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Show moreBackground of the invention: The present invention relates to a method and apparatus for collecting, manipulating, or separating particles from a fluid suspension. In particular, the present invention relates to an acoustically driven method and apparatus for separating fine particles from a fluid suspension. A variety of processes are used for separation of particles from fluid suspensions. None of the conventional separation processes has proved practicable for separation of fine (on the order of 1 .mu.m) particles. Conventional packed bed systems are subjected to prohibitively large pressure drops when processing fine particles. Mixer-settler contactors require extremely prolonged sedimentation steps when processing fine particles. Fluidized bed processes have proven unsuitable because fine particles are too susceptible to entrainment in the outflowing fluid. The efficiency of cyclone separation systems is too sensitive to particle size. For example, the optimum diameter of a cyclone processing 5 .mu.m mineral particles suspended in water would be about 1 cm, which is impractical for processes of any significant scale. Acoustic methods recently have shown promise for solving the problems of separating fine particles from fluid suspensions. Under appropriate conditions, a standing acoustic wave imposed on a fluid suspension containing fine particles will drive the particles to the nodes (positions of minimum range of acoustic pressure) and trap them there. An example of a separation method employing this principle is disclosed in U.S. Pat. No. 4,055,491, in which an ultrasonic generator is energized to set up a standing acoustic wave in a chamber containing blood and trap blood cells at the nodes of the standing wave. After the generator is de-activated, the blood cells settle downwardly in response to the acceleration of gravity to an outlet at the bottom of the chamber. Although acoustic waves have been shown to be effective in trapping fine particles in a fluid suspension, the methods heretofore used for trapping and removing particles have not exhibited the speed desirable for large-scale commercial processing. For example, the blood cell-separation method of U.S. Pat. No. 4,055,491 requires energizing the ultrasonic generator for twenty seconds to trap the blood cells and de-energizing the generator for five seconds to permit the trapped particles to settle out of the space subjected to the acoustic field. For the successful commercial application of acoustically aided separation methods, it is desirable both to accelerate the trapping of particles and to provide a removal scheme that does not require de-energizing the acoustic field. The present invention is intended to provide an acoustically driven particle separation method that quickly traps fine particles throughout a cell. The present invention also is intended to provide an acoustically driven particle separation method that can trap and remove fine particles simultaneously.
http://www.google.com/patents?vid=USPAT5085783
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Show moreBackground of the invention: The present invention relates to a novel method of preparing alkoxysilanes and oligomeric alkoxysiloxanes. The method comprises reacting a metal silicate with an acid selected from the group consisting of sulfurous acid and acids with a pKa greater than about 2.5 in the presence of an alcohol. The resultant product is then reacted with an alcohol to form the alkoxysilane or oligomeric alkoxysiloxane, depending on the starting silicate. This method is particularly valuable since the reaction conditions are mild and the reactants are readily available. Several methods of producing alkoxysilanes are known in the art. The most well known and often used of these methods involves the reaction of silicon tetrachloride with an alcohol. Despite the high yields which can be obtained, this method is disadvantageous in that it is a 2-step process initially requiring the formation of silicon tetrachloride. In order to avoid this roundabout approach, a method has been developed that yields alkoxysilanes by a 1-step reaction using elemental silicon and alcohols. Unfortunately, elemental silicon is generally produced from silica by a very endothermic and thus costly reaction. Several routes to oligomeric alkoxysiloxanes have also been developed. For instance, in one route silicon tetrachloride is treated with a limited amount of water to form a reaction mixture from which an appropriate chlorosiloxane is isolated. The chlorosiloxane is then treated with an alcohol to yield the alkoxysiloxane. Such routes, often yield mixtures from which it is difficult to separate the desired alkoxysiloxane. Kenney (et al.) in U.S. Pat. No. 4.717.773 teach an alternative route to alkoxysilanes and oligomeric alkoxysiloxanes comprising reacting a metal silicate with a strong acid-alcohol solution and then esterifying the resultant product with an alcohol. The only acids taught in this work are strong acids such as HC1. The present inventors have now discovered that alkoxysilanes and oligomeric alkoxysiloxanes can be made by reacting metal silicates with an acid selected from the group consisting of sulfurous acid or acids with a pKa greater than about 2.5 and then esterifying the resultant product with an alcohol. Summary: The present invention relates to a novel method of preparing alkoxysilanes. The method comprises reacting a metal orthosilicate with an acid selected from the group consisting of sulfurous acid and acids with a pKa greater than about 2.5 in the presence of an alcohol. The product is then esterified by reacting it with ROH to form Si(OR).sub.4 wherein R is an alkyl of 1-20 carbon atoms. The present invention also relates to a novel method of preparing oligomeric alkoxysiloxanes. The method comprises reacting a metal silicate having a framework that is the same as that of the desired alkoxysiloxane or is similar to it with an acid selected from the group consisting of sulfurous acid and acids with a pKa greater
http://www.google.com/patents?vid=USPAT5183914
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Show moreField of the invention: The present invention relates to reagents and methods for drug screening and, more particularly, neuronal cells and tissue for screening potential Alzheimer therapeutics. Background: In 1907, Alois Alzheimer described the case of a 51-year-old woman with a rapidly degenerating memory who (after a swift deterioration) died severely demented four years later. This condition, which now bears Alzheimer's name, describes a fatal degenerative dementing disorder with initial mild memory impairment that progresses unrelentingly to a total debilitating loss of mental and physical faculties. Following symptom onset, the course of the disease varies considerably from a few years to over 20 years, with a mean survival of approximately 8 years. M. A. Smith, "Alzheimer Disease," Internat. Rev. Neurobiol. 42:1 (1998). Alzheimer disease affects 10-15% of individuals over 65 years and up to 47% of individuals over the age of 80. In both clinical and autopsy series in the United States and Europe, Alzheimer disease accounts for approximately two-thirds of all dementias affecting elderly individuals. D. A. Evans et al., J. Am. Med. Assoc. 262: 2551 (1989).The most common and distinctive lesions present with the diseased brain are the neuritic senile plaques and neurofibrillary tangles. The major protein component of senile plaque cores and vascular amyloid is a small polypeptide of approximately 4.2 kDa termed amyloid-.beta.. A significant fraction of this protein is found to be associated with the cytoskeleton, presumably through its interaction with the microtubule-associated .tau. ("tau") protein. It is believed that the increased phosphorylated status of tau protein represents one of the earliest neuronal changes prior to the development of neurofibrillary tangles. Unfortunately, because of the heterogeneity of the factors thought to be responsible for Alzheimer disease and the lack of an animal model displaying the full spectrum of pathological changes, successful pharmacological interventions have not been established. What is needed is an easy, reliable method to determine the safety and efficacy of candidate therapeutics for the treatment and/or prevention of Alzheimer disease. Definitions: The term "drug" as used herein, refers to any medicinal substance used in humans or other animals. Encompassed within this definition are compound analogs, naturally occurring, synthetic and recombinant pharmaceuticals, hormones, neurotransmitters, etc. The present invention contemplates screening test compounds to identify a useful drug for the treatment of Alzheimers. Most current attempts at therapeutics for Alzheimer disease are directed at neurotransmitter deficiencies. The term "neurotransmitter" includes any compound which functions in the nervous system to result in the transmission of chemical signals between cells.
