On Dionysian Theological Methodology

Pseudo-Dionysius the Areopagite was an anonymous theologian who likely lived in Syria around the sixth century CE. He is primarily known for his advancements in the field of apophatic, or negative, theology. However, far from being against positive statements about God, Dionysius viewed them as necessary springboards for the worship of a God that is beyond word or concept. The structure of the Dionysian method for doing theology allows for the avoidance of idolatry as well as for sidestepping the charge of onto-theology in Christian God-talk. Thomas Aquinas and Hans Urs von Balthasar are theologians that each appropriated the Dionysian method and therefore displayed its usefulness in doing theology well

T.H.A.N.K.S.: Teens Helping Anyone Needing Knowledge Service

This thesis is a business plan for a new non-profit organization for volunteerism. This non-profit organization will connect college students, high school students, grade school students, and other nonprofit agencies for the purpose of providing volunteers to non-profit agencies. The enactment of the Welfare Reform Act (Temporary Assistance to Needy Families, TANF) has created a greater need for quality, well-trained volunteers in order to meet the growing demands for and needs of non-profit agencies. The □ew deadline for Welfare to Work is now 2-5 years and public assistance such as Aid to Families with Dependent Children (AFDC), food stamps, and State Assisted Child Care are no longer entitlements, but are now benefits to be earned by welfare recipients. The President\u27s Summit held in early 1997, has created an enthusiasm for volunteerism among our nation\u27s young people. Many agencies, colleges, and high schools can now compete for volunteerism grants that have been created at the state and federal levels in order to provide seed money for volunteer opportunities and programs. Now the ideal time for an organization like T.H.A.N.K.S. to compete for and receive funding. The purpose of this organization is to connect young people to volunteer opportunities in their communities. College students would train the high school volunteers and act as liaisons between the nonprofit organization and the student volunteers. This organization is based on the concept of mentoring. The end result should be increased self-esteem and self-respect for the volunteers, and better service to the clients of the participating non-profit organizations who use T.H.A.N.K.S. volunteers. One college, Lindenwood, acted as the test site for this project. Two local school districts and several non-profit organizations participated in the pilot project. Results of the pilot project produced significant data to suggest that T.H.A.N.K.S. would thrive and succeed in the St. Charles, St. Peters, and St. Louis County areas

Design, synthesis, and biological evaluation of novel MCAK and 14-3-3 protein family inhibitors.

The Borch lab is interested in the synthesis and biological evaluation of phosphopeptidomimetic prodrugs in order to disrupt proteins that are critical for cancer cell growth and proliferation. Biological evaluation of a phosphotyrosine mimetic prodrug, 1 (IC50=7µM) suggested defects in both mitosis and cytokinesis consistent with MCAK inhibition. To better understand the location of the protein-ligand interaction, a competitive ATP binding assay was run to confirm the likely binding site. Concentrations of ATP as low as 3 μM can selectively elute MCAK from the immobilized 3 ligand. To determine if the free ligand could disrupt the ATPase activity of the MCAK, a radioactive ATPase assay was run. At low micromolar concentrations, the compound inhibits the ATPase activity of the MCAK motor domain. A focused library of analogs was synthesized and analyzed for growth inhibitory activity in DG75 cells. This library resulted in compounds with IC50 values from 4-50 μM. Molecular modeling studies were carried out using the crystal structure of mammalian MCAK (pdb 1V8J) with the goal of developing higher affinity small molecule inhibitors. Docking experiments in silico exploring variations to the non-phosphate portion of 1 provided compounds with significant improvements in predicted binding affinity. The highest affinity compounds identified in silico were chosen for synthesis and evaluation in a growth inhibition assay in DG75 cells and a cell-free radioactive ATPase assay. These new compounds exhibited sub-micromolar growth inhibitory activity. To create small molecules that inhibit phosphoserine dependent interactions, we developed methodology for the synthesis of a prodrug that generates a phosphoserine peptidomimetic in cells. As a proof of principle, a small molecule inhibitor of 14-3-3 proteins was synthesized that incorporates a nonhydrolyzable difluoromethylenephosphoserine prodrug moiety. The small molecule prodrug 58 and the corresponding free phosphonate ligand 57 were evaluated for their growth inhibitory activity in DG75 leukemia cells. Compound 58 proved to be a potent inhibitor with a low mircromolar IC50 while the free ligand showed no meaningful growth inhibition at much higher concentrations. The potential cytotoxic effects of the prodrug were investigated by monitoring the cleavage of PARP, a well known caspase substrate. Significant PARP cleavage was observed by Western blot at 12 µM, suggesting 58 induces apoptosis at low micromolar concentrations. To explore a direct involvement of 14-3-3 proteins in the actions of 58 in cells, we developed an assay using a luciferase readout to monitor the 14-3-3-dependent inhibition of FOXO transcription factors. To demonstrate this disruption on a molecular level, a competitive binding assay was run using immobilized 14-3-3 tao/FOXO3a complex and free ligand 57. These experiments validated that the activity of prodrug 58 is due to 14-3-3 protein inhibition