Abstract: In one aspect, the invention features a method for identifying a drug-modulated polypeptide substrate of cereblon (CRBN). In another aspect, the invention features a method of identifying a polypeptide target of a modulator of CRBN. In yet another aspect, the invention provides methods of monitoring or characterizing the sensitivity of a subject to a modulator of CRBN.

Abstract: A stent apparatus, system, and method that senses wall shear stress by measuring fluid flow at localized areas within the stent, that processes measured information through an integrated circuit, and selectively sends power to mechanically controllable stent surfaces which results in localized geometric changes. In various embodiments the stent apparatus, system, and method sends data to outside the body in real time.

Abstract: Described in the present application are methods for preparing populations of hematopoietic stem cells (HSCs), e.g., autologous and/or allogenic HSCs, using mechanical stretching or Trpv4 agonisists, and methods of use of the HSCs in transplantation. In some embodiments, the methods include providing a population comprising hemogenic endothelial (HE) cells, and (i) contacting the HE cells with an amount of an agonist of transient receptor potential cation channel-subfamily vanilloid member 4 (Trpv4); and/or (ii) subjecting the cells to cyclic 2-dimensional stretching, for a time and under conditions sufficient to stimulating endothelial-to-HSC transition. Also provided herein are methods for treating subjects who have, bone marrow, metabolic, and immune diseases; the methods include administering to the subject a therapeutically effective amount of hematopoietic stem cells (HSCs) obtained by a method described herein.

Abstract: This invention generally provides compounds, pharmaceutical compositions, and methods for their use, which include methods that result in increased expression in an Atoh1 gene (e.g., Hath1) in a biological cell. More specifically, the invention relates to the treatment of diseases and/or disorders that would benefit from increased Atoh1 expression, e.g., a hearing impairment or imbalance disorder associated with a loss of auditory hair cells, or a disorder associated with abnormal cellular proliferation.

Abstract: Described herein are novel compositions comprising bispecific and multispecific polypeptide agents, and methods using these agents for targeting cells, such as functionally exhausted or unresponsive immune cells, that co-express the inhibitory receptors PD-1 and TIM-3. These compositions and methods are useful for the treatment of chronic immune conditions, such as persistent infections or cancer.

Abstract: Provided herein are pharmaceutical compositions for local administration of metabolic inhibitors, methods of locally administering such compositions, and rapid diagnostic methods for identifying mutant allele during the course of a surgical procedure.

Abstract: The technology described herein is directed to methods and compositions for the treatment of hypertension, e.g. pulmonary arterial hypertension, relating to inhibition of TGF?1, TGF?3, and/or GDF-15.

Abstract: Provided herein are methods of treating or reducing the risk of a cardiovascular disease using a lipid lowering agent (e.g., statin and/or PCSK9 inhibitor) and an anti-inflammatory agent (e.g., a pro-inflammatory cytokine inhibitor). Further provided herein are methods of predicting the recurrence rate of a subject who has received or is undergoing therapy for a cardiovascular disease with a lipid lowering agent on the basis of the C-reactive protein (CRP) level in the subject. In some embodiments, the recurrence rate can be reduced using an anti-inflammatory agent.

Abstract: Systems and methods execution of a magnetic resonance imaging pulse sequence including a first spin-echo echo planar imaging pulse sequence to acquire first data of a volume, a second spin-echo echo planar imaging pulse sequence comprising a first one or more diffusion gradient pulses to acquire first diffusion data of the volume, a third spin-echo echo planar imaging pulse sequence comprising a second one or more diffusion gradient pulses to acquire second diffusion data of the volume, and a fourth spin-echo echo planar imaging pulse sequence comprising a third one or more diffusion gradient pulses to acquire third diffusion data of the volume, generation of perfusion metrics based on the first data, and generation of diffusion metrics based on the first data, the first diffusion data, the second diffusion data, and the third diffusion data.

