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All sourcesNASA NTRSDOE OSTI
DOE OSTI2021

Sequence Length of HIV-1 Subtype B Increases over Time: Analysis of a Cohort of Patients with Hemophilia over 30 Years

We aimed to investigate whether the sequence length of HIV-1 increases over time. We performed a longitudinal analysis of full-length coding region sequences (FLs) during an HIV-1 outbreak among patients with hemophilia and local controls infected with the Korean subclade B of HIV-1 (KSB). Genes were amplified by overlapping RT-PCR or nested PCR and subjected to direct sequencing. Overall, 141 FLs were sequentially determined over 30 years in 62 KSB-infected patients. Phylogenetic analysis indicated that within KSB, two FLs from plasma donors O and P comprised two clusters, together with 8 and 12 patients with hemophilia, respectively. Signature pattern analysis of the KSB of HIV-1 revealed 91 signature nucleotide residues (1.1%). In total, 48 and 43 signature nucleotides originated from clusters O and P, respectively. Six positions contained 100% specific nucleotide(s) in clusters O and P. In-depth FL analysis for over 30 years indicated that the KSB FL significantly increased over time before combination antiretroviral therapy (cART) and decreased with cART. This increase occurred due to the significant increase in env and nef genes, originating in the variable regions of both genes. The increase in sequence length of HIV-1 over time suggests an evolutionary direction.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2017

A Dynamical and Statistical Characterization of U.S. Extreme Precipitation Events and Their Associated Large-Scale Meteorological Patterns

Abstract Regional patterns of extreme precipitation events occurring over the continental United States are identified via hierarchical cluster analysis of observed daily precipitation for the period 1950–2005. Six canonical extreme precipitation patterns (EPPs) are isolated for the boreal warm season and five for the cool season. The large-scale meteorological pattern (LMP) inducing each EPP is identified and used to create a “base function” for evaluating a climate model’s potential for accurately representing the different patterns of precipitation extremes. A parallel analysis of the Community Climate System Model, version 4 (CCSM4), reveals that the CCSM4 successfully captures the main U.S. EPPs for both the warm and cool seasons, albeit with varying degrees of accuracy. The model’s skill in simulating each EPP tends to be positively correlated with its capability in representing the associated LMP. Model bias in the occurrence frequency of a governing LMP is directly related to the frequency bias in the corresponding EPP. In addition, however, discrepancies are found between the CCSM4’s representation of LMPs and EPPs over regions such as the western United States and Midwest, where topographic precipitation influences and organized convection are prominent, respectively. In these cases, the model representation of finer-scale physical processes appears to be at least equally important compared to the LMPs in driving the occurrence of extreme precipitation.

54 ENVIRONMENTAL SCIENCES↗
NASA NTRS1994

Predictions of a population of cataclysmic variables in globular clusters

We have studied the number of cataclysmic variables (CVs) that should be active in globular clusters during the present epoch as a result of binary formation via two-body tidal capture. We predict the orbital period and luminosity distributions of CVs in globular clusters. The results arebased on Monte Carlo simulations combined with evolution calculations appropriate to each system formed during the lifetime of two specific globular clusters, omega Cen and 47 Tuc. From our study of these two clusters, which represent the range of core densities and states of mass segregation that are likely to be interesting, we extrapolate our results to the Galactic globlular cluster system. Although there is at present little direct observational evidence of CVs in globular clusters, we find that there should be a large number of active systems. We predict that there should be more than approximately 100 CVs in both 47 Tuc and omega Cen and several thousand in the Galactic globular cluster system. These numbers are based on two-body processes alone and represent a lower bound on the number of systems that may have been formed as a result of stellar interaction within globular clusters. The relation between these calculations and the paucity of optically detected CVs in globular clusters is discussed. Should future observations fail to find convincing evidence of a substantial population of cluster CVs, then the two-body tidal capture scenario is likely to be seriously constrained. Of the CVs we espect in 47 Tuc and omega Cen, approximately 45 and 20, respectively, should have accretion luminosities above 10(exp 33) ergs/s. If one utilizes a relation for converting accretion luminosity to hard X-ray luminosity that is based on observations of Galactic plane CVs, even these sources will not exhibit X-ray luminosities above 10(exp 33) ergs/s. While we cannot account directly for the most luminous subset of the low-luminosity globular cluster X-ray sources without assuming an evolutionary pattern that is different from that of the majority of CVs in the disk, we are able to account for all of the observed lower luminosity subset of these sources, many of which have been recently discovered through ROSAT observations. In order for our predicted integrated cluster X-ray luminosities to be consistent with observational upper limits, the relation between accretion and X-ray luminosities should be something like that inferred from the Galactic plane population of CVs. Our calculations predict a large number of systems with L(sub acc) is less than 10(exp 32) ergs/s. Although our calculations imply that globular clusters should have an enhancement of CVs relative to the number thought to be present in the Galactic disk, this enhancement is at most roughly an order of magnitude, not comparable to the factor of approximately 100 for low-mass X-ray binaries (LMXBs).

