Abstract: A microneedle or microneedle device includes a microneedle body extending from a base to a penetrating tip formed from a silk fibroin based material, which is easy to fabricate and highly biocompatible. The microneedle device can include one or more microneedles mounted to a substrate. The silk fibroin can include active agents to be transported into or across biological barriers such as skin, tissue and cell membranes. The silk fibroin microneedles can be fully or partially biodegradable and/or bioerodible. The silk fibroin is highly stable, affords room temperature storage and is implantable. The silk fibroin structure can be modulated to control the rate of active agent delivery.

Abstract: The present invention provides, among other things, a elastomeric biomaterial having enzymatically cross-linked amino acid phenolic side chains to generate highly elastic hydrogels. Materials are characterized by tunable mechanical properties, gelation kinetics and swelling properties of these new protein polymers. Provided materials are support encapsulation of cells. Methods of making and using of provided particles are also disclosed.

Abstract: The present disclosure relates to, among other things, compounds and methods for treating neuropathic pain, ocular pain, ocular inflammation, and/or dry eye and methods of detecting mutations in specific G-protein coupled receptors, such as missense mutations, and determining the extent to which these mutations alter the pharmacological response of the G-protein coupled receptor.

Abstract: A nanocomplex containing a delivery agent and a pharmaceutical agent. The nanocomplex has a particle size of 50 to 1000 nm, the delivery agent binds to the pharmaceutical agent via non-covalent interaction or covalent bonding, and the pharmaceutical agent is a modified peptide or protein formed of a peptide or protein and an added chemical moiety that contains an anionic group, a disulfide group, a hydrophobic group, a pH responsive group, a light responsive group, a reactive oxygen species responsive group, or a combination thereof.

Abstract: Methods and systems for generating output of a simulation model in a simulation system are described. In an example, a processor may retrieve observed output data from a memory. The observed output data may be generated based on a simulation operator of a simulation model. The processor may further optimize a generalization error of a distance measure between the observed output data and model output data. The model output data may be generated based on a high-fidelity operator. The processor may further determine a correction operator based on the optimized generalization error of the distance measure. The processor may further append the correction operator to the simulation operator to produce a supplemented operator. The processor may further generate supplemented output data by applying the simulation model with the supplemented operator on a set of inputs.

Abstract: Provided are mesenchymal stromal cell (MSC)-derived extracellular vesicles (EV) having tethered (membrane-bound) TGF-? (MSC-derived membrane-tethered TGF-? EV), and compositions containing such EV for use as therapeutics and immunomodulatory agents. Provided also are diagnostic methods and methods of assessing or monitoring disease status and/or progression in patients using membrane-tethered TGF-? derived from a variety of cell sources that serve as detectable, quantifiable biomarkers in biological samples. The MSC-derived membrane-tethered TGF-? EV can also be used to deliver various bioactive agents to a target cell or tissue for treating various diseases. The level of TGF-? tethered to the membrane of the EV can also be modified or manipulated in vitro or ex vivo. Such modified MSC-derived membrane-tethered TGF-? EV are useful as immunotherapeutic agents in the treatment or management of certain diseases, particularly those involving inflammation, autoimmunity, transplant rejection and cancer.

Abstract: In some embodiments, the present invention provides tissue compositions including a first silk scaffold comprising a plurality of epithelial cells, a second silk scaffold comprising a plurality of stromal cells, and a plurality of neurons. In some embodiments, provided compositions can function as physiologically relevant corneal model systems for, inter alia, testing of therapeutics for corneal disease and/or injury and production of functional corneal tissue (e.g., for transplant, etc). The present invention also provides methods for making and using provided compositions.

Abstract: Compositions, methods and kits are provided for treating complement related disorders in a subject with protein in combination having protein fusions of at least two of a CD46 protein, a CD55 protein and a CD59 protein or with a recombinant chimeric protein having at least two of a CD46 protein, a CD55 protein and a CD59 protein or with nucleic acids encoding these proteins. The composition negatively modulates classical and alternative complement pathways thereby treating complement related disorder such as macular degeneration, age-related macular degeneration, diabetic retinopathy, inflammatory bowel disease, thyroiditis, cryoglobulinaemia, fetal loss, organ graft rejection, cancer, etc.

Abstract: A nanocomplex, of particle size 50 nm to 1000 nm, containing saporin and a lipid-like compound, in which saporin binds to the lipid-like compound via non-covalent interaction or covalent bonding. The lipid-like compound has a hydrophilic moiety, a hydrophobic moiety, and a linker joining the hydrophilic moiety and the hydrophobic moiety. The hydrophilic moiety is optionally charged and the hydrophobic moiety has 8 to 24 carbon atoms. Also disclosed is a pharmaceutical composition containing such a nanocomplex and a pharmaceutically acceptable carrier. The nanocomplex is useful in treating diseases, such as cancer.

