Abstract: Provided herein are polypeptides that are truncated modified recombinant forms of ADAMTS13, nucleic acid molecules encoding the polypeptides, drug delivery compositions and pharmaceutical compositions comprising the polypeptides, and methods of using the polypeptides and compositions (e.g., in the treatment of thrombotic thrombocytopenic purpura (TTP)).

Abstract: An in vitro release test (IVRT) method and system is provided for drug release testing. The IVRT method, referred to herein as adaptive perfusion, employ tangential-flow filtration (TFF), where released drug products that are smaller than a molecular weight cutoff (MWCO) of a membrane filter pass therethrough into the permeate. Unreleased drug products are retained by the pores of the filter and are recirculated to a retentate reservoir. Fresh media is provided to the retentate in order to maintain a constant total volume for the sample as well as to maintain sink conditions for the drug release. Drug concentration in the retentate and permeate are evaluated by in situ monitoring with one or more sensors and/or by periodic removal of aliquots from the respective reservoirs. In some embodiments, the membrane filter can be conditioned prior to use in order to improve the accuracy, precision, or both of the subsequent testing.

Abstract: Vaccines that elicit broadly protective anti-influenza antibodies. The vaccines comprise nanoparticles that display HA trimers from Group 2 influenza virus on their surface. The nanoparticles are fusion proteins comprising a monomeric subunit (e.g., ferritin) joined to stabilized stem regions of Group 2 influenza virus HA proteins. The fusion proteins self-assemble to form the HA-displaying nanoparticles. Also provided are fusion proteins, and nucleic acid molecules encoding such proteins, and assays using nanoparticles of the invention to detect anti-influenza antibodies.

Abstract: Metapneumovirus (MPV) F proteins 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 MPV F proteins and/or nucleic acid molecules can be used to generate an immune response to MPV in a subject. In additional embodiments, the therapeutically effective amount of the MPV F ectodomain trimers and/or nucleic acid molecules can be administered to a subject in a method of treating or preventing MPV infection.

Abstract: Recombinant Norovirus Virus-Like Particles (VLPs) formed from recombinant Norovirus VP1 proteins, and methods of their use and production are disclosed. In several embodiments, the Recombinant Norovirus VLPs can be used to generate an immune response to Norovirus VP1 protein in a subject. In additional embodiments, an effective amount of the recombinant Norovirus VLPs can be administered to a subject in a method of inhibiting a Norovirus infection.

Abstract: Disclosed are nucleic acids and polypeptides which provide the co-expression of interleukin (IL)-21 and IL-15 by a host cell, each interleukin being bound to the cell membrane by a cell membrane anchor moiety. Also disclosed are related recombinant expression vectors, host cells, populations of cells, pharmaceutical compositions, and methods of treating or preventing cancer.

Abstract: Multidimensional MRI-based methods permit identification and categorization of brain specimens to identify sub-voxel tissue components that are specific to traumatic axon injury or other lesions. Lower dimensional MR spectral data is acquired and processed to provide multidimensional MR data of higher dimensions. One or more spectral ranges are selected that define signatures for brain injury and evaluation of the multidimensional MR data in these ranges is used to locate voxels associated with brain injury. For example, partial one dimensional data sets such as T1, T2, and mean diffusion coefficient (MD) data sets can be combined to provide two dimensional data sets such as T1-T2, MD-T2, and MD-T1 data sets. Using the spectral signatures, a specimen image can be produced showing areas of lesser or greater injury.

Abstract: Disclosed is a T cell receptor (TCR) having antigenic specificity for an HLA-A2-restricted epitope of human papillomavirus (HPV) 16 E6, E629-38. Related polypeptides and proteins, as well as related nucleic acids, recombinant expression vectors, host cells, and populations of cells are also provided. Antibodies, or an antigen binding portion thereof, and pharmaceutical compositions relating to the TCRs of the invention are also provided. Also disclosed are methods of detecting the presence of a condition in a mammal and methods of treating or preventing a condition in a mammal, wherein the condition is cancer, HPV 16 infection, or HPV-positive premalignancy.

Abstract: Methods of sample preparation for detection of nucleic acids (such as viral nucleic acids, for example, viral RNA) are provided. In some examples, the methods include contacting a sample with a solution including a buffer containing about 0-0.5 mM EDTA and a chelating resin and incubating the resulting mixture at a temperature of at least about 55° C.

Abstract: The invention features modified alphavirus or flavivirus virus-like particles (VLPs). The invention provides methods, compositions, and kits featuring the modified VLPs. The invention also features methods for enhancing production of modified VLPs for use in the prevention or treatment of alphavirus and flavivirus-mediated diseases. The invention also provides methods for delivering agents to a cell using the modified VLPs.

