Abstract: This invention relates to the compositions and methods for labeling antibodies and other proteins and targeting agents with a helical bundle protein that is functionalized with cargo. Cargos can include but are not limited to fluorescent dyes, haptens (e.g. biotin), contrast agents (e.g. gadolinium, radionuclides), chelated metals, therapeutic agents, sensitizers, or other small molecules. Specifically, provided herein are compositions having a helical bundle, that has been labeled at precisely defined locations with cargo, and that can be conjugated, attached or fused to an antibody or other targeting agent.

Abstract: Disclosed are steerable needles having a shaft that can be controllably buckled, a steering head positioned at a distal end of the shaft, a transmission for controlling the orientation of the steering head, and a base at the end of the shaft, the base optionally comprising a controller for controlling the transmission. Also disclosed are methods of using the disclosed steerable needles.

Abstract: Compositions and methods for treating fibrosis using oligonucleotide-based therapies are provided. These therapies can be used to increase expression of Bone morphogenetic protein receptor type II (BMPR2) via inhibition of upstream Open Reading Frames, thereby reducing vasoconstriction, vascular remodeling, and formation of fibrosis, particularly pulmonary arterial fibrosis related in patients in need thereof.

Abstract: The presently disclosed subject matter provides a biomimetic organ model, and methods of its production and use. In one exemplary embodiment, the biomimetic organ model can be a multi-layer model including a at least two microchannels and at least one chamber slab with at least one membrane coated with cells disposed between at least one microchannel and the at least one chamber slab. In another exemplary embodiment, the biomimetic organ disease model can be a five-layer model including a first and second microchannel with a membrane-gel layer-membrane coated or encompassing cells disposed between the microchannels. In certain embodiments, at least one device can be coupled to the biomimetic organ model that delivers an agent to at least one microchannel.

Abstract: The present disclosure relates to magnetic resonance imaging (MRI) methods comprising (i) obtaining a baseline chemical exchange saturation transfer (CEST) MRI image of a patient, (ii) administering an effective amount of a non-nutritive sweetener to the patient, and (iii) obtaining one or more test CEST MRI image of the patient subsequent to the administering step (ii); wherein the step (i) and (iii) acquisition parameters are substantially the same. The non-nutritive sweetener may include a natural or artificial sugar alcohol, polyol, or combinations or derivatives thereof.

Abstract: A nanoscale plate structure includes base plates and rib plates with nanoscale thickness and macroscopic lateral dimensions. The base plate resides in the first plane, the ribs can reside out-of-plane and form at least one strengthening rib, and additional base plates can reside in planes parallel to the first plane. The strengthening rib can be patterned such that there is no straight line path extending through a lateral dimension of the plate structure that does not intersect the at least one base plate and the at least one strengthening rib. The plates and ribs used in the structure have a thickness between about 1 nm and about 100 nm. The plate structures can be fabricated using a conformal deposition method including atomic layer deposition.

Abstract: The present invention provides compositions and methods for inhibiting one or more diacylglycerol kinase (DGK) isoform in a cell in order to enhance the cytolytic activity of the cell. In one embodiment, the cells may be used in adoptive T cell transfer. For example, in some embodiments, the cell is modified to express a chimeric antigen receptor (CAR). Inhibition of DGK in T cells used in adoptive T cell transfer increases cytolytic activity of the T cells and thus may be used in the treatment of a variety of conditions, including cancer, infection, and immune disorders.

Abstract: This invention relates to methods of treating and ameliorating congenital and neonatal hyperinsulinism and post-prandial hypoglycemia, comprising the step of administering an antagonist of the Glucagon-Like Peptide-1 (GLP-1) receptor, e.g. a GLP-1 fragment or analogue thereof.

Abstract: An electrode, the electrode including an exposed contact surface, the exposed surface comprising a contact material, the contact material comprising a MXene. A device, the device including a plurality of electrodes, each of the plurality of electrodes comprising an exposed contact surface, the exposed surface comprising a contact material, the contact material comprising a MXene. A method, the method including delivering electrical stimulation to a subject with an electrode that comprises an exposed contact surface, the exposed contact surface comprising a contact material that includes a MXene.

Abstract: The present invention relates to compositions and methods that provide novel anti-tumor therapies in cancer. In one aspect, the present invention features a hybrid neutrophil in a non-naturally occurring container, wherein the hybrid neutrophil expresses at least one neutrophil associated molecule selected from the group consisting of: Arg1, MPO, CD66b, and CD15, and at least one antigen-presenting cell (APC) associated molecule selected from the group consisting of: CD14, HLA-DR, CD32, CD64, and CD89. In another aspect, the present invention features methods of generating a hybrid neutrophil. In still another aspect, the present invention features methods of inhibiting tumor growth in a subject, treating a tumor in a subject, and increasing efficacy of an antibody against a tumor in a subject. The methods comprise (a) administering to the subject an effective amount of an anti-tumor antibody and (b) administering to or generating in the subject an effective amount of a hybrid neutrophil.

Abstract: Disclosed herein is a composition comprising a recombinant nucleic acid sequence that encodes an antibody to a Zika viral antigen, and functional fragments thereof. The invention also relates to a composition comprising the combination of a first composition that elicits an immune response in a mammal against zika virus and a second composition comprising a recombinant nucleic acid sequence encoding an antibody, a fragment thereof, a variant thereof, or a combination thereof. In some instances, the nucleic acid molecule comprises a nucleotide sequence encoding an anti-ZIKV-Envelope (anti-ZIKV E) Protein antibody.

