Abstract: The invention provides methods of using low coverage sequencing to assess the relative fraction of tumor versus normal DNA in a sample, and to assess copy number alterations present in the sample.

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: Provided herein are compounds of the formula (I): as well as pharmaceutically acceptable salts thereof, wherein the substituents are as those disclosed in the specification. These compounds, and the pharmaceutical compositions containing them, are useful for the treatment of malaria.

Abstract: A system and method for isolating target substrates includes a microfluidic chip, comprising a plurality of processing units, each processing unit comprising: an inlet port, a plurality of first chambers connected to the inlet port by a fluid channel, the fluid channel comprising a plurality of valves, a plurality of second chambers, each of the second chambers connected to a respective first chamber by a fluid channel, each fluid channel including a controllable blocking valve, and a plurality of respective outlet ports, each outlet port in fluid communication with a respective one of said second chambers and each outlet port including a blocking valve. A magnet is adjacent the microfluidic chip and is movable relative to the microfluidic chip. A valve control is capable of actuating certain ones of the controllable blocking valves in response to a control signal.

Abstract: In one aspect, the present invention provides a method of inhibiting proliferation of a multiple myeloma cell, the method comprising contacting the cell with BRD9647, thereby inhibiting proliferation of the cell. In another aspect, the present invention provides a method of treating multiple myeloma in a pre-selected subject, the method comprising administering an effective amount of BRD9647 to the subject, wherein the subject is pre-selected by detecting a mutation in an AZIN1 polynucleotide or polypeptide relative to a reference in a biological sample obtained from the subject. In another aspect, the present invention provides a method of modulating benzoylation of an agent in a cell, the method comprising contacting the cell with BRD9647, thereby modulating benzoylation of an agent in the cell.

Abstract: Provided herein are compounds, compositions, and methods that increase the infiltration of tumor cell microenvironments by immune cells. Such methods are useful for enhancing a subject's immune response against the tumor.

Abstract: The invention provides compositions and methods for treating cardiac dysfunction, particularly cachexia-associated or RAGE-associated cardiac dysfunction, using an anti-RAGE agent. The invention also provides compositions and methods for identifying therapeutic agents useful for disrupting (slowing, reducing, reversing, or preventing). The methods comprise designing or identifying agents that bind to functional sites identified on the RAGE polypeptide, wherein binding of agents to the functional site(s) inhibit RAGE-mediated cachetogenic signaling.

Abstract: The present invention features a knock-in mouse comprising a mutation in an endogenous CRBN locus and methods of use thereof.

Abstract: The present invention relates to methods for high multiplex protein or cellular constituent analysis in single cells or single isolated aggregations of cellular constituents. The methods provide for embedding cells or isolated aggregations of cellular constituents in a hydrogel mesh and labeling of cellular constituents with labeling ligands linked to a nucleic acid tag. Cellular constituents can be determined using sequencing methods.

Abstract: The embodiments disclosed herein utilized RNA targeting effectors to provide a robust CRISPR-based diagnostic with attomolar sensitivity. Embodiments disclosed herein can detect broth DNA and RNA with comparable levels of sensitivity and can differentiate targets from non-targets based on single base pair differences. Moreover, the embodiments disclosed herein can be prepared in freeze-dried format for convenient distribution and point-of-care (POC) applications. Such embodiments are useful in multiple scenarios in human health including, for example, viral detection, bacterial strain typing, sensitive genotyping, and detection of disease-associated cell free DNA.

Abstract: The embodiments disclosed herein utilized RNA targeting effectors to provide a robust CRISPR-based diagnostic with attomolar sensitivity. Embodiments disclosed herein can detect broth DNA and RNA with comparable levels of sensitivity and can differentiate targets from non-targets based on single base pair differences. Moreover, the embodiments disclosed herein can be prepared in freeze-dried format for convenient distribution and point-of-care (POC) applications. Such embodiments are useful in multiple scenarios in human health including, for example, viral detection, bacterial strain typing, sensitive genotyping, and detection of disease-associated cell free DNA.

