Abstract: The invention provides methods of making designed and constructed protein (e.g., antibody) libraries and libraries resulting from the same.

Abstract: Disclosed herein are methods for identifying compounds for the treatment of viral infection, including RNA viral infection and uses of the compounds as pharmaceutical compositions. The identified compounds modulate the RIG-I pathway in vertebrate cells.

Abstract: The present invention relates to screening methods and, in particular, to methods of screening anti-ligands libraries for identifying anti-ligands specific for differentially and/or infrequently expressed ligands. The method comprises the steps of providing a library of anti-ligands; providing a first subtractor ligand; providing a second target ligand; determining the amount of the first and second target ligands using one or more equations derived from the universal law of mass action; providing the determined amount of a first subtractor ligand; providing the determined amount of a second target ligand; providing separation means capable of use to isolate anti-ligand bound to the second target ligand from anti-ligand bound to the first subtractor ligand; exposing the library of to the first and second target ligands to permit binding of anti-ligands to ligands; and using the separation means to isolate the anti-ligand bound to second target ligand.

Abstract: This invention is directed to the discovery of improved methods of preparing cyclic peptides, cyclic peptide esters, cyclic peptide amidines, and libraries of these compounds. The invention also includes uses of these compounds and libraries for screens as drugs and binders of biologics.

Abstract: The invention discloses methods and apparatus for characterizing trace nucleic acids that are biomarkers for disease. The methods and apparatus provide increased sensitivity to such trace nucleic acids, and allow analysis of nucleic acids present in a sample at only 0.01% of the wild-type sequences. The methods and apparatus are also designed for straightforward multiplexing, thus allowing pooling of clinical samples.

Abstract: The present invention provides the means for producing libraries of peptide structures for drug screening applications that are capable of folding or assuming their native conformations independently of artificial scaffolds or flanking sequences in the proteins from which they are derived. The libraries can be highly diverse such that they are representative of the repertoire of protein structures existing in nature. The libraries can also be non-redundant or normalized such that the bias towards specific structures existing in source data sets and/or in nature is/are removed. In a particularly preferred embodiment, the present invention provides 30,000 independent fold structures produced by this method. The present invention also provides computer-readable media and systems comprising structural data in relation to the peptide libraries, and methods for displaying and screening the libraries.

Abstract: The present invention provides a fibronectin type III (Fn3) molecule, wherein the Fn3 contains a stabilizing mutation. The present invention also provides Fn3 polypeptide monobodies, nucleic acid molecules encoding monobodies, and variegated nucleic acid libraries encoding such monobodies. Also provided are methods of preparing a Fn3 polypeptide monobody, and kits to perform the methods.

Abstract: The disclosure features methods for identifying antibodies that bind to a carbohydrate moiety. Libraries coding for antibodies that bind to a carbohydrate moiety are provided. The libraries can be provided by modifying a pre-existing nucleic acid library. Antibodies that bind to a carbohydrate moiety are described.

Abstract: Methods and compositions related to high mannose glycans are described.

Abstract: The present invention provides a method for enrichment and isolation of endogenous transcription factors and their complexes. Also, this invention provides corresponding tandem arrays of concatenated transcription factor response elements (catTFRE). The method employs the property of transcription factors binding to sequence-specific DNA elements during regulation of gene expression. The catTFREs are designed and synthesized as concatenate dual copies of DNA response elements for various transcription factors. The DNA sequence of synthesized catTFRE is cloned to a target vector. Biotinylated catTFRE with 200 bp arms is prepared by PCR strategy. For enrichment and isolation of endogenous transcription factors and their complexes, the biotinylated catTFRE is immobilized to streptavidin-coated magnetic beads and then incubated with nuclear extract. Thereby endogenous transcription factors and their complexes are isolated from nuclear extract.

Abstract: Provided herein is a library that comprises a plurality of molecular beacons (MBs), each MB having a detectable label, a detectable label blocker and a modifier group. The library is used in conjunction with nanopore unzipping-dependent sequencing of nucleic acids.

Abstract: A method for high throughput screening of probes is described. These probes are useful for characterization and measurement of unbound metabolites in a fluid sample, particularly characterization and measurement of levels of unbound free fatty acids. By practice of the disclosed invention, a profile of unbound metabolites can be determined for an individual which can be used to determine the individual's relative risk for disease such as stroke, cardiac disease and cancer.

