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At least 1,315 records · Page 73

Fibroblast Growth Factor 2-A Predictor of Outcome for Patients Irradiated for Stage II-III Non-Small-Cell Lung Cancer

Purpose: The prognostic value of the tumor cell expression of the fibroblast growth factor 2 (FGF-2) in patients with non-small-cell lung cancer (NSCLC) is unclear. The present study investigated the effect of tumor cell expression of FGF-2 on the outcome of 60 patients irradiated for Stage II-III NSCLC. Methods and Materials: The effect of FGF-2 expression and 13 additional factors on locoregional control (LRC), metastasis-free survival (MFS), and overall survival (OS) were retrospectively evaluated. These additional factors included age, gender, Karnofsky performance status, histologic type, histologic grade, T and N category, American Joint Committee on Cancer stage, surgery, chemotherapy, pack-years, smoking during radiotherapy, and hemoglobin during radiotherapy. Locoregional failure was identified by endoscopy or computed tomography. Univariate analyses were performed with the Kaplan-Meier method and the Wilcoxon test and multivariate analyses with the Cox proportional hazard model. Results: On univariate analysis, improved LRC was associated with surgery (p = .017), greater hemoglobin levels (p = .036), and FGF-2 negativity (p <.001). On multivariate analysis of LRC, surgery (relative risk [RR], 2.44; p = .037), and FGF-2 expression (RR, 5.06; p <.001) maintained significance. On univariate analysis, improved MFS was associated with squamous cell carcinoma (p = .020), greater hemoglobin levels (p = .007), and FGF-2 negativity (p = .001). On multivariate analysis of MFS, the hemoglobin levels (RR, 2.65; p = .019) and FGF-2 expression (RR, 3.05; p = .004) were significant. On univariate analysis, improved OS was associated with a lower N category (p = .048), greater hemoglobin levels (p <.001), and FGF-2 negativity (p <.001). On multivariate analysis of OS, greater hemoglobin levels (RR, 4.62; p = .002) and FGF-2 expression (RR, 3.25; p = .002) maintained significance. Conclusions: Tumor cell expression of FGF-2 appeared to be an independent negative predictor of LRC, MFS, and OS.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Dosimetric Comparison of Combined Intensity-Modulated Radiotherapy (IMRT) and Proton Therapy Versus IMRT Alone for Pelvic and Para-Aortic Radiotherapy in Gynecologic Malignancies

Purpose: To perform a dosimetric comparison of intensity-modulated radiotherapy (IMRT), passive scattering proton therapy (PSPT), and intensity-modulated proton therapy (IMPT) to the para-aortic (PA) nodal region in women with locally advanced gynecologic malignancies. Methods and Materials: The CT treatment planning scans of 10 consecutive patients treated with IMRT to the pelvis and PA nodes were identified. The clinical target volume was defined by the primary tumor for patients with cervical cancer and by the vagina and paravaginal tissues for patients with endometrial cancer, in addition to the regional lymph nodes. The IMRT, PSPT, and IMPT plans were generated using the Eclipse Treatment Planning System and were analyzed for various dosimetric endpoints. Two groups of treatment plans including proton radiotherapy were created: IMRT to pelvic nodes with PSPT to PA nodes (PSPT/IMRT), and IMRT to pelvic nodes with IMPT to PA nodes (IMPT/IMRT). The IMRT and proton RT plans were optimized to deliver 50.4 Gy or Gy (relative biologic effectiveness [RBE)), respectively. Dose-volume histograms were analyzed for all of the organs at risk. The paired t test was used for all statistical comparison. Results: The small-bowel V{sub 20}, V{sub 30}, V{sub 35}, andV{sub 40} were reduced in PSPT/IMRT by 11%, 18%, 27%, and 43%, respectively (p < 0.01). Treatment with IMPT/IMRT demonstrated a 32% decrease in the small-bowel V{sub 20}. Treatment with PSPT/IMRT showed statistically significant reductions in the body V{sub 5-20}; IMPT/IMRT showed reductions in the body V{sub 5-15}. The dose received by half of both kidneys was reduced by PSPT/IMRT and by IMPT/IMRT. All plans maintained excellent coverage of the planning target volume. Conclusions: Compared with IMRT alone, PSPT/IMRT and IMPT/IMRT had a statistically significant decrease in dose to the small and large bowel and kidneys, while maintaining excellent planning target volume coverage. Further studies should be done to correlate the clinical significance of these findings.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Investigating the FLASH Effect in a Rat Brain Organotypic Model With a Novel High-Energy Electron Beam

