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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 379 records · Page 21
All sourcesNASA NTRSDOE OSTI
DOE OSTI2021

Patient-Reported Toxicity and Quality-of-Life Profiles in Patients With Head and Neck Cancer Treated With Definitive Radiation Therapy or Chemoradiation

Radiation therapy is an effective but burdensome treatment for head and neck cancer (HNC). We aimed to characterize the severity and time pattern of patient-reported symptoms and quality of life in a large cohort of patients with HNC treated with definitive radiation therapy, with or without systemic treatment.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2022

Evaluation of Long-Term Outcomes and Toxicity After Stereotactic Phosphorus-32–Based Intracavitary Brachytherapy in Patients With Cystic Craniopharyngioma

Interstitial brachytherapy based on phosphorus-32 (P-32) has an established role as a minimally invasive treatment modality for patients with cystic craniopharyngioma. However, reporting on long-term outcomes with toxicity profiles for large cohorts is lacking in the literature. The purpose of this study is therefore to evaluate the long-term visual, endocrinal, and neurocognitive functions in what is the largest patient series having received this treatment to date.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2022

The Impact of Radiation Therapy in Children and Adolescents With Metastatic Rhabdomyosarcoma

There is limited evidence to define the role of radiation therapy in children with metastatic rhabdomyosarcoma (mRMS). In the international BERNIE study, children with mRMS or non-RMS soft tissue sarcoma were randomized to receive standard chemotherapy with or without bevacizumab, with radiation therapy to all disease sites recommended after chemotherapy cycle 6. We retrospectively evaluated the impact of radiation therapy on survival in the mRMS cohort.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2021

Radiation Toxicity in Patients With Collagen Vascular Disease: A Meta-Analysis of Case-Control Studies

Several retrospective series have reported that patients with collagen vascular disease (CVD) are at increased risk of radiation (RT) toxicity. However, the evidence is mixed, and many series lack control groups. We performed a meta-analysis including only case-cohort or randomized studies that examined the risk of RT toxicity for patients with CVD compared with controls.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2022

Analysis of antibodies from HCV elite neutralizers identifies genetic determinants of broad neutralization

The high genetic diversity of hepatitis C virus (HCV) complicates effective vaccine development. We screened a cohort of 435 HCV-infected individuals and found that 2%–5% demonstrated outstanding HCV-neutralizing activity. From four of these patients, we isolated 310 HCV antibodies, including neutralizing antibodies with exceptional breadth and potency. High neutralizing activity was enabled by the use of the VH1-69 heavy-chain gene segment, somatic mutations within CDRH1, and CDRH2 hydrophobicity. Structural and mutational analyses revealed an important role for mutations replacing the serines at positions 30 and 31, as well as the presence of neutral and hydrophobic residues at the tip of the CDRH3. Based on these characteristics, we computationally created a de novo antibody with a fully synthetic VH1-69 heavy chain that efficiently neutralized multiple HCV genotypes. Finally, our findings provide a deep understanding of the generation of broadly HCV-neutralizing antibodies that can guide the design of effective vaccine candidates.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2025

Structural basis of heme scavenging by the ChtA and HtaA hemophores in Corynebacterium diphtheriae

Corynebacterium diphtheriae causes diphtheria, a potentially fatal infectious disease that damages tissues in the upper respiratory tract. In order to proliferate, this pathogen acquires the essential nutrient iron from heme (iron-protoporphyrin IX) primarily found in human hemoglobin (Hb). C. diphtheriae secretes ChtA and HtaA hemophore proteins that bind ferric heme (hemin) via conserved region (CR) domains. Here, we demonstrate that their CR domains scavenge hemin after it is spontaneously released from Hb, and define the structural basis of hemin binding to ChtA and the N-terminal CR domain from HtaA by determining X-ray crystal structures of their protein-hemin complexes. Resonance Raman and electron paramagnetic resonance experiments demonstrate that the CR domains from ChtA and HtaA engage in pentacoordinate hemin binding through a conserved iron-tyrosyl linkage, though variations in their hemin pockets alter the way they stabilize the axial tyrosine and mask hemin’s metal. The importance of these interactions is probed using isothermal titration calorimetry experiments, which represent the first quantitative assessment of CR-hemin affinity and reveal that ChtA binds hemin via an enthalpically driven process. Hemin partitioning experiments using native mass spectrometry demonstrate that the cohort of CR domains within C. diphtheriae ’s hemin-uptake system have dissociation constants for hemin between 0.8 and 22 nM, raising the possibility that affinity differences contribute to the directional flow of hemin into the cell. Collectively, the results of this work provide insight into how C. diphtheriae and other pathogenic and commensal corynebacterium species utilize CR domains to scavenge iron rich hemin from their environment.

