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DOE OSTI2022

Differential methods for assessing sensitivity in biological models

Differential sensitivity analysis is indispensable in fitting parameters, understanding uncertainty, and forecasting the results of both thought and lab experiments. Although there are many methods currently available for performing differential sensitivity analysis of biological models, it can be difficult to determine which method is best suited for a particular model. In this paper, we explain a variety of differential sensitivity methods and assess their value in some typical biological models. First, we explain the mathematical basis for three numerical methods: adjoint sensitivity analysis, complex perturbation sensitivity analysis, and forward mode sensitivity analysis. We then carry out four instructive case studies. (a) The CARRGO model for tumor-immune interaction highlights the additional information that differential sensitivity analysis provides beyond traditional naive sensitivity methods, (b) the deterministic SIR model demonstrates the value of using second-order sensitivity in refining model predictions, (c) the stochastic SIR model shows how differential sensitivity can be attacked in stochastic modeling, and (d) a discrete birth-death-migration model illustrates how the complex perturbation method of differential sensitivity can be generalized to a broader range of biological models. Finally, we compare the speed, accuracy, and ease of use of these methods. We find that forward mode automatic differentiation has the quickest computational time, while the complex perturbation method is the simplest to implement and the most generalizable.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2026

Modeling glass degradation and release of radionuclides from vitrified waste for performance assessment simulations

The release of radionuclides initially encapsulated in a slowly degrading solid waste form and contained in an eventually corroding canister defines the source term for numerical simulations for the assessment of a geologic repository for high-level radioactive waste. While the details of waste degradation, canister corrosion, and dissolution and mobilization of the radionuclides in pore water include complex chemical reaction and transport processes that are coupled to the thermal, hydrological, microbiological, and mechanical conditions in the repository, the source-term model suitable for use in a numerical performance assessment model should be a defensible abstraction of these mechanisms. We developed a radiological source-term model and implemented it into a non-isothermal flow and transport simulator. While the proposed source-term model is applicable to various waste forms, canister systems, and disposal concepts, we specifically considered radionuclide releases from vitrified high-level waste placed in a cylindrical canister disposed in a deep vertical borehole repository. In this model, waste degradation is a function of temperature, and it can be adjusted to evaluate the influence of and propagate uncertainties in pH, passivation reactions, and chemical conditions as well as geometrical factors. The time-dependent, congruent release of safety-relevant radionuclides present in the decaying inventory is then calculated. Finally, the radionuclides are mobilized by diffusive and advective transport according to the thermo-hydraulic conditions prevailing in the near field of the repository, from where they migrate through the geosphere to the accessible environment. We examine the influence of the source-term model’s parameters on performance assessment calculations through sensitivity and uncertainty propagation analyses, identifying influential factors and confirming the upper bound of their impact. These considerations align with the overarching goal of repository design, which is to demonstrate that engineered and natural barriers can collectively delay radionuclide migration for timescales far exceeding human planning, thereby providing multiple, redundant barriers against environmental contamination.

iTOUGH2↗

NASA NTRS2002

Secure Remote Access Issues in a Control Center Environment

The ISS finally reached an operational state and exists for local and remote users. Onboard payload systems are managed by the Huntsville Operations Support Center (HOSC). Users access HOSC systems by internet protocols in support of daily operations, preflight simulation, and test. In support of this diverse user community, a modem security architecture has been implemented. The architecture has evolved over time from an isolated but open system to a system which supports local and remote access to the ISS over broad geographic regions. This has been accomplished through the use of an evolved security strategy, PKI, and custom design. Through this paper, descriptions of the migration process and the lessons learned are presented. This will include product decision criteria, rationale, and the use of commodity products in the end architecture. This paper will also stress the need for interoperability of various products and the effects of seemingly insignificant details.

