Abstract: A method of generating a chronic myelogenic leukemia (CML) acquired chemoresistant culture model is provided. Such a method may comprise providing a naïve blast crisis CML cell line; administering/contacting the cell line with a mutation-inducing dose of imatinib; maintaining a culture of the treated cell line for a period of time until the treated cell line relapses and repopulates the culture; and determining the repopulated cell culture is a CML acquired chemoresistant cell line by detecting a BCR-ABL mutation, wherein the acquired chemoresistance is achieved by a BCR-ABL mutation.

Abstract: Method and systems for monitoring ion mobility spectrometers are provided. The method can include acquiring scan data, and generating a segment data set from the scan data. The method can further include deriving a subset of peak data from the segment data, where the subset of peak data has an associated set of peak metrics, and deriving a value from the subset of peak data associated with a criteria element of the associated set of peak metrics, where the criteria element has an associated range of values. The method can further include providing an indication in the event the value lies outside the associated range of values.

Abstract: The present invention relates to a crystal structure of a plasma membrane proton pump type ATPase. The invention further describes method for identification of modulators of ATPases as well as uses of such modulators. Based on the provided three dimensional structure of the ATPase, various method, such as computer implemented methods may be used for identification of modulators, such putative modulators may be further analysed using in vitro and in vivo experiments to confirm there functionality. Several modulator interaction regions are described as target of regulation by ATPase modulators.

Abstract: Provided is a mass spectrometric data analyzing method for deducing the structure of an unknown substance from data obtained by an MSn analysis, in which a structural candidate having a high degree of freedom for covering a structural change of the known substance can be created. In the mass spectrometric data analyzing method according to the present invention, a candidate of the partial structure of a known substance which is structurally similar to an unknown substance as the target of deduction is created by eliminating a part of the structure of the known substance (Step S1). Previously given candidates of known additional structural parts are individually added to each candidate of the partial structure of the known substance, thus forming various combinations (Step S5). All the structural formulae that can be derived from each combination are created as the structural candidates of the unknown substance (Step S6).

Abstract: The invention provides novel mutations, mutation combinations or mutational profiles of HIV-1 reverse transcriptase and/or protease genes correlated with phenotypic resistance to HIV drugs. More particularly, the present invention relates to the use of genotypic characterization of a target population of HIV and the subsequent correlation of this information to phenotypic interpretation in order to correlate virus mutational profiles with drug resistance. The invention also relates to methods of utilizing the mutational profiles of the invention in databases, drug development, i.e., drug design, and drug modification, therapy and treatment design, clinical management and diagnostic analysis.

Abstract: Methods and systems are described for tracking material through a production chain or operational process chain in which the material is transferred via a plurality of spatially distinct lumped masses of material (12, 14, 16, 18). A dynamic state space (430) is maintained descriptive of the plurality of spatially distinct lumped masses of material, wherein a quantity of entries in the dynamic state space is augmented or diminished dependent on a quantity of spatially distinct lumped masses being tracked. Measurements relating to an observed lumped mass of material are fused into the dynamic state space and a dynamic covariance matrix to provide an updated estimate of material in the plurality of spatially distinct lumped masses of material.

Abstract: This invention provides methods for determining drug specificity, therapeutic index and effective doses for individual patients. According to the methods of the invention, graded levels of drug are applied to a biological sample or a patient. A plurality of cellular constituents are measured to determine the activity of the drug on a target pathway and at least one off-target pathway. A drug specificity is determined by comparing the target and off target activities of the drug. A therapeutic concentration (or dose) is defined as a concentration (or dose) of the drug that induces certain response in the target pathway. A toxic concentration (or dose) is defined as a concentration (or dose) of the drug that induces certain response in the off target pathway. Therapeutic index is the ratio of the toxic concentration over therapeutic concentration. Methods are also provided to determine an effective dose of a drug for a patient by measuring the activity of the drug on the particular patient.

