Abstract: Methods of identifying predicted or actual structures of members of a chemical or physical library are provided. The methods provide for the direct identification of compound structure following combinatorial synthesis using molecular mass measurements of individual compounds, thereby eliminating the necessity of encoding synthetic steps. The analysis of mass spectrometric data for sets of related compounds reveals compounds that are missing in a group of related compounds and identifies compounds that do not belong to a group of related compounds due to unexpected chemical, physical, or biological transformations. The methods may be applied to any group of compounds originating from chemical reactions where one reactant is common to the synthetic transformation. One particular application of these methods is in the analysis of the products of combinatorial synthesis. Systems, computer programs products, and kits are additionally provided.

Abstract: A performance map is provided comprising a plurality of performance curves showing head/flow conditions at various compressor speeds, terminating at one end at surge points. The performance curves are converted into deviation curves representing deviations from the surge point at the head/flow conditions. The curves are merged into a universal compressor curve with a merge-function and a pre-defined tolerance. Imaginary map head/flow values are calculated using the universal compressor curve, merge-function, deviation curves, and performance curves at the compressor speed. A ratio of the imaginary map head/flow values is compared to a ratio of the actual head/flow values at the compressor speed to determine if the ratios are within a pre-defined tolerance. The process repeats until the ratios are within the tolerance. The molecular weight of the compressor gas is calculated using a function of the actual and imaginary flow values and/or head values.

Abstract: Systems and methods are described for processing an emission signal, such as a fluorescent signal, to compensate for noise in an excitation beam, such as a laser beam. As one example, a scanning system is described that includes an excitation signal generator that provides an excitation signal having one or more representative excitation values representative of an excitation beam; an excitation reference provider that provides at least one excitation reference value; a normalization factor generator that compares the excitation reference value to at least one representative excitation value, thereby generating a normalization factor; and a comparison processor that adjusts at least one emission value corresponding to the at least one representative excitation value based, at least in part, on the normalization factor.

Abstract: The present invention provides for a method for selecting a molecule for a population which comprises: a) selecting a first molecule with a conformation characterized by a particular set of coordinates that define the position of each atom in the first molecule; b) determining the energy of the first molecule; c) transforming the coordinates of the first molecule to the coordinates of a second structurally distinct molecule to produce a particular conformation of the second molecule characterized by a particular set of coordinates that define the position of each atom in the second molecule; d) determining the energy of the second molecule; thus, selecting either the first molecule or the second molecule for the population based on their relative energies. The selected molecule may be redefined as the first molecule and the procedure repeated iteratively so as to obtain a population of first molecules and a population of second molecules.

Abstract: Software methods for identifying associations between genetic information and particular genetic traits are described. A candidate single nucleotide polymorphism (SNP) combination is selected from a plurality of candidate SNP combinations for a gene associated with (or suspected to be associated with) a genetic trait Haplotype data associated with this candidate SNP combination are read for a plurality of individuals and grouped into a positive-responding group and a negative-responding group based on whether a predetermined trait criteria for an individual is met. A statistical analysis on the grouped haplotype data is performed to obtain a statistical measurement associated with the candidate SNP combination. The acts of selecting, reading, grouping, and performing are repeated as necessary to identify the candidate SNP combination having the optimal statistical measurement (if one exists). In one approach, all possible SNP combinations are selected and statistically analyzed.

Abstract: A method for specifying a multi-component composition without human intervention includes customer specification of at least two physical property limitations, and determination of a recommended composition meeting those limitations using a continuous model relating the physical properties to the compositional variables. The method may extend to supplying a multi-component composition by further including one or more of calculating the cost of the recommended composition, calculating the price of the recommended composition, formulating a contracted amount of the recommended composition, and billing for a contracted amount of the recommended composition.

