Abstract: Antibodies having modified constant regions so as to permit conjugation of the antibody to a payload such as a therapeutic agent are described. Preferred antibodies include a mutation at light chain position 180 (positional numbering), most preferably the mutation is to a residue selected from C, K, Q, or a non-natural amino acid. Additional mutations may also be combined with a mutation at position 180; including one or more of light chain (LC) S208, LC S171, LC S182, LC A184, LC V191, LC S202, LC S203, LC T206, heavy chain (HC) S160, HC T190, HC S443, HC S447, HC S139, HC S168, HC V170, HC V176, HC T200, HC S445 according to a positional numbering convention.

Abstract: A primary culture method in which cells contained in a tissue collected from a living body are primary cultured in vitro, in which the cells in the tissue collected from the living body are seeded and cultured on a top surface of a cell structure containing cells constituting a stroma and composed of a single layer or two or more cell layers laminated in the thickness direction.

Abstract: A non-human animal model for neurodegenerative and/or inflammatory diseases is provided, which non-human animal comprises a disruption in a C9ORF72 locus. In particular, non-human animals described herein comprise a deletion of an entire coding sequence of a C9ORF72 locus. Methods of identifying therapeutic candidates that may be used to prevent, delay or treat one or more neurodegenerative (e.g., amyotrophic lateral sclerosis (ALS, also referred to as Lou Gehrig's disease) and frontotemporal dementia (FTD)), autoimmune and/or inflammatory diseases (e.g., SLE, glomerulonephritis) are also provided.

Abstract: A combined Kunkel mutagenesis and phage-display method for producing bivalent binding agents is provided.

Abstract: Compositions, systems and methods for generating and using internal standard spike-in mixes including a combination of template spikes. Compositions, systems and methods described herein are directed to using the internal standard spike-in mixes to evaluate a set of workflow pipelines to perform differential abundance analyses on a sample containing variations of a target nucleic acid sequence of interest. Compositions, systems and methods described herein are directed to using the internal spike-in mixes to validate results obtained from differential abundance analyses performed on a sample containing variations of a target nucleic acid sequence of interest, where the variations may be of highly variable levels of relative abundance.

Abstract: Vaccine compositions including a yeast comprising an immunostimulatory polypeptide and optionally an antigenic polypeptide are provided herein. The immunostimulatory polypeptide and the antigenic polypeptide are expressed or displayed on the surface of the yeast vaccine composition. Methods of using the vaccine composition to vaccinate subjects are also provided.

Abstract: Disclosed are methods of assessing the ability of a candidate therapeutic agent to reverse, reduce or prevent renal injury by a potential toxic agent using a three-dimensional, engineered, bioprinted, biological renal tubule model. Also disclosed are methods of assessing the effect of an agent on renal function, the method comprising contacting the agent with a three-dimensional, engineered, bioprinted, biological renal tubule model. Also disclosed are models of renal disorder. In one embodiment, disclosed are models of renal fibrosis, comprising a three-dimensional, engineered, bioprinted, biological renal tubule model. Also disclosed are methods of making the model of renal disorder. In one embodiment disclosed are methods of making the model of renal fibrosis comprising contacting a three-dimensional, engineered, bioprinted, biological renal tubule model with an agent that is capable of inducing interstitial fibrotic tissue formation.

Abstract: In a first aspect, the present invention relates to a mutated Salmonella strain comprising mutations in flagellin II genes, like the fliF gene, in particular, in addition the aroA gene, the IpxR gene, the pagP gene, the pagL gene, the ydiV gene and optionally the eptA gene and further optionally, the arnT gene. In a further aspect, immunogenic compositions comprising said Salmonella strain are provided optionally together with a pharmaceutically accepted carrier, diluent or effluent. Moreover, a method for producing outer membrane vesicles of Salmonella is provided, said method comprises the steps of cultivating the Salmonella strain according to the present invention and isolating the outer membrane vesicles accordingly.

Abstract: Disclosed is a method of producing an antimicrobial peptide wherein an antimicrobial peptide gene is fused with a green fluorescent protein gene expressed insolubly in E. coli, followed by introduction into E. coli, expression, and removal of the green fluorescent protein to yield the antimicrobial peptide. This method is capable of producing the antimicrobial peptide with high yield in a simple and economical manner and is thus effective at providing native antibiotics that can replace conventional antibiotics in pharmaceutical and feed industries, requiring the development of antibiotics having a new mechanism of action that can eradicate resistant strains due to the proliferation of multiple-drug-resistant microorganisms. Furthermore, the use of an amino acid cleavage process through acid treatment, instead of using conventional cyanogen bromide, is cost-effective for the purification of a target protein from an insoluble protein, can decrease the risk of processing, and enables rapid processing.