Di Stefano, R.↗
DOE OSTI2024

Describing patterns of familial cancer risk in subfertile men using population pedigree data

STUDY QUESTION Can we simultaneously assess risk for multiple cancers to identify familial multicancer patterns in families of azoospermic and severely oligozoospermic men? SUMMARY ANSWER Here, distinct familial cancer patterns were observed in the azoospermia and severe oligozoospermia cohorts, suggesting heterogeneity in familial cancer risk by both type of subfertility and within subfertility type. WHAT IS KNOWN ALREADY Subfertile men and their relatives show increased risk for certain cancers including testicular, thyroid, and pediatric. STUDY DESIGN, SIZE, DURATION A retrospective cohort of subfertile men (N = 786) was identified and matched to fertile population controls (N = 5674). Family members out to third-degree relatives were identified for both subfertile men and fertile population controls (N = 337 754). The study period was 1966–2017. Individuals were censored at death or loss to follow-up, loss to follow-up occurred if they left Utah during the study period. PARTICIPANTS/MATERIALS, SETTING, METHODS Azoospermic (0 × 10 6 /mL) and severely oligozoospermic (<1.5 × 10 6 /mL) men were identified in the Subfertility Health and Assisted Reproduction and the Environment cohort (SHARE). Subfertile men were age- and sex-matched 5:1 to fertile population controls and family members out to third-degree relatives were identified using the Utah Population Database (UPDB). Cancer diagnoses were identified through the Utah Cancer Registry. Families containing ≥10 members with ≥1 year of follow-up 1966–2017 were included (azoospermic: N = 426 families, 21 361 individuals; oligozoospermic: N = 360 families, 18 818 individuals). Unsupervised clustering based on standardized incidence ratios for 34 cancer phenotypes in the families was used to identify familial multicancer patterns; azoospermia and severe oligospermia families were assessed separately. MAIN RESULTS AND THE ROLE OF CHANCE Compared to control families, significant increases in cancer risks were observed in the azoospermia cohort for five cancer types: bone and joint cancers hazard ratio (HR) = 2.56 (95% CI = 1.48–4.42), soft tissue cancers HR = 1.56 (95% CI = 1.01–2.39), uterine cancers HR = 1.27 (95% CI = 1.03–1.56), Hodgkin lymphomas HR = 1.60 (95% CI = 1.07–2.39), and thyroid cancer HR = 1.54 (95% CI = 1.21–1.97). Among severe oligozoospermia families, increased risk was seen for three cancer types: colon cancer HR = 1.16 (95% CI = 1.01–1.32), bone and joint cancers HR = 2.43 (95% CI = 1.30–4.54), and testis cancer HR = 2.34 (95% CI = 1.60–3.42) along with a significant decrease in esophageal cancer risk HR = 0.39 (95% CI = 0.16–0.97). Thirteen clusters of familial multicancer patterns were identified in families of azoospermic men, 66% of families in the azoospermia cohort showed population-level cancer risks, however, the remaining 12 clusters showed elevated risk for 2-7 cancer types. Several of the clusters with elevated cancer risks also showed increased odds of cancer diagnoses at young ages with six clusters showing increased odds of adolescent and young adult (AYA) diagnosis [odds ratio (OR) = 1.96–2.88] and two clusters showing increased odds of pediatric cancer diagnosis (OR = 3.64–12.63). Within the severe oligozoospermia cohort, 12 distinct familial multicancer clusters were identified. All 12 clusters showed elevated risk for 1–3 cancer types. An increase in odds of cancer diagnoses at young ages was also seen in five of the severe oligozoospermia familial multicancer clusters, three clusters showed increased odds of AYA diagnosis (OR = 2.19–2.78) with an additional two clusters showing increased odds of a pediatric diagnosis (OR = 3.84–9.32). LIMITATIONS, REASONS FOR CAUTION Although this study has many strengths, including population data for family structure, cancer diagnoses and subfertility, there are limitations. First, semen measures are not available for the sample of fertile men. Second, there is no information on medical comorbidities or lifestyle risk factors such as smoking status, BMI, or environmental exposures. Third, all of the subfertile men included in this study were seen at a fertility clinic for evaluation. These men were therefore a subset of the overall population experiencing fertility problems and likely represent those with the socioeconomic means for evaluation by a physician. WIDER IMPLICATIONS OF THE FINDINGS This analysis leveraged unique population-level data resources, SHARE and the UPDB, to describe novel multicancer clusters among the families of azoospermic and severely oligozoospermic men. Distinct overall multicancer risk and familial multicancer patterns were observed in the azoospermia and severe oligozoospermia cohorts, suggesting heterogeneity in cancer risk by type of subfertility and within subfertility type. Describing families with similar cancer risk patterns provides a new avenue to increase homogeneity for focused gene discovery and environmental risk factor studies. Such discoveries will lead to more accurate risk predictions and improved counseling for patients and their families. STUDY FUNDING/COMPETING INTEREST(S) This work was funded by GEMS: Genomic approach to connecting Elevated germline Mutation rates with male infertility and Somatic health (Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): R01 HD106112). The authors have no conflicts of interest relevant to this work.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2014