http://www.google.com/patents?vid=USPAT6548261
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Show moreField of the Invention: The present invention relates to methods and compositions for characterizing the expression patterns of genes and gene families. Specifically, the present invention provides means to generate and monitor gene expression profiles resulting from cellular and physiological changes such that the expression patterns of individual genes or groups of genes can be readily identified and characterized. Background of the invention: Developing methods to detect molecular alterations in biological samples is key to increasing our knowledge about the causes of diseases, the processes of cellular development and differentiation, and other physiological and cellular events, and in developing tools to detect, treat, alter, and monitor these conditions. Perhaps the most significant alteration that can occur in a cell is in its pattern of gene transcription, which exerts profound control on protein levels and activities. The detection of changes in mRNA levels in the thousands of genes expressed by a single cell is an important goal for many research programs. With the extensive amount of cDNA sequence information available through the efforts of genome sequencing projects, as well as those of thousands of individual laboratories, it is becoming increasingly imperative to develop technologies that can utilize this information to study the patterns of gene expression in both development and disease. Most human cancers are the result of genetic changes that result in alterations in the profile of expressed genes within a cell. Methods that can rapidly and accurately measure the expression levels of thousands of genes will play an essential role in furthering our understanding of the causes and nature of progression of human cancers, detecting and monitoring cancers and others diseases, and identifying and developing treatment methods for the diseases. Several approaches have been developed in recent years in an attempt to achieve reliable, economical measurement of patterns and levels of gene expression. These include sequencing-based methods such as expressed sequence tag (EST) databases (See e.g., Adams et al., Nature Genetics 4, 373 [19931]) and SAGE (See e.g., Velculescu et al., Science 270, 484 [1995]), PCR based methods such as differential display (See e.g., Liang et al., Cancer Res. 52, 6966 [1992]; and Liang and Pardee, Science 257, 967 [1992]), and methods based on hybridization to microarrays of EST clones or oligonucleotides (See e.g., Chee et al., Science 274, 610 [1996]; DeRisi et al., Nat. Genet. 14, 457 [1996]; Gress et al., Oncogene 13, 1819 [1996]; Maskos and Southern, Nucleic Acids Res. 21, 4663 [1993]; Pietu et al., Genome Res. 6, 492 [1996]; Schena et al., Science 270, 467 [1995]; and Schena et al., Proc. Natl. Acad. Sci. 93, 10614 [1996]) or by subtractive hybridization (See e.g., Diatchenko et al., Proc. Natl. Acad. Sci. 6025 [1996]).
http://www.google.com/patents?vid=USPAT6232065
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Show moreBackground of the invention: Angiogenesis refers to the process by which new capillary blood vessels are formed from existing microvessels, resulting in the development of a blood supply to a given area of tissue [23, 25]. It is one of the most pervasive and fundamentally essential biological processes encountered in mammalian organizations. In the healthy, adult human body, angiogenesis is a normal and important function that is critical in a variety of physiological settings, including chronic inflammation, embryonic development, reproduction, and wound healing [22, 29]. For example, angiogenesis occurs in the female reproductive system, in response to ovulation or gestation, and in the normal hair cycle [28]. Nevertheless, apart from the processes of wound healing and inflammation, angiogenesis virtually never occurs physiologically in adult tissues, except in the ovary, the endometrium, and the placenta [27]. When defective or uncontrolled, angiogenesis is also central to a number of pathological processes, including: abnormalities of wound healing in diseases such as diabetes and duodenal ulceration; chronic inflammatory disorders, such as rheumatoid arthritis, psoriasis, and periodontitis; dermatological conditions such as cutaneous malignancy, decubitus ulcers, hemangiomas, Kaposi's sarcoma, psoriasis, pyogenic granulomas, and warts; diseases of the eye, particularly diabetic retinopathy; and growth of solid tumors, both benign and malignant [22, 23, 25, 26]. The consequence of abnormal angiogenesis is either excessive or insufficient blood vessel growth. Ulcers, strokes, and heart attacks can result from the absence of angiogenesis normally required for natural healing, while excessive blood vessel proliferation may favor arthritis, blindness, and tumor growth and dissemination [29 ]. The angiogenic process is tightly regulated (in both time and space) by a variety of endogenous angiogenic and angiostatic factors. It is propelled by a mixture of growth factors and pro-angiogenic cytokines, and is moderated by a collection of inhibitors of neovascularization which interfere with steps in the angiogenic process [22, 30]. In angiogenesis, capillary sprouts are formed in response to pro-angiogenic factors. The sprouts then grow and develop, driven by endothelial cell migration and proliferation, and organize themselves into a ordendritic structure [24]. Angiogenic and anti-angiogenic molecules control the formation of new vessels via different mechanisms. Hypoxia and other ill-defined stimuli drive tumor, inflammatory, and connective tissue cells to generate angiogenic molecules, such as vascular endothelial growth factor, fibroblast growth factor, transforming growth factor beta, and platelet-derived growth factor. Natural and synthetic angiogenesis inhibitors, such as angiostatin, thalidomide, and thrombospondin, can repress angiogenesis [23].
