Research and Related Publications

The dictum, “publish or perish” is well-entrenched in the minds of researchers. When the results of basic and applied research and technology activities are distributed, background, methodology, and placement of the work in a larger context must be provided, along with appropriate references to allow other researchers to understand the nature of the work and how it fits (or doesn’t) with their own efforts.

I have many years of experience with research and highly technical publications, as witnessed by this selected list of peer-reviewed and edited items (presented alphabetically by first author), followed by a selected list of publications published as abstracts.

Research and Related Publication Experience:

Listed here are research activities that demonstrate the wide range of topics and techniques that support my basic approach not only to scientific research, but to technical problem solving of all kinds.  Such problem solving requires background and context, analysis of the problem’s technical aspects, understanding methodology and applying it (often with modifications), careful implementation of plans, collection of data, drawing appropriate and supportable conclusions, and—ultimately—increasing the store of knowledge preliminary to further investigations.

 

Sole Responsibility

Direct Interaction between Amino Acids and Nucleotides as a Possible Physicochemical Basis for the Origin of the Genetic Code1H nuclear magnetic resonance (NMR) spectroscopy was used to explore the binding constants for systems consisting of genetic code codon and anticodon mono-, di-, and trinucleotides with their cognate amino acids.  The results were analyzed using nonlinear least-squares regression analysis to several candidate models. The results showed a consistent pattern of statistically significant interaction between the anticodon nucleotides and their cognate amino acids. There was a clear preference for interactions with the 3’-5’ nucleotides; there was no interaction observed when 2’-5’ nucleotides were used.   – Laboratory for Chemical Evolution, University of Maryland, College Park.

The Binding of Physiologically Significant Protons to 2,3-Diphosphoglycerate – A 31P nuclear magnetic resonance (NMR) study was performed to understand how protons titrating in the physiologically significant pH range bound to this modulator of hemoglobin action. The results were phenomenologically similar to standard titration techniques, but the granularity of the data and application of statistical thermodynamic considerations allowed a more-detailed analysis to derive the free energy of interaction of the binding. This information was used in another study, described immediately below.  – The Johns Hopkins University, Baltimore, MD

pH Dependence of 2,3-Diphosphoglycerate Binding to Human Hemoglobin A1 – Rate equilibrium dialysis was used to study the combined effects of temperature and pH on hemoglobin function.  32P-labeled 2,3-diphosphoglycerate was used as the marker. A statistical thermodynamic approach resulted in a multidimensional scheme that allowed for a complete analysis of the various interactions.  – The Johns Hopkins University, Baltimore, MD

 

Team Member

Isolation and Characterization of E. coli DNA Polymerase I – Standard protein isolation and characterization of this enzyme, with an eye toward understanding its role in mutation and DNA repair.  – The Johns Hopkins University, Baltimore, MD.

Isolation and Characterization of Calf Thymus Chromatin – Calf thymus chromatin was used to explore the role(s) that histones play in DNA packing and genetic code transcription.  – The Johns Hopkins University, Baltimore, MD.

Isolation and Characterization of Polyoma Nucleoprotein Complex – Mouse 3T3 cells were infected with polyoma virus to allow isolation and characterization of mid-replication assemblies to further understand the general mechanism of DNA replication.  – The Johns Hopkins University, Baltimore, MD

Steady-state and Kinetic Analysis of Binding of Asialoorosomucoid to the Isolated Rabbit Hepatocyte Lectin125I-labeled asialoorosomucoid was used to explore the kinetics of binding with a lectin.  The results showed two classes of binding site.  The Johns Hopkins University, Baltimore, MD

Hepatocyte Adhesion to Carbohydrate-derivatized Surfaces. I. Surface Topography of the Rat Hepatic Lectin – Biochemical and immunohistological techniques were used to explore the topographical redistribution of the rat hepatic lectins in response to galactose-mediated cell adhesion. The work provided a measurement of lateral diffusion coefficient, suggesting no impediment to membrane in-plane diffusion, and that physical size and or lectin density of patches are restricted by kinetic or topological constraints.  – The Johns Hopkins University, Baltimore, MD

Effects of α-amanitin on Puff Formation and RNA Synthesis in D. melanogaster Salivary Glands – Salivary glands from late third-instar larvae of D. melanogaster were incubated in radionuclide-labeled RNA precursors in the presence of an known inhibitor of RNA synthesis to explore physical and functional changes as observed by liquid scintillation counting and radiomicrography. – Tulane University, New Orleans, LA

