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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 73 records · Page 4
All sourcesNASA NTRSDOE OSTI
DOE OSTI2024

Defining blood hematology reference values in female pig-tailed macaques ( Macaca nemestrina ) using the Isolation Forest algorithm

Background: Pig-tailed macaques (PTMs) are commonly used as preclinical models to assess antiretroviral drugs for HIV prevention research. Drug toxicities and disease pathologies are often preceded by changes in blood hematology. To better assess the safety profile of pharmaceuticals, we defined normal ranges of hematological values in PTMs using an Isolation Forest (iForest) algorithm. Methods: Eighteen female PTMs were evaluated. Blood was collected 1–24 times per animal for a total of 159 samples. Complete blood counts were performed, and iForest was used to analyze the hematology data to detect outliers. Results: Median, IQR, and ranges were calculated for 13 hematology parameters. From all samples, 22 outliers were detected. These outliers were excluded from the reference index. Conclusions: Using iForest, we defined a normal range for hematology parameters in female PTMs. This reference index can be a valuable tool for future studies evaluating drug toxicities in PTMs.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

An FDA-approved drug structurally and phenotypically corrects the K210del mutation in genetic cardiomyopathy models

Dilated cardiomyopathy (DCM) due to genetic disorders results in decreased myocardial contractility, leading to high morbidity and mortality rates. There are several therapeutic challenges in treating DCM, including poor understanding of the underlying mechanism of impaired myocardial contractility and the difficulty of developing targeted therapies to reverse mutation-specific pathologies. In this report, we focused on K210del, a DCM-causing mutation, due to 3-nucleotide deletion of sarcomeric troponin T (TnnT), resulting in loss of Lysine210. We resolved the crystal structure of the troponin complex carrying the K210del mutation. K210del induced an allosteric shift in the troponin complex resulting in distortion of activation Ca 2+ -binding domain of troponin C (TnnC) at S69, resulting in calcium discoordination. Next, we adopted a structure-based drug repurposing approach to identify bisphosphonate risedronate as a potential structural corrector for the mutant troponin complex. Cocrystallization of risedronate with the mutant troponin complex restored the normal configuration of S69 and calcium coordination. Risedronate normalized force generation in K210del patient-induced pluripotent stem cell–derived (iPSC-derived) cardiomyocytes and improved calcium sensitivity in skinned papillary muscles isolated from K210del mice. Systemic administration of risedronate to K210del mice normalized left ventricular ejection fraction. Collectively, these results identify the structural basis for decreased calcium sensitivity in K210del and highlight structural and phenotypic correction as a potential therapeutic strategy in genetic cardiomyopathies.

Research & Experimental Medicine↗
DOE OSTI2025

Demographic drivers of gut microbiome diversity

Abstract The gut microbiome plays a central role in orchestrating metabolic, immune, and neurological functions essential for human health. While extensive research has explored the effects of diseases and pathological conditions on gut microbiome composition, the influence of demographic factors remains underexplored, limiting our understanding of microbiome variations in disease states. This study addresses this gap by investigating the impact of demographic variables, including age, sex, and geography, on gut microbiome diversity in healthy individuals. Using the American Gut Project’s extensive dataset and the QIIME2 bioinformatics pipeline, we conducted a comprehensive analysis of microbial profiles across diverse demographic groups. Our results revealed significant age-related shifts in microbial richness and composition, and geographic location strongly influenced phylogenetic diversity. In contrast, sex exhibited limited impact on microbial diversity within healthy BMI ranges. These findings highlight the critical role of demographic factors in shaping gut microbiome diversity, providing a foundational framework to better contextualize disease-related microbiome variations and advance personalized healthcare approaches.