http://www.google.com/patents?vid=USPAT6723322
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Show moreBackground of the invention: The present invention relates generally to infectious diseases and antibodies, and, more particularly, to a new hybridoma cell line for production of anti-idiotypic monoclonal antibodies directed to an opsonic monoclonal antibody specific to mucoid exopolysaccharide of Pseudomonas aeruginosa. Description of related articles: Mucoid strains of Pseudomonas aeruginosa are the primary pulmonary pathogen for cystic fibrosis (CF) patients. Acquisition of this organism in the lungs is invariably associated with clinical decline, and there is a strong association between expression of the mucoid phenotype and growth in the lungs of CF patients. Mucoid exopolysaccharide (MEP), the primary constituent of the extracellular slime coat of mucoid strains, appears to be an important antigen in the pathophysiology of P. aeruginosa infection of CF patients. MEP expression promotes adherence of mucoid P. aeruginosa to tracheal cells and to respiratory mucins and antibodies to MEP are important to host defenses against the organism. According to earlier work (see Pier, G. B., et al., N. Engl. J. Med. 1987; 317: 793-798) induction of opsonic antibodies to MEP will probably be an important property of vaccines considered as candidates for prevention of mucoid P. aeruginosa infection in CF patients. Most CF patients respond to infection with high titers of nonopsonic antibody to MEP, and these antibodies fail to prevent progression of the infection. However, a small number of older (>12 years) CF patients have opsonic antibodies to MEP, are not infected with P. aeruginosa, and have an overall better clinical status. Furthermore, opsonic antibodies protect experimental animals from chronic mucoid P. aeruginosa lung infections. Pier, G. B., et al., Science 1990; 249: 537-540, the contents of which are incorporated herein by reference. Recently, it has been observed that the heteropolymeric nature of MEP results in the presence of both common and type-specific epitopes. In addition, the common epitopes are further divided into those that bind opsonizing antibodies and those that bind nonopsonizing antibody. Most naturally occurring antibodies to MEP function poorly in in vitro opsonophagocytic assays with complement, and are unable to protect animals following intratracheal challenge with bacteria encased in agar beads. By contrast, antibodies that are highly opsonic protect animals against infection and are found among some older CF patients who are not colonized with P. aeruginosa. Opsonizing antibodies to MEP are usually not found in younger noncolonized or chronically colonized CF patients. These findings have suggested a protective effect for the opsonizing antibodies. It is believed that opsonizing antibodies to the MEP antigen will generally protect animals, including humans, livestock, and mammals generally, from infection. MEP has become a promising vaccine candidate for the prevention of infection with P. aeruginosa in CF patients.
http://www.google.com/patents?vid=USPAT5233024
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Show moreField of the invention: The present invention relates to levuglandin derivatives as antigens for raising antibodies useful in diagnostic assays. Background of the invention: Cardiovascular disease is a broad term encompassing many pathologies of the heart and vascular system, including hypertension, stroke, aneurysm, angina, myocardial infarction, and Raynaud's disease. During 1990, cardiovascular disease caused about 43% of the deaths (more than 900,000 people) in the United States. Thus, the number of deaths from cardiovascular disease was nearly as high as the number of deaths from all other causes combined. [J. T. Shepherd, et al., "Report of the Task Force on Vascular Medicine," Circulation 89 (1): 532-35 (1994)]. Cardiovascular disease is also a leading cause of morbidity. Both patients and their families suffer a great deal from the effects of cardiovascular disease. Furthermore, there is a tremendous economic impact associated with such illness. Both the high incidence and the often-severe manifestations of cardiovascular disease necessitate that a large portion of health care workers' time be devoted to the care of patients suffering from the disease state. Moreover, sufferers of cardiovascular disease lose countless numbers of productive hours each year due to their illness. It is important to remember that cardiovascular disease affects many people besides the elderly or those having a familial predisposition. The establishment of detailed guidelines directed solely to the evaluation of congenital cardiac problems in pre-adults illustrates that the young are not immune from cardiovascular disease. [D. Driscoll et al. "Guidelines for Evaluation and Management of Common Congenital Cardiac Problems in Infants, Children, and Adolescents," Circulation 90 (4): 2180-88 (1994)]. Currently used techniques for diagnosing cardiovascular disease include electrocardiography, imaging, and measurement of risk factors. Each of these techniques is plagued by significant drawbacks. A. Electrocardiography The traditional approach to diagnosing cardiovascular disease is electrocardiography, a relatively safe and easy method. However, the method, which records electrical currents traversing the heart muscle, has been associated with false-negatives and false-positives in particular patient populations. Though a good initial indicator of various disease states, electrocardiography is an indirect and imperfect measurement of the heart's electrical activity. [M. S. Remetz and R. A. Matthay, "Cardiac Evaluation," Disease-a-Month 38 (6): 338-503 (1992)]. B. Imaging Intravascular imaging is helpful as a diagnostic tool; many of the routinely used imaging methods are quite invasive. In addition, the imaging techniques are expensive, requiring costly equipment and extensively trained personnel to conduct the studies.