Corynebacterium diphtheriae↗
DOE OSTI2024

Aligning lithium metal battery research and development across academia and industry

Successful integration of metallic lithium anodes into secondary batteries could enhance energy density and enable new forms of electrified transportation. However, the outlook for widespread lithium metal adoption in energy storage devices remains mixed. This comes in part from existing gaps in our understanding of the relationships connecting the initial state of lithium, its evolution with cycling, and end-of-life state. It remains important to develop standardized protocols for material and cell characterization, cycling performance, safety, and recycling procedures for lithium metal-based batteries. In February 2023 a cohort of scientists and engineers from academia, national laboratories, and industry gathered to converge on a list of critical challenges and action items to provide better understanding of lithium metal evolution and to enhance academic, governmental, and industrial partnerships to address these challenges. Here, we highlight the major discussion topics revolving around the manufacturing of lithium metal, its related metrology and integration into battery form factors, and best practices testing its electrochemical performance relevant to automotive applications. We introduce a power-controlled discharge testing protocol for research and development cells, in alignment between major automotive stakeholders, that may reveal lithium metal battery dynamics closer to practical driving behavior.

25 ENERGY STORAGE↗
DOE OSTI2025

Comparison of Expert Vocabulary Usage Patterns Between Mental Health and Nonmental Health Clinicians When Diagnosing Pediatric Anxiety Disorders

Objective: To compare the utilization patterns of expert vocabulary (EVo) in diagnosing pediatric anxiety between mental health and non-mental health clinical notes from electronic health records to understand the role of Evo in informing classification and decision-making in anxiety diagnoses. Study design: We conducted a retrospective study using a cohort less than age 25 from Cincinnati Children's Hospital including 897 685 patients with 61 586 446 notes. We analyzed EVo, collected from mental health clinicians, in both mental and nonmental health notes. We compared classification accuracy using EVo-based patient-level embedding from all clinical notes, mental-health notes, and nonmental health notes for 2 tasks: 1) pre-vs postdiagnosis anxiety patients, and 2) prediagnosis anxiety vs nonanxiety patients. Results: EVo usage was highest in prediagnosis anxiety, lower in nonanxiety, and lowest in post-diagnosis. Classification models using EVo features from all, mental-health, and non-mental health notes showed similar F1 scores for prediagnosis anxiety (0.70 ± 0.2 for 2 categories). For anxiety vs nonanxiety classification, all clinical and nonmental health notes had better F1 scores than mental-health notes (above 0.90 for 3 categories). There was a notable difference in class-wise performance across both tasks. Conclusions: There are significant differences in anxiety EVo use between mental health and nonmental health clinicians. Despite less anxiety-specific terminology, non-mental health notes still captured key aspects of patient presentations, emphasizing the importance of including all clinicians' notes in analysis. EVo's utility for anxiety classification is most effective in prediagnostic phases, suggesting the need for a dedicated diagnostic lexicon and further study before incorporating EVo into classification models.

feature engineering↗
DOE OSTI2023

Vaccination compartmental epidemiological models for the delta and omicron SARS-CoV-2 variants

We explore the inclusion of vaccination in compartmental epidemiological models concerning the delta and omicron variants of the SARS-CoV-2 virus that caused the COVID-19 pandemic. We expand on our earlier compartmental-model work by incorporating vaccinated populations. We present two classes of models that differ depending on the immunological properties of the variant. The first one is for the delta variant, where we do not follow the dynamics of the vaccinated individuals since infections of vaccinated individuals were rare. The second one for the far more contagious omicron variant incorporates the evolution of the infections within the vaccinated cohort. We explore comparisons with available data involving two possible classes of counts, fatalities and hospitalizations. We present our results for two regions, Andalusia and Switzerland (including the Principality of Liechtenstein), where the necessary data are available. In the majority of the considered cases, the models are found to yield good agreement with the data and have a reasonable predictive capability beyond their training window, rendering them potentially useful tools for the interpretation of the COVID-19 and further pandemic waves, and for the design of intervention strategies during these waves.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2025