Pitts, Lee↗

NASA NTRS2002

Secure Payload Access to the International Space Station

Pitts, R. Lee↗

DOE OSTI2023

Controlling solute channel formation using magnetic fields

Solute channel formation introduces compositional and microstructural variations in a range of processes, from metallic alloy solidification, to salt fingers in ocean and water reservoir flows. Applying an external magnetic field interacts with thermoelectric currents at solid/liquid interfaces generating additional flow fields. This thermoelectric (TE) magnetohydrodynamic (TEMHD) effect can impact on solute channel formation, via a mechanism recently drawing increasing attention. To investigate this phenomenon, we combined in situ synchrotron X-ray imaging and Parallel-Cellular-Automata-Lattice-Boltzmann based numerical simulations to study the characteristics of flow and solute transport under TEMHD. Observations suggest the macroscopic TEMHD flow appearing ahead of the solidification front, coupled with the microscopic TEMHD flow arising within the mushy zone are the primary mechanisms controlling plume migration and channel bias. Two TE regimes were revealed, each with distinctive mechanisms that dominate the flow. Further, we show that grain orientation modifies solute flow through anisotropic permeability. These insights led to a proposed strategy for producing solute channel-free solidification using a time-modulated magnetic field.

36 MATERIALS SCIENCE↗

DOE OSTI2018

Knockdown of pyruvate kinase type M2 suppresses tumor survival and invasion in osteosarcoma cells both in vitro and in vivo

Highlights: • Knockdown of PKM2 inhibited proliferation and induced apoptosis in OS cells. • Knockdown of PKM2 inhibited migration and invasion of OS cells. • Knockdown of PKM2 exerted its function on OS cells via multiple pathways. • OS cells with PKM2 inhibition exhibited restricted proliferation ability in vivo. Osteosarcoma (OS) is the mostly diagnosed primary bone malignancy. Emerging evidence indicates that the activity of pyruvate kinase M2 (PKM2) isoform is crucial for the survival of tumor cells. In the present study, the effect of PKM2 knockdown on the proliferation and migration of OS cells were assessed both in vitro and in vivo. Small hairpin RNA (shRNA) technology were employed to suppress the expression of PKM2 in MG-63 and Saos-2 cell lines. In vitro, shRNA-mediated knockdown of PKM2 efficiently inhibited cell proliferation, and induced G1 cell cycle arrest and apoptosis in both cell lines, which was associated with decreased expressions of cyclin D1 and Bcl-2 as well as increased expressions of Bax, cleaved-caspase-3, and cleaved-PARP. The invasion and migration potential of OS cell lines were also inhibited by PKM2 knockdown through the regulating effect of PKM2 on MMP-2 and VEGF signaling. In vivo, knockdown of PKM2 decelerated tumor growth rate and induced structure deterioration in tumor tissues. The current study for the first time showed that the activity of PKM2 was indispensable for the development and metastasis of OS, thereby providing the basic information for the future development of PKM2-based anti-OS therapies.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2017

Localised nanoscale resistive switching in GaP thin films with low power consumption

Nanoscale localisation of the electroforming-free resistive switching (RS) behaviour in polycrystalline GaP thin films has been observed for the first time. A combination of conductive atomic force microscopy and first-order reversal curve current–voltage measurements indicated that the grain boundaries are the preferred sites for the formation of the conductive switching filaments. It is proposed, based on TEM and XPS results, that local electrochemical migration of Ga ions along the grain boundaries plays a critical role in the switching mechanism. In the low-resistance (ON) state, the conduction mechanism was found to be the space-charge-limited current mechanism, while the high-resistance (OFF) state was governed by the Frenkel–Poole mechanism. Here, a high OFF/ON resistance ratio (~10 4 ) and lower power consumption than current RS devices, in addition to the easy integration of GaP with silicon substrates, make these GaP films promising for future applications in future non-volatile resistive random access memory (RRAM).

