Abstract: The invention relates to optimized adhesins and nanoparticles to which said adhesins are bound. The invention furthermore relates to providing said nanoparticles by way of in vivo contrast agents, in particular for the diagnosis of bowel cancer.

Abstract: The present invention relates to a chromatography ligand, which comprises Domain C from Staphylococcus protein A (SpA), or a functional fragment or variant thereof. The chromatography ligand presents an advantageous capability of withstanding harsh cleaning in place (CIP) conditions, and is capable of binding Fab fragments of antibodies. The ligand may be provided with a terminal coupling group, such as arginine or cysteine, to facilitate its coupling to an insoluble carrier such as beads or a membrane. The invention also relates to a process of using the ligand in isolation of antibodies, and to a purification protocol which may include washing steps and/or regeneration with alkali.

Abstract: A fusion protein of the invention comprises an immunoglobulin Fc region and a first target protein linked to the immunoglobulin Fc region. The first target protein comprises a collagen XVIII fragment, preferably endostatin. The immunoglobulin Fc region preferably comprises a hinge region, a CH2 region, and a CH3 region.

Abstract: The present invention pertains to a method for in vitro prognosticating and/or diagnosing cerebral cerebral malaria, wherein said method comprises a step of detecting non-erythroid spectrin or fragments thereof, and/or antibodies directed against non-erythroid spectrin, in a biological sample. Reagents and kits for performing this method are also disclosed.

Abstract: Methods are disclosed for producing defective ribosomal products (DRiPs) in blebs (DRibbles) by contacting cells with a proteasome inhibitor, and in some examples also an autophagy inducer, thereby producing treated cells. DRibbles can be used to load antigen presenting cells (APCs), thereby allowing the APCs to present the DRiPs and antigenic fragments thereof. Immunogenic compositions that include treated cells, isolated DRibbles, or DRibble-loaded APCs are also disclosed. Methods are also provided for using treated cells, isolated DRibbles, or DRibble-loaded APCs to stimulate an immune response, for example in a subject. For example, DRibbles obtained from a tumor cell can be used to stimulate an immune response against the same type of tumor cells in the subject. In another example, DRibbles obtained from a pathogen-infected cell or cell engineered to express one or more antigens of a pathogen can be used to stimulate an immune response against the pathogen in the subject.

Abstract: The present invention relates to methods and compositions for pretargeting delivery of therapeutic agents. In preferred embodiments, the pretargeting method comprises: a) administering a bispecific antibody with a first binding site for a disease-associated antigen and a hapten on a targetable construct; b) administering a targetable construct comprising at least one therapeutic agent. In preferred embodiments, the bispecific antibody is made by the dock-and-lock (DNL) technique. In a more preferred embodiment, the targetable construct comprises one or more SN-38 moieties.

Abstract: Crosslinking reagents and methods for using the same for analysis of protein-protein interactions, are provided. The crosslinking reagents include a trifunctional scaffold that links two protein linking groups to each other and branches to link an affinity tag, where the protein linking groups can be fragmented from the scaffold. The distance between the two protein linking groups can be selected to crosslink two proteins of a protein complex via accessible amino acid residues. Also provided are crosslinked polypeptide compounds and kits that include crosslinking reagents. These reagents and methods find use in a variety of applications in which crosslinking of proteins in desired.

Abstract: An object of the present invention is to provide a probe, a primer, a primer set and an antibody for use in the detection or selection of a dopaminergic neuron progenitor cell. The present invention provides a probe, a primer and a primer set for use in the detection or selection of a mesencephalon dopaminergic neuron progenitor cell, and preferably a dopaminergic neuron proliferative progenitor cell, which can hybridize with a nucleotide sequence of a 187A5 gene, or a complementary sequence thereto, and an antibody for use in the detection or selection of a mesencephalon dopaminergic neuron progenitor cell, and preferably a dopaminergic neuron progenitor cell, which is capable of binding to a 187A5 protein.

