Abstract: Modified external guide sequence (EGS) molecules that mediate cleavage of specific target RNAs have been constructed. The modified molecules are external guide sequence molecules for RNAse P which are designed to specifically bind to and promote RNAse P-mediated cleavage of target RNA molecules and to have enhanced nuclease resistance. Specific regions are modified to achieve enhanced stability while maintaining RNAse P activity. Modified external guide sequence molecules suitable for use in the treatment of hepatitis B viral infections have been constructed.

Abstract: The present invention describes a method for the production of two highly purified enzymes capable of degrading chondroitin sulfate polysaccharides. A multi-step purification method incorporating cell disruption, cation exchange chromatography, affinity chromatography, hydroxylapatite chromatography, high resolution ion exchange chromatography and size exclusion is outlined. A 77,000.+-.5,000 Dalton protein capable of degrading chondroitin sulfates A and C and a 55,000.+-.2,300 Dalton protein capable of degrading dermatan sulfate were isolated. The genes encoding these enzymes, chondroitinase AC and chondroitinase B, respectively, have been cloned and methods for their use are described.

Abstract: An improved barrier or drug delivery system which is highly adherent to the surface to which it is applied is disclosed, along with methods for making the barrier. In the preferred embodiment, the system is compliant, in that it is capable of conforming to the three dimensional structure of a tissue surface as the tissue bends and deforms during healing processes. The barrier or drug delivery systems is formed as a polymeric coating on tissue surfaces by applied a polymerizable monomer to the surface, and then polymerizing the monomer. The polymerized compliant coating preferably is biodegradable and biocompatible, and can be designed with selected properties of compliancy and elasticity for different surgical and therapeutic applications.

Abstract: Substituted 1-arylphthalazine compositions with the formula ##STR1## wherein R.sup.1, R.sup.2, R.sup.3 and R.sup.4 are independentlya) H,b) HO,c) R.sup.11 O--,d) halogen,e) C1-C3-alkyl,f) CF.sub.3,g) R.sup.12 CO.sub.2 --, orh) R.sup.12 CONH--;R.sup.1 and R.sup.2, or R.sup.2 and R.sup.3, or R.sup.3 and R.sup.4 can be taken together to bea) --OCH.sub.2 O--, orb) --OCH.sub.2 CH.sub.2 O--;R.sup.5 isa) H,b) C1-C6-alkyl,c) C3-C6-alkenyl,d) C3-C6-alkynyl,e) C3-C6-cycloalkyl,f) phenyl or substituted phenyl, wherein the phenyl is substituted with one or two substituents selected from the group consisting of C1-C3-alky, halogen, R.sup.12 HN--, R.sup.12 O--, CF.sub.3 --, R.sup.13 SO.sub.2 -- and CO.sub.2 R.sup.12, org) phenyl-C1-C3-alkyl or substituted phenyl-C1-C3-alkyl, wherein the phenyl is substituted with one or two substituents selected from the group consisting of C1-C3-alkyl, halogen, R.sup.12 HN--, R.sup.12 O--, CF.sub.3 --, R.sup.13 SO.sub.2 -- and --CO.sub.2 R.sup.12 ;R.sup.6 isa) R.sup.10 R.sup.11 N--,b) R.

Abstract: A method of disposing of fines material includes the step of mixing a slurry containing fines material with a slurry containing coarse material to form a slurry which contains a mixture of fines material and coarse material. The slurry containing the mixture is deposited onto an inclined surface so that liquid can drain from the mixture. The mixture contains a majority of fines material by mass.

Abstract: Disclosed are compositions with tethered growth effector molecules, and methods of using these compositions for growing cells and tissues. Growth effector molecules, including growth factors and extracellular matrix molecules, are flexibly tethered to a solid substrate. The compositions can be used either in vitro or in vivo to grow cells and tissues. By tethering the growth factors, they will not diffuse away from the desired location. By making the attachment flexible, the growth effector molecules can more naturally bind to cell surface receptors. A significant feature of these compositions and methods is that they enhance the biological response to the growth factors. The new method also offers other advantages over the traditional methods, in which growth factors are delivered in soluble form: (1) the growth factor is localized to a desired target cell population; (2) significantly less growth factor is needed to exert a biologic response.

