Abstract: A method of imaging a region of interest of a body, the body having sites outside the region which can produce image clutter. The method includes: generating a first pattern of vibration within the body to produce a localised first displacement at the region and localised first displacements at the clutter-producing sites; while the body undergoes the first displacements, generating ultrasound signals from the region, and detecting the ultrasound signals to generate a first image of the region; generating a second pattern of vibration within the body to produce a localised second displacement at the region and localised second displacements at the clutter-producing sites; while the body undergoes the second displacements, generating ultrasound signals from the region, and detecting the ultrasound signals to generate a second image of the region; and combining the first and second images to produce a third image of the region.

Abstract: Prodigiosin analogs which reactivate the p53 pathway are provided, as well as compositions of these compounds, and methods for reactivation of the p53 pathway using these compounds are provided. The prodigiosin analogs may be used to treat cancer in which p53 mutation plays a role, including prostate cancer, breast cancer, kidney cancer, ovarian cancer, lymphoma, leukemia, and glioblastoma, among others.

Abstract: The present disclosure provides antibodies that specifically bind to human OX40 receptor (OX40) and compositions comprising such antibodies. In a specific aspect, the antibodies specifically bind to human OX40 and modulate OX40 activity, e.g., enhance, activate, or induce OX40 activity, or reduce, deactivate, or inhibit OX40 activity. The present disclosure also provides methods for treating disorders, such as cancer, by administering an antibody that specifically binds to human OX40 and modulates OX40 activity, e.g., enhances, activates, or induces OX40 activity. Also provided are methods for treating autoimmune or inflammatory diseases or disorders, by administering an antibody that specifically binds to human OX40 and modulates OX40 activity, e.g., reduces, deactivates, or inhibits OX40 activity.

Abstract: The present invention relates to a protein binding to GARP in the presence of TGF-? and uses thereof.

Abstract: The present invention provides a method of treatment of prostate cancer, comprising administering a therapeutically effective amount of an inhibitor of IL-23 and/or an inhibitor of IL-23R to a mammalian patient in need thereof. The prostate cancer may be castration resistant prostate cancer (CRPC). The inhibitor may, for example, be an anti-IL-23 antibody, such as risankizumab, guselkumab or tildrakizumab. The method of treatment may further comprise administration of androgen deprivation therapy, such as enzalutamide. Also provided is a method of predicting the development of resistance to androgen deprivation therapy (ADT) in a prostate cancer in a mammalian patient and a related screening method.

Abstract: Mice comprising a modified p21-activated kinase (Pak) inhibitor domain (PID*), optionally linked with GST and capable of constitutive expression of PID are provided. Also provided are cells, tissue, and organs obtainable from such mice, and methods for producing mice comprising a modified p21-activated kinase (Pak) inhibitor domain (PID*).

Abstract: The present disclosure provides antibodies that specifically bind to human glucocorticoid-induced TNFR family related receptor (GITR) and compositions comprising such antibodies. In a specific aspect, the antibodies specifically bind to human GITR and modulate GITR activity, e.g., enhance, activate or induce GITR activity, utilizing such antibodies. The present disclosure also provides methods for treating disorders, such as cancer and infectious diseases, by administering an antibody that specifically binds to human GITR and modulates GITR activity e.g., enhances, activates or induces GITR activity.

Abstract: The present invention provides soluble single wall nanotube (SWNT) constructs functionalized with a plurality of a targeting moiety and a plurality of one or more payload molecules attached thereto. The targeting moiety and the payload molecules may be attached to the soluble SWNT via a DNA or other oligomer platform attached to the SWNT. These soluble SWNT constructs may comprise a radionuclide or contrast agent and as such are effective as diagnostic and therapeutic agents. Methods provided herein are to diagnosing or locating a cancer, treating a cancer, eliciting an immune response against a cancer or delivering an anticancer drug in situ via an enzymatic nanofactory using the soluble SWNT constructs.

Abstract: Described herein are approaches for the improved detection, identification, and/or quantification of target nucleic acids. These approaches provide a means of detecting, identifying, and/or quantifying rare target nucleic acid molecules, including DNA and RNA molecules, from the same sample, and in the same reaction, by using “hairpin barcode primers,” as the term is defined herein, to incorporate unique barcodes into target nucleic acids in a PCR pre-amplification step.

Abstract: Described herein are amorphous and crystalline forms of the androgen receptor modulator 4-[7-(6-cyano-5-trifluoromethylpyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]oct-5-yl]-2-fluoro-N-methylbenzamide. Also described are pharmaceutical compositions suitable for administration to a mammal that include the androgen receptor modulator, and methods of using the androgen receptor modulator, alone and in combination with other compounds, for treating diseases or conditions that are associated with androgen receptor activity.