Abstract: The invention relates to materials and procedures for the use of the hepcidin binding domain (HBD) on ferroportin. A 20 amino acid peptide of the HBD was synthesized and shown to recapitulate the characteristics and specificity of hepcidin binding to cell surface ferroportin. The affinity of hepcidin for the HBD peptide permits a rapid, sensitive assay of hepcidin in biological fluids.

Abstract: A heterobifunctional poly(ethylene glycol) is provided having a hydrolytically degradable linkage, a first terminus comprising an acrylate group, and a second terminus comprising a target such as a protein or pharmaceutical agent or a reactive moiety capable of coupling to a target. Hydrogels can be prepared. The hydrogels can be used as a carrier for a protein or a pharmaceutical agent that can be readily released in a controlled fashion.

Abstract: Provide herein are fusion polypeptides that comprise a CD47 extracellular domain or a variant thereof that is fused to a Fc polypeptide. The fusion polypeptides are useful for treating an immunological disease or disorder in a subject according to the methods described herein. The fusion polypeptides are capable of suppressing immunoresponsiveness of an immune cell, inhibiting production of proinflammatory cytokines, including inhibiting immune complex-induced production of cytokines.

Abstract: The present invention relates to a chromatography ligand, which comprises Domain C from Staphylococcus protein A (SpA), or a functional fragment or variant thereof. The chromatography ligand presents an advantageous capability of withstanding harsh cleaning in place (CIP) conditions, and is capable of binding Fab fragments of antibodies. The ligand may be provided with a terminal coupling group, such as arginine or cysteine, to facilitate its coupling to an insoluble carrier such as beads or a membrane. The invention also relates to a process of using the ligand in isolation of antibodies, and to a purification protocol which may include washing steps and/or regeneration with alkali.

Abstract: By detecting an antibody which immunologically reacts with amylase ?2-A in a sample, AIP or FT1DM is examined or the possibility of developing FT1DM is determined. For instance, detection of this antibody is carried out by an immunological method using an antigen which immunologically reacts with this antibody. The antigen is preferably a partial fragment containing the amino acid sequence of amino acid numbers 299 to 511 of human amylase ?2-A (SEQ ID NO: 1).

Abstract: An object of the present invention is to provide a probe, a primer, a primer set and an antibody for use in the detection or selection of a dopaminergic neuron progenitor cell. The present invention provides a probe, a primer and a primer set for use in the detection or selection of a mesencephalon dopaminergic neuron progenitor cell, and preferably a dopaminergic neuron proliferative progenitor cell, which can hybridize with a nucleotide sequence of a 187A5 gene, or a complementary sequence thereto, and an antibody for use in the detection or selection of a mesencephalon dopaminergic neuron progenitor cell, and preferably a dopaminergic neuron progenitor cell, which is capable of binding to a 187A5 protein.

Abstract: Intermediates and methods for forming activated metal complexes bound to surfaces on oxide layers, immobilizing beads to the modified surface and articles produced thereby are described. Hydroxyl groups on the oxide surfaces are reacted with a metal reagent complex of the formula Y(L-Pol)m, where Y is a transition metal, magnesium or aluminum, L is oxygen, sulfur, selenium or an amine, and “Pol” represents a passivating agent such as a methoxyethanol, a polyethylene glycol, a hydrocarbon, or a fluorocarbon. The resulting modified surface can be further reacted with a passivating agent having a phosphate functional group or a plurality of functional groups that are reactive with or that form complexes with Y.

Abstract: A method to facilitate recovery troponin I and/or troponin T from a sample comprising addition of troponin C to the sample or to a surface from which the troponin I and/or troponin T are recovered.

Abstract: Described herein is a method for the attachment of proteins to any solid support with control over the orientation of the attachment. The method is extremely efficient, not requiring the previous purification of the protein to be attached, and can be activated by UV-light. Spatially addressable arrays of multiple protein components can be generated by using standard photolithographic techniques.

Abstract: The present invention relates to vaccines comprising a bacteriophage which has been engineered to express an immunogenic protein/peptide and wherein the surface of the bacteriophage has not been modified to contain proteins/peptides designed to target the phage to receptors on the surface of specific cell types.

