Methods and compositions for X-ray induced release from pH sensitive liposomes

Compositions including pH sensitive lipid vesicles comprised of a lipid layer, an agent, and an organic halogen such that the agent is released from the vesicles after exposure to ionizing radiation. Methods of delivering the agent to a target in a subject using the compositions provided herein are also described. The methods allow for controlled release of the agent. The timing of release of the agent from the lipid vesicle may be controlled as well as the location of release by timing and localizing the exposure to ionizing radiation exposure

Methods and compositions for X-ray induced release from pH sensitive liposomes

Compositions including pH sensitive lipid vesicles comprised of a lipid layer, an agent, and an organic halogen such that the agent is released from the vesicles after exposure to ionizing radiation. Methods of delivering the agent to a target in a subject using the compositions provided herein are also described. The methods allow for controlled release of the agent. The timing of release of the agent from the lipid vesicle may be controlled as well as the location of release by timing and localizing the exposure to ionizing radiation exposure

A Model for the Hysteresis Observed in Gating of Lysenin Channels

The pore-forming toxin lysenin self-inserts to form conductance channels in natural and artificial lipid membranes containing sphingomyelin. The inserted channels exhibit voltage regulation and hysteresis of the macroscopic current during the application of positive periodic voltage stimuli. We explored the bi-stable behavior of lysenin channels and present a theoretical approach for the mechanism of the hysteresis to explain its static and dynamic components. This investigation develops a model to incorporate the role of charge accumulation on the bilayer lipid membrane in influencing the channel conduction state. Our model is supported by experimental results and also provides insight into the temperature dependence of lysenin channel hysteresis. Through this work we gain perspective into the mechanism of how the response of a channel protein is determined by previous stimuli

Observation of Nondegenerate Two-Photon Gain in GaAs

Two-photon lasers require materials with large two-photon gain (2PG) coefficients and low linear and nonlinear losses. Our previous demonstration of large enhancement of two-photon absorption in semiconductors for very different photon energies translates directly into enhancement of 2PG. We experimentally demonstrate nondegenerate 2PG in optically excited bulk GaAs via femtosecond pump-probe measurements. 2PG is isolated from other pump induced effects through the difference between measurements performed with parallel and perpendicular polarizations of pump and probe. An enhancement in the 2PG coefficient of nearly two orders-of-magnitude is reported. The results point a possible way toward two-photon semiconductor lasers.Comment: 5 pages, 5 figure

Bi-Stability, Hysteresis, and Memory of Voltage-Gated Lysenin Channels

Lysenin, a 297 amino acid pore-forming protein extracted from the coelomic fluid of the earthworm E. foetida, inserts constitutively open large conductance channels in natural and artificial lipid membranes containing sphingomyelin. The inserted channels show voltage regulation and slowly close at positive applied voltages. We report on the consequences of slow voltage-induced gating of lysenin channels inserted into a planar Bilayer Lipid Membrane (BLM), and demonstrate that these pore-forming proteins constitute memory elements that manifest gating bi-stability in response to variable external voltages. The hysteresis in macroscopic currents dynamically changes when the time scale of the voltage variation is smaller or comparable to the characteristic conformational equilibration time, and unexpectedly persists for extremely slow-changing external voltage stimuli. The assay performed on a single lysenin channel reveals that hysteresis is a fundamental feature of the individual channel unit and an intrinsic component of the gating mechanism. The investigation conducted at different temperatures reveals a thermally stable reopening process, suggesting that major changes in the energy landscape and kinetics diagram accompany the conformational transitions of the channels. Our work offers new insights on the dynamics of pore-forming proteins and provides an understanding of how channel proteins may form an immediate record of the molecular history which then determines their future response to various stimuli. Such new functionalities may uncover a link between molecular events and macroscopic processing and transmission of information in cells, and may lead to applications such as high density biologically-compatible memories and learning networks

Method of controlled drug release from a liposome carrier

Methods and compositions for the controlled release of a drug or agent from a liposome using light or radiation are disclosed. Compositions comprising liposomes having a lipid layer, wherein the liposomes contain an agent, an enzyme capable of releasing the agent from the liposome, and an enzyme activator sequestered by a molecular cage are also disclosed, in addition to methods of delivering an agent to a target in a subject

Method of fabricating thin film superconducting materials

Improved superconducting thin films are provided having very high Tc (zero) and Jc values, on the order of greater than or equal to 120K and 10^5 A/cm^2 or greater, respectively. The films of the invention are adapted for deposit and support on a compatible substrate, and include a superconductive material, most preferably Tl2Ba2Ca2Cu3O10, with up to about 10% elemental gold admixed with the superconductive material. The preferred method for fabricating the thin film superconductors comprises first forming a non-superconducting precursor film on a compatible substrate which is placed in contact with an unsintered bulk body containing thallium. The substrate with precursor film are sintered with the bulk body to form the desired superconductor material

Potential Analytical Applications of Lysenin Channels for Detection of Multivalent Ions

Transmembrane protein transporters possessing binding sites for ions, toxins, pharmaceutical drugs, and other molecules constitute excellent candidates for developing sensitive and selective biosensing devices. Their attractiveness for analytical purposes is enhanced by the intrinsic amplification capabilities shown when the binding event leads to major changes in the transportation of ions or molecules other than the analyte itself. The large-scale implementation of such transmembrane proteins in biosensing devices is limited by the difficulties encountered in inserting functional transporters into artificial bilayer lipid membranes and by the limitations in understanding and exploiting the changes induced by the interaction with the analyte for sensing purposes. Here, we show that lysenin, a pore-forming toxin extracted from earthworm Eisenia foetida, which inserts stable and large conductance channels into artificial bilayer lipid membranes, functions as a multivalent ion-sensing device. The analytical response consists of concentration and ionic-species-dependent macroscopic conductance inhibition most probably linked to a ligand-induced gating mechanism. Multivalent ion removal by chelation or precipitation restores, in most cases, the initial conductance and demonstrates reversibility. Changes in lipid bilayer membrane compositions leading to the absence of voltage-induced gating do not affect the analytical response to multivalent ions. Microscopic current analysis performed on individual lysenin channels in the presence of Cu2+ revealed complex open–closed transitions characterized by unstable intermediate sub-conducting states. Lysenin channels provide an analytical tool with a built-in sensing mechanism for inorganic and organic multivalent ions, and the excellent stability in an artificial environment recommend lysenin as a potential candidate for single-molecule detection and analysis