Abstract: Systems and methods and devices are provided for arresting or reversing the effects of myocardial remodeling and degeneration after cardiac injury, without the potential drawbacks associated with previously existing systems and methods, by at least partially occluding flow through the superior vena cava over multiple cardiac cycles, and more preferably, by adjusting the interval or degree of occlusion responsive to a sensed level of patient activity. In some embodiments, a controller is provided that actuates a drive mechanism responsive to a sensed level of patient activity to provide at least partial occlusion of the patient's superior vena cava, while a data transfer circuit of the controller provides bi-directional transfer of physiologic data to the patient's smartphone or tablet to permit display and review of such data.

Abstract: Systems and methods and devices are provided for arresting or reversing the effects of myocardial remodeling and degeneration after cardiac injury, without the potential drawbacks associated with previously existing systems and methods, by at least partially occluding flow through the superior vena cava over multiple cardiac cycles, and more preferably, by adjusting the interval or degree of occlusion responsive to a sensed level of patient activity. In some embodiments, a controller is provided that actuates a drive mechanism responsive to a sensed level of patient activity to provide at least partial occlusion of the patient's superior vena cava, while a data transfer circuit of the controller provides bi-directional transfer of physiologic data to the patient's smartphone or tablet to permit display and review of such data.

Abstract: Systems and methods and devices are provided for treating conditions such as heart failure and/or pulmonary hypertension by at least partially occluding flow through the superior vena cava for an interval spanning multiple cardiac cycles. A catheter with an occlusion device is provided along with a controller that actuates a drive mechanism to provide at least partial occlusion of the patient's superior vena cava, which reduces cardiac filling pressures, and induces a favorable shift in the patient's Frank-Starling curve towards healthy heart functionality and improved cardiac performance. The occlusion device may include a lumen obstructed by a relief valve that may permit fluid flow through the occlusion device to release an excessive build-up of pressure.

Abstract: An implant sized and shaped to be endovascularly delivered to the middle meningeal artery includes a carrier that carries a payload between first and second ends thereof. An anchor mechanism associated with the implant transitions into a swollen state in response to exposure to bodily fluids. In the swollen state, said anchor mechanism anchors the implant to the middle meningeal artery. Before or during the transition, the anchor mechanism permits endovascular delivery of the implant to the middle meningeal artery.

Abstract: Endoglin has been identified to play a functional role as a regulator of TGF?1 signaling, particular in TGF?1-mediated calcineurin expression. The present invention features methods of reducing cardiac damage, particularly in a subject undergoing chemotherapy or radiation therapy by administering a composition that inhibits endoglin activity. The present invention also features methods of treating autoimmune diseases, inflammatory diseases, organ transplantation, and conditions association with oxidative stress related to TGF?1-mediated calcineurin expression and reactive oxygen species (ROS) production by administering a composition that inhibits endoglin activity. The present invention also features methods of treating fibrotic diseases by administering a composition that inhibits endoglin activity.

Abstract: Aspects of the technology disclosed herein generally (and in part) relates to use of Angiogenin (ANG) for increasing hematopoietic reconstitution of in vivo hematopoietic cells and transplanted hematopoietic cells. Provided herein are methods and compositions useful in treatment of diseases characterized by decreased levels of hematopoietic cells, decreased levels of hematopoietic reconstitution, blood cell deficiency and prevention and treatment of radiation injury. One aspect relates to angiogenin treated hematopoietic cell compositions and methods of their use in stem cell transplantation. Treatment of hematopoietic cells with angiogenin enhances quiescence and reduces proliferative capacity of primitive hematopoietic stem cells while increasing proliferation of myeloid restricted progenitor cells. Another aspect relates to use of ANG in prophylactic and therapeutic treatment methods for radiation injury.

Abstract: An endovascular implantable shunt device for draining cerebrospinal fluid from a patient's subarachnoid space includes a shunt having opposed first and second ends, a one-way valve located at the first end of the shunt, a helical tip disposed at the second end, and a hollow passageway extending between the helical tip and one-way valve. The helical tip is constructed to penetrate a patient's sinus wall. Cerebrospinal fluid drains through the helical tip and out through the valve.

Abstract: Methods for the diagnosis and treatment of B cell Acute Lymphoblastic Leukemia (B-ALL), based in part on the detection and/or inhibition of Focal Adhesion Kinase (FAK), e.g., phosphorylated FAK (pFAK).

Abstract: Systems and methods and devices are provided for arresting or reversing the effects of myocardial remodeling and degeneration after cardiac injury, without the potential drawbacks associated with previously existing systems and methods, by at least partially occluding flow through the superior vena cava over multiple cardiac cycles, and more preferably, by adjusting the interval or degree of occlusion responsive to a sensed level of patient activity. In some embodiments, a controller is provided that actuates a drive mechanism responsive to a sensed level of patient activity to provide at least partial occlusion of the patient's superior vena cava, while a data transfer circuit of the controller provides bi-directional transfer of physiologic data to the patient's smartphone or tablet to permit display and review of such data.

Abstract: In certain embodiments, this disclosure relates to pharmaceutical formulations for polypeptide and lipophilic moiety conjugates suitable for injection into humans and other animals and methods of preparation. In certain embodiments, the disclosure relates to a method of preparing the formulation comprising lyophilizing, solubilizing in ammonium acetate, filtering to create mono-disperse particles, re-lyophilizing, and solubilizing the micelles in a dextrose solution for injection.

