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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 OSTI2015

SU-F-BRB-02: Towards Quantitative Clinical Decision On Deep Inspiration Breath Hold (DIBH) Or Prone for Left-Sided Breast Irradiation

Purpose: To develop quantitative clinical guidelines between supine Deep Inspiratory Breath Hold (DIBH) and prone free breathing treatments for breast patients, we applied 3D deformable phantoms to perform Monte Carlo simulation to predict corresponding Dose to the Organs at Risk (OARs). Methods: The RPI-adult female phantom (two selected cup sizes: A and D) was used to represent the female patient, and it was simulated using the MCNP6 Monte Carlo code. Doses to OARs were investigated for supine DIBH and prone treatments, considering two breast sizes. The fluence maps of the 6-MV opposed tangential fields were exported. In the Monte Carlo simulation, the fluence maps allow each simulated photon particle to be weighed in the final dose calculation. The relative error of all dose calculations was kept below 5% by simulating 3*10{sup 7} photons for each projection. Results: In terms of dosimetric accuracy, the RPI Adult Female phantom with cup size D in DIBH positioning matched with a DIBH treatment plan of the patient. Based on the simulation results, for cup size D phantom, prone positioning reduced the cardiac dose and the dose to other OARs, while cup size A phantom benefits more from DIBH positioning. Comparing simulation results for cup size A and D phantom, dose to OARs was generally higher for the large breast size due to increased scattering arising from a larger portion of the body in the primary beam. The lower dose that was registered for the heart in the large breast phantom in prone positioning was due to the increase of the distance between the heart and the primary beam when the breast was pendulous. Conclusion: Our 3D deformable phantom appears an excellent tool to predict dose to the OARs for the supine DIBH and prone positions, which might help quantitative clinical decisions. Further investigation will be conducted. National Institutes of Health R01EB015478.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Geographic variation in body size and sexual size dimorphism of North American Ratsnakes ( Pantherophis spp. s.l.)

Because body size affects nearly all facets of an organism’s life history, ecologists have long been interested in large-scale patterns of body-size variation, as well as why those large-scale patterns often differ between sexes. We explored body-size variation across the range of the sexually dimorphic Ratsnake complex (species of the genus Pantherophis Fitzinger, 1843 s.l.; formerly Elaphe obsoleta (Say in James, 1823)) in North America. We specifically explored whether variation in body size followed latitudinal patterns or varied with climatic variables. We found that body size did not conform to a climatic or latitudinal gradient, but instead, some of the populations with the largest snakes occurred near the core of the geographic range and some with the smallest occurred near the northern, western, and southern peripheries of the range. Males averaged 14% larger than females, although the degree of sexual size dimorphism varied between populations (range: 2%–25%). There was a weak trend for male body size to change in relation to temperature, whereas female body size did not. Our results indicate that relationships between climate and an ectotherm’s body size are more complicated than linear latitudinal clines and likely differ for males and females.

Zoology↗
DOE OSTI2024

Organochlorine pesticides and risk of papillary thyroid cancer in U.S. military personnel: a nested case-control study