http://www.google.com/patents?vid=USPAT5686250
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Show moreBackground of the invention: The use of synthetic biomaterials to sustain, augment or completely replace diseased human organs has increased tremendously over the past thirty years. Synthetic implants have cardiovascular applications such as vascular grafts, heart valves, and ventricular assist devices; extracorporeal systems; and a wide range of invasive treatment and diagnostic systems. Unfortunately, existing biomaterials suffer from problems associated with surface-induced thrombosis, or clot formation, such as thrombotic occlusion and thromboemboli, and infection. Synthetic vascular grafts having a diameter less than 6 mm are currently impracticable, because of potential thrombotic occlusion, and clinical experience with the artificial heart has been plagued with problems of thromboemboli and infection. Advances in the development of artificial organs and artificial vascular grafts have resulted in the need for nonthrombogenic materials. eThrombosis is initiated by the deposition of a plasma protein layer on the surface of the implanted biomaterial. Thereafter, platelets, fibrin, and possibly leukocytes, adhere to the deposited protein. The interactions between the plasma proteins and the surface of the implant determine the adhesion, activation and spreading of platelets, the activation of coagulation, cell attachment and protein deposition. There have been several attempts to create nonthrombogenic surfaces on polymer implants thereby increasing the blood-biocompatibility of implants. Early attempts included precoating the implants with proteins not involved in thrombosis, such as albumin, to mask the thrombogenic surface of the implant. Such implants loose their nonthrombogenic properties within a short time. Attempts have been made to mask the thrombogenic surface by coating gelatin onto implants such as ventricular assist devices. While the gelatin coating reduced the thrombi, it did not prevent thromboemboli and infection. Attempts have been made to render implants nonthrombogenic by coating the surface of the implant with polyethylene oxide to mask the thrombogenic surface of the implant. While this reduced thrombogenisis, the coupling of polyethylene oxide to the surface of the implant involves very complex procedures. There have also been attempts to prepare nonthombogenic surfaces by attaching heparin to biomaterials; heparin was selected because of heparin's potent anticoagulant properties. Such attempts required that the surface of the implant be first modified by the attachment of a coupling molecule before heparin can be attached. For example, the positively charged coupling agent tridodecylmethylammonium chloride, is coated onto an implant, which provides a positively charged surface and allows heparin, which has a high negative charge density, to be attached. The heparin slowly dissociates from the surface, to expose the positively charged, TDMAC surface which is particularly thrombogenic.
http://www.google.com/patents?vid=USPAT5455040
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Show moreBackgroun of the invention: The present invention relates to the biomedical arts for introducing electrical signals on nerve trunks. The present invention finds particular application in introducing a string of artifically generated antidromic pulses on the nerve trunk for collision blocking orthodromic pulses moving in the opposite direction along the nerve trunk and will be described with particular reference thereto. It is to be appreciated that the invention may have broader applications and may apply electrical signals on nerve trunks for other purposes. Heretofore, various techniques have been used to block nerve pulses passing along a nerve trunk. A common blocking technique was the application of DC currents on the nerve trunk. However, it has been found that the application of DC currents can be expected to cause nerve damage. To eliminate the DC current induced nerve damage, others have suggested using an oscillating current such that the induced electrical current flowed alternately in both directions along the nerve trunk. It has been found that the application of high frequency stimulation blocks the passage of nerve signals therethrough. It appears that high frequency stimulation may, in effect, be overdriving neuromuscular junctions and depleting the neurotransmitter at the terminal end. That is, rather than blocking the passage of nerve stimuli on the nerve fiber or axon, the high frequency stimulation techniques may be overworking the nerve terminal to the point of exhaustion causing a failure of proper functioning. Yet another blocking technique utilized a three electrode cuff which included a dielectric sleeve having a passage through which the nerve trunk passes. Three annular electrodes were arranged within the sleeve. A cathode was positioned near the center of the passage and a pair of anodes were positioned to either side. A signal generator was connected with the electrodes to apply an electrical pulse train that induced antidromic pulses on the nerve trunk. Each pulse of the pulse train included a rapid rise to a preselected amplitude, a 100 to 3000 microsecond plateau, and an exponential decay back to zero. This pulse train induced artifically generated antidromic pulses on the nerve trunk which traveled unidirectionally in the opposite direction to the normal pulse flow. The artificially generated antidromic pulses collided with and blocked further propagation of natural orthodromic pulses moving in the other direction on the nerve trunk. The application of a series of pulses of common polarity, again has been found to cause damage to neural tissues. To eliminate this nerve damage, others have suggested applying a low amplitude, relatively long duration rectangular wave pulse of opposite polarity between each pulse of the above-described pulse train. The opposite polarity of the rectangular wave pulse balanced the net charge flow caused by the primary pulse.
http://www.google.com/patents?vid=USPAT4608985
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Show moreTechnical Field: The present invention relates to electrochemical devices and methods for quantitative or qualitative analyses of a substance in the presence of an enzyme, particularly an oxidase enzyme. Exemplary oxidases are glucose oxidase, lactate oxidase and others, such as those below; and the invention more particularly relates to measuring the glucose, lactate, etc. in the material to be analyzed.Cross-Reference to related to U.S. Patents Application: Reference is made to copending, commonly assigned, U.S. patent application Ser. No. 407,566, filed August 12, 1982, for "Apparatus and Method for Electrochemical Measurements", the entire disclosure of which hereby is incorporated by reference.Background: Reference also is made to U.S. Pat. Nos. 3,539,455 and 4,340,448, the entire disclosures of which hereby are incorporated by reference. Such patents disclose approaches to measuring certain materials in the presence of specified enzymes of such materials, for example glucose in the presence of glucose oxidase, etc.U.S. Pat. No. 3,539,455 discloses a technique for measuring the concentration of glucose by allowing the glucose to diffuse through a membrane into an electrolyte that contains an enzyme, particularly an oxidase, such as glucose oxidase. In the electrolyte a reaction occurs to produce hydrogen peroxide. The electrical current produced during that reaction is measured as a representation of the glucose concentration. When there is interfering material in the unknown sample, which also contains the glucose means are provided by the patentee to subtract the current produced by the intefering material from the current produced by the interfering material and that material whose concentration is to be measured. The device of the U.S. Pat. No. 3,539,455 suffers from inaccuracy and instability due to the relatively low signal strength and, as the patentee recognizes, the difficulty in maintaining a uniform oxidase layer at the membrane. In U.S. Pat. No. 4,340,448 the need for an electrolyte separate from the unknown material, separated therefrom by a selective diffusing membrane, is overcome by immobilizing the enzyme directly on the cathode (working electrode) of the sensor system. The cathode and reference electrode both are inserted into an electrolyte that contains the unknown concentration of material intended for measurement. Such immobilization is achieved by confining the enzyme in a gel that is applied to the working electrode; the gel permits oxygen and glucose to diffuse therethrough. In the above mentioned application Ser. No. 407,566, there is disclosed an apparatus and method for making electrochemical measurements of certain species, especially of the type that undergo oxidation and/or reduction reactions.
