Application of a parallel 3-dimensional hydrogeochemistry HPF code to a proposed waste disposal site at the Oak Ridge National Laboratory

The objectives of this study are (1) to parallelize a 3-dimensional hydrogeochemistry code and (2) to apply the parallel code to a proposed waste disposal site at the Oak Ridge National Laboratory (ORNL). The 2-dimensional hydrogeochemistry code HYDROGEOCHEM, developed at the Pennsylvania State University for coupled subsurface solute transport and chemical equilibrium processes, was first modified to accommodate 3-dimensional problem domains. A bi-conjugate gradient stabilized linear matrix solver was then incorporated to solve the matrix equation. We chose to parallelize the 3-dimensional code on the Intel Paragons at ORNL by using an HPF (high performance FORTRAN) compiler developed at PGI. The data- and task-parallel algorithms available in the HPF compiler proved to be highly efficient for the geochemistry calculation. This calculation can be easily implemented in HPF formats and is perfectly parallel because the chemical speciation on one finite-element node is virtually independent of those on the others. The parallel code was applied to a subwatershed of the Melton Branch at ORNL. Chemical heterogeneity, in addition to physical heterogeneities of the geological formations, has been identified as one of the major factors that affect the fate and transport of contaminants at ORNL. This study demonstrated an application of the 3-dimensional hydrogeochemistry code on the Melton Branch site. A uranium tailing problem that involved in aqueous complexation and precipitation-dissolution was tested. Performance statistics was collected on the Intel Paragons at ORNL. Implications of these results on the further optimization of the code were discussed

Parallelization of a multiregion flow and transport code using software emulated global shared memory and high performance FORTRAN

The objectives of this research are (1) to parallelize a suite of multiregion groundwater flow and solute transport codes that use Galerkin and Lagrangian- Eulerian finite element methods, (2) to test the compatibility of a global shared memory emulation software with a High Performance FORTRAN (HPF) compiler, and (3) to obtain performance characteristics and scalability of the parallel codes. The suite of multiregion flow and transport codes, 3DMURF and 3DMURT, were parallelized using the DOLIB shared memory emulation, in conjunction with the PGI HPF compiler, to run on the Intel Paragons at the Oak Ridge National Laboratory (ORNL) and a network of workstations. The novelty of this effort is first in the use of HPF and global shared memory emulation concurrently to facilitate the conversion of a serial code to a parallel code, and secondly the shared memory library enables efficient implementation of Lagrangian particle tracking along flow characteristics. The latter allows long-time-step-size simulation with particle tracking and dynamic particle redistribution for load balancing, thereby reducing the number of time steps needed for most transient problems. The parallel codes were applied to a pumping well problem to test the efficiency of the domain decomposition and particle tracking algorithms. The full problem domain consists of over 200,000 degrees of freedom with highly nonlinear soil property functions. Relatively good scalability was obtained for a preliminary test run on the Intel Paragons at the Center for Computational Sciences (CCS), ORNL. However, due to the difficulties we encountered in the PGI HPF compiler, as of the writing of this manuscript we are able to report results from 3DMURF only

Genome-Wide Gene Expression Analysis Implicates the Immune Response and Lymphangiogenesis in the Pathogenesis of Fetal Chylothorax

Fetal chylothorax (FC) is a rare condition characterized by lymphocyte-rich pleural effusion. Although its pathogenesis remains elusive, it may involve inflammation, since there are increased concentrations of proinflammatory mediators in pleural fluids. Only a few hereditary lymphedema-associated gene loci, e.g. VEGFR3, ITGA9 and PTPN11, were detected in human fetuses with this condition; these cases had a poorer prognosis, due to defective lymphangiogenesis. In the present study, genome-wide gene expression analysis was conducted, comparing pleural and ascitic fluids in three hydropic fetuses, one with and two without the ITGA9 mutation. One fetus (the index case), from a dizygotic pregnancy (the cotwin was unaffected), received antenatal OK-432 pleurodesis and survived beyond the neonatal stage, despite having the ITGA9 mutation. Genes and pathways involved in the immune response were universally up-regulated in fetal pleural fluids compared to those in ascitic fluids. Furthermore, genes involved in the lymphangiogenesis pathway were down-regulated in fetal pleural fluids (compared to ascitic fluid), but following OK-432 pleurodesis, they were up-regulated. Expression of ITGA9 was concordant with overall trends of lymphangiogenesis. In conclusion, we inferred that both the immune response and lymphangiogenesis were implicated in the pathogenesis of fetal chylothorax. Furthermore, genome-wide gene expression microarray analysis may facilitate personalized medicine by selecting the most appropriate treatment, according to the specific circumstances of the patient, for this rare, but heterogeneous disease

