Abstract: Disclosed herein are meningococcal immunogenic conjugates which can elicit immune responses against meningococcal polysaccharides (PS) from groups A, C, W-135, and Y and group B factor H binding protein (fHbp). The disclosed conjugates also exhibit bactericidal activity against meningococcal A, C, W-135, Y, B, and X serogroups. Also disclosed are improved methods for preparing conjugates, such as immunogenic conjugates, including activation of a polysaccharide with a cyanylation agent at about 4° C.

Abstract: Disclosed herein are methods of eliciting an immune response to a JC polyomavirus (JCV) by administering an effective amount of an immunogenic composition including an isolated JCV VP1 polypeptide or a nucleic acid encoding the VP1 polypeptide to a subject. VP1 polypeptides and immunogenic compositions suitable for use in the methods are disclosed herein, including JCV genotype 2 VP1 polypeptides and/or JCV genotype 3 polypeptides. Also disclosed are methods of identifying a subject at risk of developing progressive multifocal leukoencephalopathy (PML). In some embodiments, the methods include obtaining a biological sample from a subject, detecting presence or absence of JCV neutralizing antibodies in the sample from the subject, and identifying that the subject is at risk of developing PML if there is an absence of detectable JCV neutralizing antibodies in the sample from the subject.

Abstract: The invention provides a chimeric antigen receptor (CAR) comprising an antigen binding domain specific for TSLPR, a transmembrane domain, and an intracellular T cell signaling domain. Nucleic acids, recombinant expression vectors, host cells, populations of cells, antibodies, or antigen binding portions thereof, and pharmaceutical compositions relating to the CARs are disclosed. Methods of detecting the presence of a proliferative disorder, e.g., cancer, in a mammal and methods of treating or preventing a proliferative disorder, e.g., cancer, in a mammal are also disclosed.

Abstract: Disclosed herein are methods for detecting, diagnosing and/or prognosing a malignant adrenocortical tumor. Also disclosed are methods of treating a malignant adrenocortical tumor, such as ACC. In some examples, the method of diagnosing and/or prognosing includes obtaining a sample comprising genomic DNA from a subject at risk of acquiring or suspected to have an adrenocortical tumor; isolating genomic DNA from the sample; and measuring the level of one or more methylated genomic CpG dinucleotide sequences in one or more of the adrenocortical genomic targets in the sample, wherein an increase in the level of methylation of the one or more genomic CpG dinucleotide sequences in the sample compared to a control indicates a malignant adrenocortical tumor.

Abstract: The invention comprises a method for inducing broadly cross-neutralizing antibodies against cutaneous and mucosal papillomavirus types or against heterologous papillomavirus types in humans comprising administering to a human in need thereof an immunogenic peptide or protein (or polynucleotide encoding therefor), where the immunogenic peptide or protein is: (a) a peptide or protein of at least 10 amino acid residues in length having a sequence corresponding to either a sequence from the N terminal amino acids 1-200 of papillomavirus L2 protein (for cross-neutralizing antibodies against cutaneous and mucosal papillomavirus types) or a sequence from the N terminal amino acids 1-88 of papillomavirus L2 protein (for cross-neutralizing antibodies against heterologous papillomavirus types), (b) a peptide or protein of at least 10 amino acid residues in length with at least 55% identity with the sequence from (a), or (c) a peptide or protein as defined in either (a) or (b) which is conjugated or fused to a protein o

Abstract: The invention provides methods of treating or preventing malaria comprising administering to an animal an effective amount of a compound of formula I: Q-Y—R1—R2??(I), wherein Q, Y, R1, and R2 are as described herein. Methods of inhibiting a plasmodial surface anion channel of a parasite in an animal are also provided. The invention also provides pharmaceutical compositions comprising a compound represented by formula I in combination with any one or more compounds represented by formulas II, V, and VI. Use of the pharmaceutical compositions for treating or preventing malaria or for inhibiting a plasmodial surface anion channel in animals including humans are also provided. Also provided by the invention are clag3 amino acid sequences and related nucleic acids, vectors, host cells, populations of cells, antibodies, and pharmaceutical compositions.

Abstract: Disclosed are specific biomarkers that allow for early testing of preeclampsia/HELLP syndrome. Thus, a method is provided predicting preeclampsia in a pregnant woman. Also disclosed is a kit comprising means for assaying a sample from a pregnant woman for the concentrations of the specific biomarkers.

Abstract: The invention provides methods and compounds for the treatment and prevention of malaria infection and transmission in a mammal by administering compounds of the invention to a mammal having or suspected of having a malaria infection. The invention also provides pharmaceutical compositions that can kill or arrest the growth of Plasmodium organisms, and especially Plasmodium falciparum, thereby preventing or blocking transmission of malaria as well as treating malaria infection.

Abstract: The present invention includes a novel protein, also referred to herein as simukunin, that inhibits the function of several physiologically important enzymes. Simukunin is a potent inhibitor of the blood coagulation cascade, inhibiting Factor Xa and functioning as an efficient anticoagulant. Simukunin also inhibits the serine proteases elastase and cathepsin and demonstrates anti-inflammatory properties. Also included are methods of making and using simukunin.