Abstract: Cypoviruses and baculoviruses are notoriously difficult to eradicate because the virus particles are embedded in micron-sized protein crystals called polyhedra. The remarkable stability of polyhedra means that like bacterial spores these insect viruses remain infectious for years in soil. Although these unique in vivo protein crystals have been extensively characterized since the early 1900s, their atomic organization remains elusive. Here we describe the 2 crystal structure of both recombinant and infectious silkworm cypovirus polyhedra determined using 5-12 micron crystals purified from insect cells. These are the smallest crystals yet used for de novo X-ray protein structure determination. It was found that polyhedra are made of trimers of the viral polyhedrin protein and contain nucleotides. Although the shape of these building blocks is reminiscent of some capsid trimers, polyhedrin has a new fold and has evolved to assemble in vivo into 3-D cubic crystals rather than icosahedral shells.

Abstract: A method for identifying an odour and/or gas, an odour and/or gas is measured with a portable electronic device comprising a chemical sensor, the chemical sensor being sensitive to different analytes. A measurement tuple is supplied which comprises a set of tuple elements with each tuple element of the set of tuple elements providing a value measured by a dedicated cell of the chemical sensor and/or under a dedicated operating condition of the chemical sensor or of a cell of the chemical sensor. The measurement tuple is compared to one or more reference tuples with each reference tuple representing an odour and/or gas and comprising a set of tuple elements and an identifier for the odour and/or gas represented by the reference tuple. One or more odour and/or gas identifiers are returned to the portable electronic device subject to a result of the comparison.

Abstract: A method for estimating an energy loss of a high polymer material is disclosed. A model of the molecular structure of the high polymer material is defined. This model includes particle models and joining chains. Potentials are defined on the particle models. A high polymer material model in which the molecular structure models are arranged at cells is defined. A structure relaxation calculation is made. Thereafter, by applying a cyclic deformation to the high polymer material model, the stress and strain are computed, and the energy loss is computed therefrom. The deformation calculation is made only when the cycle of the cyclic deformation is not equal to the oscillation cycle determined by the characteristic frequency of the potential.

Abstract: The amplification of secondary-electron multipliers in mass spectrometers is automatically adjusted by generating mass spectra with single ion signals, determining the average value of the peak heights of these single ion signals, and setting the amplification so that the average peak height assumes a desired nominal value. The amplification may be set via the supply voltage of the secondary-electron multiplier and can be increased or decreased by a desired factor using the known characteristic of the secondary-electron multiplier.

Abstract: A method and associated apparatus for topographically characterizing a workpiece. The workpiece is scanned with a scanning probe along a first directional grid, thereby scanning a reference surface and an area of interest subportion of the reference surface, at a variable pixel density including a first pixel density outside the area of interest and a second pixel density inside the area of interest to derive a first digital file characterizing topography of the workpiece. The workpiece is further scanned along the reference surface and the area of interest with the scanning probe along a second directional grid that is substantially orthogonal to the first directional grid and at a constant pixel density to derive a second digital file characterizing topography of the workpiece. A processor executes computer-readable instructions stored in memory that generate a topographical profile of the workpiece in relation to the first and second digital files.

Abstract: A method for recombinant production of a polypeptide, exemplified by the therapeutic peptide MBP8298, by recombining and optimizing the nucleic acid encoding said polypeptide, expressing said nucleic acid in a microbial host cell, isolating said polypeptide from the host, and releasing embedded polypeptide from fusion partners or peptide concatamers are explained. Such method may provide increased production or simplified downstream processing for the polypeptide of interest.

Abstract: Systems, methods, and computer-readable media for determining parameters are provided, as are methods for determining differences in one or more biological response(s) by cell(s) to factor(s). Distances or difference scores are automatically calculated between test data and reference data from a flow cytometer.

Abstract: A method for discovering pharmacologically active substances from natural products at high speed, including: obtaining an activity profile by testing pharmacological activity of a plurality of samples; obtaining mass profiles based on mass spectra resulting from analysis of the samples by mass spectrometry; and determining molecular weight of pharmacologically active substances by comparing and analyzing the activity profile and the mass profile. The method allows fast discovery of pharmacologically active substances by performing high resolution mass spectrometry for numerous components included in an extract sample of natural products and comparing with the activity test data. The information about the intensity of the activity of the pharmacologically active substances of the natural products allows effective utilization of the natural products.