Abstract: Described herein is a novel, mitochondrial encoded, open reading frame, that leads to the production of a new mitochondrial peptide. Residing within the ND-Two subunit, a specific small nucleotide polymorphism disrupts expression of this mitochondrial peptide, and is correlated with an increase in obesity and diabetes, particularly in certain ethnic populations. In vitro administration of the peptide increases insulin secretion, decreases fat accumulation and improves glucose uptake in muscle cell. Antibodies generated against the peptide can be used for detecting peptide deficiency, in addition to SNP detection, supporting diagnostic approaches. In vivo studies further revealed that administration of the peptide improves glucose tolerance, thereby providing a new therapeutic avenue for a novel diabetes therapy and decreases bodyweight, thus serving as a novel obesity therapy. Generation of synthetic analogs further enhance or abrogated activity relative to the natural peptide.

Abstract: Disclosed are compositions and methods for the co-delivery of ribonucleic acids and interferon binding proteins. Compositions include mineral coated microparticles having a mineral layer, a ribonucleic acid, and an interferon binding protein. Ribonucleic acids and interferon binding proteins can be adsorbed to the mineral layer, can be incorporated into the mineral layer, and combinations thereof. Also disclosed are methods for co-delivery of ribonucleic acids and interferon binding proteins and methods for treating inflammatory diseases using mineral coated microparticles having a mineral layer to provide co-delivery of ribonucleic acids and interferon binding proteins.

Abstract: The invention provides engineered Vibrio sp. organisms that comprise a genetic modification to either or both of the lpxL and/or lpxM genes. The organisms score substantially lower in an in vitro endotoxin assay versus the unmodified or wild type organism. The organisms preserve substantially the growth rate of the corresponding unmodified organisms. The organisms can also have an exogenous nucleic acid cloned in the organism, or an exogenous nucleic acid encoding a protein, polypeptide, or peptide expressed by the organism, and optionally secreted from the organism.

Abstract: The present disclosure is directed to providing a new skin-penetrating peptide, a fusion product with a biologically active substance bound using the same, a cosmetic composition containing the same and a pharmaceutical composition for external application to skin containing the same. The skin-penetrating peptide of the present disclosure is less likely to cause an immune response as compared to existing skin-penetrating peptides and exhibits remarkably improved skin permeability. Therefore, the biologically active substance can be effectively delivered through the skin, particularly through the stratum corneum.

Abstract: A device for positioning a processing tool: a processing tool for processing the to-be-processed workpiece's surface while pressing the surface to be processed; a movement mechanism able to displace processing tool's distal end in a first direction orthogonal to the surface to be processed and/or a second direction parallel with the surface to be processed; a force sensor able to detect a force in the first and second direction applied to the processing tool's distal end pressed onto the surface to be processed; and a control device for executing a correction step for controlling the movement mechanism so the surface to be processed is pressed while the distal end's position of the processing tool is aligned with a processing reference position on the surface to be processed, and correcting the processing tool's position so that the force in the second direction is within a specific value or less.

Abstract: The present invention provides novel microfluidic devices and methods that are useful for performing high-throughput screening assays and combinatorial chemistry. The invention provides for aqueous based emulsions containing uniquely labeled cells, enzymes, nucleic acids, etc., wherein the emulsions further comprise primers, labels, probes, and other reactants. An oil based carrier-fluid envelopes the emulsion library on a microfluidic device, such that a continuous channel provides for flow of the immiscible fluids, to accomplish pooling, coalescing, mixing, sorting, detection, etc., of the emulsion library.

Abstract: Presented herein are methods and compositions for enhancing specific enrichment of target sequences in a nucleic acid library. Off-target hybridization probes may be used to reduce binding and/or capture of off-target regions of a nucleic acid library in a targeted sequencing workflow. The off-target hybridization probes may be specific for locations known to generate off-target sequencing reads for a particular set of hybridization probes.

Abstract: The invention relates to (among other things) N-optionally substituted aryl-2-oligomer-3-alkoxypropionamides and compositions comprising the same. A compound of the invention, when administered by any of a number of administration routes, exhibits one or more advantages over corresponding compounds lacking the oligomer.