Abstract: The present invention relates to an immunoglobulin-binding protein, wherein at least one asparagine residue has been mutated to an amino acid other than glutamine or aspartic acid, which mutation confers an increased chemical stability at pH-values of up to about 13-14 compared to the parental molecule. The protein can for example be derived from a protein capable of binding to other regions of the immunoglobulin molecule than the complementarity determining regions (CDR), such as protein A, and preferably the B-domain of Staphylococcal protein A. The invention also relates to a matrix for affinity separation, which comprises an immunoglobulin-binding protein as ligand coupled to a solid support, in which protein ligand at least one asparagine residue has been mutated to an amino acid other than glutamine.

Abstract: An isolated extracellular matrix-binding protein, designated as SdrC and its corresponding amino acid and nucleic acid sequences and motifs are described. The proteins, peptides, fragments thereof or antigenic portions thereof are useful for the prevention, inhibition, treatment and diagnosis of S. aureus infection and as scientific research tools. Further, antibodies or antibody fragments to the proteins, peptides, fragments thereof or antigenic portions thereof are also useful for the prevention, inhibition, treatment and diagnosis of S. aureus infection. In particular, the proteins or antibodies thereof may be administered to wounds or used to coat biomaterials to act as blocking agents to prevent or inhibit the binding of S. aureus to wounds or biomaterials.

Abstract: Endotoxin, also known as lipopolysaccharides (LPS), is the major mediator of septic shock due to Gram-negative bacterial infection. Chemically synthesized S3 peptide, derived from Sushi3 domain of Factor C, which is the endotoxin-sensitive serine protease of the limulus coagulation cascade, binds and neutralizes LPS activity. Fluorescent tagged-S3 is shown to detect LPS-containing bacteria. For large-scale production of S3 and to mimic other pathogen-recognizing molecules, tandem multimers of the S3 gene were constructed and expressed in E. coli. Tetramer of S3 for example is shown to display an enhanced inhibitory effect on LPS-induced activities. An affinity matrix based on tetramer of S3 is also shown to be particularly efficient at removing LPS.

Abstract: Sequences encoding two immunoreactive glycoproteins were cloned from Ehrlichia canis (p153 gene) and Ehrlichia chaffeensis (p156 gene). These two glycoproteins are species-specific immunoreactive orthologs that are useful as subunit vaccines and for serologic and molecular diagnostics for E. canis and E. chaffeensis.

Abstract: The present invention provides the following partial fragment (a) or (b) of developmentally regulated endothelial cell locus-1 (Del-1) protein: (a) a protein consisting of the amino acid sequence as shown in SEQ ID NO: 6, 8, 10, 12, 18 or 24; or (b) a protein which consists of the amino acid sequence as shown in SEQ ID NO: 6, 8, 10, 12, 18 or 24 having deletion, substitution or addition of one or several amino acids, and has deposition activity onto extracellular matrix.

Abstract: A deformable stamp for patterning a surface. The stamp can be placed in contact with an entire 3-dimensional object, such as a rod, in a single step. The stamp can also be used to pattern the inside of a tube or rolled over a surface to form a continuous pattern. The stamp may also be used for fluidic patterning by flowing material through channels defined by raised and recessed portions in the surface of the stamp as it contacts the substrate. The stamp may be used to deposit self-assembled monolayers, biological materials, metals, polymers, ceramics, or a variety of other materials. The patterned substrates may be used in a variety of engineering and medical applications.

Abstract: Reagents and methods are provided for crosslinking and immobilizing biomolecules, drugs and synthetic polymers. The reagents possess (i) a thiol or amino reactive group; and (ii) a hydrazino or oxyamino moiety. Conjugates and immobilized biomolecules are also provided.

Abstract: Proteinaceous polymers having repetitive units from naturally occurring structural proteins are employed as backbones for functionalities for crosslinking to provide strongly adherent tissue adhesives and sealants. Particularly, block copolymers of elastin and fibroin are employed having lysine substitutions in spaced apart units, where the amino group can be crosslinked using difunctional crosslinking agents.