Ultrahigh dose rate (FLASH) radiation therapy is reported to reduce normal tissue toxicity while maintaining tumor control; however, mechanism(s) remain obscure. To study FLASH mechanisms in brain tissue, we developed a novel experimental platform featuring a specialized high-energy electron linear accelerator, High Intensity Gamma Ray Source (HIGS), paired with an organotypic ex vivo brain metastasis model. We varied interpulse spacing to modulate the mean dose rate (MDR) of our unique 35 MeV electron beam, while maintaining extremely high instantaneous dose rate (IDR). We characterized dosimetry and targeting accuracy of the FLASH beam with film dosimetry. We combined this FLASH beam with an organotypic rat brain slice/breast carcinoma coculture model of brain metastasis to assess effects on normal and neoplastic tissues. Live-cell and bioluminescence imaging demonstrated cancer cell growth effects, whereas normal tissue responses and immune activation were assessed using live-cell imaging, cytokine profiles, and confocal microscopy. Here, we performed comparison experiments with 20 MeV electrons from a Varian clinical linear accelerator (VCLA) using conventional dose rates. The highest IDR of the FLASH beam to date was 20.7 ± 0.6 MGy/s, with maximum MDR of 20.7 MGy/s delivered in 1 pulse of 1 µs duration. Beam targeting was accurate to <1 mm and reproducible. HIGS-FLASH and VCLA dose rates equivalently decreased cancer cell growth. HIGS-FLASH irradiation significantly increased tumor necrosis factor α and fractalkine levels and confocal microscopy revealed distinct changes in microglial morphology slices suggesting microglia activation. Our novel experimental platform produces extremely high dose rates and rapid normal/neoplastic tissue readouts for mechanistic research into the effects of FLASH radiation in the brain. HIGS-FLASH irradiation induces comparable cancer cell growth inhibition but differential effects on cytokines and microglial morphology, suggesting that acute innate immune responses may be involved in FLASH normal tissue effects in the brain.

Kay, Tyler V. [Duke University, Durham, NC (United↗

Asynchronous aging and turnover of human circulating and tissue-resident memory T cells across sites

Memory T cells are maintained in tissues as circulating effector-memory (T EM ) and tissue-resident (T RM ) populations for protective immunity, though the role of site and subset in memory persistence remains undefined. Here, in this work, we investigated age-associated dynamics of human T cells in lymphoid organs, mucosal sites, and blood over 10 decades of life using retrospective radiocarbon ( 14 C) birth dating, along with cellular, transcriptome, and epigenetic profiling. Memory T cells across peripheral sites exhibited continuous turnover with mean lifespans of 1–2 years, while the spleen contained longer-lived T cells. Over age, T EM cells expressed senescent markers and a GZMK transcriptional signature, while T RM cells maintained site-specific resident phenotypes without exhibiting features of senescence. Both T EM and T RM cells showed age-associated DNA hypomethylation, though T RM cells exhibited more epigenetically regulated genes. Together, our findings reveal asynchronous aging of human memory T cells by subset and site, as well as persistence of T RM cells without immunosenescence.

T cells↗

Continuous recovery of high-purity Kraft lignin from black liquor via simultaneous, liquid-phase acidification and purification

Here, a key advantage of the Sequential Liquid-Lignin Recovery and Purification (SLRP) process for the recovery of lignin from Kraft black liquor is the precipitation of a solvated, “liquid-lignin” phase (vs. the typical solid) during the CO 2 acidification step. Here, we have discovered that this lignin can also be maintained in a solvated state during the H 2 SO 4 acidification step if aqueous acetic acid from the Aqueous Lignin Purification with Hot Agents (ALPHA) process is incorporated into the H 2 SO 4 solution. As the liquid-lignin is converted from its salt form at pH = 9.5 to its acid form at pH = 2.5, the lignin initially solvated with water becomes solvated and thus liquefied with the organic–water solution. Maintaining the lignin in a solvated liquid state has two advantages: (1) the entire SLRP + ALPHA process, from starting black liquor to final lignin product, can be operated continuously; and (2) mass transfer of metals impurities out of the liquid-lignin phase is significantly enhanced, resulting in both a cleaner Kraft lignin product (~2000 ppm Na and 0.5-1.0 % ash) and reduced water washing.

