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NASA NTRS1994

Solar granulation and statistical crystallography: A modeling approach using size-shape relations

The irregular polygonal pattern of solar granulation is analyzed for size-shape relations using statistical crystallography. In contrast to previous work which has assumed perfectly hexagonal patterns for granulation, more realistic accounting of cell (granule) shapes reveals a broader basis for quantitative analysis. Several features emerge as noteworthy: (1) a linear correlation between number of cell-sides and neighboring shapes (called Aboav-Weaire's law); (2) a linear correlation between both average cell area and perimeter and the number of cell-sides (called Lewis's law and a perimeter law, respectively) and (3) a linear correlation between cell area and squared perimeter (called convolution index). This statistical picture of granulation is consistent with a finding of no correlation in cell shapes beyond nearest neighbors. A comparative calculation between existing model predictions taken from luminosity data and the present analysis shows substantial agreements for cell-size distributions. A model for understanding grain lifetimes is proposed which links convective times to cell shape using crystallographic results.

Noever, D. A.↗

DOE OSTI2017

Moving into advanced nanomaterials. Toxicity of rutile TiO{sub 2} nanoparticles immobilized in nanokaolin nanocomposites on HepG2 cell line

Immobilization of nanoparticles on inorganic supports has been recently developed, resulting in the creation of nanocomposites. Concerning titanium dioxide nanoparticles (TiO{sub 2} NPs), these have already been developed in conjugation with clays, but so far there are no available toxicological studies on these nanocomposites. The present work intended to evaluate the hepatic toxicity of nanocomposites (C-TiO{sub 2}), constituted by rutile TiO{sub 2} NPs immobilized in nanokaolin (NK) clay, and its individual components. These nanomaterials were analysed by means of FE-SEM and DLS analysis for physicochemical characterization. HepG2 cells were exposed to rutile TiO{sub 2} NPs, NK clay and C-TiO{sub 2} nanocomposite, in the presence and absence of serum for different exposure periods. Possible interferences with the methodological procedures were determined for MTT, neutral red uptake, alamar blue (AB), LDH, and comet assays, for all studied nanomaterials. Results showed that MTT, AB and alkaline comet assay were suitable for toxicity analysis of the present materials after slight modifications to the protocol. Significant decreases in cell viability were observed after exposure to all studied nanomaterials. Furthermore, an increase in HepG2 DNA damage was observed after shorter periods of exposure in the absence of serum proteins and longer periods of exposure in their presence. Although the immobilization of nanoparticles in micron-sized supports could, in theory, decrease the toxicity of single nanoparticles, the selection of a suitable support is essential. The present results suggest that NK clay is not the appropriate substrate to decrease TiO{sub 2} NPs toxicity. Therefore, for future studies, it is critical to select a more appropriate substrate for the immobilization of TiO{sub 2} NPs. - Highlights: • Only the MTT and AB assays were found to be suitable for cytotoxicity assessment. • Alkaline comet assay was also appropriate for genotoxicity evaluation. • All nanomaterials decreased the HepG2 cell viability and caused DNA damage. • Nanokaolin is not a suitable clay substrate for the immobilization of TiO{sub 2} NPs. • Further toxicity studies must be performed in other clays to support nanoparticles.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2013

Functional analysis of the NH{sub 2}-terminal hydrophobic region and BRICHOS domain of GKN1

