Abstract: The technology described herein is directed to targeting molecules that bind to one or more transmembrane molecules expressed in tumor vascular endothelial cells and that are capable of targeting an agent that induces cell death, for example, immunogenic or non-immunogenic cancer cell death. In another aspect, described herein are methods of treating a subject having cancer comprising administering said targeting molecules and agents, and, in certain embodiments, enhancing the immunogenic response to the cancer, for example, by enhancing intratumoral infiltration of T cells.

Abstract: The technology described herein is directed to ionic liquids and methods of drug delivery.

Abstract: The technology described herein is directed to antibody or antigen binding fragments thereof, e.g., nanobody, to PMEPA-1 overexpressed in tumor vascular endothelial cells. The antibody or antigen binding fragments to PMEPA-1 can be used to target an agent, for example, that induces cell death, for example, immunogenic or non-immunogenic cancer cell death, and in methods of treating cancer.

Abstract: The disclosure features compositions and methods that are useful for determining the fraction of tumor-derived DNA (tumor fraction; TF) in cell free DNA (cfDNA). The methods involve calculating the fraction of tumor-derived DNA in the cfDNA using a combination of copy number alteration data and fragment length distribution data.

Abstract: Systems and methods relate to selectively arranging a plurality of qubits into a spatial structure to encode a quantum computing problem. Exemplary arrangement techniques can be applied to encode various quantum computing problems. The plurality of qubits can be driven according to various driving techniques into a final state. The final state can be measured to identify an exact or approximate solution to the quantum computing problem.

Abstract: Compositions and methods for making a plurality of probes for analyzing a plurality of nucleic acid samples are provided. Compositions and methods for analyzing a plurality of nucleic acid samples to obtain sequence information in each nucleic acid sample are also provided.

Abstract: The present disclosure provides a hypoglycemia prediction algorithm (HPA) specifically designed for the unique postprandial glycemic patterns characteristic of PBH. This algorithm can predict impending hypoglycemia by performing a series of steps. The steps can include collecting data from at least one sensor. The data can comprise a concentration of glucose in the bloodstream of a subject. The data can be processed using the HPA and impending glucose concentrations can be calculated. The method can then provide for determining whether the predicted glucose concentrations are lower than a hypoglycemic threshold parameter. In response to determining that the predicted glucose concentrations are lower than the hypoglycemic threshold parameter, the method can provide for enacting an impending hypoglycemia protocol.

Abstract: The specification provides programmable base editors that are capable of introducing a nucleotide change and/or which could alter or modify the nucleotide sequence at a target site in a double-stranded nucleotide sequence, such as, a chromosome, genome, or a mitochondrial DNA (mtDNA), with high specificity and efficiency. Moreover, the disclosure provides fusion proteins and compositions comprising a programmable DNA binding protein (e.g., a mitoTALE, a mitoZFP, or a CRISPR/Cas9) and evolved double-stranded DNA deaminase domains that is capable of being delivered to a cell nucleus and/or a mitochondria and carrying out precise installation of nucleotide changes in the target a double-stranded nucleotide sequence, such as, a chromosome, genome, or mtDNA. The fusion proteins and compositions are not limited for use with mtDNA, but may be used for base editing of any double-stranded target DNA.

Abstract: Systems and methods are provided for characterizing shuttle capture events in a nanopore sensor. The method first collects time-dependent current blockage signatures for at least one bias voltage. The method then identifies each signature as corresponding to a permanent or transient event. The method then generates a protein dynamics landscape (PDL) for the transient event signatures. The PDL comprises a set of histograms of nanopore current data and characterizes current through the nanopore during shuttle capture events. The method can then comprise identifying an entrance level blockage value based on the permanent event signatures. Permanent event captures can be determined by time duration which is larger than a certain threshold time value. Applying a voltage between the fluidic chambers above a threshold voltage level can be used to control that the vast majority of events are permanent.

Abstract: Provided herein are genetically encoded voltage indicator (GEVI) variants (e.g., QuasArba, QuasArbb) of Archaerhodopsin 3 useful for applications, such as optical measurement of membrane potential. Described herein are also polynucleotides encoding the variants, nucleic acid constructs, vectors (e.g., expression vectors), cells comprising the polynucleotides, nucleic acid constructs, and vectors, and cells comprising the polypeptides; and methods of using the variants.

