Abstract: The present invention involves a multicomponent protein microarray comprising two or more components of a protein-based system entrapped within spots of a biomolecule compatible matrix arranged on a surface. Also included are methods of using the microarray for multicomponent analysis along with kits and machinery comprising the microarray.

Abstract: The present invention is directed to the preparation and use of a collection of antibody heavy chain complementarity determining region 3 (HCDR3) members, where diversity of the collection is a function of the length of the HCDR3 members. The diversity of the collection of HCDR3 regions substantially represents the natural amino acid distribution of HCDR3 in the human repertoire. This natural amino acid distribution can be represented by biasing the complete random distribution of amino acids, accordingly, in the HCDR3 encoding DNA sequence by using trinucleotide mutagenesis (TRIM) technology. A collection of HCDR3 members of the invention each can be comprised within a variable region of an antibody (or fragment thereof) to form a library of synthetic antibodies or antibody fragments. The invention also provides nucleic acid molecules encoding such diverse collection and methods of making and using the same.

Abstract: Methods are described to derive design sequences for the production of nucleic acid microarrays. The present methods use high throughput 3? sequencing of transcripts in a tissue sample or diseased state to design probes for nucleic acid microarrays. Also described are nucleic acid microarrays that possess probes directed to the extreme 3? end of transcripts in a tissue. These microarrays preferably represent alternate polyadenylation sequences that are specific to the tissue from which the transcripts are derived. Also described are methods of using the microarrays directed to the extreme 3? end of the transcript for evaluating gene expression in a tissue where there are reduced false positive and false negative results.

Abstract: This invention relates to conjugate probes and optical detection of analytes. More specifically, this invention relates to conjugate probes which are used to form an array for a biosensor employing optical detection of analytes.

Abstract: The present invention provides methods of producing libraries of compounds with enhanced desirable properties and diminished side effects as well as the compounds produced by the methods. In preferred embodiments, methods of the present invention use a universal chemical glycosylation method that employs reducing sugars and requires no protection or activation. In a preferred embodiment, the invention provides a library of neoglycoside digitoxin analogs that includes compounds with significantly enhanced cytotoxic potency toward human cancer cells and tumor-specificity, but are less potent Na+/K+-ATPase inhibitors in a human cell line than digitoxin.

Abstract: The present invention relates to a gene discovery system and gene expression systems specific for genes encoding ARE-containing mRNAs. In one aspect, the present invention relates to computational methods of selecting coding sequences of ARE-genes from databases using a one or more ARE search sequences. The ARE search sequences are from 10 to 80 nucleotides in length and comprise a sequence which is encompassed by one of the following two sequences: (a) WU/T(AU/TU/TU/TA)TWWW, SEQ ID NO. 1, wherein none or one of the nucleotides outside of the parenthesis is replaced by a different nucleotide, and wherein W represents A, U, or T; and (b) U/T(AU/TU/T/U/T)n, SEQ ID NO. 2 wherein n indicates that the search sequence comprises from 3 to 12 of the tetrameric sequences contained within the parenthesis. The method comprises extracting from the databases, those nucleic acids whose protein coding sequences are upstream and contiguous with a 3? untranslated region (UTR) that comprises one of the ARE search sequences.

Abstract: The present invention relates to artificial receptors, arrays or microarrays of artificial receptors or candidate artificial receptors, methods of and compositions for making them, and methods of using them. Each artificial receptor includes a plurality of building block compounds. In an embodiment, at least one of the building blocks includes a tether moiety. The tether can provide spacing or distance between the recognition element and the support or scaffold to which the building block is immobilized. A tether moiety can have any of a variety of characteristics or properties including flexibility, rigidity or stiffness, ability to bond to another tether moiety, and the like.

Abstract: The present invention relates to artificial receptors and arrays or microarrays of artificial receptors or candidate artificial receptors. Each member of the array includes a plurality of building block compounds, typically immobilized in a spot on a support. The present invention also includes the building blocks, combinations of building blocks, arrays of building blocks, and receptors constructed of these building blocks together with a support. The present invention also includes methods of making and using these arrays and receptors.

