March 6, 2014
Ms. Nicole Needrith
Possible Contamination of Drinking Water due to
Gas-Well Drilling and Hydraulic Fracturing
Advances in hydraulic fracturing technology have allowed previously untapped natural gas resources to be accessed in shale formations. Shale gas development has the potential to create thousands of jobs, reduce the United States’ reliance on energy imports, and play a key role in the nation’s “clean energy” initiative. Despite its advantages this process is extremely controversial, because of the uncertainty surrounding its potential impact upon the environment. The main concern is that thermogenic methane, drilling fluids, and/or wastes could contaminate water aquifers, surface water, wells, atmosphere, and soil near drilling sites. The drilling fluids are of particular concern, because they often contain hazardous and toxic chemicals to aid in the drilling process. Recent studies by Osborn et al. have suggested that thermogenic methane and drilling fluids have migrated into water aquifers due to drilling processes. However some researchers, Osborn et al. have presented data that suggest that there is little difference between pre- and post-drilling water chemistry with regards to dissolved methane and hydraulic fluids. It has been recommended that additional research should be performed to validate findings.
Ms. Pakinee Phromsiri
Discovery of RG7388, a Potent and Selective p53:
MDM2 Inhibitor in Clinical Development
MDM2 is the primary negative regulator of p53—a tumor suppressor protein that regulates the cell cycle. The use of small molecules to inhibit P53—MDM2 protein-protein interaction through binding to MDM2 has been proposed as an approach to cancer therapy. Changes made to the stereochemistry of the substituents on the five membered rings of the previous small molecule inhibitors RG7112 and MI-219 led to the discovery of a new series of compounds. In vitro studies using homogeneous time-resolved fluorescence binding (HTRF) assay and methylthiazol tetrazolium (MTT) assay indicated improved cellular potency and selectivity relative to RG7112 and MI-219. The compounds were then used in an in vivo study on normal mice to measure pharmacokinetic parameters. Due to potency, selectivity, clearance and bioavailability results obtained, RG7388 was selected for use in human osteosarcoma xenograft model in mice and displayed impressive in vivo efficacy against the implanted tumor. Western blot analysis confirmed that the RG7388 inhibitor worked on the same pathway as RG7112. RG7388 was determined to activate p53 and induce maximal apoptosis at a much lower concentration both in vitro and in vivo.