Biotechnology & Applied Microbiology↗
DOE OSTI2026

Mitigating Algorithmic Bias in Cancer Site Classification Models

Purpose Integrating artificial intelligence in cancer diagnostics has improved tumor classification beyond rule-based systems. Despite these advancements, these models may still encode demographic biases. We conducted a large-scale, applied bias-probing study of a deep learning–based cancer site classifier to quantify race information encoded in document embeddings. We then evaluated how performance changes when race-correlated embedding dimensions are removed in a post-training sensitivity analysis. Methods The cancer site classifier was trained using 3.5 million electronic cancer pathology reports from six of the National Cancer Institute's SEER registries. We trained a hierarchical self-attention network to generate 400-dimensional document embeddings. These embeddings were used to train two downstream, gradient-boosted decision tree classifiers: one to classify the cancer sites and another to predict racial categories. We identified overlapping features by intersecting the top 50 feature-importance rankings from the site and race models and computed their cumulative feature importance in each model. As a post hoc sensitivity analysis, we progressively pruned these overlapping dimensions, retrained the site model, and compared overall macro-F1 and accuracy, race-stratified macro-F1, and group fairness metrics on the basis of demographic parity and equalized odds before and after pruning. Results The analysis revealed minimal feature overlap between the cancer site and race prediction models, and the cumulative importance scores indicated a negligible influence of racial information on clinical predictions. Post-training pruning of overlapping features did not compromise the models' diagnostic accuracy, with a 0.07% loss in accuracy. Conclusion Our findings demonstrate that HiSAN-generated embeddings from SEER data can be used effectively in cancer site classification without significant demographic bias influencing the outcomes. Post-training pruning therefore functions as a practical audit and sensitivity check.

Shivanna, Abhishek [ORNL] (ORCID:0009000665228593)↗
DOE OSTI2026

Fidelity-preserving enhancement of ptychography with foundational text-to-image models

Ptychographic phase retrieval enables high-resolution imaging of complex samples but often suffers from artifacts such as grid pathology and multislice crosstalk, which degrade reconstructed images. We propose a plug-and-play (PnP) framework that integrates physics model-based phase retrieval with text-guided image editing using foundational diffusion models. By employing the alternating direction method of multipliers, our approach ensures consensus between data fidelity and artifact removal subproblems, maintaining physical consistency while enhancing image quality. Artifact removal is achieved using a text-guided diffusion image editing method (LEDITS++) with a pre-trained foundational diffusion model, allowing users to specify artifacts for removal in natural language. Demonstrations on simulated and experimental datasets show significant improvements in artifact suppression and structural fidelity, validated by metrics such as peak signal-to-noise ratio and diffraction pattern consistency. This work highlights the combination of text-guided generative models and model-based phase retrieval algorithms as a transferable and fidelity-preserving method for high-quality diffraction imaging.

image editing↗
DOE OSTI2025

CRCNS US-France Research Proposal: Collaborative Research: Encoding reward expectation in Drosophilia