36 MATERIALS SCIENCE↗

NASA NTRS1991

Excited state dynamics of thulium ions in yttrium aluminum garnets

The processes that take place in the excited states of a trivalent Thulium (Tm) ion in an Yttrium Aluminum Garnet (YAG) crystal, being relevant to the use of this system for laser applications, have been the object of several studies. We have reexamined this system focusing our attention on the dynamics of Tm following its excitation in the H-3(sub 4) level. Under these conditions the system relaxes through a cross-relaxation process. H-3(sub 4) yields F-3(sub 4), H-3(sub 6) yields F-3(sub 4), whose rate depends upon both the concentration of the Tm ion and the temperature of the crystal. The excitation spectrum obtained by monitoring the 1.8 micron emission of Tm (due to the F-3(sub 4) yields H-3(sub 6) transition) indicates an increase in the contribution to this emission from the H-3(sub 4) level relative to the H-3(sub 5) level as the Tm concentration increases; this shows the increased role played by the H-3(sub 4) level in pumping the infrared emission. Correspondingly, the duration of the luminescence originating in the H-3(sub 4) level is shortened as the concentration of Tm increases. The concentration quenching of this lifetime can be fit to a model which assumes that the cross-relaxation is due to a dipole-dipole interaction; from this fit, the intrinsic Tm lifetime in the absence of cross relaxation can be derived. We have used this lifetime to calculate the rate of the cross-relaxation process. We have evaluated this rate as a function of the temperature and found it to be fastest at 77 K. We have also calculated the microscopic interaction parameters for the cross-relaxation process by using two independent experimental features: (1) the time evolution of the emission from the H-3(sub 4) level; and (2) the spectral overlap between the H-3(sub 4) yields F-3(sub 4) emission and the H-3(sub 6) yields F-3(sub 4) absorption. We have also considered the migration of excitation among the Tm ions in the F-3(sub 4) level and calculated the relevant microparameter by the use of the relevant spectral overlap. The data are consistent with the model in which the Tm ions, once excited into the H-3(sub 4) level decay by cross-relaxation to the F-3(sub 4), and then transfer rapidly their energy to other Tm ions.

Armagan, G.↗

NASA NTRS2005

Single-Scale Retinex Using Digital Signal Processors

The Retinex is an image enhancement algorithm that improves the brightness, contrast and sharpness of an image. It performs a non-linear spatial/spectral transform that provides simultaneous dynamic range compression and color constancy. It has been used for a wide variety of applications ranging from aviation safety to general purpose photography. Many potential applications require the use of Retinex processing at video frame rates. This is difficult to achieve with general purpose processors because the algorithm contains a large number of complex computations and data transfers. In addition, many of these applications also constrain the potential architectures to embedded processors to save power, weight and cost. Thus we have focused on digital signal processors (DSPs) and field programmable gate arrays (FPGAs) as potential solutions for real-time Retinex processing. In previous efforts we attained a 21 (full) frame per second (fps) processing rate for the single-scale monochromatic Retinex with a TMS320C6711 DSP operating at 150 MHz. This was achieved after several significant code improvements and optimizations. Since then we have migrated our design to the slightly more powerful TMS320C6713 DSP and the fixed point TMS320DM642 DSP. In this paper we briefly discuss the Retinex algorithm, the performance of the algorithm executing on the TMS320C6713 and the TMS320DM642, and compare the results with the TMS320C6711.

Hines, Glenn↗

DOE OSTI2018

FOXP4-AS1 participates in the development and progression of osteosarcoma by downregulating LATS1 via binding to LSD1 and EZH2

