Abstract: Core-shell particles and methods of making and using thereof are described herein. The core is formed of or contains one or more hydrophobic materials or more hydrophobic materials. The shell is formed of or contains hyperbranched polyglycerol (HPG). The HPG coating can be modified to adjust the properties of the particles. Unmodified HPG coatings impart stealth properties to the particles which resist non-specific protein absorption and increase circulation in the blood. The hydroxyl groups on the HPG coating can be chemically modified to form functional groups that react with functional groups and adhere the particles to tissue, cells, or extracellular materials, such as proteins.

Abstract: Poly(amine-co-ester) polymers, methods of forming active agent-load polyplexes and particles therefrom, and methods of using them for delivery of nucleic acid agents with optimal uptake have been developed. Examples demonstrate critical molecular weights in combination with exposed carboxylic and/or hydroxyl groups, and methods of making. Typically, the compositions are less toxic, more efficient at drug delivery, or a combination thereof compared to a control other transfection reagents. In some embodiments, the compositions are suitable for in vivo delivery, and can be administered systemically to a subject to treat a disease or condition.

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: This application relates to methods and kits for treating ARID1A-mutant tumors, cancers, or aberrantly proliferating cells and subjects harboring the tumors, cancers, or aberrantly proliferating cells. In particular, the methods provided include administering to the subject or cell an effective amount of a pyrimidine synthesis inhibitor and administering to the subject or cell an effective amount of a DNA repair inhibitor. The kits include a) a composition comprising a pyrimidine synthesis inhibitor and b) a composition comprising a DNA repair inhibitor.

Abstract: The present invention provides compositions and methods for treating diseases or disorders using a therapeutically effective amount of a rapid-acting antidepressant (RAAD) and a therapeutically effective amount of a mTOR inhibitor and/or immunosuppressant. In certain embodiments, the RAAD and the mTOR inhibitor and/or immunosuppressant are part of a single pharmaceutical composition.

Abstract: The present disclosure provides small hairpin nucleic acid molecules capable of stimulating interferon production. The nucleic acid molecules of the present disclosure has a double-stranded section of less than 19 base pairs and at least one blunt end. In certain embodiments, the molecule comprises at least one 5?-triphosphate and/or at least one 5?-diphosphate. In certain embodiments, compounds and/or compositions of the disclosure are useful for treating, ameliorating, and/or preventing SARS-CoV-2 viral infection, and/or ameliorating, minimizing, reversing, and/or preventing persistent SARS-CoV-2 viral infection, and/or minimizing or preventing SARS-CoV-2 viral infection-derived mortality and/or lethality, in a subject. In certain embodiments, compounds and/or compositions of the disclosure are useful for treating, ameliorating, and/or preventing SARS-CoV-2 viral infection in a tumor-bearing subject.

Abstract: Non-naturally occurring tRNASec and methods of using them for recombinant expression of proteins engineered to include one or more selenocysteine residues are disclosed. The non-naturally occurring tRNASec can be used for recombinant manufacture of selenocysteine containing polypeptides encoded by mRNA without the requirement of an SECIS element. In some embodiments, selenocysteine containing polypeptides are manufactured by co-expressing a non-naturally occurring tRNASec a recombinant expression system, such as E. coli, with SerRS, EF-Tu, SelA, or PSTK and SepSecS, and an mRNA with at least one codon that recognizes the anticodon of the non-naturally occurring tRNASec.

Abstract: Parametrically pumped four-wave mixing is a key building block for many developments in the field of superconducting quantum information processing. However, undesired frequency shifts such as Kerr, cross-Ken and Stark shifts inherent with four-wave mixing, lead to difficulties in tuning up the desired parametric processes and, for certain applications, severely limit the fidelities of the resulting operations. Some embodiments include a Josephson four-wave mixing device consisting of a SQUID transmon coupled to a half-flux biased SNAIL transmon, a.k.a. capacitively shunted flux qubit. When the two transmon have matching frequencies, an interference effect cancels the negative Kerr of the SQUID transmon with the positive Kerr of the SNAIL transmon while preserving parametric four-wave mixing capabilities.

Abstract: The present disclosure relates to computer generated topographies from computer correlations of neurobehavioral phenotype mapping data and gene expression mapping data. Neurobehavioral phenotype mapping data is obtained for a selected phenotype and correlated with gene expression mapping data for one or more genes to define a phenotype-gene pair topography for each phenotype-gene pair. A score for each phenotype-gene pair is determined based on the correlation. The scores are used to identify genes, or drug targets, associated with the respective gene of the respective phenotype-gene pair. Conversely, gene expression mapping data is obtained for a selected gene and correlated with neurobehavioral phenotype mapping data for one or more phenotypes to define a gene-phenotype topography for each gene-phenotype pair. A score for each gene-phenotype pair is determined based on the correlation. The scores are used to identify a phenotype associated with the respective phenotype-gene pair.

Abstract: Genetically modified non-human animals are provided that may be used to model human hematopoietic cell development, function, or disease. The genetically modified non-human animals comprise a nucleic acid encoding human IL-6 operably linked to an IL-6 promoter. In some instances, the genetically modified non-human animal expressing human IL-6 also expresses at least one of human M-CSF, human IL-3, human GM-CSF, human SIRPa or human TPO. In some instances, the genetically modified non-human animal is immunodeficient. In some such instances, the genetically modified non-human animal is engrafted with healthy or diseased human hematopoietic cells. Also provided are methods for using the subject genetically modified non-human animals in modeling human hematopoietic cell development, function, and/or disease, as well as reagents and kits thereof that find use in making the subject genetically modified non-human animals and/or practicing the subject methods.

