Abstract: A system and method for memory allocation and management in non-uniform memory access (“NUMA”) architecture computing environments is disclosed. The system and method contemplates both hardware heterogeneity and allocation/deallocation attributes, with fine-grained memory management. NUMAlloc is centered on a binding-based memory management. On top of it, NUMAlloc proposes an “origin-aware memory management” to ensure the locality of memory allocations and deallocations, as well as a method called “incremental sharing” to balance the performance benefits and memory overhead of using transparent huge pages. It further introduced an interleaved heap to reduce the load imbalance among different nodes and an efficient mechanism for object movement. The system and method provides a scalable and increased performance alternative over other prior art memory allocators.

Abstract: A NOD.Cg-PrkdcscidH2rgtm1 Wjl/SzJ.(NOD-scid-IL2r?null, NSG) mouse which is genetically modified such that the en NSG mouse lacks functional major histocompatibility complex I (MHC I) and lacks functional major histocompatibility complex II (MHC II) is provided according to aspects of the present, invention. According to specific aspects the genetically modified NSG mouse, is a NOD.Cg-PrkdcscidH2-K1tml Bpe H2-Ab1eml Mvw H2-D1tml Bpe H2rgtm Wjl/SzJ (NSG-Kb Db)null(IAnull)) mouse, NSG-RIP-DTR (Kb Db)null(IAnull) mouse, or a NOD.Cg-B2mtmlUnePrKdcscidH2dlAb1-E?H2rgtm1 Wjl/SzJ (NSG-B2Mnull(IA IEnull)) mouse. Human, immune cells and/or human: tumor cells are administered to a genetically modified immunodeficient mouse according to aspects described herein and assays of one or more test substances can be performed using the provided mice.

Abstract: The disclosure in some aspects relates to methods and compositions for repairing mutations (e.g., compound heterozygous mutations) that are widely found in patients having certain diseases (e.g., monogenic recessive diseases). In some aspects, the disclosure provides a method for targeted allelic exchange using recombinant gene editing complex.

Abstract: Aspects of the disclosure relate to compositions and methods useful for treating Huntington's disease. In some embodiments, the disclosure provides interfering nucleic acids (e.g., artificial miRNAs) targeting the huntingtin gene (HTT) and methods of treating Huntington's disease using the same.

Abstract: Novel oligonucleotides that enhance silencing of the expression of a gene containing a single nucleotide polymorphism (SNP) relative to the expression of the corresponding wild-type gene are provided. Methods of using novel oligonucleotides that enhance silencing of the expression of a gene containing a SNP relative to the expression of the corresponding wild-type gene are provided.

Abstract: In some aspects, the disclosure relates to methods for improving titer and yield of viral vector production. In some embodiments, the methods comprise transient silencing of transgene expression during packaging of a viral vector.

Abstract: In some aspects, the disclosure relates to compositions and methods for treating fibrodysplasia ossificans progressiva (FOP) in a subject. In some aspects, the disclosure provides isolated nucleic acids, and vectors such as rAAV vectors, configured to express transgenes that inhibit (e.g., decrease) expression of mutated AVCR1 gene in muscle cells or connective tissues.

Abstract: The invention relates to inhibitory nucleic acids and rAAV-based compositions, methods and kits useful for treating Amyotrophic Lateral Sclerosis.

Abstract: Provided herein are conjugated oligonucleotides that are characterized by efficient and specific tissue distribution.

Abstract: In some aspects, the disclosure relates to recombinant adeno-associated viruses (rAAVs) comprising a nucleic acid encoding a fusion protein comprising a DNA-binding domain and a transcriptional regulator domain and methods of using the same. In some embodiments, expression of the fusion protein results in modified expression of a target gene in a cell.

Abstract: The invention provides novel polymer-protein conjugates and molecular assemblies for controlled intracellular delivery of proteins, and compositions and methods of preparation and use thereof.

Abstract: Aspects of the disclosure relate to compositions and methods useful for treating ocular ciliopathies, for example Leber congenital amaurosis (LCA). In some embodiments, the disclosure provides isolated nucleic acids comprising a transgene encoding a CEP290 protein fragment, and methods of treating ocular ciliopathies using the same.

Abstract: In some aspects, the disclosure relates to compositions and methods useful for inhibiting SOD1 expression in cells (e.g., cells of a subject). In some embodiments, the disclosure describes isolated nucleic acids engineered to express an inhibitory nucleic acid targeting endogenous SOD1 and an mRNA encoding a hardened SOD1 protein. In some embodiments, compositions and methods described by the disclosure are useful for treating Amyotrophic Lateral Sclerosis (ALS) in a subject.

Abstract: The invention provides anti-ETEC adhesin protein antibodies and methods of using the same.

Abstract: The disclosure relates to methods and compositions for regulating expression of DUX4. In some aspects, methods described by the disclosure are useful for treating a disease associated with aberrant DUX4 expression (e.g., facioscapulohumeral muscular dystrophy. FSHD).

Abstract: A flocked surface tribo-electric charge generator includes first and second contact surface electrodes; first and second flock fiber support layers a first flock fiber material flocked onto the first flock fiber support layer; a tribo-electrically second different flock fiber material flocked onto the second flock fiber support layer. A tribo-electric charge is generated by intermittent intermeshing/separation of the tribo-electrically diverse flock fiber materials of the first and second flock fiber support layers.

Abstract: A processor is configured to execute instructions stored in a memory to identify distinct vehicle operational scenarios; instantiate decision components, where each of the decision components is an instance of a respective decision problem, and where the each of the decision components maintains a respective state describing the respective vehicle operational scenario; receive respective candidate vehicle control actions from the decision components; select an action from the respective candidate vehicle control actions, where the action is from a selected decision component of the decision components, and where the action is used to control the AV to traverse a portion of the vehicle transportation network; and generate an explanation as to why the action was selected, where the explanation includes respective descriptors of the action, the selected decision component, and a state factor of the respective state of the selected decision component.

Abstract: This disclosure relates to novel targets for angiogenic disorders. Novel oligonucleotides are also provided. Methods of using the novel oligonucleotides for the treatment of angiogenic disorders (e.g., preeclampsia) are also provided.

Abstract: Autonomous vehicle operation with explicit occlusion reasoning may include traversing, by a vehicle, a vehicle transporation network. Traversing the vehicle transportation network can include receiving, from a sensor of the vehicle, sensor data for a portion of a vehicle operational environment, determining, using the sensor data, a visibility grid comprising coordinates forming an unobserved region within a defined distance from the vehicle, computing a probability of a presence of an external object within the unobserved region by comparing the visibility grid to a map (e.g., a high-definition map), and traversing a portion of the vehicle transportation network using the probability. An apparatus and a vehicle are also described.

Abstract: The disclosure provides an ex vivo method to prepare regulatory T cells, a population of regulatory T cells with enhanced properties and methods of using the population or complexes useful to induce Tregs in a mammal. The ex vivo methods allows for the generation and expansion of super regulatory T cells for the prevention, inhibition or treatment of autoimmune disorders.