Abstract: Substituted pyrazolopyrimidines and dihydropyrazolopyrimidines and related compounds, their methods of manufacture, compositions containing these compounds, and methods of use of these compounds in treating lysosomal storage disorders such as Gaucher disease are described herein. The compounds are of general Formula (I) in which variables R1-R7 and X are described in the application.

Abstract: A containment system for reducing the release of harmful respirable particles through surface openings in equipment that carries sand includes a filter-receiving member configured to be coupled over an opening in a surface of the equipment and a filter member configured to be coupled to the filter-receiving member. The filter-receiving member can have a first side, a second side, and a passageway extending from the first side to the second side. The filter can have a porosity that permits air to flow through the filter member and restricts the flow of solid particulates.

Abstract: Delivery devices for delivering encircling implants can include two separate limbs that are held together at a distal articulation by the implant being delivered. The implant can comprise a suture and/or a braided tube. The implant can extend through or over the limbs. The implant and at least a distal portion of the limbs can be compressible into a delivery shape that allows for advancement through the lumen of a delivery catheter. When the distal portion of the limbs move out of the delivery catheter, the limbs and implant can resiliently assume a loop shape that is complementary to a shape of a target around which the encircling implant is to be placed. The limbs are then retracted from along the implant to leave the implant in the desired delivery position. The delivery device can be used to place encircling implants around the heart or other targets, and the implant can be tightened to exert compressive force on the target.

Abstract: The claimed subject matter relates to allosteric modulation of A3 adenosine receptor (A3AR) and provides for the use of an A3 adenosine receptor modulator (A3RM), for the preparation of pharmaceutical compositions for modulating the A3AR in a subject, as well as pharmaceutical compositions including the same and therapeutic methods including administering to a subject an amount of an A3RM, the amount being effective to modulate A3AR activity. The A3RM according to claimed subject matter are 1H-Imidazo-[4,5-c]quinolin-4-amine derivatives. Also provided are 1H-Imidazo-[4,5-c]quinolin-4-amine derivatives.

Abstract: Isolated VHH monoclonal antibodies are disclosed that specifically bind to a Norovirus polypeptide. In some embodiments, the Norovirus is a Genogroup I Norovirus or a Genogroup II Norovirus. In other embodiments, the Norovirus is Norwalk or MD2004 virus. In some embodiments, the monoclonal antibodies specifically bind VP1. Also disclosed are compositions including the disclosed antibodies, nucleic acids encoding these antibodies, expression vectors including the nucleic acids, and isolated host cells that express the nucleic acids. The antibodies and compositions disclosed herein can be used for detecting the presence of a Norovirus in a biological sample, or detecting a Norovirus infection. Also disclosed are methods of treating and/or preventing a NoV infection.

Abstract: Methods of inhibiting undesired angiogenesis are provided, which methods include administering to a subject a therapeutically effective amount of at least one of the compounds described herein, or a pharmaceutically acceptable salt thereof.

Abstract: Methods of obtaining a cell population enriched for tumor-reactive T cells, the method comprising: (a) obtaining a bulk population of peripheral blood mononuclear cells (PBMCs) from a sample of peripheral blood; (b) specifically selecting CD8+T cells that also express PD-1 and/or TIM-3 from the bulk population; and (c) separating the cells selected in (b) from unselected cells to obtain a cell population enriched for tumor-reactive T cells are disclosed. Related methods of administering a cell population enriched for tumor-reactive T cells to a mammal, methods of obtaining a pharmaceutical composition comprising a cell population enriched for tumor-reactive T cells, and isolated or purified cell populations are also disclosed.

Abstract: Disclosed are methods of enhancing the chemotherapeutic treatment of tumor cells, reducing resistance of a cancer cell to a chemotherapeutic agent, a method of inhibiting ABCG2 or MRP1 in a mammal afflicted with cancer, and a method of increasing the bioavailability of an ABCG2 substrate drug in a mammal. The methods comprise administering peliomycin and other compounds described herein.

Abstract: Disclosed are yeast-based immunotherapeutic compositions comprising Brachyury antigens, and methods for the prevention and/or treatment of cancers characterized by the expression or overexpression of Brachyury.

Abstract: In this application is described a composition and method for inducing in a subject anti-hapten antibodies without inducing antibodies to the carrier protein. Kits for designing and making compositions with desired haptens are also described.

Abstract: The invention provides a method for detecting the presence or absence of a biomarker in a biological sample at a very low concentration comprising the steps of (a) contacting the biological sample with a capture binding sequence immobilized on a surface, (b) providing a conjugate comprising a detection binding sequence-glucose oxidase, (c) contacting the surface with the detection binding sequence-glucose oxidase conjugate, (d) separating any unbound detection binding sequence-glucose oxidase conjugate from the surface, (e) incubating the resulting surface with a glucose solution and a mixture comprising gold nanoparticles and a gold salt, wherein the gold nanoparticles have an initial particle size of about 5 nm, and (f) observing any change in color of the mixture. The invention also provides a method for diagnosing the presence of a prostate cancer biomarker in a subject and a kit for detecting or quantifying a biomarker in a biological sample.