Abstract: Compositions of matter and methods of treatment based on generation of T cells capable of ameliorating or treating pathologies associated with improper immune activation. Chimeric antigen receptor (CAR) T cells are generated which possess tolerogenic properties based on enhanced expression of NR2F6. NR2F6 is enhanced through transfection of cells with a modified siRNA sequence. NR2F6 expression is upregulated through tissue culture modification, and NR2F6 expression vectors are introduced to the cell of interest. Methods and compositions to treat autoimmunity, transplant rejection, and conditions associated with pathological immune activation.

Abstract: An intake device for a gas turbine engine includes a snorkel and a particle separator. The snorkel is configured to be mounted to a panel defining at least a portion of a gas flow path within the gas turbine engine. The snorkel includes a tubular body extending between a closed end and an open end opposite the closed end. The snorkel further includes an inlet aperture formed through the tubular body adjacent the closed end. At least a portion of the snorkel is configured to be disposed within the gas flow path. The particle separator is mounted to the snorkel downstream of the inlet aperture. The particle separator includes at least one gas flow passage extending between a flow inlet and a flow outlet. The at least one gas flow passage is configured to remove particulate matter from the at least one gas flow passage upstream of the flow outlet.

Abstract: An intake device for a gas turbine engine includes a snorkel and a particle separator. The snorkel is configured to be mounted to a panel defining at least a portion of a gas flow path within the gas turbine engine. The snorkel includes a tubular body extending between a closed end and an open end opposite the closed end. The snorkel further includes an inlet aperture formed through the tubular body adjacent the closed end. At least a portion of the snorkel is configured to be disposed within the gas flow path. The particle separator is mounted to the snorkel downstream of the inlet aperture. The particle separator includes at least one gas flow passage extending between a flow inlet and a flow outlet. The at least one gas flow passage is configured to remove particulate matter from the at least one gas flow passage upstream of the flow outlet.

Abstract: A gas turbine engine includes an intake device. The intake device includes a snorkel and a filter case. The snorkel includes a tubular body and an inlet aperture. The tubular body extends between a closed end and an open end opposite the closed end. The inlet aperture is formed through the tubular body proximate the closed end. The tubular body forms a first portion of a gas flow path for a bleed gas from the inlet aperture to the open end. The filter case is connected to the tubular body. The filter case extends between a first end and a second end. The filter case includes a sidewall extending from the first end to the second end. The sidewall surrounds a filter cavity. The filter case is configured to receive the bleed gas from the open end of the tubular body. The filter case and the snorkel form a unitary component.

Abstract: Disclosed are means of stimulating systemic immunity and reduction of post-surgery tumor metastasis through the concurrent intralymphatic inhibition of NR2F6 and treatment with cannabidiol. In some embodiments NR2F6 is inhibited by high pressure transient delivery of short interfering RNA into tumor draining lymph nodes concurrent with systemic administration of cannabidiol. This combination may be performed together with means that induce immunogenic tumor cell death. Through the combination of immunogenic cell death and immune stimulation, the invention provides a means of enhancing the abscopal effect and in some embodiments to cause immunological mediated destruction primary and secondary neoplasia.

Abstract: Disclosed are means, methods and compositions of matter useful for suppressing pathological production of new blood vessels in conditions such as cancer and wet macular degeneration. In one embodiment the invention provides silencing of NR2F6 using nucleic acid based approaches such as RNA interference, antisense oligonucleotides, or DICER. In another embodiment, the invention teaches the administration of small molecule NR2F6 inhibitors as means of selectively inhibiting pathological but not healthy angiogenesis.

Abstract: An intake device for a gas turbine engine includes a snorkel and a housing. The snorkel includes a tubular body and an inlet aperture. The tubular body extends between a closed end and an open end opposite the closed end. The inlet aperture is formed through the tubular body proximate the closed end. The housing is mounted to the snorkel. The housing includes an inner wall, an outer wall, a side wall, a settling chamber, and an outlet tube. The inner wall is adjacent the snorkel. The outer wall is opposite the inner wall. The side wall extends from the inner wall to the outer wall. The settling chamber is within the side wall between the inner wall and the outer wall. The settling chamber is fluidly coupled with the open end. The outlet tube extends through the housing from the settling chamber to an exterior of the housing.

Abstract: Disclosed are means, methods and compositions of matter useful for suppressing pathological production of new blood vessels in conditions such as cancer and wet macular degeneration. In one embodiment the invention provides silencing of NR2F6 using nucleic acid based approaches such as RNA interference, antisense oligonucleotides, or DICER. In another embodiment, the invention teaches the administration of small molecule NR2F6 inhibitors as means of selectively inhibiting pathological but not healthy angiogenesis.

Abstract: Disclosed are compounds useful for alteration of NR2F6 activity. In some embodiments of the invention compounds disclosed are utilized for stimulation of NR2F6 activity, alone, or in combination with PKC activation. In other embodiments, the invention teaches use of compounds for inhibition of NR2F6 activation. Stimulation of NR2F6 within the context of the invention is useful, intra alia, for induction of immune inhibition, or stimulation of cellular proliferation without significant induction of differentiation. Inhibition of NR2F6 is desired in situations where the practitioner of the invention seeks to augment immune response, or induce cellular differentiation. In another embodiment, inhibition of NR2F6 expression is desired in situations where inhibition of cancer or cancer stem cells is needed.