Abstract: A microfluidic device includes a first layer of a porous material with pores having a first average pore size and a liquid-receiving area through which a liquid sample is received into the microfluidic device. A second layer of another porous material, with pores of a second average pore size, is stacked below the first layer and has a channel with a starting end positioned at least in part in an overlapping manner with the liquid-receiving area. The channel has a terminating end extending laterally at a predetermined wicking distance from the starting end. The first average pore size and the second average pore size cause a wicking effect in which at least some of the liquid sample flows along the channel at least a portion of the wicking distance between the starting end and the terminating end.

Abstract: Provided herein are compositions and methods for vaccination and research applications. In particular, provided herein are non-neuroinvasive herpesviruses and alpha herpesviruses and uses thereof.

Abstract: Provided herein are compositions and methods for vaccination and research applications. In particular, provided herein are non-neuroinvasive herpesviruses and alpha herpesviruses and uses thereof.

Abstract: A method was developed to prepare silk fibroin microspheres using lipid vesicles as templates to efficiently load therapeutic agents in active form for controlled release. The lipids are subsequently removed through the use of a dehydration agent, such as methanol or sodium chloride, resulting in ?-sheet structure dominant silk microsphere structures having about 2 ?m in diameter. The therapeutic agent can be entrapped in the silk microspheres and used in pharmaceutical formulations for controlled-release treatments.

Abstract: A polymer fiber formed of statistical copolymers, each of which contains zwitterionic repeat units and hydrophobic repeat units, the zwitterionic repeat units constituting 20-75 wt % of the statistical copolymer and the hydrophobic repeat units being characterized in that a homopolymer formed thereof has a glass transition temperature above room temperature. Also disclosed is a fibrous membrane containing such polymer fibers in which greater than 90% of the polymer fibers are each independently rib bon-shaped fibers or wrinkly fibers. A method of preparing such a fibrous membrane is disclosed as well.

Abstract: Methods and corresponding apparatus and systems for assessing cellular metabolic activity are disclosed. In one aspect, a cell can be illuminated with optical radiation in order to cause multi-photon excitation of at least one endogenous metabolic cofactor in that cell and cause the excited metabolic cofactor to emit fluorescent radiation. A detector can be used to detect the fluorescent radiation emitted by the excited endogenous metabolic cofactor. A computer processor can analyze the fluorescent radiation to derive the following parameters: (1) using a computer processor to analyze the intensity of the fluorescent radiation, (2) a fluorescence lifetime of at least one of the excited metabolic cofactor, (3) a parameter indicative of mitochondrial clustering in the cell. These parameters can be used to assess at least one metabolic process of the cell.

Abstract: Multi-step methods for the in vitro production of enucleated red blood cells and the enucleated red blood cells thus prepared are provided. Such enucleated red blood cells may express fusion proteins comprising an antigen binding protein which allows the red blood cell to bind a toxin or an antigen of a pathogen. Also described herein are methods for neutralizing a toxin or pathogen in a subject by administering enucleated red blood cells that express any of the fusion proteins provided herein.

Abstract: A composition, as well as methods using the composition, for detection or quantification of a molecule at a singlet state (e.g., singlet oxygen). The composition includes one or more nanoparticles, and the nanoparticle has an energy donor, an energy acceptor associated with the energy donor, and an energy transfer mechanism between the energy donor and the energy acceptor.

Abstract: Identified compounds demonstrate protein kinase inhibitory activity. More specifically, the compounds having the structures below (I) are demonstrated to inhibit receptor interacting kinase 2 (RIPK2) and/or Activin-like kinase 2 (ALK2). Compounds that are either dual RIPK2/ALK2 inhibitors or that preferentially inhibit RIPK2 or ALK2 could provide therapeutic benefit.

Abstract: Described are non-toxigenic Clostridium difficile strains and spores. Also described are vaccines comprising the Clostridium difficile spores. Further described are methods of preventing or treating a Clostridium difficile infection in a subject in need thereof.

Abstract: In some embodiments, the present invention provides methods including the steps of providing one or more human somatic cells, causing transient increased expression of OCT4, KLF4, SOX2, and cMYC in the somatic cells forming modified somatic cells, providing a plurality of inactivated embryonic fibroblasts, associating the modified somatic cells with the inactivated embryonic fibroblasts in a culture media comprising 20% KO DMEM xeno-free serum replacement and at least 15 ng/ml recombinant bFGF to form human induced neural stem cells.