Abstract: Atomized particles within a desired size range (e.g., 1 micron to about 5 microns) are produced from two immiscible fluids, a first fluid source containing the formulation to be atomized, and a second fluid source which is contained in a pressure chamber surrounding at least the area where the first liquid is to be provided. The invention provides methods for: the production of templates for microfabrication, such as particles that serve as templates for self-assembly of monolayers; the creation of small particles to serve as building blocks for the microassembly of objects; and the use of an atomizate to etch configurations and/or patterns onto the surface of an object by removing a selected portion of the surface.

Abstract: Cultured brain slices are treated with a free radical generator, in the presence of a lysosomal enzyme inhibitor (specifically an inhibitor of two cathepsins). The treated brain slices rapidly develop autofluorescent lipofuscin granules—a universal feature of brain aging. Other correlates of the aged brain are also induced by this treatment, thereby providing an in vitro model for (1) the study of brain aging; (2) assessment of anti-brain aging drugs; and (3) therapeutics directed at the clinical condition referred to as neuronal ceroidlipofuscinosis.

Abstract: The need for the delivery of insulin by injection can be reduced or eliminated by delivering an aerosolized monomeric insulin formulation. Repeatability of dosing and more particularly the repeatability of the blood concentration versus time profile is improved relative to regular insulin. The blood concentration versus time profile is substantially unaffected by specific aspects of the patient's breathing maneuver at delivery. Further, the rate at which blood glucose is lowered is increased by the use of monomeric insulin. Particles of insulin and in particular monomeric insulin delivered to the surface of lung tissue will be absorbed into the circulatory system. The monomeric insulin may be a dry powder but is preferably in a liquid formulation delivered to the patient from a hand-held, self-contained device which automatically releases an aerosolized burst of formulation.

Abstract: Atomized particles within a desired size range (e.g., 1 micron to about 5 microns) are produced from two immiscible fluids, the first a fuel source containing the formulation to be atomized, and a second fluid source which is contained in a pressure chamber surrounding at least the area where the first liquid is to be provided. The invention provides a method for the formation of small, relatively uniform fuel particles for use in internal combustion engines and a nozzle-type apparatus for providing the particles to a combustion chamber.

Abstract: The need for the delivery of insulin by injection can be reduced or eliminated by delivering an aerosolized monomeric insulin formulation. Repeatability of dosing and more particularly the repeatability of the blood concentration versus time profile is improved relative to regular insulin. The blood concentration versus time profile is substantially unaffected by specific aspects of the patient's breathing maneuver at delivery. Further, the rate at which blood glucose is lowered is increased by the use of monomeric insulin. Particles of insulin and in particular monomeric insulin delivered to the surface of lung tissue will be absorbed into the circulatory system. The monomeric insulin may be a dry powder but is preferably in a liquid formulation delivered to the patient from a hand-held, self-contained device which automatically releases an aerosolized burst of formulation.

Abstract: The libido of adult human female patients is increased by the intrapulmonary delivery of testosterone. A formulation of testosterone is aerosolized and inhaled into a patient's lungs where particles of testosterone deposits on lung tissue and then enter the patient's circulatory system. The patient's testosterone level is enhanced well above baseline levels for a short period and subsides to baseline levels with normal metabolism thereby providing desired short term effects on enhanced libido without undesirable effects of long term enhanced testosterone levels. Additional formulations are provided including formulations for aerosolized delivery of sildenafil citrate which are delivered to male or female patients.

Abstract: The present invention provides a method of assaying for and arresting, preventing and/or reversing the impairment of central and peripheral nervous system function comprising reducing &bgr;-amyloid plaque burden by the administration of compounds that reduce apoE expression. The compounds used in the method of the invention may be: 1) inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase; 2) inhibitors of cholesterol biosynthesis; 3) inhibitors of protein isoprenylation, specifically geranylgeranylation; and/or 4) inhibitors of NF-&kgr;B activation or function. Assays for compounds with inhibit apoE expression from microglial cells are also disclosed.

Abstract: The need for the delivery of insulin by injection can be reduced or eliminated by delivering an aerosolized monomeric insulin formulation. Repeatability of dosing and more particularly the repeatability of the blood concentration versus time profile is improved relative to regular insulin. The blood concentration versus time profile is substantially unaffected by specific aspects of the patient's breathing maneuver at delivery. Further, the rate at which blood glucose is lowered is increased by the use of monomeric insulin. Particles of insulin and in particular monomeric insulin delivered to the surface of lung tissue will be absorbed into the circulatory system. The monomeric insulin may be a dry powder but is preferably in a liquid formulation delivered to the patient from a hand-held, self-contained device which automatically releases an aerosolized burst of formulation.

Abstract: A semiconductor nanocrystal compound is described capable of linking to an affinity molecule. The compound comprises (1) a semiconductor nanocrystal capable of emitting electromagnetic radiation and/or absorbing energy, and/or scattering or diffracting electromagnetic radiation—when excited by an electromagnetic radiation source or a particle beam; and (2) at least one linking agent, having a first portion linked to the semiconductor nanocrystal and a second portion capable of linking to an affity molecule. The compound is linked to an affinity molecule to form a semiconductor nanocrystal probe capable of bonding with a detectable substance. Subsequent exposure to excitation energy will excite the semiconductor nanocrystal in he probe, causing the emission of electromagnetic radiation.

Abstract: An ophthalmic formulation is disclosed which reduces dilation in dim light and reduces redness.

