Abstract: Disclosed are compositions and methods for treating diseases of the mammalian eye, and in particular, complications of the retina associated with Usher syndrome IB (USH1B). Further disclosed are compositions and methods for treating diseases of the mammalian inner ear, and in particular, complications of ear hair cells associated with Usher syndrome IB (USH1B). The disclosure provides improved AAV-based, dual vector systems that facilitate the expression of full-length proteins whose coding sequences exceed that of the polynucleotide packaging capacity of an individual AAV vector. Described herein are modified hybrid dual vector systems that shift the coding sequence for the MY07A tail domain from the front-half vector to the back-half vector by altering the split point (e.g., from between exons 23 and 24, to between exons 21 and 22), in order to eliminate the production of truncated MY07A protein.

Abstract: Embodiments of methods are disclosed for inhibiting, regulating and/or otherwise affecting or managing the pri-miR-17-92 cluster, and certain pre-miRNA's embedded in the cluster as well as the pre-miRNA's themselves as isolated forms, as members of a library, present in oncogenic and/or polycystic cell lines and/or that are present in breast cancer, prostate cancer and/or polycystic kidney disease in animals or humans, or present in any other disease in which the pri-miR-17-92 cluster and the certain pre-miRNAs within in it cause or contribute to disease. The methods utilize compounds that target the structural feature or features of the pri-miR-17-92 cluster and/or the certain pre-miRNA's. The pre-miRNA's are members of the pre-miRNA-X group which includes one or more of pre-miR-17, pre-miR-18a, pre-miR-19a, pre-miR-19b-1, pre-miR-20a, and pre-miR-92a-1 or any combination thereof. The compounds incorporate a dimeric formula of a binding moiety for the certain pre-miRNA-X's.

Abstract: Disclosed are capsid-modified rAAV expression vectors, as well as infectious virions, compositions, and pharmaceutical formulations containing them. Also provided are methods of preparing and using the disclosed capsid-protein-mutated rAAV constructs in a variety of diagnostic and therapeutic modalities, including, inter alia, as mammalian cell-targeting delivery agents, and as human gene therapy vectors. Also disclosed are large-scale production methods for capsid-modified rAAV expression vectors, viral particles, and infectious virions having improved transduction efficiencies over those of the corresponding, un-modified, rAAV vectors, as well as use of the disclosed compositions in the manufacture of medicaments for a variety of in vitro and/or in vivo applications.

Abstract: The present invention provides methods and compositions for treating and/or preventing age related macular degeneration and other conditions involving macular degeneration, ocular neovascularization, or ocular inflammation. In an exemplary embodiment, a method is disclosed that involves administering an expression vector that delivers a secretable and cell penetrating CARD to a subject in need of treatment or prevention of age-related macular degeneration or another condition involving macular degeneration or ocular neovascularization.

Abstract: The present invention provides AAV capsid proteins comprising modification of one or a combination of the surface-exposed lysine, serine, threonine and/or tyrosine residues in the VP3 region. Also provided are rAAV virions comprising the AAV capsid proteins of the present invention, as well as nucleic acid molecules and rAAV vectors encoding the AAV capsid proteins of the present invention. Advantageously, the rAAV vectors and virions of the present invention have improved efficiency in transduction of a variety of cells, tissues and organs of interest, when compared to wild-type rAAV vectors and virions.

Abstract: Methods and computer systems are described herein for identifying small molecules that bind to selected RNA structural features (e.g., to RNA secondary structures). Also described are compounds and compositions that modulate RNA function and/or activity.

Abstract: Aspects of the disclosure relate to chimeric antigen receptors (CARs) comprising an antigen binding domain (e.g., anti-TSHR), transmembrane domain (e.g., CD28), and a cytoplasmic domain (e.g., CD27, CD-137, etc.) and a safety mechanism comprising an inducible apoptosis trigger. In some aspects, the disclosure relates to use of the CARs in T cells, compositions, kits and methods for the treatment of thyroid cancers.

Abstract: The invention relates to methods of treating cell proliferative disorders. The invention further relates to pharmaceutical compositions for treating cell proliferative disorders, especially cancer.

Abstract: In this vein, we present CTLAP, a fluorogenic probe that is rapidly activated by CTL and displays good selectivity over CTB and CTV, the closest competing analytes for CTL activity probes. CTLAP exhibits intrinsically low background fluorescence, which we attribute to the notably low quantum yield measured for the probe. CTLAP demonstrates markedly higher turn-on ratios (24-fold) and moderately improved enzyme selectivity (6- to 10-fold) when compared to Z-FR-AMC (10-fold turn-on ratio, 6- to 7-fold selectivity), a commercially available CTL-selective probe commonly used to detect CTL activity in mixed samples. Optimum selectivity for CTL is achieved within 10 min of incubation with the enzyme, suggesting that CTLAP is amenable for rapid detection of CTL, even in the presence of competing cathepsins.

