Abstract: A specialized cannula and intraluminal cannula placement apparatus allow the insertion of an intraluminal cannula through a previously inserted standard I.V. catheter so that the intraluminal cannula extends beyond the end of a standard catheter. By using an intraluminal cannula of appropriate length, the intraluminal cannula may be used to bypass a flexure-caused obstruction in a vein during the administration of fluids in patients who are unable to cooperate with medical or veterinary procedures, most particularly with human infants, geriatric patients, and animals. Use of the specialized cannula and intraluminal cannula placement apparatus does not require removal of the previously placed I.V. catheter. The exterior diameter of the specialized cannula has a smaller diameter than the interior diameter of the previously placed standard I.V. catheter. A specially adapted seal seals the space between the inserted specialized cannula and a standard Luer hub of an I.V. catheter.

Abstract: A computer-based process retrieves information organized in documents containing text and/or coded representations of text. The process involves obtaining and labeling a selected set of documents based on content quality, and extracting and representing features from each document in the selected set. The extracted and selected features are modified, and models are constructed using parametric learning algorithms. The constructed models are capable of assigning a label to each document. The model parameters are instantiated using a first subset of the selected set of documents. Parameters are chosen by validating the corresponding model against at least a second subset of the full document set. The constructed models also are capable of assigning labels to similar documents outside a selected subset not previously given to the process of model construction.

Abstract: Methods for the treatment of inflammatory and ulcerative diseases of the bowel (e.g., Crohn's disease and ulcerative colitis) with a therapeutically effective dose less than 50 mg. of opioid antagonists (e.g., naltrexone, nalmefene or naloxone) are disclosed. An embodiment of the invention includes a method of pharmaceutical treatment comprising orally administering to a human subject having Crohn's disease or ulcerative colitis a therapeutic pharmaceutical composition once per day in the evening or at bedtime, wherein the pharmaceutical composition comprises form about 3 mg to about 4.5 mg of naltrexone, nalmefene, naloxone, or a hydrochloride salt thereof in an immediate release solid dosage formulation.

Abstract: A forward synthetic method is described that utilizes recursive application of established organic chemical reactions to derive more complex synthons from available reagents than are available from the reagent synthons themselves. The product of each reaction serves as the starting point for further reactions thereby permitting the generation of multiple complex molecular structures. This synthon generation procedure typically yields 20 ? 30 new structures within the limits of easily accessible syntheses based upon each starting reagent. More complex syntheses yield even more structures. The generated synthons are characterized with a molecular structural descriptor possessing a neighborhood property and can be further characterized with features. The synthons are searched for three dimensional shape and feature similarity to molecular fragments derived from query molecules, typically pharmacological molecules of interest.

Abstract: Steric features inherent in the three dimensional disposition of atoms in molecules can be represented as multiplets using a defined set of steric descriptors. The resulting multiplets can be encoded in a compressed form of bitstring known as a bitmap. Such bitmaps can be generated in compressed form and used to compare individual conformers or ensembles of conformers of molecules to each other without decompression. Such comparisons are useful in molecular similarity analysis, in molecular diversity analysis, in database searching, and in conformational analysis.

Abstract: A computer implemented method is disclosed for analyzing a large data set of chemical compounds for which there is a measured activity in the same assay for each compound to determine the structural units which are responsible for the observed activity of the compounds.

Abstract: The static and electrostatic interaction energy fields between probe atoms and the atoms of a topomerically aligned fragment placed in a three-dimensional grid may be used to derive a CoMFA model. The topomeric CoMFA model coefficients may be used to predict partial activity values for fragments not derived from molecules of the activity series. The partial activities can be summed to provide a predicted activity for all fragment positions of the activity series molecules. A Virtual Library in which topomerically aligned fragments are associated with their respective steric and electrostatic interaction energies can be searched for fragments similar in shape to the fragments derived from the molecules of the activity series. The identified fragments can be used with the topomeric CoMFA coefficients to predict their activity if used in the molecular activity series.