Highlights: •NH{sub 2}-terminal and BRICHOS domain of GKN1 inhibited tumor cell growth. •NH{sub 2}-terminal and BRICHOS domain of GKN1 regulated cell cycle. •NH{sub 2}-terminal and BRICHOS domain of GKN1 inhibited epigenetic regulators. -- Abstract: Gastrokine 1 (GKN1) protects the gastric antral mucosa and promotes healing by facilitating restitution and proliferation after injury. GKN1 is down-regulated in Helicobacter pylori-infected gastric epithelial cells and loss of GKN1 expression is tightly associated with gastric carcinogenesis. However, the underlying mechanisms as a tumor suppressor are largely unknown. Presently, the hydrophobic region and BRICHOS domain of GKN1, pGKN1{sup D13N}, pGKN1{sup Δ68–199}, and pGKN1{sup Δ1–67,165–199} were shown to suppress gastric cancer cell growth and recapitulate GKN1 functions. As well, the hydrophobic region and BRICHOS domain of GKN1 had a synergistic anti-cancer effect with 5-FU on tumor cell growth, implying that the NH{sub 2}-terminal hydrophobic region and BRICHOS domain of GKN1 are sufficient for tumor suppression, thereby suggesting a therapeutic intervention for gastric cancer. Also, its domain inducing endogenous miR-185 directly targeted the epigenetic effectors DNMT1 and EZH2 in gastric cancer cells. Our results suggest that the NH{sub 2}-terminal hydrophobic region and BRICHOS domain of GKN1 are sufficient for its tumor suppressor activities.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2017

TEAD4-YAP interaction regulates tumoral growth by controlling cell-cycle arrest at the G1 phase

TEA domain transcription factor 4 (TEAD4), which has critical functions in the process of embryonic development, is expressed in various cancers. However, the important role of TEAD4 in human oral squamous cell carcinomas (OSCCs) remain unclear. Here we investigated the TEAD4 expression level and the functional mechanism in OSCC using quantitative reverse transcriptase-polymerase chain reaction, Western blot analysis, and immunohistochemistry. Furthermore, TEAD4 knockdown model was used to evaluate cellular proliferation, cell-cycle analysis, and the interaction between TEAD4 and Yes-associated protein (YAP) which was reported to be a transcription coactivator of cellular proliferation. In the current study, we found that TEAD4 expression increased significantly in vitro and in vivo and correlated with tumoral size in OSCC patients. TEAD4 knockdown OSCC cells showed decreased cellular proliferation resulting from cell-cycle arrest in the G1 phase by down-regulation of cyclins, cyclin-dependent kinases (CDKs), and up-regulation of CDK inhibitors. We also found that the TEAD4-YAP complex in the nuclei may be related closely to transcriptions of G1 arrest-related genes. Taken together, we concluded that TEAD4 might play an important role in tumoral growth and have potential to be a therapeutic target in OSCCs. - Highlights: • TEAD4 contributes to tumor progression in OSCCs. • TEAD4 knockdown results in cell-cycle arrest at the G1phase in OSCC cells. • In TEAD4 knockdown cells, the amount of YAP in the nucleus decreases. • Activation of the TEAD4-YAP complex is an important factor in OSCC tumor growth. • TEAD4 might be a critical biomarker and a therapeutic target for OSCCs.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2017

The Maize Mid-Complementing Activity Homolog Cell Number Regulator13/Narrow Odd Dwarf Coordinates Organ Growth and Tissue Patterning

Organogenesis occurs through cell division, expansion, and differentiation. How these cellular processes are coordinated remains elusive. The maize ( Zea mays ) leaf provides a robust system to study cellular differentiation due to its distinct tissues and cell types. The narrow odd dwarf ( nod ) mutant displays defects at both the cellular and tissue level that increase in severity throughout growth. nod mutant leaves have reduced size due to fewer and smaller cells compared with the wild type. The juvenile-to-adult transition is delayed, and proximal distal-patterning is abnormal in this mutant. Differentiation of specialized cells such as those forming stomata and trichomes is incomplete. Analysis of nod-1 sectors suggests that NOD plays a cell-autonomous function in the leaf. We cloned nod positionally and found that it encodes CELL NUMBER REGULATOR13 (CNR13), the maize MID-COMPLEMENTING ACTIVITY homolog. CNR13/NOD is localized to the membrane and is enriched in dividing tissues. Transcriptome analysis of nod mutants revealed overrepresentation of cell wall, hormone metabolism, and defense gene categories. Here, we propose that NOD coordinates cell activity in response to intrinsic and extrinsic cues.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2017

National Cancer Database Analysis of Proton Versus Photon Radiation Therapy in Non-Small Cell Lung Cancer

