Abstract: Examples are described for dynamically applying a digital watermark to a file, such as a dataset of genomic sequencing data. In one example, a method of dynamically applying a watermark to at least a portion of a file includes generating a first random seed, generating an ordered pseudorandom set of integers, generating a second random seed, selecting, using the second random seed, a subset of the ordered pseudorandom set of integers, the subset corresponding to identifiers of data locations in the file, and modifying data at data locations in the file corresponding to at least a portion of the identifiers included in the subset to generate a watermarked file. The genomic data file may be an ordered Binary Alignment Map (BAM) file storing sequencing data or a Variant Call Format (VCF) file or a list of variants storing genomic variation data.

Abstract: A glomerulus on a chip (GOAC) to recapitulate the human glomerular filtration barrier, the structure responsible for filtering the blood and preventing the loss of proteins, is provided using human podocytes and glomerular endothelial cells seeded into microfluidic chips. In long-term cultures, cells maintain their morphology, form capillary-like structures and express slit diaphragm proteins. This system recapitulates functions and structure of the glomerulus, including permselectivity. When exposed to sera from patients with anti-podocyte autoantibodies, the chips show albuminuria proportional to patients' proteinuria, phenomenon not observed with sera from healthy controls or individuals with primary podocyte defects. Also shown is its applicability for renal disease modeling and drug testing.

Abstract: The present disclosure relates in some aspects to chimeric signaling receptors containing an extracellular domain capable of binding a molecule, such as an immunosuppressive cytokine, and a MyD88-containing intracellular domain capable of engaging a signaling pathway to activate an immune cell. In some aspects, the disclosure further relates to engineered cells, such as T cells, and compositions comprising the chimeric signaling receptors or engineered cells, and methods and uses thereof. In some embodiments, the cells may further express a genetically engineered recombinant antigen receptor directed against an antigen, such as a chimeric antigen receptor (CAR) or recombinant T cell receptor (TCR) and, in some cases, secrete a recombinant molecule, for example, a bispecific antibody.

Abstract: The present invention provides an advancement in the art of cardiac pacemakers. The invention provides a novel and unobvious pacemaker system that comprises at least one pacemaker and that is, to a large extent, self-controlled, allows for long-term implantation in a patient, and minimizes current inconveniences and problems associated with battery life. The invention further includes a mechanism in which at least two pacemakers are implanted in a patient, and in which the pacemakers communicate with each other at the time of a given pacing or respiratory event, without any required external input, and adjust pacing parameters to respond to the patient's need for blood flow. The invention further provides a novel design for a pacemaker in which the pacemaker electrode is connected to the pacemaker body by a lead that is configured to allow the pacemaker to lie parallel to the epicardial surface and to reduce stress on the pacemaker and heart tissue.

Abstract: Zebrafish are a powerful model for investigating cardiac repair due to their unique regenerative abilities, scalability, and compatibility with many genetic tools. However, characterizing the regeneration process in live adult zebrafish hearts has proved challenging because adult fish are opaque and explanted hearts in conventional culture conditions experience rapid declines in morphology and physiology. To overcome these limitations, we fabricated a fluidic device for culturing explanted adult zebrafish hearts with constant media perfusion that is also compatible with live imaging. Unlike hearts cultured in dishes for one week, the morphology and calcium activity of hearts cultured in the device for one week were largely similar to freshly explanted hearts.

Abstract: Zebrafish are a powerful model for investigating cardiac repair due to their unique regenerative abilities, scalability, and compatibility with many genetic tools. However, characterizing the regeneration process in live adult zebrafish hearts has proved challenging because adult fish are opaque and explanted hearts in conventional culture conditions experience rapid declines in morphology and physiology. To overcome these limitations, we fabricated a fluidic device for culturing explanted adult zebrafish hearts with constant media perfusion that is also compatible with live imaging. Unlike hearts cultured in dishes for one week, the morphology and calcium activity of hearts cultured in the device for one week were largely similar to freshly explanted hearts.

Abstract: Examples are described for dynamically encrypting and/or decrypting a file formed of multiple blocks of ordered data. In one example, a method of dynamically encrypting a file to enable partial decryption of the file includes generating, using a secret key and one or more initialization vectors, a keystream for the multiple blocks of ordered data, encrypting the multiple blocks of ordered data of the file by performing a logical operation of the keystream with the multiple blocks of ordered data in a one-to-one correspondence, and building a file index of the file to identify location information of the multiple blocks of ordered data. The method may further include dynamically decrypting at least a portion of the file by decrypting at least one selected block of encrypted data of the file using a portion of the keystream, the portion of the keystream corresponding to the at least one selected block.

Abstract: Examples are described for dynamically applying a digital watermark to a file, such as a dataset of genomic sequencing data. In one example, a method of dynamically applying a watermark to at least a portion of a file includes generating, using a secret key, a first random seed, generating, using the first random seed, an ordered pseudorandom set of integers, generating, using entity information and timing information, a second random seed, selecting, using the second random seed, a subset of the ordered pseudorandom set of integers, and modifying data at data locations in the file corresponding to at least a portion of the identifiers included in the subset to generate a watermarked file. The method may further include performing a check to determine whether the watermark is present in a file using a sequence of watermark elements that are generated based on the secret key.

Abstract: A dietary composition and method for treating kidney damage and/or disease with a fasting-mimicking diet is provided. The method includes a step of identifying a subject having kidney damage. A low sodium fasting-mimicking diet with a specific dietary composition is administered to the subject for a first time period of 1 to 10 days.