The fruit fly Drosophila melanogaster has been a valuable model for investigating the genetic and neural bases that underlie learning and memory. Early and most current studies use basic behavior conditioning protocols to study learning in controlled laboratory settings. More recently, the ability to transgenically manipulate many of the brain neurons in the fruit fly with exquisite specificity, and the recent knowledge of the synaptic ‘connectome’ of the fruit fly brain, makes these animals almost unique as a comprehensive model for studies of learning, memory and motivated behavior. In fact, the connectome has revealed many types of new connections that had until now been overlooked. Within this context, the thesis of this proposal is that studies of learning and memory will be greatly enhanced by using more sophisticated means for evaluating memory representations, such as have been developed in vertebrates, and combining those studies with information from the connectome guided by computational modelling. We propose to push beyond the boundaries of existing conditioning protocols for fruit flies to investigate more complex memory representations. In particular, we will investigate the function of reinforcement pathways in relation to the absence of expected reinforcement. More specifically, we propose a series of experiments designed to investigate the memory representations in fruit flies when an expected consequence of a Conditioned Stimulus (CS) fails to occur. Although studies have evaluated how this failure can establish extinction memory for the CS, our studies will go beyond studying extinction. Specifically, we predict that in Drosophila when a CS is associated with a failed expectation of an appetitive food reinforcement it will acquire aversive value, and vice versa for a failed expectation of an aversive reinforcer. We combine these studies with manipulations of reinforcement pathways in the CNS inspired from the connectome, iteratively knitted in with established computational models. Intellectual Merit: The concept of reinforcement expectation and incentive contrast have been influential in the development of studies of associative learning in mammals. These questions are particularly challenging to answer in vertebrates because they require exquisite cellular, temporal, and genetic specificity of experimental manipulations. The recent development of work with identified neurons and their connectomes makes the larval and adult fly brains ripe as models for pushing our understanding of neural bases for these higher- order conditioning phenomena. Broader Impacts: Public health: These analyses and the conceptual framework of prediction error processing underlying them have a profound impact on our understanding of reinforcement-related behavior in humans, including monetary rewards and the mnemonic consequences of traumatic experiences, and for pathologies of the dopamine reinforcement system. Educational: This project will provide interdisciplinary training for postdoctoral researchers, Ph.D. and undergraduate students. The PIs will act as co-supervisors or mentors of students working in the different labs via face-to-face and internet-based technologies. We will also work with ASU’s award-winning Ask- A-Biologist program. This is an online science program designed to enrich the learning experiences of students of all ages and to provide classroom material for use by K-12 teachers. We will develop an extension of a game developed under a prior NSF award, and the new game will include modules to teach K-12 students about how insects learn. We will also integrate into the AAB site a program developed by a collaborator (B Gerber) at the Leibniz Institut für Neurobiologie, Magdeburg, and now in use in schools in Germany, to teach K-12 students how to train animals using the fruit fly larval learning paradigm. Underrepresented groups: All PIs will work with their university offices of Academic Diversity and Equal Opportunity for reaching underrepresented students.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

Risks Associated with Sharing the MOSSAIC APIs

The MOSSAIC APIs contain two files which, in theory, could be used to discover information about the pathology report data from the SEER registries on which the AI models were trained. In this document, we explain the contents of these files and assess the associated risk. APPENDIX A contains a set of slides to aid in the dissemination of this information.

97 MATHEMATICS AND COMPUTING↗
DOE OSTI2025

LDRD 2024 Annual Report: Laboratory Directed Research and Development Program Activities

One fundamental question underlying all living organisms is the need to understand their hierarchical organizations and physical changes with the necessary spatial and temporal resolutions under physiological or pathological conditions. This is a multi-scale challenge requiring imaging from sub-nanometers to micrometers in a cellular context. While individual imaging techniques are available, there is a critical need to integrate them into a workflow capability. Our objective is to develop an integrated multi-disciplinary and multi-scale bioimaging capability at Brookhaven National Laboratory (BNL). The capability expands BNL’s existing facility operation program in bioimaging and positions BNL in a leadership position in bioimaging research. The capability also addresses the grand challenges of the Department of Energy (DOE) science programs for national bioenergy sustainability and security.

99 GENERAL AND MISCELLANEOUS↗
DOE OSTI2026

Human RNome Project draft human RNome sequence of GM12878, B-cell line, obtained by mass-spectrometry sequencing, long-read sequencing and short-read sequencing.

Here we report the first draft of the human RNome sequence, a reference map of RNA chemical modifications in a human B-cell line. RNA carries a diverse repertoire of chemical modifications that regulate gene expression, cellular function, and responses to physiological and pathological cues. Yet, unlike the genome, no reference map of RNA modifications is available for any human cell. To generate this resource, the Human RNome Project Consortium analyzed a shared RNA preparation from the well-characterized GM12878 B-cell line using short-read sequencing, long-read direct RNA sequencing, and mass spectrometry, generating more than 7.1 billion sequencing reads spanning approximately 1.2 trillion nucleotides. The resulting maps of the human RNome reveal that RNA modifications are organized according to function, transcript architecture, and cellular identity. Modifications concentrate at functional centers of ribosomal and transfer RNAs, follow the canonical topology of N6-methyladenosine in coding transcripts, and form coordinated hotspots in immune regulatory genes. This first reference human RNome provides a foundation for understanding how RNA chemistry shapes cellular identity, human disease, and the development of RNA-based therapeutics.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

Proteome-wide characterization of PTMs reveals host cell responses to viral infection and identifies putative antiviral drug targets

