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All sourcesNASA NTRSDOE OSTI
DOE OSTI2024

Proteogenomic characterization of difficult-to-treat breast cancer with tumor cells enriched through laser microdissection

Abstract Background Breast cancer (BC) is the most commonly diagnosed cancer and the leading cause of cancer death among women globally. Despite advances, there is considerable variation in clinical outcomes for patients with non-luminal A tumors, classified as difficult-to-treat breast cancers (DTBC). This study aims to delineate the proteogenomic landscape of DTBC tumors compared to luminal A (LumA) tumors. Methods We retrospectively collected a total of 117 untreated primary breast tumor specimens, focusing on DTBC subtypes. Breast tumors were processed by laser microdissection (LMD) to enrich tumor cells. DNA, RNA, and protein were simultaneously extracted from each tumor preparation, followed by whole genome sequencing, paired-end RNA sequencing, global proteomics and phosphoproteomics. Differential feature analysis, pathway analysis and survival analysis were performed to better understand DTBC and investigate biomarkers. Results We observed distinct variations in gene mutations, structural variations, and chromosomal alterations between DTBC and LumA breast tumors. DTBC tumors predominantly had more mutations inTP53,PLXNB3, Zinc finger genes, and fewer mutations inSDC2,CDH1,PIK3CA,SVIL, andPTEN. Notably, Cytoband 1q21, which contains numerous cell proliferation-related genes, was significantly amplified in the DTBC tumors. LMD successfully minimized stromal components and increased RNA–protein concordance, as evidenced by stromal score comparisons and proteomic analysis. Distinct DTBC and LumA-enriched clusters were observed by proteomic and phosphoproteomic clustering analysis, some with survival differences. Phosphoproteomics identified two distinct phosphoproteomic profiles for high relapse-risk and low relapse-risk basal-like tumors, involving several genes known to be associated with breast cancer oncogenesis and progression, includingKIAA1522,DCK,FOXO3,MYO9B,ARID1A,EPRS,ZC3HAV1, andRBM14. Lastly, an integrated pathway analysis of multi-omics data highlighted a robust enrichment of proliferation pathways in DTBC tumors. Conclusions This study provides an integrated proteogenomic characterization of DTBC vs LumA with tumor cells enriched through laser microdissection. We identified many common features of DTBC tumors and the phosphopeptides that could serve as potential biomarkers for high/low relapse-risk basal-like BC and possibly guide treatment selections.

Oncology↗
DOE OSTI2023

Stellar Characterization and Radius Inflation of Hyades M-dwarf Stars from the APOGEE Survey

We present a spectroscopic analysis of a sample of 48 M-dwarf stars (0.2 M ⊙ < M < 0.6 M ⊙ ) from the Hyades open cluster using high-resolution H-band spectra from the Sloan Digital Sky Survey/Apache Point Observatory Galactic Evolution Experiment (APOGEE) survey. Our methodology adopts spectrum synthesis with LTE MARCS model atmospheres, along with the APOGEE Data Release 17 line list, to determine effective temperatures, surface gravities, metallicities, and projected rotational velocities. The median metallicity obtained for the Hyades M dwarfs is [M/H] = 0.09 ± 0.03 dex, indicating a small internal uncertainty and good agreement with optical results for Hyades red giants. Overall, the median radii are larger than predicted by stellar models by 1.6% ± 2.3% and 2.4% ± 2.3%, relative to a MIST and DARTMOUTH isochrone, respectively. We emphasize, however, that these isochrones are different, and the fractional radius inflation for the fully and partially convective regimes have distinct behaviors depending on the isochrone. Using a MIST isochrone there is no evidence of radius inflation for the fully convective stars, while for the partially convective M dwarfs the radii are inflated by 2.7% ± 2.1%, which is in agreement with predictions from models that include magnetic fields. For the partially convective stars, rapid rotators present on average higher inflation levels than slow rotators. The comparison with SPOTS isochrone models indicates that the derived M-dwarf radii can be explained by accounting for stellar spots in the photosphere of the stars, with 76% of the studied M dwarfs having up to 20% spot coverage, and the most inflated stars with ~20%–40% spot coverage.