Purpose: To analyze outcomes and predictors associated with proton radiation therapy for non-small cell lung cancer (NSCLC) in the National Cancer Database. Methods and Materials: The National Cancer Database was queried to capture patients with stage I-IV NSCLC treated with thoracic radiation from 2004 to 2012. A logistic regression model was used to determine the predictors for utilization of proton radiation therapy. The univariate and multivariable association with overall survival were assessed by Cox proportional hazards models along with log–rank tests. A propensity score matching method was implemented to balance baseline covariates and eliminate selection bias. Results: A total of 243,822 patients (photon radiation therapy: 243,474; proton radiation therapy: 348) were included in the analysis. Patients in a ZIP code with a median income of <$46,000 per year were less likely to receive proton treatment, with the income cohort of $30,000 to $35,999 least likely to receive proton therapy (odds ratio 0.63 [95% confidence interval (CI) 0.44-0.90]; P=.011). On multivariate analysis of all patients, non-proton therapy was associated with significantly worse survival compared with proton therapy (hazard ratio 1.21 [95% CI 1.06-1.39]; P<.01). On propensity matched analysis, proton radiation therapy (n=309) was associated with better 5-year overall survival compared with non-proton radiation therapy (n=1549), 22% versus 16% (P=.025). For stage II and III patients, non-proton radiation therapy was associated with worse survival compared with proton radiation therapy (hazard ratio 1.35 [95% CI 1.10-1.64], P<.01). Conclusions: Thoracic radiation with protons is associated with better survival in this retrospective analysis; further validation in the randomized setting is needed to account for any imbalances in patient characteristics, including positron emission tomography–computed tomography staging.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

DOE OSTI2014

Microparticles generated during chronic cerebral ischemia deliver proapoptotic signals to cultured endothelial cells

Highlights: • Microparticles are elevated in the plasma in a rodent model of chronic cerebral ischemia. • These microparticles initiate apoptosis in cultured cells. • Microparticles contain caspase 3 and they activate receptors for TNF-α and TRAIL. - Abstract: Circulating microparticles (MPs) are involved in many physiological processes and numbers are increased in a variety of cardiovascular disorders. The present aims were to characterize levels of MPs in a rodent model of chronic cerebral hypoperfusion (CCH) and to determine their signaling properties. MPs were isolated from the plasma of rats exposed to CCH and quantified by flow cytometry. When MPs were added to cultured endothelial cells or normal rat kidney cells they induced cell death in a time and dose dependent manner. Analysis of pellets by electron microscopy indicates that cell death signals are carried by particles in the range of 400 nm in diameter or less. Cell death involved the activation of caspase 3 and was not a consequence of oxidative stress. Inhibition of the Fas/FasL signaling pathway also did not improve cell survival. MPs were found to contain caspase 3 and treating the MPs with a caspase 3 inhibitor significantly reduced cell death. A TNF-α receptor blocker and a TRAIL neutralizing antibody also significantly reduced cell death. Levels of circulating MPs are elevated in a rodent model of chronic cerebral ischemia. MPs with a diameter of 400 nm or less activate the TNF-α and TRAIL signaling pathways and may deliver caspase 3 to cultured cells.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2017

Differential gene expression profiling of human adipose stem cells differentiating into smooth muscle-like cells by TGFβ1/BMP4