A TALE OF A RICH CLUSTER AT z ∼ 0.8 AS SEEN BY THE STAR FORMATION HISTORIES OF ITS EARLY-TYPE GALAXIES

We present a detailed stellar population analysis for a sample of 24 early-type galaxies (ETGs) belonging to the rich cluster RX J0152.7-1357 at z = 0.83. We have derived the age, metallicity, abundance pattern, and star formation history (SFH) for each galaxy individually to further characterize this intermediate-z reference cluster. We then study how these stellar population parameters depend on the local environment. This provides a better understanding on the formation timescales and subsequent evolution of the substructures in this cluster. We have also explored the evolutionary link between z ∼ 0.8 ETGs and those in the local universe by comparing the trends that the stellar population parameters followed with galaxy velocity dispersion at each epoch. We find that the ETGs in Coma are consistent with being the (passively evolving) descendants of the ETG population in RX J10152.7-1357. Furthermore, our results favor a downsizing picture, where the subclumps centers were formed first. These central parts contain the most massive galaxies, which formed the bulk of their stars in a short, burst-like event at high z. On the contrary, the cluster outskirts are populated with less-massive, smaller galaxies that show a wider variety of SFHs. In general, they present extended star formation episodes over cosmic time, which seems to be related to their posterior incorporation into the cluster around 4 Gyr after the initial event of formation.