Abstract: Methods of clonal analysis of functional genomic assays are provided. Aspects of the invention include transducing a population of target cells with a packaged viral effector library made up of a plurality of effector construct subsets, wherein each effector construct subset of the library includes a plurality of effector constructs having a common effector cassette linked to a distinct clonal barcode. Inclusion of distinct clonal barcodes in the effector construct subset allows for determination of the clonal representation of an effector construct subset in transduced target cells that exhibit a specific phenotype. Aspects of the invention further include compositions, e.g., libraries and components thereof, which find use in practicing the methods.

Abstract: The invention relates to agents and to pharmaceutical compositions for reducing the formation of amyloid and/or for promoting the disaggregation of amyloid proteins. The compositions may also be used to detect amyloid.

Abstract: Methods, compositions, systems and kits to amplify or improve amplification of target-specific amplification products by reducing non-specific amplification products (e.g., primer-dimers) when amplifying multiple different nucleotide regions. The methods, compositions, systems and kits described herein may include, or include the use of, one or more resolvases that recognize and bind to and/or cut an aberrant DNA structure.

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. These libraries can be screened for antigen-specific V-regions using eukaryotic cells engineered to express the amplified V-region-encoding nucleic acids or using bacterial phage display techniques. In the latter, 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.

Abstract: The invention relates to a novel use of a Bordetella adenylcyclase toxin in the manufacturing of vectors for targeting in vivo a molecule of interest, specifically to CD11b expressing cells. The invention also relates to an immunogenic composition that primes immune responses, to pharmaceutical compositions and to a new vector for molecule delivery to CD11b expressing cells.

Abstract: The invention relates generally to methods and apparatus for conducting analyzes, particularly microfluidic devices for the detection of target analytes.

Abstract: The present invention provides, in part, an antibody display system that simultaneously uses a secretion and a display mode. Embodiments of the invention provide a system in which a bait complexed with a monovalent antibody fragment can be captured prior to secretion in a host cell by virtue of surface displaying an antibody light chain and utilizing the covalent interaction of this light chain with the heavy chain of an antibody molecule that is co-expressed in the same host. Polypeptides, polynucleotides and host cells useful for making the antibody display system are also provided along with methods of using the system for identifying antibodies that bind specifically to an antigen of interest.

Abstract: A eukaryotic expression vector capable of displaying a multi-chain polypeptide on the surface of a host cell is provided, such that the biological activity of the multi-chain polypeptide is exhibited at the surface of the host cell. Such a vector allows for the display of complex biologically active polypeptides, e.g., biologically active multi-chain polypeptides such as immunoglobulin Fab fragments. The present invention describes and enables the successful display of a multi-chain polypeptide on the surface of a eukaryotic host cell. Preferred vectors are described for expressing the chains of a multi-chain polypeptide in a host cell separately and independently (e.g., under separate vector control elements, and/or on separate expression vectors, thus forming a matched vector set).

Abstract: The invention relates to methods and compositions that enable the rapid generation of high-order combinations of genetic elements, and that provide a barcoded basis for rapid characterization of the specific combination of genetic elements encoded within a single cell or in a pooled population.

Abstract: The invention relates to the field of medicine. The invention provides methods for generating glatiramer-acetate-specific human T-cell lines, and assays that use these T-cell lines for demonstrating immunological identity between glatiramer acetate preparations. These assays allow sensitive and accurate comparison of glatiramer acetate preparations, and find utility as lot-release assays.

Abstract: A eukaryotic expression vector capable of displaying a multi-chain polypeptide on the surface of a host cell is provided, such that the biological activity of the multi-chain polypeptide is exhibited at the surface of the host cell. Such a vector allows for the display of complex biologically active polypeptides, e.g., biologically active multi-chain polypeptides such as immunoglobulin Fab fragments. The present invention describes and enables the successful display of a multi-chain polypeptide on the surface of a eukaryotic host cell. Preferred vectors are described for expressing the chains of a multi-chain polypeptide in a host cell separately and independently (e.g., under separate vector control elements, and/or on separate expression vectors, thus forming a matched vector set).

Abstract: This invention provides a multiscale platform for coordinating behavior using synthetic biology. The platform reduces the impact of underlying noise, making outputs more coherent and reliable at the macroscopic level.

