Abstract: The present invention provides a nanodisc with a membrane scaffold protein. The nanodisc includes a membrane scaffold protein, a telodendrimer and a lipid. The membrane scaffold protein can be apolipoprotein. The telodendrimer has the general formula PEG-L-D-(R)n, wherein D is a dendritic polymer; L is a bond or a linker linked to the focal point group of the dendritic polymer; each PEG is a poly(ethylene glycol) polymer; each R is and end group of the dendritic polymer, or and end group with a covalently bound hydrophobic group, hydrophilic group, amphiphilic compound, or drug; and subscript n is an integer from 2 to 20. Cell free methods of making the nanodiscs are also provided.

Abstract: The present invention provides compounds and pharmaceutical compositions of peptidomimetic ligands. The peptidomimetic ligands can be conjugated with phosphonate drugs. The compounds and pharmaceutical compositions of the present invention are useful in the treatment of osteoporosis and for the promotion of bone growth due to their specificity for the ?4?1 integrin on mesenchymal stem cells and for the surface of bone.

Abstract: A system and method for the safe delivery of treatment energy to a patient, which includes verification of system integrity before, during, or after the delivery of treatment energy and provides several mechanisms for rapid termination of the delivery of potentially harmful energy to the patient when a fault condition in the device and/or system is identified. The system may include an energy generator having processing circuitry to determine if there is a fault condition in the system and to automatically terminate a delivery of treatment energy when the processing circuitry determines there is a fault condition. The method may generally include performing a series of pre-checks, synchronizing a treatment energy delivery to the proper segment of the heart's depolarization pattern, configuring the system for treatment energy delivery, delivering the treatment energy, and performing post-treatment evaluation.

Abstract: The present invention provides a nanodisc with a membrane scaffold protein. The nanodisc includes a membrane scaffold protein, a telodendrimer and a lipid. The membrane scaffold protein can be apolipoprotein. The telodendrimer has the general formula PEG-L-D-(R)n, wherein D is a dendritic polymer; L is a bond or a linker linked to the focal point group of the dendritic polymer; each PEG is a poly(ethylene glycol) polymer; each R is and end group of the dendritic polymer, or and end group with a covalently bound hydrophobic group, hydrophilic group, amphiphilic compound, or drug; and subscript n is an integer from 2 to 20. Cell free methods of making the nanodiscs are also provided.

Abstract: Techniques are disclosed to automate TLS certificate rotation. For example, a certificate rotation event may be detected from a certificate management tool. The certificate rotation event may be associated with a first certificate and may indicate that the first certificate is to be updated with a second certificate. An application server that is running on a host and to which the first certificate is bound may be identified. A certificate identifier for the second certificate may be provided to one or more agents running on the host. A distribution service may obtain certificate information, e.g., a public key, a private key, or a certificate identifier for the second certificate, from the certificate rotation tool. Some or all of the certificate information for the second certificate may be obtained by the one or more agents running on the host. The one or more agents may instruct the application server to bind the second certificate.

Abstract: The present disclosure provides pro-angiogenic proteoglycan mimetics that can provide a provisional, pro-angiogenic scaffold to support tissue regeneration while limiting systemic exposure to VEGF activity. These mimetics can protect a collagen matrix from rapid degradation, and in conjunction with EPCs promote angiogenesis in order to accelerate ischemic wound healing. For example, the provided compounds can be delivered from the end of a catheter following balloon angioplasty to coat the collagen exposed areas, prevent platelet binding and thrombosis, support capture of EPCs from blood to facilitate reendothelialization, and reduce late-lumen loss (neointimal hyperplasia).

Abstract: The present invention provides a nanodisc with a membrane scaffold protein. The nanodisc includes a membrane scaffold protein, a telodendrimer and a lipid. The membrane scaffold protein can be apolipoprotein. The telodendrimer has the general formula PEG-L-D-(R)n, wherein D is a dendritic polymer; L is a bond or a linker linked to the focal point group of the dendritic polymer; each PEG is a poly(ethylene glycol) polymer, each R is and end group of the dendritic polymer, or and end group with a covalently bound hydrophobic group, hydrophilic group, amphiphilic compound, or drug; and subscript n is an integer from 2 to 20. Cell free methods of making the nanodiscs are also provided.

Abstract: The present disclosure provides pro-angiogenic proteoglycan mimetics that can provide a provisional, pro-angiogenic scaffold to support tissue regeneration while limiting systemic exposure to VEGF activity. These mimetics can protect a collagen matrix from rapid degradation, and in conjunction with EPCs promote angiogenesis in order to accelerate ischemic wound healing. For example, the provided compounds can be delivered from the end of a catheter following balloon angioplasty to coat the collagen exposed areas, prevent platelet binding and thrombosis, support capture of EPCs from blood to facilitate reendothelialization, and reduce late-lumen loss (neointimal hyperplasia).

Abstract: A method of communicating time correlated vector data within a network includes reading, by a transmitting node, a first vector data including a plurality of elements, selecting, by the transmitting node, a subset of elements of the plurality of elements based on a criteria and sending, by the transmitting node, the subset of elements to a receiving node. The receiving node receives the subset of elements and estimates a plurality of elements not included in the subset of elements based on a previously received subset of element based on a second vector data. The first vector data and the second vector data are part of a time series of vectors.

