Abstract: Engineered transcriptional activator-like effectors (TALEs) are versatile tools for genome manipulation with applications in research and clinical contexts. One current drawback of TALEs is that the 5? nucleotide of the target is specific for thymine (T). TALE domains with alternative 5? nucleotide specificities could expand the scope of DNA target sequences that can be bound by TALEs. Another drawback of TALEs is their tendency to bind and cleave off-target sequence, which hampers their clinical application and renders applications requiring high-fidelity binding unfeasible. This disclosure provides methods and strategies for the continuous evolution of proteins comprising DNA-binding domains, e.g., TALE domains. In some aspects, this disclosure provides methods and strategies for evolving such proteins under positive selection for a desired DNA-binding activity and/or under negative selection against one or more undesired (e.g., off-target) DNA-binding activities.

Abstract: Embodiments disclosed herein provide methods of using somatic mutations in mitochondrial genomes to retrospectively infer cell lineages in native contexts and to serve as genetic barcodes to measure clonal dynamics in complex cellular populations. Further, somatic mutations in mitochondrial DNA (mtDNA) are tracked by single cell genomic approaches for simultaneous analysis of single cell lineage and state. Applicants further show that mitochondrial mutations can be readily detected with contemporary single cell transcriptomic and epigenomic technologies to concomitantly capture gene expression profiles and chromatin accessibility, respectively.

Abstract: The present invention provides constructs comprising modified riboswitches to regulate expression of a transgene within a subject. Methods of treating a disease, specifically an eye disease, are also contemplated.

Abstract: There is described a nucleic acid molecule comprising a nucleotide sequence encoding a functional dystrophin protein. Also described is a vector, a host cell and a pharmaceutical composition comprising the nucleic acid molecule; use of the nucleic acid molecule in therapy, such as in the treatment of a muscular dystrophy; and a method of treating muscular dystrophy, the method comprising administering a therapeutically effective amount of the nucleic acid molecule to a patient suffering from a muscular dystrophy.

Abstract: A sensor device for detecting static modulus of elasticity in situ comprising: top and bottom frame end plates, said top and bottom frame end plates connected by at least two frame side bars; a dry cavity connected to said top frame end plate comprising a piston, precompression mechanism, and piston transfer plate; a displacement measurement gauge extending from said dry cavity along a longitudinal axis of said sensor device having a first end in contact with said piston transfer plate and a second end in contact with a bottom inner face of said bottom frame end plate; and a top inner face connected to said piston transfer plate, wherein a portion of elastomeric material is positioned on said bottom and top inner faces, said elastomeric material positioned to prevent contact with either bottom or top inner faces except for a portion along the longitudinal axis of the displacement measurement gauge.

Abstract: Systems and methods are disclosed for making a quantum network node. A plurality of scoring function F values are calculated for an array of at least two photonic crystal cavity unit cells, each having a lattice constant a and a hole having a length Hx and a width Hy. A value of a, a value of Hx, and a value of Hy are selected for which a scoring function value is at a maximum. A waveguide region and the array of at least two photonic crystal cavity unit cells based on the selected values are formed on a substrate. At least one ion between a first photonic crystal cavity unit cell and a second photonic crystal cavity unit cell are implanted and annealed into a quantum defect. A coplanar microwave waveguide is formed on the substrate in proximity to the array of at least two photonic crystal cavity unit cells.

Abstract: The present invention generally relates to systems and methods for treating certain oxidative stress conditions. In one aspect, compositions and methods of the invention can be used to treat a subject having an oxidative stress condition, for example, a subject having pulmonary fibrosis. In some embodiments, an inhibitor of ERp57 (for example, thiomuscimol) and/or an inhibitor of GSTP (for example, TLK-199) may be used to treat the subject. Also provided in certain aspects of the present invention are kits for such therapies, methods for promoting such therapies, and the like.

Abstract: An instrumented trail-making task (iTMT) platform includes a wearable sensor and interactive interface technology configured to identify cognitive-cognitive impairment in individuals such as older adults. The iTMT platform may be programmed with neuropsychological tests for assessing individuals. The iTMT may provide information on visual search, scanning, speed of processing, mental flexibility, and/or executive functions as well as physical biomarkers of motor performance including slowness, weakness, exclusion, and/or motor planning error. Results of tests administered by the iTMT system may be reported to a patient or caregiver and used in identifying cogni-tive-motor impairment among individuals suffering from cognitive impairment, dementia, and/or those with frailty status, and/or cognitive frailty, and/or high risk of falling, and/or high likelihood of decline in cognitive-motor over time.

Abstract: A method for detecting a two-qubit correlated dephasing error includes accessing a signal of a quantum system, where the quantum system includes a plurality of qubits. Every qubit has a nonzero rate of dephasing and some qubits have a nonzero rate of correlated dephasing. The signal further includes information about a matrix that includes diagonal elements and off-diagonal elements. The off-diagonal elements of the matrix are 2s-sparse. The method further includes performing randomized measurements of the off-diagonal elements of the matrix and recovering the matrix based on a direct measurement of the diagonal elements of the matrix.