Abstract: The present invention describes improved microfluidic systems and procedures for fabricating improved microfluidic systems, which contain one or more levels of microfluidic channels. The methods for fabrication the systems disclosed can provide a convenient route to topologically complex and improved microfluidic systems. The microfluidic systems can include three-dimensionally arrayed networks of fluid flow paths therein including channels that cross over or under other channels of the network without physical intersection at the points of cross over. The microfluidic networks can be fabricated via replica molding processes utilizing mold masters including surfaces having topological features formed by photolithography. The present invention also involves microfluidic systems and methods for fabricating complex patterns of materials, such as biological materials and cells, on surfaces utilizing the microfluidic systems.

Abstract: It has been found that syntaxin binds and regulates the nucleotide binding folds (NBFs) of sulfonylurea receptors (SURs) in a ATP- and ADP-dependent manner. The present invention therefore provides methods for identifying compounds that effect the binding between a syntaxin protein and a NBF1 and/or NBF2 of a sulfonylurea receptor (SUR). Compounds identified using the method of the invention are useful for treating and/or preventing diseases and/or conditions that have, as their underlying basis, a dysregulation of KAT 191 channels.

Abstract: On a carrier surface, a layer of S-layer proteins is produced as a carrier of functional molecules. A solution containing S-layer proteins in the form of monomers or oligomers is brought into contact with the carrier surface. Electrochemical conditions are produced in the solution such that the S-layer proteins (SU) have an electrical net charge by establishing an electrochemical potential difference between the solution and the carrier surface such that the S-layer proteins accumulate on the carrier surface. A two-dimensional crystalline structure is formed in the layer, and this can occur at a time separate from the deposition of the S-layer proteins, and under different electrochemical conditions.

Abstract: The present invention is a method for a covalent ligation of one or more molecules to one or more surfaces, that is site-specific and both rapid and high yielding. The covalent ligation to the surface is based on the reaction of an azide and a phosphinothioester to form an amide bond. The method of the invention is particularly well-suited to the immobilization of peptides, proteins or protein fragments to surfaces.

Abstract: This invention relates to hepatitis B virus (“HBV”) core antigen particles that are characterized by multiple immunogen specificities. More particularly, the invention relates to HBV core antigen particles comprising immunogens, epitopes, or other related structures, crosslinked thereto by ligands which are HBV capsid-binding peptides that selectively bind to HBV core protein. Such particles may be used as delivery systems for a diverse range of immunogenic epitopes, including the HBV capsid-binding peptides, which advantageously also inhibit and interfere with HBV viral assembly by blocking the interaction between HBV core protein and HBV surface proteins. Mixtures of different immunogens and/or capsid-binding peptide ligands may be crosslinked to the same HBV core particle. Such resulting multicomponent or multivalent HBV core particles may be advantageously used in therapeutic and prophylactic vaccines and compositions, as well as in diagnostic compositions and methods using them.

Abstract: A heterobifunctional poly(ethylene glycol) is provided having a hydrolytically degradable linkage, a first terminus comprising an acrylate group, and a second terminus comprising a target such as a protein or pharmaceutical agent or a reactive moiety capable of coupling to a target. Hydrogels can be prepared. The hydrogels can be used as a carrier for a protein or a pharmaceutical agent that can be readily released in a controlled fashion.

Abstract: Provided is a method for immobilizing a biomolecule on a solid substrate. The method includes coating the solid substrate with silane anhydride to introduce an anhydride functional group onto a surface of the solid substrate; obtaining a carboxyl group from the anhydride functional group by hydrolysis; reacting the carboxyl group with carbodiimide and succinimide to activate the carboxyl group; and contacting the biomolecule with the solid substrate having the activated carboxyl group on its surface to immobilize the biomolecule on the solid substrate.

Abstract: Arrays including microparticles having probe and marker moieties are used for the detection of a target in a sample. Microparticles are randomly immobilized on at least a portion of a substrate. A detection scheme is performed to detect the marker associated with the microparticle and the identity of the probe, and any target bound to the probe.

