Abstract: The present disclosure provides engineered cross-type-nucleic-acid targeting nucleic acids and compositions thereof. Nucleic acid sequences encoding the engineered cross-type-nucleic-acid targeting nucleic acids, as well as expression cassettes, vectors and cells comprising such nucleic acid sequences, are described. Also, methods are disclosed for making and using the engineered cross-type-nucleic-acid targeting nucleic acids and compositions thereof.

Abstract: Provided herein are methods and related compositions for administering viral vectors and synthetic nanocarriers comprising an immunosuppressant. In some embodiments, the methods and compositions provided herein achieve improved transgene expression and/or immune response reduction, such as downregulated IgM and/or IgG immune responses.

Abstract: A method for assaying target molecules in a sample liquid, the method comprising: providing an impedance monitoring device operably connected to an impedance analyzer; adding a sample liquid suspected of having target molecules to the well thereby permitting binding of target molecules to the capture molecules; monitoring impedance of the well; and determining the presence, amount or concentration of target molecules in the liquid sample from the monitored impedance. The device includes a nonconducting substrate having a well, at least two electrodes fabricated on a bottom of the well and on a same plane, wherein the surfaces of the at least two electrodes are modified with capture molecules configured to bind target molecules in a liquid sample, and at least two connection pads electrically connected to the at least two electrodes.

Abstract: An intracellular selection system allows screening for peptide bioactivity and stability. Randomized recombinant peptides are screened for bioactivity in a tightly regulated expression system, preferably derived from the wild-type lac operon. Bioactive peptides thus identified are inherently protease- and peptidase-resistant. Also provided are bioactive peptides stabilized by a stabilizing group at the N-terminus, the C-terminus, or both. The stabilizing group can be a small stable protein, such as the Rop protein, glutathione sulfotransferase, thioredoxin, maltose binding protein, or glutathione reductase, an ?-helical moiety, or one or more proline residues.

Abstract: Methods for treating a subject for pancreatic cancer via administration of small anti-inflammatory peptides are disclosed. The peptides may be administered in conjunction with another therapeutic agent, such as a chemotherapeutic agent, or therapeutic regimen. In some cases, the anti-inflammatory peptide that finds use in the subject methods has the amino acid sequence Lys-Phe-Arg-Lys-Ala-Phe-Lys-Arg-Phe-Phe (SEQ ID NO:1) or a multimer, derivative, or variant thereof.

Abstract: ?-Substituted ?-amino acids, ?-substituted ?-amino acid derivatives, and ?-substituted ?-amino acid analogs and (bio)isosteres and their use as chemotherapeutic agents are disclosed. The ?-substituted ?-amino acid derivatives and ?-substituted ?-amino acid analogs and (bio)isosteres are selective LAT1/4F2hc substrates and exhibit rapid uptake and retention in tumors expressing the LAT1/4F2hc transporter. Methods of synthesizing the ?-substituted ?-amino acid derivatives and ?-substituted ?-amino acid analogs and methods of using the compounds for treating cancer are also disclosed. The ?-substituted ?-amino acid derivatives and ?-substituted ?-amino acid analogs exhibit selective uptake in tumor cells expressing the LAT1/4F2hc transporter and accumulate in cancerous cells when administered to a subject in vivo. The ?-substituted ?-amino acid derivatives and ?-substituted ?-amino acid analogs and (bio)isosteres exhibit cytotoxicity toward several tumor types.

Abstract: Aspects of the present invention relate to peptides having antimicrobial activity. In certain aspects, the invention relates to peptides having potent antimicrobial activity, broad-spectrum antimicrobial activity, and/or the ability to kill otherwise antibiotic-resistant microbes, or microbes protected by biofilms.

Abstract: Fused pyrimidine compounds having a saturated, unsaturated or aromatic A ring fused to a pyrimidine ring and having a complex substituents at the 2 position and a substituted amine at the 4 position of the pyrimidine ring as well as optional aliphatic, functional and/or aromatic components substituted at other positions of the pyrimidine ring and A ring are disclosed. These compounds are inhibitors of the AAA proteasome complex containing p97 and are effective medicinal agents for treatment of diseases associated with p97 bioactivity such as cancer.

Abstract: A transgenic animal is provided. In certain embodiments, the transgenic animal comprises a genome comprising: an immunoglobulin light chain locus comprising: a) a functional immunoglobulin light chain gene comprising a transcribed variable region encoding: i. light chain CDR1, CDR2 and CDR3 regions that are composed of 2 to 5 different amino acids; and ii. a light chain framework; and, operably linked to the functional immunoglobulin light chain gene: b) a plurality of pseudogene light chain variable regions each encoding: i. light chain CDR1, CDR2 and CDR3 regions that are composed of the same 2 to 5 different amino acids as the CDRs of the functional gene; and ii. a light chain framework that is identical in amino acid sequence to the light chain framework of the transcribed variable region.

