National Institutes of Health, a Component of the US Dept. of Health & Human Services

Other

The United States of America As Represented by the Department of Health

The United States of America As Represented by the Secretary of

Washington University

The Uab Research Foundation

David D Roberts

Henry C Krutzsch

Jeffrey S Isenberg

Howard C Krivan

Victor Ginsburg

Nenghua Guo

Sukhbir Kaur

William A Frazier

Joanne Murphy-Ullrich

Michael L Pendrak

John M Sipes

Neng-hua Guo

Eric Negre

Joseph L Bryant

John K Inman

Stacey L Schultz-Cherry

Glenn Sugden

Christian Hugo

David R Soto Pantoja

Justin Maxhimer

Chengyu Liu

Ginsburg Victor

Christine Krutzsch, Legal Representative

Sizhuang (Steve) Yan

Philip J Browning

Sizhuang Steve Yan

Solange M F Ribeiro

This disclosure relates to methods of producing induced pluripotent (iPS), multipotent, and/or lineage-committed stem cells from differentiated cells, maintaining iPS, multipotent, and/or lineage-committed cells in culture, and re-differentiating the iPS and multipotent stem cells into any desired lineage-committed cell type.

Methods for generation of pluripotent and multipotent cells

Methods of reducing cytotoxicity of a chemotherapeutic agent to non-cancer cells by administering to a subject with cancer an effective amount of an agent that inhibits CD47 signaling and a DNA damaging agent, such as an anthracycline, topoisomerase inhibitor, or nucleotide synthesis inhibitor, are provided. Example disclosed methods reduce cardiotoxicity. In one example, the methods include administering to a subject with cancer an effective amount of a CD47 antisense morpholino oligonucleotide and an anthracycline such as doxorubicin. Methods of increasing cytotoxicity of a chemotherapeutic agent in cancer cells by administering to a subject with a tumor an effective amount of an agent that inhibits CD47 signaling and a DNA damaging agent such as an anthracycline, topoisomerase inhibitor, or nucleotide synthesis inhibitor, are also provided. In some embodiments, the inhibitor of CD47 signaling is administered to the subject before, during, or after the administration of the DNA damaging agent.

Methods for modulating chemotherapeutic cytotoxicity

Provided herein are compositions for preventing, ameliorating, and/or reducing tissue ischemia and/or tissue damage due to ischemia, increasing blood vessel diameter, blood flow and tissue perfusion in the presence of vascular disease including peripheral vascular disease, atherosclerotic vascular disease, coronary artery disease, stroke and influencing other conditions, by suppressing CD47 and/or blocking TSP1 and/or CD47 activity or interaction. Influencing the interaction of CD47-TSP1 in blood vessels allows for control of blood vessel diameter and blood flow, and permits modification of blood pressure and cardiac function. Under conditions of decreased blood flow, for instance through injury or atherosclerosis, blocking TSP1-CD47 interaction allows blood vessels to dilate and increases blood flow, tissue perfusion and tissue survival.

Prevention of tissue ischemia and related methods

The present disclosure relates to systems, non-transitory computer-readable media, and methods for communication using multiple media content items stored on both a sending device and a receiving device. In particular, in one or more embodiments, the disclosed systems receive an application package. The application generates a message from input text and matches a portion of the text input to an audio content item using mapping data. The application generates a message including the text input and an identifier to the audio content item. A receiving system receives an application package. The application receives the message and locates the audio content item on the application package using the identifier and presents the message, including the text and the audio content item.

Systems and methods for media content communication

Described herein is the discovery that cancer stem cells (CSCs) can be induced to differentiate by altering CD47 signaling. Provided herein are methods and compositions for inducing differentiation of cancer stem cells, for instance irreversible differentiation, including methods of treating subjects with cancer such as breast cancer, colon cancer, lung cancer, ovarian cancer, or melanoma, and including metastatic as well as primary cancer. Also provided are methods for treating subjects with triple negative breast cancers involving forcing differentiation of bCSCs of the subjects through targeting of CD47.

Methods to eliminate cancer stem cells by targeting CD47

The insect trap includes a tube member of an undefined length that includes a concave wire mesh inserted into distal ends, and secured thereto via a sleeve cap. An item of bait is inserted inside of the tube member in order to lure an insect therein. The concave wire mesh is open on either end such that an insect is able to enter inside of the tube member, but unable to exit. End cap members may be used to permanently seal off the distal ends of the tube member. The tube member is configured to rest on a ground surface. An outer screen member is laid over top of the tube member. The outer screen member is adapted to be secured to the ground surface via anchors.