09 BIOMASS FUELS↗

Energy-efficient cooperative resource allocation and task scheduling for Internet of Things environments

Offloading Internet of Things (IoT) tasks to the cloud for further processing might not always lead to an optimal execution time, particularly in situations such as resource contention, under-provisioning, over-provisioning, and fragmentation. In addition, dynamically optimizing the number of Virtual Machines (VMs) for resource scheduling in order to meet application requirements remains a major research challenge. Further, existing resource scheduling algorithms focus primarily on minimizing operational costs while maximizing resource sharing and utilization. Considering energy utilization as part of the resource allocation and scheduling process as an optimization objective for maintaining load balancing has often been neglected. To address these challenges and more, we propose a cooperative energy-aware resource allocation and scheduling strategy based on a Technique for Order of Preference by Similarity to Ideal Solution (TOPSIS) multi-criteria decision-making method. Here we used the Grid Workloads Archive dataset to evaluate our proposed approach named TOPREAL. Experimental results with respect to the allocation of VM resources when considering processing a large segment of tasks indicate that TOPREAL outperforms existing algorithms in terms of energy savings, with an average improvement of 40.25%, while maintaining an average improvement of 16.21% when it comes to execution time. Results also demonstrate that our method can save an average of 78.06 processing hours and 63,215kJ of energy when compared to existing scheduling algorithms. These results demonstrate the effectiveness of our proposed model and the viability of using multi-criteria decision-making techniques such as TOPSIS to solve the resource allocation and scheduling problem in edge environments.

32 ENERGY CONSERVATION, CONSUMPTION, AND UTILIZATI↗

Robust constrained tension control for high-precision roll-to-roll processes

Tension control is critical for maintaining good product quality in most roll-to-roll (R2R) production systems. Previous work has primarily focused on improving the disturbance rejection performance of tension controllers. Here, a robust linear parameter-varying model predictive control (LPV-MPC) scheme is designed to enhance the tension tracking performance of a pilot R2R system for deposition of materials used in flexible thin film applications. The performance of a tension controller may degrade due to disturbances associated with model uncertainties and the slowly-changing dynamics in R2R systems. We introduce a method that separately treats these two sources of disturbance. The controller utilizes an incremental model to eliminate the errors caused by the mismatch between the nominal model and the actual system. A tube-based MPC formulation combined with scheduled parameters adequately updates models and corrects for the time-varying dynamics. Constraints on the rated motor torque are incorporated in the MPC to maintain the controller reliability and avoid machine failures. We illustrate the operation of our control algorithm through simulation of an actual R2R system. The controller outperforms the benchmarks in terms of fast transient response and offset-free tension tracking. Furthermore, it also demonstrates immunity from variations due to parametric uncertainties.

42 ENGINEERING↗

Implementation of a hybrid particle code with a PIC description in r–z and a gridless description in ϕ into OSIRIS

For many plasma physics problems, three-dimensional and kinetic effects are very important. However, such simulations are very computationally intensive. Fortunately, there is a class of problems for which there is nearly azimuthal symmetry and the dominant three-dimensional physics is captured by the inclusion of only a few azimuthal harmonics. Recently, it was proposed [1] to model one such problem, laser wakefield acceleration, by expanding the fields and currents in azimuthal harmonics and truncating the expansion. The complex amplitudes of the fundamental and first harmonic for the fields were solved on an r–z grid and a procedure for calculating the complex current amplitudes for each particle based on its motion in Cartesian geometry was presented using a Marder's correction to maintain the validity of Gauss's law. In this paper, we describe an implementation of this algorithm into OSIRIS using a rigorous charge conserving current deposition method to maintain the validity of Gauss's law. We show that this algorithm is a hybrid method which uses a particles-in-cell description in r–z and a gridless description in ϕ. We include the ability to keep an arbitrary number of harmonics and higher order particle shapes. Examples for laser wakefield acceleration, plasma wakefield acceleration, and beam loading are also presented and directions for future work are discussed.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗

Using hybrid implicit Monte Carlo diffusion to simulate gray radiation hydrodynamics

This work describes how to couple a hybrid Implicit Monte Carlo Diffusion (HIMCD) method with a Lagrangian hydrodynamics code to evaluate the coupled radiation hydrodynamics equations. This HIMCD method dynamically applies Implicit Monte Carlo Diffusion (IMD) [1] to regions of a problem that are opaque and diffusive while applying standard Implicit Monte Carlo (IMC) [2] to regions where the diffusion approximation is invalid. We show that this method significantly improves the computational efficiency as compared to a standard IMC/Hydrodynamics solver, when optically thick diffusive material is present, while maintaining accuracy. Two test cases are used to demonstrate the accuracy and performance of HIMCD as compared to IMC and IMD. The first is the Lowrie semi-analytic diffusive shock [3]. The second is a simple test case where the source radiation streams through optically thin material and heats a thick diffusive region of material causing it to rapidly expand. We found that HIMCD proves to be accurate, robust, and computationally efficient for these test problems.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗

An Eulerian projection method for quasi-static elastoplasticity

A well-established numerical approach to solve the Navier-Stokes equations for incompressible fluids is Chorin's projection method, whereby the fluid velocity is explicitly updated, and then an elliptic problem for the pressure is solved, which is used to orthogonally project the velocity field to maintain the incompressibility constraint. In this paper, we develop a mathematical correspondence between Newtonian fluids in the incompressible limit and hypo-elastoplastic solids in the slow, quasi-static limit. Using this correspondence, we formulate a new fixed-grid, Eulerian numerical method for simulating quasi-static hypo-elastoplastic solids, whereby the stress is explicitly updated, and then an elliptic problem for the velocity is solved, which is used to orthogonally project the stress to maintain the quasi-staticity constraint. We develop a finite-difference implementation of the method and apply it to an elasto-viscoplastic model of a bulk metallic glass based on the shear transformation zone theory. We show that in a two-dimensional plane strain simple shear simulation, the method is in quantitative agreement with an explicit method. Like the fluid projection method, it is efficient and numerically robust, making it practical for a wide variety of applications. We also demonstrate that the method can be extended to simulate objects with evolving boundaries. Here, we highlight a number of correspondences between incompressible fluid mechanics and quasi-static elastoplasticity, creating possibilities for translating other numerical methods between the two classes of physical problems.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗

High-order asynchrony-tolerant finite difference schemes for partial differential equations

Synchronizations of processing elements (PEs) in massively parallel simulations, which arise due to communication or load imbalances between PEs, significantly affect the scalability of scientific applications. We have recently proposed a method based on finite-difference schemes to solve partial differential equations in an asynchronous fashion – synchronization between PEs is relaxed at a mathematical level. While standard schemes can maintain their stability in the presence of asynchrony, their accuracy is drastically affected. In this work, we present a general methodology to derive asynchrony-tolerant (AT) finite difference schemes of arbitrary order of accuracy, which can maintain their accuracy when synchronizations are relaxed. We show that there are several choices available in selecting a stencil to derive these schemes and discuss their effect on numerical and computational performance. We provide a simple classification of schemes based on the stencil and derive schemes that are representative of different classes. Their numerical error is rigorously analyzed within a statistical framework to obtain the overall accuracy of the solution. Results from numerical experiments are used to validate the performance of the schemes.

