Abstract: This invention pertains to methods for generating large quantities of DNA security markers by combinatorial variation techniques using polymorphic fragment length DNA for unique identification security marker applications such as explosive ink used in dye/smoke pack and cash carrying boxes.

Abstract: Disclosed herein is a method for the preparation of oligonucleotide microarrays obviating the drawbacks to an extent, such as time consuming complex chemical reactions, preparation of modified supports/oligomer modifying reagents, use of activating/condensing reagent, low signal to noise ratio, poor immobilization and hybridization efficiencies, etc. Further, the prepared arrays can be used to detect single or multiple nucleotide mismatches using hybridization assay.

Abstract: The present invention relates generally to the field of diagnostic and detection assays. More particularly, the present invention provides methods and reagents including biochips for detecting the presence of, or distinguishing between, one or more analytes in a sample.

Abstract: Methods and systems for identifying and selecting nucleic acid probes for detecting a target with a nucleic acid probe array or comparative genome hybridization microarray, comprising selecting a plurality of potential target sequences, generating a plurality of candidate probes from the target sequences, filtering the plurality of candidate probes by analyzing candidate probes for selected probe properties in silico. Microarrays comprising probes selected by the methods of the invention are particularly useful for comparative genome hybridization and location analysis.

Abstract: The present invention relates generally to methods for producing normalized nucleic acid libraries in which each member of the library can be isolated with approximately equivalent probability. In particular, the present methods comprise subtractive hybridization of a nucleic acid library with haptenylated (e.g., biotinylated, avidinated or streptavidinated) nucleic acid molecules that are complementary to one or more of the nucleic acid molecules of the library, such that the variation in the abundances of the individual nucleic acid molecules in the library is reduced. The invention also relates to production of normalized nucleic acid libraries (particularly cDNA libraries) in which contaminating nucleic acid molecules have been reduced or eliminated, and to normalized nucleic acid libraries produced by such methods.

Abstract: Provided herein are sets of mass labels. Each mass label in a set includes: 1) a mass marker moiety; 2) a mass normalization moiety; and 3) a cleavable linker connecting the mass marker moiety to the mass normalization moiety. Each mass marker moiety is characterized as having a mass different from that of all other mass marker moieties in the set as determined by mass spectrometry. Further, each mass normalization moiety ensures that each mass label in the set has substantially the same mass as determined by mass spectrometry.

Abstract: A sensor for detecting the presence of predetermined chemical/biological molecules, the sensor having a MOSFET device (2, 3, 6, 7, 9, 10, 12, 13), the gate having an array of nanoscale fingers (6,7), and on fingers or in spaces between the fingers, chemical/biological receptor molecules (15) suitable for selectively binding with the predetermined chemical/biological molecules, the sensor also having circuitry (4, 5, 11, 12) for measuring a change in a change in drain current of the FET caused by the predetermined chemical/biological molecules becoming bound to the receptor molecules. Sensitivity and reliability can be increased compared to capacitive sensors.

Abstract: Genomic imprinting is a parent of origin-dependent gene silencing that involves marking of alleles in the germline and differential expression in somatic cells of the offspring. Imprinted genes and abnormal imprinting have been implicated in development, human disease, and embryonic stem cell transplantation. We have established a model system for genomic imprinting using pluripotent 8.5 d.p.c. mouse embryonic germ (EG) cell lines derived from an interspecific cross. We find that allele-specific imprinted gene expression has been lost in these cells. However, partial restoration of allele-specific silencing can occur for some imprinted genes after in vitro differentiation of EG cells into somatic cell lineages, indicating the presence of a gametic memory that is separable from allele-specific gene silencing. We have also generated a library containing most methylated CpG islands.

Abstract: A series of methods that utilize the incremental truncation of nucleic acids are described to create a plurality of modified nucleic acids and hybrid polypeptides. A plurality of substantially all possible single base-pair deletions of a given nucleic acid sequence is created. A method of making shuffled incremental truncated nucleic acids, which is independent of nucleic acid sequence homology, is also described. These methods can be used in protein engineering, protein folding, protein evolution, and the chemical synthesis of novel hybrid proteins and polypeptides.

