Abstract: The present invention relates to the detection of a target nucleic acid sequence by a PTOCE (PTO Cleavage and Extension) assay. The present invention detects a target nucleic acid sequence in which the PTO (Probing and Tagging Oligonucleotide) hybridized with the target nucleic acid sequence is cleaved to release a fragment and the fragment is hybridized with the CTO (Capturing and Templating Oligonucleotide) to form an extended duplex, followed by detecting the presence of the extended duplex. The extended duplex provides signals (generation, increase, extinguishment or decrease of signals) from labels indicating the presence of the extended duplex and has adjustable Tm value, which are well adoptable for detection of the presence of the target nucleic acid sequence.

Abstract: A method for manufacturing a biochip is provided. First, a first self-assembled monolayer is coated on a substrate. Next, a plurality of first biomedical molecular dots are formed on the first self-assembled monolayer by micro-titration technique. After the bonding reaction between the first biomedical molecular point and the first self-assembled monolayer, a second self-assembled monolayer is deposited on the surface of the first self-assembled monolayer by evaporation. The second self-assembled monolayer attached on the plurality of first biomedical molecular dots and the first self-assembled monolayer not bonded to the substrate are removed, so that the first biomedical molecular dots immobilized on the first self-assembled monolayer are exposed. Finally, a second biomedical molecular layer is immobilized on the exposed portions of the first biomedical molecular dots.

Abstract: The present invention overcomes the inadequacies inherent in the known methods for generating libraries of antibody-encoding polynucleotides by specifically designing the libraries with directed sequence and length diversity. The libraries are designed to reflect the preimmune repertoire naturally created by the human immune system, with or without DH segments derived from other species, and are based on rational design informed by examination of publicly available databases of antibody sequences.

Abstract: Provided is a surface having metal regions and an interstitial region having a composition that differs from the metal regions, wherein a continuous gel layer coats the surface across the metal regions and the interstitial regions. Nucleic acids or other analytes can be attached to the continuous gel layer such that a greater amount is attached over the metal regions than over the interstitial region. Also provided are methods for making such surfaces. Methods are also provided for making an array of nucleic acids or other analytes using such surfaces.

Abstract: A microarray is designed capture one or more molecules of interest at each of a plurality of sites on a substrate. The sites comprise base pads, such as polymer base pads, that promote the attachment of the molecules at the sites. The microarray may be made by one or more patterning techniques to create a layout of base pads in a desired pattern. Further, the microarrays may include features to encourage clonality at the sites.

Abstract: A metering device, a metering element, and a method for operating same, the metering element having a storage container open on one side for receiving the substances to be metered and a plunger which is axially movable and reversibly seals the opening of the storage container and which preferably has at least one centrally located metering opening for metering the substances provided in the storage container, the plunger including a separation device for particles.

Abstract: A custom-made matrix suitable for receiving a tissue sample is described as well as the use thereof to obtain a multiplex histological preparation. The invention also relates to a multiplex biopsy array comprising tissue and/or cell samples arranged in a matrix material and to a method for the preparation of a multiplex biopsy array. Methods for preparing blocks of matrix material to be used in multiplex biopsy arrays are also described, as well as methods for loading biopsy samples in said blocks, and methods for treating and processing said blocks to form biopsy arrays. The biopsy arrays made using the block of matrix material can be used to prepare sections and slides for histological procedures, including quantitative analyses and parallel processing.

Abstract: Highly specific and novel methods for reversible hydrazone solid-phase extraction (rHSPE) are provided for glycan or glycopeptide isolation from proteins, peptides, and other contaminants for glycan and glycopeptide analysis. Glycans or glycopeptides in complex mixtures can be conjugated onto solid support or affinity or chemical tags via reversible hydrazone bond. The conjugation methods of the present invention are chemically specific and provide unique means for the removal of other non-glycan containing molecules in the complex sample before the glycans or glycopeptides are hydrolyzed and recovered for analysis. The hydrazone formation and hydrolysis of the novel methods allows for the analysis of glycans and glycopeptides. The hydrazide coating on the solid-phase surfaces are useful for surface glycan capture and on target glycan analysis. Uses of the information generated by the inventive methods for diagnosis and treatment are also disclosed.