42 ENGINEERING↗

Super-time-stepping schemes for parabolic equations with boundary conditions

In this work, we present a super-time-stepping scheme for numerically solving parabolic partial differential equations with Dirichlet boundary conditions (BC). Using the general Forward Euler scheme, one can show that by taking varying step sizes there is the potential of propagating the solution forward in time by a greater amount than with uniform step sizes, while maintaining the same order of accuracy. As shown in previous works, if one further requires that the scheme have the Convex Monotone Property (CMP), then there exists a scheme which results in linear, monotone stability of the solution. This monotone stability is highly desirable in many physical situations, such as thermal diffusion, where the physical system will not oscillate, but will behave monotonically. However, the schemes devised in previous works do not include situations that have a boundary condition, and the inclusion of boundary conditions will henceforth be our focus. It is shown that a particular Runge-Kutta-Gegenbauer class of schemes [5] will maintain the CMP even in the presence of Dirichlet BC.

97 MATHEMATICS AND COMPUTING↗

Assessment of diffuse-interface methods for compressible multiphase fluid flows and elastic-plastic deformation in solids

This work describes three diffuse-interface methods for the simulation of immiscible, compressible multiphase fluid flows and elastic-plastic deformation in solids. The first method is the localized-artificial-diffusivity approach of Cook, Subramaniam et al., and Adler and Lele, in which artificial diffusion terms are added to the individual phase mass fraction transport equations and are coupled with the other conservation equations. The second method is the gradient-form approach that is based on the quasi-conservative method of Shukla et al., in which the diffusion and sharpening terms (together called regularization terms) are added to the individual phase volume fraction transport equations and are coupled with the other conservation equations. The third approach is the divergence-form approach that is based on the fully conservative method of Jain et al., in which the regularization terms are added to the individual phase volume fraction transport equations and are coupled with the other conservation equations. In the present study, all three diffuse-interface methods are used in conjunction with a four-equation, multicomponent mixture model, in which pressure and temperature equilibria are assumed among the various phases. The primary objective of this work is to compare these three methods in terms of their ability to: maintain constant interface thickness throughout the simulation; conserve mass, momentum, and energy; and maintain accurate interface shape for long-time integration. The second objective of this work is to consistently extend these methods to model interfaces between solid materials with strength. To assess and compare the methods, they are used to simulate a wide variety of problems, including (1) advection of an air bubble in water, (2) shock interaction with a helium bubble in air, (3) shock interaction and the collapse of an air bubble in water, and (4) Richtmyer–Meshkov instability of a copper–aluminum interface. The current work focuses on comparing these methods in the limit of relatively coarse grid resolution, which illustrates the true performance of these methods. In conclusion, this is because it is rarely practical to use hundreds of grid points to resolve a single bubble or drop in large-scale simulations of engineering interest.

97 MATHEMATICS AND COMPUTING↗

A high-order finite difference method for moving immersed domain boundaries and material interfaces

Here, we present a high-order sharp treatment of immersed moving domain boundaries and material interfaces, and apply it to the advection-diffusion equation in two and three dimensions. The spatial discretization combines dimension-split finite difference schemes with an immersed boundary treatment based on a weighted least-squares reconstruction of the solution, providing stable discretizations with up to sixth order accuracy for diffusion terms and third order accuracy for advection terms. The temporal discretization relies on a novel strategy for maintaining high-order temporal accuracy in problems with moving boundaries that minimizes implementation complexity and allows arbitrary explicit or diagonally-implicit Runge-Kutta schemes. The approach is broadly compatible with popular PDE-specialized Runge-Kutta time integrators, including low-storage, strong stability preserving, and diagonally implicit schemes. Through numerical experiments we demonstrate that the full discretization maintains high-order spatial and temporal accuracy in the presence of complex 3D geometries and for a range of boundary conditions, including Dirichlet, Neumann, and flux conditions with large jumps in coefficients.

97 MATHEMATICS AND COMPUTING↗

Rheological Behavior of Xanthan Gum Solution Related to Shear Thinning Fluid Delivery for Subsurface Remediation

