Abstract: Devices and methods are disclosed for the treatment or repair of regurgitant cardiac valves, such as a mitral valve. An annuloplasty device can be placed in the coronary sinus to reshape the mitral valve and reduce mitral valve regurgitation. A protective device can be placed between the annuloplasty device and an underlying coronary artery to inhibit compression of the underlying coronary artery by the annuloplasty device in the coronary sinus. In addition, the protective device can inhibit compression of the coronary artery from inside the heart, such as from a prosthetic mitral valve that exerts radially outward pressure toward the coronary artery. The annuloplasty device can also create an artificial inner ridge or retaining feature projecting into the native mitral valve region to help secure a prosthetic mitral valve.

Abstract: Viral infection has been suspected in the development of primary Sjögren's syndrome (pSS). Using a custom viral microarray, hepatitis delta virus (HDV) genomes and antigens were detected in minor salivary glands of patients with pSS. Expression of HDV antigens in healthy mice led to a Sjögren's syndrome-like pathogenesis characterized by a reduction in salivary flow, increase in lymphocytic foci, and the development of an autoantibody profile similar to HDV-positive patients. Also described herein is the detection of HDV in patients diagnosed with lymphoma. Expression of HDV antigen in healthy mice resulted in the development of tertiary lymphoid structures characteristic of the early stages of lymphoma. A sensitive, nested qPCR assay to detect HDV transcript and/or HDV genome in patient samples is also described.

Abstract: Described herein is the use of rabbit hybridoma technology, along with a panel of truncated mesothelin domain fragments, to identify anti-mesothelin mAbs that bind specific regions of mesothelin. In one aspect of the present disclosure, the rabbit mAbs bind an epitope that is not part of Region I. In particular, the identified mAbs (YP187, YP223, YP218 and YP3) bind either Region II (391-486), Region III (487-581) or a native conformation of mesothelin with subnanomolar affinity. These antibodies do not compete for binding with the mesothelin-specific immunotoxin SS1P or mesothelin-specific antibody MORAb-009. In another aspect, disclosed is a high-affinity rabbit mAb that binds Region I of mesothelin (YP158). YP158 binds native mesothelin protein in cancer cells and tissues with high affinity and specificity.

Abstract: Described herein is the identification of human monoclonal antibodies that bind GPC3 or heparan sulfate (HS) chains on GPC3 with high affinity. The antibodies described herein are capable of inhibiting HCC cell growth and migration. Provided are human monoclonal antibodies specific for GPC3 or HS chains on GPC3, including immunoglobulin molecules, such as IgG antibodies, as well as antibody fragments, such as single-domain VH antibodies or single chain variable fragments (scFv). Further provided are compositions including the antibodies that bind GPC3 or HS chains on GPC3, nucleic acid molecules encoding these antibodies, expression vectors comprising the nucleic acids, and isolated host cells that express the nucleic acids. Methods of treating cancer and/or inhibiting tumor growth or metastasis are also provided. Further provided are methods of detecting cancer in a subject and confirming a diagnosis of cancer in a subject.

Abstract: In T lymphocytes, p38 mitogen activated protein kinase (MAPK) can be activated through an alternative pathway that involves phosphorylation at tyrosine 323. Disclosed herein is the identification of a minimal region of the growth arrest and DNA damage-inducible alpha (Gadd45?) protein that is required for binding to and inhibition of tyrosine 323-phosphorylated p38 in T cells. The disclosed Gadd45? polypeptides inhibit proliferation of T cells in response to T cell receptor stimulation, inhibit differentiation of T cells into Th1 or Th17 cells, inhibit the production of proinflammatory cytokines, and reduce tumor formation and growth of inflammatory cancers, such as pancreatic cancer.

Abstract: Methods for preparing an oligosaccharide—protein carrier immunogenic conjugate or a polysaccharide—protein carrier immunogenic conjugate. The methods include obtaining an oligosaccharide or polysaccharide having a KDO moiety located at the terminal reducing end of the oligosaccharide or polysaccharide that includes a carbonyl functional group; and reacting the carbonyl functional group of the KDO moiety with an aminooxylated protein carrier molecule resulting in a conjugate that includes a covalent oxime bond between the oligosaccharide and the protein carrier or the polysaccharide and the protein carrier.

Abstract: Compositions and methods are provided for the treatment or prevention of RSV disease by modulating RSV infection and immunity. In particular, amino acid sequences in the RSV G glycoprotein, containing the chemokine motif defined as C-X-X-X-C (or CX3C), are identified that are essential in causing RSV infection and disease. The chemokine motif is biologically active and participates in virus binding to and infection of susceptible cells. The prevention or treatment of RSV infection is achieved by interfering with the motif, such as by administering a vaccine in which the motif is altered or by administration or induction of blocking molecules that inhibit the biological activity of the motif.

Abstract: The present invention relates to a vaccine for increasing the immunogenicity of a tumor antigen thus allowing treatment of cancer, as well as a vaccine that increases the immunogenicity of a viral antigen, thus allowing treatment of viral infection, including immunodeficiency virus (HIV) infection. In particular, the present invention provides a fusion protein comprising a defensin fused to either a tumor antigen or viral antigen which is administered as either a protein or nucleic acid vaccine to elicit an immune response effective in treating cancer or effective in treating or preventing viral infection.

Abstract: An isolated, pure homogeneous population of mammalian astrocyte restricted precursor cells which is CD44 immunoreactive and which generate astrocytes but not oligodendrocytes is provided. Methods for isolating and using these mammalian astrocyte restricted precursor cells are also provided.