Abstract: Some aspects of this disclosure provide strategies, systems, reagents, methods, and kits that are useful for the targeted editing of nucleic acids, including editing a single site within the genome of a cell or subject, e.g., within the human genome. The disclosure provides fusion proteins of nucleic acid programmable DNA binding proteins (napDNAbp), e.g., Cas9 or variants thereof, and nucleic acid editing proteins such as cytidine deaminase domains (e.g., novel cytidine deaminases generated by ancestral sequence reconstruction), and adenosine deaminases that deaminate adenine in DNA. Aspects of the disclosure relate to fusion proteins (e.g., base editors) that have improved expression and/or localize efficiently to the nucleus. In some embodiments, base editors are codon optimized for expression in mammalian cells. In some embodiments, base editors include multiple nuclear localization sequences (e.g., bipartite NLSs), e.g., at least two NLSs.

Abstract: A method of screening is provided including providing a combination of a plurality of proliferating cell types wherein each proliferating cell type has a unique associated barcode within its genome that is different from other proliferating cell types of the plurality and wherein each proliferating cell type includes an exogenous gene that when expressed produces an associated phenotype to the proliferating cell type which alters proliferation of the cell type, introducing a perturbation to one or more of the plurality of proliferating cell types, inducing expression of one or more of the exogenous genes, determining the relative number of unique associated barcodes after a period of proliferation, and comparing the relative number of unique associated barcodes to a control relative number of unique associated barcodes to indicate the effect of the perturbation on the one or more of the plurality of proliferating cell types.

Abstract: Computer-implemented system and method are disclosed herein for fine tuning a neural network model. The method includes seeking, in a loss landscape, a nonlinear path with a loss barrier from a loss function associated with a first neural network model. The method further includes altering, in response to said seeking, one or more mechanisms of the first neural network model to induce a second neural network model.

Abstract: A tape for collecting tissue samples in a manner compatible with imaging in a transmission electron microscopy (TEM) system, includes a tape substrate having two side walls forming a trough. The trough is defined by a bottom surface of the tape substrate and internal surfaces of the side walls, with an open side therebetween. A support film is attached to a top surface of the tape substrate, and a plurality of apertures is spaced at predetermined locations along the length of the tape substrate, each aperture being covered by the support film. The tape includes a stacked configuration in which the tape substrate is wound in layers, the bottom surfaces of the side walls in one layer being in contact with the support film in an immediately adjacent layer. The apertures in the second layer are aligned within the trough of the first layer, between the side walls.

Abstract: In some embodiments, a mass spectrometry tag may comprise a linker region, a mass balance region, and a reporter region. The mass spectrometry tag may be configured to fragment in a mass spectrometer via an energy dependent process to produce multiple reporter molecules. For example, the reporter region of the tag may be configured to produce at least two reporter molecules via fragmentation. In some embodiments, one or more regions of the tag may comprise at least one heavy isotope. In some such embodiments, the ability to fragment into multiple reporter molecules as well as the placement and/or number of heavy isotope(s) allows the mass spectrometry tag to be distinguished from other similar mass spectrometry tags. In some such embodiments, the ability to distinguish between tags having the same or substantially similar total mass to charge ratio and reporter region mass may allow the system to have a greater multiplexing capacity than conventional systems.

Abstract: Provided herein are compounds useful for the treatment of various proliferative diseases. These compounds, as well as pharmaceutically acceptable salts thereof may be formulated in pharmaceutical compositions, and may be used in methods of treatment and/or prophylaxis of proliferative diseases, including cancer, and more specifically, pancreatic cancer.

Abstract: Disclosed herein are non-myeloablative antibody-toxin conjugates and compositions that target cell surface markers, such as the CD34, CD45 or CD117 receptors, and related methods of their use to effectively conditioning a subject's tissues (e.g., bone marrow tissue) prior to engraftment or transplant. The compositions and methods disclosed herein may be used to condition a subject's tissues in advance of, for example, hematopoietic stem cell transplant and advantageously such compositions and methods do not cause the toxicities that are commonly associated with traditional conditioning methods.

Abstract: Provided herein are polymeric particles and compositions (i.e., “backpacks”) that can adhere to cells and provide delivery of payload agents to those cells, and/or direct therapeutic activity of those cells.

Abstract: Provided herein, in some embodiments, are recombinant viral genomes comprising an inhibitory oligonucleotide that reduces inflammation for use, for example, in gene therapy.

Abstract: The present invention is based, in part, on the discovery of the human-specific regulatory control of cGAS and the structure of the active human cGAS-DNA complex, as well as compositions comprising the modified hcGAS polypeptide, hcGAS-DNA complex, hcGAS-DNA-ATP complex, and methods of screening for modulators of the structure, expression, and/or activity of such polypeptides and complexes.