Abstract: A method for producing libraries of structurally and stereochemically diverse molecules that can be screened for biological or chemical activity. A library of 91 heterocyclic compounds composed of 16 distinct scaffolds was synthesized through a sequence of phosphine-catalyzed ring-forming reactions, Tebbe reactions, Diels-Alder reactions, and, in some cases, hydrolysis to illustrate the methods. Three compounds inhibiting migration of human breast cancer cells are identified from the library.

Abstract: A microfluidic flow cell for removably interfacing with a removable-member for performing a reaction therebetween. The microfluidic flow cell device comprises at least one reaction portion defining with the removable-member a reaction chamber when in an interfaced position thereof. The microfluidic flow cell comprises at least one fluid-receiving portion for receiving a fluid therein and being in fluid communication with the reaction chamber. When the microfluidic flow cell and the removable-member are in the interfaced position, the cell is adapted to allow for the fluid in the fluid-receiving portion to flow to the reaction chamber. Devices, systems and methods comprising this microfluidic flow cell are also disclosed.

Abstract: Techniques for differentiating isobaric species are described. An isobaric species may be substituted with a tagging species identified using mass spectrometry. The isobaric species may be a subunit of a first polymer having a defined sequence, e.g., the isobaric species may be an amino acid in a protein or a peptide sequence. A tagging species may be substituted for the isobaric species in a second polymer having an otherwise identical sequence as the first polymer. The second polymer may have the same number of sequences as the first polymer, and substantially the same sequence of subunits, with a few exceptions such as the tagging species for the isobaric species. The first polymer and the second polymer may be prepared in the same reaction vessel. A polymer/protein of defined subunit sequence containing an isobaric species or a tagging species may be analyzed by mass spectrometry to determine the sequence.

Abstract: The invention provides methods for quantitatively analyzing a plurality of analytes in a sample. Also described are general and specific internal standards useful in such analysis. In particular embodiments, these standards are described as useful in liquid chromatography/mass spectroscopy systems, which are also described herein. Moreover, in certain embodiments, the quantification methods of the present invention are useful in increasing the precision and/or accuracy of multiple analyte quantification for analytes contained in a single sample mixture using known analyte derivatives simultaneously analyzed, and compared to the unknown analytes.

Abstract: The invention relates to a method for quantitatively identifying relevant HLA-bound peptide antigens from primary tissue specimens on a large scale without labeling approaches. This method can not only be used for the development of peptide vaccines, but is also highly valuable for a molecularly defined immunomonitoring and the identification of new antigens for any immunotherapeutic strategy in which HLA-restricted antigenic determinants function as targets, such as a variety of subunit vaccines or adoptive T-cell transfer approaches in cancer, or infectious and autoimmune diseases.

Abstract: The present invention relates to multiplexed assays for the diagnosis of RANTES-based disorders. Essentially, a single, high information content RANTES assay is used to simultaneously determine an individual's disposition towards a disease as well as the onset and progression of the disease (or response to treatment). As such, the (single) analysis has the particular advantage of always producing data useful in the longitudinal monitoring (of individuals) for a disease. In specific example, the discovery relates RANTES isoforms with the predisposition, onset and progression of T2D, CHF, MI, and cancer. All isoforms of particular blood and urine borne proteins—containing protein phenotype data—are monitored in a single, high throughput analysis able to acquire data relevant to the stages of the disease (or treatment).

Abstract: The invention provides a combinatorial library, a method for preparation of that combinatorial library, a method for sequence identification, a method for sequencing the elements of combinatorial libraries of oligonucleotides and/or oligonucleotide analogues, the use of a linker to generate combinatorial libraries and a sequence identification set. More precisely, the objective of the invention is the ability to “read” sequences of selected elements of combinatorial libraries of freely modified synthetic oligonucleotides. The solution may be used both for researching for leading compounds in the pharmaceutical industry, and as a tool for studying the properties of oligonucleotides in the aspect of their potential use in experimental antisense or antigen therapy. The invention develops an appropriate strategy for determining the structure of isolated library elements, as usefulness of the combinatorial library depends on the ability to recognize the structure of its elements.

Abstract: The present invention relates to novel genetic markers associated with response of a patient with esophageal cancer (ECa) to chemoradiation therapy, and particularly to methods and kits for predicting an ECa patient's response to chemoradiation therapy by genotyping of the markers.