Discovery of Proteoforms Associated With Alzheimer's Disease Through Quantitative Top-Down Proteomics

The complex nature of Alzheimer's disease (AD) and its heterogenous clinical presentation has prompted numerous large-scale - omic analyses aimed at providing a global understanding of the pathophysiological processes involved. AD involves isoforms, proteolytic products, and posttranslationally modified proteins such as amyloid beta (Aβ) and microtubule-associated protein tau. Top-down proteomics directly measures these species and thus, offers a comprehensive view of pathologically relevant proteoforms that are difficult to analyze using traditional proteomic techniques. Here, we broadly explored associations between proteoforms and clinicopathological traits of AD by deploying a quantitative top-down proteomics approach across frontal cortex of 103 subjects selected from the ROS and MAP cohorts. The approach identified 1213 proteins and 11,782 proteoforms, of which 154 proteoforms had at least one significant association with a clinicopathological phenotype. One important finding included identifying Aβ C-terminal truncation state as the key property for differential association between amyloid plaques and cerebral amyloid angiopathy. Furthermore, various N-terminally truncated forms of Aβ had noticeably stronger association with amyloid plaques and global cognitive function. Additionally, we discovered six VGF neuropeptides that were positively associated with cognitive function independent of pathological burden. The database of brain cortex proteoforms provides a valuable context for functional characterization of the proteins involved in AD and other late-onset brain pathologies.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2025

The temporal onset of associations of cortical proteins with cognitive resilience vary during late life

Background: Cortical proteins associated with cognitive resilience have been identified but their temporal onset in older adults is unknown. We present a multistage approach to first identify cortical proteins associated with cognitive resilience and then examine their associated temporal onset. Methods: We used data from a subset of 1088 decedents from two cohort-studies who had selected reaction monitoring proteomics from the dorsolateral prefrontal cortex, and at least 3 cognitive assessments. Cognition was assessed using a composite derived from 19 tests. We first used linear mixed-effects models to identify cortical proteins associated with cognitive resilience. We then used functional mixed-effects models to examine non-linear associations between proteins and cognitive resilience to identify their temporal onset. Results: Mean age at death was 90 years (SD = 6.4); 69 % were female. On average, cognition started to decline at around 15 years before death, with accelerated decline in the last 7 years. We identified 40 proteins associated with cognitive resilience, of which 17 proteins also showed non-linear associations. Non-linear associations indicated that higher levels of 10 proteins were associated with slower cognitive decline between 23 and 4 years before death. In contrast, higher levels of 7 proteins were associated with faster decline only within the last 7 years before death. Conclusions: Cognitive resilience proteins are differentially related to late-life cognitive aging; the onset of proteins that maintain cognition may begin many years before the onset of proteins that hasten cognitive decline. The temporal onset of cognitive resilience proteins may be crucial for timing efficacious interventions.

Zammit, Andrea↗
DOE OSTI2024

Vascular endothelial growth factor receptor-1 (FLT1) interactions with amyloid-beta in Alzheimer’s disease: A putative biomarker of amyloid-induced vascular damage

We have identified FLT1 as a protein that changes during Alzheimer's disease (AD) whereby higher brain protein levels are associated with more amyloid, more tau, and faster longitudinal cognitive decline. Given FLT1's role in angiogenesis and immune activation, we hypothesized that FLT1 is upregulated in response to amyloid pathology, driving a vascular-immune cascade resulting in neurodegeneration and cognitive decline. We sought to determine (1) if in vivo FLT1 levels (CSF and plasma) associate with biomarkers of AD neuropathology or differ between diagnostic staging in an aged cohort enriched for early disease, and (2) whether FLT1 expression interacts with amyloid on downstream outcomes, such as phosphorylated tau levels and cognitive performance. Additionally, we sought to replicate FLT1 interactions in the brain. The results showed that higher levels of FLT1 in CSF and post-mortem brain tissue related to increased tau, particularly among amyloid positive individuals. These analyses help clarify the potential utility of FLT1 as a biomarker among individuals with evidence of brain amyloidosis.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2022