Abstract: It has been discovered microparticles formed from natural or synthetic polymer with thicker walls have significantly enhanced echogenicity as compared with microparticles having thinner walls. The effect of wall thickness has been determined experimentally as well as inserted into a formula for use in predicting the optimum conditions. In the preferred embodiment, the polymers are synthetic biodegradable polymers and the wall thickness is between about 100 and 660 nm, although wall thicknesses from about 20 nm to in excess of 500 nm can be used. The microparticles are manufactured with a diameter suitable for the targeted tissue to be imaged, for example, with a diameter of between 0.5 and 8 microns for intravascular administration, and a diameter of between 0.5 and 5 mm for oral administration for imaging of the gastrointestinal tract or other lumens.

Abstract: The present invention relates to biologically useful material in the form of a pseudocapsid formed from papovavirus major capsid antigen and excluding minor capsid antigens, which pseudocapsid incorporates exogenous material. The invention also relates to a method of using the pseudocapsids as vectors for exogenous material transfer, especially gene transfer in the therapy of genetic disorders, or other uses such as antibody or drug targeting.

Abstract: Transdermal transport of molecules during sonophoresis (delivery or extraction) can be further enhanced by application of an electric field, for example, electroporation or iontophoresis. In a preferred embodiment the ultrasound is low frequency ultrasound which induces cavitation of the lipid layers of the stratum corneum (SC). This method provides higher drug transdermal fluxes, allows rapid control of transdermal fluxes, and allows drug delivery or analyte extraction at lower ultrasound intensities than when ultrasound is applied in the absence of an electric field.

Abstract: A drip edge for use on a building roof for directing water off of the roof, away from the building and, preferably, into a gutter is provided. The drip edge includes a planar body portion which is positioned under the roofing shingles. An open throat portion, which is substantially U-shaped, can fit over an existing protruding drip edge. A downwardly extending leg portion has a lower flexible section which ends in an outwardly directed foot portion. The drip edge can be installed over an existing drip edge, allowing retrofit of the new drip edge. The drip edge can be used with a variety of gutter designs. The drip edge prevents water from getting between the fascia and the gutter inner wall, protecting the building from water damage and the gutter from damage due to ice accumulation, for example.

Abstract: Plasma EPCR has been isolated, characterized and shown to block cellular protein C activation and APC anticoagulant activity. Plasma EPCR appears to be about 43,000 daltons and circulates at approximately 100 ng/ml (98.4.+-.27.8 ng/ml, n=22). Plasma EPCR bound activated protein C with an affinity similar to that of recombinant soluble EPCR (Kd.sub.app approximately 30 nM), and inhibits both protein C activation on an endothelial cell line and APC anticoagulant activity in a one-stage factor Xa clotting assay. Soluble plasma EPCR appears to attenuate the membrane-bound EPCR augmentation of protein C activation and the anticoagulant function of activated protein C. Soluble EPCR has also been detected in urine. Levels of soluble EPCR can rise in inflammatory disease associated with vascular injury and appear to be correlated with inflammation and disease states associated with abnormal coagulation.

Abstract: Controlled release compositions and methods for inducing pseudopregnancy in gilts and sows are disclosed. In the preferred embodiment, the formulation includes polylactide microspheres releasing estradiol 17.beta. at physiologically useful levels over a period of time between five and thirty days. Following induction of pseudopregnancy, the pseudopregnancy can be terminated and estrus induced by administration of a compound such as PGF2.alpha.. The advantages of inducing pseudopregnancy followed by induction of estrus are that the breeding patterns of large numbers of gilts and sows can be controlled.

Abstract: Applications of low-frequency (20 KHz) ultrasound enhances transdermal transport of high-molecular weight proteins. This method includes a simultaneous application of ultrasound and protein on the skin surface in order to deliver therapeutic doses of proteins across the skin. Examples demonstrate in vitro and in vivo administration of insulin (molecular weight 6,000 D), and in vitro administration of gamma interferon (molecular weight 17,000 D), and erythropoeitin (molecular weight 48,000 D).

