Abstract: A concentric tube steerable device includes a plurality of tubes having a nested, concentric configuration. The tubes include an outer tube and an inner tube that extends coaxially within the outer tube. The inner tube terminates at a tip, and a pose of the tip is effectuated through individual or collective rotation or translation of the tubes about a tube axis. The concentric tube steerable device includes an actuator for rotating at least one tube about a respective tube axis, and a translator for translating at least one tube along a respective tube axis. Each tube includes a precurved portion and a corresponding axis of precurvature. For at least one tube, a flexural rigidity of the tube along its axis of precurvature is less than a flexural rigidity of the tube along a second axis that is perpendicular to the axis of precurvature, thereby improving stability of the tube.

Abstract: An in vitro expansion process for rapid expansion of antigen specific T cells, such as allogeneic antigen specific T cells comprising the steps culturing in a gas permeable vessel a population of PBMCs (such as allogeneic PBMCs) in the presence of antigen, for example a peptide or peptide mix relevant to a target antigen(s), in the presence of an exogenous cytokine characterized in that the expansion to provide the desired population of T cells is 14 days or less, for example 9, 10, 11 or 12 days, such as 10 days. The disclosure also extends to T cell populations generated by and obtained from the method and the use of same in therapy.

Abstract: Provided is a sensing system for wireless and passive monitoring of strain during a manufacturing process that depends on force to apply the energy into the manufacturing process, the sensing system comprising: at least one surface acoustic wave (SAW) sensor for detecting strain, the at least one SAW sensor being positioned in a force path located on or in the structure of one or more objects under test; and at least one transceiving antenna arrangement being connectable to the at least one SAW sensor, wherein the at least one SAW sensor and the at least one transceiving antenna arrangement are arranged to receive energy from an interrogation signal and output a strain response signal detected by the at least one SAW sensor in response to the interrogation signal.

Abstract: Coronavirus S ectodomain trimers stabilized in a prefusion conformation, nucleic acid molecules and vectors encoding these proteins, and methods of their use and production are disclosed. In several embodiments, the coronavirus S ectodomain trimers and/or nucleic acid molecules can be used to generate an immune response to coronavirus in a subject. In additional embodiments, the therapeutically effective amount of the coronavirus S ectodomain trimers and/or nucleic acid molecules can be administered to a subject in a method of treating or preventing coronavirus infection.

Abstract: A liquid cooled thermal heat sink is provided. A plurality of jet orifices provide an exit for pressurised liquid to exit a plenum chamber and impinge on a thermal surface whereby they effect a cooling of the thermal surface, the heated liquid being transferred through an exit channel to dissipate heat away from the thermal surface.

Abstract: The invention provides methods for inducing, enhancing or increasing satellite cell proliferation, and an assay for screening for a candidate compound for inducing, enhancing or increasing satellite cell proliferation. Also provided are methods for repairing or regenerating a damaged muscle tissue of a subject.

Abstract: The present invention relates to RNA constructs, and particularly, although not exclusively, to mRNA constructs and saRNA replicons and to nucleic acids and expression vectors encoding such RNA constructs. The invention extends to the use of such RNA constructs in therapy, for example in treating diseases and/or in vaccine delivery. The invention extends to pharmaceutical compositions comprising such RNA constructs, and methods and uses thereof.

Abstract: Compositions and methods are described herein for transdifferentiation of multipotent stromal cells into cells that can express insulin.

Abstract: Some aspects of this disclosure provide methods for phage-assisted continuous evolution (PACE) of proteases. Some aspects of this invention provide methods for evaluating and selecting protease inhibitors based on the likelihood of the emergence of resistant proteases as determined by the protease PACE methods provided herein. Some aspects of this disclosure provide strategies, methods, and reagents for protease PACE, including fusion proteins for translating a desired protease activity into a selective advantage for phage particles encoding a protease exhibiting such an activity and improved mutagenesis-promoting expression constructs. Evolved proteases that recognize target cleavage sites which differ from their canonical cleavage site are also provided herein.

Abstract: The disclosure provides methods and compositions for treating blood diseases/disorders, such as sickle cell disease, hemochromatosis, hemophilia, and beta-thalassemia. For example the disclosure provides therapeutic guide RNAs that target the promotor of HBG1/2 to generate point mutations that increase expression of fetal hemoglobin. As another example, the disclosure provides therapeutic guide RNAs that target mutations in HBB, Factor VIII, and HFE to treat sickle cell disease, beta-thalassemia, hemophilia and hemochromatosis. 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 are in complex with nucleic acids, such as guide RNAs (gRNAs), which target the fusion proteins to a DNA sequence (e.g., an HBG1 or HBG2 protmoter sequence, or an HFE, GBB, or F8 gene sequence).