Abstract: A method of and apparatus for identifying and/or characterising a sample that may incorporate two or more isomeric or isobaric compounds such as hydroxylated metabolites. The method involves modelling an ensemble of possible structures for each of two or more known isomeric or isobaric compounds, calculating a theoretical collision cross-section for each modelled structure, averaging the calculated values for each known compound to provide a theoretical collision cross-section value for each known compound. A travelling wave ion mobility cell is used to measuring a collision cross-section value for the sample compound and the measured value is then compared with the theoretical values to identify which of the two or more known compounds the sample compound most closely resembles.

Abstract: A method utilizing characteristic x-ray emission from a single thin film or multilayer thin film when an electron beam impinges at a grazing angle with respect to the surface of the sample to capture structural and physical properties of the layers such as layer thickness, interfacial roughness, and stoichiometry of the sample.

Abstract: The crystal structure of ligand-bound EGLN1 catalytic domain of prolyl hydroxylase is disclosed. These coordinates are useful in computer aided drug design for identifying compounds that regulate EGLN1 prolyl hydroxylase and thereby regulate HIF-regulated disorders.

Abstract: The invention relates to the detection and quantification of polypeptides using mass spectrometry. Specifically, the invention provides a method for testing whether a target polypeptide is present in a sample of a set of polypeptides, a method for deriving a value for distinguishing polypeptides of a set of polypeptides from each other, a database containing values for distinguishing each polypeptide of a set of polypeptides from each other, and an apparatus for configuring a mass scan of a mass spectrometer to test whether a target polypeptide of a set of polypeptides is present in a sample of the set.

Abstract: The computational drug discovery method disclosed herein permits a user to specify a three dimensional representation of a molecular fragment derived from a query molecule involved in a drug interaction that then serves as a template to which fragments derived from molecules in database libraries may be aligned. The likely activity of the substitution of the fragment from the database library for the fragment from the query molecule may then be predicted by appropriate shape characterization and CoMFA analysis. The spatial three dimensional representation of the query fragment may be developed from binding data, crystallographic data, modeling data, or any other biophysical or biochemical technique.

Abstract: A processing application receives peak information associated with multiple known references samples. The processing application partitions a spectrum into multiple different sized range bins such that a substantially equal number of the peaks associated with the known reference samples reside into each of the multiple different sized range bins. To identify a set of candidate reference samples in a library of reference samples that potentially are a good match an unknown sample under test, the processing application compares peaks associated with the unknown sample to the multiple different sized range bins. The greater the number of range bin matches based on peaks in the unknown sample and peaks in a corresponding reference sample, the greater the likelihood that the unknown sample matches the corresponding reference sample.

Abstract: A method sequentially obtains observation data with respect to a plurality of samples for a test subject and obtains content of a target component contained in each of the plurality of samples. The method subsequently estimates a plurality of independent components, which are separated from the observation data with respect to each of the samples, and calculates a mixing coefficient corresponding to the target component with respect to each of the samples, based on the estimated plurality of independent components. The method then determines a regression equation of a calibration curve, based on the obtained contents of the target component contained in the plurality of samples and the mixing coefficients of the respective samples.

Abstract: Methods for generating putative ligand structures capable of altering the activity of a target effector molecule comprise: constructing an elongated monomer of the target effector molecule; constructing a three dimensional model of the target effector molecule under the influence of elongation using empirical three dimensional data, the model including a conformation revealing the binding portion of the target effector molecule to a putative ligand structure; generating a plurality of computational models of the target effector molecule; filtering the plurality of computational models against the three dimensional model created experimentally using a reiterative simulation analysis algorithm operable to identify and select a plurality of computational models having a root-mean square deviation below a predetermined threshold when compared to the three dimensional model of the target effector molecule; screening a plurality of ligands to rank the binding strength of each ligand with the plurality of computatio

Abstract: The invention provides methods and apparatus for characterizing complex polymeric mixture of interest. Candidate solutions are eliminated from a solution space using one or more experimental measurements of a polymeric mixture of interest. The elimination step can be repeated one or more times using different experimental measurements produced by various chemical and physical protocols, so that the remaining candidate solutions converge to describe the actual polymeric mixture under investigation. Once the composition of the complex polymeric mixture has been characterized, the information thus generated can be used to facilitate, for example, the manufacture of a bio-equivalent of the complex polymeric mixture.