79 ASTRONOMY AND ASTROPHYSICS↗
NASA NTRS1994

ROSAT PSPC observations of NGC 4636: Interaction with Virgo gas ?

ROSAT Position Sensitive Proportional Counter (PSPC) observations of NGC 4636 have provided a deep image of the galaxy and its surroundings, which reveal the presence of emission well outside the optical galaxy. The source emission is measured out to r approximately 18 min, where the instrument support structure prevents us at this time from following it farther out. The nature of this emission is not fully understood, but could be evidence that the Virgo cluster gas extends as far out as this galaxy (greater than 3 Mpc from M87). Spectral analysis of the X-ray emission suggests a relatively cool (kT approximately 0.5 to 0.9 keV) interstellar medium, with temperatures increasing with radius. However, the detailed properties of the interstellar gas cannot be unambiguously determined with the present data, since the results we obtain depend strongly on the choice of the spectral model. Comparison of the spectral distributions in concentric annuli clearly indicates significant differences with radius, which can be parameterized as a general increase of the temperature. For low cosmic abundance models, kT varies from approximately 0.55 keV in the inner 1 min to approximately 0.8 keV at r approximately 6 to 8 min. Outside 8 min the average temperature is higher than in the inner region (kT approximately 0.8 to 1.2 keV) and the low-energy absorption is significantly lower. For 100% cosmic abundance and galactic line-of-sight absorption, multi-temperature fits are required, suggesting the possibility that the interstellar medi um is inhomogeneous.

Trinchieri, G.↗
NASA NTRS2005

Identification of a typical flight patterns

Method and system for analyzing aircraft data, including multiple selected flight parameters for a selected phase of a selected flight, and for determining when the selected phase of the selected flight is atypical, when compared with corresponding data for the same phase for other similar flights. A flight signature is computed using continuous- valued and discrete-valued flight parameters for the selected flight parameters and is optionally compared with a statistical distribution of other observed flight signatures, yielding a typicality scores for the same phase for other similar flights. A cluster analysis is optionally applied to the flight signatures to define an optimal collection of clusters. A level of atypicality for a selected flight is estimated, based upon an index associated with the cluster analysis.

Irving C Statler↗
NASA NTRS2005

Identification of atypical flight patterns

Method and system for analyzing aircraft data, including multiple selected flight parameters for a selected phase of a selected flight, and for determining when the selected phase of the selected flight is atypical, when compared with corresponding data for the same phase for other similar flights. A flight signature is computed using continuous-valued and discrete-valued flight parameters for the selected flight parameters and is optionally compared with a statistical distribution of other observed flight signatures, yielding atypicality scores for the same phase for other similar flights. A cluster analysis is optionally applied to the flight signatures to define an optimal collection of clusters. A level of atypicality for a selected flight is estimated, based upon an index associated with the cluster analysis.

Statler, Irving C.↗
DOE OSTI2020

Activity Time-Use Patterns and Experienced Satisfaction: Travel Behavioral Dynamics from the 2010–2013 American Time-Use Survey Data