Post-translational modifications (PTMs) are biochemical modifications that can significantly alter protein structure, function, stability, localization, and interactions with other molecules, thereby activating or inactivating intracellular processes. A growing body of research has begun to highlight the role of PTMs, including phosphorylation, ubiquitination, acetylation, and redox modifications, during virus-host interactions. Collectively, these PTMs regulate key steps in mounting the host immune response and control critical host pathways required for productive viral replication. This has led to the conception of antiviral therapeutics that focus on controlling host protein PTMs, potentially offering pathogen-agnostic treatment options and revolutionizing our capacity to prevent virus transmission. On the other hand, viruses can hijack the host cellular PTM machinery to modify viral proteins in promoting viral replication and evading immune surveillance. PTM regulation during virus-host interactions is complex and poorly mapped, and the development of effective PTM-targeted antiviral drugs will require a more comprehensive understanding of the cellular pathways essential for virus replication. In this review, we discuss the roles of PTMs in virus infection and how technological advances in mass spectrometry-based proteomics can capture systems-level PTM changes during viral infection. Additionally, we explore how such knowledge is leveraged to identify PTM-targeted candidates for developing antiviral drugs. Looking ahead, studies focusing on the discovery and functional elucidation of PTMs, either on the host or viral proteins, will not only deepen our understanding of molecular pathology but also pave the way for developing better drugs to fight emerging viruses.

Immunology↗
DOE OSTI2025

Case Report: Differential diagnosis of hematuria in the emergency department: emphasizing double J stent-inferior vena cava fistula

Introduction Hematuria, a common clinical indicator of genitourinary tract pathology, arises from diverse etiologies including calculi, infections, malignancies, trauma, and iatrogenic causes. Initial evaluation requires hemodynamic assessment, identification of underlying causes, and urinary drainage optimization. This report highlights a rare case of iatrogenic hematuria secondary to double-J stent migration into the inferior vena cava. Case presentation A Chinese male presented with acute left flank pain and gross hematuria persisting for 4 h. Diagnostic imaging revealed a left ureteral stone, prompting double-J stent placement at a local hospital. Despite intervention, hematuria worsened, necessitating abdominal CT. Imaging identified proximal migration of the left double-J stent into the inferior vena cava, with no evidence of vascular injury. Due to concerns regarding inadequate drainage and infection risk, conservative management without catheter clamping was initiated prior to referral. Definitive treatment involved ureteroscopic stent removal under direct visualization at our institution, resulting in rapid symptom resolution. Conclusion This case emphasizes three critical clinical insights: (1) Persistent postoperative hematuria warrants consideration of iatrogenic causes, particularly following urologic device placement. (2) Imaging modalities, especially CT, are indispensable for detecting atypical stent migration. (3) Comprehensive history-taking must include prior urologic interventions to guide differential diagnosis. While double-J stent migration into major vessels remains exceptionally rare, its recognition prevents delayed management of potentially life-threatening complications. Clinicians should maintain heightened vigilance for device-related hematuria in patients with refractory symptoms post-procedurally, ensuring prompt imaging evaluation and multidisciplinary intervention when indicated.

Qi, Wenqi↗
DOE OSTI2024

Quantum-enhanced photoprotection in neuroprotein architectures emerges from collective light-matter interactions