Abstract: The present invention provides nucleic acid arrays and methods of using the same for detecting gene expression in animal models of osteoarthritis or other inflammatory diseases. The nucleic acid arrays of the present invention comprise polynucleotide probes for genes that are differentially expressed in osteoarthritis-affected cartilage tissues as compared to non-osteoarthritic cartilage tissues. In one embodiment, a nucleic acid array of the present invention comprises a plurality of polynucleotide probe sets, each of which is capable of hybridizing under stringent or nucleic acid array hybridization conditions to a different respective tiling sequence selected from Table C, or the complement thereof.

Abstract: The biosensor comprises a modular biorecognition element and a modular flexible arm element. The biorecognition element and the flexible arm element are each labeled with a signaling element. The flexible arm contains an analog of an analyte of interest that binds with the biorecognition element, bringing the two signaling elements in close proximity, which establishes a baseline fluorescence resonance energy transfer (FRET). When an analyte of interest is provided to the biosensor, the analyte will displace the analyte analog, and with it, the signaling module of the modular flexible arm, causing a measurable change in the FRET signal in a analyte concentration dependent manner. The modularity of different portions of the biosensor allows functional flexibility. The biosensor operates without additional development reagents, requiring only the presence of analyte or target for function.

Abstract: Anti-angiogenic peptides that inhibit VEGF-mediated activation or proliferation of endothelial cells are disclosed. Such peptides may be used to inhibit VEGF binding to the VEGFR2 receptor (also known as the kinase domain receptor or KDR). Such peptides may also be used to inhibit VEGF-mediated activation of endothelial cells in angiogenesis-associated diseases such as cancer, inflammatory diseases, eye diseases and skin disorders.

Abstract: The present invention provides a biological substance-immobilized gel which comprises a gel containing 2%-7% by mass of N,N-dimethylacrylamide and a biological substance immobilized on and/or in the gel.

Abstract: The present invention relates to a gene discovery system and gene expression systems specific for genes encoding ARE-containing mRNAs. In one aspect, the present invention relates to computational methods of selecting coding sequences of ARE-genes from databases using aone or more ARE search sequences. The ARE search sequences are from 10 to 80 nucleotides in length and comprise a sequence which is encompassed by one of the following two sequences: (a) WU/T(AU/TU/TU/TA)TWWW, SEQ ID NO. 1, wherein none or one of the nucleotides outside of the parenthesis is replaced by a different nucleotide, and wherein W represents A, U. or T; and (b) U/T(AU/TU/T/U/T)n, SEQ ID NO. 2, wherein n indicates that the search sequence comprises from 3 to 12 of the tetrameric sequences contained within the parenthesis. The method comprises extracting from the databases, those nucleic acids whose protein coding sequences are upstream and contiguous with a 3?untranslated region (UTR) that comprises one of the ARE search sequences.

Abstract: The present invention pertains to methods related to cloning nucleic acids from biological samples, particularly pathological tissue samples. This method includes hybridizing a population of oligonucleotide sequence probes comprising degenerate sequence tags to a fixed tissue, isolating the hybridized oligonucleotide sequence probes and amplifying the sequence tags in the hybridized oligonucleotide sequence probes. This method can be utilized to identify genes associated with disease and to quantitate the expression of disease-related transcripts. The method can also be used to identify truncated mRNAs.

Abstract: Ex-vivo isolated human CD25+CD4+ T regulatory cells, CD25+CD4+ Tr cell clones derived therefrom, a method of isolating clones and the use of ex-vivo isolated human CD25+CD4+ Tr cells or cell-clones as immunomodulators, immunosuppressive agents or for the identification of molecules that modulate the immune response.