Central to the theory of activity-based approaches is the role of time-use and its impacts on various decision processes related to individual activity-travel patterns, thereby determining ones’ daily well-being. This research aims at quantifying and investigating the underlying correlation of time-use and happiness using the repeated cross-section data from the 2010-2013 American Time Use Survey Well-Being module. The survey specifically records reported levels of activity satisfaction as measured through – happiness, meaningfulness, tiredness, sadness and stress experienced from activity participation. Using these scores, we first construct a composite degree of activity satisfaction that a person experiences using latent class cluster analysis. A series of regression models are then estimated to jointly analyze episodic duration and satisfaction separately for each of years from 2010-2013, by controlling for socioeconomics, household lifecycle stages (29-groups based on age, gender, marital status and presence of children), activity characteristics and global life and health assessment measures. Overall, model estimation results reveal a strong negative correlation between episodic duration and happiness from individual activity engagement patterns. This correlation pattern is temporally stable for the years 2010-2013, with minor variations. Results also suggest that household lifecycle stage has a major impact on activity time-use and satisfaction behavior. Further, single parent and younger couples (25 years to 45 years) with children are more likely to engage in longer and less happy episodes due to family commitments. The model findings also show a strong correlation between health conditions and activity happiness.

Ravulaparthy, Srinath↗
NASA NTRSDate not supplied

Estimation of 3D Woven Design Sensitivities Using a Rapid Multiscale Analysis Technique

Highly-refined finite element models of three-dimension (3D) woven composite systems currently require excessive computational demands that limit their use in sensitivity analysis, uncertainty quantification, and optimization. An alternative analysis methodology was developed using the NASA Multiscale Analysis Tool (NASMAT) where multiscale models of a 3D woven composite (including inter-tow matrix voids and constituent failure) can be completed on a single central processing unit (CPU) on the order of ~30s. To develop inputs and validation data for the NASMAT model, coupon and acid-digesting testing and x-ray computed tomography were performed. The NASMAT inputs were parameterized using a set of 25 input variables and distributions. These inputs were randomly sampled to generate a total of 100,000 NASMAT analyses that could be used to understand the influence of different material and geometric properties on the warp and weft-direction stiffness and strength. These analyses (including pre/post-processing) were performed in less than eight hours on a 120 CPU cluster. The computational efficiency of the NASMAT model enabled a sensitivity analysis to be performed, and dominant input variables were able to be identified. Key results were consistent with theoretical and experimental observations for the specific 3D woven system studied in this work.

NASMAT↗
NASA NTRS1985

An analysis of the Basel star catalog

The standard Bahcall-Soneira (1980) Galaxy model is compared with the data from the 12 fields in the Basel star catalog that are at Galactic latitudes above 20 deg and have E(B-V) of less than 0.1 mag. Good agreement is found between the calculated and observed color distributions, as well as star counts, for all the fields. The globular cluster feature that is observed in the luminosity function of globular clusters near M(v) = +1 to +4 mag is also present in the spheroid field stars. It is possible to assign some of the spheroid stars from the standard two-component Galaxy model (thin disk plus de Vaucouleurs spheroid) to a third stellar component (a thick disk with a spheroid luminosity function) without disturbing the agreement with observations.

Bahcall, J. N.↗
NASA NTRSDate not supplied

Estimation of 3D Woven Design Sensitivities Using a Rapid Multiscale Analysis Technique

Highly-refined finite element models of three-dimension (3D) woven composite systems currently require excessive computational demands that limit their use in sensitivity analysis, uncertainty quantification, and optimization. An alternative analysis methodology was developed using the NASA Multiscale Analysis Tool (NASMAT) where multiscale models of a 3D woven composite (including inter-tow matrix voids and constituent failure) can be completed on a single central processing unit(CPU)on the order of ~30 s. To develop inputs and validation data for the NASMAT model, coupon and acid-digesting testing and x-ray computed tomography were performed. The NASMAT inputs were parameterized using a set of 25 input variables and distributions. These inputs were randomly sampled to generate a total of 100,000 NASMAT analyses that could be used to understand the influence of different material and geometric properties on the warp and weft-direction stiffness and strength. These analyses (including pre/post-processing) were performed in less than eight hours on a 120 CPU cluster. The computational efficiency of the NASMAT model enabled a sensitivity analysis to be performed, and dominant input variables were able to be identified. Key results were consistent with theoretical and experimental observations for the specific 3D woven system studied in this work.

