Abstract: The present invention concerns combinatorial libraries of conformationally constrained polypeptide sequences and their uses. In particular, the present invention concerns combinatorial libraries of conformational epitopes and their uses.

Abstract: Methods for producing stem cell banks, preferably human, which optionally may be transgenic, e.g., comprised of homozygous MHC allele cell lines are provided. These cells are produced preferably from parthenogenic, IVF, or same-species or cross-species nuclear transfer embryos or by dedifferentiation of somatic cells by cytoplasm transfer. Methods for using these stem cell banks for producing stem and differentiated cells for therapy, especially acute therapies, and for screening for drugs for disease treatment are also provided.

Abstract: The invention generally relates to compositions and methods for designing and producing functional DNA binding effector molecules and associated customized services, tool kits and functional assays. In some aspects, the invention provides methods and tools for efficient assembly of customized TAL effector molecules. Furthermore, the invention relates to uses of TAL effector molecules and functional evaluation of such TAL by, for example, customized assays.

Abstract: The disclosure relates generally to the targeting of genes to, and their integration into, an immunoglobulin (antibody) heavy chain locus. In particular, the methods described herein contemplate replacing the single rearranged heavy chain V, D, and J genes of a B cell lymphoma such as DT40 with independently rearranged VH-D-JH genes of chicken, in a system for generating immunoglobulin diversity. Also contemplated is replacement of the chicken VH-D-JH with rearranged VH-D-JH genes of other vertebrates including human in a system for generating immunoglobulin diversity, with the exception of any substitution disclosed and claimed in PCT application WO 2009/029315 A2. Also described is construction of a diverse chicken immunoglobulin heavy chain VDJ library in DT40 by homologous gene replacement of the single endogenous rearranged VDJ gene with a chicken VDJ repertoire using the described targeting vectors.

Abstract: The present disclosure relates to novel triple tag sequences that may comprise a 6× histidine tag, a c-myc tag and a V5 tag. The present disclosure also provides polynucleotides, proteins, vectors and host cells that comprise the triple tag sequence of the present disclosure, including libraries of such polynucleotides, proteins, vectors and host cells. The novel triple tag sequences of the present disclosure may be used in phage display vectors and phage libraries and in methods for detection, screening, capture, purification, quantitation, and/or recovery of proteins of interest to which they are linked. Proteins of interest include antibodies such as single chain antibodies, single chain antibodies, and Fab fragments of antibodies or peptides such as non-antibody peptides.

Abstract: A sensor chip for detecting an immune response against a virus, the sensor chip including a substrate having a surface and a plurality of virus-like particles or capsid fragments bound to discrete locations on the surface of the substrate. Detection devices containing the sensor chip and methods of detecting anti-viral immune responses are also described herein.

Abstract: By using Escherichia coli which comprises a 16S rRNA derived from a heterologous organisms, the expression efficiency of a variety of genes which were difficult to be expressed in Escherichia coli, including those from unknown microorganisms, can be improved.

Abstract: Systems, methods, and devices for determining various properties of cells are provided herein. In one aspect, the method includes measuring one or more variables based on physical and/or chemical characteristics of a cell or its environment. The method further includes calculating one or more quantifiable metrics based on a mathematical expression including one or more of the variables, where those metrics correlate with at least one of the growth characteristics of the cell, the motility characteristics of the cell, the oncogenic potential of the cell, or the metastatic potential of the cell. Various aspects of systems and devices for determining various properties of cells are also provided herein.

Abstract: The present invention provides reagents and methods for identifying translation enhancing elements, as well as isolated translation enhancing elements and their use in protein expression reagents and methods.

Abstract: The present invention provides a polynucleotide vector system used during polypeptide display that can be used to facilitate transfer of pools of polynucleotides encoding antigen binding proteins of interest. The present invention also provides methods that allow seamless conversion of pools of polynucleotides encoding antigen binding proteins using a restriction enzyme digestion and ligation strategy.