Abstract: The field of the present invention is in the area of mass spectroscopy and purity analysis. Specifically the invention is related to determining the purity of sample of materials. The invention also relates to identifying an unknown sample. The present invention also provides a web-based system for scientists to interact with a computer to implement the method. Further the scientist is able to upload and download information to and from the method to and from a database or laboratory information management system. The present invention also provides for an efficient hardware architecture to implement the method.

Abstract: Methods which may be implemented in computer systems for screening a database of candidate molecules to determine whether any particular subset of candidate molecules may be docked to a target molecule. These methods determine the force field of a target molecule only once and may be used for screening a large number of candidate molecules.

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 process for the prediction and the optimization of the output of a plant producing products form incoming materials. The incoming materials are classified according to various physical characteristics and costs. The desired or ordered products are also classified according to price and physical requirements. The incoming materials information and the product information is entered into a database which is accessible by a computing device. The computing device then calculates the optimal production process by calculating a plurality of production cycles and selecting the cycle with the optimum profitability. The computing device is programmed with non-linear equations derived from a regressive analysis of data collected from samples of incoming materials and products.

Abstract: A computer system for analyzing nucleic acid sequences is provided. The computer system is used to perform multiple methods for determining unknown bases by analyzing the fluorescence intensities of hybridized nucleic acid probes. The results of individual experiments may be improved by processing nucleic acid sequences together. Comparative analysis of multiple experiments is also provided by displaying reference sequences in one area and sample sequences in another area on a display device.

Abstract: Structural alignment methods are described that compare the sequences of two or more structural features of molecules. The methods provide for a rigorous statistical analysis that can detect structural similarities in molecules regardless of the similarity in their primary sequences. Thus, the methods can be used to predict and explain functional properties of molecules from their three-dimensional conformation. The methods use databases of different structural features against which a query sequence can be searched. By combining the search results from the various databases, the functional properties of molecules can be predicted and serve as a basis for the efficient design of ligands, substrate analogues, inhibitors or pharmaceutical species thereof.

Abstract: Methods and compositions for determining the three dimensional structure of a particle are provided. In the subject methods, a plurality of images of the identically heavy atom labeled particles of interest is obtained. Each of the images in the plurality is obtained by rigidly attaching at least four heavy atom clusters to the particle of interest and imaging the particle in an electron microscope. The three-dimensional structure of the particle is then derived from the plurality of images of the labeled particle. This derivation step preferably includes an alignment step in which the orientation of the images is determined using the heavy atom cluster projections. In preferred embodiments, the heavy atom clusters serve to reveal particle homogeneity, particle location, particle orientation, image artifacts, and image parameters required for computational image restoration. The subject methods are particularly suited for use in determining the three dimensional structure of biological particles, e.g.

Abstract: A method of establishing a synthesis path in a multiplicity of potentially interlinakable reactions, and a computer program to prepare a synthesis path.

Abstract: If conditions for measuring a storage quantity of O2 in a catalyst are satisfied, a target air-fuel ratio is switched to a rich value after the end of a fuel-cut state. The quantity of a rich component contained in an exhaust gas flowing into a catalyst during a period of time period is calculated. The quantity of a rich component required to consume all O2 absorbed by the catalyst in the fuel-cut state is calculated. The computed quantity of a rich component is taken as a storage quantity of O2 in the catalyst. Since the air-fuel ratio of exhaust gas is changed to a rich value, to improve exhaust gas cleaning, during the computation of a storage quantity of O2, the storage quantity of O2 in the catalyst can be computed without worsening emission of exhaust gas.

Abstract: The present invention provides a method for monitoring degradation of Hb-based blood substitutes, in a sample. This method comprises determining a concentration of met-Hb within the sample, by applying a calibration algorithm for met-Hb to an absorbance obtained from the sample at one or more than one wavelengths, and using the concentration of met-Hb, as a measurement of degradation of the Hb-based blood substitutes. Using this assay, a concentration of met-Hb that is equal to or greater than 3% may be used as an indicator of degradation of Hb. Alternatively, by obtaining samples over a period of time, the concentration of met-Hb and the concentration of Hb-based blood substitute may be determined in each of these samples, and an increase in the concentration of met-Hb over the period of time is an indicator of degradation of Hb.

