Abstract: Engineered nucleases are promising tools for genome manipulation and determining off-target cleavage sites of these enzymes is of great interest. This disclosure provides in vitro selection methods that interrogate 1011 DNA sequences for their ability to be cleaved by active nucleases, e.g., ZFNs and TALENs. The method revealed hundreds of thousands of DNA sequences that can be cleaved in vitro by two ZFNs, CCR5-224 and VF2468, which target the endogenous human CCR5 and VEGF-A genes, respectively. Analysis of the identified sites in cultured human cells revealed CCR5-224-induced mutagenesis at nine off-target loci. This disclosure provides an energy compensation model of ZFN specificity in which excess binding energy contributes to off-target ZFN cleavage. It was also observed that TALENs can achieve cleavage specificity similar to or higher than that observed in ZFNs.

Abstract: The present disclosure provides soluble truncated mutant programmed death-ligand 1 (PD-L1) peptides. Polynucleotides and vectors encoding the soluble truncated mutant PD-L1 peptides are also provided. Further, methods of using the soluble truncated mutant peptides to promote differentiation of CD4+ effector T (Th1) cells into Foxp3+ regulatory T (Treg) cells are provided.

Abstract: The present invention relates to chimeric antigen receptor (CAR)-T cells, and particularly, although not exclusively, to anti-CD4 CARs, and to their use in immunotherapy, and for treating, preventing or ameliorating cancer, such as T-cell lymphomas, various microbial infections, such as HIV and TB, and also autoimmune disease. The invention is especially concerned with the use of CAR-engineered mucosal-associated invariant T (MAIT) cells, and to novel methods for stimulating, isolating and expanding highly purified MAIT cells, which can then be engineered into such CAR-MAIT cells. The invention extends to genetic constructs per se, and to their use in generating the CAR-MAIT cells, and to transduced CAR-MAIT cells per se. The invention also extends to various medical uses of the constructs and transduced CAR-MAIT cells, and to pharmaceutical compositions comprising these constructs and CAR-MAIT cells.

Abstract: The present disclosure relates to a wearable electrical ankle pump massage bidirectional exerciser. The adopted technical solution is that the wearable electrical ankle pump massage bidirectional exerciser includes a vamp plate and a calf plate. A base is rotatably connected to a lower side of the vamp plate, a swing airbag for driving the vamp plate is arranged on an upper part of a rear side of the base, side supporting plates are arranged on both sides of the vamp plate, and side massage airbags are arranged on both sides of an upper part of the calf plate. An equipment box is provided on a bottom of the base, a first air pump group is arranged inside the equipment box, and the first air pump group is configured to drive the swing airbag and the side massage airbags.

Abstract: The present invention comprises compositions, methods, and devices for enhancing an endogenous immune response against a cancer. Devices and methods provide therapeutic immunity to subjects against cancer.

Abstract: In an embodiment, the present disclosure pertains to a method of making magnetic nanoparticles through the utilization of a microfluidic reactor. In some embodiments, the microfluidic reactor includes a first inlet, a second inlet, and an outlet. In some embodiments, the method includes applying a magnetic nanoparticle precursor solution into the first inlet of the microfluidic reactor through a first flow rate and applying a reducing agent into the second inlet of the microfluidic reactor through a second flow rate. In some embodiments, the magnetic nanoparticles are produced in the microfluidic reactor and collected from the outlet of the microfluidic reactor. In an additional embodiment, the present disclosure pertains to a composition including a plurality of magnetic nanoparticles. In a further embodiment, the present disclosure pertains to a microfluidic reactor.

Abstract: The invention provides methods of diagnosing neuropathic corneal pain by the detection of neuromas, such as micro-neuromas, on the cornea. The invention also features systems for detecting the presence of anatomical features located on an ocular tissue surface that may be a marker for neuropathic corneal pain. The systems feature an in vivo confocal microscope and a computer N programmed with a neural network to automate the analysis of the microscope images. The invention provides methods of using the system to identify a micro-neuroma in images collected of an ocular surface and methods of diagnosing neuropathic corneal pain and monitoring treatment of neuropathic corneal pain using a system of the invention.

Abstract: Provided are chimeric VEGF-binding proteins and nucleic acids (e.g., a vector) encoding chimeric VEGF-binding proteins, methods and host cells for producing these proteins and nucleic acids, and pharmaceutical compositions containing these proteins and nucleic acids. Also provided are methods of treating an angiogenic disease or disorder that include administering at least one of the chimeric VEGF-binding proteins or at least one of the nucleic acids (e.g., a vector) encoding a chimeric VEGF-binding protein.

Abstract: Reperfusion injury is limited during endovascular therapies (e.g., revascularization and/or reperfusion of end organ tissues) by conditioning the tissues against reperfusion injury using an optical fiber catheter to deliver far red and near infrared (R/NIR) light to the tissues. The light may be multiple wavelength or single wavelength light, and may have one or more wavelengths selected from the range of 510 to 830 nm. The R/NIR light may be delivered concurrently with the endovascular therapy, or in other instances may be delivered before or after a particular therapy.

Abstract: The disclosure provides adenosine deaminases that are capable of deaminating adenosine in DNA. The disclosure also provides fusion proteins comprising a Cas9 (e.g., a Cas9 nickase) domain and adenosine deaminases that deaminate adenosine in DNA. In some embodiments, the fusion proteins further comprise a nuclear localization sequence (NLS), and/or an inhibitor of base repair, such as, a nuclease dead inosine specific nuclease (dISN).

