Abstract: The present invention relates to bifunctional compounds, which find utility as modulators of targeted ubiquitination, especially inhibitors of a variety of polypeptides and other proteins which are degraded and/or otherwise inhibited by bifunctional compounds according to the present invention. In particular, the present invention is directed to compounds, which contain on one end a VHL ligand which binds to the ubiquitin ligase and on the other end a moiety which binds a target protein such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of that protein. The present invention exhibits a broad range of pharmacological activities associated with compounds according to the present invention, consistent with the degradation/inhibition of targeted polypeptides.

Abstract: Systems and methods for formal verification of programs. The systems and methods provide a new game-theoretical, strategy-based compositional semantic model for concurrency, a set of formal linking theorems for composing multithreaded and multicore concurrent layers, and a compiler that supports certified thread-safe compilation and linking. Verification of an overlay interface can include determining an intermediate strategy for a primitive operation running on an underlay interface and refining that intermediate strategy to a strategy running on the overlay interface by applying a vertical and a horizontal composition rule. The refined strategy can then be composed with compatible strategies running on the overlay interface according to a parallel composition rule. Strategies may be compatible when rely conditions imposed by each strategy satisfy guarantees provided by the other strategies. The system and method of formal verification can be applied to formal verification of smart contracts.

Abstract: The present invention provides methods and compositions for treating and preventing lung injuries due to or associated with coronavirus infections that cause Severe Acute Respiratory Syndrome, including COVID-19. More specifically the present invention provides methods for treating or preventing the lung injuries associated with SARS-CoV-2 infections, such as acute lung injury (ALI), lung fibrosis, and acute respiratory distress syndrome (ARDS). The methods comprise administering a therapeutically effective amount of a pharmaceutical composition comprising a protein kinase inhibitor compound having MAP3K2/MAP3K3 inhibition activity, such as pazopanib or nintedanib, or a pharmaceutically acceptable salt, solvate, or prodrug thereof, to a patient in need thereof. The present invention also provides devices for administering the compositions.

Abstract: Provided herein, in some embodiments, are compositions and methods for producing a molecular expression map of a biological sample using Deterministic Barcoding in Tissue for spatial omics sequencing (DBiT-seq).

Abstract: The present invention includes DNP derivatives that are useful for preventing or treating a metabolic disease or disorder in a subject in need thereof. In certain embodiments, the subject is further administered at least one additional therapeutic agent.

Abstract: Provided herein are methods of determining tumoral sensitivity to hormonal (endocrine) therapy based upon an index of estrogen receptor (ER)- and progesterone receptor (PR)-related genes, referred to as the sensitivity to endocrine therapy index (SETER/PR index), and may have additional consideration for the proportion of ER gene (ESRI) RNA transcripts that contain a mutation relative to the value of the SETER/PR index. Further provided are methods of treating breast cancer patients determined to be sensitive to an endocrine therapy by the SETER/PR index.

Abstract: Systems, methods, and computer-readable storage media facilitating automated testing of datasets including natural language data are disclosed. In the disclosed embodiments, rule sets may be used to condition and transform an input dataset into a format that is suitable for use with one or more artificial intelligence processes configured to extract parameters and classification information from the input dataset. The parameters and classes derived by the artificial intelligence processes may then be used to automatically generate various testing tools (e.g., scripts, test conditions, etc.) that may be executed against a test dataset, such as program code or other types of data.

Abstract: The invention provides compositions and methods for preventing and treating infection by Plasmodium sporozoites.

Abstract: Techniques for providing hardware-efficient fault-tolerant quantum operations are provided. In some aspects a cavity and an ancilla transmon are used to implement a quantum operation by encoding a logical qubit using more than two energy levels of the cavity, encoding information using more than two energy levels of the ancilla transmon, and creating an interaction between the cavity and the ancilla transmon that decouples at least one error type in the ancilla transmon from the cavity.

Abstract: Techniques for implementing robust quantum logic gates are provided and described. In some aspects, a quantum logic gate between a plurality of cavities comprising a first cavity and a second cavity is implemented by performing a first beam splitter operation between the first cavity and the second cavity using a coupling transmon that is dispersively coupled to both the first cavity and the second cavity, and performing a controlled phase shift operation between the second cavity and an ancilla transmon that is dispersively coupled to the second cavity but not dispersively coupled to the first cavity.