Highlights: • We first confirmed that FOXP4-AS1 is overexpressed in OS, and is the independent risk factor in OS prognosis. • We further clarified that Upregulated FOXP4-AS1 promotes the proliferation, migration and cell cycle, but inhibits apoptosis of OS cells. • Finally, we demonstrated that FOXP4-AS1 participates in the development and progression of OS by downregulating LATS1. Osteosarcoma (OS) is the most common malignant bone tumor in children and adolescents. LncRNA has been confirmed to participate in a variety of cancers. The purpose of this study was to explore the effect of FOXP4-AS1 on the development of osteosarcoma (OS) and its underlying mechanism. FOXP4-AS1 expressions in 60 OS tissues and paracancerous tissues were detected by qRT-PCR (quantitative real-time polymerase chain reaction). We confirmed that FOXP4-AS1 was overexpressed in OS tissues than that of paracancerous tissues. The disease-free survival and overall survival of OS patients were not correlated with age, gender and tumor location, but remarkably correlated with FOXP4-AS1 expression, tumor size and lung metastasis. For in vitro experiments, MG63 cells expressed a higher expression of FOXP4-AS1, whereas U2OS cells expressed a lower expression, which were selected for the following studies. Overexpressed FOXP4-AS1 led to enhanced proliferation, migration and invasion, shortened G0/G1 phase, as well as inhibited cell cycle. Knockdown of FOXP4-AS1 in MG63 cells obtained the opposite results. Furthermore, RIP assay indicated that FOXP4-AS1 could inhibit LATS1 expression by binding to LSD1 and EZH2, so as to participate in OS development. In conclusion, these results revealed that FOXP4-AS1 is overexpressed in OS, and is the independent risk factor in OS prognosis. Upregulated FOXP4-AS1 promotes the proliferation, migration and cell cycle, but inhibits apoptosis of OS cells. Furthermore, FOXP4-AS1 participates in the development and progression of OS by downregulating LATS1 via binding to LSD1 and EZH2.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2015

Thrombospondin-1, -2 and -5 have differential effects on vascular smooth muscle cell physiology

Introduction: The thrombospondins (TSPs) are matricellular proteins that exert multifunctional effects by binding cytokines, cell-surface receptors and other proteins. TSPs play important roles in vascular pathobiology and are all expressed in arterial lesions. The differential effects of TSP-1, -2, and -5 represent a gap in knowledge in vascular smooth muscle cell (VSMC) physiology. Our objective is to determine if structural differences of the TSPs imparted different effects on VSMC functions critical to the formation of neointimal hyperplasia. We hypothesize that TSP-1 and -2 induce similar patterns of migration, proliferation and gene expression, while the effects of TSP-5 are different. Methods: Human aortic VSMC chemotaxis was tested for TSP-2 and TSP-5 (1–40 μg/mL), and compared to TSP-1 and serum-free media (SFM) using a modified Boyden chamber. Next, VSMCs were exposed to TSP-1, TSP-2 or TSP-5 (0.2–40 μg/mL). Proliferation was assessed by MTS assay. Finally, VSMCs were exposed to TSP-1, TSP-2, TSP-5 or SFM for 3, 6 or 24 h. Quantitative real-time PCR was performed on 96 genes using a microfluidic card. Statistical analysis was performed by ANOVA or t-test, with p < 0.05 being significant. Results: TSP-1, TSP-2 and TSP-5 at 20 μg/mL all induce chemotaxis 3.1 fold compared to serum-free media. TSP-1 and TSP-2 induced proliferation 53% and 54% respectively, whereas TSP-5 did not. In the gene analysis, overall, cardiovascular system development and function is the canonical pathway most influenced by TSP treatment, and includes multiple growth factors, cytokines and proteases implicated in cellular migration, proliferation, vasculogenesis, apoptosis and inflammation pathways. Conclusions and relevance: The results of this study indicate TSP-1, -2, and -5 play active roles in VSMC physiology and gene expression. Similarly to TSP-1, VSMC chemotaxis to TSP-2 and -5 is dose-dependent. TSP-1 and -2 induces VSMC proliferation, but TSP-5 does not, likely due conservation of N-terminal domains in TSP-1 and -2. In addition, TSP-1, -2 and -5 significantly affect VSMC gene expression; however, little overlap exists in the specific genes altered. This study further delineates TSP-1, -2 and -5's contributions to processes related to VSMC physiology. - Highlights: • We examined the effects of three different thrombospondins on smooth muscle cells. • Thrombospondins −1, −2, −5 all increase smooth muscle cell migration. • Thrombospondins −1 and −2, but not −5, increase smooth muscle cell proliferation. • All three thrombospondins exhibit temporally distinct patterns of gene expression. • Thrombospondins −1 and −2 display distinct patterns of gene expression.