79 ASTRONOMY AND ASTROPHYSICS↗
DOE OSTI2021

The superatomic state beyond conventional magic numbers: Ligated metal chalcogenide superatoms

The field of cluster science is drawing increasing attention due to the strong size and composition-dependent properties of clusters and the exciting prospect of clusters serving as the building blocks for materials with tailored properties. However, identifying a unifying central paradigm that provides a framework for classifying and understanding the diverse behaviors is an outstanding challenge. One such central paradigm is the superatom concept that was developed for metallic and ligand-protected metallic clusters. The periodic electronic and geometric closed shells in clusters result in their properties being based on the stability they gain when they achieve closed shells. This stabilization results in the clusters having a well-defined valence allowing them to be classified as superatoms – thus, extending the periodic table to a third dimension. This perspective focuses on extending the superatomic concept to ligated metal-chalcogen clusters that have recently been synthesized in solutions and form assemblies with counterions that have wide-ranging applications. Here we illustrate that the periodic patterns emerge in the electronic structure of ligated metal-chalcogenide clusters. The stabilization gained by the closing of their electronic shells allows for the prediction of their redox properties. Further investigations reveal how the selection of ligands may control the redox properties of the superatoms. These ligated clusters may serve as chemical dopants for two-dimensional semiconductors to control their transport characteristics. Superatomic molecules of multiple metal-chalcogen superatoms allow for the formation of nano pn junctions ideal for directed transport and photon harvesting. As a result, the perspective outlines future developments, including the synthesis of magnetic superatoms.

36 MATERIALS SCIENCE↗
DOE OSTI2016

A latitudinal diversity gradient in terrestrial bacteria of the genus Streptomyces

We show that Streptomyces biogeography in soils across North America is influenced by the regional diversification of microorganisms due to dispersal limitation and genetic drift. Streptomyces spp. form desiccation-resistant spores, which can be dispersed on the wind, allowing for a strong test of whether dispersal limitation governs patterns of terrestrial microbial diversity. We employed an approach that has high sensitivity for determining the effects of genetic drift. Specifically, we examined the genetic diversity and phylogeography of physiologically similar Streptomyces strains isolated from geographically distributed yet ecologically similar habitats. We found that Streptomyces beta diversity scales with geographic distance and both beta diversity and phylogenetic diversity manifest in a latitudinal diversity gradient. This pattern of Streptomyces biogeography resembles patterns seen for diverse species of plants and animals, and we therefore evaluated these data in the context of ecological and evolutionary hypotheses proposed to explain latitudinal diversity gradients. The data are consistent with the hypothesis that niche conservatism limits dispersal, and historical patterns of glaciation have limited the time for speciation in higher-latitude sites. Most notably, higher-latitude sites have lower phylogenetic diversity, higher phylogenetic clustering, and evidence of range expansion from lower latitudes. In addition, patterns of beta diversity partition with respect to the glacial history of sites. Furthermore, the data support the hypothesis that extant patterns of Streptomyces biogeography have been driven by historical patterns of glaciation and are the result of demographic range expansion, dispersal limitation, and regional diversification due to drift.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

Microsolvation in V + (H 2 O) n Clusters Studied with Selected-Ion Infrared Spectroscopy

Gas phase ion-molecule clusters of the form V + (H 2 O) n (n = 1-30) are produced by laser vaporization in a supersonic expansion. These ions are analyzed and mass-selected with a time-of-flight mass spectrometer and investigated with infrared laser photodissociation spectroscopy. The small clusters (n ≤ 7) are studied with argon tagging, while the larger clusters are studied via the elimination of water molecules. The vibrational spectra for the small clusters include only free O-H stretching vibrations, while larger clusters exhibit red-shifted hydrogen bonding vibrations. The spectral patterns reveal that the coordination around V + ions is completed with four water molecules. A symmetric square-planar structure forms for the n = 4 ion, and this becomes the core ion in larger structures. Clusters up to n = 8 have mostly two-dimensional structures, but hydrogen bonding networks evolve to three-dimensional structures in larger clusters. The free O-H vibration of AAD (acceptor-acceptor-donor) coordinated surface molecules converges to a frequency near that of bulk water by the cluster size of n = 30. However, the splitting of this vibration for AAD- versus AD-coordinated molecules is still different compared to other singly-charged or doubly-charged cation-water clusters. Finally, this indicates that cation identity and charge-site location in the cluster can produce discernible spectral differences for clusters in this size range.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2014