Abstract: Implantable shunt devices and methods for draining cerebrospinal fluid from a patient's subarachnoid space include a shunt having opposed first and second ends, the second end being constructed to penetrate a wall of a sigmoid, transverse, straight, or sagittal sinus of the patient, a one-way valve, a hollow passageway extending between the second end and the one-way valve such that cerebrospinal fluid can be drained through the second end and out through the valve, and a mechanism coupled to the shunt and configured to anchor the shunt at a desired location proximal to the subarachnoid space.

Abstract: An endovascular implantable shunt device for draining cerebrospinal fluid from a patient's subarachnoid space includes a shunt having opposed first and second ends, a one-way valve located at the first end of the shunt, a tip disposed at the second end, and a hollow passageway extending between the tip and one-way valve. The tip is constructed to penetrate a patient's sinus wall. Cerebrospinal fluid drains through the tip and out through the valve.

Abstract: Disclosed are methods of treating a muscle disease and improving normal muscle function by administering a therapeutically effective amount of an isoprenoid antibiotic. Also disclosed are methods of upregulating hnRNP L and hnRNP L targets by administering a therapeutically effective amount of an isoprenoid antibiotic. Methods of screening compounds for use in treating muscle disease and improving muscle function are also described.

Abstract: Implantable shunt devices and methods for draining cerebrospinal fluid from a patient's subarachnoid space include a shunt having opposed first and second ends, the second end being constructed to penetrate a wall of a sigmoid, transverse, straight, or sagittal sinus of the patient, a one-way valve, a hollow passageway extending between the second end and the one-way valve such that cerebrospinal fluid can be drained through the second end and out through the valve, and a mechanism coupled to the shunt and configured to anchor the shunt at a desired location proximal to the subarachnoid space.

Abstract: Matrix metalloproteases (MMPs) play many important roles in normal and pathological remodeling processes including atherothrombotic disease, inflammation, angiogenesis and cancer. This invention relates to the activation of protease-activated receptor-1 (PAR-1) by endogenous platelet MMP-1 collagenase on the surface of platelets. Exposure of platelets to fibrillar collagen converts the surface-bound pro-MMP-1 zymogen to active MMP-1, which promotes aggregation through PAR-1. MMP-1 is shown to cleave the PAR-1 extracellular domain at a novel site, which then strongly activates Rho-GTP signaling pathways, cell shape change and motility, and MAPK signaling. Blockade of MMP-PAR1 suppresses thrombogenesis under arterial flow conditions and inhibited thrombosis in animals. These studies provide a link between matrix-dependent activation of metalloproteases and platelet-G protein signaling and identify MMP-1/PAR-1 as a new target for the treatment and prevention of arterial thrombosis and other thrombotic diseases.

Abstract: Systems and methods and devices are provided for arresting or reversing the effects of myocardial remodeling and degeneration after cardiac injury, without the potential drawbacks associated with previously existing systems and methods, by at least partially occluding flow through the superior vena cava over multiple cardiac cycles, and more preferably, by adjusting the interval or degree of occlusion responsive to a sensed level of patient activity. In some embodiments, a controller is provided that actuates a drive mechanism responsive to a sensed level of patient activity to provide at least partial occlusion of the patient's superior vena cava, while a data transfer circuit of the controller provides bi-directional transfer of physiologic data to the patient's smartphone or tablet to permit display and review of such data.

Abstract: Endoglin has now been shown to be an important target of therapy to reduce disease symptoms associated with heart failure, particularly cardiac fibrosis. Soluble Endoglin is identified as an anatogonist to TGF?1 activity, while membrane-bound Endoglin is identified as a necessary component to promote TGF?1 activity in heart failure. The present invention therefore features methods and kits for treatment of subject having heart failure or a related disorder by administering a composition that decreases TGF?1 signaling through either direct inhibition of membrane-bound Endoglin or promoting expression of soluble Endoglin.

Abstract: Systems and methods and devices are provided for arresting or reversing the effects of myocardial remodeling and degeneration after cardiac injury, without the potential drawbacks associated with previously existing systems and methods, by at least partially occluding flow through the superior vena cava over multiple cardiac cycles, and more preferably, by adjusting the interval or degree of occlusion responsive to a sensed level of patient activity. In some embodiments, a controller is provided that actuates a drive mechanism responsive to a sensed level of patient activity to provide at least partial occlusion of the patient's superior vena cava, while a data transfer circuit of the controller provides bi-directional transfer of physiologic data to the patient's smartphone or tablet to permit display and review of such data.

Abstract: Matrix metalloproteases (MMPs) play many important roles in normal and pathological remodeling processes including atherothrombotic disease, inflammation, angiogenesis and cancer. This invention relates to the activation of protease-activated receptor-1 (PAR-1) by endogenous platelet MMP-1 collagenase on the surface of platelets. Exposure of platelets to fibrillar collagen converts the surface-bound pro-MMP-1 zymogen to active MMP-1, which promotes aggregation through PAR-1. MMP-1 is shown to cleave the PAR-1 extracellular domain at a novel site, which then strongly activates Rho-GTP signaling pathways, cell shape change and motility, and MAPK signaling. Blockade of MMP-PAR1 suppresses thrombogenesis under arterial flow conditions and inhibited thrombosis in animals. These studies provide a link between matrix-dependent activation of metalloproteases and platelet-G protein signaling and identify MMP-1/PAR-1 as a new target for the treatment and prevention of arterial thrombosis and other thrombotic diseases.

Abstract: Disclosed herein are novel compositions and methods for the inhibition of Plexin B2-mediated Angiogenin activity. Such compositions and methods are useful, for example, for the treatment of cancer, the treatment of wet AMD and the inhibition of angiogenesis. Also disclosed herein are methods of determining whether a test agent is a modulator of Plexin B2 activity.