Abstract: Toxin derivatives are prepared by proteolytic treatment of holotoxin, and their toxicity is reduced by contacting the preparation with a ligand, which can be a metal or an antibody or another ligand. This ligand selectively binds to the toxin but not to the toxin derivative. Removing the ligand and toxin bound to the ligand further reduces toxicity. A second ligand is used to remove conjugates of the toxin and the first ligand. Compositions contain the purified derivative, optionally plus the toxin and the ligand.

Abstract: A heterobifunctional poly(ethylene glycol) is provided having a hydrolytically degradable linkage, a first terminus comprising an acrylate group, and a second terminus comprising a target such as a protein or pharmaceutical agent or a reactive moiety capable of coupling to a target. Hydrogels can be prepared. The hydrogels can be used as a carrier for a protein or a pharmaceutical agent that can be readily released in a controlled fashion.

Abstract: The present invention relates to binding moieties comprising at least one monomeric V-like domain (VLD) derived from a non-antibody ligand, the at least one monomeric V-like domain being characterized in that at least one CDR loop structure or part thereof is modified or replaced such that the solubility of the modified VLD is improved when compared with the unmodified VLD.

Abstract: This invention relates to a process for preparing a hapten-protein-polysaccharide conjugate and a hapten-protein conjugate by reacting a protein with a hapten to produce a hapten-protein conjugate, followed by reacting the hapten-protein conjugate with a polysaccharide to provide a conjugate mixture including the hapten-protein conjugate and a hapten-protein-polysaccharide conjugate. This invention also includes the process described above with the addition of a pharmaceutically acceptable medium or delivery vehicle into the conjugate mixture. The invention further includes the process described above where the hapten is luteinizing hormone releasing hormone peptides derived from E coil, or malaria derived peptides.

Abstract: A method for making a medical device having at least one biomolecule immobilized on a substrate surface is provided. One method of the present invention includes immobilizing a biomolecule comprising an unsubstituted amide moiety on a biomaterial surface. Another method of the present invention includes immobilizing a biomolecule on a biomaterial surface comprising an unsubstituted amide moiety. Still another method of the present invention may be employed to crosslink biomolecules comprising unsubstituted amide moieties immobilized on medical device surfaces. Additionally, one method of the present invention may be employed to crosslink biomolecules comprising unsubstituted amide moieties in solution, thereby forming a crosslinked biomaterial or a crosslinked medical device coating.

Abstract: Autographa californica nucleopolyhedrovirus (AcNPV) is a baculovirus widely employed as a vector for the expression of foreign genes and pest control. Although baculoviruses efficiently replicate in the nuclei of arthropod cells, the dynamics and mechanism of DNA replication within the infected cell are still poorly understood. Thus, to study such viral DNA replication, the availability of peptide ligands specific for DNA-binding protein (DBP) is needed. This work resulted in the selection of peptide ligands specifically binding to DBP for AcNPV from the FliTrx™ random peptide display library, which entails the amplification, cloning of the DBP gene from AcNPV, the construction of the expression plasinid for DBP, and the expression and purification of the recombinant His.Tag AcNPV DBP which was used as a target molecule for the selection of the peptide ligands. The affinity of peptide ligands was measured by ELISA procedures.

Abstract: Methods for improving binding of a proteinaceous substance to cell-wall material of a Gram-positive bacterium are disclosed. The proteinaceous substance includes an AcmA cell-wall binding domain, homolog or functional derivative thereof. The method includes treating the cell-wall material with a solution capable of removing a cell-wall component such as a protein, lipoteichoic acid or carbohydrate from the cell-wall material and contacting the proteinaceous substance with the cell-wall material.

Abstract: The invention relates to sequences of amino acids with the capacity to facilitate transport of an effector across a biological membrane. More specifically, the present invention relates to novel peptide transporters that specifically target certain cell types for the intracellular delivery of drugs and therapeutic agents.

Abstract: Targeting molecules are provided for use in delivering imaging agents to epithelial tissue. The targeting molecule comprises a polypeptide that forms a closed covalent loop, contains at least three peptide domains having ?-sheet character, each of the domains being separated by domains lacking ?-sheet character. The targeting molecule specifically binds to a basolateral factor attached to a basolateral domain of an epithelial cell surface causing internalization of a linked imaging agent into the cells. The polypeptide or imaging agent may be linked to a peptide amino acid sequence that directs delivery of the imaging agent to a carcinoma cell, a nucleus, or an endoplasmic reticulum.