NASMAT↗
NASA NTRS1995

Constraints on the formation history of the elliptical galaxy NGC 3923 from the colors of its globular clusters

We present a study of the colors of globular clusters associated with the elliptical galaxy NGC 3923. Our final sample consists of Wasington system C and T(sub 1) photometry for 143 globular cluster candidates with an expected contamination of no more than 10%. We find that the color distribution of the NGC 3923 globular cluster system (GCS) is broad and appears to have at least two peaks. A mixture modeling analysis of the color distribution indicates that a two-component model is favored over a single-component one at a high level of confidence (greater than 99%). This evidence for more than one population in the GCS of NGC 3923 is similar to that previously noted for the four other elliptical galaxies for which similar data have been published. Furthermore, we find that the NGC 3923 GCS is redder than the GCSs of previously studed elliptical galaxies of similar luminosity. The median metallicity inferred from our (C-(T(sub 1)))(sub 0) colors is (Fe/H)(sub med) = -0.56, with an uncertainty of 0.14 dex arising from all sources of uncertainty in the mean color. This is more metal rich than the median metallicity found for the GCS of M87 using the same method, (Fe/H)(sub med) = -0.94. Since M87 is more luminous than NGC 3923, this result points to significant scatter about any trend of higher GCS metallicity with increasing galaxy luminosity. We also show that there is a color gradient in the NGC 3923 GCS corresponding to about -0.5 dex in Delta(Fe/H)/Delta(log r). We conclude that the shape of the color distribution of individual GCSs and the variation in mean color among the GCSs of ellipticals are difficult to understand if elliptical galaxies are formed in a single protogalactic collapse. Models in which ellipticals and their globular clusters are formed in more than one event, such as a merger scenario, are more successful in accounting for these observations.

Zepf, Stephen E.↗
DOE OSTI2019

The Atmospheric River Tracking Method Intercomparison Project (ARTMIP): Quantifying Uncertainties in Atmospheric River Climatology

Atmospheric rivers (ARs) are now widely known for their association with high-impact weather events and long-term water supply in many regions. Researchers within the scientific community have developed numerous methods to identify and track of ARs—a necessary step for analyses on gridded data sets, and objective attribution of impacts to ARs. These different methods have been developed to answer specific research questions and hence use different criteria (e.g., geometry, threshold values of key variables, and time dependence). Furthermore, these methods are often employed using different reanalysis data sets, time periods, and regions of interest. The goal of the Atmospheric River Tracking Method Intercomparison Project (ARTMIP) is to understand and quantify uncertainties in AR science that arise due to differences in these methods. This paper presents results for key AR-related metrics based on 20+ different AR identification and tracking methods applied to Modern-Era Retrospective Analysis for Research and Applications Version 2 reanalysis data from January 1980 through June 2017. We show that AR frequency, duration, and seasonality exhibit a wide range of results, while the meridional distribution of these metrics along selected coastal (but not interior) transects are quite similar across methods. Furthermore, methods are grouped into criteria-based clusters, within which the range of results is reduced. AR case studies and an evaluation of individual method deviation from an all-method mean highlight advantages/disadvantages of certain approaches. For example, methods with less (more) restrictive criteria identify more (less) ARs and AR-related impacts. Finally, this paper concludes with a discussion and recommendations for those conducting AR-related research to consider.

Rutz, Jonathan J.↗
DOE OSTI2021

Physics from Cosmic Surveys (Final Report)

The main focus of the PI during this time was leading the effort to produce cosmological results on the data set from the first three years from the Dark Energy Survey (DES). The analysis combines weak gravitational lensing and maps of the galaxy distribution, supplemented by estimates of the redshifts of galaxies. This will ultimately lead to 33 papers, culminating in a single paper that brings all this together and provides a constraint on the clustering parameter σ 8 .This will be directly compared to the constraint obtained by high-redshift experiments, such as the Planck satellite, extrapolated forward assuming the CDM model. If the two values disagree, as they currently seem to at the 2-sigma level, this will be an indication that the model is incorrect or incomplete. These papers are expected to be submitted in January, 2021. Leading this effort, with help from many others, has been the primary research focus of the PI during this grant.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗
DOE OSTI2021