Abstract: Disclosed herein are expression vectors which display a passenger polypeptide on the outer surface of a biological entity. As disclosed herein the displayed passenger polypeptide is capable of interacting or binding with a given ligand. Also disclosed are methods of making and using the expression vectors. N/C terminal fusion expression vectors and methods of making and using are also disclosed.

Abstract: The invention provides a replicable genetic package displaying a cyclic peptide having at least one intramolecular bond between amino acid side chains. Also provided are a method of preparing such a genetic package displaying cyclic peptides having at least one intramolecular bond. Further provided is a library of replicable genetic packages displaying cyclic peptides each having at least one intramolecular cyclic bond between amino acid side chains; and a method of producing such a library.

Abstract: Methods and compositions are disclosed for introducing molecular switch functionality into a protein affinity reagent to render its binding to a target molecule sensitive to an environmental trigger, such as pH, while maintaining binding affinity to the target molecule. Combinatorial libraries created by the method are also disclosed.

Abstract: Disclosed are living, three-dimensional tissue constructs for in vitro scientific and medical research, arrays thereof, and methods of making said tissues and arrays.

Abstract: The invention relates to bacterial cell surface display of post-translationally modified heterologous proteins. Provided is an isolated nucleic acid construct encoding a proteinaceous substance comprising, from the N-terminus to the C-terminus, at least (a) an N-terminal a lantibiotic leader sequence; (b) an amino acid sequence of interest to be post-translationally modified to a dehydroresidue- or thioether-bridge containing polypeptide; (c) a hydrophilic cell-wall spanning domain; (d) a sortase recognition motif; (e) a hydrophobic membrane spanning domain and (f) a C-terminal charged membrane anchoring domain. Also provided is a Gram-positive host cell expressing the construct, as well as a library of host cells.

Abstract: Recombinant P4 bacteriophage containing modified tail fibers having a base plate attachment region (BPAR) from a P2 bacteriophage gene H product and a heterologous receptor binding domain (RBD) are disclosed. Methods for the use of the recombinant P4 bacteriophage, such as to detect the presence of a target bacterium in a sample, are also described.

Abstract: Focused libraries of vectors or genetic packages that display, display and express, or comprise a member of a diverse family of antibody peptides, polypeptides or proteins and collectively display, display and express, or comprise at least a portion of the focused diversity of the family. The libraries have length and sequence diversities that mimic that found in native human antibodies.

Abstract: The invention relates to a method of generating junctional variability in the nucleotide sequence of a polynucleotide of interest present in an intrachromosomal substrate/context in a eukaryotic cell which is competent for canonical Non Homologous End Joining pathway (NHEJ) repair, involving the generation of double-strand break (DSB) in the DNA sequence of said polynucleotide, and involving the use of polymerase Terminal Deoxynucleotidyl Transferase (TdT) in conditions enabling said TdT to add Non-templated nucleotides (N nucleotides) before ligation through the canonical Non Homologous End Joining pathway (NHEJ) thereby allowing a mutagenic repair to take place at the DSB site.

Abstract: The present invention refers to a method for identifying hetero-multimeric ubiquitins with binding capability to a ligand. Furthermore, the invention provides DNA libraries encoding for a population of said hetero-multimeric ubiquitins as well as protein libraries obtained by expression of said DNA libraries, cells and phages containing said DNA or proteins, polynucleotides encoding for said fusion proteins and vectors comprising said polynucleotides. Further new binding proteins based on hetero-multimeric ubiquitin being able to bind specifically with high affinity to selected ligands are provided.

Abstract: Focused libraries of vectors or genetic packages that display, display and express, or comprise a member of a diverse family of antibody peptides, polypeptides or proteins and collectively display, display and express, or comprise at least a portion of the focused diversity of the family. The libraries have length and sequence diversities that mimic that found in native human antibodies.

Abstract: Eukaryotic cell display libraries for use in panning processes comprising expressed biomolecules for specific and selective binding and enrichment to solid material surfaces including, for example, metal, magnetic, and semiconducting surfaces. Display can be regulated. Peptide and protein display on yeast cells are preferred. Solid materials can be fabricated in the presence of cell display libraries which have been subjected to panning against the solid materials. Nanoparticles can be grown in the presence of the biomolecules from reactive precursors. The nanoparticles can show quantum confinement effects. Self-healing films can be prepared.