Innovative Mathematical Modeling In Environmental Remediation

There are two different ways to model reactive transport: ad hoc and innovative reaction-based approaches. The former, such as the Kd simplification of adsorption, has been widely employed by practitioners, while the latter has been mainly used in scientific communities for elucidating mechanisms of biogeochemical transport processes. It is believed that innovative mechanistic-based models could serve as protocols for environmental remediation as well. This paper reviews the development of a mechanistically coupled fluid flow, thermal transport, hydrologic transport, and reactive biogeochemical model and example-applications to environmental remediation problems. Theoretical bases are sufficiently described. Four example problems previously carried out are used to demonstrate how numerical experimentation can be used to evaluate the feasibility of different remediation approaches. The first one involved the application of a 56-species uranium tailing problem to the Melton Branch Subwatershed at Oak Ridge National Laboratory (ORNL) using the parallel version of the model. Simulations were made to demonstrate the potential mobilization of uranium and other chelating agents in the proposed waste disposal site. The second problem simulated laboratory-scale system to investigate the role of natural attenuation in potential off-site migration of uranium from uranium mill tailings after restoration. It showed inadequacy of using a single Kd even for a homogeneous medium. The third example simulated laboratory experiments involving extremely high concentrations of uranium, technetium, aluminum, nitrate, and toxic metals (e.g., Ni, Cr, Co). The fourth example modeled microbially-mediated immobilization of uranium in an unconfined aquifer using acetate amendment in a field-scale experiment. The purposes of these modeling studies were to simulate various mechanisms of mobilization and immobilization of radioactive wastes and to illustrate how to apply reactive transport models for environmental remediation. © 2011 Elsevier Ltd

MPT0B098, a Microtubule Inhibitor, Suppresses JAK2/STAT3 Signaling Pathway through Modulation of SOCS3 Stability in Oral Squamous Cell Carcinoma.

Microtubule inhibitors have been shown to inhibit Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signal transduction pathway in various cancer cells. However, little is known of the mechanism by which the microtubule inhibitors inhibit STAT3 activity. In the present study, we examined the effect of a novel small-molecule microtubule inhibitor, MPT0B098, on STAT3 signaling in oral squamous cell carcinoma (OSCC). Treatment of various OSCC cells with MPT0B098 induced growth inhibition, cell cycle arrest and apoptosis, as well as increased the protein level of SOCS3. The accumulation of SOCS3 protein enhanced its binding to JAK2 and TYK2 which facilitated the ubiquitination and degradation of JAK2 and TYK2, resulting in a loss of STAT3 activity. The inhibition of STAT3 activity led to sensitization of OSCC cells to MPT0B098 cytotoxicity, indicating that STAT3 is a key mediator of drug resistance in oral carcinogenesis. Moreover, the combination of MPT0B098 with the clinical drug cisplatin or 5-FU significantly augmented growth inhibition and apoptosis in OSCC cells. Taken together, our results provide a novel mechanism for the action of MPT0B098 in which the JAK2/STAT3 signaling pathway is suppressed through the modulation of SOCS3 protein level. The findings also provide a promising combinational therapy of MPT0B098 for OSCC

MPT0B098 modulates JAK2/STAT3 pathway in OSCC cells.

<p>(<b>A</b>) OEC-M1 cells were treated with MPT0B098 (0.25 μM) for the indicated times. The phosphorylated STAT3 (pSTAT3) and total level of STAT3 were determined by Western blotting. The level of STAT3 mRNA was determined by RT-PCR. GAPDH was used as loading control. (<b>B</b>) Western blot analysis of STAT3 levels after 48 hrs transfection of OEC-M1 cells with control shRNA (NS) or two shRNA constructs (shSTAT3 #1, #2) against STAT3. GAPDH was used as loading control. These shRNA transfactants were treated MPT0B098 for 24 hrs and caspases-3 activity was assessed. The data are represented as mean ± SE; *, <i>p</i><0.05; **, <i>p</i><0.01 versus vehicle control. (<b>C</b>) Western blot analysis of endogenous STAT3 protein level in OSCC cells. GAPDH was used as loading control. (<b>D</b>) OSCC cells were incubated with various concentrations of MPT0B098 for 24 hrs and caspases-3 activity was assessed. Data are presents as mean ± SE relative to vehicle control from three replicate experiments. *, <i>p</i><0.05; **, <i>p</i><0.01; ***, <i>p</i><0.001. (<b>E</b>) OEC-M1 and HSC-3 cells were treated with 0.25 μM of MPT0B098 for indicated times. The phosphorylated proteins (p-JAK1, p-JAK2 and p-TYK2) and total level of proteins (JAK1, JAK2 and TYK2) were determined by Western blotting. GAPDH was used as loading control.</p