Abstract: Disclosed are methods, compositions and kits related to making double-tagged DNA libraries from RNA/DNA samples. A double-tagged oligonucleotide (DTO) is employed to efficiently add two different tags to ends of DNAs to make a double-tagged DNA libraries. Also disclosed are methods to make mate pair libraries using the double-tagged oligonucleotide, and methods to make double-tagged single stranded DNA. The double-tagged DNA libraries of the invention are ready to be used on next generation sequencing machines.

Abstract: The invention provides methods of introducing diversity into antibody molecules comprising introducing or substituting at least one amino acid sequence in the CDR of the target antibody together with at least one amino acid in the FW region spanning the 3 amino acid adjoining the CRD on each side. The resulting diverse antibodies with variant CDRs and FW region sequences comprising diverse amino acid sequences are also described. These polypeptides regions, herein referred to as 3+CDR3+, that form the gist of the invention contribution described herein provide a flexible and simple source of sequence diversity that can be used as a source for expressing and identifying diverse antibodies or antigen binding polypeptides. Libraries comprising a plurality of these polypeptides are also provided. In addition, methods of and compositions for generating and using these polypeptides and libraries are provided.

Abstract: The present invention provides methods and systems for discretized, combinatorial processing of regions of a substrate such as for the discovery, implementation, optimization, and qualification of new materials, processes, and process sequence integration schemes used in integrated circuit fabrication. A substrate having an array of differentially processed regions thereon is processed by delivering materials to or modifying regions of the substrate.

Abstract: Provided herein are methods of integrating one or more exogenous nucleic acids into one or more selected target sites of a host cell genome. In certain embodiments, the methods comprise contacting the host cell genome with one or more integration polynucleotides comprising an exogenous nucleic acid to be integrated into a genomic target site, and a nuclease capable of causing a double-strand break near or within the genomic target site.

Abstract: Provided are novel types of hybrid cyclic libraries that contain a known protein binding domain of a natural product. Also provided are synthetic methods to make such libraries and methods for the deconvolution of hits using partially split-pooled library compounds. Such methods are applicable for use with the entire human proteome to screen such libraries that bind and for the identification of hits.

Abstract: The embodiments describe methods for controlling the particles generated when cleaning and drying a wafer in a spin rinse dryer (SRD) module. In some embodiments, the substrate surface is cooled by dispensing deionized (DI) water across the surface of the substrate, while the substrate rests on the SRD chuck. In addition, a method for controlling the particles generated when sleeves in a processing module or SRD contact a substrate surface during a clamping operation or when the sleeves are removed from the substrate surface is provided. A bottom edge or lip of the sleeves and/or the surface of the wafer contacting the sleeve is wetted during clamping/unclamping operations. Alternatively, the substrate may be wetted prior to clamping/unclamping operations.

Abstract: A testing device uses a selectively deformable substrate to capture and retain spherical beads for genetic experimentation. A method of fabricating the device is described in which a silicon substrate can be coated with a photosensitive, bio-compatible polymer for photolithographic patterning using a single mask exposure. The polymer is patterned with a matrix of wells, each well capable of expansion to accept placement of a bead in the well, and contraction to secure the bead in the well. The polymer can exhibit piezoelectric properties that cause it to respond mechanically to a selected electrical excitation.

Abstract: Provided are methods of diagnosing an early immune activation by detecting T-cell immune response cDNA 7 (TIRC7); in particular, TIRC7 as an early biomarker for the detection of transplant rejection in a non-invasive diagnostic methods is described that replaces biopsy intervention with a simple diagnostic method for monitoring after transplantation and furthermore, kits for uses in such methods of diagnosis are provided.

Abstract: An interface is provided for storing microfluidic samples in a nanoliter sample chip. A fluid access structure provides a fluid access region to a selected subset of sample wells from an array of sample wells. A fluid introduction mechanism introduces a sample fluid to the fluid access region so that the sample wells in the selected subset are populated with the sample fluid without the unselected sample wells being populated with the sample fluid.