Abstract: This disclosure provides methods for monitoring an immune response. Methods comprise linking a polynucleotide sequence encoding a heavy chain variable region and a polynucleotide sequence encoding a light chain variable region from a single lymphocyte from a biological sample obtained before an immune response and linking a polynucleotide sequence encoding a heavy chain variable region and a polynucleotide sequence encoding a light chain variable region from a single lymphocyte from a biological sample obtained during or after an immune response. Methods further comprise performing high-throughput sequencing of the linked (paired) sequences from before the immune response and from during or after the immune response, and comparing the resulting sequence reads.

Abstract: In one aspect, the disclosure relates to compositions, methods, and devices pertaining to polymeric nanoparticle compositions (pNP), pNP compositions comprising a therapeutic agent, devices comprising a drug-coated balloon comprising a disclosed pNP comprising a therapeutic agent, and methods for treating peripheral artery disease using the disclosed compositions and devices. In further aspects, the pNP comprises a poly (lactic-co-glycolic) acid possessing a positive charge for firm attachment to the balloon matrix, followed by adhesion to the negatively charged bilayer of the vascular wall. In still further aspects, the therapeutic agent comprises a resveratrol or derivative thereof, a quercetin or derivative thereof, or combinations thereof. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present disclosure.

Abstract: A method of treating prostate cancer in a patient comprising administering to the patient a pharmaceutical composition including a first therapeutic including a TLK1B inhibitor, or a pharmaceutically acceptable salt, solvate, ester, amide, clathrate, stereoisomer, enantiomer, prodrug or analog thereof, and a second therapeutic including an antiandrogen or a pharmaceutically acceptable salt, solvate, ester, amide, clathrate, stereoisomer, enantiomer, prodrug or analog thereof.

Abstract: There is provided a method for reconstructing a 3D image, comprising: obtaining Doppler ultrasound images depicting a blood vessel and measurement of blood flow in the blood vessel, and 2D camera images captured by a camera depicting fiducial objects randomly distributed within a viscous material and spaced apart by random distances on a surface of the individual, computing 3D coordinates within a world coordinate system for pixels of the Doppler images using an external reference of an ultrasound transducer pose computed by analysis of relative changes in locations of the fiducial objects within sequential camera images, and computing a respective estimated blood flow for pixels of the Doppler images at locations within the blood vessel, reconstructing a 3D image from 3D voxels computed from the 3D coordinates of pixels of the Doppler images, including respective estimated blood flow, wherein the 3D image depicts the blood vessel and blood flow.

Abstract: Compounds of the formula (I) and pharmaceutically acceptable salts thereof: (I) wherein the substituents are defined in the specification. The compounds are hyperpolarisation activated cyclic-nucleotide modulated ion channel 2 (HCN2) inhibitors. Also disclosed are pharmaceutical compositions comprising the compounds, and the use of the compounds for the treatment or prevention of medical conditions mediated by HCN2, including neuropathic pain.

Abstract: The present disclosure provides compositions comprising encapsulated engineered bacteria. The bacteria may be engineered to act as sensors of biomarkers, such as inflammation, as well as to produce diagnostic or therapeutic agents.

Abstract: Male-sterile EGMS rice lines, both conventional and herbicide-tolerant, and their Fi hybrids are disclosed. The EGMS lines can produce Fi hybrids with high yield, desirable agronomic traits, and good milling characteristics.

Abstract: A replacement heart valve device is disclosed. In some embodiments, the device includes a frame coupled to one or more leaflets that are moveable between open and closed configurations. In some embodiments, the frame comprises at least two frame sections that join at a pair of commissural posts. In some embodiments, the device may be geometrically accommodating to adapt to different vasculature shapes and sizes and/or to be able to change size while implanted within a growing patient.

Abstract: A method and system for label-free detection of pathogenic and antibiotic resistant bacteria is disclosed. The method includes fabricating a G-FET/peptide device having a synthesized peptide probe capable of recognizing and binding to a bacterial target; performing electric-field assisted binding of at least one bacterial cell of the bacterial target to the G-FET/peptide device; and electrically detecting the binding of the at least one bacterial cell to the G-FET/peptide device.

Abstract: A non-contact system for the sensing of pH includes a hyperspectral imaging device configured to capture a hyperspectral image of a fluid, a flow cell configured to enable the capturing of a hyperspectral image of a fluid, a process, and a memory. The memory includes instructions stored thereon, which, when executed by the processor, cause the system to generate a hyperspectral image of the fluid in the flow cell, generate several spectral signals based on the hyperspectral image, provide the spectral signal as an input to a machine learning network, and predict by the machine learning network a pH of a fluid.

Abstract: Systems and methods for accelerated online adaptive radiation therapy (“ART”) are described. The improvements to online ART are generally provided based on the use of textural analysis and machine learning algorithms implemented with a hardware processor and a memory. The described systems and methods enable more efficient and accurate online adaptive replanning (“OLAR”), which can also be implemented in clinically acceptable timeframes. For example, OLAR can be reduced from taking 10-30 minutes down to 5-10 minutes.