Abstract: The disclosed subject matter relates to a force-clamp spectrometer that enables operation in constant force mode and allows for automated data acquisition and analysis, using feedback electronics and software. The disclosed subject matter also relates to methods of using the force-clamp spectrometer for the measurement of the dynamics of chemical reactions. The methods may include, but are not limited to, the measurement of the dynamics of substrate folding and unfolding, as well as bond cleavage and bond formation.

Abstract: The invention provides a method tar increasing the stability and/or activity of a polypeptide at low pH and/or elevated temperatures The invention farther provides a method for increasing the melting temperature of a polypeptide. Also provided are paleoenzymologically reconstructed thioredoxin polypeptides having activity at higher temperatures and/or lower pH than extant thioredoxin polypeptides, as well as paleoenzymologically reconstructed thioredoxin polypeptides having higher melting temperatures than extant thioredoxin polypepetides.

Abstract: The invention provides a method for increasing the stability and/or activity of a polypeptide at low pH and/or elevated temperatures. The invention further provides a method for increasing the melting temperature of a polypeptide. Also provided are paleoenzymologically reconstructed thioredoxin polypeptides having activity at higher temperatures and/or lower pH than extant thioredoxin polypepetides, as well as paleoenzymologically reconstructed thioredoxin polypeptides having higher melting temperatures than extant thioredoxin polypepetides.

Abstract: A method of delivering a therapeutic compound to an in vivo target site having a selected pH, temperature, ligand concentration or binding-molecule characteristic. The method includes entrapping the therapeutic compound in an encapsulated microparticle composition that, when exposed to a selected target stimulus related to pH, temperature, radiation, or the presence of a selected ligand or ion-channel activator, decondenses to release compound into the target site. The encapsulated microparticle composition consists of a condensed-phase particle matrix containing the compound to be delivered in entrapped form, and a stimulus-responsive lipid bilayer membrane formed around the matrix. Localized perturbation of the lipid membrane, and influx of monovalent counterions into the polymer matrix, in response to the selected target stimulus, causes matrix swelling and compound release from the particles.

Abstract: An microparticle composition and its method of use in drug delivery and diagnostic applications are disclosed. Also disclosed are methods of storing and administering drug compounds at high concentration in condensed-phase microparticles.

Abstract: A microparticle composition for use in compound delivery, when the composition is exposed to a selected target stimulus related to pH, temperature, radiation, or the presence of a selected ligand or ion-channel activator, is disclosed. The composition includes a condensed-phase particle matrix containing the compound to be delivered in entrapped form, and a stimulus-responsive lipid bilayer membrane formed around the matrix. Localized perturbation of the lipid membrane, and influx of monovalent counterions into the polymer matrix, in response to the selected target stimulus, causes matrix swelling and compound release from the particles.

Abstract: An microparticle composition and its method of use in drug delivery and diagnostic applications are disclosed. Also disclosed are methods of storing and administering drug compounds at high concentration in condensed-phase microparticles.

Abstract: A diode device (10) containing a microparticle polymer element (12) is described. Also described are mechanical switching devices that employ the microparticle polymer element.