Abstract: A system for monitoring impedance of excitable cells in vitro, which includes a device for monitoring cell-substrate impedance at 20 millisecond resolution, which includes a nonconductive substrate with one or more electrode arrays fabricated in one or more wells, wherein cell attachment on the substrate can result in a detectable change in impedance between electrodes within each electrode array; an impedance analyzer capable of impedance measurement at 20 millisecond time resolution; electronic circuitry that can engage said device and selectively connect said two or more electrode arrays of said device to said impedance analyzer; and a software program that controls said electronic circuitry and records and analyzes data obtained from said impedance analyzer.

Abstract: Methods of treating subjects having diseases, disorders, or conditions, including disorders associated with cholesterol homeostasis, responsive to IL-10, including methods of administration and dosing regimens associated therewith, are provided, More particularly, the present disclosure relates to optimized dosing parameters to achieve and maintain efficacy in the treatment and/or prevention of metabolic diseases, disorders and conditions in a subject, while minimizing the adverse effects associated therewith. Particular embodiments are directed to the treatment and/or prevention of abnormally high levels of cholesterol and/or manifestation(s) of hypercholesterolemia in as subject.

Abstract: Genetically manipulated cells, lysates of such cells, systems, and methods of use thereof are provided, where one or more enzymes in a pathway of interest are genetically modified to incorporate a peptide sequence that provides for relocation of the protein, e.g., to the periplasm, so as to sequester the enzyme, and where the enzyme controls flux in the pathway of interest.

Abstract: Disclosed are synthetic nanocarrier methods, and related compositions, comprising administering MHC Class I-restricted and/or MHC Class II-restricted epitopes of an antigen and immunosuppressants in order to generate tolerogenic immune responses against the antigen, such as the generation of antigen-specific CD8+ regulatory T cells.

Abstract: Disclosed herein are viral vectors for use in recombinant molecular biology techniques. In particular, the present disclosure relates to self-limiting viral vectors comprising genes encoding site-specific endonucleases as well as recognition sequences for site-specific endonucleases such that expression of the endonuclease in a cell cleaves the viral vector and limits its persistence time. In some embodiments, the viral vectors disclosed herein also carry directives to delete, insert, or change a target sequence.

Abstract: Provided herein are methods and devices for obtaining nucleotide sequence information from nucleic acid and nucleic acid samples. The methods involve modifying and manipulating nucleic acids while in movement (flow) and without reliance on fixation, amplification or hybridization techniques. The methods and devices are sensitive enough to detect signal from and thus interrogate single nucleic acids on an individual basis rather than as a bulk population.

Abstract: Provided herein are compositions and methods for the treatment or prevention of pathogenic infections.

Abstract: Heterocyclic compounds are described that are lysophosphatidic acid receptor ligands that are useful in the treatment of lysophosphatidic acid receptor-dependent diseases and conditions, including but not limited to diseases involving fibrosis, such as fibrosis of the heart, kidney, liver and lung, and scleroderma; inflammatory diseases such as diabetic nephropathy and inflammatory bowel disease; ocular diseases such as diseases involving retinal degeneration; nerve diseases such as pruritus and pain. Non-limiting examples of those compounds include (RS)-3-Cyclopropyl-2-{4-[3-methyl-4-((R)-1-phenyl-ethoxycarbonylamino)-isoxazol-5-yl]-benzyloxy}-propionic acid and (R)-1-(4?-{5-[1-(2-Chloro-phenyl)-ethoxycarbonylamino]-4-fluoro-pyrazol-1-yl}-2-fluoro-biphenyl-4-yl)-cyclopropanecarboxylic acid.

Abstract: The present invention provides oligonucleotide constructs, sets of such oligonucleotide constructs, and methods of using such oligonucleotide constructs to provide validated sequences or sets of validated sequences corresponding to desired ROIs. Such validated ROIs and constructs containing these have a wide variety of uses, including in synthetic biology, quantitative nucleic acid analysis, polymorphism and/or mutation screening, and the like.

Abstract: The invention features methods for rapidly and sensitively identifying molecular targets in medical, industrial, and environmental samples. The invention labels target molecules and then images them using large area imaging. Diagnostic tests based on the invention can be rapid, ultrasensitive, quantitative, multiplexed, and automated. A broad range of infectious agents (e.g., bacteria, viruses, fungi, and parasites) and molecules (e.g., proteins, DNA, RNA, hormones, and drugs) can be detected by the methods. The invention enables rapid, ultra-sensitive, cost-effective, and portable assays. The ability of the invention to detect low levels of target molecules rapidly and cost-effectively results from the combination of high intensity labeling, formats that facilitate rapid reaction kinetics, and large area imaging based using either instrumentation made from off-the-shelf commercial components or no instrumentation at all.