Insect trap

Described herein is the discovery that cell and tissue survival can be dramatically increased following radiation exposure through inhibition of the interaction between TSP-1 and CD47. This effect is shown using antisense molecules, peptides, and antibodies, which can now be used as radioprotectant agents. These agents find application in minimizing, reducing and/or preventing tissue damage following intentional and accidental radiation exposure, as well as increasing the therapeutic efficacy of radiation therapies by protecting non-target tissue from incidental radiation damage and by increasing tumor ablation following radiation treatment.

Radioprotectants targeting thrombospondin-1 and CD47

Provided herein are methods for preventing, ameliorating, and/or reducing tissue ischemia and/or tissue damage due to ischemia, increasing blood vessel diameter, blood flow and tissue perfusion in the presence of vascular disease including peripheral vascular disease, atherosclerotic vascular disease, coronary artery disease, stroke and influencing other conditions, by suppressing CD47 and/or blocking TSP1 and/or CD47 activity or interaction. Influencing the interaction of CD47-TSP1 in blood vessels allows for control of blood vessel diameter and blood flow, and permits modification of blood pressure and cardiac function. Under conditions of decreased blood flow, for instance through injury or atherosclerosis, blocking TSP1-CD47 interaction allows blood vessels to dilate and increases blood flow, tissue perfusion and tissue survival.

Prevention of tissue ischemia and related compositions

An equine training apparatus used in conjunction with: 1) a bridle supporting a bit, 2) a noseband, 3) riding reins connected to the bit, and 4) a breastplate, the apparatus comprising a head communication assembly comprising a cord member having a first end attached to a first O-ring, a second end attached to a second O-ring and noseband connection means between said first end and said second end and dividing said cord member into a first fork and a second fork; a sliding member in slidable engagement with said first fork and said second fork; and fork-body connection means for anchoring said sliding member to any of a breast plate, neckstrap, girth, cinch or the like. The sliding member acts as a pulley about which at least one fork is disposed and, when anchored to body tack via fork-body connection means provides a pivot point about which each fork may act; the sliding member effectively divides force applied through the reins into a mouth force component and a nose force component.

Equine training device

A manhole cover includes a security device, preferably located beneath an upper surface thereof. A cover removing apparatus includes a magnetic element to hold the cover, when a pin of the apparatus is engaged with the security device of the cover. A push force, which may be applied through a port in the upper surface of the cover, for example, by the pin member, can deform, and thereby unlock, a spring-loaded locking member of the security device. The security device may further include at least one elongate member, which is caused to move from a first position to a second position, by the push force, in order to disengage the cover from a manhole, so that the cover may be removed from the manhole.

Manhole cover security and removal

The present invention relates to compositions and methods for the production of biliverdin and methods of treatment and prevention. In particular, the invention concerns methods for producing biliverdin in yeast, especially, and other microorganisms.

Methods for the production of biliverdin

Provided herein are compositions and methods for preventing, ameliorating, and/or reducing tissue ischemia and/or tissue damage due to ischemia, increasing blood vessel diameter, blood flow and tissue perfusion in the presence of vascular disease including peripheral vascular disease, atherosclerotic vascular disease, coronary artery disease, stroke and influencing other conditions, by suppressing CD47 and/or blocking TSP1 and/or CD47 activity or interaction. Influencing the interaction of CD47-TSP1 in blood vessels allows for control of blood vessel diameter and blood flow, and permits modification of blood pressure and cardiac function. Under conditions of decreased blood flow, for instance through injury or atherosclerosis, blocking TSP1-CD47 interaction allows blood vessels to dilate and increases blood flow, tissue perfusion and tissue survival. This in turn reduces or prevents tissue necrosis and death. The therapeutics identified herein allow for precise regulation of blood flow to tissues and organs which need it, while substantially avoiding systemic complications. Methods and compositions described herein can be used to increase tissue survival under conditions of trauma and surgery, as well as conditions of chronic vascular disease. Also disclosed are methods for the treatment of elderly subjects using agents that affect TSP1 and CD47 and thereby affect tissue perfusion. Additionally, provided herein are compositions and methods for influencing blood coagulation, allowing for controlled increased or decreased blood clotting. Additionally, provided herein are compositions and methods for decreasing blood flow, as in the case of cancer through mimicking the effects of TSP1 and CD47 on blood vessel diameter and blood flow.

Growing community of inventors

Bethesda, MD, United States of America

David D Roberts