Uncovering novel mutational signatures by de novo extraction with SigProfilerExtractor

Mutational signature analysis is commonly performed in cancer genomic studies. Here, we present SigProfilerExtractor, an automated tool for de novo extraction of mutational signatures, and benchmark it against another 13 bioinformatics tools by using 34 scenarios encompassing 2,500 simulated signatures found in 60,000 synthetic genomes and 20,000 synthetic exomes. For simulations with 5% noise, reflecting high-quality datasets, SigProfilerExtractor outperforms other approaches by elucidating between 20% and 50% more true-positive signatures while yielding 5-fold less false-positive signatures. Applying SigProfilerExtractor to 4,643 whole-genome- and 19,184 whole-exome-sequenced cancers reveals four novel signatures. Two of the signatures are confirmed in independent cohorts, and one of these signatures is associated with tobacco smoking. In summary, this report provides a reference tool for analysis of mutational signatures, a comprehensive benchmarking of bioinformatics tools for extracting signatures, and several novel mutational signatures, including one putatively attributed to direct tobacco smoking mutagenesis in bladder tissues.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

A data mining approach to investigate food groups related to incidence of bladder cancer in the BLadder cancer Epidemiology and Nutritional Determinants International Study

Abstract At present, analysis of diet and bladder cancer (BC) is mostly based on the intake of individual foods. The examination of food combinations provides a scope to deal with the complexity and unpredictability of the diet and aims to overcome the limitations of the study of nutrients and foods in isolation. This article aims to demonstrate the usability of supervised data mining methods to extract the food groups related to BC. In order to derive key food groups associated with BC risk, we applied the data mining technique C5.0 with 10-fold cross-validation in the BLadder cancer Epidemiology and Nutritional Determinants study, including data from eighteen case–control and one nested case–cohort study, compromising 8320 BC cases out of 31 551 participants. Dietary data, on the eleven main food groups of the Eurocode 2 Core classification codebook, and relevant non-diet data (i.e. sex, age and smoking status) were available. Primarily, five key food groups were extracted; in order of importance, beverages (non-milk); grains and grain products; vegetables and vegetable products; fats, oils and their products; meats and meat products were associated with BC risk. Since these food groups are corresponded with previously proposed BC-related dietary factors, data mining seems to be a promising technique in the field of nutritional epidemiology and deserves further examination.

Nutrition & Dietetics↗
DOE OSTI2021

Lifetime risk of suicide among survivors of the atomic bombings of Japan

Abstract Aims The long-term physical health effects of the atomic bombings of Hiroshima and Nagasaki are well characterised, but the psychological effects remain unclear. Therefore, we sought to determine whether measures of exposure severity, as indirect measures of psychological trauma arising from exposure to the atomic bombings, are associated with suicide mortality among atomic bomb survivors. Methods The Life Span Study is a prospective cohort study of 93 741 Japanese atomic bomb survivors who were located within 10 km of the hypocentre in Hiroshima or Nagasaki at the time of the bombings in 1945, and 26 579 residents of Hiroshima and Nagasaki who were not in either city at the time of the bombings, matched to survivors on city, sex and age. Measures of exposure severity included: proximity to the hypocentre, type of shielding between the survivor and the blast and self-reported occurrence of acute radiation and thermal injuries. Date of death was obtained from the Japanese National Family Registry system. Cause of death was obtained from death certificates. Adjusted hazard ratios (HRs) were estimated from Cox regression models overall and stratified by sex and age. Results During the 60-year follow-up period (1950–2009), 1150 suicide deaths were recorded among 120 231 participants (23.6 per 100 000 person-years): 510 among 70 092 women (17.2 per 100 000 person-years) and 640 among 50 139 men (33.6 per 100 000 person-years). Overall, there was no association of proximity, type of shielding or the occurrence of acute injuries with suicide mortality. Among those <25 years of age at the time of the bombings, increased suicide risk was observed for survivors outside v . shielded inside any structure (HR: 1.24; 95% confidence interval (CI): 1.03, 1.48; interaction p = 0.054) and for those who reported flash burns (HR: 1.32; 95% CI: 1.00, 1.73; interaction p = 0.025). Sex-stratified analyses indicated that these associations were limited to men. Among women, closer proximity to the hypocentre was associated with a non-significant increase in suicide risk, with a positive association between proximity and suicide risk observed among women <15 years of age (HR: 1.09 per km; 95% CI: 1.00, 1.18; interaction p = 0.067). Conclusions Proximity to the hypocentre, shielding and acute injury presence do not generally appear to influence suicide mortality among atomic bomb survivors. However, heterogeneity may exist by age and sex, with younger survivors potentially more sensitive to psychological trauma. Coupled with other studies, our results suggest the importance of long-term monitoring of mental health among young populations exposed to catastrophic events or mass trauma.