Abstract: The present invention relates to a plurality of isotopically labeled compounds (“tag isotopomers”) and individual labeled compounds, which are useful for labeling samples of analytes, such as biological compounds. The present invention further relates to methods of labeling and quantifying analytes using these tag isotopomers.

Abstract: The invention relates to novel methods of detecting alterations in cell cycle regulation in a cell or a cell population and screening for agents capable of modulating cell cycle regulation through the use of multiparameter assays and a fluorescence-activated cell sorter (FACS) machine.

Abstract: The present invention relates to a method for conversion of a target nucleic acid molecule according to a predetermined nucleotide code into a converted nucleic acid molecule. The converted nucleic acid molecule has utility for determining the nucleotide sequence of the target nucleic acid molecule, for example, using a nanopore.

Abstract: In some embodiments, the invention relates to methods for creating a monoclonal antibody that specifically binds to antigen. The method may start from a polyclonal population of antibodies such as a non-specific polyclonal population or a polyclonal population of antibodies that specifically bind to the antigen. The method includes obtaining nucleic acid molecules encoding heavy and light immunoglobulin chains (or variable regions thereof) of multiple immunoglobulins from an animal; obtaining mass spectra information of peptide fragments of a population of polyclonal immunoglobulins that specifically bind to an antigen of choice; comparing and/or correlating the mass spectra information of the peptide fragments of the polyclonal immunoglobulins with predicted mass spectra information of predicted amino acid sequences encoded by the nucleic acid molecules, and then assembling the heavy and light chains to create an antibody (or variable region thereof) that specifically binds to the antigen.

Abstract: The present invention relates generally to a methodology for the isolation, purification and identification of peptide ligands presented by MHC positive cells. In particular, the methodology of the present invention relates to the isolation, purification and identification of these peptide ligands from soluble class I and class II MHC molecules which may be uninfected, infected, or tumorgenic. The methodology of the present invention broadly allows for these peptide ligands and their comcomittant source proteins thereof to be identified and used as markers for infected versus uninfected cells and/or tumorgenic versus nontumorgenic cells with said identification being useful for marking or targeting a cell for therapeutic treatment or priming the immune response against infected cells.

Abstract: The invention relates, in part, to the improved analysis of carbohydrates. In particular, the invention relates to the analysis of carbohydrates, such as N-glycans and O-glycans found on proteins and saccharides attached to lipids. Improved methods, therefore, for the study of glycosylation patterns on cells, tissue and body fluids are also provided. Information from the analysis of glycans, such as the glycosylation patterns on cells, tissues and in body fluids, can be used in diagnostic and treatment methods as well as for facilitating the study of the effects of glycosylation/altered glycosylation. Such methods are also provided. Methods are further provided to assess production processes, to assess the purity of samples containing glycoconjugates, and to select glycoconjugates with the desired glycosylation.

Abstract: The present invention is useful in screening for biomarkers associated with any other disease or condition. Such diseases and conditions range from the neurological diseases, autoimmune diseases and cancers identified above as well as any other disease or condition that has a biomarker such as an antibody or other characterizing protein or biomolecule associated with the disease or progression of the disease. The large ligand libraries of the invention can be used directly in biological fluid, under the appropriate experimental conditions and according to the processes recited herein, to screen for such markers and without the need to use fewer support members (e.g. about 100,000 or less) or without the need to transfer such peptoids or ligands to a microarray before screening the biological fluid. In addition, the ligand libraries may also be used to screen for cell based receptors that specifically relate to a particular cell surface marker.

Abstract: The invention relates to an isolated plant GDSL-lipase polypeptide differentially expressed between the different steps of the plant development and/or the different tissues of the plant, a nucleic acid molecule encoding it, and a plant or part of plant genetically engineered to not express it at least partially.

Abstract: Immunogenic Escherichia coli O157:H7 (0157) proteins expressed during infection of a mammal, are described. In particular, 0157 proteins expressed specifically in vivo during human and cattle infection were identified. These proteins, mapped to the backbone, O-islands (OIs) and pO157. Because these-proteins are expressed during infection, and might help pathogens adapt to and counter hostile in vivo environments, those proteins identified in this study are useful as targets for drug and vaccine development. Also, such proteins are useful as markers of 0157 infection in stool specimens. Also described are methods of identifying immunogenic proteins.