Abstract: The invention provides a method of identifying an antigen from a pathogen or a disease antigen comprising the use of an adenoviral vector array comprising two or more different adenoviral vectors, wherein each adenoviral vector comprises a nucleic acid sequence encoding a different antigen of a pathogen. The adenoviral vectors are administered to antigen presenting cells (APCs) in vitro or to an animal in vivo. The immunogenicity of the antigen is measured by screening for an immune response from effector T lymphocytes in vitro and by screening for the absence of pathogen-induced disease onset in vivo.

Abstract: A method for fabricating a micro-organ device includes printing a micro-organ on a microchip using a cell suspension in a syringe controlled by a computer-aided tissue engineering system, wherein the cell suspension comprises cells suspended in a solution containing a material that functions as a scaffold, and wherein the printing is performed with the computer-aided tissue engineering system according to a predetermined pattern. A micro-organ device includes at least one micro-chamber each housing a micro-organ; and at least one microfluidic channel connected to the micro-chamber, wherein the micro-organ comprises cells arranged in a configuration that includes spacing between portions of the cells to facilitate diffusion exchange between the cells and a medium supplied from the at least one microfluidic channel.

Abstract: The present invention is related to a system for the heterologous expression of a monoclonal Antibody (mAb) or a fragment or derivative thereof, said system comprising at least one ciliate host cell, and incorporated, into said ciliate host cell, at least one heterologous nucleic acid molecule encoding for said monoclonal Antibody, or a fragment or derivative thereof.

Abstract: The present invention relates to a device for isolating and recovering a biomolecule from a test sample. The device includes a support and at least one peelable layer deposited on at least a portion of the support. The peelable layer includes a substrate having a target component immobilized on the substrate. The device is effective for isolating and recovering a biomolecule having affinity to the target component. The present invention also relates to systems and methods of using the device. The present invention also relates to a biomolecule elution strip and related methods.

Abstract: The present disclosure provides for proprotein and activatable proprotein compositions. A proprotein contains a functional protein (i.e. a full length protein or functional fragment thereof) which is coupled to a peptide mask that inhibits the binding of the functional protein to its target or binding partner. An activatable proprotein contains a functional protein coupled to a peptide mask, and further coupled to an activatable linker, wherein in an non-activated state, the peptide mask inhibits binding of the functional protein to its target or binding partner and in an activated state the peptide mask does not inhibit binding of the functional protein to its target or binding partner. Proproteins can provide for reduced toxicity and adverse side effects that could otherwise result from binding of a functional protein at non-treatment sites if it were not inhibited from binding its binding partner. Proproteins can further provide improved biodistribution characteristics.

Abstract: Microfabricated platforms can be used to study a heterogeneous panel of biosamples in a realistic in vivo setting. The platform can be formed of a polymer (e.g., a hydrogel) and can be constructed for implantation into an animal host for in vivo testing. The platform can have a plurality of testing regions therein that are constructed to allow exposure of the testing region to the host stroma when implanted in vivo. For example, the microfabricated platform can be used for screening different cancer cell-lines (e.g., to identify which cell line responds to an anti-cancer drug) or for screening different biomaterials (e.g., to identify a composition with ideal host response for a specific implantable device).

Abstract: A somatic stem cell that is CD10+, CXCR4+, and CD31+ and another somatic stem cell that is CD 105+, CD44+, and nestin+. Also disclosed are both a method of preparing these stem cells and a method of using them to treat degenerative diseases, e.g., a muscle-degenerative disease. The invention further includes making and using liver cells derived from the somatic cell that is CD105+, CD44+, and nestin+.

Abstract: The present invention relates to a system comprising coupling products formed by a monomer of a protein chosen from Lingo-1, Lingo-2, Lingo-3 and Lingo-4 and by a probe emitting a signal when said monomer undergoes conformational changes, and to a screening method using said system, enabling ligands of a protein chosen from Lingo-1, Lingo-2, Lingo-3 and Lingo-4 to be identified. The present invention is industrially applicable in the field of methods for detecting molecules, for detecting interaction between molecules and for molecular screening, and also in the medical field.

