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Allergic diseases are a growing health concern in industrialized countries. Despite a number of effective therapeutic options for the prevention and treatment of the pathophysiologic responses which characterize allergic diseases, the induction of true allergen desensitization remains an elusive therapeutic goal. Only immunotherapy (IT) has been shown to have any effect on the underlying hypersensitivities which mediate allergic reactions, and traditional protein-based allergen IT has a limited scope of efficacy. However, a number of reagents collectively termed DNA‐based immunotherapeutics have proven highly effective in both the prevention and reversal of Th2-mediated hypersensitivity states in mouse models of allergic disease. Four basic DNA-based immunotherapeutic modalities have been used for these studies. These include immunization with gene vaccines, allergen mixed with immunostimulatory oligodeoxynucleotide (ISS-ODN), and physical allergen-ISS-ODN conjugates (AIC), as well as immunomodulation with ISS-ODN alone. Results from many laboratories have generated guarded optimism that DNA-based immunotherapeutics may be effective for the reversal of allergic hypersensitivity states in humans, and several clinical trials have already been initiated. This review will focus on our present understanding of the biological activities of DNA-based immunotherapeutics and their application to the treatment of allergic diseases., Institutos Nacionales de Salud, Dynavax Thecnologies Corporation, Depto. de Medicina, Fac. de Medicina, TRUE, pub

In reversed-phase liquid chromatography, temperature significantly affects analyte retention factor. The dependence of analyte retention can be expressed either simply being 1) dependent on temperature alone, or more complex being dependent on 2) mobile phase pH, buffer, and temperature, or 3) mobile phase composition and temperature. Analyte retention commonly increases with decreasing temperature. Temperature assisted solute focusing (TASF) takes advantage of this effect by decreasing the temperature of the head of the column to focus analytes. Temperature is increased to release the concentrated analyte bands, improving method limits of detection. Simple expressions for the temperature dependence of retention allowed capillary scale TASF to be extended to the analytical scale. Understanding more complex dependencies of analyte retention on experimental conditions allows for the optimization of chromatographic separations. We explored the effect of pH and buffer selection on the retention of ionizable analytes when mobile phase pH is near analyte pKa. Buffer ionization enthalpy affects pH change with temperature. Thus, when mobile phase pH is near analyte pKa, buffer selection can be used to modify the temperature dependence of retention. We also compared the ability of mobile phase composition and temperature dependent retention expressions to predict retention for 101 compounds. To extend predictions of the effect of experimental conditions on retention, we explored functional group contributions to thermodynamic parameters. We demonstrated that the temperature dependence of retention, enthalpy, is additive for 39 functional groups, where each functional group’s contribution is temperature and mobile phase composition dependent. Predicted enthalpies show reasonable agreement with literature but demonstrate that different functional groups behave differently on columns with different chemistries and ligand densities. However, functional group contributions accura