Abstract: Myelodysplastic syndrome (MDS) hematopoietic stem and progenitor cells (HSPC) translocate endosomal Toll-Like receptor (TLR)-9 to the plasma membrane, thereby sensitizing these clonal propagating cells to respective ligands in the microenvironment. TLR9 is the cognate receptor for RNA:DNA hybrids (R-loops) and unmethylated CpG oligonucleotides in oxidized mitochondrial DNA, the latter of which is abundant in the bone marrow microenvironment as a result of massive medullary pyroptotic cytolytic cell death. Both ligands are important danger-associated molecular patterns (DAMPs) triggering innate immune activation and chronic inflammation that contributes to MDS pathogenesis. In an effort to neutralize these DAMPs and disrupt this feed-forward inflammatory cascade, a chimeric protein was designed fusing the external epitopes of TLR9 to the Fc domain of human IgG4 to serve as a decoy receptor or ligand trap recognizing extracellular RNA:DNA hybrids (R-loops) and oxidized mitochondrial DNA.

Abstract: Disclosed are compositions and methods for treating disease or condition caused or exacerbated by S100A9 activity, such as myelodysplastic syndromes (MDS) using a composition comprising an effective amount of a CD33/S100A9 inhibitor.

Abstract: Embodiments of a system and method for low-latency content streaming are described. In various embodiments, multiple data fragments may be sequentially generated. Each data fragment may represent a distinct portion of media content generated from a live content source. Each data fragment may include multiple sub-portions. Furthermore, for each data fragment, generating that fragment may include sequentially generating each sub-portion of that fragment. Embodiments may include, responsive to receiving a request for a particular data fragment from a client during the generation of a particular sub-portion of that particular data fragment, providing the particular sub-portion to the client subsequent to that particular sub-portion being generated and prior to the generation of that particular data fragment being completed in order to reduce playback latency at the client relative to the live content source.

Abstract: Disclosed are compositions and methods for treating disease or condition caused or exacerbated by S100A9 activity, such as myelodysplastic syndromes (MDS) using a composition comprising an effective amount of a CD33/S100A9 inhibitor.

Abstract: Disclosed herein is a chimeric polypeptide, comprising at least a portion of the TIM3 receptor ectodomain and a fusion moiety for solubilizing the TIM3 receptor. Also disclosed is a method for treating a hematological cancer in a subject that involves administering to the subject a therapeutically effective amount of the disclosed chimeric polypeptide. Also disclosed is a method for enhance hematopoiesis in a subject, comprising administering to the subject a therapeutically effective amount of the disclosed chimeric polypeptide.

Abstract: Disclosed are molecules for treating non-del(5q) MDS that mimic allelic deficiency in de15q MDS to sensitize the malignant clones of patient without del(5q). The disclosed molecule contains an inhibitor of Cdc25C, an inhibitor of PP2Ac?, or a combination thereof, and a toll like receptor-9 (TLR9) targeting ligand. The molecule can also contain lenalidomide, or an analogue or derivative thereof. Also disclosed is a composition comprising the disclosed molecule in a pharmaceutically acceptable carrier. Also disclosed is a method for treating non-del(5q) myelodysplastic syndrome (MDS) in a subject by administering to the subject a therapeutically effective amount of the disclosed pharmaceutical composition.

Abstract: Disclosed herein are chimeric antigen receptor (CAR) polypeptides that can be used with adoptive cell transfer to target and kill cancer cells that express TLR9 on their surface. Also disclosed are immune effector cells, such as T cells or Natural Killer (NK) cells that are engineered to express these CARs. Therefore, also disclosed are methods of providing an anti-tumor immunity in a subject with a TLR9-expressing cancer that involves adoptive transfer of the disclosed immune effector cells engineered to express the disclosed CARs.

Abstract: The present disclosure relates to a method for diagnosing in a subject the progression from myelodysplastic syndrome (MDS) to acute myelogenous leukemia (AML). Also disclosed are methods of treating AML in a subject diagnosed by the disclosed methods.

Abstract: Disclosed herein are CAR-T cells with enhanced tumor infiltration. As disclosed herein, infiltrating lymphocytes (T and NK) within tumor tissue are absent of CX3CR1, a key chemokine receptor specific for lymphocytes. Therefore, disclosed herein are CAR-T cells that co-express CX3CR1 to enhance the infiltration of CAR-T cells into the tumor tissue. Also disclosed herein are CAR-T cells that co-express IL-15 in order to activate infiltration of NK cell. In some embodiments, the disclosed CAR-T cells express both CX3CR1 and IL-15 in combination with the CAR polypeptide. In some embodiments, the disclosed CAR-T cells further express EGFR in combination with the CAR polypeptide.