Abstract: Provided are methods of treating diabetes and/or obesity in a subject in need thereof, and methods of increasing the amount of cholic acid-7-sulfate (CA7S) in a subject. Further provided herein are methods of administering CA7S to a subject. Also provided are compositions and kits comprising cholic acid-7-sulfate, or a salt thereof for use in the treatment of diabetes and/or obesity.

Abstract: A family of bioactive compounds identified in self-resolving inflammatory exudates is disclosed. The compounds give UV chromophores characteristics of a conjugated triene double bond system coupled to an auxochrome allylic to the triene. Further elucidation of the compounds reveals that they have an oxylipin backbone conjugated to a peptide or amino acid moiety via an auxochrome. In some embodiments the auxochrome is sulfur. However, the auxochrome may be NH, CH2 or O. The compounds have potent bioactivity, in vitro, and, in vivo, including promoting resolution of infection, stimulating macrophage phagocytosis of bacteria; protecting tissues from neutrophil mediated damage, promoting tissue repair and regeneration and preventing or limiting second organ reflow/reperfusion damage.

Abstract: Target analyte detection devices include a housing having a potentiostat and a microcontroller coupled to the potentiostat. The device also includes a substrate having a plurality of electrodes on a first surface of the substrate. A first set of electrodes of the plurality of electrodes defines a first sample detection region. The substrate is removably attachable to the housing such that the first set of electrodes is coupled to the potentiostat upon attaching the substrate to the housing. The device also includes a magnet assembly couplable to a second surface of the substrate. The magnet assembly includes a magnet positioned in the magnet assembly such that a magnetic field from the magnet extends through the substrate and the first set of electrodes into an area above the first sample detection region upon coupling the magnet assembly to the substrate.

Abstract: This disclosure relates to nanoparticles comprising a core comprising a poly(ester amide) polymer comprising a repeating unit of Formula (Ia): and a repeating unit of Formula (Ib): wherein W1, W2, X1, A1, X2, A2, and X3 are as described herein, a payload molecule within the core, and a surface layer comprising a targeting ligand that binds or reacts selectively with a receptor on the outside surface of a cell. Methods of making such nanoparticles, and methods of using such nanoparticles as drug delivery vehicles, are also provided.

Abstract: Methods and compositions for the treatment of conditions associated with pharyngeal airway muscle collapse while the subject is in a non-fully conscious state, e.g., sleep apnea and snoring, comprising administration of a norepinephrine reuptake inhibitor (NRI) and a muscarinic receptor antagonist.

Abstract: The invention relates to the compositions of synthetic oligo-?-(1?6)-2-amino-2-deoxy-D-glu-copyranosides conjugated to carriers, and methods for making and use same.

Abstract: Embodiments described herein provide anti-fibulin-3 antibodies, recombinant proteins that bind specifically to fibulin-3, compositions and the treatment methods comprising these antibodies and recombinant proteins.

Abstract: Provided herein are methods and pharmaceutical compositions for the treatment of obesity-associated conditions using cadherin-11 antagonists.

Abstract: The present invention provides a method and an apparatus for controlling a flexible manipulator including a plurality of bendable mechanisms via a control apparatus. The control apparatus includes a drive-mode selecting unit allows for the selection of a movement mode which may provide a bending movement, an angled view movement, or a remote center movement.

Abstract: In some aspects, the disclosure provides methods of modulating the level of proteasome inhibitor resistance of a cell, the methods comprising manipulating the level of expression or activity of a subunit of the 19S proteasome in the cell. In some aspects, cells in which the level of a 19S subunit is modulated, e.g., reduced, are provided. In some aspects, methods of identifying agents that reduce proteasome inhibitor resistance are provided. In some aspects, methods of classifying cancers according to predicted proteasome inhibitor resistance are provided. In some aspects, methods of killing or inhibiting proliferation of cancer cells, e.g., proteasome inhibitor resistant cancer cells, are provided. In some aspects, methods of treating cancer, e.g., proteasome inhibitor resistant cancer, are provided.

Abstract: Compositions and methods for treating cancer that include administering a therapeutically effective amount of a tumor suppressor mRNA complexed with a delivery vehicle as described herein, e.g., a nanoparticle.