http://www.google.com/patents?vid=USPAT4655880
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Show moreBackground of the invention: The present invention relates to the art of random access memories. It finds particular application in connection the testing of large scale memories and will be described with particular reference thereto. The invention will also find uses in other applications of electronic memories. A significant amount of work has been done in the recent years to obtain fast and very large memory systems. As a result, the density of semiconductor memory chips has increased dramatically. The increase in density and size of the memories has resulted in a corresponding increase in the difficulty of testing of such memories. A multi-mega bit random access memory (RAM) requires extended amounts of time in order to test cell stuck-at faults and other varieties of possible faults. To overcome this problem, two general approaches have been developed. First, researchers have attempted to develop efficient test generation methods, and second, memories including built-in self-testing capabilities have been proposed. Several innovative test methods for random access memories have been reported. These methods can be categorized into two classes; One set of methods are based on a stuck-at fault model. Representative examples of proposed methods based on this model include, J. Knaizuk and C. R. P. Hartman, "An optimal method for testing stuck-at faults in ransom access memories", IEEE Trans. Comp., vol. 26(11) , pp. 1141-1144, November 1977; R. Nair, S. M. Thatte and J. A. Abraham, "Efficient methods for testing semiconductor random access memories", IEEE Trans. Comp., vol. 27(6), pp. 572-576, June 1978; R. Nair, "Comments on an optimal method for testing stuck-at faults in random access memories", IEEE Trans. Comp., vol. 28(3) , pp. 258-261, March 1979; R. Dekker, F. Beenker and L. Thijssen, "A realistic fault model and test method for static random access memories", IEEE Trans. CAD, vol. 9(6), pp. 567-572, June 1990; R. Dekker, F. Beenker and L. Thijssen, "Fault modeling and test method development for static random access memories", Proc. Int. Pest Conf., pp. 343-352, 1988; A. Birolini, W. Buchel and D. Heavner, "Test and screening strategies for large memories", Proc. European Test Conf., pp. 276-283, 1989; T. Fuja, C. Heegard and R. Goodman, "Linear sum codes for random access memories", IEEE Trans. Comp. , vol 37(9) , pp. 1030-1042, September 1988; C. A. Papachristou and N. B. Sahgal, "An improved method for detecting functional faults in semiconductor random access memories", IEEE Trans. Comp., vol. 34(2), pp. 110-116, February 1975; J. Savir, W. H. McAnney and S. R. Vecchio, "Fault propagation through embedded multiport memories", IEEE Trans. Comp., vol. 36(5), pp. 592-602, May 1987; R. David, A. Fuentes and B. Courtois
http://www.google.com/patents?vid=USPAT5377148
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Show moreTechnical Field: The present invention relates generally, as indicated, to apparatus and method for electrochemical measurements and to electrochemical measurements of certain species, especially of the type that undergo oxidation and/or reduction reactions, and/or other types of reactions. Background of prior articles: In U.S. Pat. Nos. 3,260,656 and 4,076,596 is presented information concerning principles of operation of prior art sensors, detectors, methods, etc. for detecting the concentration in fluids of an electrochemically active species. The entire disclosures of such patents hereby are incorporated by reference. As used in such patents and herein "fluids" includes gases, liquids, vapors, mixtures thereof, and virtually any other material in which an electrochemically active species may occur and/or be detected. In the past, detection of the concentration of oxygen as an electrochemically active species in a material was performed by measuring current flow developed by oxidation or reduction reactions. The present invention contemplates such oxygen concentration detection and also detection of other electrochemically active materials by oxidation of reduction current generated technique and/or other reactions that generate an electrical parameter that can be measured, such as current or voltage. Primarily, electrochemically active species ordinarily means any group of identical chemical entities, such as ions, molecules, atoms, etc., which are capable of being separated by electrochemical type reaction, such as oxidation or reduction, or other reaction, to yield an electrical parameter, such as current or voltage, that may be detected as a representation of the concentration, for example, of such species. A conventional approach to measuring oxygen concentration has been to place two electrodes 1, 2 (as seen in FIG. 1), one a working electrode (the cathode, for example of gold, platinum or other noble metal or carbon) and the other a reference electrode (the anode, for example of silver, silver-silver chloride or other material), in an electrolyte 3 having the species, the concentration of which is to be measured. A voltage from source 4 is applied across the electrodes causing a reduction reaction at the cathode, an oxidation reaction at the anode, while maintaining a charge balance in the electrolyte. Exemplary equations for the reduction and oxidation reactions are shown, respectively in equations 1 and 2 below. ##STR1## The current flowing between the electrodes 1, 2 would result from the reactions occurring in the electrolyte; and such current would have a proportional relationship to the concentration of the electrochemically active species and could be measured by a meter 5. Such method is disclosed, for example, in the above mentioned patents.