Cleaning Images with Gaussian Process Regression

Many approaches to astronomical data reduction and analysis cannot tolerate missing data: corrupted pixels must first have their values imputed. This paper presents astrofix, a robust and flexible image imputation algorithm based on Gaussian process regression. Through an optimization process, astrofix chooses and applies a different interpolation kernel to each image, using a training set extracted automatically from that image. It naturally handles clusters of bad pixels and image edges and adapts to various instruments and image types. For bright pixels, the mean absolute error of astrofix is several times smaller than that of median replacement and interpolation by a Gaussian kernel. We demonstrate good performance on both imaging and spectroscopic data, including the SBIG 6303 0.4 m telescope and the FLOYDS spectrograph of Las Cumbres Observatory and the CHARIS integral-field spectrograph on the Subaru Telescope.

42 ENGINEERING↗
DOE OSTI2022

Search for Spatial Correlations of Neutrinos with Ultra-high-energy Cosmic Rays

For several decades, the origin of ultra-high-energy cosmic rays (UHECRs) has been an unsolved question of high-energy astrophysics. One approach for solving this puzzle is to correlate UHECRs with high-energy neutrinos, since neutrinos are a direct probe of hadronic interactions of cosmic rays and are not deflected by magnetic fields. In this paper, we present three different approaches for correlating the arrival directions of neutrinos with the arrival directions of UHECRs. The neutrino data are provided by the IceCube Neutrino Observatory and ANTARES, while the UHECR data with energies above ∼50 EeV are provided by the Pierre Auger Observatory and the Telescope Array. All experiments provide increased statistics and improved reconstructions with respect to our previous results reported in 2015. The first analysis uses a high-statistics neutrino sample optimized for point-source searches to search for excesses of neutrino clustering in the vicinity of UHECR directions. The second analysis searches for an excess of UHECRs in the direction of the highest-energy neutrinos. The third analysis searches for an excess of pairs of UHECRs and highest-energy neutrinos on different angular scales. None of the analyses have found a significant excess, and previously reported overfluctuations are reduced in significance. Based on these results, we further constrain the neutrino flux spatially correlated with UHECRs.

79 ASTRONOMY AND ASTROPHYSICS↗
NASA NTRS1975

Continuous observations of long-term variations in cosmic X-ray sources

Results are reported for the Charged Particle Measurements Experiment which was conducted on board IMP-7 to detect X-ray fluxes from the sun, the galactic center, Tau X-1, and Sco X-1 over a nine-month period. Autocorrelation analysis of the data indicates a probable 80-day periodicity in the flux from Sco X-1, a 110-day periodicity in the flux from the galactic center, no periodicities in the flux from Tau X-1, and a strong 27-day periodicity in the solar X-ray flux. A transient event detected within the cluster of sources constituting the galactic center is reported which lasted about two months and had a flux roughly equal to the regular flux from this area. It is noted that this was the only transient event detected in the whole area under continuous observation for the duration of the experiment.

Wende, C. D.↗
NASA NTRS1988

An assessment of AVIRIS data for hydrothermal alteration mapping in the Goldfield Mining District, Nevada