Abstract: In some aspects, the present disclosure provides compounds of the formula: wherein the variables are as defined herein. In some embodiments, these compounds may be used to reduce the pain of a patient. These compounds may be used in pain relief and show an improved pharmaceutical profile relative to other commonly used opiates and opioid derivatives.

Abstract: Provided herein are compositions and methods related to extending viable preservation of organs and tissues. The compositions comprise superoxide dismutase, catalase, vitamin E, and glutathione, and optionally, a preservation solution (e.g., University of Wisconsin solution). Also provided are methods of preserving the contractile function of a contractile tissue, as well as kits comprising the compositions described herein.

Abstract: Provided herein are compositions and methods for eliciting a desired immune response in a subject in need thereof. The compositions and methods are particularly useful as anti-cancer immune therapy by exploiting a subject's propensity for drug (e.g small molecule) hypersensitivity. Of particular significance is the application in personalized immune therapy for cancer patients utilizing or repurposing existing FDA approved drugs.

Abstract: A tunable non-reciprocal frequency limiter with an asymmetric micro-electro-mechanical resonator has two independent transducer ports. One port has a film stack including a 10 nm hafnium zirconium oxide (HZO) and another port has a film stack including a 120 nm aluminum nitride (AlN) film. These film stacks are deposited on top of 70 nm single crystal silicon substrate applying CMOS compatible fabrication techniques. The asymmetric transducer architecture with dissimilar electromechanical coupling coefficients force the resonator into mechanical nonlinearity on actuation with transducer having larger coupling. A proof-of-concept electrically-coupled channel filter is demonstrated with two such asymmetric resonators at ˜253 MHz with individual Qres of ˜870 and a non-reciprocal transmission ratio (NTR) ˜16 dB and BW3 dB of 0.25%.

Abstract: Methods and integrated circuit architectures for assuring the protection of intellectual property between third party IP providers, system designers (e.g., SoC designers), fabrication entities, and assembly entities are provided. Novel design flows for the prevention of IP overuse, IP piracy, and IC overproduction are also provided. A comprehensive framework for forward trust between 3PIP vendors, SoC design houses, fabrication entities, and assembly entities can be achieved, and the unwanted modification of IP can be prevented.

Abstract: A Fin Bulk Acoustic Resonator (FinBAR) includes a fin integrally fabricated on a substrate of a glass or a semiconductor, an inner electrode deposited on the fin, a piezoelectric layer disposed on the inner electrode, an outer electrode deposited on the piezoelectric layer, a first electrode and a second electrode formed on the top surface of the substrate and connected to the inner and outer electrodes respectfully. The fin is characterized with a larger height than its width. A FinBAR array including a number of the FinBARs with different fin widths sequentially located on one chip is capable of continuously filtering frequencies in UHF and SHF bands.

Abstract: Provided herein are compositions of carbonic anhydrase and inhibitors thereof for the treatment of subjects with certain conditions such as heart disease.

Abstract: A composition is provided herein directed to a mixture of one or more Lactobacillus sp. and a phenolic compound. In a specific embodiment, disclosed is a Lactobacillus/phenol mixture that has been lyophilized to form a Lactobacillus/phenol lyophilized mixture. The Lactobacillus/phenol mixture of Lactobacillus/phenol lyophilized mixture may be packaged in a capsule, emulsion, or tablet such that the Lactobacillus are protected in a gastrointestinal tract for transport to an intestine of a subject. In another embodiment, a method for treating Type-1 diabetes including orally administering to a diabetic or pre-diabetic subject, or a subject at risk for becoming pre-diabetic or diabetic, a composition comprising an effective amount of Lactobacillus/phenol mixture or lyophilized mixture. In still a further embodiment, of improving immune function in a subject, comprising administering to the subject, the composition comprising an effective amount of Lactobacillus/phenol mixture or lyophilized mixture.

Abstract: Provided herein are targeted effector fusion proteins, complexes thereof, and uses thereof. The targeted effector fusion proteins can include an effector protein that can be linked to a targeting moiety. Monomer targeted effector fusion proteins can form homogeneous or heterogeneous complexes. The targeted effector fusion proteins and complexes thereof can be formulated as pharmaceutical formulations. The targeted effector fusion proteins, complexes thereof, and formulations thereof can be administered to a subject in need thereof.

Abstract: Embodiments of the present disclosure provide methods, apparatus, systems, computing devices, computing entities for setting deprocessing parameters used in conducting hardware deprocessing on a hardware.

Abstract: Aspects of the disclosure relate to compositions and methods for predicting prognosis and classifying risk of subjects having certain cancers, for example acute myeloid leukemia (AML). In some embodiments, methods described by the disclosure comprise a step of assessing the mRNA expression of certain leukemic stem cell (LSC)-enriched genes in a subject to produce a predictive score for pediatric AML. In some embodiments, methods described by the disclosure comprise a step of assessing the mRNA expression of certain genes of pharmacological relevance for standard chemotherapy consisting of Cytarabine (also known as Ara-C), daunorubicin and etoposide in a subject to produce a predictive score for pediatric AML.