Abstract: The present invention aims to develop a method for specimen preparation, which ensures the maintenance of both tissue morphology and nucleic acid quality (particularly RNA quality). The present invention further aims to prepare a specimen by this method, from which desired cells are then collected by microdissection and analyzed for gene expression. A method for specimen preparation from various frozen or unfrozen organs or tissues (excluding hard tissues) of the whole body, which comprises the following steps: 1) fixing a target organ or tissue with PFA fixative; and 2) embedding the same in paraffin by the AMeX method.

Abstract: Luminescent reporter compounds that are rotaxanes having the structure where B—Z—C is a reporter molecule based on a cyanine, squaric acid, or other reporter, and K is a macrocycle that encircles and interlocks with the reporter molecule. Applications of the reporter compounds are provided, as well as reactive intermediates used to synthesize the reporter compounds, and methods of synthesizing the reporter compounds.

Abstract: Provided herein are sets of mass labels. Each mass label in a set includes: 1) a mass marker moiety; 2) a mass normalisation moiety; and 3) a cleavable linker connecting the mass marker moiety to the mass normalisation moiety. Each mass marker moiety is characterized as having a mass different from that of all other mass marker moieties in the set as determined by mass spectrometry. Further, each mass normalization moiety ensures that each mass label in the set has substantially the same mass as determined by mass spectrometry.

Abstract: The present invention relates to novel methods for sequencing and mapping genetic markers in polynucleotide sequences using Type-IIs restriction endonucleases. The methods herein described result in the “capturing” and determination of specific oligonucleotide sequences located adjacent to Type-IIs restriction sites. The resulting sequences are useful as effective markers for use in genetic mapping, screening and manipulation.

Abstract: A protein scaffold based on a consensus sequence of the tenth fibronectin type III (FN3) repeat from human fibronectin, including isolated nucleic acids that encode a protein scaffold, vectors, host cells, and methods of making and using thereof have applications in diagnostic and/or therapeutic compositions, methods and devices. In particular, protein scaffold molecules binding to IgG based on the consensus sequence have been identified as useful for diagnostic and/or therapeutic applications.

Abstract: Methods of amplifying nucleic acid on a solid support are described. Beads and template, each in known concentrations, are employed so a range of template to bead ratios can be exploited. Where the beads contain primers, the template can be amplified. After amplification, non-covalently bound template is removed, so as to leave beads with extended primers (or beads with primers that were not extended).

Abstract: A method for manufacturing synthetic genes and combinatorial DNA and protein libraries, termed here Divide and Conquer-DNA synthesis (D&C-DNA synthesis) method. The method can be used in a systematic and automated way to synthesize any long DNA molecule and, more generally, any combinatorial molecular library having the mathematical property of being a regular set of strings. The D&C-DNA synthesis method is an algorithm design paradigm that works by recursively breaking down a problem into two or more sub-problems of the same type. The division of long DNA sequences is done in silico. The assembly of the sequence is done in vitro. The D&C-DNA synthesis method protocol consists of a tree, in which each node represents an intermediate sequence. The internal nodes are created in elongation reactions from their daughter nodes, and the leaves are synthesized directly. After each elongation only one DNA strand passes to the next level in the tree until receiving the final product.

Abstract: The present invention provides methods for cancer detection and diagnosis. The present invention provides a method of selectively amplifying hypomethylated tumor DNA sequences derived from a subject for detection of cancer. This method utilizes differential methylation to allow for the selective amplification of tumor specific sequences from DNA mixtures that contain a high proportion of normal host DNA. The invention also provides methods of using the amplified tumor DNA sequences for evaluation of methylation.

Abstract: Methods and compositions for diagnosing and treating Noonan syndrome and neoplastic disorders are provided herein.

Abstract: The present invention provides a method for identifying a modulator or mediator of a biological activity, which activity includes antigenicity and or immunogenicity, said method comprising the step of: (i) producing a gene fragment expression library derived from defined nucleotide sequence fragments; and (ii) assaying the expression library for at least an amino acid sequence derived from step (i) for a biological activity wherein that activity is different from any activity the amino acid sequence may have in its native environment.

Abstract: A protein scaffold based on a consensus sequence of fibronectin type III (FN3) proteins, such as the tenth FN3 repeat from human fibronectin (human Tenascin), including isolated nucleic acids that encode a protein scaffold, vectors, host cells, and methods of making and using thereof have applications in diagnostic and/or therapeutic compositions, methods and devices. In particular, protein scaffold molecules binding to IgG have been identified as useful for diagnostic and/or therapeutic applications.

