Abstract: Compositions and methods for gene editing are provided. The methods employ an oligo-based annealing mechanism that is rooted in the process of DNA replication rather than homologous recombination (HR). Oligo incorporation efficiencies are comparable and often exceed those of CRISPR/cas9 editing without the need for double strand breaks (DSBs). By relying on the multiplex annealing of oligos rather than DSBs the process is highly scalable across a genomic region of interest and can generate many scarless modifications of a chromosome simultaneously. Combinatorial genomic diversity can be generated across a population of cells in a single transformation event; genomic landscapes can be traversed through successive iterations of the process, and genome-wide changes can be massively parallelized and amplified through systematic strain mating.

Abstract: In various aspects and embodiments the invention provides compositions and methods useful in the treatment of inflammatory disease, in particular, multiple sclerosis.

Abstract: The invention provides a method of treating retinal degenerations, such as but not limited to anterior segment ocular disorders and/or age-related macular degeneration (AMD), in a subject, the method comprising administering to the subject a pharmaceutical composition comprising an effective amount of a compound of formula (1) or formula (2). In a further aspect, the invention provides compounds of formula (2). In certain embodiments, the compounds of the invention prevent or minimize cellular assault, such as oxidative stress-related cellular assault, and/or promote cell viability.

Abstract: A method is disclosed. The method includes: a) receiving node identifiers from nodes of a plurality of nodes in a computer network; b) determining a plurality of node committees in a sampler graph comprising a plurality of nodes, wherein the node is present in a node committee in the plurality of node committees; c) and i) generating a random string; ii) performing a proof of work process using the random string and a hash function; iii) if the proof of work process yields a solution that is acceptable, then broadcasting the solution to all other nodes in the plurality of nodes, wherein the other nodes verify the solution; and iv) if the other nodes verify the solution, the node is elected to a subcommittee for the node committee, wherein the subcommittee updates the sampler graph; and d) repeating steps b) and c) until a leader committee is determined.

Abstract: Compositions and methods of use thereof for delivering nucleic acid cargo into cells are provided. The compositions typically include (a) a 3E10 monoclonal antibody or an antigen binding, cell-penetrating fragment thereof; a monovalent, divalent, or multivalent single chain variable fragment (scFv); or a diabody; or humanized form or variant thereof, and (b) a nucleic acid cargo including, for example, a nucleic acid encoding a polypeptide, a functional nucleic acid, a nucleic acid encoding a functional nucleic acid, or a combination thereof. Elements (a) and (b) are typically non-covalently linked to form a complex.

Abstract: This disclosure demonstrates an approach that translates synthetic DNA codes to spatial codes registered in nanoliter microchambers for multiplexed measurement of nearly any type of molecular targets (e.g., miRNAs, mRNAs, intracellular and surface proteins) in single cells.

Abstract: Methods are disclosed for treating periodontal disease, peri-implantitis, or to preserve a tooth socket in a subject. These methods include selecting a subject with periodontal disease, peri-implantitis, or in need of tooth socket preservation; and locally administering into the periodontium of the subject a therapeutically effective amount of a tissue-nonspecific alkaline phosphatase (TNAP) polypeptide, or a nucleic acid molecule encoding the recombinant TNAP polypeptide. Methods are also disclosed for i) promoting alveolar bone regeneration in the subject; ii) increasing attachment of a periodontal ligament to a root surface of a tooth in the subject; iii) increasing cementum formation; and/or iv) increasing mineralization in a tooth in the subject. Pharmaceutical compositions are also disclosed that are of use in these methods.

Abstract: The present invention provides methods and compositions for treating and preventing lung injuries due to or associated with viral infections, such as those due to coronaviruses that cause Severe Acute Respiratory Syndrome, including COVID-19. More specifically the present invention provides methods for treating or preventing the lung injuries often associated with these 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/AP3K3 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 present invention provides compositions, methods, and kits related to reverse transcriptases derived from E.r. maturase.

Abstract: The invention provides a BASEHIT screening method for identifying proteins that are involved in host-microbe interactions which may function as therapeutic targets.

Abstract: The present invention includes a method of preventing and/or treating a fibrotic lung disease in a subject. In certain embodiments, the method comprises administering to the subject a thyroid receptor ?-agonist. The invention further comprises compositions useful within the invention, as well as kits comprising compositions useful within the invention.