Regenerative repair of the vascular system is challenging from the perspectives of translational medicine and tissue engineering. There are fundamental hurdles in front of creating bioartificial arteries, which involve recaputilation of the three-layered structure under laboratory settings. Obtaining and maintaining smooth muscle characteristics is an important limitation, as the transdifferentiated cells fail to display mature phenotype. This study aims to shed light on the smooth muscle differentiation of human adipose stem cells (hASCs). To this end, we first acquired hASCs from lipoaspirate samples. Upon characterization, the cells were induced to differentiate into smooth muscle (SM)-like cells using a variety of inducer combinations. Among all, TGFβ1/BMP4 combination had the highest differentiation efficiency, based on immunohistochemical analyses. hSM-like cell samples were compared to hASCs and to the positive control, human coronary artery-smooth muscle cells (hCA-SMCs) through gene transcription profiling. Microarray findings revealed the activation of gene groups that function in smooth muscle differentiation, signaling pathways, extracellular modeling and cell proliferation. Our results underline the effectiveness of the growth factors and suggest some potential variables for detecting the SM-like cell characteristics. Evidence in transcriptome level was used to evaluate the TGFβ1/BMP4 combination as a previously unexplored effector for the smooth muscle differentiation of adipose stem cells. - Highlights: • Human adipose stem cells (hASCs) were isolated, characterized and cultured. • Growth factor combinations were evaluated for their effectiveness in differentiation using IHC. • hASCs were differentiated into smooth muscle (SM)-like cells using TGF-β1 and BMP4 combination. • Microarray analysis was performed for hASCs, SM-like cells and coronary artery-SMCs. • Microarray data was used to perform hierarchical clustering and interpretation of activated pathways.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2013

Geometrical investigation of the kinetic evolution of the magnetic field in a periodic flux rope

Flux ropes are bundles of magnetic field wrapped around an axis. Many laboratory, space, and astrophysics processes can be represented using this idealized concept. Here, a massively parallel 3D kinetic simulation of a periodic flux rope undergoing the kink instability is studied. The focus is on the topology of the magnetic field and its geometric structures. The analysis considers various techniques such as Poincaré maps and the quasi-separatrix layer (QSL). These are used to highlight regions with expansion or compression and changes in the connectivity of magnetic field lines and consequently to outline regions where heating and current may be generated due to magnetic reconnection. The present study is, to our knowledge, the first QSL analysis of a fully kinetic 3D particle in cell simulation and focuses the existing QSL method of analysis to periodic systems.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗

DOE OSTI2016

Moisture Risk in Unvented Attics Due to Air Leakage Paths - Minneapolis Minnesota

IBACOS completed an initial analysis of moisture damage potential in an unvented attic insulated with closed-cell spray polyurethane foam. To complete this analysis, the research team collected field data, used computational fluid dynamics to quantify the airflow rates through individual airflow (crack) paths, simulated hourly flow rates through the leakage paths with CONTAM software, correlated the CONTAM flow rates with indoor humidity ratios from Building Energy Optimization software, and used "Warme und Feuchte instationar Pro two-dimensional modeling" to determine the moisture content of the building materials surrounding the cracks. Given the number of simplifying assumptions and numerical models associated with this analysis, the results indicate that localized damage due to high moisture content of the roof sheathing is possible under very low airflow rates. Reducing the number of assumptions and approximations through field studies and laboratory experiments would be valuable to understand the real-world moisture damage potential in unvented attics.

Array↗

DOE OSTI2014

Amyloid precursor protein regulates migration and metalloproteinase gene expression in prostate cancer cells

Highlights: • APP knockdown reduced proliferation and migration of prostate cancer cells. • APP knockdown reduced expression of metalloproteinase and EMT-related genes. • APP overexpression promoted LNCaP cell migration. • APP overexpression increased expression of metalloproteinase and EMT-related genes. - Abstract: Amyloid precursor protein (APP) is a type I transmembrane protein, and one of its processed forms, β-amyloid, is considered to play a central role in the development of Alzheimer’s disease. We previously showed that APP is a primary androgen-responsive gene in prostate cancer and that its increased expression is correlated with poor prognosis for patients with prostate cancer. APP has also been implicated in several human malignancies. Nevertheless, the mechanism underlying the pro-proliferative effects of APP on cancers is still not well-understood. In the present study, we explored a pathophysiological role for APP in prostate cancer cells using siRNA targeting APP (siAPP). The proliferation and migration of LNCaP and DU145 prostate cancer cells were significantly suppressed by siAPP. Differentially expressed genes in siAPP-treated cells compared to control siRNA-treated cells were identified by microarray analysis. Notably, several metalloproteinase genes, such as ADAM10 and ADAM17, and epithelial–mesenchymal transition (EMT)-related genes, such as VIM, and SNAI2, were downregulated in siAPP-treated cells as compared to control cells. The expression of these genes was upregulated in LNCaP cells stably expressing APP when compared with control cells. APP-overexpressing LNCaP cells exhibited enhanced migration in comparison to control cells. These results suggest that APP may contribute to the proliferation and migration of prostate cancer cells by modulating the expression of metalloproteinase and EMT-related genes.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2016