Abstract: Novel small molecule proteolysis-targeting chimeras (PROTACs) are provided, along with methods for their use as RIPK1 kinase degraders. The small molecule PROTACs described herein are useful in treating and/or preventing RIPK1 kinase-related diseases, such as cancer, neurodegenerative disorders, and inflammatory diseases. Also provided are methods for promoting RIPK1 kinase degradation in a cell using the compounds and compositions described herein.

Abstract: A process for forming multifunctional carbon nanotubes-glass fiber-epoxy composites with high density interfaces for microwave absorption and structural materials application useful as a multifunctional microwave absorption and low-weight structural material without a need of additional coating.

Abstract: The invention provides methods of modulating and regulating NHD protein-protein interactions through nicotinamide mononucleotide, analogs and derivatives thereof, such as NAD+. Such modulation may be useful in methods of treating and preventing cancer, aging, cell death, radiation damage, radiation exposure, among others, may improve DNA repair, cell proliferation, cell survival, among others, and may increase the life span of a cell or protect it against certain stresses, among others.

Abstract: Disclosed are combination therapies including administration of I-DASH inhibitors and PGE2 antagonists, and the use of such therapies in the treatment of cell proliferative diseases.

Abstract: Provided herein are methods of reducing or eliminating undifferentiated pluripotent stem cells, where the methods comprise contacting an effective amount of a compound to a heterogeneous cell population or sample comprising or suspected of comprising differentiated cell types and undifferentiated pluripotent stem cells, whereby the contacting selectively reduces or eliminates undifferentiated pluripotent stem cells from the cell population or sample. Also provided are methods for obtaining a population of stem cell-derived cell types substantially free of undifferentiated pluripotent stem cells as well as isolated populations of such of stem cell-derived cell types.

Abstract: In a method for sensing translocation of a molecule through a nanopore, a molecule in a first fluidic solution in a first fluidic reservoir that is in direct fluidic connection with the nanopore is directed to a nanopore inlet and translocated through the nanopore to a nanopore outlet and through a fluidic passage that is in direct fluidic connection with the nanopore outlet, to a second fluidic solution in a second fluidic reservoir disposed in direct fluidic connection with the fluidic passage. The fluidic passage has at least one fluidic section in which a length of the fluidic section is greater than a width of the fluidic section. Translocation of the molecule through the nanopore is sensed by measuring the electrical potential local to the fluidic passage during the translocation of the molecule.

Abstract: The present invention generally relates to systems and methods for imaging or determining nucleic acids, for instance, within cells. In some embodiments, the transcriptome of a cell may be determined. Certain embodiments are directed to determining nucleic acids, such as mRNA, within cells at relatively high resolutions. In some embodiments, a plurality of nucleic acid probes may be applied to a sample, and their binding within the sample determined, e.g., using fluorescence, to determine locations of the nucleic acid probes within the sample. In some embodiments, codewords may be based on the binding of the plurality of nucleic acid probes, and in some cases, the codewords may define an error-correcting code to reduce or prevent misidentification of the nucleic acids. In certain cases, a relatively large number of different targets may be identified using a relatively small number of labels, e.g., by using various combinatorial approaches.

Abstract: The present disclosure concerns hyperthermic devices for treating vascular involvements related to cancer therapies, such as surgery. In specific embodiments, the device is configured to provide therapeutic heating to destroy vessel-encasing tumors while still protecting the vessel itself. In particular embodiments, the devices utilize two opposing semi-cylindrical shells that encase the vessel in need of treatment of a tumor thereon. In other devices, a flexible substrate is guided under and around the vessel and tumor thereon.

Abstract: Multi-wavelength light is directed to an optic including a substrate and metasurface optical components deposited on a surface of the substrate. The metasurface optical components comprise a pattern of silicon dielectric resonators with nonperiodic gap distances between adjacent dielectric resonators. Incident light directed to the metasurface optical components is scattered and phase-shifted by the configuration of the gap distances and the widths and thicknesses of the dielectric resonators. Each dielectric resonator has a rectangular cross-section such that a first phase shift is imparted for a transverse-electric (TE) component of the incident light and a second phase shift is imparted for a transverse-magnetic (TM) component of the incident light.

Abstract: Oral formulations comprising one or more proteasome inhibitors for use as a treatment of coronavirus infection in a subject. Also disclosed are the use of such for the treatment or prevention of SARS-CoV-2 infection in humans.