Abstract: The invention relates to a method for generating a gene mosaic by somatic in vivo recombination, comprising: e) in a single step procedure (vii) transforming a cell with at least one gene A having a sequence homology of less than 99.5% to another gene to be recombined that is an integral part of the cell genome or presented in the framework of a genetic construct, (viii) recombining said genes, (ix) generating a gene mosaic of the genes at an integration site of a target genome, wherein said at least one gene A has a single flanking target sequence either at the 5? end or 3? end anchoring to the 5? or 3? end of said integration site, and f) selecting clones comprising the gene mosaic, as well as a method of producing a diversity of gene mosaics and gene assembly.

Abstract: The present invention relates to a method for obtaining useful data for the diagnosis, prognosis or monitoring of colorectal cancer (CRC) progression, to a method for the diagnosis of CRC, to a method for the prognosis of CRC and to a kit for carrying out said methods.

Abstract: The present invention relates to protein chips useful for the large-scale study of protein function where the chip contains densely packed reaction wells. The invention also relates to methods of using protein chips to assay simultaneously the presence, amount, and/or function of proteins present in a protein sample or on one protein chip, or to assay the presence, relative specificity, and binding affinity of each probe in a mixture of probes for each of the proteins on the chip. The invention also relates to methods of using the protein chips for high density and small volume chemical reactions. Also, the invention relates to polymers useful as protein chip substrates and methods of making protein chips. The invention further relates to compounds useful for the derivatization of protein chip substrates.

Abstract: Focused libraries of vectors or genetic packages that display, display and express, or comprise a member of a diverse family of antibody peptides, polypeptides or proteins and collectively display, display and express, or comprise at least a portion of the focused diversity of the family. The libraries have length and sequence diversities that mimic that found in native human antibodies.

Abstract: Recombinant adeno-associated viral (AAV) capsid proteins are provided. Methods for generating the recombinant adeno-associated viral capsid proteins and a library from which the capsids are selected are also provided.

Abstract: The present invention relates to totipotent, nearly totipotent and pluripotent stem cells that are hemizygous or homozygous for MHC antigens and methods of making and using them. These cells are useful for reduced immunogenicity during transplantation and cell therapy. The cells of the present invention may be assembled into a bank with reduced complexity in the MHC genes.

Abstract: The present invention provides systems, vectors and methods for isolation of enhanced ligand-binding proteins from combinatorial libraries displayed on the inner membrane of a host cell.

Abstract: Panels of mammalian cell samples, kits and methods of use thereof. The panels comprise samples or sets of samples of immortalized primary cells, obtained from different tissues and organs of healthy and/or diseased donors. The cell panels are useful in assays for testing effects of drug candidates, e.g. for activity and toxicity.

Abstract: The present disclosure relates general to devices, systems, and methods of using such devices in creating and handling hanging drops of fluid. The present disclosure also relates to cell culture devices, methods and/or systems of using such devices as well as the use of cell culture devices, for example, for research and high throughput screening.

Abstract: In one embodiment, a testing device includes a substrate and a plurality of spatially distinct fungal cultures disposed on the substrate.

Abstract: The present invention includes methods for selective binding of inorganic materials and the compositions that made up of the selecting agent and the target materials. One form of the present invention is a method for selecting crystal-binding peptides with binding specificity including the steps of contacting one or more amino acid oligomers with one or more single-crystals of a semiconductor material so that the oligomers may bind to the crystal and eluting the bound amino acid oligomers from the single-crystals.

Abstract: The present invention relates to methods and kits for diagnosing systemic lupus erythematosus (SLE) in a subject. Particularly, the present invention relates to a specific antibody profile useful in diagnosing SLE in a subject.

Abstract: Methods of isolating at least one cell of interest, methods of making fixed arrays, arrays comprising a glass substrate bonded to a patterned siloxane structure having inlets, outlets and microchannels, array kits, and methods of making microfluidic apparati are provided in the present application.