Ultrasonic Absorption Properties of Human HemoglobinIn vitro research to explore the mechanisms by which ultrasound is absorbed by proteins. The work consisted of measuring ultrasonic absorption of samples of human hemoglobin obtained from a local hospital as a function of dehydration state. The distinctions between bound and free water in the samples were found to be of importance in understanding these mechanisms. – University of Rochester, Rochester, NY

 

Advisory Role

A Quantitative Assay of Biologically Important Compounds in Simulated Primitive Earth Experiments A mixture of candidate prebiotic Earth gases were subject to high-voltage, high-frequency electric discharge to examine the chemical yields of various molecules as a function of energy input to get a better insight into the relative role of electric discharges on the primitive Earth.  – Laboratory for Chemical Evolution, University of Maryland, College Park.

Trace Elements in Chemical Evolution – This work was done to explore the origin of the essentiality of trace elements in present biological systems; the possible roles of trace elements in chemical evolution; and the origin of enzymatic activity with metal ions, i.e., the origin of metalloenzymes.Electric discharge experiments have been performed in a plausible primitive earth atmosphere consisting of methane, nitrogen, and water over an aqueous phase of an ammonia-ammonium buffer solution. In some experiments, ions of metal elements, calcium, magnesium, zinc, iron and molybdenum were introduced. Gas phase products and amino acids in the liquid phase were analyzed by gas chromatography. With trace metal ions, fewer organic compounds in the gas phase and larger amounts of amino acids were obtained than without them. The results have shown the possible importance of trace elements in chemical evolution and the origin of life on the earth.  – Laboratory for Chemical Evolution, University of Maryland, College Park.

Synthesis and Properties of an all-D Model Ribonuclease S-Peptide – As part of an effort to understand the origins of biochirality, the S-peptide of RNAse was constructed with solid-phase synthesis, using all-D amino acids. Circular dichroism (CD) studies of the D-peptide showed a peak of positive ellipticity whereas a negative ellipticity peak for the L-peptide was observed in the same region. The effects of temperature and trifluoroethanol on the far-ultraviolet CD spectra of D- and L-peptides were similar but of opposite sign, confirming the expectation that the L-peptide has the propensity to form an α-helical structure which is enantiomeric with respect to that formed by the L-peptide. In the presence of S-protein, the L-peptide showed hydrolytic activity against the substrate cytidine-2′:3′-monophosphate, whereas the D-peptide was inactive.  – Laboratory for Chemical Evolution, University of Maryland, College Park.

Nonrandomness in Prebiotic Peptide Synthesis –  Phosphoanhydrides of alanine with guanosine monophosphate, uridine monophosphate, and adenosine monophosphate were synthesized and characterized to investigate the specificity of peptide bond formation in a model terrestrial prebiotic environment. The differential reactivity of the amino acids results in nearest-neighbor preferences during the peptide synthesis, whereas the nature of the nucleotides and the presence of complementary polynucleotides had no influence on the specificity. These results suggest that some peptides would have been more abundant than others on the prebiotic earth and have implications for the study of the origins of the genetic code and protein synthesis.  – Laboratory for Chemical Evolution, University of Maryland, College Park.

Modeling Sea-Ice Meltwater Effects on 18O Concentrations in Arctic Surface Waters – The project was carried out to test the use of data from the Strategic Environmental Distributed Active Archive Resource (SEDAAR), which provided access to and use of high-value Department of Defense data for environmental research and remediation applications. The work showed how SEDAAR was integrated into the project, and provided an evaluation of the effectiveness of the SEDAAR data and platform. – Consortium for International Earth Science Information Network, Washington, D.C. Office.

Russian Environment and Health Mapping – SEDAAR (see above) data were used to explore the possible impact of environmental problems on the health of a population, based on the spread of 137Cs in two areas where nuclear accidents had taken place. Although a major goal of the project—to perform meaningful statistical analysis of available data—was not possible owing to the ambiguous origins of the data and associated coarse granularity–the project did result in generating data compatible with the ARC/INFO geographic information system (GIS) for later use by other researchers.  – Consortium for International Earth Science Information Network, Washington, D.C. Office.