, and low side effects. Overcoming the difficulty of releasing cargo from endocytosed LNPs remains a significant hurdle. Here, in this study, we investigate the fundamental properties of nonviral RNA nanoparticles pertaining to the activation of topological transformations of endosomal membranes and RNA translocation into the cytosol. We show that, beyond composition, LNP fusogenicity can be prescribed by designing LNP nanostructures that lower the energetic cost of fusion and fusion–pore formation with a target membrane. The inclusion of structurally active lipids leads to enhanced LNP endosomal fusion, fast evasion of endosomal entrapment, and efficacious RNA delivery. For example, conserving the lipid make-up, RNA–LNPs havingcuboplexnanostructures are significantly more efficacious at endosomal escape than traditionallipoplexconstructs.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Direct observation of the collective modes of the charge density wave in the kagome metal CsV 3 Sb 5

A recently discovered group of kagome metals AV 3 Sb 5 (A = K, Rb, Cs) exhibit a variety of intertwined unconventional electronic phases, which emerge from a puzzling charge density wave phase. Understanding of this charge-ordered parent phase is crucial for deciphering the entire phase diagram. However, the mechanism of the charge density wave is still controversial, and its primary source of fluctuations—the collective modes—has not been experimentally observed. Here, we use ultrashort laser pulses to melt the charge order in CsV 3 Sb 5 and record the resulting dynamics using femtosecond angle-resolved photoemission. We resolve the melting time of the charge order and directly observe its amplitude mode, imposing a fundamental limit for the fastest possible lattice rearrangement time. These observations together with ab initio calculations provide clear evidence for a structural rather than electronic mechanism of the charge density wave. Our findings pave the way for a better understanding of the unconventional phases hosted on the kagome lattice.

36 MATERIALS SCIENCE↗
DOE OSTI2025

Strong, ductile, and hierarchical hetero-lamellar-structured alloys through microstructural inheritance and refinement

The strength−ductility trade-off exists ubiquitously, especially in brittle intermetallic-containing multiple principal element alloys (MPEAs), where the intermetallic phases often induce premature failure leading to severe ductility reduction. Hierarchical heterogeneities represent a promising microstructural solution to achieve simultaneous strength−ductility enhancement. However, it remains fundamentally challenging to tailor hierarchical heterostructures using conventional methods, which often rely on costly and time-consuming processing. Here, we report a multiscale microstructural inheritance and refinement strategy to process “structural hierarchy precursors” in as-cast heterogeneous Al 0.7 CoCrFeNi MPEAs, which lead directly to a hierarchical hetero-lamellar structure (HLS) after simple rolling and annealing. Interestingly, it takes only 10 min of annealing time, two orders of magnitude less than that required to render the state-of-the-art properties during conventional processing of Al 0.7 CoCrFeNi, for us to achieve record-high strength−ductility combinations via the hierarchical HLS design that sequentially stimulates multiple unusual deformation and reinforcement mechanisms. In particular, the HLS-enabled high hetero-deformation-induced (HDI) internal stress triggers profuse <111>-type dislocations on over five independent slip systems in the supposedly brittle intermetallic phase and activates extensive stacking faults (SFs) and nanotwinning in the adjoining soft phase with a rather high SF energy. These unexpected, dynamically reinforcing hetero-deformation mechanisms across multiple length scales facilitate high sustained HDI strain hardening, along with a salient microcrack-mediated extrinsic ductilization effect, suggesting that the proposed microstructural inheritance and refinement strategy provides an efficient, fast, and low-cost approach to overcome the strength−ductility trade-off in a broad range of structural materials.

Science & Technology - Other Topics↗
DOE OSTI2024

Discovery of highly potent and ALK2/ALK1 selective kinase inhibitors using DNA-encoded chemistry technology