Occupancy schedules learning process through a data mining framework

Building occupancy is a paramount factor in building energy simulations. Specifically, lighting, plug loads, HVAC equipment utilization, fresh air requirements and internal heat gain or loss greatly depends on the level of occupancy within a building. Developing the appropriate methodologies to describe and reproduce the intricate network responsible for human-building interactions are needed. Extrapolation of patterns from big data streams is a powerful analysis technique which will allow for a better understanding of energy usage in buildings. A three-step data mining framework is applied to discover occupancy patterns in office spaces. First, a data set of 16 offices with 10 minute interval occupancy data, over a two year period is mined through a decision tree model which predicts the occupancy presence. Then a rule induction algorithm is used to learn a pruned set of rules on the results from the decision tree model. Finally, a cluster analysis is employed in order to obtain consistent patterns of occupancy schedules. Furthermore, the identified occupancy rules and schedules are representative as four archetypal working profiles that can be used as input to current building energy modeling programs, such as EnergyPlus or IDA-ICE, to investigate impact of occupant presence on design, operation and energy use in office buildings.

32 ENERGY CONSERVATION, CONSUMPTION, AND UTILIZATI↗
DOE OSTI2021

Signature of a Massive Rotating Metal-poor Star Imprinted in the Phoenix Stellar Stream

The Phoenix stellar stream has a low intrinsic dispersion in velocity and metallicity that implies the progenitor was probably a low-mass globular cluster. In this work we use Magellan/Magellan Inamori Kyocera Echelle (MIKE) high-dispersion spectroscopy of eight Phoenix stream red giants to confirm this scenario. In particular, we find negligible intrinsic scatter in metallicity ($σ$([FE II/H]) = ${0.04}_{-0.03}^{+0.11}$) and a large peak-to-peak range in [Na/Fe] and [Al/Fe] abundance ratios, consistent with the light element abundance patterns seen in the most metal-poor globular clusters. However, unlike any other globular cluster, we also find an intrinsic spread in [Sr II/Fe] spanning ~1 dex, while [Ba II/Fe] shows nearly no intrinsic spread ($σ$([Ba II/H]) = ${0.03}_{-0.02}^{+0.10}$). This abundance signature is best interpreted as slow-neutron-capture element production from a massive fast-rotating metal-poor star (15–20 $M$ ⊙ , $v$ ini /$v$ crit = 0.4, [Fe/H] = -3.8). The low inferred cluster mass suggests the system would have been unable to retain supernovae ejecta, implying that any massive fast-rotating metal-poor star that enriched the interstellar medium must have formed and evolved before the globular cluster formed. Furthermore, neutron-capture element production from asymptotic giant branch stars or magneto-rotational instabilities in core-collapse supernovae provide poor fits to the observations. We also report one Phoenix stream star to be a lithium-rich giant ($A$(Li) = 3.1 ± 0.1). At [Fe/H ] = -2.93; it is among the most metal-poor lithium-rich giants known.

79 ASTRONOMY AND ASTROPHYSICS↗
DOE OSTI2014

Change detection and classification of land cover in multispectral satellite imagery using clustering of sparse approximations (CoSA) over learned feature dictionaries

Neuromimetic machine vision and pattern recognition algorithms are of great interest for landscape characterization and change detection in satellite imagery in support of global climate change science and modeling. We present results from an ongoing effort to extend machine vision methods to the environmental sciences, using adaptive sparse signal processing combined with machine learning. A Hebbian learning rule is used to build multispectral, multiresolution dictionaries from regional satellite normalized band difference index data. Land cover labels are automatically generated via our CoSA algorithm: Clustering of Sparse Approximations, using a clustering distance metric that combines spectral and spatial textural characteristics to help separate geologic, vegetative, and hydrologie features. We demonstrate our method on example Worldview-2 satellite images of an Arctic region, and use CoSA labels to detect seasonal surface changes. In conclusion, our results suggest that neuroscience-based models are a promising approach to practical pattern recognition and change detection problems in remote sensing.