Abstract: The invention provides compositions and methods for prevention and treatment of diseases associated with ?-amyloid formation and/or aggregation. Such methods encompass the induction of an immune response against N-terminal truncated and/or post-translationally modified A? peptides. These peptides are further used in compositions and methods for the diagnosis of diseases associated with ?-amyloid formation and/or aggregation.

Abstract: This invention provides methods and systems for identifying and typing toxicity of chemical compositions, as well as for screening new compositions for toxicity. The invention involves detecting alterations in gene or protein expression and hence establishing molecular profiles in isolated mammalian LSCs contacted with various chemical compositions of known and unknown toxicities, and correlating the molecular profiles with toxicities of the chemical compositions.

Abstract: Disclosed here is a method for measuring the kinetics (i.e., the molecular flux rates—synthesis and breakdown or removal rates) of a plurality of proteins or organic metabolites inn living systems. The methods may be accomplished in a high-throughput, large-scale automated manner, by using existing mass spectrometric profiling techniques and art well known in the fields of static proteomics and static organeomics, without the need for additional biochemical preparative steps or analytic/instrumental devices.

Abstract: The Wnt signaling pathways are involved in embryo development as well as in tumorigenesis. Dishevelled (Dvl) tranduces Wnt signals from the receptor Frizzled (Fz) to downstream components in canonical and non-canonical Wnt signaling pathways, and the Dvl PDZ domain plays an essential role in both pathways, and the Dvl PDZ domain binds directly to Fz receptors. In the present invention using NMR-assisted virtual ligand screening, several compounds were identified and were found to bind to the Dvl PDZ domain. Molecular dynamics simulation was used to analyze the binding between the PDZ domain and these compounds in detail. These compounds provide a basis for rational design of high-affinity inhibitors of the PDZ domain, which can block Wnt signaling by interrupting the Fz-Dvl interaction.

Abstract: The invention relates to genotyping and blood cell antigen determination. In particular, the invention addresses discriminating the RHD*DIIIa-CE(4-7)-D or RHD*DIIIa-CE(4-7)-D)-like blood type variants, from RHD*DIIIa, RHD*DIVa-2 and other blood type variants. The invention provides methods for genotyping a subject, comprising: a) determining at least 4 markers in a sample that has been obtained from the subject, wherein the markers comprise: (i) the presence or absence of an RHCE*C allele; (ii) the presence or absence of an RHD/RHCE hybrid exon 3 (RHD/CE Hex03) allele; (iii) the absence of, or a single nucleotide polymorphism (SNP) variant within, any one of position 602 of exon 4, position 667 of exon 5, or position 819 of exon 6 of RHD; and (iv) the absence of, or SNP variant within, position 1048 of RHD exon 7. The invention also provides probes, primers and kits for use in such methods.

Abstract: The invention provides a method for diagnosing amyotrophic lateral sclerosis (ALS) in a subject, a method for assessing the effectiveness of a drug in treating ALS, and a method for determining the site of onset of ALS in a subject. Each method comprises (a) obtaining a sample from the subject, (b) analyzing the proteins in the sample by mass spectroscopy, and (c) determining a mass spectral profile for the sample. In some embodiments, the method comprises comparing the mass spectral profile of the sample to the mass spectral profile of a positive or a negative standard.

Abstract: A system and method for imaging biological samples on multiple surfaces of a support structure are disclosed. The support structure may be a flow cell through which a reagent fluid is allowed to flow and interact with the biological samples. Excitation radiation from at least one radiation source may be used to excite the biological samples on multiple surfaces. In this manner, fluorescent emission radiation may be generated from the biological samples and subsequently captured and detected by detection optics and at least one detector. The detected fluorescent emission radiation may then be used to generate image data. This imaging of multiple surfaces may be accomplished either sequentially or simultaneously. In addition, the techniques of the present invention may be used with any type of imaging system. For instance, both epifluorescent and total internal reflection methods may benefit from the techniques of the present invention.

Abstract: Provided is an improved method for the detection of specific polymorphic alleles in a mixed DNA population. The method comprises enriching the relative percentage of a given polymorphic allele that is exponentially amplifiable by PCR. Also provided are methods for selectively enriching target nucleic acid, for example, fetal nucleic acid in a maternal sample. In the case of detecting fetal nucleic acid in a maternal sample, a restriction enzyme is introduced that can discriminate between the alleles of a polymorphic site. Preferably, the maternal allele is digested and nucleic acid comprising the paternal allele is relatively enriched.