60 APPLIED LIFE SCIENCES↗

NASA NTRS1990

Real-time data system: Incorporating new technology in mission critical environments

If the Space Station Freedom is to remain viable over its 30-year life span, it must be able to incorporate new information systems technologies. These technologies are necessary to enhance mission effectiveness and to enable new NASA missions, such as supporting the Lunar-Mars Initiative. Hi-definition television (HDTV), neural nets, model-based reasoning, advanced languages, CPU designs, and computer networking standards are areas which have been forecasted to make major strides in the next 30 years. A major challenge to NASA is to bring these technologies online without compromising mission safety. In past programs, NASA managers have been understandably reluctant to rely on new technologies for mission critical activities until they are proven in noncritical areas. NASA must develop strategies to allow inflight confidence building and migration of technologies into the trusted tool base. NASA has successfully met this challenge and developed a winning strategy in the Space Shuttle Mission Control Center. This facility, which is clearly among NASA's most critical, is based on 1970's mainframe architecture. Changes to the mainframe are very expensive due to the extensive testing required to prove that changes do not have unanticipated impact on critical processes. Systematic improvement efforts in this facility have been delayed due to this 'risk to change.' In the real-time data system (RTDS) we have introduced a network of engineering computer workstations which run in parallel to the mainframe system. These workstations are located next to flight controller operating positions in mission control and, in some cases, the display units are mounted in the traditional mainframe consoles. This system incorporates several major improvements over the mainframe consoles including automated fault detection by real-time expert systems and color graphic animated schematics of subsystems driven by real-time telemetry. The workstations have the capability of recording telemetry data and providing 'instant replay' for flight controllers. RTDS also provides unique graphics animated by real-time telemetry such as workstation emulation of the shuttle's flight instruments and displays of the remote manipulator system (RMS) position. These systems have been used successfully as prime operational tools since STS-26 and have supported seven shuttle missions.

Muratore, John F.↗

NASA NTRS2017

Aeolus -A Mission to Study the Thermal and Wind Environment of Mars

Aeolus is a small satellite mission to observe surface and atmospheric forcing and general circulation of Mars, by measuring surface energy balance, atmospheric temperatures, aerosols and clouds, and winds. Critically, Aeolus will make these measurements at all local times of day, providing information on both seasonal and diurnal variability. To date, direct measurements of Martian wind speeds have only been possible at the surface, only during daylight hours, and over small areas limited by rover traverse capabilities. From orbit, thermal measurements (e.g., estimates from assumed geostrophic balance) as well as images of dust storms and dune migration have provided inputs to derive current data sets on Martian winds. However, Mars General Circulation models demonstrate that wind speeds derived from these indirect measurements may be in error by 50 to 100%. For this reason, direct wind velocity measurements have been deemed "High Priority" by MEPAG (Mars Exploration Program Analysis Group); measuring wind speeds and corresponding thermal data is vital to understanding the climate of Mars. Aeolus will carry four Spatial Heterodyne Spectrometers (SHS), coupled to two orthogonal viewing telescopes. These high-resolution near-infrared spectrometers will measure CO2 (daytime absorption) and O2 (day and night emission) lines in the Martian atmosphere. Doppler shifts in these lines can be measured during Martian day and night, resolving wind speeds down to ~5 m/s. Orthogonal views allow the spectrometers to capture wind vectors over all observation locations. Aeolus will also carry the atmospheric limb-viewing Thermal Limb Sounder (TLS) to measure atmospheric temperatures, water ice clouds, and dust abundances across all altitudes where winds are measured. Finally, the Surface Radiometric Sensor Package (SuRSeP), a nadir viewing radiometer, will measure the total reflected solar and emitted thermal radiance, surface temperature, and water cloud and dust total column abundances. The combined spectral and thermal measurements will provide a new understanding of the global energy balance, dust transport processes, and climate cycles in the Martian atmosphere. Aeolus will consist of a single satellite in a near-polar orbit, allowing it to pass over all local times, with the baseline mission observing all seasons of an entire Martian year (two Earth years). Aeolus was one of two Martian smallsat concepts selected for study through the Planetary Science Deep Space SmallSat Studies program. This talk will provide an overview of the mission, including science rationale, instruments, spacecraft, and mission operations concept.

