Winners and Losers: Formula versus Competitive Funding of Agricultural Research

Research and Development/Tech Change/Emerging Technologies, O3, O4, Q16,

Winners and Losers: Formula versus Competitive Funding of Agricultural Research

State Agricultural Experiment Stations (SAESs) were established with federal formula funding by the Hatch Act of 1887. In 1955, the Hatch Act was amended and a number of subsequent formula funding programs were consolidated under the USDA Cooperative States Research Service (CSRS), which today is known as the Cooperative Research, Education and Extension Service (CSREES). Currently, all of the Hatch funds and a small amount of other formula funds go to SAESs. In 1977, CSRS established its first competitive research grant program. However, this program remained quite small until 1990, when it was re-named the National Research Initiative (NRI) Competitive Grants Program with a much larger funding authorization. Currently, the SAESs account for 60% of U.S. public agricultural research, with 7% of SAESs funding obtained from Hatch funds and 2.3% from NRI Grant funds (Huffman & Evenson, 2006b, pp. 107, 117- 118). Hence, the SAES system has become relatively diversified in its funding sources after starting with only Hatch funding

A Cell-Surface Membrane Protein Signature for Glioblastoma.

We present a systems strategy that facilitated the development of a molecular signature for glioblastoma (GBM), composed of 33 cell-surface transmembrane proteins. This molecular signature, GBMSig, was developed through the integration of cell-surface proteomics and transcriptomics from patient tumors in the REMBRANDT (n = 228) and TCGA datasets (n = 547) and can separate GBM patients from control individuals with a Matthew\u27s correlation coefficient value of 0.87 in a lock-down test. Functionally, 17/33 GBMSig proteins are associated with transforming growth factor β signaling pathways, including CD47, SLC16A1, HMOX1, and MRC2. Knockdown of these genes impaired GBM invasion, reflecting their role in disease-perturbed changes in GBM. ELISA assays for a subset of GBMSig (CD44, VCAM1, HMOX1, and BIGH3) on 84 plasma specimens from multiple clinical sites revealed a high degree of separation of GBM patients from healthy control individuals (area under the curve is 0.98 in receiver operating characteristic). In addition, a classifier based on these four proteins differentiated the blood of pre- and post-tumor resections, demonstrating potential clinical value as biomarkers

Inherently safer technology gaps analysis study.

Approved for public release; further dissemination unlimited

Comprehensive Analysis of MGMT Promoter Methylation: Correlation with MGMT Expression and Clinical Response in GBM

O6-methylguanine DNA-methyltransferase (MGMT) promoter methylation has been identified as a potential prognostic marker for glioblastoma patients. The relationship between the exact site of promoter methylation and its effect on gene silencing, and the patient's subsequent response to therapy, is still being defined. The aim of this study was to comprehensively characterize cytosine-guanine (CpG) dinucleotide methylation across the entire MGMT promoter and to correlate individual CpG site methylation patterns to mRNA expression, protein expression, and progression-free survival. To best identify the specific MGMT promoter region most predictive of gene silencing and response to therapy, we determined the methylation status of all 97 CpG sites in the MGMT promoter in tumor samples from 70 GBM patients using quantitative bisulfite sequencing. We next identified the CpG site specific and regional methylation patterns most predictive of gene silencing and improved progression-free survival. Using this data, we propose a new classification scheme utilizing methylation data from across the entire promoter and show that an analysis based on this approach, which we call 3R classification, is predictive of progression-free survival (HR  = 5.23, 95% CI [2.089–13.097], p<0.0001). To adapt this approach to the clinical setting, we used a methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) test based on the 3R classification and show that this test is both feasible in the clinical setting and predictive of progression free survival (HR  = 3.076, 95% CI [1.301–7.27], p = 0.007). We discuss the potential advantages of a test based on this promoter-wide analysis and compare it to the commonly used methylation-specific PCR test. Further prospective validation of these two methods in a large independent patient cohort will be needed to confirm the added value of promoter wide analysis of MGMT methylation in the clinical setting

The somatic genomic landscape of glioblastoma

We describe the landscape of somatic genomic alterations based on multidimensional and comprehensive characterization of more than 500 glioblastoma tumors (GBMs). We identify several novel mutated genes as well as complex rearrangements of signature receptors, including EGFR and PDGFRA. TERT promoter mutations are shown to correlate with elevated mRNA expression, supporting a role in telomerase reactivation. Correlative analyses confirm that the survival advantage of the proneural subtype is conferred by the G-CIMP phenotype, and MGMT DNA methylation may be a predictive biomarker for treatment response only in classical subtype GBM. Integrative analysis of genomic and proteomic profiles challenges the notion of therapeutic inhibition of a pathway as an alternative to inhibition of the target itself. These data will facilitate the discovery of therapeutic and diagnostic target candidates, the validation of research and clinical observations and the generation of unanticipated hypotheses that can advance our molecular understanding of this lethal cancer

The Somatic Genomic Landscape of Glioblastoma

We describe the landscape of somatic genomic alterations based on multi-dimensional and comprehensive characterization of more than 500 glioblastoma tumors (GBMs). We identify several novel mutated genes as well as complex rearrangements of signature receptors including EGFR and PDGFRA. TERT promoter mutations are shown to correlate with elevated mRNA expression, supporting a role in telomerase reactivation. Correlative analyses confirm that the survival advantage of the proneural subtype is conferred by the G-CIMP phenotype, and MGMT DNA methylation may be a predictive biomarker for treatment response only in classical subtype GBM. Integrative analysis of genomic and proteomic profiles challenges the notion of therapeutic inhibition of a pathway as an alternative to inhibition of the target itself. These data will facilitate the discovery of therapeutic and diagnostic target candidates, the validation of research and clinical observations and the generation of unanticipated hypotheses that can advance our molecular understanding of this lethal cancer

Collisions of highly excited xenon atoms

The collisional ionization of xenon high Rydberg atoms by various target gases is investigated. Ground state xenon atoms are excited by an electron impact-photoexcitation method to the selected high Rydberg states where n has a value between 25 and 4. Absolute rate constants are measured for the ionization of these atoms in collision under conditions of zero electric field and small electric fields. The experimental method is discussed and the results are compared with other experiments and with theory

Systems analysis of decontamination options for civilian vehicles.

The objective of this project, which was supported by the Department of Homeland Security (DHS) Science and Technology Directorate (S&amp;T) Chemical and Biological Division (CBD), was to investigate options for the decontamination of the exteriors and interiors of vehicles in the civilian setting in order to restore those vehicles to normal use following the release of a highly toxic chemical. The decontamination of vehicles is especially challenging because they often contain sensitive electronic equipment, multiple materials some of which strongly adsorb chemical agents, and in the case of aircraft, have very rigid material compatibility requirements (i.e., they cannot be exposed to reagents that may cause even minor corrosion). A systems analysis approach was taken examine existing and future civilian vehicle decontamination capabilities