T24 HRAS transformed NIH/3T3 mouse cells (GhrasT-NIH/3T3) in serial tumorigenic in vitro/in vivo passages give rise to increasingly aggressive tumorigenic cell lines T1-A and T2-A and metastatic cell lines T3-HA and T4-PA

Cancer cells often arise progressively from “normal” to “pre-cancer” to “transformed” to “local metastasis” to “metastatic disease” to “aggressive metastatic disease”. Recent whole genome sequencing (WGS) and spectral karyotyping (SKY) of cancer cells and tumorigenic models have shown this progression involves three major types of genome rearrangements: ordered small step-wise changes, more dramatic “punctuated evolution” (chromoplexy), and large catastrophic steps (chromothripsis) which all occur in random combinations to generate near infinite numbers of stochastically rearranged metastatic cancer cell genomes. This paper describes a series of mouse cell lines developed sequentially to mimic this type of progression. This starts with the new GhrasT-NIH/Swiss cell line that was produced from the NIH/3T3 cell line that had been transformed by transfection with HRAS oncogene DNA from the T24 human bladder carcinoma. These GhrasT-NIH/Swiss cells were injected s.c. into NIH/Swiss mice to produce primary tumors from which one was used to establish the T1-A cell line. T1-A cells injected i.v. into the tail vein of a NIH/Swiss mouse produced a local metastatic tumor near the base of the tail from which the T2-A cell line was established. T2-A cells injected i.v. into the tail vein of a nude NIH/Swiss mouse produced metastases in the liver and one lung from which the T3-HA (H=hepatic) and T3-PA (P=pulmonary) cell lines were developed, respectively. T3-HA cells injected i.v. into a nude mouse produced a metastasis in the lung from which the T4-PA cell line was established. PCR analysis indicated the human T24 HRAS oncogene was carried along with each in vitro/in vivo transfer step and found in the T2-A and T4-PA cell lines. Light photomicrographs indicate that all transformed cells are morphologically similar. GhrasT-NIH/Swiss cells injected s.c. produced tumors in 4% of NIH/Swiss mice in 6–10 weeks; T1-A cells injected s.c. produced tumors in 100% of NIH/Swiss mice in 7–10 days. T1-A, T-2A, T3-HA and T4-PA cells when injected i.v. into the tail produced local metastasis in non-nude or nude NIH/Swiss mice. T4-PA cells were more widely metastatic than T3-HA cells when injected i.v. into nude mice. Evaluation of the injected mice indicated a general increase in metastatic potential of each cell line in the progression as compared to the GhrasT-NIH/3T3 transformed cells. A new photomicrographic technique to follow growth rates within six preselected 2×2 mm{sup 2} grids per plate is described. Average doubling times of the transformed cells GhrasT-NIH/3T3 (17 h), T1A (17.5 h), T2A (15.5 h), T3-HA (17.5 h) and T4-PA (18.5 h) (average 17.2 h) were significantly faster (P=0.006) than NIH Swiss primary embryonic cells and NIH/3T3 cells (22 h each). This cell series is currently used in this lab for studies of cancer cell inhibitors, mitochondrial biogenesis and gene expression and is available for further study by other investigators for intra- and inter-laboratory comparisons of WGS, transcriptome sequencing, SKY and other analyses. The genome rearrangements in these cells together with their phenotypic properties may help provide more insights into how one tumorigenic progression occurred to produce the various cell lines that led to the highly metastatic T4-PA cell line. - Highlights: • A tumor progression model derived from a new T24 HRAS transformed NIH/3T3 cell line. • T1-A, T2-A, T3-HA, T4PA lines derived from GhrasT-NIH/3T3, T1-A, T2-A, T3-HA tumors. • PCR detected the human HRAS oncogene in T2-A and T4-PA metastatic tumors. • These five new cell lines showed a progressive increase in tumorigenic potential. • New method obtained doubling times using daily photomicrographs of gridded plates.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2017