and winds↗

DOE OSTI2017

Representative Elementary Volume (REV) in spatio-temporal domain: A method to find REV for dynamic pores

One of the potential risks associated with subsurface storage of CO 2 is the seepage of CO 2 through existing faults and fractures. There have been a number of studies devoted to this topic. Some of these studies show that geochemistry, especially mineralization, plays an important role in rendering the faults as conduits for CO 2 movement while others show that mineralization due to CO 2 injection can result in seep migration and flow diversion. Therefore, understanding the changes in reservoir properties due to pore alterations is important to ensure safe long term CO 2 storage in the subsurface. We study the changes in the Representative Elementary Volume (REV) of a rock due to reactive kinetics over a time, using a statistical approach and pore-scale CO 2 -rock interactiondata. The goal of this study is to obtain the REV of a rock property that accounts for pore-scale changes over time due to reactive kinetics, and we call this as spatiotemporal REV. Scale-up results suggest that the REV changes with time when CO 2 -rock interaction is considered. It is hypothesized that the alteration in pore structure introduces more heterogeneity in the rock, and because of this the magnitude of REV increases. Furthermore, it is possible that these noticeable changes in REV at pore-scale may have an impact when analyzed at the reservoir scale.

54 ENVIRONMENTAL SCIENCES↗

DOE OSTI2022

Grain growth kinetics of the gamma phase metallic uranium

We report metallic uranium is a leading fuel form for sodium cooled fast reactors as an enabling technology of future nuclear energy systems. Mechanistic understanding of fuel behaviors and kinetics under thermodynamic equilibrium and highly non-equilibrium conditions are essential for evaluating fuel performance. It is important to understand and predict the grain and pore evolutions of metallic fuels under thermal and irradiation conditions. However, very limited data are available on the grain growth kinetics and mechanisms of pure gamma phase uranium. In this paper, the pure gamma uranium pellets with different grain structures were fabricated by combining high-energy ball milling and spark plasma sintering. Isothermal annealing tests were performed to investigate the grain growth behavior of the pure gamma phase uranium with different initial grain sizes. A parabolic relationship in grain growth with time was identified for the submicron-sized (374 nm) sample. In contrast, for the nano-sized (137 nm) sample, the grain growth shows a linear relationship with time. The activation energies of grain growth were determined as 199.5 KJ/mol and 80.6 KJ/mol for nano-sized and submicron-sized grain structures, respectively. For the nano-sized sample, the rate-control step of grain growth is dominated by the triple-junction migration, in which the grain boundary triple junction drags the grain growth, leading to a higher activation energy than the bulk diffusion. The dominating mechanism for the submicron-sized sample is grain boundary diffusion. The mechanistic understanding and critical data obtained on the kinetics of pure uranium phases will be useful to evaluate fuel behavior under thermodynamic equilibrium conditions and develop a high fidelity model to predict fuel performance.