Background: The effects of organochlorine pesticide (OCP) exposure on the development of human papillary thyroid cancer (PTC) are not well understood. A nested case-control study was conducted with data from the U.S. Department of Defense Serum Repository (DoDSR) cohort between 2000 and 2013 to assess associations of individual OCPs serum concentrations with PTC risk. Methods: This study included 742 histologically confirmed PTC cases (341 females, 401 males) and 742 individually-matched controls with pre-diagnostic serum samples selected from the DoDSR. Associations between categories of lipid-corrected serum concentrations of seven OCPs and PTC risk were evaluated for classical PTC and follicular PTC using conditional logistic regression, adjusted for body mass index category and military branch to compute odds ratios (OR) and 95% confidence intervals (CIs). Effect modification by sex, birth cohort, and race was examined. Results: There was no evidence of associations between most of the OCPs and PTC, overall or stratified by histological subtype. Overall, there was no evidence of an association between hexachlorobenzene (HCB) and PTC, but stratified by histological subtype HCB was associated with significantly increased risk of classical PTC (third tertile above the limit of detection (LOD) vs. <LOD, OR = 1.61, 95% CI, 1.09, 2.38; p for trend = 0.05) and significantly decreased risk of follicular variant PTC (third tertile above the limit of detection (LOD) vs. <LOD, OR = 0.38, 95% CI, 0.16, 0.91; p for trend = 0.04). Further stratified by sex, risk of classical PTC was higher for females (third tertile above LOD vs. <LOD, OR = 2.23, 95% CI: 1.23, 4.06; p-trend = 0.02) than for males (OR = 1.22, 95%CI: 0.72–2.08; p-trend = 0.56), though the test for interaction by sex was not statistically significant (p-interaction = 0.30). Similarly, β-hexachlorocyclohexane (β-HCCH) was associated with a higher risk for classical PTC for women with concentrations ≥LOD versus <LOD (OR = 1.76, 95% CI: 1.07, 2.89), while the effects were null for men. There were no consistent trends when stratified by race or birth year. Conclusions: The U.S. Environmental Protection Agency has classified HCB and other OCPs we studied here as probable human carcinogens. Our findings of increased risks for classical PTC associated with increased concentrations of HCB and β-HCCH, which were stronger among females, should be replicated in future studies of other populations.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

Lead Exposure during Early Human Development and DNA Methylation of Imprinted Gene Regulatory Elements in Adulthood

Here, lead exposure during early development causes neurodevelopmental disorders by unknown mechanisms. Epidemiologic studies have focused recently on determining associations between lead exposure and global DNA methylation; however, such approaches preclude the identification of loci that may alter human disease risk. The objective of this study was to determine whether maternal, postnatal, and early childhood lead exposure can alter the differentially methylated regions (DMRs) that control the monoallelic expression of imprinted genes involved in metabolism, growth, and development. Questionnaire data and serial blood lead levels were obtained from 105 participants (64 females, 41 males) of the Cincinnati Lead Study from birth to 78 months. When participants were adults, we used Sequenom EpiTYPER assays to test peripheral blood DNA to quantify CpG methylation in peripheral blood leukocytes at DMRs of 22 human imprinted genes. Statistical analyses were conducted using linear regression. Mean blood lead concentration from birth to 78 months was associated with a significant decrease in PEG3 DMR methylation (β = –0.0014; 95% CI: –0.0023, –0.0005, p = 0.002), stronger in males (β = –0.0024; 95% CI: –0.0038, –0.0009, p = 0.003) than in females (β = –0.0009; 95% CI: –0.0020, 0.0003, p = 0.1). Elevated mean childhood blood lead concentration was also associated with a significant decrease in IGF2/H19 (β = –0.0013; 95% CI: –0.0023, –0.0003, p = 0.01) DMR methylation, but primarily in females, (β = –0.0017; 95% CI: –0.0029, –0.0006, p = 0.005) rather than in males, (β = –0.0004; 95% CI: –0.0023, 0.0015, p = 0.7). Elevated blood lead concentration during the neonatal period was associated with higher PLAGL1/HYMAI DMR methylation regardless of sex (β = 0.0075; 95% CI: 0.0018, 0.0132, p = 0.01). The magnitude of associations between cumulative lead exposure and CpG methylation remained unaltered from 30 to 78 months. Our findings provide evidence that early childhood lead exposure results in sexdependent and gene-specific DNA methylation differences in the DMRs of PEG3, IGF2/H19, and PLAGL1/HYMAI in adulthood.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2014