Abstract: Disclosed is a microcapsule encoded depending on the kind of a target substance included therein. The encoded microcapsule has a hydrophilic liquid core including the target substance and a hydrophobic shell surrounding the liquid core. The encoded microcapsule includes graphical codes introduced on the surface of the shell.

Abstract: The invention relates to novel variants that associate with Alzheimer's disease AD and their use in kits as a means for diagnosing AD; and also their use in nucleic acid molecules or cells/cell lines for identifying novel therapeutic, label of identification means.

Abstract: A eukaryotic expression vector capable of displaying a multi-chain polypeptide on the surface of a host cell is provided, such that the biological activity of the multi-chain polypeptide is exhibited at the surface of the host cell. Such a vector allows for the display of complex biologically active polypeptides, e.g., biologically active multi-chain polypeptides such as immunoglobulin Fab fragments. The present invention describes and enables the successful display of a multi-chain polypeptide on the surface of a eukaryotic host cell. Preferred vectors are described for expressing the chains of a multi-chain polypeptide in a host cell separately and independently (e.g., under separate vector control elements, and/or on separate expression vectors, thus forming a matched vector set).

Abstract: A eukaryotic expression vector capable of displaying a multi-chain polypeptide on the surface of a host cell is provided, such that the biological activity of the multi-chain polypeptide is exhibited at the surface of the host cell. Such a vector allows for the display of complex biologically active polypeptides, e.g., biologically active multi-chain polypeptides such as immunoglobulin Fab fragments. The present invention describes and enables the successful display of a multi-chain polypeptide on the surface of a eukaryotic host cell. Preferred vectors are described for expressing the chains of a multi-chain polypeptide in a host cell separately and independently (e.g., under separate vector control elements, and/or on separate expression vectors, thus forming a matched vector set).

Abstract: The present invention relates to the fields of microbiology, molecular biology and protein biochemistry. More particularly, it relates to compositions and methods for analyzing and altering (e.g., enhancing or inhibiting) protein folding and solubility.

Abstract: The present invention relates to humanisation of antibodies in vivo. The invention provides non-human vertebrates, cells, populations and methods useful for humanising chimaeric antibodies in vivo. Using the present invention it is possible straightforwardly and rapidly to obtain antigen-specific antibodies that are fully human (ie, comprising human variable and constant regions) and have undergone recombination, junctional diversification, affinity maturation and isotype switching in vivo in a non-human vertebrate system. Furthermore, such antibodies are humanised (eg, totally human)—and selected—totally in vivo, and as such the present invention harnesses in vivo filtering for expressibility, affinity and biophysical characteristics in the context of the desired human variable and constant region pairings. This is avoids problems of down-grading antibody characteristics when humanising the constant region of chimaeric antibodies in vitro.

Abstract: Provided herein are methods of selective screening. In addition, various targeting proteins and sequences, as well as methods of their use, are also provided.

Abstract: The present disclosure provides technologies for achieving cell patterning, as well as patterned cell arrays achieved with such technologies. Provided apparatus and methods are useful in a variety of contexts and provide particular advantages with respect to assessing living cell arrays and/or their responsiveness to stimuli, including identifying and/or characterizing complex cellular responses.

Abstract: Methods for producing and identifying fragments of proteins, and more particularly to methods for generating and identifying soluble protein domains are disclosed based on a method for generating a library of nucleic acid fragments from nucleic acid encoding a desired polypeptide, and more especially a library of essentially, randomly sampled fragments of coding DNA sequence predominantly of defined size range and a method for selecting cloned gene fragments from the library that encode soluble protein domains.

Abstract: The present invention is drawn to the generation of micropatterns of biomolecules and cells on standard laboratory materials through selective ablation of a physisorbed biomolecule with oxygen plasma. In certain embodiments, oxygen plasma is able to ablate selectively physisorbed layers of biomolecules (e.g., type-I collagen, fibronectin, laminin, and Matrigel) along complex non-linear paths which are difficult or impossible to pattern using alternative methods. In addition, certain embodiments of the present invention relate to the micropatterning of multiple cell types on curved surfaces, multiwell plates, and flat bottom flasks. The invention also features kits for use with the subject methods.

Abstract: Provided is a microarray platform for the culture of cells atop combinatorial matrix mixtures; enabling the study of differentiation in response to a multitude of microenvironments in parallel.

Abstract: The present invention provides methods for early diagnosis of Alzheimer's disease and for determining the efficacy of a treatment for Alzheimer's disease in an Alzheimer's patient, i.e., monitoring Alzheimer's disease progression, utilizing cellular blood markers; as well as kits for carrying out these methods.

