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In situ vitrification model development and implementation plan
This document describes the In Situ Vitrification (ISV) Analysis Package being developed at the INEL to provide analytical support for (ISV) safety analysis and treatment performance predictions. Mathematical models and features which comprise this analysis package are presented and the proposed approach to model development and implementation is outlined. The objective of this document is two fold: to define preliminary design information and modeling objectives so that ISV modeling personnel can effectively modify existing models and formulate new models which are consistent with the objectives of the ISV treatability study and to provide sufficient technical information for internal and external reviewers to detect any shortcomings in model development and implementation plans. 27 refs., 17 figs., 3 tabs
Glutathione <em>S</em>-transferase P1 (<em>GSTP1</em>) directly influences platinum drug chemosensitivity in ovarian tumour cell lines
BACKGROUND: Chemotherapy response in ovarian cancer patients is frequently compromised by drug resistance, possibly due to altered drug metabolism. Platinum drugs are metabolised by glutathione S-transferase P1 (GSTP1), which is abundantly, but variably expressed in ovarian tumours. We have created novel ovarian tumour cell line models to investigate the extent to which differential GSTP1 expression influences chemosensitivity. METHODS: Glutathione S-transferase P1 was stably deleted in A2780 and expression significantly reduced in cisplatin-resistant A2780DPP cells using Mission shRNA constructs, and MTT assays used to compare chemosensitivity to chemotherapy drugs used to treat ovarian cancer. Differentially expressed genes in GSTP1 knockdown cells were identified by Illumina HT-12 expression arrays and qRT–PCR analysis, and altered pathways predicted by MetaCore (GeneGo) analysis. Cell cycle changes were assessed by FACS analysis of PI-labelled cells and invasion and migration compared in quantitative Boyden chamber-based assays. RESULTS: Glutathione S-transferase P1 knockdown selectively influenced cisplatin and carboplatin chemosensitivity (2.3- and 4.83-fold change in IC(50), respectively). Cell cycle progression was unaffected, but cell invasion and migration was significantly reduced. We identified several novel GSTP1 target genes and candidate platinum chemotherapy response biomarkers. CONCLUSIONS: Glutathione S-transferase P1 has an important role in cisplatin and carboplatin metabolism in ovarian cancer cells. Inter-tumour differences in GSTP1 expression may therefore influence response to platinum-based chemotherapy in ovarian cancer patients
Three-dimensional lanthanide-organic frameworks based on di-, tetra-, and hexameric clusters
Three-dimensional lanthanide-organic frameworks formulated as (CH3)2NH2[Ln(pydc)2] · 1/2H2O [Ln3+ ) Eu3+ (1a)
or Er3+ (1b); pydc2- corresponds to the diprotonated residue of 2,5-pyridinedicarboxylic acid (H2pydc)], [Er4(OH)4(pydc)4(H2O)3] ·H2O
(2), and [PrIII
2PrIV
1.25O(OH)3(pydc)3] (3) have been isolated from typical solvothermal (1a and 1b in N,N-dimethylformamide -
DMF) and hydrothermal (2 and 3) syntheses. Materials were characterized in the solid state using single-crystal X-ray diffraction,
thermogravimetric analysis, vibrational spectroscopy (FT-IR and FT-Raman), electron microscopy, and CHN elemental analysis.
While synthesis in DMF promotes the formation of centrosymmetric dimeric units, which act as building blocks in the construction
of anionic ∞
3{[Ln(pydc)2]-} frameworks having the channels filled by the charge-balancing (CH3)2NH2
+ cations generated in situ by
the solvolysis of DMF, the use of water as the solvent medium promotes clustering of the lanthanide centers: structures of 2 and 3
contain instead tetrameric [Er4(μ3-OH)4]8+ and hexameric |Pr6(μ3-O)2(μ3-OH)6| clusters which act as the building blocks of the networks,
and are bridged by the H2-xpydcx- residues. It is demonstrated that this modular approach is reflected in the topological nature of
the materials inducing 4-, 8-, and 14-connected uninodal networks (the nodes being the centers of gravity of the clusters) with
topologies identical to those of diamond (family 1), and framework types bct (for 2) and bcu-x (for 3), respectively. The
thermogravimetric studies of compound 3 further reveal a significant weight increase between ambient temperature and 450 °C with
this being correlated with the uptake of oxygen from the surrounding environment by the praseodymium oxide inorganic core
Ligand Influences on Copper Molybdate Networks: The Structures and Magnetism of [Cu(3,4‘-bpy)MoO 4
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