Background Superradiance is the phenomenon of many identical quantum systems absorbing and/or emitting photons collectively at a higher rate than any one system can individually. This phenomenon has been studied analytically in idealized distributions of electronic two-level systems (TLSs), each with a ground and excited state, as well as numerically in realistic photosynthetic nanotubes and cytoskeletal architectures. Methods Superradiant effects are studied here in idealized toy model systems and realistic biological mega-networks of tryptophan (Trp) molecules, which are strongly fluorescent amino acids found in many proteins. Each Trp molecule acts as a chromophore absorbing in the ultraviolet spectrum and can be treated approximately as a TLS, with its 1 L a excited singlet state; thus, organized Trp networks can exhibit superradiance. Such networks are found, for example, in microtubules, actin filaments, and amyloid fibrils. Microtubules and actin filaments are spiral-cylindrical protein polymers that play significant biological roles as primary constituents of the eukaryotic cytoskeleton, while amyloid fibrils have been targeted in a variety of neurodegenerative diseases. We treat these proteinaceous Trp networks as open quantum systems, using a non-Hermitian Hamiltonian to describe interactions of the chromophore network with the electromagnetic field. We numerically diagonalize the Hamiltonian to obtain its complex eigenvalues, where the real part is the energy and the imaginary part is its associated enhancement rate. We also consider multiple realizations of increasing static disorder in either the site energies or the decay rates. Results We obtained the energies and enhancement rates for realistic microtubules, actin filament bundles, and amyloid fibrils of differing lengths, and we use these values to calculate the quantum yield, which is the ratio of the number of photons emitted to the number of photons absorbed. We find that all three of these structures exhibit highly superradiant states near the low-energy portion of the spectrum, which enhances the magnitude and robustness of the quantum yield to static disorder and thermal noise. Conclusion The high quantum yield and stable superradiant states in these biological architectures may play a photoprotective rolein vivo, downconverting energetic ultraviolet photons—absorbed from those emitted by reactive free radical species—to longer, safer wavelengths and thereby mitigating biochemical stress and photophysical damage. Contrary to conventional assumptions that quantum effects cannot survive in large biosystems at high temperatures, our results suggest that macropolymeric collectives of TLSs in microtubules, actin filaments, and amyloid fibrils exhibit increasingly observable and robust effects with increasing length, up to the micron scale, due to quantum coherent interactions in the single-photon limit. Superradiant enhancement and high quantum yield exhibited in neuroprotein polymers could thus play a crucial role in information processing in the brain, the development of neurodegenerative diseases such as Alzheimer’s and related dementias, and a wide array of other pathologies characterized by anomalous protein aggregates.

Physics↗
DOE OSTI2024

Decoding FGF/FGFR Signaling: Insights into Biological Functions and Disease Relevance

Fibroblast Growth Factors (FGFs) and their cognate receptors, FGFRs, play pivotal roles in a plethora of biological processes, including cell proliferation, differentiation, tissue repair, and metabolic homeostasis. This review provides a comprehensive overview of FGF-FGFR signaling pathways while highlighting their complex regulatory mechanisms and interconnections with other signaling networks. Further, we briefly discuss the FGFs involvement in developmental, metabolic, and housekeeping functions. By complementing current knowledge and emerging research, this review aims to enhance the understanding of FGF-FGFR-mediated signaling and its implications for health and disease, which will be crucial for therapeutic development against FGF-related pathological conditions.

Edirisinghe, Oshadi↗
DOE OSTI2024

Loss of Mitochondrial Tusc2/Fus1 Triggers a Brain Pro-Inflammatory Microenvironment and Early Spatial Memory Impairment

Brain pathological changes impair cognition early in disease etiology. There is an urgent need to understand aging-linked mechanisms of early memory loss to develop therapeutic strategies and prevent the development of cognitive impairment. Tusc2 is a mitochondrial-resident protein regulating Ca 2+ fluxes to and from mitochondria impacting overall health. We previously reported that Tusc2 –/– female mice develop chronic inflammation and age prematurely, causing age- and sex-dependent spatial memory deficits at 5 months old. Therefore, we investigated Tusc2-dependent mechanisms of memory impairment in 4-month-old mice, comparing changes in resident and brain-infiltrating immune cells. Interestingly, Tusc2 –/– female mice demonstrated a pro-inflammatory increase in astrocytes, expression of IFN-γ in CD4 + T cells and Granzyme-B in CD8 + T cells. We also found fewer FOXP3 + T-regulatory cells and Ly49G + NK and Ly49G + NKT cells in female Tusc2 –/– brains, suggesting a dampened anti-inflammatory response. Moreover, Tusc2 –/– hippocampi exhibited Tusc2- and sex-specific protein changes associated with brain plasticity, including mTOR activation, and Calbindin and CamKII dysregulation affecting intracellular Ca2 + dynamics. Overall, the data suggest that dysregulation of Ca 2+ -dependent processes and a heightened pro-inflammatory brain microenvironment in Tusc2 –/– mice could underlie cognitive impairment. Thus, strategies to modulate the mitochondrial Tusc2- and Ca 2+ - signaling pathways in the brain should be explored to improve cognitive health.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