http://www.google.com/patents?vid=USPAT4571292
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Show moreField of the invention: The invention relates to the field of gene expression and gene therapy, and to novel vectors for these uses. In particular, the invention relates to the development and use of an artificial or synthetic chromosome as a vector for gene expression and gene therapy, especially in humans. The invention enables the controlled construction of stable synthetic or artificial chromosomes from isolated purified DNA. With this DNA, a functional chromosome is formed in a cell and maintained as an extrachromosomal element. The artificial chromosome performs the essential chromosomal functions of naturally-occurring chromosomes so as to permit the chromosome to function as an effective vector for gene therapy when therapeutic DNA is included in the chromosome. Background of the invention: The genetic manipulation of cells aimed at correcting inherited or acquired disease is referred to as gene therapy. Until now, most clinical studies in this field have focused on the use of viral gene therapy vectors. Based on the results of these studies, it is becoming clear that current viral gene therapy vectors have severe clinical limitations. These include immunogenicity, cytopathicity, inconsistent gene expression, and limitations on the size of the therapeutic gene. For these reasons, much attention has been recently focused on the use of non-viral gene therapy vectors. In particular, synthetic mammalian chromosomes would be useful vectors for facilitating a variety of genetic manipulations to living cells. The advantages of synthetic mammalian chromosomes include high mitotic stability, consistent and regulated gene expression, high cloning capacity, and non-immunogenicity. Artificial chromosomes were first constructed in S. cerevisiae in 1983 (Murray et al., Nature 305:189-193 (1983), and in S. pombe in 1989 (Hahnenberger et al., Proc. Natl. Acad Sci. USA 86:577-581 (1989). For many reasons, it has not been obvious whether similar vectors could be made in mammalian cells.First, multicellular organisms (and thus the progenitors of mammalian cells) diverged from yeast over 1 billion years ago. Although there are similarities among living organisms, in general, the similarities among two organisms are inversely related to the extent of their evolutionary divergence. Clearly, yeast, a unicellular organism, is radically different biologically from a complex multicellular vertebrate. Second, yeast chromosomes are several orders of magnitude smaller than mammalian chromosomes. In S. cerevisiae and S. pombe, the chromosomes are 0.2 to 2 megabases and 3.5-5.5 megabases in length, respectively. In contrast, mammalian chromosomes range in size from approximately 50 megabases to 250 megabases. Since there is a significant difference in size, it is not clear, a priori, whether constructs comparable to yeast artificial chromosomes can be constructed and transfected into mammalian cells.
http://www.google.com/patents?vid=USPAT6348353
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Show moreField of the invention: The present invention is directed to a real-time imaging system and method that is particularly useful in the medical field, and more particularly, to a system and method for imaging and analysis of tissue and other samples using optical coherence tomography.Background of the invention: A variety of imaging techniques are used for the medical diagnosis and treatment of patients. Ultrasound imaging represents a prevalent technique. Ultrasound uses sound waves to obtain a cross-sectional image of an object. These waves are radiated by a transducer, directed into the tissues of a patient, and reflected from the tissues. The transducer also operates as a receiver to receive the reflected waves and electronically process them for ultimate display. Another imaging technique is referred to as Optical Coherence Tomography (OCT). OCT uses light to obtain a cross-sectional image of tissue. The use of light allows for faster scanning times than occurs in ultrasound technology. The depth of tissue scan in OCT is based on low coherence interferometry. Low coherence interferometry involves splitting a light beam from a low coherence light source into two beams, a sampling beam and a reference beam. These two beams are then used to form an interferometer. The sampling beam hits and penetrates the tissue, or other object, under measurement. The sampling or measurement beam is reflected or scattered from the tissue, carrying information about the reflecting points from the surface and the depth of tissue. The reference beam hits a reference reflector. For example, a mirror or a diffraction grating, and reflects from the reference reflector. The reference reflector either moves or is designed such that the reflection occurs at different distances from the beam splitting point and returns at a different point in time or in space, which actually represents the depth of scan. The time for the reference beam to return represents the desirable depth of penetration of tissue by the sampling beam. When the reflected beams meet, intensities from respective points with equal time delay form interference. A photodetector detects this interference and converts it into electrical signals. The signals are electronically processed and ultimately displayed, for example, on a computer screen or other monitor.Optical coherence tomography (OCT) is a relatively new, non-invasive optical imaging technique. OCT is analogous in principle to pulse-echo ultrasound imaging, but near-infrared light waves instead of acoustic waves are employed to probe the sample specimen. OCT has been primarily applied to imaging of biological tissues, providing micron-scale resolution in three dimensions to a depth of a few millimeters without contacting the tissue. We here disclose a number of advanced designs and techniques that extend the utility of OCT and/or are based on OCT. A number of papers and other references are cited below.
http://www.google.com/patents?vid=USPAT7061622
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Show moreBackground of the invention: The present invention relates to biomedical electrodes. It finds particular application in electrodes for surrounding a nerve trunk to introduce electrical stimuli thereon for the purpose of generating action potentials that propagate in only one direction from the cuff. The present invention may find other utility. Heretofore, others have used electrical stimuli to create action potentials that in turn cause the release of a neurotransmitter that may result in a measurable physiological response. Many of these prior art stimulation techniques applied the electrical stimuli to peripheral nerves subserving muscle or peripheral sense organs, bypassing the higher levels of the nervous system. It has also been found that electrical signals can be applied to other excitable tissue directly, such as muscle. Although the applied electrical signals can cause the nervous system to activate appropriate muscles or other organ responses, another potentially important use is to block the naturally generated action potentials traveling along a nerve fiber. Specifically, the proper application of electrical signals can block nerve impulses traveling up the nerve trunk toward the brain to arrest pain signals, phantom limb signals in amputees, and the like. Analogously, appropriately generated action potentials can block nerve impulses traveling on the nerve trunk to eliminate nerve impulses which cause unwanted physiological activity. For example, the stimuli can block signals which cause spasmodic behavior, hiccups, and the like. A potential application is to cause the controlled relaxation of the external urinary bladder or sphincter in paralyzed patients who have lost this control. With proper application of electrical signals, a paraplegic with a loss of voluntary bladder control can void the contents of the bladder. Various electrical potentials have been applied between a cathode and an anode to suppress the transmission of unwanted nerve action potentials. Some researches have used DC currents flowing from the anode to the cathode to block natural nerve impulses. Others have used high frequency sinusoidal stimulation to block natural nerve impulses. In the past, electrical stimuli have been applied to the nerves for the purpose of generating unidirectional propagating action potentials with cuffs containing three electrodes. The prior art electrode cuff included a dielectric, i.e., electrically non-conductive, cylindrical tube or sleeve. Three annular electrodes were disposed along the inner surface of the sleeve. A cathode electrode was commonly positioned centrally in the sleeve and a pair of anode electrodes were positioned to either side thereof and displaced from the ends of the sleeve. The electrodes have been utilized to introduce a string of artificially generated antidromic pulses which propagate unidirectionally in the opposite direction to the normal orthodromic pulse flow.
