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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 415 records · Page 23
All sourcesNASA NTRSDOE OSTI
DOE OSTI2021

KIBRA connects Hippo signaling and cancer

The Hippo signaling pathway is a tumor suppressor pathway that plays an important role in tissue homeostasis and organ size control. KIBRA is one of the many upstream regulators of the Hippo pathway. It functions as a tumor suppressor by positively regulating the core Hippo kinase cascade. However, there are accumulating shreds of evidence showing that KIBRA has an oncogenic function, which we speculate may arise from its functions away from the Hippo pathway. In this review, we have attempted to provide an overview of the Hippo signaling with a special emphasis on evidence showing the paradoxical role of KIBRA in cancer.

60 APPLIED LIFE SCIENCES↗
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

DYNC1H1 regulates NSCLC cell growth and metastasis by IFN-γ-JAK-STAT signaling and is associated with an aberrant immune response

Highlights: • DYNC1H1 is upregulated and its high expression predicted poor outcomes in NSCLC. • Loss of function of DYNC1H1 inhibits cell growth and metastasis of NSCLC cells in vitro. • DYNC1H1 knockdown inhibited metastasis of NSCLC cells in vivo. • DYNC1H1 loss of function suppresses IFN-γ-JAK-STAT signaling pathway in NSCLC. • DYNC1H1 expression is correlated with aberrant immune response in NSCLC indicated by analysis of TCGA immune data. It is urgent to identify new biomarkers and therapeutic targets to ameliorate the clinical prognosis of patients with lung cancer. The functional significance and molecular mechanism of dynein cytoplasmic 1 heavy chain 1 (DYNC1H1) in nonsmall cell lung cancer (NSCLC) progression is still elusive. In our current study, publicly available data and Western blotting experiments confirmed that DYNC1H1 expression was upregulated in lung cancer samples compared with noncancerous samples. Quantitative real-time PCR (qPCR) results indicated that high DYNC1H1 expression in lung cancer tissues was significantly associated with clinical tumor stage and distal metastasis; moreover, its high expression was negatively correlated with prognosis. Functional experiments demonstrated that DYNC1H1 loss of function caused a significant decrease in cell viability and cell proliferative ability, inhibition of the cell cycle, and promotion of both migration potential and invasion potential in vitro. Animal experiments by tail vein injection of lung cancer cells showed that DYNC1H1 knockdown significantly decreased lung cancer metastasis. Mechanistically, the results from a human protein array showed changes in the IFN-γ-JAK-STAT signaling pathway, and analysis of The Cancer Genome Atlas (TCGA) immune data demonstrated that disturbance of the immune microenvironment might be involved in the impaired growth and metastatic ability mediated by DYNC1H1 loss in NSCLC. DYNC1H1 might serve as a promising biological marker of prognosis and a potential clinical therapeutic target for patients with NSCLC.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

G protein nucleolar 3 promotes Non-Hodgkin lymphoma progression by activating the Wnt/β-catenin signaling pathway

G protein nucleolar 3 (GNL3), which acts as an oncoprotein in various carcinomas, is associated with tumor progression; however, little is known regarding GNL3 function in non-Hodgkin lymphoma (NHL). In this study, we first used in silico analysis to determine associations between GNL3 and diffuse large B-cell lymphoma (DLBCL). We then examined the effect of GNL3 on NHL progression, including cell proliferation, apoptosis, and cell cycle progression, and determined its underlying molecular mechanism using in vitro lymphoma cell lines and in vivo mouse xenograft models. We found that GNL3 mRNA levels were markedly higher in DLBCL tissues than in normal tissues, with these higher levels associated with poor prognosis. Additionally, GNL3 overexpression promoted NHL cell proliferation and cell cycle progression and reduced apoptosis in vitro, and enhanced tumorigenesis in an in vivo xenograft model. Moreover, we found that GNL3 upregulated the levels of Wnt/β-catenin signaling pathway-related factors and downstream target genes, whereas the opposite result was observed in GNL3-silenced cells. Furthermore, a rescue experiment using a Wnt/β-catenin inhibitor (XAV939) confirmed that GNL3 promotes NHL progression by activating the Wnt/β-catenin signaling pathway. These findings demonstrated that GNL3 functions as an oncogenic driver in NHL via the Wnt/β-catenin pathway.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2020