11 NUCLEAR FUEL CYCLE AND FUEL MATERIALS↗

DOE OSTI2025

The Mystery of Baselevel Controls in the Incision History of the Central Colorado Plateau

Erosion can remain active and changing in landscapes long after tectonic drivers have ceased, potentially due to local-geologic controls, climate changes, or geodynamics. We present new fluvial incision-rate histories and terrain analyses of the Colorado River system through the central Colorado Plateau to understand what has caused the variable erosion across this post-orogenic landscape. Results from new cosmogenic and luminescence dating of fluvial terrace and upland gravel deposits in Glen and Meander Canyons establish incision-rate histories that are marked by an Early-Middle Pleistocene erosion hiatus, followed by ~200 m of rapid incision over the last ~350 kyr. Projection of fluvial topography from above knickzones of the Colorado River drainage system roughly agree with the observed magnitude of recent incision and reflect a common baselevel fall from Pliocene river integration through Grand Canyon, which is still propagating through the drainage. A response-time model indicates that baselevel fall from integration likely took 2–4 Myr to reach the central Colorado Plateau and 100s kyr to travel across the study area, potentially accounting for incision rate changes in the fluvial terrace records of Meander and Glen Canyons. The upstream-migrating incision has likely been partitioned into multiple waves across the landscape due to the local geologic controls of lava damming, salt tectonics, and heterogenous bedrock. As baselevel fall from Pliocene Colorado River integration diffuses upstream, it can only account for perhaps a quarter of the total ~2 km of exhumation in the central Colorado Plateau, demanding an unknown driver for significant erosion in the Pliocene.

58 GEOSCIENCES↗

DOE OSTI2014

The systemic delivery of an oncolytic adenovirus expressing decorin inhibits bone metastasis in a mouse model of human prostate cancer

In an effort to develop a new therapy for prostate cancer bone metastases, we have created Ad.dcn, a recombinant oncolytic adenovirus carrying the human decorin gene. Infection of PC-3 and DU-145, the human prostate tumor cells, with Ad.dcn or a non-replicating adenovirus Ad(E1-).dcn resulted in decorin expression; Ad.dcn produced high viral titers and cytotoxicity in human prostate tumor cells. Adenoviral-mediated decorin expression inhibited Met, the Wnt/β- catenin signaling axis, vascular endothelial growth factor A, reduced mitochondrial DNA levels, and inhibited tumor cell migration. To examine the anti-tumor response of Ad.dcn, PC-3-luc cells were inoculated in the left heart ventricle to establish bone metastases in nude mice. Ad.dcn, in conjunction with control replicating and non-replicating vectors were injected via tail vein. The real-time monitoring of mice, once a week, by bioluminescence imaging and X-ray radiography showed that Ad.dcn produced significant inhibition of skeletal metastases. Analyses of the mice at the terminal time point indicated a significant reduction in the tumor burden, osteoclast number, serum TRACP 5b levels, osteocalcin levels, hypercalcemia, inhibition of cancer cachexia, and an increase in the animal survival. Finally, based on these studies, we believe that Ad.dcn can be developed as a potential new therapy for prostate cancer bone metastasis.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2015

TILTING JUPITER (A BIT) AND SATURN (A LOT) DURING PLANETARY MIGRATION

We study the effects of planetary late migration on the gas giants’ obliquities. We consider the planetary instability models from Nesvorný and Morbidelli, in which the obliquities of Jupiter and Saturn can be excited when spin–orbit resonances occur. The most notable resonances occur when the s{sub 7} and s{sub 8} frequencies, changing as a result of planetary migration, become commensurate with the precession frequencies of Jupiter’s and Saturn’s spin vectors. We show that Jupiter may have obtained its present obliquity by crossing of the s{sub 8} resonance. This would set strict constraints on the character of migration during the early stage. Additional effects on Jupiter’s obliquity are expected during the last gasp of migration when the s{sub 7} resonance was approached. The magnitude of these effects depends on the precise value of the Jupiter’s precession constant. Saturn’s large obliquity was likely excited by capture into the s{sub 8} resonance. This probably happened during the late stage of planetary migration when the evolution of the s{sub 8} frequency was very slow, and the conditions for capture into the spin–orbit resonance with s{sub 8} were satisfied. However, whether or not Saturn is in the spin–orbit resonance with s{sub 8} at the present time is not clear because the existing observations of Saturn’s spin precession and internal structure models have significant uncertainties.

79 ASTRONOMY AND ASTROPHYSICS↗