Abstract: The present invention relates generally to the field of crystallography. More particularly, the present invention provides crystalline forms of a complex between granulocyte macrophage-colony stimulating factor (GM-CSF) and its receptor (GM-CSFR). The present invention further provides methods for the design and selection of modulators of GM-CSF/GM-CSFR interaction and signaling as well as signaling of other cytokines.

Abstract: An apparatus for elemental analysis of particles such as single cells or single beads by mass spectrometry is described. The apparatus includes means for particle introduction; means to vaporize, atomize and ionize elements associated with a particle; means to separate the ions according to their mass-to-charge ratio; means to detect the separated ions, means to digitize the output of the means to detect the ions; means to transfer and/or to process and/or record the data output of the means to digitize, having means to detect the presence of a particle in a mass spectrometer; and means to synchronize one of the means for ion detection, data digitization, transfer, processing and recording with the means to detect the presence of a particle. Methods and computer readable code implementing aspects of the apparatus, and for reducing the rates of data generation, digitization, transfer, processing and recording are also described.

Abstract: A system and method are providing for analyzing radiation signature data (i.e., spectral data) produced by a detector device against stored data representing the computed interaction of known radioisotopic spectra with a representative cross section for each of a small number of material groups. Each material group comprises materials expected to be in a detection path of the detector and which exhibit similar cross sections. Comparative analysis is made of the spectral data received from the detector for threat materials to determine whether the spectral data indicates presence of a threat material in the interrogated space. The system and method is not limited to any particular detector type, and may be used with any detector that produces spectral data.

Abstract: A hand held ion tester includes a housing sufficiently small to be conveniently held in a human hand. A sample chamber is formed in the housing and has a sample inlet in the upper surface of the housing. An ion selective electrode is positioned in the sample chamber so as to be in liquid communication with samples positioned in the sample chamber. A key board and a display are positioned on the upper surface of the housing and a central processing unit contained within the housing is electrically coupled to the ion selective electrode, the key board and the display. The central processing unit is designed and connected to receive signals from the ion selective electrode, process the signals and display processed information on the display.

Abstract: Protein samples are processed to create a mixture of modified and unmodified or overlapping peptides which are analyzed using mass spectrometry. Correlations between the MS/MS spectra of peptide pairs allow the noise in individual MS/MS spectra to be greatly reduced. A small number of peptide reconstructions can be generated that are likely to contain the correct one. This allows for the de novo reconstruction of protein sequences and peptide and modification identification through a database search using extremely fast pattern matching, rather than time-consuming matching of spectra against databases.

Abstract: In one embodiment a method to determine at least one low temperature property of the lubricant oil is disclosed. This method comprises obtaining a base stock, generating a DSC curve of wax versus temperature using a heating curve for the base stock, correlating the heating curve of the base stock with a MRV for a formulated oil, and determining the MRV of the lubricant oil from the correlation of the base stock to the MRV of the corresponding desired base oil.

Abstract: A method for automatically identifying groups of related peaks generated in a chromatography-mass spectrometry experiment comprises automatically choosing a time window defining a region of interest for mass spectral data generated by the experiment; automatically constructing a plurality of extracted ion chromatograms (XICs) for mass spectral peaks observed within the region of interest; automatically detecting and characterizing chromatogram peaks within each XIC and automatically generating synthetic analytical fit peaks thereof; automatically discarding a subset of the synthetic analytical peaks which do not satisfy noise reduction rules; automatically performing a respective cross-correlation score calculation between each pair of synthetic analytical fit peaks; and automatically identifying groups of correlated peaks in at least one mass spectrum within the region of interest.

Abstract: A method for matching a precursor ion with one or more related product ions includes providing input data sets obtained from sample injections, each of the data sets including a precursor ion and one or more product ions, normalizing the input data sets in accordance with a single retention time for the precursor ion, determining which product ions are within a predetermined retention time window with respect to the single retention time, and, if a product ion is within the predetermined retention time window for a specified number of the input data sets, determining that the product ion is related to the precursor having the single retention time. An apparatus for analyzing a sample includes a chromatography module, a mass-spectrometry module in communication with the chromatography module, and control unit in communication with the chromatography module and the mass-spectrometry module.