Neural Correlates of Gender Differences in Reputation Building

Gender differences in cooperative choices and their neural correlates were investigated in a situation where reputation represented a crucial issue. Males and females were involved in an economic exchange (trust game) where economic and reputational payoffs had to be balanced in order to increase personal welfare. At the behavioral level, females showed a stronger reaction to negative reputation judgments that led to higher cooperation than males, measured by back transfers in the game. The neuroanatomical counterpart of this gender difference was found within the reward network (engaged in producing expectations of positive results) and reputation-related brain networks, such as the self-control network (engaged in strategically resisting the temptation to defect) and the mentalizing network (engaged in thinking about how one is viewed by others), in which the dorsolateral prefrontal cortex (DLPFC) and the medial (M)PFC respectively play a crucial role. Furthermore, both DLPFC and MPFC activity correlated with the amount of back transfer, as well as with the personality dimensions assessed with the Big-Five Questionnaire (BFQ-2). Males, according to their greater DLPFC recruitment and their higher level of the BFQ-2 subscale of Dominance, were more focused on implementing a profit-maximizing strategy, pursuing this target irrespectively of others’ judgments. On the contrary, females, according to their greater MPFC activity and their lower level of Dominance, were more focused on the reputation per se and not on the strategic component of reputation building. These findings shed light on the sexual dimorphism related to cooperative behavior and its neural correlates.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2018

Preconception paternal bisphenol A exposure induces sex-specific anxiety and depression behaviors in adult rats

Bisphenol A (BPA), an environmental endocrine-disrupting compound, has drawn a great attention for its adverse effect on behavioral development. Maternal exposure to this compound has been reported to induce anxiety and depression in offspring, but the effect of its paternal exposure is rarely discussed. This study investigated whether preconception paternal BPA exposure can affect the emotions of male rats and their offspring. Eighteen adult male rats (F0) received either a vehicle or 50 μg/kg/day BPA diet for 21 weeks and were then mated with non-exposed females to produce offspring (F1). The affective behaviors of F0 and F1 rats were evaluated in the open-field test, the elevated-plus maze and the forced swimming test, and their serum corticosterone were then examined. BPA exposure induced increased anxiety behaviors along with increased serum corticosterone in F0 rats. This paternal exposure also led to increased anxiety behaviors in F1 females and aggravated depression behaviors in both sexes of F1 rats. Furthermore, only F1 females exhibited increased serum corticosterone. Overall, these data indicate that preconception paternal exposure to a low dose of BPA may induce transgenerational sex-specific impairments in the affection of adult rats.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

Age at release affects developmental physiology and sex-specific phenotypic diversity of hatchery steelhead trout (Oncorhynchus mykiss)

Most steelhead trout hatcheries increase growth rate during rearing to produce and release yearling smolts for harvest augmentation, but natural steelhead exhibit variable age of smoltification, so this common rearing practice may not be ideal for programs focused on recovering imperiled wild stocks; therefore, it is important to investigate and compare alternative hatchery rearing methods that promote life history diversity. Over six consecutive years, the Winthrop National Fish Hatchery on the Methow River, WA reared and released paired groups of age-1 (S1) and age-2 (S2) steelhead smolts. To understand how the two rearing methods affected developmental ontogeny and life-history, fish were sampled prior to hatchery release for factors associated with smoltification (size, gill Na+/K+ ATPase activity, and a qualitative smolt phenotype) and sexual maturation (sex, pituitary and testis mRNA transcripts, gonadosomatic index, and plasma 11-ketotestosterone). Our objectives were to quantify levels of smoltification and male maturation during hatchery rearing, combine metrics to estimate residualism (failure to migrate upon release), and compare the treatments by sex. Overall, S2 rearing produced 7.8% more smolts and 44-fold (4.4 vs. 0.1%) more precociously mature males than S1 rearing. Conversely, S1 rearing produced 31.6% more residuals than S2 rearing. While the proportion of total male residuals was comparable between treatments, the S1 treatment produced approximately five-fold more female residuals (20.6 vs. 4.2%). Because residuals contribute minimally to adult returns and the number of returning adult females is critical to the success of salmonid supplementation efforts, developing rearing techniques that maximize migration in females is a management priority. Physiological assessments are useful for characterizing and quantifying the effects and risks of different hatchery rearing regimes on steelhead life-history, in addition to providing sex-specific guidance to inform and optimize conservation management goals in supplementation programs.