Abstract: The present invention relates to a filamentous phage display method wherein the polypeptides of interest displayed on the phage particle are cotranslationally translocated across the cytoplasmic membrane of Gram-negative bacteria based on the signal recognition particle pathway. This method is particularly suitable for polypeptides, which are known to be difficult to display on phages, and for proteins of cDNA libraries and other combinatorial libraries, in particular when derived from very fast folding, stable protein scaffolds. The invention further relates to phage or phagemid vectors useful in the method comprising a gene construct coding for a fusion polypeptide comprising the polypeptide to be displayed on the phage particle and an N-terminal signal sequence promoting cotranslational translocation.

Abstract: The present invention relates to a differential diagnostic method using flow cytometry, performed by means of differential fluorescent marking of biological agents, such as cells and pathogens of interest, with fluorescent substances. The diagnostic method generally consists in performing fluorescent marking of biological agents with gradual concentrations of fluorescent substances, and in analysing the reactivity profile of IgG1 to the biological agents. The present invention further relates to a diagnostic kit.

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

Abstract: The invention provides cells or populations of cells, including non-human animals or non-human mammals having these cells, where the cells or populations of cells are stably tagged, uniquely identified and genetically barcoded by one or more detectable, e.g., fluorescent, proteins; and methods of making and using them. In alternative embodiments, the invention provides methods for tagging, uniquely identifying or genetically barcoding a cell, a population of cells, or a culture of cells by stably transferring, transfecting, transducing, infecting or implanting one or more nucleic acids encoding readable or detectable, e.g., fluorescent, moieties into the cells. In alternative embodiments, the nucleic acids are stably inserted into the cells such that the readable or detectable, e.g., fluorescent, genetic barcoding becomes a stable, heritable characteristic of the cell.

Abstract: The present invention relates to a method and a kit for monitoring an immune status after transplant. The kit for monitoring an immune status after transplant and the method for monitoring an immune status of an individual after transplant as provided in the present invention make it easy and accurate to determine an immune status in the individual after transplant and thus have an effect of reducing overuse of an immunosuppressive agent prescribed after transplant and also have an effect of conveniently managing an immune status of each patient.

Abstract: The invention relates to a method for determining the ability of a candidate antibody to keep a first cell and a second cell close to one another, said method comprising the following steps: bringing said candidate antibody in contact with (i) a first cell expressing, in the extracellular portion of its plasma membrane, a first protein that is known to be or is suspected of being recognized by the candidate antibody and (ii) a second cell expressing, in the extracellular portion of the plasma membrane, a second protein that is also known to be or suspected of being recognized by the candidate antibody, each of the proteins being labeled with a member of a pair of FRET partners, and measurement of the FRET signal and comparison with the signal measured in the absence of the candidate antibody. The invention also relates to a reagent kit for carrying out this method.

Abstract: Herein is reported a method of selecting a cell expressing a bispecific antibody comprising the steps of (a) generating a population of eukaryotic cells by transduction with a population of lentiviral virus particles, whereby each cell of the population of cells displays a membrane-bound full length antibody which is encoded by the lentiviral nucleic acid, and which specifically binds to two or more antigens or two or more epitopes on the same antigen, and (b) selecting from the population of eukaryotic cells a cell depending on the properties of the displayed membrane-bound full length antibody, whereby each lentiviral virus particle of the population of lentiviral virus particles comprises a bicistronic expression cassette comprising the EV71-IRES for the expression of the membrane-bound antibody.

Abstract: The present disclosure relates to a method for selecting a pool of molecules comprising detecting if the pool of molecules has binding specificity to an agent. A method for selecting a pool of biological markers in or on a cell, a composition comprising a pool of molecules, a method for delivering a therapeutic agent, and a method for diagnosing a condition in a subject are also provided.

Abstract: A microarray substrate including a piece of fluoropolymer whose surface is modified with polydopamine, in which the polydopamine forms an array of microspots on the surface of the fluoropolymer piece, and allows immobilization of molecules or cells. A microarray including the substrate, a microfluidic system designed for dispensing reagents onto selected locations on the surface of substrates, and a method for preparing the substrate and the microarray, in which a dopamine solution is dispensed onto the fluoropolymer piece using the microfluidic system, and forms an array of polydopamine microspots serving as the reaction sites for microarray analysis.