Abstract: An improved method of culturing cells for cell therapy applications that includes growing desired cells in the presence of antigen-presenting cells and/or feeder cells and with medium volume to surface area ratio of up to 1 ml/cm2 if the growth surface is not comprised of gas permeable material and up to 2 ml/cm2 if the growth surface is comprised of gas permeable material. The desired cells are at a surface density of less than 0.5×106 cells/cm2 at the onset of a production cycle, and the surface density of the desired cells plus the surface density of the antigen presenting cells and/or feeder cells are at least about 1.25×105 cells/cm2.

Abstract: The present invention generally relates to imaging cells, for example, to determine phenotypes and/or genotypes in populations of cells. In some aspects, cells may be analyzed, e.g., imaged, to determine their phenotype, and their genotypes may be determined by exposing the cells to nucleic acid probes, e.g., as in smFISH. MERFISH, FISH, in situ hybridization, or other suitable techniques. In some cases, the cells may be exposed to a nucleic acid comprising an identification portion, which may be used to distinguish the cells from each other. In some embodiments, the cells may be exposed to a nucleic acid comprising an expression portion, e.g. a gene, or coding region for a non-translated RNA, etc., that when expressed, produces a protein, RNA, DNA, or the like that may alter the phenotype of the cell or the variable nucleic acid sequence can consist of promoters, gene regulatory elements, transcription factor binding sites, Cas9 guide RNA coding regions, etc. that otherwise alter the phenotype of the cell.

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 disclosure provides adenosine deaminases that are capable of deaminating adenosine in DNA to treat Hutchin-son-Gilford progeria syndrome (HOPS). The disclosure also provides fusion proteins, guide RNAs and compositions comprising a Cas9 (e.g., a Cas9 nickase) domain and adenosine deaminases that deaminate adenosine in DNA, for example in a LNA gene. In some embodiments, adenosine deaminases provided herein are used to correct a C1824T mutation in LMNA. In some embodiments, the methods and compositions provided herein are used to treat Hutchinson-Gilford progeria syndrome (HGPS).

Abstract: One aspect of the invention provides a trocar including: a central cylinder defining a central channel and having a distal end adapted and configured for insertion within a subject; one or more gas outlets located within the central cylinder proximate to the distal end of the trocar; and one or more liquid outlets located within the central cylinder on a proximal side of the one or more gas outlets. The one or more liquid outlets are adapted and configured to dispense a liquid when an endoscope is withdrawn from a fully extended position within the central channel of the trocar to a position proximate to the one or more liquid outlets. Distal advancement of the endoscope to a position adjacent to the one or more gas outlets removes liquid from a distal end of the endoscope.

Abstract: According to aspects of embodiments described herein, an optical computing device (100) comprises a plurality of input waveguides (101), a photonic meta-surface (103) in contact with the plurality of input waveguides, and a plurality of output waveguides (105) in contact with the transformational meta-surface. The optical computing device may be configured to perform a mathematical operation may be a matrix multiplication. A computer-implemented method (300) of designing an optical computing device includes a plurality of input waveguides, a photonic meta-surface, and a plurality of output waveguides, the method includes exciting each input waveguide one-by-one (303) and measuring the energy at the input region and the output region (305) to determine a contribution of the current input waveguide. The sum of contributions (307) of all input waveguides are compared to a target transformation (315) to determine a loss value used to update a set of design parameters (317).

Abstract: Compounds of the formula (I) and pharmaceutically acceptable salts thereof: 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: Methods of evaluating viscous compositions are disclosed. These methods may be used to evaluate volumetric properties of fluids including peanut butter. The methods may include preparing a surface for testing by leveling and flattening a viscous composition, placing a drop of a liquid on the flattened leveled surface, evaluating the observed contact angle between the drop and the surface, and then comparing the observed contact angle to a reference contact angle.

Abstract: A first fluidic solution having a first ionic concentration is provided in a first fluidic reservoir in direct fluidic connection with a nanopore. A second fluidic solution, having a second ionic concentration, is provided in a second fluidic reservoir disposed in fluidic connection with the nanopore through a fluidic passage having at least one fluidic section in which the section length is greater than the section width. The electrical potential local to the fluidic passage is measured, and the resistance of both the fluidic passage the nanopore are determined based on the fluidic passage electrical potential. The fluidic passage resistance is compared with the nanopore resistance and at least one of the first and second ionic concentrations is adjusted based on the comparison. The measuring, determining, comparing, and adjusting steps are conducted until the fluidic passage resistance is between about 0.1 times and about 10 times the nanopore resistance.

Abstract: A method of controlling an electricity distribution network, wherein the electricity distribution network is a mesh network including a plurality of loads and there is a voltage-source converter connected to a point in the network. The method comprises, while using the voltage-source converter to try to hold the voltage magnitude constant at said point, establishing a record of how, at said point, the real power flowing between the network and the voltage-source converter varies with variation of the reactive power that the voltage-source converter causes to flow between itself and the network, using a reactive-power value, proportional to the sum of the reactive-power draws of the loads, in order to look up a real-power value from the record, and configuring the voltage-source converter to supply into the network at said point reactive and real power at said reactive- and real-power values, respectively.