Abstract: Heterogeneous compound databases can be searched for compounds which are likely to have the same biological activity as a known (query) molecule. Query molecules and the molecules in the database are split into fragments according to common fragmentation rules. Fragments are aligned in a uniform conformation according to a topomeric alignment process and interaction energy fields, typically steric fields, between a probe and the fragment atoms are generated to capture the fragment shapes. Comparison of the fields for the query fragments with the fields for the database compound fragments yields a measure of shape similarity. Searches for similarly shaped substructures and cores can also be readily accomplished. Pharmacophoric style features can be defined for the topomerically aligned fragments but with user specified weighting of the importance of each. Differences in features are defined with the same dimensionality as shape so that both shape and features can be used to search.

Abstract: To improve the burning efficiency of fuel supplied to a turbine engine by electronic fuel injectors under control of a fuel injection control system, a nebulizer of unique design is employed with the fuel injectors to further reduce the individual fuel cell size from that provided by the pulsing of fuel from the fuel injector. At least one nebulizer is used with at least one fuel injector, having means for injecting fuel in pulses into the nebulizer and thence into the combustion chamber of a turbine engine, and an electronic control unit to receive and interpret input sensor signals from selected operating functions of the engine and to generate and direct fuel injection signals to modify the pulse duration and/or frequency of fuel injection in response to a deviation from a selected operating function, such as the desired operating speed, caused by variable operating loads encountered by the turbine engine.

Abstract: Steric features inherent in the three dimensional disposition of atoms in molecules can be represented as multiplets using a defined set of steric descriptors. The resulting multiplets can be encoded in a compressed form of bitstring known as a bitmap. Such bitmaps can be generated in compressed form and used to compare individual conformers or ensembles of conformers of molecules to each other without decompression. Such comparisons are useful in molecular similarity analysis, in molecular diversity analysis, in database searching, and in conformational analysis.

Abstract: The use for biological screening purposes of a subset (library) of a large combinatorially accessible chemical universe increases the efficiency of the screening process only if the subset contains members representative of the total diversity of the universe. In order to insure inclusion in the subset of molecules representing the total diversity of the universe under consideration, valid molecular descriptors which quantitatively reflect the diversity of the molecules in the universe are required. A unique validation method is used to examine both a new three dimensional steric metric and some prior art metrics. With this method, the relative usefulness/validity of individual metrics can be ascertained from their application to randomly selected literature data sets.

Abstract: A computer implemented application development (authoring) system permits objects (such as VBX custom controls) to be graphically inserted into the program under development by dragging and dropping associated icons into one of four views. The properties associated with the object may than be assigned settings. Development of a complete application is accomplished by visually arranging, ordering, and interconnecting the objects without the necessity of writing any code. The four views of Output, Map, Multitrack, and Workform may be synchronized so that changes made to the program in one view are simultaneously reflected in all other views. The system generates as output a script listing the objects and their properties which is then executed by a separate run time program. The system permits use of objects written to a standard specification and the addition at any time of additional objects written to that.

Abstract: The problem of how to select out of a large chemically accessible universe molecules representative of the diversity of that universe is resolved by the discovery of a method to validate molecular structural descriptors. Using the validated descriptors, optimally diverse subsets can be selected. In addition, from the universe, molecules with characteristics similar to a selected molecule can be identified. The validated descriptors also enable the generation of a huge virtual library of potential product molecules which could be formed by combinatorial arrangement of structural variations and cores. In this virtual library it is possible to search billions of possible product compounds in relatively short time frames.

Abstract: The use for biological screening purposes of a subset (library) of a large combinatorially accessible chemical universe increases the efficiency of the screening process only if the subset contains members representative of the total diversity of the universe. In order to insure inclusion in the subset of molecules representing the total diversity of the universe under consideration, valid molecular descriptors which quantitatively reflect the diversity of the molecules in the universe are required. A unique validation method is used to examine both a new three dimensional steric metric and some prior art metrics. With this method, the relative usefulness/validity of individual metrics can be ascertained from their application to randomly selected literature data sets.