Abstract: The present disclosure provides methods for producing expression constructs comprising linking a plurality of unlinked nucleic acids, including nucleic acid encoding a marker protein.

Abstract: The present invention provides novel processes for the large scale preparation of arrays of polymer sequences wherein each array includes a plurality of different, positionally distinct polymer sequences having known monomer sequences. The methods of the invention combine high throughput process steps with high resolution photolithographic techniques in the manufacture of polymer arrays.

Abstract: Described herein are engineered antibody constant domain molecules, such as CH2 or CH3 domain molecules, comprising at least one mutation, or comprising at least one complementarity determining region (CDR), or a functional fragment thereof, engrafted in a loop region of the CH2 domain. The CH2 domain molecules described herein are small, stable, soluble, exhibit little to no toxicity and are capable of binding antigen.

Abstract: The present invention concerns a protein mixture comprising at least a first fusion protein comprising a protein or protein fragment, and an interaction domain and a protein translocation sequence, which effects that the fusion protein upon expression in a bacterium is translocated through the cytoplasmic membrane in an essentially unfolded state and at least a second fusion protein comprising a protein or protein fragment, and an interaction domain and a protein translocation sequence which effects that the fusion protein is translocated through the cytoplasmic membrane upon expression in a bacterium in an essentially folded state, wherein the interaction domain of the first protein can bind to those of the second protein.

Abstract: The invention relates to a zinc finger polypeptide library in which each polypeptide comprises more than one zinc finger which has been at least partially randomized, and to a set of zinc finger polypeptide libraries which encode overlapping zinc finger polypeptides, each polypeptide comprising more than one zinc finger which has been at least partially randomized, and which polypeptide may be assembled after selection to form a multifinger zinc finger polypeptide.

Abstract: Arrays of single molecules and methods of producing an array of single molecules are described. Arrays with defined volumes between 10 attoliters and 50 picoliters enable single molecule detection and quantitation.

Abstract: The present invention provides methods and systems for discretized, combinatorial processing of regions of a substrate such as for the discovery, implementation, optimization, and qualification of new materials, processes, and process sequence integration schemes used in integrated circuit fabrication. A substrate having an array of differentially processed regions thereon is processed by delivering materials to or modifying regions of the substrate.

Abstract: Disclosed are methods for design and synthesis of siRNA libraries, siRNA libraries produced thereby, siRNA molecules, and uses thereof.

Abstract: Disclosed herein are systems for monitoring chemical reactions. The systems can comprise a lighting device, a camera device for obtaining an image of the chemical reaction mixtures and an analyzer program to process data obtained from the image. Also disclosed are methods of monitoring the progress of chemical reactions using these systems.

Abstract: A system and method of increasing productivity of OLED material screening includes providing a substrate that includes an organic semiconductor, processing regions on the substrate by combinatorially varying parameters associated with the OLED device production on the substrate, performing a first characterization test on the processed regions on the substrate to generate first results, processing regions on the substrate in a combinatorial manner by varying parameters associated with the OLED device production on the substrate based on the first results of the first characterization test, performing a second characterization test on the processed regions on the substrate to generate second results, and determining whether the substrate meets a predetermined quality threshold based on the second results.

Abstract: In a process of fabricating a tissue array, a tissue block is sliced to obtain sheet-form pieces of tissue, and each of the sheet-form pieces is closely rolled around a guide member to form a spiral shape tissue around the guide member. Then, the spiral shape tissues are inserted in an axial direction into holes arrayed in a base block.

Abstract: Provided herein is a set of reagents comprising: a plurality of at least three probe libraries, wherein each library of the plurality comprises one or more probe sets that are each specific for a target; and at least one of the libraries comprises a probe set that is present in another of the libraries. The plurality of libraries can be hybridized to spatially separated targets, simultaneously or sequentially. The identity of a spatially separated target can be determined by identifying which combination of the multiple libraries hybridize thereto.

Abstract: In a process of fabricating a tissue array, a tissue block is sliced to obtain sheet-form pieces of tissue, and each of the sheet-form pieces is closely rolled around a guide member to form a spiral shape tissue around the guide member. Then, the spiral shape tissues are inserted in an axial direction into holes arrayed in a base block.