Abstract: The invention relates to methods of identifying and characterizing properties of polymers to provide information about the polymer such as the charge of the polymer, the number and types or characteristics of units of the polymer and the sequence of the polymers. The invention also relates to methods of sequencing polymers such as nucleic acids, polypeptides and polysaccharides and methods for identifying a polysaccharide-protein interaction.

Abstract: A multi-analyte diagnostic system for use with a computer. The diagnostic system includes a flow analyzer including a co-planar light source-optical detector array, the flow analyzer being communicatable with the computer. The diagnostic system also includes a memory medium readable by the computer and storing computer instructions. The instructions include the following steps. A biological sample is run through the flow analyzer. The identity and quantity of at least one analyte of interest in the biological fluid is determined substantially simultaneously to the sample-running step.

Abstract: The present invention is directed to computer automated methods and systems for identifying and characterizing biomolecules in a biological sample. Mass spectrometry measurements are obtained on biomolecules in a sample. These measurements are analyzed to determine the abundance of the biomolecules in the sample, and the abundance measurements are coupled with one or more distinguishing characteristics of biomolecules they are associated with, thereby permitting computer-mediated comparison of abundances of biomolecules from multiple biological samples.

Abstract: A method of analysing crystalline texture from data defining the orientation of crystals in a sample of polycrystalline material comprises, for each crystal, determining the orientation of a first direction in the sample, with respect to a common reference frame fixed to the crystal structure of each crystal. A number of crystals sharing a similar orientation of the first direction with respect to the reference frame are selected and for each, the orientation is determined of a second direction in the sample with respect to the reference frame. A number of crystals sharing a similar orientation of the second direction with respect to the reference frame are selected and a crystal texture corresponding to the orientation of the selected crystals with respect to the first and second directions within the sample is determined and/or represented.

Abstract: An LED-based spectrophotometer uses a reconstruction algorithm, based on spectral information of an illumination source and a reference spectrophotometer, to convert integrated multiple illuminant measurements from a non-fully illuminant populated color sensor into a fully populated spectral curve using a reference database. A non-linear model, such as a fuzzy inference system (FIS), is used to reconstruct spectra.

Abstract: An interpretation of a chemical name is used to identify information pertaining to a substance identified by the chemical name, even if the chemical name is unfamiliar. Initially, a chemical name is acquired that identifies a chemical substance. Chemical structural information is derived from the chemical name. Based on the chemical structural information, a database entry or other resource is identified pertaining to the chemical substance.

Abstract: A technique for automatically analyzing mass spectrographic data from mixtures of chemical compounds has a series of screens designed to eliminate or reduce incorrect peak identifications due to background noise, system resolution, system contamination, multiply charged ions and isotope substitutions. With such a technique, mass spectrograph data analysis may be greatly simplified by the identification of probable spurious signals, and analysis will become simpler and more accurate.

Abstract: The monoisotopic mass peak of an experimentally obtained mass spectrum (262) for a sample molecule is determined using a cross correlation method. A model spectrum (261), having a known monoisotopic peak position, is created based on knowledge of the sample molecule. A set of correlation values are calculated from intensity values IMODEL, IEXP for a selected mutual alignment between the spectra. A cross correlation analysis is used to find the best agreement between the model and the experimental mass spectrum, represented by a best value of a quality factor. The position of the monoisotopic peak of the model spectrum showing the best agreement with the experimental mass spectrum is selected as the best approximation of the monoisotopic peak of the experimental spectrum. Knowing the charge state of the analysed section of the mass spectrum it is possible to determine the monoisotopic mass of the sample molecule.

Abstract: The present invention provides machine readable media embedded with the three-dimensional molecular structure coordinates of PLP-dependent enzyme, and subsets thereof, including binding pockets, methods of using the structure to identify and design affecters, including inhibitors and activator, mutants of PSH, and compounds and compositions that affect PSH activity.