Abstract: An agent which increases pyrimidine to purine ration in a cell without decreasing pyrimidine synthesis for use in a method of treating a solid tumor in a subject in need thereof, optionally in combination with an immune-modulating drug.

Abstract: The invention features methods that are useful for treatment of a patient at increased risk for infection and for selecting a patient for treatment for an infection. In various embodiments, the infection is coronavirus disease 2019 (COVID-19), sepsis, or other respiratory infections.

Abstract: The present invention provides a synthetic MMACHC polynucleotide comprising a polynucleotide encoding MMACHC that is codon-optimized for expression in a human. Also provided is a polypeptide encoded by a synthetic MMACHC polynucleotide, an expression vector comprising a MMACHC gene sequence under the control of a chicken beta actin (CBA) promoter, and an expression vector comprising a synthetic MMACHC polynucleotide. Methods of treating cobalamin C deficiency and for detecting or tracking exogenous MMACHC are also provided.

Abstract: An optically controlled, multi-transmitter magnetic resonance imaging system for multi-nuclear, high field applications is disclosed. In one embodiment, the MRI system may include a dual-tuned radio-frequency (RF), on-coil power amplifier for amplifying RF power signals at two or more frequencies for the multi-nuclear excitations for use in a dual-tuned coil MRI device or a nested coil MRI device. In one particular implementation, the dual-tuned amplifier of the MRI system may receive optical carrier signals through the broadband optical interface to control the on-coil amplifiers. A variable effective inductor circuit for use in tuning the dual-tuned amplifier is also disclosed. The variable effective inductor circuit includes a gallium nitride (eGaN) field effect transistor (FET) device connected to an inductor.

Abstract: Provided herein are methods of producing a distinct bilayer culture of retinal epithelial cells (RPE) with photoreceptor cells and/or photoreceptor precursor cells (PR/PRP). Further provided herein is a therapy comprising transplantation of the RPE and PR/PRP bilayer as well as methods for testing candidate drugs using the bilayer.

Abstract: Provided is a method of inhibiting viral replication, including contacting one or more cells that has been infected or contacted with a flavivirus with an effective amount of niclosamide, temoporfin, nitazoxanide, tizoxanide, erythrosin B, methylene blue. Contacting one or more cells that have been infected with a flavivirus may include administering the compound to a mammal, a human, or other subject. The flavivirus may be Dengue virus serotype 1, Dengue virus serotype 2, Dengue virus serotype 3, Dengue virus serotype 4, yellow fever virus, West Nile virus, Zika virus, Japanese encephalitis virus, tick-born encephalitis virus, Powassan virus, St. Louis encephalitis virus, or other flavivirus.

Abstract: Methods are disclosed for treating a cone rod homeobox transcription factor (CRX) autosomal dominant retinopathy in a subject. These methods include administering to the subject an effective amount of a nucleic acid molecule comprising a retinal specific promoter operably linked to a nucleic acid molecule encoding a CRX protein. Compositions are disclosed that include an effective amount of a nucleic acid molecule comprising a retinal specific promoter operably linked to a nucleic acid molecule encoding CRX, for use in treating a CRX autosomal dominant retinopathy in a subject. A retinal specific promoter is disclosed that includes the nucleotide sequence of SEQ ID NO: 1.

Abstract: Embodiments of immunogens comprising a recombinant Mumps (MuV) F ectodomain trimer stabilized in a prefusion conformation or a recombinant Measles (MeV) F ectodomain trimer stabilized in a prefusion conformation are provided. Also provided are embodiments of immunogens comprising chimeric proteins comprising the recombinant MuV or MeV F ectodomain trimer and one or more MuV HN or MeV H ectodomains. Also disclosed are nucleic acids encoding the immunogens and methods of their production. Methods for inducing an immune response in a subject by administering a disclosed immunogen to the subject are also provided. In some embodiments, the immune response treats or inhibits MuV and/or MeV infection in a subject.

Abstract: The invention features compositions and methods for the prevention or treatment of one or more strains of Chikungunya virus, as well as other alphavirus-mediated diseases.

Abstract: A star polymer of formula O[P1]-([X]-A[P2]-[Z]-[P3])n where O is a core; A is a polymer arm attached to the core; X is a linker molecule between the core and the polymer arm; Z is a linker molecule between the end of the polymer arm and P3; P1, P2 and P3 are each independently one or more pharmaceutically active compounds that act extracellularly or intracellularly, n is an integer number; [ ] denotes that the group is optional; and at least one of P1, P2 or P3 is present.