Activin receptor type 1 (ACVR1; ALK2) and activin receptor like type 1 (ACVRL1; ALK1) are transforming growth factor beta family receptors that integrate extracellular signals of bone morphogenic proteins (BMPs) and activins into Mothers Against Decapentaplegic homolog 1/5 (SMAD1/SMAD5) signaling complexes. Several activating mutations in ALK2 are implicated in fibrodysplasia ossificans progressiva (FOP), diffuse intrinsic pontine gliomas, and ependymomas. The ALK2 R206H mutation is also present in a subset of endometrial tumors, melanomas, non-small lung cancers, and colorectal cancers, and ALK2 expression is elevated in pancreatic cancer. Using DNA-encoded chemistry technology, we screened 3.94 billion unique compounds from our diverse DNA-encoded chemical libraries (DECLs) against the kinase domain of ALK2. Off-DNA synthesis of DECL hits and biochemical validation revealed nanomolar potent ALK2 inhibitors. Further structure-activity relationship studies yielded center for drug discovery (CDD)-2789, a potent [NanoBRET (NB) cell IC50: 0.54 μM] and metabolically stable analog with good pharmacological profile. Crystal structures of ALK2 bound with CDD-2281, CDD-2282, or CDD-2789 show that these inhibitors bind the active site through Van der Waals interactions and solvent-mediated hydrogen bonds. CDD-2789 exhibits high selectivity toward ALK2/ALK1 in KINOMEscan analysis and NB K192 assay. In cell-based studies, ALK2 inhibitors effectively attenuated activin A and BMP-induced Phosphorylated SMAD1/5 activation in fibroblasts from individuals with FOP in a dose-dependent manner. Thus, CDD-2789 is a valuable tool compound for further investigation of the biological functions of ALK2 and ALK1 and the therapeutic potential of specific inhibition of ALK2.

Jimmidi, Ravikumar↗
DOE OSTI2025

Spatial profiling of the interplay between cell type- and vision-dependent transcriptomic programs in the visual cortex

How early sensory experience during “critical periods” of postnatal life affects the organization of the mammalian neocortex at the resolution of neuronal cell types is poorly understood. We previously reported that the functional and molecular profiles of layer 2/3 (L2/3) cell types in the primary visual cortex (V1) are vision-dependent [S. Chenget al.,Cell185, 311–327.e24 (2022)]. Here, we characterize the spatial organization of L2/3 cell types with and without visual experience. Spatial transcriptomic profiling based on 500 genes recapitulates the zonation of L2/3 cell types along the pial–ventricular axis in V1. By applying multitasking theory, we suggest that the spatial zonation of L2/3 cell types is linked to the continuous nature of their gene expression profiles, which can be represented as a 2D manifold bounded by three archetypal cell types. By comparing normally reared and dark reared L2/3 cells, we show that visual deprivation-induced transcriptomic changes comprise two independent gene programs. The first, induced specifically in the visual cortex, includes immediate-early genes and genes associated with metabolic processes. It manifests as a change in cell state that is orthogonal to cell-type-specific gene expression programs. By contrast, the second program impacts L2/3 cell-type identity, regulating a subset of cell-type-specific genes and shifting the distribution of cells within the L2/3 cell-type manifold. Through an integrated analysis of spatial transcriptomics with single-nucleus RNA-seq data, we describe how vision patterns cortical L2/3 cell types during the critical period.

Science & Technology - Other Topics↗
DOE OSTI2026

Identification of potent inhibitors of JUN N-terminal kinases for treatment of endometriosis and associated pain

Endometriosis, defined as the ectopic growth of endometrial tissue outside of the uterine cavity, is an inflammatory and hormone-dependent disease that causes excruciating pelvic pain, infertility, and significantly decreases quality of life in affected patients. The JUN N-terminal kinases (JNKs) are a leading class of nonhormonal therapeutic targets that have been validated in preclinical models of endometriosis and in a Phase 1/2 clinical trial. Despite their therapeutic potential, JNK inhibitors with increased potency and specificity are needed to address the inflammatory pathology of endometriosis and to prevent disease progression. Leveraging a DNA-encoded chemical library collection of ~4 billion compounds, we identified lead inhibitor CDD-2428 and optimized derivatives, CDD-2728 and CDD-3013, with excellent binding affinity to JNK1-3 (K d = 0.12 to 3.7 nM), enhanced selectivity, metabolic stability, and cellular permeability. Crystallographic and biochemical studies confirmed that CDD-3013 exhibited superior kinase selectivity with improved efficacy compared to existing JNK inhibitors. In primary endometriosis cell models, CDD-2728 and CDD-3013 suppressed JNK-dependent inflammatory signaling, dampening pathways linked to pain, invasion, angiogenesis, and macrophage recruitment. In an endometriosis mouse model, both CDD-2728 and CDD-3013 reduced endometriotic lesion size, macrophage infiltration, and cellular proliferation, showing in vivo efficacy. When tested in a lipopolysaccharide-induced hyperalgesia model, CDD-2728 and CDD-3013 decreased markers of induced pain, as measured by changes in a dynamic weight bearing test and Grimace scores. These findings nominate CDD-2728 and CDD-3013 as potent, nonhormonal therapeutic candidates for endometriosis with broad anti-inflammatory and analgesic activity, addressing a critical unmet clinical need.