Abstract: The present invention relates to a method of pooling samples to be analyzed for a categorical variable, wherein the analysis involves a quantitative measurement of an analyte, said method of pooling samples comprising providing a pool of n samples wherein the amount of individual samples in the pool is such that the analytes in the samples are present in a molar ratio of x0:x1:x2:x(n?1), and wherein x is equal to a positive value other than 1 representing the pooling factor.

Abstract: An array is formed with a protective cover on a substrate. The protective cover is patterned to produce an array of openings to the substrate. Desired material is deposited on the substrate through the openings. The protective cover may then be removed. In one embodiment, the protective cover is a conformal polymer, such as di-para-xylylene. It may be removed by mechanical peeling. The material may be biological material such as DNA. The protective cover may be used to prevent non-specific hybridization in inter-spot regions by performing hybridization with the cover still in place. Hybridization that occurs in such regions between the spots may be removed with removal of the protective cover.

Abstract: This invention is in the field of homeostasis analysis. More particularly, it relates to systems and methods for analyzing persistent homeostatic perturbations, i.e. chronic stress, by measuring levels of biomarkers that are related to chronic stress. This invention is also directed to systems and methods for analyzing the molecular mechanisms of chronic stress.

Abstract: The invention provides biomolecule binding ligands, collections of biomolecule binding ligands, and their use in the purification of biological mixtures and in the identification of ligands having an affinity for a substance.

Abstract: A method for production of a chemical library is provided, where the method involves: reacting, in a single vessel, a) a plurality, x, of aldehydes and/or ketones; and b) either (i) a plurality, y, of nucleophiles, (ii) a plurality, z, of electrophiles or both (i) and (ii); in the presence of c) a cascade catalyst capable of catalyzing reaction between said plurality of aldehydes and/or ketones and said plurality of nucleophiles, said plurality of electrophiles or both; to obtain a mixture of x-y ?-nucleophile substituted aldehydes and/or ketones, xz ?-electrophile substituted aldehydes and/or ketones or xyz ?-nucleophile substituted, ?-electrophile substituted aldehydes and/or ketones; and the chemical libraries thus produced.

Abstract: Embodiments of the present invention relate to a buffer composition for an integrated nucleic acid amplification and hybridization reaction. The buffer comprise about 50-20 OmM of a salt, about 10-30 mM Tris-HCI, about 2-10M Water soluble magnesium salt, about 0.05-1.5% surfactant, about 0.05-0.15 mg/ml stabilizing protein about 50-300 nM of one or more primers, about 20-15 OuM of one or more dNTPs, about 5-15% glycerine, about 0.5-1.5% formamide and at least about 5 unit/ml polymerase.

Abstract: The present invention provides novel peptidomimetic macrocycles and methods for their preparation and use, as well as amino acid analogs and macrocycle-forming linkers, and kits useful in their production.

Abstract: Methods of recombining nucleic acids, including homologous nucleic acids, are provided. Families of gene shuffling oligonucleotides and their use in recombination procedures, as well as polymerase and ligase mediated recombination methods are also provided.

Abstract: The present disclosure describes scFv antibody libraries, antibodies isolated from the libraries, and methods of producing and using the same.

Abstract: The disclosure relates to methods for modulating plant growth and organogenesis using dominant-negative receptor-like kinases.

Abstract: Fluorescence Labelling This invention generally relates to techniques for fluorescence labelling, and to methods, apparatus and computer program code for processing fluorescence signal data. A method of determining respective first and second degree-of-labelling signals for different respective first and second fluorophores associated with a common entity, the method comprising: determining a first fluorescence signal from said first and second fluorophores under first conditions; determining a second fluorescence signal from said first and second fluorophores under second conditions different to said first conditions; and determining said first and second degree-of-labelling signals for said first and second fluorophores from said first and second fluorescence signals; and wherein said determining of said first and second degree-of-labelling signals is responsive to at least one coupling value (c12; c21) representing a coupling of energy between said fluorophores.

Abstract: A protein scaffold based on a consensus sequence of the tenth fibronectin type III (FN3) repeat from human fibronectin, preferably human Tenascin, that binds to human TNF? including isolated nucleic acids that encode a protein scaffold, vectors, host cells, and methods of making and using thereof have applications in diagnostic and/or therapeutic compositions, methods and devices.