Airborne Visible and Infrared Imaging Spectrometer (AVIRIS) data were acquired over the Goldfield Mining District, Nevada, in September 1987. Goldfield is one of the group of large epithermal precious metal deposits in Tertiary volcanic rocks, associated with silicic volcanism and caldera formation. Hydrothermal alteration consists of silicification along fractures, advanced agrillic and argillic zones further away from veins and more widespread propylitic zones. An evaluation of AVIRIS data quality was performed. Faults in the data, related to engineering problems and a different behavior of the instrument while on-board the U2, were encountered. Consequently, a decision was made to use raw data and correct them only for dark current variations and detector read-out-delays. New software was written to that effect. Atmospheric correction was performed using the flat field correction technique. Analysis of the data was then performed to extract spectral information, mainly concentrating on the 2 to 2.45 micron window, as the alteration minerals of interest have their distinctive spectral reflectance features in this region. Principally kaolinite and alunite spectra were clearly obtained. Mapping of the different minerals and alteration zones was attempted using ratios and clustering techniques. Poor signal-to-noise performance of the instrument and the lack of appropriate software prevented the production of an alteration map of the area. Spectra extracted locally from the AVIRIS data were checked in the field by collecting representative samples of the outcrops.

Carrere, Veronique↗
NASA NTRS2000

Participation In The AXAF Program As Interdisciplinary Scientist

We have supported the Advanced X-ray Astrophysics Facility (AXAF) project through specific studies and research in X-ray astronomy. Our research in X-ray astronomy has been concentrated in three projects: the ROSAT Deep Survey, the ROSAT All-sky Cluster Survey, and the study of moderate to high redshift clusters discovered serendipitously in long ROSAT pointings utilizing the wavelet transform. We have continued to develop the techniques and catalogues described in the publications listed below. The PI continued to participate in the SWG and attended its meetings except where conflicts existed. The Co-I supported the PI and attended all meetings in order to provide continuity. A post-doctoral fellow (Rosati) was hired to fully develop the techniques described above and make them applicable to the AXAF program. The results are described in the publications below. We continued to provide analysis of scientific and technical issues to the project scientist as appropriate. We made detailed simulations of the AXAF deep survey program and have made this available to the project and the ASC. The principal scientific results, discussed in great detail in the publications listed below, are as follows: (1) The wavelet transform is now a fine working tool for the analysis of faint X-ray sources especially clusters. (2) The analysis of the ROSAT DEEP CLUSTER SURVEY has given important constraints on cosmology particularly on the matter content of the universe and the amplitude of the fluctuations that created the galaxies and clusters. (3) The ROSAT DEEP SURVEY in the Lockman Hole has given an important'deep survey in the X-ray band that gives vital data on the distribution and evolution of X-ray sources. It is an important and complementary data base to compare with the AXAF deep fields. (4) The Northern ROSAT All Sky Cluster Survey now has a complete catalog and is again important and complementary to AXAF/ Chandra studies of clusters which are deeper but in a narrower area. These projects have had a significant impact on the whole field and have set up some excellent experiments to be undertaken with the AXAF/Chandra telescope such as the Chandra Deep Field South.

Giacconi, Riccardo↗
NASA NTRS1989

5S ribosomal ribonucleic acid sequences in Bacteroides and Fusobacterium: evolutionary relationships within these genera and among eubacteria in general

The 5S ribosomal ribonucleic acid (rRNA) sequences were determined for Bacteroides fragilis, Bacteroides thetaiotaomicron, Bacteroides capillosus, Bacteroides veroralis, Porphyromonas gingivalis, Anaerorhabdus furcosus, Fusobacterium nucleatum, Fusobacterium mortiferum, and Fusobacterium varium. A dendrogram constructed by a clustering algorithm from these sequences, which were aligned with all other hitherto known eubacterial 5S rRNA sequences, showed differences as well as similarities with respect to results derived from 16S rRNA analyses. In the 5S rRNA dendrogram, Bacteroides clustered together with Cytophaga and Fusobacterium, as in 16S rRNA analyses. Intraphylum relationships deduced from 5S rRNAs suggested that Bacteroides is specifically related to Cytophaga rather than to Fusobacterium, as was suggested by 16S rRNA analyses. Previous taxonomic considerations concerning the genus Bacteroides, based on biochemical and physiological data, were confirmed by the 5S rRNA sequence analysis.

NASA Discipline Exobiology↗