Abstract: The application relates to proteome analysis in single cells. Specifically, disclosed are high throughput methods of detecting proteins in single cells using barcoding, aptamers and single cell sequencing. Solid supports used in recording the cell-of-origin of target proteins and target proteins expressed in the cell-of-origin are disclosed. Additionally, methods of detecting proteins and mRNA in single cells are disclosed. Additionally, methods of detecting protein interactions are disclosed. Additionally, methods of detecting post translationally modified proteins in single cells are disclosed. The application also relates to solid supports or beads and methods of producing said solid supports or beads for use in the described methods.

Abstract: The present invention generally relates to a controlled fluidic device to develop spatially complex environments to enhance the rate of evolution in cell populations. The method further provides an enhanced understanding in the emergence, for example, drug resistance during cancer chemotherapy.

Abstract: A method of identifying compounds as direct inhibitors of Keap1-Nrf2 interaction through high-throughput screening and lead development. The direct inhibitors of Keap1-Nrf2 interaction are more specific and free of various undesirable effects than existing indirect inhibitors, and are potential drug candidates of chemopreventive and therapeutic agents for treatment of various diseases or conditions involving oxidative stress and/or inflammation, including but not limited to cancers, diabetes, Alzheimer's, and Parkinson's. Novel compounds are identified and methods of preventing or treating diseases or conditions related to Keap1-Nrf2 interaction activity by use of the novel compounds identified or compositions containing such compounds are also disclosed.

Abstract: The embodiments disclosed herein utilized RNA targeting effectors to provide a robust CRISPR-based diagnostic with attomolar sensitivity. Embodiments disclosed herein can detect both DNA and RNA with comparable levels of sensitivity and can differentiate targets from non-targets based on single base pair differences. Moreover, the embodiments disclosed herein can be prepared in freeze-dried format for convenient distribution and point-of-care (POC) applications. Such embodiments are useful in multiple scenarios in human health including, for example, viral detection, bacterial strain typing, sensitive genotyping, and detection of disease-associated cell free DNA.

Abstract: The embodiments disclosed herein utilized RNA targeting effectors to provide a robust CRISPR-based diagnostic with attomolar sensitivity. Embodiments disclosed herein can detect broth DNA and RNA with comparable levels of sensitivity and can differentiate targets from non-targets based on single base pair differences. Moreover, the embodiments disclosed herein can be prepared in freeze-dried format for convenient distribution and point-of-care (POC) applications. Such embodiments are useful in multiple scenarios in human health including, for example, viral detection, bacterial strain typing, sensitive genotyping, and detection of disease-associated cell free DNA.

Abstract: The present invention includes methods of treating patients with acute myeloid leukemia across a range of genetic subtypes with DHODH inhibitors, such as 6-fluoro-2-(2?-fluoro-[1,1?-biphenyl]-4-yl)-3-methylquinoline-4-carboxylic acid).

Abstract: The invention generally provides a sieve valve including: a substrate defining a channel; a flexible membrane adapted and configured for deployment at an intersection with the channel; and one or more protrusions extending into the channel from the substrate or the flexible membrane. The one or more protrusions define a plurality of recesses extending beyond the intersection between the channel and the flexible membrane; A microfluidic circuit including one or more sieve valves. In particular embodiments, the circuit comprises one or more input/output valves. The one or one or more input/output valves can include one or more input valves and one or more output valves. The microfluidic circuit can further include a mixing circuit. At least one of the sieve valves can be positioned between the one or more input/output valves and the mixing circuit. The invention further provides methods of using the device for the analysis of samples comprising cells.

Abstract: The present disclosure relates to methods for treating a neurodegenerative disorder by administering an effective amount of an agent that inhibits or reduces translation of amyloid precursor protein. In some embodiments, the neurodegenerative disorder is Alzheimer's disease or Down syndrome. Also disclosed are methods for decreasing amyloid-beta production in a subject's brain. Further disclosed is a method for restoring or maintaining iron homeostasis in a subject's brain.

Abstract: Disclosed herein are methods and compositions useful in targeting a payload to, or editing a target nucleic acid, where a governing gRNA molecule is used to target, optionally inactivate, a Cas9 molecule or a Cas9 molecule/gRNA complex.