Chiral Four-Wave Mixing Signals with Circularly Polarized X-ray Pulses

Chiral four-wave mixing signals are calculated using the irreducible tensor formalism. Different polarization and crossing angle configurations allow to single out the magnetic dipole and the electric quadrupole interactions. Other configurations can reveal that the chiral interaction occurs at a given step within the nonlinear interaction pathways. Applications are made to the study of valence excitations of S-ibuprofen by chiral stimulated X-ray Raman signals at the carbon K-edge and by chiral visible 2D electronic spectroscopy.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2020

Lipo-chitooligosaccharides as regulatory signals of fungal growth and development

Lipo-chitooligosaccharides (LCOs) are signaling molecules produced by rhizobial bacteria that trigger the nodulation process in legumes, and by some fungi that also establish symbiotic relationships with plants, notably the arbuscular and ecto mycorrhizal fungi. Here, we show that many other fungi also produce LCOs. We tested 59 species representing most fungal phyla, and found that 53 species produce LCOs that can be detected by functional assays and/or by mass spectroscopy. LCO treatment affects spore germination, branching of hyphae, pseudohyphal growth, and transcription in non-symbiotic fungi from the Ascomycete and Basidiomycete phyla. Our findings suggest that LCO production is common among fungi, and LCOs may function as signals regulating fungal growth and development.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

Clustering earthquake signals and background noises in continuous seismic data with unsupervised deep learning

The continuously growing amount of seismic data collected worldwide is outpacing our abilities for analysis, since to date, such datasets have been analyzed in a human-expert intensive, supervised fashion. Moreover, analyses that are conducted can be strongly biased by the standard models employed by seismologists. In response to both of these challenges, we develop a new unsupervised machine learning framework for detecting and clustering seismic signals in continuous seismic records. Our approach combines a deep scattering network and a Gaussian mixture model to cluster seismic signal segments and detect novel structures. To illustrate the power of the framework, we analyze seismic data acquired during the June 2017 Nuugaatsiaq, Greenland landslide. We demonstrate the blind detection and recovery of the repeating precursory seismicity that was recorded before the main landslide rupture, which suggests that our approach could lead to more informative forecasting of the seismic activity in seismogenic areas.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

Computational design of highly signalling-active membrane receptors through solvent-mediated allosteric networks

Abstract Protein catalysis and allostery require the atomic-level orchestration and motion of residues and ligand, solvent and protein effector molecules. However, the ability to design protein activity through precise protein–solvent cooperative interactions has not yet been demonstrated. Here we report the design of 14 membrane receptors that catalyse G protein nucleotide exchange through diverse engineered allosteric pathways mediated by cooperative networks of intraprotein, protein–ligand and –solvent molecule interactions. Consistent with predictions, the designed protein activities correlated well with the level of plasticity of the networks at flexible transmembrane helical interfaces. Several designs displayed considerably enhanced thermostability and activity compared with related natural receptors. The most stable and active variant crystallized in an unforeseen signalling-active conformation, in excellent agreement with the design models. The allosteric network topologies of the best designs bear limited similarity to those of natural receptors and reveal an allosteric interaction space larger than previously inferred from natural proteins. The approach should prove useful for engineering proteins with novel complex protein binding, catalytic and signalling activities.

Chemistry↗
DOE OSTI2021

cGAS-like receptors sense RNA and control 3'2'-cGAMP signalling in Drosophila

Cyclic GMP–AMP synthase (cGAS) is a cytosolic DNA sensor that produces the second messenger cG[2'–5']pA[3'–5']p (2'3'-cGAMP) and controls activation of innate immunity in mammalian cells. Animal genomes typically encode multiple proteins with predicted homology to cGAS, but the function of these uncharacterized enzymes is unknown. Here we show that cGAS-like receptors (cGLRs) are innate immune sensors that are capable of recognizing divergent molecular patterns and catalysing synthesis of distinct nucleotide second messenger signals. Crystal structures of human and insect cGLRs reveal a nucleotidyltransferase signalling core shared with cGAS and a diversified primary ligand-binding surface modified with notable insertions and deletions. We demonstrate that surface remodelling of cGLRs enables altered ligand specificity and used a forward biochemical screen to identify cGLR1 as a double-stranded RNA sensor in the model organism Drosophila melanogaster. We show that RNA recognition activates Drosophila cGLR1 to synthesize the novel product cG[3'–5']pA[2'–5']p (3'2'-cGAMP). A crystal structure of Drosophila stimulator of interferon genes (dSTING) in complex with 3'2'-cGAMP explains selective isomer recognition, and 3'2'-cGAMP induces an enhanced antiviral state in vivo that protects from viral infection. Similar to radiation of Toll-like receptors in pathogen immunity, our results establish cGLRs as a diverse family of metazoan pattern recognition receptors.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