Abstract: The present invention relates in part to devices, systems, and methods for the production and characterization of engineered tissue constructs. The devices and methods generate decellularized tissue constructs that can be recellularized using donor cells for high-throughput studies of organ physiology, and/or organ pathology. The devices and methods can be used with the systems to mechanically and electrically stimulate the engineered tissue constructs under culture or physiological conditions to detect and assess the presence and degree of any organ pathologies.

Abstract: Systems and methods for formal verification of programs. The systems and methods provide a new game-theoretical, strategy-based compositional semantic model for concurrency, a set of formal linking theorems for composing multithreaded and multicore concurrent layers, and a compiler that supports certified thread-safe compilation and linking. Verification of an overlay interface can include determining an intermediate strategy for a primitive operation running on an underlay interface and refining that intermediate strategy to a strategy running on the overlay interface by applying a vertical and a horizontal composition rule. The refined strategy can then be composed with compatible strategies running on the overlay interface according to a parallel composition rule. Strategies may be compatible when rely conditions imposed by each strategy satisfy guarantees provided by the other strategies. The system and method of formal verification can be applied to formal verification of smart contracts.

Abstract: Described herein are the association BV677278 (READ1) with reading disability and language impairment, as well as the synergistic interaction of DCDC2 risk haplotypes or alleles with KIAA0319 risk allele.

Abstract: Disclosed herein are methods and agents for the treatment of cancer using p53-independent apoptosis to reduce the number of p53-depleted or p53-mutated cancer cells that have amplified HER2 gene. Also disclosed herein are methods and agents for the treatment of HER2-positive cancer in individuals with Li-Fraumeni Syndrome.

Abstract: The invention provides methods for selective targeting of live cells, which have undergone or are undergoing radiation or chemotherapy, at a site of interest with a cell-penetrating polypeptide. In one embodiment of the invention, the method comprises contacting the live cells with a cell-penetrating polypeptide comprising cell-penetrating determinants so that the cell-penetrating polypeptide binds extracellular DNA near or around the live cells so as to form a complex or association therewith such that the complex or associated polypeptide-DNA so bound bind the live cells and penetrates the live cells thereby selectively targeting live cells at a site of interest with a cell-penetrating polypeptide.

Abstract: The present invention includes compositions and methods for treating stroke in sickle cell anemia (SCA) patients. In certain embodiments, the patient is administered certain ENPP1- or ENNP3-containing polypeptides, mutants, or mutant fragments thereof.

Abstract: The present invention provides compositions and methods of preparing airway cells. In one aspect, an epithelial airway cell derived from an induced pluripotent stem (iPS) cell characterized by expression of airway cell surface markers and an ability to proliferate is described. In another aspect, methods of differentiating an iPS into an epithelial airway cell is provided. Engineered lungs, methods of making such engineered lungs comprising the epithelial airway cells and treating respiratory disorders are also disclosed.

Abstract: The invention provides compositions and methods for identifying DNA methylation. In one embodiment, the invention provides a method for detecting N6-methyladenine.

Abstract: The present invention provides methods and compositions for treating and preventing lung injuries due to or associated with coronavirus infections that cause Severe Acute Respiratory Syndrome, including COVID-19. More specifically the present invention provides methods for treating or preventing the lung injuries associated with SARS-CoV-2 infections, such as acute lung injury (ALI), lung fibrosis, and acute respiratory distress syndrome (ARDS). The methods comprise administering a therapeutically effective amount of a pharmaceutical composition comprising a protein kinase inhibitor compound having MAP3K2/MAP3K3 inhibition activity, such as pazopanib or nintedanib, or a pharmaceutically acceptable salt, solvate, or prodrug thereof, to a patient in need thereof. The present invention also provides devices for administering the compositions.

Abstract: The invention provides compositions and methods for binding and inhibiting renalase. In one embodiment, the renalase binding molecule inhibits renalase activity. Thus, in diseases and conditions where a reduction of renalase activity is beneficial, such inhibitory renalase binding molecules act as therapeutics.