http://www.google.com/patents?vid=USPAT4628942
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Show moreBackground of the invention: The present invention relates to the biomedical arts for introducing electrical signals on nerve trunks. The present invention finds particular application in inducing a stream of artifically generated antidromic pulses on the nerve trunk for collision blocking orthodromic pulses moving in the opposite direction on the nerve trunk and will be described with particular reference thereto. The invention may have broader applications including generating action potentials on nerve trunks for other purposes and monitoring naturally occuring nerve impulses. Various techniques have been used to block nerve pulses passing along a nerve trunk. Commonly, an electrode cuff including a dielectric sleeve and three symmetric electrodes were positioned around a nerve trunk. The three electrodes were arranged symmetrically within the sleeve, with an annular cathode positioned in the center and a pair of annular anodes were positioned to either side. A signal generator was connected with the electrodes to apply an electrical pulse train that induced action potentials on the nerve trunk. One blocking technique was the application of DC currents on the nerve trunk. However, it has been found that the application of DC and unidirectionally pulsed currents induced nerve damage. To eliminate the DC current induced nerve damage, others have used a bipolar current wave forms such that the average electrical charge passed through an electrode is approximately zero. In one technique, a train of pulses was applied to the cuff electrodes. Each pulse of an exemplary pulse train included a rapid rise to a preselected amplitude, a 200 to 1000 microsecond plateau, and an exponential decay back to zero. The ends of the cuff have been defined as the "arrest" end and the "escape" end. No action potential was intended to emerge from the "arrest" end and the colliding pulse emerges from the "escape" end. This pulse train induced artifically generated antidromic pulses traveling unidirectionally on the nerve trunk. The antidromic pulses collided with and blocked orthodromic pulses traveling in the other direction. To eliminate nerve damage that may result from monopolar stimulation, a relatively long duration, low amplitude rectangular pulse of opposite polarity was applied between each pulse of the first polarity pulse train. Although it was intended that current should flow within the cuff from the anodes to the cathode, some current (secondary current) also flowed outside the cuff in the body tissue, creating a virtual cathode along the nerve outside the cuff. This secondary current tended to generate unwanted action potentials near the arrest end of the cuff that traveled along the nerve trunk in the orthodromic or undesired direction.
http://www.google.com/patents?vid=USPAT4649936
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Show moreBackground of the invention: The present invention relates to Magnetic Resonance Imaging (MRI) arts. More particularly, the invention relates to providing audio information as part of an imaging pulse sequence, to provide instructions and other information to a patient undergoing a MRI procedure. The basics of Magnetic Resonance Imaging are well known. In a typical MRI system an object, such as the human body, is placed within a gradient magnetic construction which forms a uniform magnetic field. When the object is subjected to this uniform magnetic field, the nuclei in the object attempt to align with the polarizing field, but precess about it in random order at their characteristic Larmor frequency. Thereafter, the object is excited by a pulse sequence which acts to tip the nuclei. When a pulse is switched off, the nuclei precess back toward their equilibrium position during which a response is emitted and detected by an RF receiver. Numerous unique pulse sequences exist for MRI investigations. When utilized to produce images, magnetic field gradients are employed. Typically, the region to be imaged is scanned by pulse sequences during which the field gradients vary according to the particular sequence used. The resulting set of received MRI signals are digitized and processed to reconstruct an image employing one of many well known reconstruction techniques. A pulse program generator or pulse sequence generator of the MRI system stores and uses the pulse sequences to provide signals that control the operation of the RF transmitters, RF receivers, gradient coils, etc. of a MRI system. Software code which defines different pulse sequences is loaded into writable control storage areas of the pulse program generator. The code, which includes instructions, is a type of computer program that is executed by the pulse program generator to specify pulse program generator outputs and also specifies the duration of such outputs. Since the program generator is writable, various MRI pulse sequences can be specified by simply downloading different instructions into the pulse program generator control storage. Thus, different instruction sequences corresponding to numerous MRI pulse sequences are able to be maintained on a host computer storage and downloaded for use by the MRI system. The pulse sequences which typically have been provided to a pulse program generator have been limited to those which are capable of being analytically expressed, such as those based on sine, cosine, tangent, and exponential functions. However, very recently, MRI systems have been developed which allow the downloading of arbitrary signal patterns to the pulse program generator, allowing an arbitrary pattern of signals to be used as the pulse sequence controlling the gradient coils of an MRI system.
http://www.google.com/patents?vid=USPAT5709207
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Show moreField of the invention: This invention relates to a bandage which continuously provides curative cell products to a wound. More particularly, the invention relates to: a bandage having a chamber for containing cells and cell culture media, said bandage having a cell product permeable membrane; to genetically engineered cells useful in said bandage; and to a method for producing such cells. Backgroung of the invention: The treatment of wounds in mammals, both animals and humans, has historically involved a simple passive bandage which provides physical protection and, to some extent, reduces infection. The treatment has progressed from this simple bandage to more active treatments. In serious wounds, particularly burns, skin grafting and skin sheets have been applied. Eventually the skin cells "take" and fill in the wound. Attempts have been made to expedite healing by introduction of various growth factors directly into the wound, see Brown G. L., Curtsinger L., Jurkiewicz M. J., Nahi F., Schultz G., (1991) "Stimulation of Healing of Wounds by Epidermal Growth Factor," Plast. Reconstr. Surg , Vol. 88, pp. 189-194; Brown G. L., Nanney L. B., Griffen J., Cramer A. B., Yancey J. M., Curtsinger L., Holtzin L., Schultz G., Jurkiewicz M. J., and Lynch J. B. (1989)."Enhancement of Wound Healing by Topical Treatment with Epidermal Growth Factor," New England J. Med., Vol. 321, pp. 76-79; ten Dijke P., Iwata K. K., "Growth Factors for Wound Healing" (1989) Biotechnology, Vol. 7, pp. 793-798; Pierce G. F., Mustoe T. A., Altrock B. W. Deuel T. F., Thomason A., (1991), "The Role of Platelet Derived Growth Factor in Wound Healing Cellular Biochemistry," Vol. 45, pp. 319-316; and, "EGF and PDGF-Alpha in Wound Healing and Repair," Schultz Rotatori and Clark, J. of Cellular Biochemistry, Volume 45, pp. 346-352 (1991). Growth factors encourage the proliferation and/or differentiation of the cells in the tissue within and around the wound. Several attempts have been made to introduce these growth factors into the wound by means of a topical gel or the like, applied over the surface of the wound. Such growth factor containing gels have several drawbacks. The amount of growth factor contained in these gels is fixed. Over time, the enzymes produced from the patient's own tissue may degrade the gel and/or the growth factor. The isolation and purification of the growth factor may decrease its biological activity. Attempts nave been made to drip the growth factor directly into the wound. However, this method of application is not continuous and does not provide a uniform amount of arowth factor to the different areas of the wound. In addition, many growth factors have a short half life, thus the amount of growth factor delivered to the wound substantially decreases with time. Finally, the cost of the isolated, purified growth factors is extremely high.