Abstract: The present invention is relates to a compound of formula (I), wherein X1, X2 and X3 are, independently of each other, N or CH; with the proviso that at least two of X1 X2 and X3 are N; Y is N or CH; W is H or F; with the proviso that when W is F, then X1, X2 and X3 are N; R1 and R2 are independently of each other (i) a morpholinyl of formula (II) wherein the arrow denotes the bond in formula (I); and wherein R3 and R4 are independently of each other H, C1-C3alkyl optionally substituted with one or two OH, C1-C2fluoroalkyl, C1-C2alkoxy, C1alkoxyC1-C3alkyl, CN, or C(O)O—C1-C2alkyl; or R3 and R4 form together a bivalent residue —R5R6— selected from C1-C3alkylene optionally substituted with 1 to 4 F, —CH2—O—CH2—, —CH2—NH—CH2—, or any of the structures wherein the arrows denote the bonds in formula (II); or (ii) a saturated 6-membered heterocyclic ring Z selected from thiomorpholinyl and piperazinyl, optionally substituted by 1 to 3 R7; wherein R7 is independently at each occurrence C1-C3alkyl optionally substitu

Abstract: The present invention provides compositions and methods for regulating the specificity and activity of T cells. In one embodiment, the invention provides a type of chimeric antigen receptor (CAR) wherein the CAR is termed a “KIR-CAR” which is a CAR design comprising a component of a receptor naturally found on natural killer (NK) cells. In one embodiment, the NK receptor includes but is not limited to a naturally occurring activating and inhibitory receptor of NK cells known as a killer cell immunoglobulin-like receptor (KIR).

Abstract: The presently disclosed subject matter provides systems and methods for producing a three-dimensional model of a human cervix. A microdevice is provided for culturing human cervical cells. The microdevice can include an upper microchannel including live ectocervical epithelial cells. The microdevice can include a lower microchannel including a first parallel lane and a second parallel lane including stromal media. The first and the second parallel lanes can be lined with live vascular endothelial cells. The lower microchannel can include a third parallel lane including uterine fibroblasts and live smooth muscle cells embedded in hydrogel. The first, second, and third lanes of the lower microchannel can be separated by protrusion structures. The third parallel lane can be positioned in the lower microchannel in between the first and the second parallel lanes. The microdevice can further include a porous membrane positioned in between the upper microchannel and the lower microchannel.

Abstract: The present disclosure provides gene edited modified immune cells or precursors thereof (e.g., gene edited modified T cells) comprising an exogenous T cell receptor (TCR) and/or a chimeric antigen receptor (CAR) having specificity for a target antigen, and an insertion and/or deletion in one or more endogenous gene loci, wherein the endogenous gene loci encode regulators of T cell function, thereby resulting in immune cells having enhanced function. Compositions and methods of treatment are also provided. The present invention provides methods of screening for TCR- or CAR-T cells with enhanced immune function (e.g., T cell efficacy, T cell memory, and/or T cell persistence).

Abstract: Provided are methods for optical communication, comprising: generating a phase difference signal with heterodyne or homodyne phase-locked-loop (PLL) from between an optical input signal and a local laser source; controlling the local laser source with the phase difference signal; demodulating the optical input signal using the local laser source as a carrier signal to generate a baseband output signal; and controlling the heterodyne or homodyne PLL and the demodulation with an electrical oscillator signal. Also provided are related methods.

Abstract: The present invention includes mutant AID, APOBEC, and Tet enzymes with improved functions. In one aspect the invention provides APOBEC fusion proteins comprising hyperactive deamination activity. In another aspect, the invention provides AID mutant proteins comprising hyperactive deamination activity. In yet another aspect, the invention provides mutant Tet proteins capable of stalling oxidation at a 5-hydroxymethylcytosine (hmC).

Abstract: The present invention provides a humanized antibody or antibody fragment comprising (a) a humanized light chain comprising 1) Complementarity Determining Region (CDR)-L1, the sequence of which is identical to the sequence of SEQ ID NO: 3; 2) CDR-L2, the sequence of which is identical to the sequence of SEQ ID NO: 4; and 3) CDR-L3, the sequence of which is identical to the sequence of SEQ ID NO: 5, and (b) a humanized heavy chain comprising 1) CDR-H1, the sequence of which is identical to the sequence of SEQ ID NO: 6; 2) CDR-H2, the sequence of which is identical to the sequence of SEQ ID NO: 7; and 3) CDR-H3, the sequence of which is identical to the sequence of SEQ ID NO: 8, as well as methods for treating, diagnosing, and monitoring the progression of HIT. The present invention also provides methods for assessing the antigenicity and ability to cause HIT of anionic anticoagulants.

Abstract: The invention provides compositions and methods for adoptive T cell therapy in treating a variety of disorders including cancer, infections, and autoimmune disorders. In one embodiment, the invention provides a universal immune receptor (UnivIR) that comprises an extracellular label binding domain, a transmembrane domain, and a cytoplasmic domain or otherwise an intracellular domain.

Abstract: The invention provides compositions and methods for treating diseases associated with expression of CD20 or CD22. The invention also relates to chimeric antigen receptor (CAR) specific to CD20 or CD22, vectors encoding the same, and recombinant T or natural killer (NK) cells comprising the CD20 CAR or CD22 CAR. The invention also includes methods of administering a genetically modified T cell or NK cell expressing a CAR that comprises a CD20 or CD22 binding domain.