Middleton, Mollie A. (ORCID:0009000905577865)↗
DOE OSTI2019

Radiation-Related Risk of Cancers of the Upper Digestive Tract among Japanese Atomic Bomb Survivors

As a follow-up to the comprehensive work on solid cancer incidence in the Life Span Study (LSS) cohort of atomic bomb survivors between 1958 and 1998, we report here on updated radiation risk estimates for upper digestive tract cancers. In this study, we added 11 years of follow-up (1958–2009), used improved radiation dose estimates, considered effects of smoking and alcohol consumption and performed dose-response analyses by anatomical sub-site. In examining 52 years'worth of data, we ascertained the occurrence of 394 oral cavity/pharyngeal cancers, 486 esophageal cancers and 5,661 stomach cancers among 105,444 subjects. The radiation risk for oral cavity/pharyngeal cancer, other than salivary gland, was elevated but not significantly so. In contrast, salivary gland cancer exhibited a strong linear dose response with excess relative risk (ERR) of 2.54 per Gy [95% confidence interval (CI): 0.69 to 6.1]. Radiation risk decreased considerably with increasing age at time of exposure (–66% per decade, 95% CI: –88% to –32%). The dose response for esophageal cancer was statistically significant under a simple linear, linear-quadratic and quadratic model. Both linear-quadratic and quadratic models described the data better than a simple linear model and, of the two, the quadratic model showed a marginally better fit based on the Akaike Information Criteria. Sex difference in linear ERRs was not statistically significant; however, when the dose-response shape was allowed to vary by sex, statistically significant curvature was found among males, with no evidence of quadratic departure from linearity among females. The risk for stomach cancer increased significantly with dose and there was little evidence for quadratic departure from linearity among either males or females. The sex-averaged ERR at age 70 was 0.33 per Gy (95% CI: 0.20 to 0.47). The ERR decreased significantly (–1.93 power of attained age, 95% CI: –2.94 to –0.82) with increasing attained age, but not with age at exposure, and was higher in females than males (P = 0.02). Our results are largely consistent with the results of prior LSS analyses. Salivary gland, esophageal and stomach cancers continue to show significant increases in risk with radiation dose. Adjustment for lifestyle factors had almost no impact on the radiation effect estimates. Further follow-up of the LSS cohort is important to clarify the nature of radiation effects for upper digestive tract cancers, especially for oral cavity/pharyngeal and esophageal cancers, for which detailed investigation for dose-response shape could not be conducted due to the small number of cases.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2022

Droughts Reduce Growth Rates and Increase Vulnerability to Increasingly Frequent and Severe Drying Events in an Aquatic Ectotherm

Many aquatic organisms are experiencing increasingly severe and frequent droughts and drying events. Simultaneously, drought effects are carrying over to nondrought years as ecosystems remain in incomplete states of recovery. Aquatic organisms are thus faced with fewer sequential years under degraded environmental conditions to prepare for increasingly severe droughts and potential drying events. We assessed the effect of droughts and sex on the growth, mass, and mass-dependent estivation potential of long-lived aquatic salamanders (Greater Sirens, Siren lacertina) that estivate during drying events brought on by severe droughts. We calculated growth rates of S. lacertina based on mark–recapture data spanning 11 yr of a severe drought local minimum (of past 50 yr) in the southeastern United States. Sirens showed a distinct seasonal gain in body length and mass from March through September and little growth for the rest of the year. Gains during the growth season were strongly reduced by drought conditions. Although male and female sirens were predicted to reach a similar maximum body size, females grew much slower. Recruitment into drying event ‘‘size refugia’’ is constrained by drying event severity (determines minimum size required), frequency (determines available time between events to grow), and environmental conditions between drying events (determines the rate of growth). Thus, increases in drying event severity and frequency will require faster growth to a larger body size for successful recruitment into a size class that is resistant to drying events. The slower growth of females and reduction of growth during suboptimal years (mild to moderate droughts) suggest that the life history strategy of Greater Sirens for persisting through drying events potentially increases their demographic susceptibility to the predicted effects of climate change.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2013