Abstract: Provided herein are methods and compositions for treating disease-states associated with presence of increased number of ErbB4+ pro-inflammatory macrophages in a subject in need thereof. The methods include providing an activator of ErbB4 and administering a therapeutically effective amount of the activator to the subject. The compositions include an activator of ErbB4. In one embodiment, the activation of ErbB4 is Neuregulin-4.

Abstract: Methods of treating a subject using a T cell therapy are disclosed herein. The methods include increasing BCL11B expression in hematopoietic stem and progenitor cells (HSPCs), pluripotent stem cells, or mature T cells to form modified cells and administering a therapeutically effective amount of the modified cells to the subject for the T cell therapy. BCL11B expression in the HSPCs, pluripotent stem cells, or mature T cells increases production and/or proliferation of T cells from the HSPCs and/or the pluripotent stem cells, and/or increases proliferation of the T cells.

Abstract: The present invention provides a novel design for sheaths intended for medical procedures. The sheath includes structures that anchor the sheath in a cavity or space when deployed but are at the same time retractable such that the sheath can be removed without tearing the tissue defining the space.

Abstract: An open coiled pacemaker lead is provided that has improved structural stability and functional life in vivo. The open coiled lead includes an electrically conductive material that is coated or covered by a thin layer of electrically insulative material. The coated coiled lead has adequate spacing between adjacent coils, and has a lumen of sufficient diameter, to allow for infiltration of biological connective tissue onto the surface of the coated coil when maintained in vivo for a sufficient amount of time. Infiltration of the connective tissue essentially uniformly along the entire coiled lead strengthens and lengthens the functional life of the coated coil lead.

Abstract: The invention relates to a novel drug delivery vehicle. Various embodiments of the invention provide a hybrid polymerized liposomal nanoparticle comprising both polymerizable lipids and non-polymerizable lipids. Therapeutic agents can be loaded into the polymerized liposomal nanoparticle and targeting agents can be conjugated to the surface of the polymerized liposomal nanoparticle. Also described in the invention are methods, compositions and kits that utilize the hybrid polymerized liposomal nanoparticle to treat disease conditions such as various cancers.

Abstract: The invention relates to a novel drug delivery vehicle. Various embodiments of the invention provide a hybrid polymerized liposomal nanoparticle comprising both polymerizable lipids and non-polymerizable lipids. Therapeutic agents can be loaded into the polymerized liposomal nanoparticle and targeting agents can be conjugated to the surface of the polymerized liposomal nanoparticle. Also described in the invention are methods, compositions and kits that utilize the hybrid polymerized liposomal nanoparticle to treat disease conditions such as various cancers.

Abstract: The invention provides methods for treating neutropenia in a subject in need thereof comprising providing a composition comprising a retinoid agonist and administering an effective amount of the composition to the subject to treat neutropenia, thereby treating neutropenia to the subject in need thereof.

Abstract: A method for mobilizing leukemia cells which are ?4 integrin positive to the peripheral blood of a human subject, the method comprising administering to the human subject an effective amount of an antisense compound to ?4 integrin. The cells may be mobilized from bone marrow. The antisense compound is: 5?-MeCMeUG AGT MeCTG TTT MeUMeCMeC AMeUMeU MeCMeU-3? wherein, (a) each of the 19 internucleotide linkages of the oligonucleotide is an O,O-linked phosphorothioate diester; (b) the nucleotides at the positions 1 to 3 from the 5? end are 2?-O-(2-methoxyethyl) modified ribonucleosides; (c) the nucleotides at the positions 4 to 12 from the 5? end are 2?-deoxyribonucleosides; (d) the nucleotides at the positions 13 to 20 from the 5? end are 2?-O-(2-methoxyethyl) modified ribonucleosides; and (e) all cytosines are 5-methylcytosines (MeC), or a pharmaceutically acceptable salt thereof.

Abstract: The present invention provides advancements in the art of cardiac pacemakers. The invention provides a pacemaker system that comprises at least one pacemaker and that is, to a large extent, self-controlled, allows for long-term implantation in a patient, and minimizes current inconveniences and problems associated with battery life. The invention further includes a mechanism in which at least two pacemakers are implanted in a patient, and in which the pacemakers communicate with each other at the time of a given pacing or respiratory event, without any required external input, and adjust pacing parameters to respond to the patient's need for blood flow. The invention further provides a design for a pacemaker in which the pacemaker electrode is connected to the pacemaker body by a lead that is configured to allow the pacemaker to lie parallel to the epicardial surface and to reduce stress on the pacemaker and heart tissue.

Abstract: An artificial chamber including a first conduit, a second conduit, a third conduit, and a wall defining a space; in which the first conduit and the second conduit are positioned opposite one another; in which the third conduit is opposite the wall; and in which the wall has a concave surface is disclosed. The chamber can be part of a system for providing pulmonary support. The system includes the chamber and a first pump connected to the third conduit, and connected to a fourth conduit; in which the chamber receives fluid via the first conduit and the second conduit, in which the first pump receives fluid from the chamber via the third conduit; and in which the fourth conduit transports fluid from the first pump to a first blood vessel. Methods of making a chamber and a system, and methods of using the chamber and system are also disclosed.

Abstract: Provided herein are methods and compositions for treating disease-states associated with presence of increased number of ErbB4+ pro-inflammatory macrophages in a subject in need thereof. The methods include providing an activator of ErbB4 and administering a therapeutically effective amount of the activator to the subject. The compositions include an activator of ErbB4. In one embodiment, the activation of ErbB4 is Neuregulin-4.