Abstract: There is disclosed a method and a computer system enabling high-throughput combinatorial synthesis and screening of lighting phosphors. The system links hardware instrumentation for synthesis and screening. It records, sorts, and analyzes photo-metric data gathered from the combinatorial studies, along with the characteristics of the combinatory processes. The system provides a database as the data storage and query engine, an analysis module as the processor for analytical operations, and an interface for accepting the user's input and displaying the analysis results and other information requested by the user.

Abstract: A method of reducing noise in assay data collected in assaying measurables in a sample can provide replicate assay data for each of a plurality of measurables for one or more assay samples. The method can further provide a filtering function that identifies noise in replicate assay data. The method can also include a step of applying the filtering function to the replicate assay data to generate noise data. The method can also model the noise data to generate a noise model; and apply the noise model to the replicate assay data to reduce noise present in the replicate assay data.

Abstract: A system and method for computer-aided drug design is less restricted by accuracy of calculated ligand-receptor binding affinity, better copes with the flexibility of ligands and its effect on binding affinity, and limits the generation of undesirable compounds and the likelihood of biasing results with assumptions made in development.

Abstract: The present invention relates to novel screening methods which enable the selection of neurokinin-1 (NK-1) receptor antagonist compounds which do not possess significant inhibitory potency towards cytochrome P450 enzymes, in particular, CYP2D6. The present invention also relates to a method of generating a pharmacophore model for the CYP2D6 inhibitory activity of NK-1 receptor antagonist compounds; to methods for the discovery of molecules that are potential NK-1 receptor antagonist compounds which do not possess significant inhibitory potency towards the CYP2D6 enzyme; to methods of modeling the features of the CYP2D6 pharmacophore useful in selecting NK-1 receptor antagonist molecules which do not possess significant potency towards CYP2D6.

Abstract: Spectrographic instruments at remote site locations measure near infrared absorbance spectra for unknown materials and transmit the absorbance spectra to a central web site where, the measurements are standardized to be the same as if they were measured by a master instrument. The standardized absorbance spectra are then compared with a library of spectra stored at the central web site to select a subset of absorbance spectra from the library which most closely correlate with the absorbance spectrum received from the remote sites. The library spectra are obtained from measurements on materials, the measurable characteristics of which are known. From the selected subset, equations are developed relating the measurable characteristics of the unknown material to the absorbance spectra and from these equations, the measurable characteristics of the unknown materials are determined. The results of this analysis are then transmitted back to the remote site locations electronically.

Abstract: Method for generating intra-particle crystallographic parameter maps and histograms of a chemically pure crystalline particulate substance. Spectral imaging, in general, and focus-fusion multi-layer spectral imaging, in particular, combined with pattern recognition classification analysis are performed on individual particles for forming sets of single-particle spectral fingerprint data, characterized by single-particle spectral fingerprint spectra. Spectral shifts are identified in the single-particle spectral fingerprint data, for forming intra-particle crystallographic region groups each featuring sub-sets of intra-particle spectral fingerprint pattern data, where selected data elements in each sub-set are shifted relative to corresponding data elements in remaining sub-sets in the same intra-particle crystallographic region group.

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: There is disclosed a material characterization method. The method may include any combination of several potential steps. According to one of the steps multiple material samples are applied to multiple sensors in an array of sensors. In another step, one or more of the sensors of the array are electrically contacted. In another step, electrical connections are formed between selected sensors and electronic test and measurement apparatus. In another step, electric signals are sent to and received from the sensors in the array wherein the signals correspond to thermal, electrical, mechanical or other properties of the material samples. Preferably, some of the equipment (e.g., the electrical connections) used in the method are standardized to allow equipment such as sensor arrays to be interchangeable with equipment such as the electronic test and measurement apparatus.