http://www.google.com/patents?vid=USPAT5487889
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Show moreThe invention relates to improvements in methods and apparatus for bending beams or like objects to a desired profile. Description of the prior articles: Among the various fields of use, the invention has application in the bending of ship beams or rib frame members from straight mill products to prescribed profiles. Alternatively, the invention may be used to straighten distorted beams or other elongated members. In prior techniques, a beam is usually bent in a three-point loading system where the beam is laterally supported by a pair of spaced elements while an opposed third ram element advances laterally against the beam midway between the spaced support elements until the beam is plastically bent to a desired angle. Inherent in this widely used approach is the introduction of transverse loading or shear throughout the stressed zone of the beam between the spaced support elements. The transverse loading may develop a permanent twist in a beam of nonsymmetrical cross section, which is objectionable for numerous reasons. Twisting of an otherwise plane beam profile makes handling, supporting, and measurement of the beam during bending operations difficult. Further, beams twisted out of plane are not readily stacked for storage or transport and, more critically, are difficult to properly align during their fabrication into a hull assembly. Another result of the stress distribution in a three-point loading system is a nonuniform bending moment in the work area of the beam between the support elements which reaches a maximum at the center ram. Under this condition, the beam yields principally at the ram and develops what is termed a plastic hinge where excessive strains are produced in a limited area. This local type of permanent deformation is generally characterized by unpredictable material behavior in terms of the relationship between load and deformation and in terms of spring-back. The resulting curvature produced in the work area of the beam is nonuniform along its length and may be visualized as a central, sharply curved area of relatively small radius and adjacent, relatively straight areas. This kinked shape is not readily superposed with a smoothly curved profile. Thus, where a beam is successively bent along its length to conform to a given profile, substantial compromise must be made with deviations from the profile, and/or smaller and more frequent bends must be made. A problem commonly occurs with the bending of beams of nonsymmetric cross section where the lack of geometrical balance about the desired bending plane requires, for force equilibrium conditions, a bending moment or component perpendicular to the principal applied moment to maintain the beam in a plane. Typically in commercial practice, either this requirement is ignored or the beam is restrained from bending out of the principal plane by a rigid constraint during bending operations.
http://www.google.com/patents?vid=USPAT3952572
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Show moreBackground of the invention: The epithelium is the first line of defense against a variety of pathogens. Epithelial cells produce low molecular weight antimicrobial peptides, antibacterial enzymes, and antiproteases. Optimal methods of specifically targeting therapeutic molecules to epithelial cells have been lacking in the art. There is a continuing need in the art for methods of providing therapeutic agents to respiratory epithelia cells in diseases such as cyptic fibrosis, asthma, and emphysema, and to intestinal epithelial cells, for example, in inflammatory bowel diseases. Summary of the invention: It is an object of the invention to provide bifunctional molecules useful for delivery of therapeutic molecules and methods for delivering therapeutic molecules to cells. These and other objects of the invention are provided by one or more embodiments as described below. In one embodiment the invention provides a fusion protein. The fusion protein comprises a single chain Fv molecule directed against a human transcytotic receptor covalently linked to a therapeutic protein. The therapeutic protein may be, for example, .alpha..sub.1 -antitrypsin, a cytokine, such as interleukin-2 or interleukin-10, or a peptide antibiotic. Suitable peptide antibiotics include aerosporin, amphomycin, aspartocin, bacitracins, caperomycins, colistins, dactinomycins, glumamycins, gramicidin D, gramicidin S, mikamycin B, polymixins, pristinamycin, siomycin, staphylomycin S, thiostrepton, tyrocidines, tyrothricin, valinomycin, vancomycin, veramycin B. Any therapeutic protein which one wants delivered to epithelial cells may be used. The fusion protein may further comprise a linker region of less than 50, 40, 30, 20, or 10 amino acid residues. The linker can be covalently linked to and between the single chain Fv molecule and the therapeutic protein. Also provided according to another aspect of the invention is a method of delivering a therapeutic protein to an epithelial cell. The method comprises: administering a fusion protein as described above to a patient, whereby the therapeutic protein is delivered to an epithelial cell. The epithelial cell may be an airway epithelial cell or an intestinal lumen cell, for example. The liver may also be targeted. The administration mode may be any known in the art. However, inhalation and intravenous administration have been found to be both convenient and efficient.Nucleic acid molecules are also provided by the present invention. These encode a fusion protein comprising a single chain Fv molecule directed against a transcytotic receptor covalently linked to a therapeutic protein. The therapeutic protein may be, for example, .alpha..sub.1 -antitrypsin, a cytokine, such as interleukin-2 or interleukin-10, or a peptide antibiotic. Any therapeutic protein which one wants delivered to epithelial cells may be used. The fusion protein may further comprise a linker region of less than 50, 40, 30, 20, or 10 amino acid residues.
http://www.google.com/patents?vid=USPAT6261787
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