Abstract: The present invention relates to compositions comprising a decellularized tissue. The present invention also provides an engineered three dimensional lung tissue exhibiting characteristics of a natural lung tissue. The engineered tissue is useful for the study of lung developmental biology and pathology as well as drug discovery.

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: An optical amplifier device employing a Mach-Zehnder Interferometer (MZI) that reduces the amount of residual pump power in the optical output of the amplifier is disclosed. The MZI amplifier employs two geometrically linear optical amplifier arms or two multi-spatial-mode racetrack optical amplifiers to amplify a signal with a pumping beam, with the signal output port having extremely low levels of residual pump power. The MZI optical amplifier is a silicon photonic integrated circuit, with all optical amplifiers, couplers, phase shifters, and optical attenuators formed of silicon photonic integrated circuit elements. The MZI optical amplifier may include one, two, or three MZI stages, and multiple MZI optical amplifiers may be used in parallel or sequentially to achieve higher overall signal gain or power. The MZI optical amplifier may employ Brillouin-scattering-based amplifiers, Raman-based integrated waveguide optical amplifiers, or Erbium-doped integrated waveguide optical amplifiers.

Abstract: Compositions, systems, and methods for preparation of polypeptides having multiple iterations of non-standard amino acids are provided. The compositions and method can be used to produce recombinant proteins at a greater yield than the same or similar polypeptides made using conventional compositions, systems, and methods. Accordingly, in some embodiments, the polypeptides are ones that could not be made using conventional methods and reagents, or could not be made a sufficient yield or purity to serve a practical purpose using conventional methods and reagents. Polypeptides made using the disclosed compositions, systems, and methods are also provided.

Abstract: The present disclosure provides a method of treating cancer by immune checkpoint blockade, or selecting patients for treatment with immune checkpoint blockers, by detecting tumors with high levels of T-lymphocytes with low levels of activation and proliferation. In various embodiments the tissue sample may be from a conventional biopsy. In various embodiments the cancer may be non-small cell lung cancer.

Abstract: Identification of immunodominant Babesia microti antigens using genome-wide immunoscreening is described. Candidate antigens were screened against sera from patients with clinical babesiosis. Also described are diagnostic assays with high sensitivity and specificity for detecting B. microti-specific antibodies in patient samples using the identified immunodominant antigens.

Abstract: The present application describes a waveform processor for control of quantum mechanical systems. The waveform processor may be used to control quantum systems used in quantum computation, such as qubits. According to some embodiments, a waveform processor includes a first sequencer configured to sequentially execute master instructions according to a defined order and output digital values in response to the executed master instructions, and a second sequencer coupled to the first sequencer and configured to generate analog waveforms at least in part by transforming digital waveforms according to digital values received from the first sequencer. The analog waveforms are applied to a quantum system. In some embodiments, the waveform processor further includes a waveform analyzer configured to integrate analog waveforms received from a quantum system and output results of said integration to the first sequencer.

Abstract: A method includes: a) receiving node identifiers from nodes of a plurality of nodes in a computer network; b) determining a plurality of node committees in a sampler graph comprising a plurality of nodes, wherein the node is present in a node committee in the plurality of node committees; c) and i) generating a random string; ii) performing a proof of work process using the random string and a hash function; iii) if the proof of work process yields a solution that is acceptable, then broadcasting the solution to all other nodes in the plurality of nodes, wherein the other nodes verify the solution; and iv) if the other nodes verify the solution, the node is elected to a subcommittee for the node committee, wherein the subcommittee updates the sampler graph; and d) repeating steps b) and c) until a leader committee is determined.

Abstract: Compositions and methods of use thereof for delivering nucleic acid cargo into cells are provided. The compositions typically include (a) a 3E10 monoclonal antibody or an antigen binding, cell-penetrating fragment thereof; a monovalent, divalent, or multivalent single chain variable fragment (scFv); or a diabody; or humanized form or variant thereof, and (b) a nucleic acid cargo including, for example, a nucleic acid encoding a polypeptide, a functional nucleic acid, a nucleic acid encoding a functional nucleic acid, or a combination thereof. Elements (a) and (b) are typically non-covalently linked to form a complex.