Abstract: A method for creating physiologically active compounds, comprising the following steps: (1) generating a compound database storing molecular structures covering all the combinations of at least one substitution site selected from substitutable sites existing on a basic molecular skeleton and utilizable substituents; and (2) extracting molecular structures satisfying requirements for exhibiting the physiological activity from the compound database.

Abstract: The present invention provides a method for the chromatographic fingerprinting, chemical and therapeutic standardization, bar-coding of the fingerprints and preparation of a data base for Enterprise Resource Planning (ERP) and Customer Relationship Management (CRM) machines and applications of medicines in general and traditional medicines in particular; this invention includes a software based instrumental method and a novel method of fingerprinting and standardization is proposed for the above purpose and the said method for the chromatographic finger printing which facilitates to correlate the traditional therapeutic standardization methods with the chemical properties of the medicines and humors and provides a rational basis to understand the methods used for the said purpose.

Abstract: This invention provides a method for predicting pharmacokinetic properties of molecules comprising the steps of:

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: The present invention provides for a method for selecting a molecule for a population which comprises: a) selecting a first molecule with a conformation characterized by a particular set of coordinates that define the position of each atom in the first molecule; b) determining the energy of the first molecule; c) transforming the coordinates of the first molecule to the coordinates of a second structurally distinct molecule to produce a particular conformation of the second molecule characterized by a particular set of coordinates that define the position of each atom in the second molecule; d) determining the energy of the second molecule; thus, selecting either the first molecule or the second molecule for the population based on their relative energies. The selected molecule may be redefined as the first molecule and the procedure repeated iteratively so as to obtain a population of first molecules and a population of second molecules.

Abstract: An LED-based spectrophotometer uses a reconstruction algorithm, based on spectral information of an illumination source and a reference spectrophotometer, to convert integrated multiple illuminant measurements from a non-fully illuminant populated color sensor into a fully populated spectral curve using a reference database. A non-linear model, such as a fuzzy inference system (FIS), is used to reconstruct spectra.

Abstract: A sensor-array based materials characterization apparatus includes a sensor array disposed on a substrate; electronic test circuitry for sending and receiving electrical signals; electronic circuitry for routing signals between selected sensors and the electronic test circuitry; and a computer or processor. Preferably, all or part of the electronic test and signal routing circuitry is contained on the same substrate as the sensor array. Additional circuitry and a processor or computer may be physically separate from the substrate carrying the sensor array, and may be connected to the sensor array substrate. During use, multiple samples are applied to the multiple sensors in the array, and signals are sent to and received from selected sensors. Integration of the electronic test and signal routing circuitry onto the same substrate as the sensor array allows for a high density of sensors on a single substrate, permitting rapid analysis of combinatorial libraries.

Abstract: A computational method for the discovery and design of therapeutic compounds is provided. The methods used rely on an accurate inter-conversion of three-dimensional molecular spatial information between two alternative orthogonal representations. These methods enhance the accuracy for determining ab initio phases of macromolecular crystallographic structures at any desired experimental resolution limit. The computational technique employed utilizes a software program and associated algorithms. This method is an improvement over the current methods of drug discovery which often employs a random search through a large library of synthesized chemical compounds or protein molecules for bio-activity related to a specific therapeutic use.

Abstract: The polar surface area of molecules is computed without reference to three dimensional molecular structures using a linear equation incorporating counts of nitrogens, oxygens, and related atom clusters. Methods and systems for predicting intestinal absorption of candidate compounds use the polar surface area and the octanol/water partition coefficient as descriptors.

Abstract: The disclosure relates to a method of estimating the polar component of the solvation energy for a molecule embedded in different media. In one embodiment, the molecule is partially embedded in a membrane. For an atom of the molecule, the polar component of the atom's solvation energy is represented as a combination of at least a self-energy term and a screening-effect term. The self-energy term represents the contribution to the atom's polar component made by the membrane and the molecule's other atoms located inside the membrane. The screening-effect term represents the typically negative contribution to the atom's polar component made by the molecule's other atoms located outside the membrane. An analytical function is used to calculate the self-energy term. In a preferred embodiment, the analytical function is a function of the distance from the atom to the membrane, the van der Waals radius of the atom, and the thickness of the membrane.