Signal amplification in a solid-state sensor through asymmetric many-body echo

Electronic spins of nitrogen–vacancy centres in diamond constitute a promising system for micro- and nanoscale magnetic sensing, because of their operation under ambient conditions, ease of placement in close proximity to sensing targets and biological compatibility. At high densities, the electronic spins interact through dipolar coupling, which typically limits but can also potentially enhance sensing performance. Here we report the experimental demonstration of many-body signal amplification in a solid-state, room-temperature quantum sensor. Our approach uses time-reversed two-axis-twisting interactions, engineered through dynamical control of the quantization axis and Floquet engineering in a two-dimensional ensemble of nitrogen–vacancy centres. We observe that optimal amplification occurs when the backward evolution time equals twice the forward evolution time, in sharp contrast to the conventional Loschmidt echo. These observations can be understood as resulting from an underlying time-reversed mirror symmetry of the microscopic dynamics, providing key insights into signal amplification and opportunities for practical entanglement-enhanced quantum sensing.

quantum information↗
DOE OSTI2025

A miniature CRISPR–Cas10 enzyme confers immunity by inhibitory signalling

Microbial and viral co-evolution has created immunity mechanisms involving oligonucleotide signalling that share mechanistic features with human antiviral systems1. In these pathways, including cyclic oligonucleotide-based antiphage signalling systems (CBASSs) and type III CRISPR systems in bacteria and cyclic GMP–AMP synthase–stimulator of interferon genes (cGAS–STING) in humans, oligonucleotide synthesis occurs upon detection of virus or foreign genetic material in the cell, triggering the antiviral response2, 3–4. Here, in an unexpected inversion of this process, we show that the CRISPR-related enzyme mCpol synthesizes cyclic oligonucleotides constitutively as part of an active mechanism that represses a toxic effector. Cell-based experiments demonstrated that the absence or loss of mCpol-produced cyclic oligonucleotides triggers cell death, preventing the spread of viruses that attempt immune evasion by depleting host cyclic nucleotides. Structural and mechanistic investigation revealed mCpol to be a di-adenylate cyclase whose product, c-di-AMP, prevents toxic oligomerization of the effector protein 2TMβ. Analysis of cells by fluorescence microscopy showed that lack of mCpol allows 2TMβ-mediated cell death due to inner membrane collapse. These findings unveil a powerful defence strategy against virus-mediated immune suppression, expanding our understanding of the role of oligonucleotides in immunity.

Doherty, Erin E↗
DOE OSTI2024

Genomes of multicellular algal sisters to land plants illuminate signaling network evolution

Zygnematophyceae are the algal sisters of land plants. Here we sequenced four genomes of filamentous Zygnematophyceae, including chromosome-scale assemblies for three strains of Zygnema circumcarinatum . We inferred traits in the ancestor of Zygnematophyceae and land plants that might have ushered in the conquest of land by plants: expanded genes for signaling cascades, environmental response, and multicellular growth. Zygnematophyceae and land plants share all the major enzymes for cell wall synthesis and remodifications, and gene gains shaped this toolkit. Co-expression network analyses uncover gene cohorts that unite environmental signaling with multicellular developmental programs. Our data shed light on a molecular chassis that balances environmental response and growth modulation across more than 600 million years of streptophyte evolution.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

Real Time implementation of Artificial Intelligence compression algorithm for High-Speed Streaming Readout signals

The new generation of high-energy physics experiments plans to acquire data in streaming mode. With this approach, it is possible to access the information of the whole detector (organized in time slices) for optimal and lossless triggering of data acquisitions. With this approach, data rates, especially in large detectors, are often very high, and the network is likely to be the bottleneck for the entire Streaming Read Out system. The aim of this work is to study the implementation of a lossy compression algorithm based on Artificial Intelligence: an Autoencoder. With Machine Learning it is possible to achieve a high compression ratio and fast inference time with only a small degradation of the signals, almost negligible for the specific application. This work explores different configurations of the Autoencoder and the implementation on different hardware. Different Autoencoder configurations are explored to find the best trade-off between compression ratio and reconstruction loss, both for signals and energy spectrum. Different hardware implementations are also explored to find the best platform to achieve real-time performance for the specific application.