Abstract: Disclosed is a method for searching, identifying, or validating a marker CACNA2D1 of tumor-initiating cells. The method comprises a step of immunizing an animal using HEP-12 cells originating from a recurrent tumor and rich in originating cells. Also disclosed is a monoclonal antibody specially recognizing CACNA2D1 or antigen-binding fragments thereof, and the use thereof for treating or preventing tumors or diseases or conditions related to CACNA2D1.

Abstract: The present invention provides a fluorescent silica-based nanoparticle that allows for precise detection, characterization, monitoring and treatment of a disease such as cancer. The nanoparticle has a range of diameters including between about 0.1 nm and about 100 nm, between about 0.5 nm and about 50 nm, between about 1 nm and about 25 nm, between about 1 nm and about 15 nm, or between about 1 nm and about 8 nm. The nanoparticle has a fluorescent compound positioned within the nanoparticle, and has greater brightness and fluorescent quantum yield than the free fluorescent compound. The nanoparticle also exhibits high biostability and biocompatibility. To facilitate efficient urinary excretion of the nanoparticle, it may be coated with an organic polymer, such as poly(ethylene glycol) (PEG). The small size of the nanoparticle, the silica base and the organic polymer coating minimizes the toxicity of the nanoparticle when administered in vivo.

Abstract: Compounds that are not related to NAD, and which target PARP1-histone H4 interaction are provided, as well as compositions of these compounds, and methods for specific inhibition of poly(ADP-ribose) polymerase 1 (PARP-1) using these compounds are provided. These PARP-1 inhibitors may be used to treat cancer in which PARP-1 activation or biologic activity plays a role, including prostate cancer, breast cancer, kidney cancer, ovarian cancer, lymphoma, leukemia, and glioblastoma, among others.

Abstract: The present invention provides a fluorescent silica-based nanoparticle that allows for precise detection, characterization, monitoring and treatment of a disease such as cancer. The nanoparticle has a range of diameters including between about 0.1 nm and about 100 nm, between about 0.5 nm and about 50 nm, between about 1 nm and about 25 nm, between about 1 nm and about 15 nm, or between about 1 nm and about 8 nm. The nanoparticle has a fluorescent compound positioned within the nanoparticle, and has greater brightness and fluorescent quantum yield than the free fluorescent compound. The nanoparticle also exhibits high biostability and biocompatibility. To facilitate efficient urinary excretion of the nanoparticle, it may be coated with an organic polymer, such as poly(ethylene glycol) (PEG). The small size of the nanoparticle, the silica base and the organic polymer coating minimizes the toxicity of the nanoparticle when administered in vivo.

Abstract: The present invention provides a compound of formula I; wherein R1 is an alkyl pyrazole or an alkyl carboxamide, and R2 is a hydroxycycloalkyl; or a pharmaceutically acceptable salt thereof, and compositions containing these compounds, for use to treat a brain tumor, particularly glioblastoma. The invention provides effective treatment of a brain tumor and can be used by oral administration of a compound of Formula I as further described herein. The invention also provides a method to treat a subject having a brain tumor such as glioblastoma, wherein the method comprises administering to the subject an effective amount of a compound of Formula I. Gene signatures correlated with successful treatment using these methods are also disclosed.

Abstract: Described herein are amorphous and crystalline forms of the androgen receptor modulator 4-[7-(6-cyano-5-trifluoromethylpyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3,4]oct-5-yl]-2-fluoro-N-methylbenzamide. Also described are pharmaceutical compositions suitable for administration to a mammal that include the androgen receptor modulator, and methods of using the androgen receptor modulator, alone and in combination with other compounds, for treating diseases or conditions that are associated with androgen receptor activity.

Abstract: Disclosed are methods for sequencing immune cell receptor repertoires from immune cell populations, and kits containing primer mixtures for the sequencing of immune cell receptor repertoires.

Abstract: The present disclosure provides compounds comprising modified oligonucleotides for use in CRISPR. In certain embodiments, such modified oligonucleotides provide improved properties of crRNA.

Abstract: The present invention relates to methods for haplotype determination and, m particular, haplotype determination at the whole genome level as well as targeted haplotype determination.

Abstract: The instant disclosure provides antibodies that specifically bind to human CTLA-4 and antagonize CTLA-4 function. Also provided are pharmaceutical compositions comprising these antibodies, nucleic acids encoding these antibodies, expression vectors and host cells for making these antibodies, and methods of treating a subject using these antibodies.