Abstract: Disclosed are immunogenic peptides, related fusion proteins, nucleic acids encoding the peptides or fusion proteins, conjugates, expression vectors, host cells, and antibodies. Also, disclosed are pharmaceutical compositions, vaccines for use in the treatment or prevention of cancer, e.g., alveolar rhabodomyosarcoma, methods of stimulating a T cell to kill a tumor cell, methods of stimulating CD4+ and CD8+ T cells, and methods of treating or preventing cancer are further provided herein.

Abstract: The present invention provides methods/techniques and apparatus for displaying an angulation of a cassette and thus a patient at a time when an x-ray image is taken to provide for a better comparison of day to day improvement of the patient. More specifically, the present invention, allows a movable object to roll freely within in a passageway within an enclosure in relation to an angulation of a cassette. In order to correlate the position of the movable object in the enclosure with the angle at which the cassette is currently placed, a plurality of markers are disposed in or protruded from the inner surface of the passageway. Based upon the position of the movable object in relation to a particular marker at the time an x-ray is taken, the user can identify the angulation at which the cassette is currently positioned.

Abstract: Disclosed are inhibitors of the plasmodial surface anion channel (PSAC) inhibitors and the use thereof in treating or preventing malaria in an animal such as a human, comprising administering an effective amount of an inhibitor or a combination of inhibitors. An example of such an inhibitor is a compound of formula I, or a pharmaceutically acceptable salt thereof, wherein R1 to R7 are as described herein.

Abstract: The present invention relates to a variant of a parent polypeptide comprising an Fc region, which variant binds an Fc gamma receptor (Fc?R) with lower affinity than the parent polypeptide and comprises a deletion of at least one amino acid in about position 100 to about position 150 in the Fc region and related nucleic acids, vectors, host cells and methods of producing the variant and methods for preventing or treating a disorder in a mammal.

Abstract: The invention provides an isolated or purified T cell receptor (TCR) having antigenic specificity for a cancer antigen, e.g., a renal cell carcinoma antigen, wherein the TCR recognizes the cancer antigen in a major histocompatibility complex (MHC)-independent manner. Also provided are related polypeptides, proteins, nucleic acids, recombinant expression vectors, isolated host cells, populations of cells, antibodies, or antigen binding portions thereof, and pharmaceutical compositions. The invention further provides a method of detecting the presence of cancer in a host and a method of treating or preventing cancer in a host using the inventive TCRs or related materials.

Abstract: The present invention provides for novel methods for regulating and detecting the cytosine methylation status of DNA. The invention is based upon identification of a novel and surprising catalytic activity for the family of TET proteins, namely TET1, TET2, TET3, and CXXC4. The novel activity is related to the enzymes being capable of converting the cytosine nucleotide 5-methylcytosine into 5-hydroxymethylcytosine by hydroxylation.

Abstract: The present invention provides methods for producing cell populations enriched for stable, regulatory T cells (Tregs). In particular, the invention relates to methods for culturing T cells such that the final culture is enriched for stable, regulatory T cells. It also relates to methods for stabilizing regulatory T cells. Also provided are compositions enriched for stable, regulatory T cells, which are useful for treating individuals in need of such treatment. The methods and compositions disclosed herein can also be used to treat an individual suffering from an immune-mediated disease.

Abstract: In one embodiment, the invention provides a multiclade HIV plasmid DNA or viral vector vaccine including components from different clades of Env (optionally Env chimeras) and Gag-Pol-(optionally)Nef from a singlr clade. The vaccine of the invention may further include V1, V2, V3, or V4 deletions or combinations thereof. In another embodiment, the invention provides multiclade HIV envelope immunogens.

Abstract: The present invention is directed to the induction and characterization of a humoral immune response targeting “entry-relevant” gp41 structures. In its broadest aspect, the present invention is directed to methods of raising a neutralizing antibody response to a broad spectrum of HIV strains and isolates. The present invention targets particular molecular conformations or structures that occur at the cell surface of HIV during viral entry into host cells. Such a humoral response can be generated in vivo as a prophylactic measure in individuals to reduce or inhibit the ability of HIV to infect uninfected cells in the individual's body. Such a response can also be employed to raise antibodies against “entry relevant” gp41 structures. These antibodies can be employed for therapeutic uses, and as tools for further illuminating the mechanism of HIV cell entry.

Abstract: The present invention provides a compound of the formula (I) or (II, wherein R1 is H, alkyl, alkenyl or aryl, R2 is H, alkyl or aryl, R3 is H, a alkyl, alkenyl or aryl, R4 and R4-R8 are independently R10, C(O)R10 or SO2R10, wherein R10 is H, alkyl, alkenyl or aryl, and R9 is R9a, C(O)R9a or SO2R9a, wherein R9a is H, alkyl, alkenyl or aryl. R9a can be unsubstituted or substituted with one or more oxo(?O), OR9b, OC(O)R9b, OSO2R9b, NHR9b, NHC(O)R9b and NHSO2R9b groups. R9b is H, alkyl, alkenyl, or aryl. R9b can be unsubstituted or substituted with one or more groups such as oxo(?O), OR9c, CO2R9c, CO2R9c and OC(O)R9c. R9c is H, or a unsubstituted or substituted alkyl, alkenyl or aryl. The present invention further provides a composition comprising at least one compound of the present invention and a pharmaceutically acceptable carrier, alone or in combination with at least one additional active agent.

Abstract: The present invention relates to approaches, methods, pharmaceuticals and uses directed to the curative treating or preventing of Primary Progressive Multiple Sclerosis (PP-MS), by using 2,3-dimethoxy-5-methyl-6-(10-hydroxydecyl)-1,4-benzoquinone (Idebenone) as the active agent.