Documentation of a Linked-Population Viability Model to Evaluate Recovery Options for Snake River Fall Chinook Salmon

We developed an age- and life-history based population viability analysis model for linked populations of fall Chinook salmon (LPVA). LPVA was designed to quantify the costs and benefits of re-establishing access to an upstream spawning area using managed reconnection options such as hatchery stocking and translocation. The model incorporates stochasticity in the age at which salmon return to spawn, sex ratio, juvenile life history, and survival rates. Response variables include the proportion of replicate populations that persisted for 80 y (roughly 20 generations), the linked population’s growth rate, λ, time to extinction and summaries of population sizes including average female spawner abundance, final female spawner abundance, and total female abundance. This report attempts to provide a complete model description, including simulation of management options and options for simulating forward with a joint distribution of parameters based on their likelihoods with respect to historical data. Intermediate results illustrating the Bayesian approach to identifying poorly-known parameters are reported here. LPVA simulates reconnection of linked populations by representing management processes such as trapping of adults migrating upstream at two dams and juveniles migrating downstream, and hatchery operations for one or two hatcheries. The purpose of the model is to support efforts to recover the threatened Snake River fall Chinook salmon ESU by evaluating population viability using existing spawning areas with and without a hatchery and to assess the potential costs and benefits of programs to re-establish an upstream spawning area.

Jager, Henriette (Yetta) I.↗
DOE OSTI2015

Nanoscale Molecules Under Thermodynamic Control:" Digestive Ripening" or " Nanomachining"

Overall Research Goals and Specific Objectives: Nanoscale materials are becoming ubiquitous in science and engineering, and are found widely in nature. However, their formation processes and uniquely high chemical reactivities are not understood well, indeed are often mysterious. Over recent years, a number of research teams have described nanoparticle synthesis, and aging, thermal treatment, or etching times have been mentioned. We have used the terms “digestive ripening” and “nanomachining” and have suggested that thermodynamics plays an important part in the size adjustment to monodisperse arrays being formed. Since there is scant theoretical understanding of digestive ripening, the overall goal in our research is to learn what experimental parameters (ligand used, temperature, solvent, time) are most important, how to control nanoparticle size and shape after initial crude nanoparticles have been synthesized, and gain better understanding of the chemical mechanism details. Specific objectives for the past twentynine months since the grant began have been to (1) Secure and train personnel;as of 2011, a postdoc Deepa Jose, female from the Indian Institute of Science in Bangalore, India; Yijun Sun, a second year graduate student, female from China; and Jessica Changstrom, female from the USA, GK12 fellow (program for enhancing teaching ability) are actively carrying out research. (2) Find out what happens to sulfur bound hydrogen of thiol when it interacts with gold nanoparticles. Our findings are discussed in detail later. (3) Determine the effect of particle size, shape, and temperature on dodecyl thiol assited digestive ripening of gold nanoparticles. See our discussions later. (4) To understand in detail the ligand interaction in molecular clusters and nanoparticles (5) Determine the effect of chain length of amines on Au nanoparticle size under digestive ripening conditions (carbon chain length varied from 4-18). (6) Determine the catalytic activity of gold superlattices obtained by digestive ripening for oxidation of CO to CO2 at room temperature. (7) Determine the photocatalytic activity of metal nanoparticles like Au, Ag,Cu, and Pd supported on TiO2 toward photocatalytic hydrogen production.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2019

Growth performance of hybrid poplar clones on two agricultural sites with and without early irrigation and fertilization