Abstract: Techniques for quantum error correction of a multi-level system are provided and described. In some aspects, techniques for encoding a state of a multi-level quantum system include encoding a quantum information in a two-mode state of two quantum mechanical oscillators. Techniques for protecting the two-mode state against dephasing and energy loss are described.

Abstract: A method for decreasing formation of one or more chemiexcitation-induced dark cyclobutane pyrimidine dimers (dCPDs) in a cell or DNA molecule in a subject, who has been exposed to UV radiation, is provided. The method comprises administering to the subject an effective amount of a dCPD quencher within 8 hours after the exposure. The dCPD quencher is selected from the group consisting of ellagic acid, Porphyra Umbilicalis Extract (including Porphyra Umbilicalis Extract (and) Sodium Lactate (and) Lecithin), mycosporine-like amino acids (MAAs) and synthetic analogues thereof, Scutellaria Baicalensis Root Extract, Chrysanthemum Morifolium Leaf Extract, ferulic acid, fused-ring cyanoacrylates, curcumin, epigallocatechin gallate, Scutellaria Baicalensis Root Extract (and) Acacia Catechu Wood Extract, sorbic acid, Polygonum Cuspidatum Root Extract, Acacia Catechu Extract, dipicolinic acid, squalene, Lonicera Japonica (Honeysuckle) Flower Extract, beta-carotene and combinations thereof.

Abstract: This invention provides herbal compositions useful for increasing the therapeutic index of chemotherapeutic compounds. This invention also provides methods useful for improving the quality of life of an individual undergoing chemotherapy. Furthermore, this invention improves the treatment of disease by increasing the therapeutic index of chemotherapy drugs by administering the herbal composition PHY906 to a mammal undergoing such chemotherapy.

Abstract: The present-disclosure relates to the discovery of novel 2-amino-dihydropteridinone compounds and analogues thereof, which are capable of inhibiting phosphatidylinositol phosphate kinases. In certain embodiments, the compounds of the present disclosure can be used to treat p53-null cancer in a subject. In other embodiments, the compounds of the present disclosure can be used to treat metabolic disorders in a subject, including but not limited to type 2 diabetes and/or obesity.

Abstract: Genetically modified non-human animals expressing human EPO from the animal genome are provided. Also provided are methods for making non-human animals expressing human EPO from the non-human animal genome, and methods for using non-human animals expressing human EPO from the non-human animal genome. These animals and methods find many uses in the art, including, for example, in modeling human erythropoiesis and erythrocyte function; in modeling human pathogen infection of erythrocytes; in in vivo screens for agents that modulate erythropoiesis and/or erythrocyte function, e.g. in a healthy or a diseased state; in in vivo screens for agents that are toxic to erythrocytes or erythrocyte progenitors; in in vivo screens for agents that prevent against, mitigate, or reverse the toxic effects of toxic agents on erythrocytes or erythrocyte progenitors; in in vivo screens of erythrocytes or erythrocyte progenitors from an individual to predict the responsiveness of an individual to a disease therapy.

Abstract: The present invention is directed to bi-functional compounds which find use as pharmaceutical agents in the treatment of disease states and/or conditions which are mediated through macrophage migration inhibitory factor (MIF) or immunoglubin G (IgG). The present invention is also directed to pharmaceutical compositions which comprise these bi-functional compounds as well as methods for treating disease states and/or conditions which are mediated through MIF/IgG or where MIF/IgG is a contributing factor to the development and perpetuation of diseases and/or conditions, especially including autoimmune diseases and cancer, among others. The purpose of the present invention is to provide a molecular strategy to lower plasma MIF/IgG level in patients with autoimmune diseases or certain types of cancers.

Abstract: Biodegradable contraceptive implants and methods of making and using thereof, are preferably formed of poly(?-pentadecalactone-co-p-dioxanone) [poly(PDL-co-DO)], a family of polyester copolymers that degrade slowly in the presence of water. The material is suitable as the basis of a biodegradable contraceptive implant that provides sustained release of a progestin at a rate similar to a commercially available nondegradable implant. In a preferred embodiment, the progestin is levonorgestrel (LNG), a hormone that prevents pregnancy by preventing the release of an egg from the ovary or by preventing fertilization of the egg by sperm. The implant may be inserted subcutaneously, allowing degradation over a period of up to about 18 or 24 months, eliminating the need for removal by a trained practitioner.

Abstract: The invention relates to novel, scalable synthetic routes that allow for direct reduction of enones to the corresponding saturated alcohols. The invention relates, in certain aspects, to synthetic routes that allow for the reduction of enones to the corresponding ketones. Such reactions take place under mild conditions, are compatible with a wide range of functional groups, and expand the repertoire of existing green chemistry methodology. In certain embodiments, the reactions are run in aqueous solvent.

Abstract: The invention features methods that are useful for treatment of a patient at increased risk for infection and for selecting a patient for treatment for an infection. In various embodiments, the infection is coronavirus disease 2019 (COVID-19), sepsis, or other respiratory infections.

Abstract: Provided herein, in some embodiments, are devices, systems and methods for high-throughput single-cell polyomics (e.g., genomic, epigenomic, proteomic and/or phenotypic profile) analyses.