Abstract: The invention relates to materials and methods for diagnosis and treatment of chronic fatigue syndrome/myalgic encephalitis. A number of genes are identified which are expressed at abnormal levels in patients affected by CFS/ME as compared to normal healthy individuals. These genes include those encoding defensin ?1, haemoglobin ?, CXCR4, tubulin beta 1, serine/threonine kinase 17B, HLA DRss4 and prostaglandin D2 synthase. The genes identified provide objective disease markers that may be used in diagnostic tests to support the diagnosis of CFS/ME or for monitoring the effectiveness of therapy. They also provide a rational basis for classifying CFS/ME patients according to the biochemical lesion underlying their symptoms and enable provision of appropriate targeted therapies.

Abstract: The invention relates to the detection or prediction of metastases of head and neck squamous cell carcinoma (HNSCC) with the use of gene expression profiles. A gene signature has been identified which is able to detect or predict the occurrence of these metastases better than current clinical methods. Part of the invention are micro-arrays comprising this signature and methods for performing the detection and/or prediction.

Abstract: The present invention provides methods and compositions for performing multi-step nucleic acid mediated synthesis of a highly diverse collection of molecules, for example, small molecules and polymers. In the method, in at least two steps, multiple reaction intermediates and/or products are produced in the same step by different chemical reactions.

Abstract: A high throughput preparation of a plurality of different lubricating oil compositions for combinatorial libraries and subsequent high throughput screening for lubricant performance is provided. The methods can advantageously be optimized using combinatorial chemistry, in which a database of combinations of lubricating oil compositions are generated. As market conditions vary and/or product requirements or customer specifications change, conditions suitable for forming desired products can be identified with little or no downtime.

Abstract: A combinatorial lubricating oil composition library is provided including at least a plurality of different lubricating oil compositions comprising (a) a major amount of a base oil of lubricating viscosity and (b) at least one lubricating oil additive. Methods for preparing same are also provided.

Abstract: Aspects of the invention relate to the design and synthesis of nucleic acid libraries containing non-random mutations or variants. Aspects of the invention provide methods for assembling libraries containing high densities of predetermined variant sequences. Certain embodiments relate to the design and synthesis of nucleic acid libraries that express a predetermined polypeptide from a library of nucleic acids having silent sequence variants. Certain embodiments relate to the design and synthesis of nucleic acid libraries that express predetermined RNA variants that encode the same polypeptide sequence.

Abstract: Early developing stage-specific liver proteins and the genes coding for them that have been isolated and sequenced are provided, and these genes and proteins can be utilized to diagnose and/or treat a wide variety of liver disorders and other ailments. Since the early developing liver proteins of the invention arise during embryogenesis when the liver and other organs are in transition from an undifferentiated state to a differentiated one, these proteins are involved in tissue differentiation and thus can be utilized in methods of diagnosing and treating a variety of liver diseases and other disorders including those relating to oncogenesis and tissue repair. Antibodies recognizing early developing liver proteins and peptides are also provided.

Abstract: A nucleotide molecule comprising a selectable gene flanked by anL1 and anL2 attachment sites of a bacteriophage and additionally comprising an origin of replication. This can be used to create a baculovirus-based gene library.

Abstract: The present application pertains to products and methods related to the ability of short nucleotide oligomers to bind the tertiary or globular structure of nucleic acids. This application discloses libraries of short oligomers and methods for using these libraries.

Abstract: The invention provides compounds of general formulae I-IV or pharmaceutically acceptable salts thereof: The invention also provides methods of preparing the compounds, pharmaceutical compositions comprising the compounds and use of the compounds for the preparation of medicaments intended to modulate the activity of one or more members of the G-protein coupled receptor (GPCR) class. Compounds of the invention may be used to create a compound library for use in screening for agents which modulate signalling through GPCRs.