Potential Role of Malassezia restricta in Pterygium Development

Pterygium is a condition affecting the ocular surface, marked by a triangular-shaped growth of fibrotic tissue extending from the nasal conjunctiva toward the corneal center, potentially causing visual impairment. While ultraviolet (UV )light exposure is the primary risk factor for pterygium, its underlying cause remains unclear. In order to better understand the true genesis of pterygium development, we investigated pterygium tissue and compared it with healthy conjunctiva controls. Given the eye’s direct environmental exposure, we analyzed the microbiota composition using metagenomic sequencing of pterygium tissue to identify microbes potentially associated with this condition. Metagenomic sequencing revealed a higher prevalence of the fungus Malassezia restricta in five pterygium samples, confirmed by in situ hybridization. The CHIT1 gene, which plays a role in antifungal defenses, displayed the highest expression in five pterygium tissue samples compared to healthy conjunctiva controls, suggesting the potential involvement of Malassezia restricta in pterygium development. Gene expression profiling of pterygium highlighted an IL-33 and IL-4 gene expression signature, along with an increased presence of M2 macrophages, emphasizing their role in promoting fibrosis—a hallmark feature of pterygium. The detection of Malassezia restricta in the pterygium samples and associated molecular changes provides novel insights into the ocular microbiome and raises the possibility of Malassezia’s involvement in pterygium pathology.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2025

Structural Insights into the Dynamics of Water in SOD1 Catalysis and Drug Interactions

Superoxide dismutase 1 (SOD1) is a crucial enzyme that protects cells from oxidative damage by converting superoxide radicals into H 2 O 2 and O 2 . This detoxification process, essential for cellular homeostasis, relies on a precisely orchestrated catalytic mechanism involving the copper cation, while the zinc cation contributes to the structural integrity of the enzyme. This study presents the 2.3 Å crystal structure of human SOD1 (PDB ID: 9IYK), revealing an assembly of six homodimers and twelve distinct active sites. The water molecules form a complex hydrogen-bonding network that drives proton transfer and sustains active site dynamics. Our structure also uncovers subtle conformational changes that highlight the intrinsic flexibility of SOD1, which is essential for its function. Additionally, we observe how these dynamic structural features may be linked to pathological mutations associated with amyotrophic lateral sclerosis (ALS). By advancing our understanding of hSOD1’s mechanistic intricacies and the influence of water coordination, this study offers valuable insights for developing therapeutic strategies targeting ALS. Our structure’s unique conformations and active site interactions illuminate new facets of hSOD1 function, underscoring the critical role of structural dynamics in enzyme catalysis. Moreover, we conducted a molecular docking analysis using SOD1 for potential radical scavengers and Abelson non-receptor tyrosine kinase (c-Abl, Abl1) inhibitors targeting misfolded SOD1 aggregation along with oxidative stress and apoptosis, respectively. The results showed that CHEMBL1075867, a free radical scavenger derivative, showed the most promising docking results and interactions at the binding site of hSOD1, highlighting its promising role for further studies against SOD1-mediated ALS.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2024

Products and methods for organ protection with noble nanoparticles

Products and methods for redirecting the pathological biochemical process of accumulation of reduced pyridine nucleotides under deleterious hypoxia conditions toward the reduction of the precursor salt and the biosynthesis of biologically compatible, antioxidant noble metal nanoparticles and the simultaneous restoring of the tissue redox state are provided. The products and methods have application in the treatment of hypoxia and hypoxia-related diseases and disorders. Such products and methods are also useful in organ transplantation and recovery, in screening of anti-hypoxia agents, and in detecting elevated levels of the reducing equivalents of the redox state, for example, NADH, NADPH, GSH, and TrxSH 2 , in cells, tissues, or organs.

Rozhkova, Elena A.↗