Abstract: A computer implemented system and method for determining the isotopic anatomy of molecules. The system receives a user identified molecule that is to be analyzed, makes an initial guess as to the isotopic anatomy of the molecule, and iteratively refines the initial guess based on one or more observations made by the user. When sufficient iterations have been performed, the system outputs information about the isotopic anatomy of the molecule. The information may then be stored, displayed on a monitor, analyzed for making other conclusions, and/or printed.

Abstract: The structure of C3c in complex with the complement inhibitor, compstatin, and use of this information for rational design or identification of complement-inhibiting drugs are disclosed.

Abstract: The current invention concerns a method for identifying the elemental composition of and/or quantifying the presence of mono-isotopic elements in a molecule in a sample by computing a solution of a system of linear equations ??Ei?n?=Fi, whereby the set of numbers Fi comprises said set of relative peak heights from the aggregated isotopic distribution and the coefficients Ei? of said linear system comprise powers and/or power sums of roots r?,i?. The present invention also provides a method for analysing at least part of an isotopic distribution of a sample, comprising obtaining data comprising at least one probability qj with which a j'th aggregated isotopic variant of said molecule with mass number Aj occurs within said aggregated isotopic distribution; and computing a probability qi with which an i'th aggregated isotopic variant occurs within said aggregated isotopic distribution, by taking a linear combination of said at least one probability qj.

Abstract: A method for analysis, control, and manipulation for improvement of the chemical reaction rate of a protein-mediated reaction is provided. Enzymes, which typically comprise protein molecules, are very efficient catalysts that enhance chemical reaction rates by many orders of magnitude. Enzymes are widely used for a number of functions in chemical, biochemical, pharmaceutical, and other purposes. The method identifies key protein vibration modes that control the chemical reaction rate of the protein-mediated reaction, providing identification of the factors that enable the enzymes to achieve the high rate of reaction enhancement. By controlling these factors, the function of enzymes may be modulated, i.e., the activity can either be increased for faster enzyme reaction or it can be decreased when a slower enzyme is desired.

Abstract: Methods, computer systems, and computer program products for antibody engineering. A variant set for an antibody of interest is constructed by identifying, using a plurality of rules, a plurality of positions in the antibody of interest and, for each respective position in the plurality of positions, substitutions for the respective position. The plurality of positions and the substitutions for each respective position in the plurality of position collectively define an antibody sequence space. A variant set comprising a plurality of variants of the antibody is selected. A property of all or a portion of the variants in the variant set is measured. A sequence-activity relationship is modeled between (i) one or more substitutions at one or more positions of the antibody of interest represented by the variant set and (ii) the property measured for all or the portion of the variants in the variant set.

Abstract: A method and apparatus for wavelet based elemental spectrum analysis is described. The system and method set forth allows for elemental decomposition of sampling spectral data to determine the presence of materials in the interrogated object. The method utilized and set forth implements wavelet decomposition of a spectrum and elemental analysis without requiring an empty background spectrum for subtraction of the background noise from the sampling spectrum. The system and method measures the presence of elements present in the sample being analyzed. The system may also measure the ratio of elements present in the sample being analyzed.

Abstract: A system and method for identifying a material passing through a nanopore filter wherein an electrical signal is detected as a result of the passage and that signal is processed in real-time using mathematical and statistical tools to identify the molecule. A carrier molecule is preferably attached to one or more molecule(s) under consideration using a non-covalent bond and the pore in the nanopore filter is sized so that the molecule rattles around in the pore before being discharged without passing through the filter pore. The present invention includes not only a method and system for identifying the molecule(s) under consideration but also a kit for setting up the filter as well as mathematical tools for analyzing the signals from the sensing circuitry for the molecule(s) under consideration.

Abstract: Techniques for analyzing one or more protein structures. In one aspect of the invention, the technique comprises the following steps. A normalized second-order hydrophobic moment is determined for a protein structure. The normalized second-order hydrophobic moment is then used for analysis of the protein structure. A scoring function in accordance with the normalized second-order hydrophobic moment for the protein structure may be determined. A score for the protein structure may then be generated using the scoring function. The scoring function may represent an integral of the normalized second-order hydrophobic moment. The scores may be generated for a plurality of protein structures. The scores generated for the plurality of protein structures may then be compared.

Abstract: A molecular orbital computing device, method, program, and a recording medium recorded with the program, capable of computing electronic states at a high speed by an elongation method, are provided.