Abstract: The nuclear receptor for the steroid hormone 1&agr;,25-dihydroxyvitamin D3, its ligand binding domain, three-dimensional model thereof and a method for selection of suitable vitamin D3 binding to the 1&agr;,25-dihydroxyvitamin D3 receptor. A three-dimensional model for residues 142-427 of the ligand binding domain of the human nuclear receptor for 1&agr;,25-dihydroxyvitamin D3 used to identify the interaction of the conformationally flexible natural hormone 1&agr;,25(OH)2D3 and a number of related analogs with the receptor ligand binding domain. A method for identification and generation of new potential analog drug forms of dihydroxyvitamin D3.

Abstract: Computer programs and computer-implemented methods are disclosed for extracting, analyzing and comparing data from biomolecular binding experiments. The invention receives a set of values corresponding to the interaction of one or more target samples with probes on one or more arrays of biomolecular probes, and uses the values to generate one or more probability values indicating the probability that a molecular species complementary to the probe set is not present in the target samples, or is present at levels greater than or less than one or more reference levels. The probability values are generated by comparing the values for individual probes in a probe set with values for a calibration set, which may include a null set, spiked probe sets, or housekeeping probe sets. Normalized experimental values are generated for sets of probes on the arrays using statistical methods. Data is output in the form of data files including normalized experimental values and probability values for probe sets in the arrays.

Abstract: This invention relates to methods and apparatus for determining the multi-dimensional topology of a substance (system) within a volume (space). A method according to a preferred embodiment of the invention comprises the steps of: acquiring a set of relative values for the density (scalar properties) of the volume, each value for a given location (point) within the volume; interpolating a set of functions to generate a continuous relative density for the volume; identifying critical points of the continuous relative density by using an eigenvector following method; and associating critical points with one another by following a gradient path of the continuous relative density between the critical points. The method is applicable to a wide range of data relating to fields such as crystallography, fluid dynamics, edge detection, and financial markets, to determine the topology of structures contained therein.

Abstract: A molecular similarity evaluation method has steps of: (a) obtaining an upper threshold and a lower threshold from one of a value specific to an atom included in a first molecule, a value specific to an atom included in a second molecule of which correlation with respect to the atom in the first molecule is to be evaluated, or another value obtained from these values; (b) calculating the correlation between the atom in the first molecule and the atom in the second molecule, using the upper and lower thresholds; and (c) evaluating the similarity between the first and second molecules based on the correlation obtained in the step (b).

Abstract: A process for determination of three-dimensional macromolecular atomic structures of proteins is provided. A plurality of gene products are clustered into at least one family of homologous sequences. At least one protein encoded by a sequence selected from each of the families is prepared, purified and characterized. The purified proteins are crystallized in parallel against crystallization screens. Diffraction data produced by the crystallized proteins is measured using a multi-wavelength anomalous diffraction method. The diffraction data is analyzed by using a multi-wavelength anomalous diffraction phasing method, an atomic model is built, and the model is refined based on the diffraction data to determine a three-dimensional macromolecular atomic structure for each of the crystallized proteins.

Abstract: Compositions of binding compounds for CXC chemokine receptor 4 and methods for identifying binding compounds for CXC chemokine receptor 4 are provided. Also provided are therapeutic agents comprising such compounds.

Abstract: An experimental space comprising levels of factors is designed according to an incomplete block design and an experimental space comprising levels of factors is designed by random selection. Separate combinatorial high throughput screening experiments are effected on each experimental space to produce sets of results and best results are selected from the sets. A system for conducting an experiment includes a reactor for effecting a combinatorial high throughput screening method on an experimental space to produce results and a programmed controller that defines an experimental space comprising levels of factors according to an incomplete block design and defines an experimental space comprising levels of factors by random selection.