Abstract: Immunoglobulin libraries are provided that contain randomly assembled FR1, CDR1, FR2, CDR2, FR3, CDR3 and FR4 sequences of heavy or light chain immunoglobulin variable regions. The libraries exhibit a degree of repertoire diversity not found in natural immune systems and can be used to express novel immunoglobulins. The libraries can be used for screening antibodies with the target specificity of interest. The resultant antibodies can be fully human and non-immunogenic.

Abstract: A biochip substrate which is free from cross-contamination due to spot spreading or contact with spots adjacent to each other, and a biochip using the same. A biochip substrate on which multiple valleys for immobilizing biological substances are formed so as to prevent cross-contamination due to spot spreading or contact with spots adjacent to each other, and a biochip using the same are provided. Moreover, it is found out that a desired binding in a target molecule contained in a test sample occurs at a detectable level in a solution system even in the case where a valley have such a small capacity as 1 nL to 10 nL.

Abstract: The present invention relates to arrays comprising between 2 and 12.000 nucleic acid molecules, comprising a first set of nucleic acid molecules that comprise a nucleotide sequence that is able to hybridize to a gene that is used for normalization. The array may further comprise a second set of nucleic acid molecules that comprise nucleic acid sequences capable of hybridizing to nucleic acid molecules that are expressed in clinical relevant samples such as, for example, breast tissue. The invention further relates to a method for normalizing data. Further provided are methods of using an array according to the invention for distinguishing clinical samples.

Abstract: The present invention is directed to a method for the generation of binding proteins derived from the protein super-family of ubiquitin like proteins with modifications in their alpha helical region as well as to a protein obtainable by said method. Furthermore, the invention provides the use of a protein for the specific recognition, binding and neutralization of a predescribed target molecule, for the detection, quantitative determination, separation and/or for the isolation of a corresponding binding partner and the use of a protein of the invention, for diagnosis, prophylaxis and treatment of diseases in which the corresponding binding partner is directly or indirectly involved.

Abstract: The invention provides polynucleotide vectors and linkers and methods for designing and making single chain variable fragment (“ScFv”) libraries. The invention also provides polynucleotide vectors and linkers and methods for reformatting the ScFv library into Fab and IgG formats for high throughput production and screening.

Abstract: A method for electrochemical removal of acid-labile protecting groups on an electrode microarray using an organic solution is disclosed. The solution comprises a hydrazine derivative and a salt in an organic solvent. The hydrazine derivative has at least one hydrazine group having at least one hydrogen. The hydrazine derivative provides acidic reagent when an electrode is active and isolates the acidic reagent to the area around the active electrode. The salt is an organic salt or ionic liquid having a concentration sufficient to provide electrochemical conductivity under an applied voltage. During the applied voltage, acidic reagent is generated, which removes acid-labile protecting groups thereby allowing continued addition of monomers to build a custom microarray of oligonucleotides, peptides, or other polymers.

Abstract: The invention describes a method for the synthesis of compounds comprising the steps of: (a) compartmentalizing two or more sets of primary compounds into microcapsules; such that a proportion of the microcapsules contains two or more compounds; and (b) forming secondary compounds in the microcapsules by chemical reactions between primary compounds from different sets. The invention further allows for the identification of compounds which bind to a target component of a biochemical system or modulate the activity of the target, and which is co-compartmentalized into the microcapsules.

Abstract: The present invention relates to a recombinant binding protein comprising at least one derivative of the Src homology 3 domain (SH3) of the FYN kinase, wherein at least one amino acid in or positioned up to two amino acids adjacent to the src loop and/or at least one amino acid in or positioned up to two amino acids adjacent to the RT loop is substituted, deleted or added. Furthermore, the invention is directed to fusion proteins comprising a binding protein according to the invention fused to a pharmaceutically and/or diagnostically active component. In addition, the invention concerns nucleotides coding for these binding and/or fusion proteins as well as corresponding vectors and host cells. Last but not least, the present invention relates to the use of binding and/or fusion proteins of the present invention for preparing a medicament or a diagnostic means as well as to pharmaceutical or diagnostic compositions comprising said binding and/or fusion proteins.