Xanthan gum, a biopolymer, forms shear thinning fluids which can be used as delivery media to improve the distribution of remedial amendments injected into heterogeneous subsurface environments. The rheological behavior of the shear thinning solution needs to be known to develop an appropriate design for field injection. In this study, the rheological properties of xanthan gum solutions were obtained under various chemical and environmental conditions relevant to delivery of remedial amendments to groundwater. Higher xanthan concentration raised the absolute solution viscosity and increased the degree of shear thinning. Addition of remedial amendments (e.g., phosphate, sodium lactate, ethyl lactate) caused the dynamic viscosity of xanthan gum to decrease, but the solutions maintained shear-thinning properties. Use of simple salt (e.g. Na+, Ca2+) to increase the solution ionic strength also decreased the dynamic viscosity of xanthan and the degree of shear thinning, although the effect is a function of xanthan gum concentration and diminished as the xanthan gum concentration was increased. At high xanthan concentration, addition of salt to the solution increased dynamic viscosity. In the absence of sediments, xanthan gum solutions maintain their viscosity properties for months. However, xanthan gum solutions were shown to lose dynamic viscosity over a period of days to weeks when contacted with saturated site sediment. Loss of viscosity is attributed to physical and biodegradation processes.

Zhong, Lirong↗

Molecular basis of the structural stability of a Top7-based scaffold at extreme pH and temperature conditions

The development of stable scaffolds that can tolerate environmental extremes has an immense potential for applications in industry and defense. Recently, we have engineered an eight-residue loop into the de novo designed Top7 protein, which specifically binds the glycoprotein CD4. The robust properties of the Top7, coupled with the ease in production, make it a robust scaffold to design novel functionalities for use under extreme environmental conditions. In the present work, a series of explicit-solvent molecular dynamics simulations are reported which investigates the effect of mutations and extreme conditions of temperature and pH on the structure, stability, and dynamics of the native and engineered Top7. These simulations indicate that i. The structural dynamics of the engineered and native Top7 in solution are equivalent under corresponding conditions of pH and temperature. Ensemble-averaged structures of the native and engineered Top7 maintain the overall tertiary structure pattern, albeit with loss of helical content when at low pH and high-temperature conditions. Mutations of residues E43A, D46A, E67A, E69A, EA81A along the ?-helices of the engineered Top7 did not lead to significant changes in the native fold under pH 2 and 400 K, suggesting that the helices can accommodate varying sequences. iii. The anti-parallel ?-sheet is the structural core responsible for the stability of the native and engineered Top7 and is well maintained under extreme pH and temperature conditions. These findings indicate that the insertion of an eight-residue loop into the structure of Top7 does not adversely affect the global fold or the structural stability of the Top7 scaffold.

59 BASIC BIOLOGICAL SCIENCES↗

A multiscale model to understand the interface chemistry, contacts, and dynamics during lithium stripping

A reversible Li-metal electrode, paired with a solid electrolyte, is critical for attaining higher energy density and safer batteries beyond the current lithium-ion cells. A stable stripping process may be even harder to attain as the stripping process will remove Li-atoms from the surface, and naturally reduce surface contact area, if not self-corrected by other mechanisms, such as diffusion and plastic deformation under an applied external stack pressure. Here, we capture these mechanisms occurring at multiple length- and time- scales, i.e., interface interactions, vacancy hopping, and plastic deformation, by integrating density functional theory (DFT) simulations, kinetic Monte Carlo (KMC), and continuum finite element method (FEM). By assuming the self-affine nature of multiscale contacts, we predict the steady-state contact area as a function of stripping current density, interface wettability, and stack pressure. We further estimate the exponential increase of overpotential due to contact area loss to maintain the same stripping current density. We demonstrate that a lithiophilic interface requires less stack pressure to reach the same steady-state contact area fraction than a lithiophobic interface. A “tolerable steady-state” contact area loss for maintaining stable stripping is estimated at 20 %, corresponding to a 10 % increase in overpotential. To constrain contact loss within the tolerance, the required stack pressure is 0.1, 0.5, and 2 times the yield strength of lithium metal for three distinct interfaces, lithiophilic Li/lithium oxide(Li2O), Li/lithium lanthanum zirconium oxide(LLZO), and lithiophoblic Li/lithium fluoride(LiF), respectively. The modeling results agree with experiments on the impact of the stack pressure quantitatively, while the discrepancy in stripping rate sensitivity is attributed to the simplifying interface interaction in our simulations. Overall, this multiscale simulation framework demonstrates the importance of electrochemical-mechanical coupling in understanding the dynamics of the Li/SE interface during stripping.

Feng, Min↗