Growth, clone rank, genotype x environment interaction, and effects of early fertilization and irrigation were evaluated for 56 hybrid poplar clones after three years’ growth on two agricultural sites in Indiana, USA. Forty-eight percent of the clones were Populus deltoides x P. nigra (DxN) crosses made with a female parent of Minnesota provenance, with the hybrids or female parent screened in Minnesota for survival, growth rate, and disease tolerance or resistance. Forty-one percent of the clones had at least one parent from provenances that are more southerly and/or have more moderate climates of provenance origin than Minnesota. Eleven percent of the clones were screened in Minnesota but were either not DXN crosses or did not have parents from Minnesota provenances in their parentage. Height growth averaged 1.78 m per year for all clones over all treatments and 2.02 m per year for the fastest- growing six clones (top 10 th percentile). Tree bole volume for the fastest-growing 10 % of the clones was 70 % larger than the average of two commercial standard clones. The clonal effect was dominant in comparison to site, treatment, and interaction effects. The fertilizer, irrigation, and fertilizer x irrigation treatments tended to increase growth, but the statistical significance of the treatment effects differed by site, and the treatments explained only a small portion of the variance. Clone rank was the same on both sites, regardless of treatment, except for the fertilizer x irrigation treatment. DxN clones linked to Minnesota parentage out-performed most clones of more southerly or other more moderate climatic origins, in these tests conducted far south of Minnesota. The data provide further evidence of broad adaptability of DxN hybrids with female P. deltoides parents of Minnesota provenance, possibly eliminating the need for narrow breeding zones and reducing the number of screening tests needed at different latitudes, saving time and money. Tests are planned to further analyze and possibly extend this inference.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2018

Probiotic Lactobacillus acidophilus Strain INMIA 9602 Er 317/402 Administration Reduces the Numbers of Candida albicans and Abundance of Enterobacteria in the Gut Microbiota of Familial Mediterranean Fever Patients

Intestinal microorganisms play a crucial role in health and disease. The disruption of host–microbiota homeostasis has been reported to occur not only during disease development but also as a result of medication. Familial Mediterranean fever (FMF) is an inflammatory genetic disease characterized by elevated systemic reactivity against the commensal gut microbiota and high levels of Candida albicans in the gut. This study’s major objective was to investigate the effects of commercial probiotic Narine on the relative abundance of gut bacteria (specifically, enterobacteria, lactobacilli, Staphylococcus aureus, and enterococci) of C. albicans carrier and non-carrier FMF patients in remission. Our main finding indicates that the probiotic reduces numbers of C. albicans and abundance of enterobacteria in male and female patients of C. albicans carriers and non-carriers. It has pivotal effect on Enterococcus faecalis: increase in male non-carriers and decrease in female ones regardless of C. albicans status. No effect was seen for Lactobacillus and S. aureus. Our data suggest that M694V/V726A pyrin inflammasome mutations leading to FMF disease may contribute to gender-specific differences in microbial community structure in FMF patients. The study’s secondary objective was to elucidate the gender-specific differences in the gut’s microbial community of FMF patients. The tendency was detected for higher counts of enterobacteria in female FMF subjects. However, the small number of patients of these groups preclude from conclusive statements, pointing at the need for additional investigations with appropriate for statistical analysis groups of subjects involved in the study.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2026

Comparison of gene expression in the skin tissue of gray, humpback, and fin whales

Analyses of gene expression in the skin of several species of whales identified genes that are differentially expressed in association with environmental factors, suggesting that skin transcriptomics may provide a valuable tool for assessing physiological responses in marine mammals. Previous work exploring differing levels of gene expression has focused on odontocetes with comparatively limited investigation of skin gene expression has been explored in mysticetes. Here, we describe the identity of genes expressed in skin tissue of three species of baleen whales to establish a baseline of gene expression and compare gene identity and expression patterns across species. We also evaluate sex-specific differences in skin gene expression through a comparison of expression levels between males and females in gray and humpback whales. A total of 16 skin tissue samples were collected from free-ranging gray, humpback and fin whales off the central Oregon coast in the eastern North Pacific. Comparison of the expressed genes in the humpback and gray whale skin tissue to the blue whale reference database identified enriched gene ontology terms in the skin tissue of each species, suggesting genes over-represented in the whale skin related to cell epithelial development, regulation of gene expression and cell maintenance . Comparison of gene expression between male and female samples revealed sex-specific differences in gray and humpback whales. A differential gene expression analysis identified several x-linked genes that have been previously identified and show gene expression differences in male and female cetaceans, such as ZFX, DDX3X and USP9X. Establishing baseline skin gene expression profiles for these three baleen whale species sampled off the Oregon coast provides a foundation for linking transcriptome variation with physiological condition and environment.