97 MATHEMATICS AND COMPUTING↗
DOE OSTI2017

Extending a Tandem Mass Spectral Library to Include MS{sup 2} Spectra of Fragment Ions Produced In-Source and MS{sup n} Spectra

Tandem mass spectral library searching is finding increased use as an effective means of determining chemical identity in mass spectrometry-based omics studies. We previously reported on constructing a tandem mass spectral library that includes spectra for multiple precursor ions for each analyte. Here we report our method for expanding this library to include MS{sup 2} spectra of fragment ions generated during the ionization process (in-source fragment ions) as well as MS{sup 3} and MS{sup 4} spectra. These can assist the chemical identification process. A simple density-based clustering algorithm was used to cluster all significant precursor ions from MS{sup 1} scans for an analyte acquired during an infusion experiment. The MS{sup 2} spectra associated with these precursor ions were grouped into the same precursor clusters. Subsequently, a new top-down hierarchical divisive clustering algorithm was developed for clustering the spectra from fragmentation of ions in each precursor cluster, including the MS{sup 2} spectra of the original precursors and of the in-source fragments as well as the MS{sup n} spectra. This algorithm starts with all the spectra of one precursor in one cluster and then separates them into sub-clusters of similar spectra based on the fragment patterns. Herein, we describe the algorithms and spectral evaluation methods for extending the library. The new library features were demonstrated by searching the high resolution spectra of E. coli extracts against the extended library, allowing identification of compounds and their in-source fragment ions in a manner that was not possible before. .

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗
DOE OSTI2021

Incorporating space and time into random forest models for analyzing geospatial patterns of drug-related crime incidents in a major U.S. metropolitan area

The opioid crisis has hit American cities hard, and research on spatial and temporal patterns of drug-related activities including detecting and predicting clusters of crime incidents involving particular types of drugs is useful for distinguishing hot zones where drugs are present that in turn can further provide a basis for assessing and providing related treatment services. In this study, we investigated spatiotemporal patterns of more than 52,000 reported incidents of drug-related crime at block group granularity in Chicago, IL between 2016 and 2019. We applied a space-time analysis framework and machine learning approaches to build a model using training data that identified whether certain locations and built environment and sociodemographic factors were correlated with drug-related crime incident patterns, and establish the top contributing factors that underlaid the trends. Space and time, together with multiple driving factors, were incorporated into a random forest model to analyze these changing patterns. We accommodated both spatial and temporal autocorrelation in the model learning process to assist with capturing the changes over time and tested the capabilities of the space-time random forest model by predicting drug-related activity hot zones. Overall, we focused particularly on crime incidents that involved heroin and synthetic drugs as these have been key drug types that have highly impacted cities during the opioid crisis in the U.S.

97 MATHEMATICS AND COMPUTING↗
DOE OSTI2025

Introducing a Markov chain-based time calibration procedure for multi-channel particle detectors: application to the SuperFGD and ToF detectors of the T2K experiment

Inter-channel mis-synchronisation can be a limiting factor to the time resolution of high performance timing detectors with multiple readout channels and independent electronics units. In these systems, time calibration methods employed must be able to efficiently correct for minimal mis-synchronisation between channels and achieve the best detector performance. We present an iterative time calibration method based on Markov Chains, suitable for detector systems with multiple readout channels. Starting from correlated hit pairs alone, and without requiring an external reference time measurement, the method solves for fixed per-channel offsets, with precision limited only by the intrinsic single-channel resolution. A mathematical proof that the method is able to find the correct time offsets to be assigned to each detector channel in order to achieve inter-channel synchronisation is given, and it is shown that the number of iterations to reach convergence within the desired precision is controllable with a single parameter. Numerical studies are used to confirm unbiased recovery of true offsets. Finally, the application of the calibration method to the Super Fine-Grained Detector (SuperFGD) and the Time of Flight (TOF) detector at the upgraded T2K near detector (ND280) shows good improvement in overall timing resolution, demonstrating the effectiveness in a real-world scenario and scalability.