Abstract: A method is disclosed for the treatment of neuropsychopharmacological disorders which are associated with or result from excessive activation of the N-methyl-D-aspartate receptor complex, which method comprises administering an effective neuropsychopharmacological disorder-treating amount of a compound possessing partial agonist properties for the strychnine insensitive glycine modulatory sites of N-methyl-D-aspartate receptors. Exemplary of partial agonists which are useful in the method of the invention are 1-aminocyclopropanecarboxylic acid, and associated derivates thereof. Novel injectable pharmaceutical compositions are also disclosed.

Abstract: A method for identifying a microorganism having a reduced adaptation to a particular environment comprising the steps of:(1) providing a plurality of microorganisms each of which is independently mutated by the insertional inactivation of a gene with a nucleic acid comprising a unique marker sequence so that each mutant contains a different marker sequence, or clones of the said microorganism;(2) providing individually a stored sample of each mutant produced by step (1) and providing individually stored nucleic acid comprising the unique marker sequence from each individual mutant;(3) introducing a plurality of mutants produced by step (1) into the said particular environment and allowing those microorganisms which are able to do so to grow in the said environment;(4) retrieving microorganisms from the said environment or a selected part thereof and isolating the nucleic acid from the retrieved microorganisms;(5) comparing any marker sequences in the nucleic acid isolated in step (4) to the unique marker sequ

Abstract: Vectors and a method for the identification of affector RNA molecules, such as ribozymes, external guide sequences, anti-sense RNA, and triple helix-forming RNA, that inhibit expression of target RNA molecules are disclosed. The method identifies functional affector RNA molecules by screening or selecting for those RNA molecules that inhibit expression of a fusion transcript, which includes the sequence of an RNA molecule of interest, from a library of potential affector RNA molecules. The vectors include a reporter gene encoding the fusion transcript including the RNA molecule of interest and RNA encoding the reporter protein. The vectors also include a second reporter gene encoding a second reporter protein. Expression of the second reporter protein can be used both to detect transformation or transfection of the vector into cells and as a control for effects on the expression of the first reporter protein that are not due to inhibition of expression of the RNA molecule of interest.

Abstract: Analogs of regulators of complement activation (RCA) proteins which have altered specificities and affinities for the targets C3b and/or C4b are described. These analogs are obtained by substituting amino acids which effect the binding of these proteins, identified as amino acids 35, 64-65, 92-94 (C4b) and the sequence S-T-K-P-(P-I-C)-Q (amino acids at positions 54-61 of SEQ ID NO. 13) (C3b) in the CR1 protein can be transferred to corresponding regions of CR1 or of additional members of the RCA family. Analogs can also be designed by substituting amino acids which affect the binding of these proteins into homologous regions of noncorresponding SCRs of CR1 or other family members.

Abstract: Antibodies to the large subunit of DNA-dependent RNA polymerase II (Pol II LS) and methods of use thereof, including use as research tools and for the diagnosis of proliferative diseases such as cancer and the screening of anti-cancer therapies, and a method for delivering molecules to predetermined sites in the nucleus of a cell using a molecule containing the C-terminal domain of the Pol II LS protein. The anti-Pol II LS antibodies are highly specific for phosphorylated Pol II LS and bind to the C-terminal domain of the Pol II LS molecule in a phosphorylation-dependent manner.

Abstract: Particles are provided that are not rapidly cleared from the blood stream by the macrophages of the reticuloendothelial system, and that can be modified to achieve variable release rates or to target specific cells or organs. The particles have a core of a multiblock copolymer formed by covalently linking a multifunctional compound with one or more hydrophobic polymers and one or more hydrophilic polymers, and contain a biologically active material. The terminal hydroxyl group of the poly(alkylene glycol) can be used to covalently attach onto the surface of the particles biologically active molecules, including antibodies targeted to specific cells or organs, or molecules affecting the charge, lipophilicity or hydrophilicity of the particle. The surface of the particle can also be modified by attaching biodegradable polymers of the same structure as those forming the core of the particles.

Abstract: The invention provides a composition for delivery of an active agent comprising a plurality of lamellar particles of a biodegradable polymer which is at least in part crystalline, and an active agent adsorbed to at least most of the particles. Preferably the biodegradablepolymer is at least 5% by weight crystalline. Preferred biodegradable polymers are poly(L-lactide) (L.PLA) or copolymers or blends of L.PLA. The particles are especially useful for the immobilization of antigens or allergens for vaccines.