Abstract: The present invention provides screening kits, compositions, and diagnostic methods for determining whether a subject has a predisposition to, or likelihood of having, a substance use disorder by determining a nucleic acid methylation profile from a biological sample from the subject, wherein a given profile indicates that the subject has a predisposition to a substance use disorder.

Abstract: The present invention provides oligonucleotide constructs, sets of such oligonucleotide constructs, and methods of using such oligonucleotide constructs to provide validated sequences or sets of validated sequences corresponding to desired ROIs. Such validated ROIs and constructs containing these have a wide variety of uses, including in synthetic biology, quantitative nucleic acid analysis, polymorphism and/or mutation screening, and the like.

Abstract: Methods for synthetic antibodies, methods for making synthetic antibodies, methods for identifying ligands, and related methods and reagents.

Abstract: This document provides methods and materials for determining the identity of the terminal nucleotide (e.g., the 3? terminal nucleotide) of a nucleic acid molecule. For example, methods and materials for using RNA-DNA chimeric primers during a primer extension reaction followed by treatment with one or more RNAse enzymes to prepare nucleic acid molecules that can be analyzed to identify the terminal nucleotides added to the RNA-DNA chimeric primers during the primer extension are provided.

Abstract: The present invention relates among others 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: Disclosed herein are compositions and methods of identifying a subject at risk for preterm birth and selecting effective therapies for preventing preterm birth in the subject. The disclosed methods generally involve determining the identity of one or more nucleotides in the progesterone receptor (PR) gene of the subject.

Abstract: The present invention provides a method for detecting mutations in the PALB2 gene in pancreatic cancer patients and in individuals having a family history of pancreatic cancer. Methods are also provided for diagnosing a predisposition to pancreatic cancer, for predicting a patient's response to pancreatic cancer therapies, and for treating pancreatic cancer, based on presence of a PALB2 mutation or abberant PALB2 gene expression in a patient.

Abstract: The present invention relates to expression cassettes libraries of expression vectors comprising the same, wherein each vector comprises at least one gene of interest and a promoter operatively linked thereto wherein each promoter comprises a nucleic acid, whose sequence is randomly mutated with respect to that of another in the library and cells comprising the same. Methods utilizing either the libraries or cells of this invention, in optimizing gene expression, protein expression, or optimized gene or protein delivery are described.

Abstract: Methods and systems for obtaining and processing optical signal data from analytical reactions, and in processing signal data from arrays of sequence-by-incorporation processes to identify nucleotide sequences of template nucleic acids and larger nucleic acid molecules, e.g., genomes or fragments thereof are described. Defining and applying a 2-dimensional software mask allows for obtaining signal data from arrays with higher signal to noise than where the mask is not applied.

Abstract: Provided herein are optimized methods for performing multiplexed detection of a plurality of sequence variations. Also provided are methods for performing multiplexed amplification of target nucleic acid.

Abstract: Isolated polynucleotides and polypeptides and recombinant DNA constructs useful for improving agronomic traits, compositions (such as plants or seeds) comprising these recombinant DNA constructs, and methods utilizing these recombinant DNA constructs. The recombinant DNA construct comprises a polynucleotide operably linked to a promoter that is functional in a plant, wherein said polynucleotide encodes a GSH1 polypeptide.

Abstract: The present invention relates to a method for immobilizing nucleic acids on a support, comprising the provision of a nucleic acid with a stretch of nucleotides of only one basetype and the immobilization of said nucleic acid on a support by crosslinking by light, wherein said crosslinking by light is performed at a wavelength of about 300-500 nm, preferably at a wavelength of 365 nm. The present invention further relates to a method for the analysis of nucleic acids immobilized according to the invention, which comprises the hybridization of the immobilized nucleic acid with complementary and mismatch segments. Furthermore, the present invention relates to immobilized nucleic acids obtainable by the method of the invention, the use of accordingly immobilized nucleic acids for the production of nucleic acid arrays and a diagnostic kit, comprising an array of nucleic acids which are immobilized according to the present invention.

Abstract: The present invention provides methods of obtaining structural information about a biopolymer sample. The methods include labeling portions of a biopolymer, such as DNA or RNA, linearizing the biopolymer in some cases, and determining the distance between the labels. The user can then compare different samples' between-label distances to qualitatively compare different samples and to assay a given sample for additions or deletions of nucleotides in the regions flanked by the labels. The methods also permit sequencing of biopolymers.