Rossi, Fabio (ORCID:0009000385713885)↗
DOE OSTI2025

Statistically elucidated responses from low-signal contrast mechanisms in ultrafast electron microscopy

The emergence of ultrafast electron microscopy (UEM) has enabled the discovery of strongly correlated dynamic mechanisms, including electron–phonon coupling, structural phase transitions, thermal transport, and electromagnetic deflection. Most UEM systems operate stroboscopically, meaning that the technique is susceptible to artifacts, mistakes, and misinterpretation of the data due to extensive experimental effort. In contrast to the ultrafast designation, data acquisition is extraordinarily slow because the electron beam has significantly reduced signal compared to traditional transmission electron microscopy due to pulsing the electron beam. Consequently, the sample may drift, tilt, or undergo irreversible structural changes that are independent of the time-resolved dynamics throughout the experimental time frame. Furthermore, these datasets require significant user interpretation that can be problematic when proper controls are not implemented thoroughly. Here, we demonstrate a new algorithm designed to separate ultrafast structural dynamics from long-term artifacts using a LiNbO 3 sample experiencing electrically driven surface acoustic wave propagation. Additionally, we provide examples of the impact of user bias when analyzing the data and provide a methodology, which enables the extraction of time-resolved responses when the image signal is extraordinarily low. Overall, the goal of this publication is to provide methods that validate the experimental results and reduce researcher biases during UEM data interpretation.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗
DOE OSTI2020

Super-resolution and signal separation in contact Kelvin probe force microscopy of electrochemically active ferroelectric materials

In this work, imaging mechanisms in contact Kelvin probe force microscopy (cKPFM) are explored via information theory-based methods. Gaussian processes are used to achieve super-resolution in the cKPFM signal, effectively extrapolating across the spatial and parameter space. Tensor factorization is applied to reduce the multidimensional signal to the tensor convolution of the scalar functions that show a clear trending behavior with the imaging parameters. These methods establish a workflow for the analysis of the multidimensional datasets that can then be related to the relevant physical mechanisms. We also provide an interactive Google Colab notebook that goes through all the analyses discussed in the paper.

36 MATERIALS SCIENCE↗
DOE OSTI2021

Initial operation and data processing on a system for real-time evaluation of Thomson scattering signals on the Large Helical Device

A scalable system for real-time analysis of electron temperature and density based on signals from the Thomson scattering diagnostic, initially developed for and installed on the NSTX-U experiment, was recently adapted for the Large Helical Device and operated for the first time during plasma discharges. During its initial operation run, it routinely recorded and processed signals for four spatial points at the laser repetition rate of 30 Hz, well within the system’s rated capability for 60 Hz. We present examples of data collected from this initial run and describe subsequent adaptations to the analysis code to improve the fidelity of the temperature calculations.

47 OTHER INSTRUMENTATION↗
DOE OSTI2024

Using a multistate mapping approach to surface hopping to predict the ultrafast electron diffraction signal of gas-phase cyclobutanone

Using the recently developed multistate mapping approach to surface hopping (multistate MASH) method combined with SA(3)-CASSCF(12,12)/aug-cc-pVDZ electronic structure calculations, the gas-phase isotropic ultrafast electron diffraction (UED) of cyclobutanone is predicted and analyzed. After excitation into the n-3s Rydberg state (S2), cyclobutanone can relax through two S2/S1 conical intersections, one characterized by compression of the CO bond and the other by dissociation of the α–CC bond. Subsequent transfer into the ground state (S0) is then achieved via two additional S1/S0 conical intersections that lead to three reaction pathways: α ring-opening, ethene/ketene production, and CO liberation. The isotropic gas-phase UED signal is predicted from the multistate MASH simulations, allowing for a direct comparison to the experimental data. This work, which is a contribution to the cyclobutanone prediction challenge, facilitates the identification of the main photoproducts in the UED signal and thereby emphasizes the importance of dynamics simulations for the interpretation of ultrafast experiments.

Chemistry↗
DOE OSTI2025

The polarized-signal density matrix: A practical way to recover molecular frame information from isotropic samples

We present a novel approach to model ultrafast time-dependent nonlinear optical polarization sensitive signals emitted from randomly oriented molecules. By projecting the laboratory-frame analyzer polarization axis into the molecular-frame and linking that axis with the density matrix through a tensor product, we demonstrate an approach to find a specific molecular orientation that yields a good approximation to simulated four-wave mixing signals produced by the same model but with averaging over molecular orientation.

Thurston, Richard L↗