Abstract: A method of inducing transposition in a transgenic embryo, sperm and egg is described, comprising the steps of (a) generating a first adult transgenic organism comprising within its genome one or more copies of a transposon; (b) generating a second adult transgenic organism comprising within its genome one or more copies of a gene encoding a transposase cognate for the transposon and/or a sequence capable of regulating expression of the gene encoding the transposase; (c) crossing the first adult transgenic organism with the second transgenic adult organism to provide a progeny which comprises, in the genome of one or more of its cells, both (i) one or more copies of the transposon and (ii) a gene encoding a transposase cognate for the transposon, wherein the gene encoding the transposase is under the control of one or more inducible regulatory sequences which permit expression of the transposase, and (d) expressing the gene encoding the transposase in the embryo, sperm or egg to cause mobilisation of the tran

Abstract: A method of producing a chemical compound library comprises extracting at least one extract from at least one species of plant; processing at least one of the extract(s) to remove at least one type of chemical interference to produce a processed extract; chromatographically separating the processed extract into a plurality of chromatographic fractions, each containing an amount of chemical compounds; determining the amount of chemical compounds in at least one of the chromatographic fractions; and normalizing the chromatographic fractions in which the amounts were determined to produce normalized chromatographic fractions, each such fraction comprising from about 1 microgram to about 500 micrograms of each of from one to seven chemical compounds that were present in lower concentrations in the extract and that each have a log P of from about ?1 to about 5 and a molecular weight less than about 1000 Daltons; thereby to produce a chemical compound library from at least one species of plant.

Abstract: The aim of the invention is to investigate the bonding of substances to target molecules. This is achieved by means of a densely packed device wherein various target molecules are bonded in a large number of sample areas. Cross-contamination and evaporation need to be minimized. The active surface of the sample areas have to be maximized. The inventive solution resides in the use of carrier plates, containing densely packed capillary structures and having a very large inner surface despite small outer dimensions. 1000 times more molecules can be bonded than on a flat outer surface of a comparable size. Cross contamination is avoided by the lack of cross links between the capillaries. Evaporation is minimized by a small outer surface. After the inner surface of the capillaries has been silanized, peptides and peptidomimetics are synthesized in a locally targeted manner.

Abstract: The present invention includes a method and composition of storing and preserving biofilms for input and output of high-density information. One form of the present invention is a fabricated biofilm storage device with a biologic material applied to a substrate to form, e.g., a dry thin film stable at room temperature for extended periods of time. Another form of the present invention is a method of fabricating a biofilm storage device in which a biologic material is applied to a substrate under conditions that promote alignment of the biologic material on the substrate. The composition, method, and kit of the present invention have universal application in biologics, magnetics, optics and microelectronics.

Abstract: A method for the isolation of CDRs in a defined framework that is stable and soluble in reducing environment is described as well as thus obtainable scFv. Starting from such scFv with defined framework a scFv library can be generated wherein the framework is conserved while at least one complementary determining region (CDR) is randomized. Such library, e.g. in yeast cells, is suitable for screening for antibody/CDR-interactions or for screening for antibodies.

Abstract: The present invention relates to a method of producing new chemical entities comprising the steps of: (i) taking a chemical entity as the template to prepare a molecularly imprinted polymer (MIP), (ii) removing the template from the MIP, (iii) using the specific binding sites of the MIP to direct, or facilitate, the syntheses of new chemical entities for the generation of compound libraries using molecularly imprinted polymers, and to a use of such compound libraries.

Abstract: The invention relates to a device for applying a plurality of microdroplets to a substrate (65) comprising a plate (50) provided with a plurality of bore holes (51) and a bottom (52) which is connected to said plate (50), and is provided with a plurality of channels (53). The device is characterized in that each bore (51) of the plate (50) is assigned to a single channel (53) of the bottom (52). The invention also relates to a method for producing this device, the use of this device for applying a plurality of microdroplets to a substrate (65), as well as a method for applying a plurality of microdroplets to a substrate (65).