Abstract: A method is provided for constructing, identifying and using new therapeutic or diagnostic proteins capable of binding to a target cell. The new proteins are derived by mutating a binding subunit of a wild type heteromeric cytotoxic protein to create a library of microorganism clones producing mutant proteins which are then screened for their ability to specifically bind to and kill a target cell.

Abstract: Compositions and methods are provided for generating three frame cDNA expression libraries for functional screening of proteins. The invention includes sets of 5? adapters for cloning cDNA molecules in which the sets include three adapters that can be used to clone a particular cDNA in all three reading frames. The libraries so generated have greater complexity of expressed open reading frames, and thus can improve the success of functional protein screens, such as two hybrid screens. The adapters also have recombination sites for efficient cloning and transfer between systems.

Abstract: New modifiers were synthesized for incorporation of a methacrylic function in 3?-, 5?- and internal positions of oligonucleotides during solid phase synthesis. A modifier was used for synthesis of 5?-methacrylated oligonucleotides for preparation of microarrays by a co-polymerization method.

Abstract: The present invention in one aspect relates to a method for synthesizing a bifunctional complex comprising a molecule and an identifier polynucleotide identifying at least some of the chemical entities which have participated in the synthesis of the molecule in accordance with the methods of the present invention. The invention also relates to a library of different bifunctional complexes. The library of the invention can be used e.g. for identifying drug leads. Furthermore, the present invention is based on the principle that chemical entities initially provided on a building block oligonucleotide (i.e. a building block having an oligonucleotide part which is linked to a chemical entity) can be brought into reactive proximity without the use of a template comprising a set of covalently linked codons.

Abstract: A data processing method for an estimation of compound-protein interaction using both chemical substance information, such as a chemical property of the compound, and biological information, such as sequence information of genes to rationally and efficiently screen compounds. First space representing space coordinates of a first chemical substance group and second space representing space coordinates of a second chemical substance group are defined, and the first chemical substance group is characterized by a first characteristic amount and the second chemical substance group is characterized by a second characteristic amount, and map transformation of the coordinates of the first space and the coordinates of the second space results in the solution so as to increase the correlation between the first space and the second space using a multivariable analysis technique or a machine learning method.

Abstract: Computer processing methods and/or systems for minimizing and/or optimizing data strings in accordance with rules and options. Minimized data strings can represent data sequences important in certain biologic analyses and/or syntheses. In specific embodiments, a request is generated by a user at a client system and received by a server system. The server system accesses initial data indicated or provided by the client system. The server system then performs an analysis to minimize the data needed for further reactions. In specific embodiments, a server can use proprietary methods or data at the server side while protecting those proprietary methods and data from access by the client system.

Abstract: The present invention provides solid supports comprising a surface bound array of dendrons and methods for using the same.

Abstract: The present disclosure relates to methods for efficient synthesis, cloning, transformation and screening of large diverse libraries of polynucleotide variants comprising well-defined nucleotide differences relative to a reference polynucleotide.

Abstract: [Task] A process of fabricating a tissue array block; a process of fabricating a tissue array sheet; a tissue array block; a tissue array chip; a system of fabricating a tissue array block; and a system of fabricating a tissue array sheet are proposed, in which the tissue array block can be fabricated even in the case of that having a small thickness, is little affected by tissue hardness and, when having been processed into a tissue array chip, does not suffer any defect in a piece of tissue or at a site of interests, enables the collection of pieces of tissue from a dispersed area, also enables the establishment of positional relationship between the inside of a tissue piece and the inside of a tissue block, and scarcely affects the utilization of the tissue block remaining after collecting the pieces of tissue. [Solving Means] A tissue block B1 is sliced to fabricate roll-shaped pieces of tissue t2. Then, the roll-shaped tissue pieces t2 are inserted into a base block B2 to give a tissue array block B3.

Abstract: Provided herein are methods for generating diverse polypeptide and nucleic acid molecule libraries and collections, and the collections and libraries; methods for selecting variant polypeptides and nucleic acid molecules from the libraries; and molecules selected from the libraries. Exemplary of the polypeptides and nucleic acid molecules are antibodies and nucleic acids encoding the antibodies (including antibody fragments and domain exchanged antibodies). Also provided herein are methods of displaying polypeptides such as antibodies, for example on the surface of genetic packages, such as phage; and libraries and collections of the displayed polypeptides and vectors for producing the displayed polypeptides, libraries and collections. Exemplary of the displayed antibodies are domain exchanged antibodies.