Abstract: Multivalent immunogenic molecules comprise a carrier molecule containing at least one functional T-cell epitope and multiple different carbohydrate fragments each linker to the carrier molecule and each containing at least one functional B-cell epitope. The carrier molecule inputs enhanced immunogenicity to the multiple carbohydrate fragments. The carbohydrate fragments may be capsular oligosaccharide fragments from Streptococcus pneumoniae, which may be serotypes 1, 4, 5, 6B, 9V, 14, 18C, 19F or 23F, or Neisseria meningitidis, which may be serotype A, B, C, W-135 or Y. Such oligosaccharide fragments may be sized from 2 to 5 kDa. Alternatively, the carbohydrate fragments may be fragments of carbohydrate-based tumor antigens, such as Globo H, LeY or STn. The multivalent molecules may be produced by random conjugation or site-directed conjugation of the carbohydrate fragments to the carrier molecule.

Abstract: The invention pertains to synthetic (s) peptides derived from the viral regulatory protein R (Vpr) of the human immunodeficiency virus type 1 (HIV-1), particularly the chemical synthesis of the 96 amino acid full length Vpr protein (sVpr1-96), of a 47 amino acid long N-terminal (sVpr1-47), of a 49 amino acid long C-terminal fragment (sVpr48-96) as well as fragments thereof (sVpr1-20 and sVpr21-40) and further approximately 15 amino acid long fragments of sVpr1-96. As fragments or full length products of the HIV-1 regulatory protein, those products are used in biological assays, for molecular and structural characterization of Vpr and domains thereof, as well as for the development of anti-Vpr antibodies directed against Vpr peptide sequences.

Abstract: In a dextran coated surface disposed on a carrier, the connections between the dextran and the carrier surface are formed by a photolinker, the dextran coating being attached to the carrier surface by co-immobilization of a mixture of dextran and the photolinker.

Abstract: This invention provides materials and methods for the site specific attachment of virtually any moiety to a layered silicate surface. The methods involve covalently attaching the moiety to an arginine tag; and contacting the arginine tag with the layered silicate (e.g., mica) surface.

Abstract: The present invention relates to a composition comprsing a peptide immunogen useful for the prevention and treatment of Alzheimer's Disease. More particularly, the peptide immunogen comprises a main functional/regulatory site, an N-terminal fragment of Amyloid ? (A?) peptide linked to a helper T cell epitope (Th) having multiple class II MHC binding motifs. The peptide immunogen elicit a site-directed immune response against the main functional/regulatory site of the A? peptide and generate antibodies, which are highly cross-reactive to the soluble A?1-42 peptide and the amyloid plaques formed in the brain of Alzheimer's Disease patients. The antibodies elicited being cross reactive to the soluble A?1-42 peptide, promote fibril disaggregation and inhibit fibrillar aggregation leading to immunoneutralization of the “soluble A?-derived toxins”; and being cross-reactive to the amyloid plaques, accelerate the clearance of these plaques from the brain.

Abstract: A method is provided for applying a fluid onto a surface of a solid substrate. The method employs a distribution member having an upper surface and a lower surface, and including a permeable portion having channels therethough. The distribution member is positioned such that the lower surface of the distribution member is in opposing relation to the surface of the substrate. Once the distribution member is in position, the fluid is dispensed onto the upper surface of the permeable portion of the distribution member such that the fluid penetrates the distribution member and is retained thereby. In addition, a distribution pressure differential is applied between the upper and lower surfaces without using mechanical means such as a squeegee so that a portion of the fluid passes through the channels of the permeable portion of the distribution member and onto the solid substrate surface.

Abstract: Cytokines and their receptors have proven usefulness in both basic research, animal models, and as therapeutics. The present invention provides a new cytokine receptor designated as “mouse Zcytor16,” which can bind and antagonize the IL-TIF cytokine.