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 invention relates to a method of preparing a library of template polynucleotides with uniform sequence representation and to use of a library of templates prepared using this method for solid-phase nucleic acid amplification. In particular, the invention relates to a method of preparing a library of template polynucleotides which have common sequences at their 5? ends and at their 3? ends, which contains even representation of all the fragments present in a starting sample of nucleic acid before fragmentation. The invention is especially applicable to the preparation of short insert libraries, where the sample fragments are less than 150 base pairs in length.

Abstract: Methods for improving antibodies by a variety of DNA diversification and selection procedures are provided. Improvements include increases in affinity, alterations in specificity and effector function, as well as reduced antigenicity, e.g. humanization. Libraries of recombinant antibody sequences are provided, as are cells expressing members of such libraries. Novel phage display vectors are provided. Methods for the coevolution of an antibody and its cognate antigen are provided. Coevolution is used to evolve HIV envelope proteins with increased antigenicity and broadly neutralizing antibodies that interact therewith. Methods of improving antibodies for use in the detection of biological warfare agents are provided.

Abstract: The present invention is directed to designing a collection of protein variants.

Abstract: A system and method for the detection of an analyte using multiplexing of the sensing elements is described. In one embodiment, a sensor array includes sensing elements, and probes bound to one or more sensing elements. The sensor array is formed from a supporting member to which a plurality of sensing elements may be coupled. The sensing element may have a predefined shape, size or location. A signal may be produced when a target analyte interacts with a probe. In one embodiment, the identity of the target may be determined by the detection of the signals produced and the shapes of the sensing elements. Each analyte may be given a unique code that is represented by one or more sensing elements.

Abstract: A microarray includes a substrate, a plurality of fine particles disposed on the substrate at regular intervals, and a plurality probes coupled with the fine particles.

Abstract: A method of preparing a dispersion of polymeric particles is disclosed. Monomers are emulsion polymerized in the presence of an ionic monomer to produce highly charged polymeric particles. At least 50% of the ionic monomer in the dispersion is bound to the polymeric particles.

Abstract: A method for promoting the in vitro multiplication of human melanocytes and/or the freezing thereof, notably human melanocytes obtained from individuals of phototype IV, V or VI or from hyperpigmentary lesions entails introducing into a culture of same, a thus effective amount of at least one 1-phenyl-3-(2-thiazolyl)-2-thiourea (PTU) compound or PTU analogue or PTU mimetic selected from the group consisting of vitamin C, arbutin, hydroquinone, kojic acid or acid or ester derivative thereof, ellagic acid, aminophenol derivative, procysteine or derivative thereof, niacinamide, isothiocyanate, thiocyanate, lucinol and mixtures thereof; also provided thereby can be melanocyte libraries, co-cultures and reconstructed epidermides and/or reconstructed skin that are highly pigmented which are useful for the study of pigmentation disorders, for the screening of cosmetic or dermatological active agents, or for the treatment of skin lesions, in particular in individuals with a high phototype.

Abstract: The invention relates to a method of analysing molecular targets contained in a complex mixture, comprising the following steps consisting in: a) bringing the mixture of molecular targets to be analysed into contact with an array of different types of primary probes, whereby each type of primary probe forming the array can bind specifically to a type of target selected from among the molecular targets, under conditions that enable specific binding between the molecular targets and the primary probes; b) optionally eliminating the primary probes that are not bound specifically to a molecular target; c) separating the molecular targets and the primary probes which are bound specifically in a probe/target complex, such as to recover the array of primary probes representing a fingerprint of the molecular targets to be analysed; and d) quantitatively analysing the primary probes eluted in step c.

Abstract: The use of a selective chemical and bioorthogonal reaction providing a covalent ligation such as the Staudinger ligation, in targeted molecular imaging and therapy is presented, more specifically with interesting applications for pre-targeted imaging or therapy. Current pre-targeted imaging is hampered by the fact that it relies solely on natural/biological targeting constructs (i.e. biotin/streptavidin). Size considerations and limitations associated with their endogenous nature severely limit the number of applications. The present invention describes how the use of an abiotic, bio-orthogonal reaction which forms a stable adduct under physiological conditions, by way of a small or undetectable bond, can overcome these limitations.