Abstract: A method of modulation of synthesis capacity on and cleavage properties of synthetic oligomers from solid support is described. The method utilizes linker molecules attached to a solid surface and co-coupling agents that have similar reactivities to the coupling compounds with the surface functional groups. The preferred linker molecules provide an increased density of polymers and more resistance to cleavage from the support surface. The method is particularly useful for synthesis of oligonucleotides, oligonucleotides microarrays, peptides, and peptide microarrays. The stable linkers are also coupled to anchor molecules for synthesis of DNA oligonucleotides using on support purification, eliminating time-consuming chromatography and metal cation presence. Oligonucleotides thus obtained can be directly used for mass analysis, DNA amplification and ligation, hybridization, and many other applications.

Abstract: Described microfluidic technology focused on: 1) direct integration of microfluidic devices with solidified liquid tissue samples, 2) subordination of architectural and operational principles of microfluidic devices specific tissue structure and needs and/or 3) on-chip sample acquisition integrated with the detection measurement within the same device. In contrast to conventional methods of off-chip sample prep and subsequent insertion into a detection device, new applications are possible on solidified liquid or solid tissue samples, such as in situ PCR.

Abstract: A novel N-acetyl-5-N,4-O-carbonyl-protected dibutyl sialyl phosphate donor for sialylation of both primary and sterically hindered secondary acceptors to prepare sialosides with high yield and ?-selectivity is disclosed. Methods for making disaccharide building blocks comprising ?(2?3), ?(2?6), ?(2?8), ?(2?8)/?(2?9) alternate, and ?(2?9) sialosides are provided. methods for one-pot synthesis of complex sialosides are disclosed. Libraries of sialosides and methods for using the libraries for detection and receptor binding analysis of surface glycoproteins or pathogens and cancer cells are disclosed. Methods for distinguishing between hemagglutinin (HA) from various strains of influenza are provided.

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 invention provides a method of forming a plurality of re-constitutable doses of at least one drug in a plurality of wells, the method including the steps of (i) placing a known amount of said drug in a suitable carrier to form a first composition having a known concentration (ii) placing at least two selected amounts of that first composition into individual wells and (iii) converting the first composition into a transportable form that can later be converted into a second composition having a known concentration and (iv) sealing the wells.

Abstract: The present invention relates to methods for increasing the diversity of monoclonal antibodies produced against an antigen. The methods of the invention utilize immunization of a murine host defective in one or more enzymes involved in a post-translational modification of a polypeptide or a modification of a lipid, wherein said modification is exposed on a cell surface. The invention also relates to monoclonal antibodies produced by these methods and which are not produced when a normal mouse is immunized with the same antigen. The invention further relates to compositions comprising these monoclonal antibodies, as well as to such monoclonal antibodies bound or conjugated to a toxin, a detectable marker or to a solid support.

Abstract: Disclosed are methods of for constructing a bead-displayed library of oligonucleotide probes (or sequence-modified capture moieties such as protein-nucleic acid conjugates) by ligation of a capture probe, having an analyte-specific sequence, to an anchor probe that is attached, at its 5?-end, (or possibly at the 3? end) to an encoded carrier such as a color-coded microparticle (“bead”). Such a library can also be constructed by elongation of an anchor probe, using a second probe as the elongation template, wherein the second probe has an anchor-specific subsequence and an analyte-specific subsequence.

Abstract: The disclosure relates to the genome-wide identification of “rearrangement hotspots”. The disclosure also relates to a microarray chip system for use in detecting genomic rearrangements and a method of manufacturing a microarray chip system useful for detecting genomic rearrangements. The disclosure also relates to methods for detecting genomic rearrangements associated with genetic diseases. The disclosure further relates to methods for using copy number variants in chromosome 2 for detecting Tourette Syndrome.