Abstract: An assay comprises contacting cells containing a conformationally altered protein with test compound and determining if the altered protein is cleared. The cells may be scrapie-infected neuroblastoma cells. Another assay comprises contacting organ or tissue homogenate (at pH 5.0 or less) with test compound to determine if altered protein in the homogenate is 10 cleared. The homogenate may be brain homogenate from a transgenic mouse infected with human prions. Compounds which are found to clear the altered protein are useful in preventing, arresting and/or reversing (i.e. treating) a disease associated with the conformationally altered protein.

Abstract: A patient interface system for collecting and transferring data from a patient to a remote monitoring system, as well as methods for its use, are provided. The subject system comprises: (a) a data collection means comprising an edema sensing means and an interrogation means; (b) a processing means for processing the collected data; and (c) a communication means for transferring said collected data from said interface means to a remote monitoring system and receiving instructional data from a remote monitoring system. The subject system finds use in the remote monitoring of a variety of conditions, particularly in the remote monitoring of cardiac associated diseases.

Abstract: The need for the delivery of insulin by injection can be reduced or eliminated by a method whereby an aerosolized insulin formulation is delivered to a patient's lungs and the rate at which the insulin is absorbed into the blood is increased by the use of an inhale-exhale breathing maneuver. Particles of insulin delivered to the surface of lung tissue will be absorbed into the circulatory system. The rate of absorption is enhanced by instructing the patient to inhale maximally and thereafter exhale maximally. This maneuver causes a spike in the rate at which insulin enters the circulatory system thereby increasing the rate at which glucose is removed from the circulatory system. The insulinmay be a dry powder but is preferably in a liquid formulation delivered to the patient from a hand-held, self-contained device which automatically releases an aerosolized burst of formulation.

Abstract: The invention is directed to a stable capillary microjet and a monodisperse aerosol formed when the microjet dissociates. A variety of devices and methods are disclosed which allow for the formation of a stream of a first fluid (e.g. a liquid) characterized by forming a stable capillary microjet over a portion of the stream wherein the microjet portion of the stream is formed by a second fluid (e.g. a gas). The second fluid is preferably in a different state from the first fluid—liquid-gas or gas-liquid combinations. However, the first and second fluids may be two different fluids in miscible in each other.

Abstract: An assay method is disclosed which isolates and detects the presence of a disease related conformation of a protein (e.g., PrPSc) present in a sample also containing the non-disease related conformation of the protein (e.g., PrPC). The sample is treated (e.g., contacted with protease) in a manner which hydrolyzes the disease related conformation and not the non-disease related conformation. The treated sample is contacted with a binding partner (e.g., a labeled antibody which binds PrPSc) and the occurrence of binding provides and indication that PrPSc is present. Alternatively the PrPSc of the treated sample is denatured (e.g., contacted with guanadine) or unfolded. The unfolded PrPSC is contacted with a binding partner and the occurrence of binding indicates the presence of PrPSc in the sample.

Abstract: Electroporation is performed in a controlled manner in either individual or multiple biological cells or biological tissue by monitoring the electrical impedance, defined herein as the ratio of current to voltage in the electroporation cell. The impedance detects the onset of electroporation in the biological cell(s), and this information is used to control the intensity and duration of the voltage to assure that electroporation has occurred without destroying the cell(s). This is applicable to electroporation in general. In addition, a particular method and apparatus are disclosed in which electroporation and/or mass transfer across a cell membrane are accomplished by securing a cell across an opening in a barrier between two chambers such that the cell closes the opening. The barrier is either electrically insulating, impermeable to the solute, or both, depending on whether pore formation, diffusive transport of the solute across the membrane, or both are sought.

Abstract: The present invention provides aeration methods using spherical gas bubbles having a size on the order of 0.1 to 100 microns in size. A device of the invention for producing a monodispersion of bubbles includes a source of a stream of gas which is forced through a liquid held under pressure in a pressure chamber with an exit opening therein. The stream of gas surrounded by the liquid in the pressure chamber flows out of an exit orifice of the chamber into a liquid thereby creating a monodispersion of bubbles with substantially uniform diameter. The bubbles are small in size and produced with a relatively small amount of energy relative to comparable systems. Applications of the aeration technology range from oxygenating sewage with monodispersions of bubbles to oxygenation of water for fish maintenance.

Abstract: Images created by electrical impedance tomography (EIT) are used to adjust one or more electrical parameters and obtain a desired degree of electroporation of cells in tissue. The parameters include current, voltage and a combination thereof. The cells are subjected to conditions such that they become permeabilized but are preferably not subjected to conditions which result in irreversible pore formation and cell death. The electroporation can analyze cell membranes, diagnose tissues and the patient as well as to move materials into and out of cells in a controlled manner.

Abstract: Atomized particles within a desired size range (e.g., 1 micron to about 5 microns) are produced from two immiscible fluids, the first a fuel source containing the formulation to be atomized, and a second fluid source which is contained in a pressure chamber surrounding at least the area where the first liquid is to be provided. The invention provides a method for the formation of small, relatively uniform fuel particles for use in internal combustion engines and a nozzle-type apparatus for providing the particles to a combustion chamber.

Abstract: A method of allowing a community of users to self-administer a hearing test via a computer system accessed over the Internet is disclosed. A web site is generated which is accessible by a community of users over the Internet. The web site presents a screen to a user which gives instructions on responding to sounds. Electronic data is sent to users which instructs the user's computer to generate a series of sounds at different amplitudes and frequencies. The user blocks sound to one ear and responds to sounds detected by the other ear. The responses are analyzed against a known standard to provide information on user hearing.