Abstract: A computer implemented software method enables the prediction of the pKa of an arbitrary molecule based upon a knowledge of the molecular structure of that molecule and a statistical analysis of the molecular structures of a group of molecules (training set) for which the pKa is known. Hierarchical atom connectivity trees are constructed for the training set and the various atoms types identified in each molecule are associated in a bit string for that molecule and also associated with the experimentally determined pKa for that molecule. PLS analysis of the training set data yields coefficients associated with each atom type represented in the bit strings. A hierarchical atom connectivity tree may then be constructed for the molecule of interest. The predicted pKa is determined by multiplying the number of occurrences of each atom type in the molecule of interest by the PLS coefficient determined for that atom type and summing the resulting multiplications.

Abstract: A vending machine for the sale of both food and non-food products has a plurality of adjustable shelves and adjustable product dividers. Products are dispensed from the shelves by the action of a computer controlled transporter mounted on carriages permitting movement of the transporter both horizontally and vertically in an X-Z plane across the face of the product shelving. Rotation of the transporter in front of a selected product engages a product delivery mechanism which gently and safely slides the product off the shelf onto the transporter. A movable wall within the transporter pushes the delivered product aside, thereby clearing the way for the dispensing of additional products. Multiple products may safely be collected in each cycle. Products are carried to a delivery station for retrieval by the customer. After product delivery, the transporter is discharged of any residual items.

Abstract: Barrier-free multiple level residential housing can be constructed by employing ramps between adjacent housing levels where the housing levels are offset by one half the normal full story height found in multiple story houses. The ramps are constructed in a stacked and side-by-side manner so that the full standard height between housing levels is maintained between the ramps that are stacked one above the other.

Abstract: A vending machine for the sale of both food and non-food products has a plurality of adjustable shelves and adjustable product dividers. Products are dispensed from the shelves by the action of a computer controlled transporter mounted on carriages permitting movement of the transporter both horizontally and vertically in an X-Z plane across the face of the product shelving. Rotation of the transporter in front of a selected product engages a product delivery mechanism which gently and safely slides the product off the shelf onto the transporter. A movable wall within the transporter pushes the delivered product aside, thereby clearing the way for the dispensing of additional products. Multiple products may safely be collected in each cycle. Products are carried to a delivery station for retrieval by the customer. After product delivery, the transporter is discharged of any residual items.

Abstract: The distribution of chemical compounds in high-dimensional molecular descriptor space can be viewed in two dimensions by applying the projection method of this invention. This method has particular usefulness for viewing the relationships of a large number of compounds such as found in a large scale HTS or virtual combinatorial library. After selecting a representative subset of the larger data set of comounds, initially components from the high-dimensional descriptor space are determined by PCA. In order to relax an NLM projection using the PCA components as a start, the stress function is modified to reflect a local horizon beyound which the separation of the compounds is not meaningfully measureable. The resulting two dimensional projections provide a clear insight into the distribution of the chemical compounds in the higher dimensional space.

Abstract: The method of this invention identifies distinctive items of information from a larger body of information on the basis of similarities or dissimilarities among the items and achieves a significant increase in speed as well as the ability to balance the representativeness and diversity among the identified items by applying selection criteria to randomly chosen subsamples of all the information. The method is illustrated with reference to the compound selection requirements of medicinal chemists. Compound selection methods currently available to chemists are based on maximum or minimum dissimilarity selection or on hierarchical clustering. The method of the invention is more general and incorporates maximum and minimum dissimilarity-based selection as special cases. In addition, the number of iterations required to select the items is a multiple of the group size which, at its greatest, is approximately the square root of the population size.