Single-cell RNA sequencing reveals intrinsic and extrinsic regulatory heterogeneity in yeast responding to stress

From bacteria to humans, individual cells within isogenic populations can show significant variation in stress tolerance, but the nature of this heterogeneity is not clear. To investigate this, we used single-cell RNA sequencing to quantify transcript heterogeneity in single Saccharomyces cerevisiae cells treated with and without salt stress to explore population variation and identify cellular covariates that influence the stress-responsive transcriptome. Leveraging the extensive knowledge of yeast transcriptional regulation, we uncovered significant regulatory variation in individual yeast cells, both before and after stress. Moreover, we discovered that a subset of cells appears to decouple expression of ribosomal protein genes from the environmental stress response in a manner partly correlated with the cell cycle but unrelated to the yeast ultradian metabolic cycle. Live-cell imaging of cells expressing pairs of fluorescent regulators, including the transcription factor Msn2 with Dot6, Sfp1, or MAP kinase Hog1, revealed both coordinated and decoupled nucleocytoplasmic shuttling. Together with transcriptomic analysis, our results suggest that cells maintain a cellular filter against decoupled bursts of transcription factor activation but mount a stress response upon coordinated regulation, even in a subset of unstressed cells.

59 BASIC BIOLOGICAL SCIENCES↗

NASA NTRSDate not supplied

Multiscale Analysis of Thermo-Mechanical Behavior of Boron Nitride-Reinforced Epoxy Nanocomposites

The effect of size, shape, morphology, and arrangement of micro constituents of Boron Nitrite (BN) nanoplatelet/epoxy composites on their properties were investigated using a multi scale approach that includes Molecular Dynamics (MD) and micromechanics. The thermo-mechanical properties of the composites were evaluated using molecular theory and the analysis showed that the elastic constants of BN/epoxy composites were not severely affected by temperature. Also, the micromechanical analysis of Generalized Method of Cells (GMC) was utilized at higher length scale to evaluate elastic properties of the composites, for different geometries and arrangements of micro constituents. The predicted results of the analysis showed that the size, aspect ratios, morphology, and the arrangements of inclusions in BN/epoxy nanocomposites all have remarkable effect on the mechanical performances of the material systems.

nanocomposites↗

DOE OSTI2018

Comparative Analysis of the Formation of γH2AX Foci in Human Mesenchymal Stem Cells Exposed to {sup 3}H-Thymidine, Tritium Oxide, and X-Rays Irradiation

We performed a comparative study of the formation of γН2АХ foci (a marker of DNA doublestrand breaks) in human bone marrow mesenchymal stem cells after 24-h incubation with {sup 3}Н-thimidin and tritium oxide with low specific activities (50-800 MBq/liter). The dependence of the number of γH2AX foci on specific activity of 3H-thymidine was described by a linear equation y=2.21+43.45x (R{sup 2}=0.96), where y is the number of γH2AX foci per nucleus and x is specific activity in 1000 MBq/liter. For tritium oxide, the relationship was described by a linear equation y=2.52+6.70x (R{sup 2}=0.97). Thus, the yield of DNA double-strand breaks after exposure to {sup 3}H-thymidine was 6.5-fold higher than after exposure to tritium oxide. Comparison of the effects of tritium oxide and X-ray radiation on the yield of DNA double-strand breaks showed that the relative biological efficiency of tritium oxide in a dose range of 3.78-60.26 mGy was 1.6-fold higher than that of X-ray radiation. Improvement of the methods of analysis of DNA double-strand breaks repair foci is highly promising in the context of creation of highly sensitive biodosimetry technologies for tritium compounds in humans.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