Sremba, Angela↗
DOE OSTI2024

Sex Differences in Odds of Brain Metastasis and Outcomes by Brain Metastasis Status after Advanced Melanoma Diagnosis

Sex differences in cancer are well-established. However, less is known about sex differences in diagnosis of brain metastasis and outcomes among patients with advanced melanoma. Using a United States nationwide electronic health record-derived de-identified database, we evaluated patients diagnosed with advanced melanoma from 1 January 2011–30 July 2022 who received an oncologist-defined rule-based first line of therapy (n = 7969, 33% female according to EHR, 35% w/documentation of brain metastases). The odds of documented brain metastasis diagnosis were calculated using multivariable logistic regression adjusted for age, practice type, diagnosis period (pre/post-2017), ECOG performance status, anatomic site of melanoma, group stage, documentation of non-brain metastases prior to first-line of treatment, and BRAF positive status. Real-world overall survival (rwOS) and progression-free survival (rwPFS) starting from first-line initiation were assessed by sex, accounting for brain metastasis diagnosis as a time-varying covariate using the Cox proportional hazards model, with the same adjustments as the logistic model, excluding group stage, while also adjusting for race, socioeconomic status, and insurance status. Adjusted analysis revealed males with advanced melanoma were 22% more likely to receive a brain metastasis diagnosis compared to females (adjusted odds ratio [aOR]: 1.22, 95% confidence interval [CI]: 1.09, 1.36). Males with brain metastases had worse rwOS (aHR: 1.15, 95% CI: 1.04, 1.28) but not worse rwPFS (adjusted hazard ratio [aHR]: 1.04, 95% CI: 0.95, 1.14) following first-line treatment initiation. Among patients with advanced melanoma who were not diagnosed with brain metastases, survival was not different by sex (rwOS aHR: 1.06 [95% CI: 0.97, 1.16], rwPFS aHR: 1.02 [95% CI: 0.94, 1.1]). This study showed that males had greater odds of brain metastasis and, among those with brain metastasis, poorer rwOS compared to females, while there were no sex differences in clinical outcomes for those with advanced melanoma without brain metastasis.

60 APPLIED LIFE SCIENCES↗
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↗
NASA NTRS1972

Experimental investigation of the visual field dependency in the erect and supine positions

The increasing utilization of simulators in many fields, in addition to aeronautics and space, requires the efficient use of these devices. It seemed that personnel highly influenced by the visual scene would make desirable subjects, particularly for those simulators without sufficient motion cues. In order to evaluate this concept, some measure of the degree of influence of the visual field on the subject in necessary. As part of this undertaking, 37 male and female subjects, including eight test pilots, were tested for their visual field dependency or independency. A version of Witkin's rod and frame apparatus was used for the tests. The results showed that nearly all the test subjects exhibited some degree of field dependency, the degree varying from very high field dependency to nearly zero field dependency in a normal distribution. The results for the test pilots were scattered throughout a range similar to the results for the bulk of male subjects. The few female subjects exhibited a higher field dependency than the male subjects. The male subjects exhibited a greater field dependency in the supine position than in the erect position, whereas the field dependency of the female subjects changed only slightly.

Lichtenstein, J. H.↗
NASA NTRS1974

Molding apparatus

Apparatus for compression molding of thermosetting plastics compositions including interfitting hollow male and female components is reported. The components are adapted to be compressed to form a rocket nozzle in a cavity. A thermal jacket is provided exteriorly adjacent to the female component for circulating a thermal transfer fluid to effect curing of a thermosetting plastics material being molded. Each of the male and female components is provided with suitable inlets and outlets for circulating a thermal transfer fluid.

Heier, W. C.↗