Abstract: Antibodies having dual specificity for two different but structurally related antigens are provided. The antibodies can be, for example, entirely human antibodies, recombinant antibodies, or monoclonal antibodies. Preferred antibodies have dual specificity for IL-1? and IL-1? and neutralize IL-1? and IL-1? activity in vitro and in vivo. An antibody of the invention can be a full-length antibody or an antigen-binding portion thereof. Methods of making and methods of using the antibodies of the invention are also provided. The antibodies, or antibody portions, of the invention are useful for detecting two different but structurally related antigens (e.g., IL-1? and IL-1?) and for inhibiting the activity of the antigens, e.g., in a human subject suffering from a disorder in which IL-1? and/or IL-1? activity is detrimental.

Abstract: Described herein are the preparation and use of novel bromo-phosphonomethylphenylalanine amino acid derivatives (BrPmp) and BrPmp-containing peptides as specific, irreversible protein tyrosine phosphatase inhibitors, which are suitable for application in peptide synthesis. These derivatives are particularly advantageous since their synthesis is both easy and scalable, and they are suitable for peptide synthesis. The BrPmp derivatives described herein can be appropriately protected to allow for solid phase peptide synthesis (SPPS) and incorporation into peptides for preparation of protein tyrosine phosphatase inhibitors and inhibitor libraries. The peptides and peptide libraries can be used to identify new protein tyrosine phosphatase specific sequences and profile protein tyrosine phosphatase activity in cell lysates, diagnostic samples and biopsy samples.

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 invention provides a method of identifying biologically active compounds comprising: (a) designing a first library of compounds of formula (1) to scan molecular diversity wherein each compound of the library has at least two pharmacophoric groups R1 to R5 as defined below and wherein compound of the library has same number of pharmacophoric groups; (b) assaying the first library of compounds in one or more biological assay(s); and (c) designing a second library wherein each compound of the second library contains one or more additional pharmacophoric group with respect to the first library; such that the/each component of the first and second library is a compound of formula (1).

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 provides methods for concentrating and pooling liquid suspensions of biological specimens containing analytes of interest in a dry state. The dried biological specimens containing analytes of interest are reconstituted and released from the matrix for subsequent analysis in concentrated form.

Abstract: The present invention provides novel algorithms for designing oligonucleotides that do not substantially hybridize to a small group of unwanted transcripts, while hybridizing to most other transcripts. Such oligonucleotides are particularly useful as primers for reverse transcription. The invention also provides compositions containing oligonucleotides that do not substantially hybridize to a small group of unwanted transcripts, while hybridizing to most other transcripts.

Abstract: The present invention provides methods and systems for discretized, combinatorial processing of regions of a substrate such as for the discovery, implementation, optimization, and qualification of new materials, processes, and process sequence integration schemes used in integrated circuit fabrication. A substrate having an array of differentially processed regions thereon is processed by delivering materials to or modifying regions of the substrate.

Abstract: The present disclosure is directed to methods and/or systems producing and providing uses sets of oligonucleotide conjugates for assays and detections and related systems and/or kits. Certain methods are directed to a method for detecting one or more biological targets of a sample in a detection assay, comprising: providing a molecular probe, comprising a binding moiety and an oligonucleotide sequence, to a sample comprising one or more biological targets; binding the one or more biological targets with the binding moiety; providing a detectable component to the sample, wherein the detectable component comprises a signal generating moiety conjugated to an oligonucleotide sequence complementary to the oligonucleotide sequence of the molecular probe; hydridizing the oligonucleotide sequence of the target-bound molecular probe to the detectable component; and detecting a signal generated from the hydridized detectable component. Various other embodiments, applications etc. are disclosed herein.

Abstract: The present invention provides methods and systems for discretized, combinatorial processing of regions of a substrate such as for the discovery, implementation, optimization, and qualification of new materials, processes, and process sequence integration schemes used in integrated circuit fabrication. A substrate having an array of differentially processed regions thereon is processed by delivering materials to or modifying regions of the substrate.

Abstract: The present invention refers to novel hetero-multimeric proteins obtained from modified ubiquitin capable of binding the extradomain B of fibronectin (ED-B) with high affinity. Furthermore, the invention refers to fusion proteins comprising said recombinant protein fused to a pharmaceutically and/or diagnostically active component. The invention is further directed to the use of said proteins in medical treatment methods.

Abstract: Methods for design of genetic circuits are provided.