DOE OSTI2022

Carbon-negative production of acetone and isopropanol by gas fermentation at industrial pilot scale

Many industrial chemicals that are produced from fossil resources could be manufactured more sustainably through fermentation. In this work, we describe the development of a carbon-negative fermentation route to producing the industrially important chemicals acetone and isopropanol from abundant, low-cost waste gas feedstocks, such as industrial emissions and syngas. Using a combinatorial pathway library approach, we first mined a historical industrial strain collection for superior enzymes that we used to engineer the autotrophic acetogen Clostridium autoethanogenum. Next, we used omics analysis, kinetic modeling and cell-free prototyping to optimize flux. Finally, we scaled-up our optimized strains for continuous production at rates of up to ~3 g/L/h and ~90% selectivity. Life cycle analysis confirmed a negative carbon footprint for the products. Unlike traditional production processes, which result in release of greenhouse gases, our process fixes carbon. These results show that engineered acetogens enable sustainable, high-efficiency, high-selectivity chemicals production. We expect that our approach can be readily adapted to a wide range of commodity chemicals.

59 BASIC BIOLOGICAL SCIENCES↗

NASA NTRS2003

A Comparison between Growth Morphology of "Eutectic" Cells/Dendrites and Single-Phase Cells/Dendrites

Directionally solidified (DS) intermetallic and ceramic-based eutectic alloys with an in-situ composite microstructure containing finely distributed, long aspect ratio, fiber, or plate reinforcements are being seriously examined for several advanced aero-propulsion applications. In designing these alloys, additional solutes need to be added to the base eutectic composition in order to improve heir high-temperature strength, and provide for adequate toughness and resistance to environmental degradation. Solute addition, however, promotes instability at the planar liquid-solid interface resulting in the formation of two-phase eutectic "colonies." Because morphology of eutectic colonies is very similar to the single-phase cells and dendrites, the stability analysis of Mullins and Sekerka has been extended to describe their formation. Onset of their formation shows a good agreement with this approach; however, unlike the single-phase cells and dendrites, there is limited examination of their growth speed dependence of spacing, morphology, and spatial distribution. The purpose of this study is to compare the growth speed dependence of the morphology, spacing, and spatial distribution of eutectic cells and dendrites with that for the single-phase cells and dendrites.

Tewari, S. N.↗

NASA NTRS1994

Inhibition of murine splenic T lymphocyte proliferation by 2-deoxy-D-glucose-induced metabolic stress

Female Swiss-Webster mice were injected with the glucose analogue 2-deoxy-D-glucose (2-DG), which when administered to rodents induces acute periods of metabolic stress. A single or multiple injections of 2-DG invoked a stress response, as evidenced by increases in serum corticosterone levels. The influence of this metabolic stressor on the blastogenic potential of splenic T lymphocytes was then examined. It was found that one, two, or three injections of 2-DG resulted in depressed T cell proliferative responses, with an attenuation of the effect occurring by the fifth injection. The 2-DG-induced inhibition of T cell proliferation was not attributable to 2-DG-induced cytolysis, as in vitro incubation of naive T cells with varying concentrations of 2-DG did not result in a reduction in cell number or viability, and flow cytometric analysis demonstrated that percentages of CD3, CD4, and CD8 splenic T cells were not altered as a result of 2-DG-induced stress. Incubating naive T cells in varying concentrations of 2-DG resulted in a dose-dependent inhibition of T cell blastogenic potential. Following in vivo exposure to 2-DG, T cell proliferation did not return to normal levels until 3 days after the cessation of 2-DG injections. Administering the beta-adrenergic receptor antagonist propranolol did not reverse the inhibited lymphoproliferation in 2-DG-treated mice. The inhibition in T cell proliferation was not observed, however, in mice that had been adrenalectomized or hypophysectomized and injected with 2-DG.(ABSTRACT TRUNCATED AT 250 WORDS).

Non-NASA Center↗