Abstract: Disclosed are methods, devices, and techniques useful for enhancing function of an organ or cellular graft through photoceutical manipulation. In one embodiment a hematopoietic graft is treated with one or more wavelengths of low level laser irradiation at a sufficient energy to enhance homing and engraftment. In another embodiment the recipient long bones are treated with one or more wavelengths of low level laser irradiation at a sufficient energy to enhance chemoattraction and growth factor secretion on recipient stromal cells. Application of the invention includes areas of cellular transplants such as islet and hepatic cell grafts.

Abstract: Cancer associated inflammation has been reported to act as an immune suppressive mechanism through augmentation of myeloid suppressor cells, as well as downregulation of T cell receptor (TCR) signaling through the cleavage of the CD3 zeta chain. The teachings herein show the effects of concurrent anti-inflammatory treatment of dendritic cells (DC) using cannabidiol (CBD) together with inhibition of an immunological checkpoint, that is, silencing of NR2F6. Mixed lymphocyte cultures are used to increased potency of dendritic cells to stimulate allogeneic T cell proliferative and cytokine responses by the combination of NR2F6 gene silencing together with CBD. CBD alone appeared to inhibit DC maturation and allogestimulatory activity. These data support the utilization of small molecule inhibitors of NR2F6 together with CBD as combination therapies for immune modulation.

Abstract: Disclosed are means of stimulating systemic immunity and reduction of post-surgery tumor metastasis through the concurrent intralymphatic inhibition of NR2F6 and treatment with cannabidiol. In some embodiments NR2F6 is inhibited by high pressure transient delivery of short interfering RNA into tumor draining lymph nodes concurrent with systemic administration of cannabidiol. This combination may be performed together with means that induce immunogenic tumor cell death. Through the combination of immunogenic cell death and immune stimulation, the invention provides a means of enhancing the abscopal effect and in some embodiments to cause immunological mediated destruction primary and secondary neoplasia.

Abstract: Disclosed are compositions of matter, cells, and methodologies for generation of chimeric antigen receptor (CAR) cells with inhibited or absent NR2F6 activity. In one embodiment, a CAR possessing affinity to a tumor antigen is transfected onto T cells that possess reduced or absent NR2F6 activity, said reduction or absence of NR2F6 activity leading to increased production of cytokines associated with inhibition of tumor growth, metastasis or angiogenesis, and/or augmentation of tumor cytotoxicity. Inhibition of NR2F6 activity may be performed ex vivo on said T cells or in vivo by administration of small molecule inhibitors, siRNA, shRNA or gene editing. In some embodiments other immune cells are substituted for CAR-T cells.

Abstract: Disclosed are compositions of matters, cells, and treatment protocols useful for induction of anticancer responses in a patient suffering from cancer. In one embodiment the invention provides the use of NR2F6 silencing or gene editing in cord blood cells possessing anti-tumor activity in order to induce potentiated killer cells suitable for therapeutic use. In one embodiment said allogeneic cord blood killer cells are administered to initiate a cascade of antitumor immune responses, with initially responses mediated by allogeneic killer cells, and followed by endogenous immune responses.

Abstract: Disclosed are antigen specific cancer vaccines in which immunogenic epitopes are produced intracellularly by administration of modified mRNA encoding said immunogenic epitopes. In one embodiment of the invention, said modified mRNA encodes peptides derived from the protein survivin. By directly inducing gene expression of the antigens to which an immune response is desired, immunogenic peptides are generated intracellularly, thus allowing for a wider repertoire of epitopes to be presented to the adaptive immune system, which augments likelihood of successful induction of immunity.

Abstract: Disclosed are means, methods, and compositions of matter useful for generation of cancer inhibitory effector cells producing interleukin-17 (IL-17). In one embodiment a cellular population is obtained, said cellular population is exposed to agents capable of inhibiting NR2F6, whereby said inhibition of NR2F6 results in upregulation of IL-17 production, said upregulation of IL-17 production associated with acquisition of anti-tumor activity.

Abstract: Disclosed are means, methods, and compositions of matter for stimulation of T regulatory (Treg) cells by cannabidiol. In one embodiment, administration of cannabidiol is performed in an animal suffering from autoimmunity. In situations of autoimmunity, cannabidiol induces generation of Treg cells while other agents or therapies may be used to expand such cells in vitro and/or in vivo. In some embodiments the administration of cannabidiol is performed together with agents such as low dose interleukin-2 in order to treat inflammatory conditions such as arthritis or other conditions associated with reduction in Treg cells such as pregnancy failure, type 1 diabetes, or graft versus host disease.

Abstract: Described are compositions of matter, protocols, and treatment means for induction of immune mediated killing in dogs suffering from cancer. The invention provides means of extracting peripheral blood from a canine patient, expanding immunocytes capable of killing cancer cells in vitro, and re-administering said immunocytes into a patient in need of therapy. In one embodiment, immunocytes expanded are T cells possessing tumor cytotoxic activity induced by stimulation of NKG2D.

Abstract: Described are compositions of matter, protocols, and treatment means for induction of immune mediated killing in dogs suffering from cancer. The invention provides means of extracting peripheral blood from a canine patient, expanding immunocytes capable of killing cancer cells in vitro, and re-administering said immunocytes into a patient in need of therapy. In one embodiment, immunocytes expanded are T cells possessing tumor cytotoxic activity induced by stimulation of NKG2D.

Abstract: Described are compositions of matter, protocols, and treatment means for induction of immune mediated killing in dogs suffering from cancer. The invention provides means of extracting peripheral blood from a canine patient, expanding immunocytes capable of killing cancer cells in vitro, and re-administering said immunocytes into a patient in need of therapy. In one embodiment, immunocytes expanded are T cells possessing tumor cytotoxic activity induced by stimulation of NKG2D.