Massachusetts Institute of Technology

The Penn State Research Foundation

Other

Wisconsin Alumni Research Foundation

Jue Wang

Robert Samuel Langer

David A Edwards

Jeffrey Mintzes

Donghao Chen

Rita Vanbever

Jon Asher Wolff

Dina Katabi

Deepak Vasisht

David M Neville

Yuan Xie

Stuart J Knechtle

A system for localization of a radio frequency source in a region includes a first plurality of antennas disposed about the region, a second plurality of antennas disposed about the region, a first radio frequency positioning module in communication with the first plurality of antennas and configured to determine a plurality of spatially separated candidate locations in the region for the radio frequency source, a second radio frequency positioning module in communication with the second plurality of antennas and configured to determine a sub-region of the region, the sub-region including the radio frequency source, and a resolution module for identifying a subset of the candidate locations in the sub-region of the region.

Radio frequency localization

Processors and methods disclosed herein include a cache memory unit, n processor cores where n&#x2267;1, a controller connected to the cache memory unit and to each of the n processor cores, and n obstruction monitoring units, where each obstruction monitoring unit is connected to the controller and to a different one of the n processor cores, and where during operation of the electronic processor, each obstruction monitoring unit is configured to detect an obstruction corresponding to an operation from the processor core connected to the obstruction monitoring unit before the operation executes in the cache memory unit.

Obstruction-aware cache management

The invention generally relates to a method for pulmonary delivery of therapeutic, prophylactic and diagnostic agents to a patient wherein the agent is released in a sustained fashion, and to particles suitable for use in the method. In particular, the invention relates to a method for the pulmonary delivery of a therapeutic, prophylactic or diagnostic agent comprising administering to the respiratory tract of a patient in need of treatment, prophylaxis or diagnosis an effective amount of particles comprising a therapeutic, prophylactic or diagnostic agent or any combination thereof in association with a charged lipid, wherein the charged lipid has an overall net charge which is opposite to that of the agent upon association with the agent. Release of the agent from the administered particles occurs in a sustained fashion.

Particles for inhalation having sustained release properties

The invention generally relates to a method for pulmonary delivery of therapeutic, prophylactic and diagnostic agents to a patient wherein the agent is released in a sustained fashion, and to particles suitable for use in the method. In particular, the invention relates to a method for the pulmonary delivery of a therapeutic, prophylactic or diagnostic agent comprising administering to the respiratory tract of a patient in need of treatment, prophylaxis or diagnosis an effective amount of particles comprising a polycationic complexing agent which is complexed with a therapeutic, prophylactic or diagnostic agent or any combination thereof having a charge capable of complexing with the polycationic complexing agent upon association with the bioactive agent. The particles can further comprise a pharmaceutically acceptable carrier. The amount of polycationic complexing agent present in the particles is an amount sufficient to sustain the release of diagnostic, therapeutic or prophylactic agent from the particles. For example, the amount of complexing agent present can be at about 5% weight/weight (w/w) or more of the total weight of the complexing agent and therapeutic, diagnostic or prophylactic agent. Release of the agent from the administered particles occurs in a sustained fashion.

Particles incorporating a surfactant and/or a hydrophilic or hydrophobic complex of a positively or negatively charged therapeutic agent and a charged molecule of opposite charge for drug delivery to the pulmonary system, and methods for their synthesis and administration are provided. In a preferred embodiment, the particles are made of a biodegradable material and have a tap density less than 0.4 g/cm and a mass mean diameter between 5 &mgr;m and 30 &mgr;m, which together yield an aerodynamic diameter of the particles of between approximately one and three microns. The particles may be formed of biodegradable materials such as biodegradable polymers. For example, the particles may be formed of poly(lactic acid) or poly(glycolic acid) or copolymers thereof. Alternatively, the particles may be formed solely of a therapeutic or diagnostic agent and a surfactant. Surfactants can be incorporated on the particle surface for example by coating the particle after particle formation, or by incorporating the surfactant in the material forming the particle prior to formation of the particle. Exemplary surfactants include phosphoglycerides such as dipalmitoyl phosphatidylcholine (DPPC). The particles can be effectively aerosolized for administration to the respiratory tract to permit systemic or local delivery of wide a variety of therapeutic agents. Formation of complexes of positively or negatively charged therapeutic agents with molecules of opposite charge can allow control of the release rate of the agents into the blood stream following administration.

Preparation of novel particles for inhalation

Particles incorporating a surfactant and/or a hydrophilic or hydrophobic complex of a positively or negatively charged therapeutic agent and a charged molecule of opposite charge for drug delivery to the pulmonary system, and methods for their synthesis and administration are provided. In a preferred embodiment, the particles are made of a biodegradable material and have a tap density less than 0.4 g/cm.sup.3 and a mass mean diameter between 5 .mu.m and 30 .mu.m, which together yield an aerodynamic diameter of the particles of between approximately one and three microns. The particles may be formed of biodegradable materials such as biodegradable polymers. For example, the particles may be formed of poly(lactic acid) or poly(glycolic acid) or copolymers thereof. Alternatively, the particles may be formed solely of a therapeutic or diagnostic agent and a surfactant. Surfactants can be incorporated on the particle surface for example by coating the particle after particle formation, or by incorporating the surfactant in the material forming the particle prior to formation of the particle. Exemplary surfactants include phosphoglycerides such as dipalmitoyl phosphatidylcholine (DPPC). The particles can be effectively aerosolized for administration to the respiratory tract to permit systemic or local delivery of wide a variety of therapeutic agents. Formation of complexes of positively or negatively charged therapeutic agents with molecules of opposite charge can allow control of the release rate of the agents into the blood stream following administration.

Preparation of particles for inhalation

Disclosed is a method of inhibiting a rejection response by a primate to a transplanted organ. One exposes the primate to a mutant diphtheria toxin linked to anti-CD3 antibody so as to largely eliminate the host's peripheral blood T cell lymphocyte population. At the same time as, or after, the exposure step one administers to the primate's thymus gland donor lymphocytes. Transplantation of the organ follows. The primate is tolerized to the transplanted organ.

Growing community of inventors

Clifton, NJ, United States of America

Jue Wang