calibration and fitting methods↗
DOE OSTI2024

Frosted Tracks

SAND2025-01893O Frosted Tracks is a software tool to group trajectories according to sequences of their behavior. The goal is to start with a very large number of trajectories and identify groups that exhibit similar behavior patterns. The application combines TICC and Metric DBSCAN clustering algorithms for behavioral segmentation and labeling of air/sea trajectory data. Sandia National Laboratories is a multimission laboratory managed and operated by National Technology & Engineering Solutions of Sandia, LLC, a wholly owned subsidiary of Honeywell International Inc., for the U.S. Department of Energy’s National Nuclear Security Administration under contract DE-NA0003525.

Dalbey, Keith↗
DOE OSTI2017

Whole-Genome and Epigenomic Landscapes of Etiologically Distinct Subtypes of Cholangiocarcinoma

Cholangiocarcinoma (CCA) is a hepatobiliary malignancy exhibiting high incidence in countries with endemic liver-fluke infection. We analysed 489 CCAs from 10 countries, combining whole-genome (71 cases), targeted/exome, copy-number, gene expression, and DNA methylation information. Integrative clustering defined four CCA clusters - Fluke- Positive CCAs (Clusters 1/2) are enriched in ERBB2 amplifications and TP53 mutations, conversely Fluke-Negative CCAs (Clusters 3/4) exhibit high copy-number alterations and PD-1/PD-L2 expression, or epigenetic mutations (IDH1/2, BAP1) and FGFR/PRKA-related gene rearrangements. Whole-genome analysis highlighted FGFR2 3’UTR deletion as a mechanism of FGFR2 upregulation. Integration of non-coding promoter mutations with protein-DNA binding profiles demonstrates pervasive modulation of H3K27me3-associated sites in CCA. Clusters 1 and 4 exhibit distinct DNA hypermethylation patterns targeting either CpG islands or shores - mutation signature and subclonality analysis suggests that these reflect different mutational pathways. Lastly, our results exemplify how genetics, epigenetics and environmental carcinogens can interplay across different geographies to generate distinct molecular subtypes of cancer.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS1993

Constraints on chemical evolution models from QSOALS abundances

Models of the formation and early chemical evolution of our Galaxy are guided and constrained by our knowledge of abundances in globular cluster stars and halo field stars. The abundance patterns identified in halo and disk stars should be discernible in absorption lines of gas clouds in forming galaxies which are accidentally lying in front of background QSO's. Conversely, the ensemble of QSO absorption line systems (QSOALS) at each redshift may suggest a detailed model for the formation of our Galaxy that is testable using abundance patterns in halo stars.

Lauroesch, J. T.↗
NASA NTRS2003

Control of T lymphocyte morphology by the GTPase Rho

BACKGROUND: Rho family GTPase regulation of the actin cytoskeleton governs a variety of cell responses. In this report, we have analyzed the role of the GTPase Rho in maintenance of the T lymphocyte actin cytoskeleton. RESULTS: Inactivation of the GTPase Rho in the human T lymphocytic cell line HPB-ALL does not inhibit constitutively high adhesion to the integrin beta1 substrate fibronectin. It did however result in the aberrant extension of finger-like dendritic processes on the substrates VCAM-1, Fn, and mAb specific to beta1 integrins. Time-lapse video microscopy demonstrated that C3 induced extensions were primarily the result of an altered pseudopod elongation rather than retraction. Once the stellate pseudopodia extended, none retracted, and cells became completely immobile. Filipodial structures were absent and the dendritic-like processes in C3 treated cells were rich in filamentous actin. Immunolocalization of RhoA in untreated HPB-ALL cells spreading on fibronectin demonstrated a diffuse staining pattern within the pseudopodia. In C3 treated cells, clusters of RhoA were pronounced and localized within the altered extensions. CONCLUSIONS: GTPase Rho is actively involved in the regulation of T lymphocyte morphology and motility.

Non-NASA Center↗