Madasu, Chandrashekhar [Department of Pathology an↗
DOE OSTI2021

Metabolic engineering strategies for sesquiterpene production in microorganism

Sesquiterpenes are a large variety of terpene natural products, widely existing in plants, fungi, marine organisms, insects, and microbes. Value-added sesquiterpenes are extensively used in industries such as: food, drugs, fragrances, and fuels. With an increase in market demands and the price of sesquiterpenes, the biosynthesis of sesquiterpenes by microbial fermentation methods from renewable feedstocks is acquiring increasing attention. Synthetic biology provides robust tools of sesquiterpene production in microorganisms. This review presents a summary of metabolic engineering strategies on the hosts and pathway engineering for sesquiterpene production. Advances in synthetic biology provide new strategies on the creation of desired hosts for sesquiterpene production. Especially, metabolic engineering strategies for the production of sesquiterpenes such as: amorphadiene, farnesene, bisabolene, and caryophyllene are emphasized in: Escherichia coli , Saccharomyces cerevisiae , and other microorganisms. Herein, challenges and future perspectives of the bioprocess for translating sesquiterpene production into practical industrial work are also discussed.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Element differentiation with a Hartmann- based X-ray phase imaging system

Significant efforts are currently ongoing in X-ray imaging to provide multimodal imaging systems, targeting better sensitivity and specificity for both biomedical or non-destructive testing applications. Knowing the elemental composition of specific structures, such as breast microcalcifications in mammography, would help to differentiate malign and benign tumours. Standard X-ray Phase Contrast Imaging techniques provide only qualitative information on elements with similar absorption properties. However, their chemical composition can be determined from the measurement of the phase as it is directly related to the optical index of elemental materials. We will show new experimental results obtained with an X-ray phase imaging system based on a Hartmann mask. Early data treatment succeeded in retrieving both the real and imaginary parts of the refractive index. The system demonstrates the capability to discriminate materials based on elemental composition.

36 MATERIALS SCIENCE↗
DOE OSTI2023

Emission factors of industrial boilers burning biomass-derived fuels

Boilers are combustion devices that provide process heat and are integral to many industrial facilities. Historically, outside of the pulp and paper industry, most boilers burned fossil fuels, although interest in decarbonization has been leading to an increased use of renewable fuels in boilers. These boilers, including those in the biorefineries, are often large sources of air pollutant emissions, and the characterization of these emissions is critical to obtaining air permits and ensuring protection of the surrounding air quality. Several industrial boilers and new biorefineries allow utilization of biomass-derived fuels (e.g. wastewater sludge, lignin, etc.) produced during their operation as a fuel for the boiler to meet process energy needs. However, there is limited empirical data on emission factors for the burning of unconventional fuels, such as solid-gas mixtures containing biomass residues. To fill this gap, we carry out a comprehensive data survey, collecting information on emission factors for boilers burning either a single or a mixture of solid and gaseous biomass-derived fuels. We review multiple hard-to-obtain and unconventional data sources, such as air permit applications, stack test data, and industry-sponsored data collection efforts, to compile emission factors for biomass-derived fuels. We then compare this data with wood residue emission factors from the U.S. Environmental Protection Agency’s AP-42 emission factor database. Our results indicate that the emission factors for boilers burning unconventional fuels vary widely depending on the fuel composition, boiler type, and fuel characteristics. Overall, we find that median emission factors of selected biomass-derived fuels are typically lower than those of wood residue boilers in AP-42. The information collected herein could be useful to permitting agencies and industries utilizing boilers who may want to reduce the carbon impact of their facilities by combusting biomass-derived wastes for process energy needs, for more accurate emission estimation for permitting.