Abstract: Methods for fabricating sublithographic, nanoscale microstructures in two-dimensional square and rectangular arrays utilizing self-assembling block copolymers, and films and devices formed from these methods are provided.

Abstract: Microdevices containing a predetermined preferential axis of magnetization are disposed in an array having discreet regions. Under influence of a magnetic field, the microdevices can have at least twelve discrete orientations, and can advantageously be flipped upside down in place. Microdevices can be coded in a manner that supports a coding space of at least 102, 103, 106 or even 1010 or more choices, and can include one or more chemically reactive sites. The regions can be defined by long and short bars, in which microdevices span gaps between the longer bars, and the shorter bars measure less than 60% of such gaps. Preferred embodiments are also provided to produce microfabricated microdevices for magnetic assembly-based arraying.

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: A method to make libraries of hybrid polynucleotide molecules of two parental polynucleotide molecules utilizing single-stranded DNA was invented. Example of the method comprises several steps: (i) preparation of two single-stranded polynucleotide molecules comprising sequences containing one or more parts of homology and one or more parts of heterology, (ii) random or non-random fragmentation of said polynucleotides, (iii) hybridization of the fragmented molecules followed by de novo polynucleotide synthesis (i.e. polynucleotide chain elongation) on the hybridized molecules, (iv) separation of the chain elongation products (i.e. double-stranded polynucleotide molecules) into single-stranded polynucleotide molecules (denaturation) (v) hybridization of the resultant single-stranded polynucleotide molecules followed by de novo polynucleotide synthesis on the hybridized molecules, and (vi) repeating at least two further cycles of steps (iv) and (v).

Abstract: The present invention provides a method for detecting and differentiating disease states with high sensitivity and specificity. The method allows for a determination of whether a cell-based sample contains abnormal cells and, for certain diseases, is capable of determining the histologic type of disease present. The method detects changes in the level and pattern of expression of the molecular markers in the cell-based sample. Panel selection and validation procedures are also provided.

Abstract: The invention relates to the field of molecular recognition or detection of discontinuous or conformational binding sites or epitopes corresponding to a binding molecule, in particular in relation to protein-protein protein-nucleic acid, nucleic acid-nucleic acid or biomolecule-ligand interactions. The invention provides a synthetic molecular library allowing testing for, identification, characterisation or detection of a discontinuous binding site capable of interacting with a binding molecule, the library having been provided with a plurality of molecules, each molecule of the molecules comprising at least one first segment linked to a second segment, each segment having the capacity of being a potential single part of a discontinuous binding site.

Abstract: A microarray includes a substrate, a siloxane resin layer represented by the following general formula 1 or 2 and includes a siloxane resin having a molecular weight of about 1,000 to about 10,000: where R1 and R2 are independently hydrocarbons having 1 to 30 carbon atoms and X1 and X2 are independently a hydroxyl, aldehyde, carboxyl amino, amide, thiol halo, or sulfonate group, and a plurality of oligomer probes coupled with the siloxane resin layer.

Abstract: A method of producing a chemical compound library comprises extracting at least one extract from at least one species of plant; processing at least one of the extract(s) to remove at least one type of chemical interference to produce a processed extract; chromatographically separating the processed extract into a plurality of chromatographic fractions, each containing an amount of chemical compounds; determining the amount of chemical compounds in at least one of the chromatographic fractions; and normalizing the chromatographic fractions in which the amounts were determined to produce normalized chromatographic fractions, each such fraction comprising from about 1 microgram to about 500 micrograms of each of from one to seven chemical compounds that were present in lower concentrations in the extract and that each have a log P of from about ?1 to about 5 and a molecular weight less than about 1000 Daltons; thereby to produce a chemical compound library from at least one species of plant.