Abstract: The present invention provides a compound of formula (I): A-B-C (I), wherein A is a hydrophobic moiety; B is a peptide, wherein the peptide forms a beta-sheet; and C is a hydrophilic targeting ligand, wherein the hydrophilic targeting ligand is a LLP2A prodrug, LLP2A, LXY30, LXW64, DUPA, folate, a LHRH peptide, a HER2 ligand, an EGFR ligand, or a toll-like receptor agonist CpG oligonucleotides. The present invention also provides nanocarriers comprising compounds of the present invention, nanofibril formation from the nanocarriers, and methods of using the nanocarriers for treating diseases and imaging.

Abstract: The present disclosure related to compounds of Formula I and Formula I and to their pharmaceutically acceptable salts, pharmaceutical compositions, methods of use, and methods for their preparation. The compounds disclosed herein are useful for modulating RAD52 activity and may be used in the treatment of disorders in which RAD52 activity is implication, such as a cancer.

Abstract: The present invention provides compositions and methods comprising conjugates with a polymeric backbone, e.g., polyvinyl alcohol (PVA), covalently linked histone deacetylase (HDAC) inhibitors, such as butyrate or propionate, and covalently linked retinoids, such as all-trans retinoic acid (RA). The methods and compositions of the invention are useful for the treatment or prevention of cancer or metabolic diseases in tissues such as the colon or liver.

Abstract: Methods and compositions are provided for hybrid telodendrimers and nanocarriers containing such hybrid telodendrimers.

Abstract: Techniques are disclosed to automate TLS certificate rotation. For example, a certificate rotation event may be detected from a certificate management tool. The certificate rotation event may be associated with a first certificate and may indicate that the first certificate is to be updated with a second certificate. An application server that is running on a host and to which the first certificate is bound may be identified. A certificate identifier for the second certificate may be provided to one or more agents running on the host. A distribution service may obtain certificate information, e.g., a public key, a private key, or a certificate identifier for the second certificate, from the certificate rotation tool. Some or all of the certificate information for the second certificate may be obtained by the one or more agents running on the host. The one or more agents may instruct the application server to bind the second certificate.

Abstract: The present invention relates to the discovery of compounds that can be used to treat and/or prevent heart failure in a subject. In certain embodiments, the compounds of the invention are sulfide:quinone oxidoreductase (SQOR) inhibitors. In other embodiments, the compounds of the invention increase physiological levels of H2S in the subject. In yet other embodiments, administration of the compounds of the invention treats, ameliorates, and/or prevents hypertension, and/or atherosclerosis, and/or pathological cardiac remodeling that leads to heart failure in the subject.

Abstract: The present invention provides amphiphilic telodendrimers that aggregate to form nanocarriers characterized by a hydrophobic core and a hydrophilic exterior. The nanocarrier core may include amphiphilic functionality such as cholic acid or cholic acid derivatives, and the exterior may include branched or linear poly(ethylene glycol) segments. Nanocarrier cargo such as hydrophobic drugs and other materials may be sequester in the core via non-covalent means or may be covalently bound to the telodendrimer building blocks. Telodendrimer structure may be tailored to alter loading properties, interactions with materials such as biological membranes, and other characteristics.

Abstract: The present invention provides methods of treating a subject having a primary inflammatory disease or disorder comprising administering to the subject a composition comprising a conjugate of an LLP2A peptidomimetic ligand and a bisphosphonate drug, wherein the composition comprising the LLP2A-bisphosphonate conjugate enhances the delivery of mesenchymal stem cells to a site of inflammation. Methods of enhancing an anti-inflammatory or immunomodulatory property of mesenchymal stem cells, comprising administering to a subject in need thereof the mesenchymal stem cells and a composition comprising a conjugate of an LLP2A peptidomimetic ligand and a bisphosphonate drug, are also provided.

Abstract: The present invention provides compounds and pharmaceutical compositions of peptidomimetic ligands. The peptidomimetic ligands can be conjugated with phosphonate drugs. The compounds and pharmaceutical compositions of the present invention are useful in the treatment of osteoporosis and for the promotion of bone growth due to their specificity for the ?4?1 integrin on mesenchymal stem cells and for the surface of bone.

Abstract: The present invention provides amphiphilic telodendrimers that aggregate to form nanocarriers characterized by a hydrophobic core and a hydrophilic exterior. The nanocarrier core may include amphiphilic functionality such as cholic acid or cholic acid derivatives, and the exterior may include branched or linear poly(ethylene glycol) segments. Nanocarrier cargo such as hydrophobic drugs and other materials may be sequester in the core via non-covalent means or may be covalently bound to the telodendrimer building blocks. Telodendrimer structure may be tailored to alter loading properties, interactions with materials such as biological membranes, and other characteristics.

Abstract: Methods and compositions are described herein for covalently linking an antibody to a molecular payload. Compositions are described herein containing an antibody covalently linked to a molecular payload.