09 BIOMASS FUELS↗
DOE OSTI2023

On unifying randomized methods for inverse problems

This work unifies the analysis of various randomized methods for solving linear and nonlinear inverse problems with Gaussian priors by framing the problem in a stochastic optimization setting. By doing so, we show that many randomized methods are variants of a sample average approximation (SAA). More importantly, we are able to prove a single theoretical result that guarantees the asymptotic convergence for a variety of randomized methods. Additionally, viewing randomized methods as an SAA enables us to prove, for the first time, a single non-asymptotic error result that holds for randomized methods under consideration. Another important consequence of our unified framework is that it allows us to discover new randomization methods. Here, we present various numerical results for linear, nonlinear, algebraic, and PDE-constrained inverse problems that verify the theoretical convergence results and provide a discussion on the apparently different convergence rates and the behavior for various randomized methods.

42 ENGINEERING↗
DOE OSTI2023

An autoencoder compression approach for accelerating large-scale inverse problems

Abstract Partial differential equation (PDE)-constrained inverse problems are some of the most challenging and computationally demanding problems in computational science today. Fine meshes required to accurately compute the PDE solution introduce an enormous number of parameters and require large-scale computing resources such as more processors and more memory to solve such systems in a reasonable time. For inverse problems constrained by time-dependent PDEs, the adjoint method often employed to compute gradients and higher order derivatives efficiently requires solving a time-reversed, so-called adjoint PDE that depends on the forward PDE solution at each timestep. This necessitates the storage of a high-dimensional forward solution vector at every timestep. Such a procedure quickly exhausts the available memory resources. Several approaches that trade additional computation for reduced memory footprint have been proposed to mitigate the memory bottleneck, including checkpointing and compression strategies. In this work, we propose a close-to-ideal scalable compression approach using autoencoders to eliminate the need for checkpointing and substantial memory storage, thereby reducing the time-to-solution and memory requirements. We compare our approach with checkpointing and an off-the-shelf compression approach on an earth-scale ill-posed seismic inverse problem. The results verify the expected close-to-ideal speedup for the gradient and Hessian-vector product using the proposed autoencoder compression approach. To highlight the usefulness of the proposed approach, we combine the autoencoder compression with the data-informed active subspace (DIAS) prior showing how the DIAS method can be affordably extended to large-scale problems without the need for checkpointing and large memory.

Mathematics↗
DOE OSTI2024

Absolute nuclear charge radius by Na-like spectral line separation in high-Z elements

Abstract We describe a novel technique to determine absolute nuclear radii of high- Z nuclides. Utilizing accurate theoretical atomic structure calculations together with precise measurements of extreme ultraviolet transitions in highly charged ions this method allows for precise determinations of absolute nuclear charge radii based upon the well-known nuclear radii of their neighboring elements. This method can work for elements without stable isotopes, and its accuracy may be competitive with current methods (electron scattering and muonic x-ray spectroscopy).

Hosier, A. (ORCID:0000000328366605)↗
DOE OSTI2020

Topological background discrimination in the PandaX-III neutrinoless double beta decay experiment

The PandaX-III experiment plans to search for neutrinoless double beta decay (0ν ββ ) of 136 Xe in the China JinPing underground Laboratory (CJPL). The experiment will use a high pressure gaseous time projection chamber (TPC) to register both the energy and the electron track topology of an event. This article is devoted to demonstrate our particular detector setup capabilities for the identification of 0ν ββ and the consequent background reduction. As software tool we use REST, a framework developed for the reconstruction and simulation of TPC-based detector systems. We study the potential for background reduction by introducing appropriate parameters based on the properties of 0ν ββ events. We exploit for the first time not only the energy density of the electron track-ends, but also the electron scattering angles produced by an electron near the end of its trajectory. To implement this, we have added new algorithms for detector signal and track processing inside REST. Their assessment shows that background can be reduced by about 7 orders of magnitude while keeping 0ν ββ efficiency above 20% for the PandaX-III baseline readout scheme, a two-dimensional 3 mm pitch stripped readout. More generally, we use the potential of REST to handle 2D/3D data to assess the impact on signal-to-background significance at different detector granularities, and to validate the PandaX-III baseline choice. Finally, we demonstrate the additional potential to discriminate surface background events generated at the readout plane in the absence of to, by making use of event parameters related with the diffusion of electrons.

Majorana↗