Abstract: A method of calibrating an ion trap having electrodes to which main RF trapping and resonant ejection voltages are applied comprises: identifying, for each of a plurality of ion types having different respective mass-to-charge ratios, an optimum resonant ejection voltage amplitude at which a mass peak quality is optimized when the ion trap mass analyzer is operated at a selected scan rate; determining a best-fit function of the form Vreseject=mc(a+bm), where Vreseject and m represent resonant ejection voltage amplitude and mass-to-charge ratio and a, b and c are constants; identifying, for each of a plurality of ion types, a respective RF voltage amplitude at which ions of each respective type are ejected from the ion trap using a resonant ejection voltage calculated according to the best-fit function; and determining a second best-fit function relating the identified trapping voltage amplitudes to mass-to-charge; ratio.

Abstract: The present invention provides a Sortilin crystal and methods for growing said crystal. The invention furthermore provide methods for design of specific ligands based on the crystal structure of Sortilin. The present invention also relates to the preparation and use of such ligands for the preparation of a medicament for the treatment of disease, damage or disorders of the central and peripheral nervous systems.

Abstract: The overall material constant of a composite material is computed where the composite material includes multiple kinds of material components in a matrix phase, each of the material constants of the material components and the matrix phase being known. First, for the composite material, an equation, having the material constant of a virtual composite material as an unknown, is prepared by defining the virtual composite material in which each of the material components is dispersed in a form of spherical particles in the matrix phase at a known volume fractions. Next, the overall material constant of the virtual composite material is found as the overall material constant of the composite material by solving the equation. In this case, the equation is a recursive equation which is obtained using the self-consistent method. The volume fraction of a material component in the composite material is computed using the equation.

Abstract: A method of characterizing an object includes determining a depth-wise composition of the object at a measurement site within the object. A property of the object within a region adjacent to the measurement site can, optionally, be estimated based on the determining. Another method of characterizing an object includes disposing at least a portion of an object within a measurement region of a metrology tool, aligning a feature of the object and a location of a designated measurement site within the measurement region relative to each other, and performing a performing a compositional analysis of a portion of the object occupying the measurement site. Various apparatus for performing these methods are also disclosed, as are methods of monitoring manufacturing processes based on these methods.

Abstract: The present invention relates to a fuel identification system and method normally applied to internal combustion engine vehicles of the flex-fuel type by means of which it is possible to identify the composition of the fuel used at each point in time, particularly the ratio used in a gasoline/ethanol blend or detect the presence of air or fuel in the vapor state in the fuel line, using the same device that heats the fuel.

Abstract: A mass spectrometer is disclosed wherein an ion signal is split into a first and second signal. The first and second signals are multiplied by different gains and are digitised. Arrival time and intensity pairs are calculated for both digitised signals and the resulting time and intensity pairs are combined to form a high dynamic range spectrum. The spectrum is then combined with other corresponding spectra to form a summed spectrum.

Abstract: The invention is a process for finding the accurate masses of subfragments comprising an unknown compound from the accurate-mass mass spectral data of the unknown compound obtained on a mass spectrometer. This process generates these accurate masses of subfragments using mass differences of fragment ions and a listing of plausible masses. In this way, the accurate masses of subfragments, useful for generating modular structures, can be obtained very rapidly.

Abstract: Disclosed is a method for determining the quality, expressed in terms of a quality value, of an biomolecule sample, based on measured data of the biomolecule sample, by extracting a number of prescribed features from the measured data using data analysis, and determining the quality value from the extracted features using a quality algorithm.

Abstract: Systems and methods are provided for defining a nucleic acid construct for integration at locus L of an organism. Nucleic acid requests are received, each such request specifying a genetic change to L. The request are expanded into component polynucleotides which are then arranged into {AR1, . . . , ARm} different arrangements, each ARi in {AR1, . . . , ARm} defining a different arrangement of the component polynucleotides. A score Si for each ARi in {AR1, . . . , ARm} is determined based on whether source constructs encoding a portion ofARi are physically present. An ARf in {AR1, . . . , ARm} is selected based on the score for ARf. Primer pairs are calculated to amplify the portions of ARf not represented in the source constructs. The portions of ARf amplified by the primer pairs and the portions of ARf in the source constructs, ordered by ARf, define the nucleic acid construct.