Abstract: Human somatic cells obtained from individuals with a genetic heart condition are reprogrammed to become induced pluripotent stem cells (iPS cells), and differentiated into cardiomyocytes for use in analysis, screening programs, and the like.

Abstract: Disclosed herein are expression vectors which display a passenger polypeptide on the outer surface of a biological entity. As disclosed herein the displayed passenger polypeptide is capable of interacting or binding with a given ligand. Also disclosed are methods of making and using the expression vectors. N/C terminal fusion expression vectors and methods of making and using are also disclosed.

Abstract: Antigen-specific immunoglobulin V-regions are identified from a library of nucleic acids amplified using polymerase chain reaction using leader sequence-specific forward primers. The use of leader sequence primers allows all V-region sequences to be amplified (including those with extensive 5? end mutations) without loss of the original 5? V gene segment sequence. A second V-region library is made using a larger than conventional set of 5? V-region primers. The sequence errors introduced into the amplification products by this method are corrected using sequence information obtained in the products amplified by the V-region primers to screen the library created using the leader sequence primers. Amino acid sequence information from fragments of donor immunoglobulins can be used to assist in the identification of nucleic acids encoding the heavy and light chains of donor antibodies as well as to design primers to amplify such nucleic acids.

Abstract: A gene construct comprising a programmed-cell-death executioner gene having a nuclear localization signal, a deleted signal peptide, an inhibitor-resistant binding site, a promoter, and an activator. A method of making a gene construct, by modifying a programmed-cell-death executioner gene by adding a nuclear localization signal, deleting a signal peptide, mutating a binding site for an inhibitor to make it inhibitor-resistant, adding a promoter for exclusive expression in selected cells, and adding an activator. A method of eliminating undesired cells from a patient. A method of treating cancer. An array comprising at least two gene constructs wherein all of the gene constructs differ with respect to the programmed-cell-death executioner gene and the nuclear localization signal. A method of personalizing anti-cancer treatment. A method of increasing DNase 1 resistance to actin binding. A method of increasing catalytic activity of DNase 1 binding.

Abstract: The invention relates to a minimized phage display vector comprising at least a cloning cassette, a phage display cassette and a bacterial cassette, said cloning cassette comprising a nucleic acid sequence encoding a polypeptide corresponding at least to the intra-domain loop of a constant domain of an antibody. It also relates to their uses for the production of libraries of phages, each phage expressing on its surface a binding protein to be screened for its capacity to bind a binding partner.

Abstract: The invention relates to a method for manufacturing an anti-RhD recombinant polyclonal antibody composition (anti-RhD rpAb). The method comprises obtaining a collection of cells transfected with a library of anti-RhD antibody expression vectors, wherein each cell in the collection is capable of expressing from a VH and VL comprising nucleic acid segment, one member of the library, which encodes a distinct member of anti-RhD recombinant polyclonal antibody composition and is located at the same site in the genome of individual cells in said collection. The cells are cultured under suitable conditions for expression of the recombinant polyclonal antibody, which is obtained from the cells or culture supernatant. Nucleic acid segments encoding the anti-RhD rpAb are introduced into the cells by transfection with a library of vectors for site-specific integration.

Abstract: Compositions are provided that comprise antibody against membrane proteins such as chemokine receptors. In particular, monoclonal human antibodies against human CXCR4 are provided that are capable of inhibiting HIV infection and chemotaxis in human breast cancer cells. The antibodies can be used as prophylactics or therapeutics to prevent and treat HIV infection and cancer, for screening drugs, and for diagnosing diseases or conditions associated with interactions with chemokine receptors.

Abstract: A method is described to identify secreted proteins identified with stages of malignancy of cancer. The proteins are initially identified by trapping them with a fluorescent protein containing vector that can insert in any gene. The secreted proteins are initially identified by their fluorescence. Secreted proteins identifying tumors with specific degrees of malignancy are isolated to determine if they can serve as markers of cancer progression.