Psychiatry↗
DOE OSTI2025

Tethered from the Head and from the Tail: The Structure of Hydroxyl-Functionalized Ionic Liquids

Ionic liquids with special functionalities are synthesized with the specific purpose of creating new patterns of interaction in the condensed phase. This Letter discusses the case of alcohol-functionalized ILs, the so-called HFILs, which are part of the larger cohort of task-specific ionic liquids. We find that this small chemical modification can cause massive changes in the liquid landscape when the cationic tails are longer. For prototypical ionic liquids, larger alkyl tails act as separators of charge networks, but in the case of HFILs these become physical charge network linkers. The OH functionality adds a large repertoire of interactions and correlations that were mostly unavailable to traditional ILs.

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

Block Design with Common Reference Samples Enables Robust Large-Scale Label-Free Quantitative Proteome Profiling

Label-free quantitative proteomics has become an increasingly popular tool for profiling global protein abundances. However, one major weakness is the potential performance drift of the LC-MS platform over time, which in turn limits its utility for analyzing large-scale sample sets. To address this, in this work we introduce an experimental and data analysis scheme based on a block-design with common controls within each block for enabling LC-MS-based large-scale label-free quantification. In this scheme, a large number of samples (e.g., >100 samples) are analyzed in smaller, and more manageable blocks, minimizing instrument drift and variability within a block. Furthermore, each designated block also contains common controls (or reference) samples for normalization within and across blocks. We demonstrated the effectiveness of this method by profiling the proteome response of human macrophage THP-1 cells to 11 engineered nanomaterials (ENMs) at two different doses. A total of 116 samples were analyzed in six blocks, yielding an average coverage of 4500 proteins per sample. The data revealed consistent quantification of proteins across all six blocks, as shown by highly stable quantification of house-keeping proteins in all samples and high levels of quantification correlation among samples from different blocks. The data also demonstrated that label-free quantification is robust and accurate enough to quantify even very subtle abundance changes as well as large fold-changes without potential ratio compression as often encountered with isobaric labeling. Our streamlined workflow is easy to implement and can be readily adapted to other large cohort studies for reproducible label-free proteome quantification.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

Functional Design of Peptide Materials Based on Supramolecular Cohesion

Peptide materials offer a broad platform to design biomimetic soft matter, and filamentous networks that emulate those in extracellular matrices and the cytoskeleton are among the important targets. Given the vast sequence space, a combination of computational approaches and readily accessible experimental techniques is required to design peptide materials efficiently. Here, we report here on a strategy that utilizes this combination to predict supramolecular cohesion within filaments of peptide amphiphiles, a property recently linked to supramolecular dynamics and consequently bioactivity. Using established coarse-grained simulations on 10,000 randomly generated peptide sequences, we identified 3500 likely to self-assemble in water into nanoscale filaments. Atomistic simulations of small clusters were used to further analyze this subset of sequences and identify mathematical descriptors that are predictive of intermolecular cohesion, which was the main purpose of this work. We arbitrarily selected a small cohort of these sequences for chemical synthesis and verified their fiber morphology. With further characterization, we were able to link the latent heat associated with fiber to micelle transitions, an indicator of cohesion and potential supramolecular dynamicity within the filaments, to calculated hydrogen bond densities in the simulation clusters. Based on validation from in situ synchrotron X-ray scattering and differential scanning calorimetry, we conclude that the phase transitions can be easily observed by very simple polarized light microscopy experiments. We are encouraged by the methodology explored here as a relatively low-cost and fast way to design potential functions of peptide materials.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