Abstract: Provided are an integrated inductor structure and an integrated circuit. The integrated inductor structure includes: at least two plane inductors, which are sequentially stacked, and different plane inductors are formed in metal layers with different functional modules; and at least one connection part, which is arranged between two adjacent functional modules, and each two adjacent plane inductors are electrically connected through the connection part.

Abstract: Disclosed are compositions and methods for targeted treatment of TLR9-expressing cancers. In particular, disclosed herein are molecules or conjugates containing a TLR9 targeting ligand, such as a CpG oligodeoxynucleotide, and a cytotoxic nanoparticle that targets TLR9-expressing malignant cells. Also disclosed is a pharmaceutical composition comprising a molecule disclosed herein in a pharmaceutically acceptable carrier. Also disclosed is a method for treating a TLR9-positive cancer in a subject that involves administering to the subject a therapeutically effective amount of a disclosed pharmaceutical composition.

Abstract: Disclosed are compositions and methods for targeted treatment of cancers, such as TLR9-expressing cancers. In particular, molecules containing a TLR9 targeting ligand, such as a CpG oligodeoxynucleotide, that target lytic peptides to TLR9-expressing malignant cells are disclosed.

Abstract: Embodiments of a system and method for low-latency content streaming are described. In various embodiments, multiple data fragments may be sequentially generated. Each data fragment may represent a distinct portion of media content generated from a live content source. Each data fragment may include multiple sub-portions. Furthermore, for each data fragment, generating that fragment may include sequentially generating each sub-portion of that fragment. Embodiments may include, responsive to receiving a request for a particular data fragment from a client during the generation of a particular sub-portion of that particular data fragment, providing the particular sub-portion to the client subsequent to that particular sub-portion being generated and prior to the generation of that particular data fragment being completed in order to reduce playback latency at the client relative to the live content source.

Abstract: Myelodysplastic syndrome (MDS) hematopoietic stem and progenitor cells (HSPC) translocate endosomal Toll-Like receptor (TLR)-9 to the plasma membrane, thereby sensitizing these clonal propagating cells to respective ligands in the microenvironment. TLR9 is the cognate receptor for RNA:DNA hybrids (R-loops) and unmethylated CpG oligonucleotides in oxidized mitochondrial DNA, the latter of which is abundant in the bone marrow microenvironment as a result of massive medullary pyroptotic cytolytic cell death. Both ligands are important danger-associated molecular patterns (DAMPs) triggering innate immune activation and chronic inflammation that contributes to MDS pathogenesis. In an effort to neutralize these DAMPs and disrupt this feed-forward inflammatory cascade, a chimeric protein was designed fusing the external epitopes of TLR9 to the Fc domain of human IgG4 to serve as a decoy receptor or ligand trap recognizing extracellular RNA:DNA hybrids (R-loops) and oxidized mitochondrial DNA.

Abstract: The present disclosure relates to a method for diagnosing in a subject the progression from myelodysplastic syndrome (MDS) to acute myelogenous leukemia (AML). Also disclosed are methods of treating AML in a subject diagnosed by the disclosed methods.

Abstract: Embodiments of a system and method for low-latency content streaming are described. In various embodiments, multiple data fragments may be sequentially generated. Each data fragment may represent a distinct portion of media content generated from a live content source. Each data fragment may include multiple sub-portions. Furthermore, for each data fragment, generating that fragment may include sequentially generating each sub-portion of that fragment. Embodiments may include, responsive to receiving a request for a particular data fragment from a client during the generation of a particular sub-portion of that particular data fragment, providing the particular sub-portion to the client subsequent to that particular sub-portion being generated and prior to the generation of that particular data fragment being completed in order to reduce playback latency at the client relative to the live content source.

Abstract: In various implementations, a server is configured to execute instructions stored in storage that when executed perform operations that include receiving a hypertext transfer protocol (HTTP) request to stream a video segment of multimedia content to a client device. The video segment is of a video sub-stream of the multimedia content. The operations further include sending the video segment and an audio segment to the client device based on the HTTP request for the video segment. The sending pushes the video segment and/or the audio segment to the client device. The audio segment is of an audio sub-stream of the multimedia content. A plurality of segment sets may be pushed based on the HTTP request for the video segment. Each segment set can include an additional video segment and an additional audio segment that correspond to at least partially concurrent portions of the multimedia content.

Abstract: Disclosed herein is a chimeric polypeptide, comprising at least a portion of the TIM3 receptor ectodomain and a fusion moiety for solubilizing the TIM3 receptor. Also disclosed is a method for treating a hematological cancer in a subject that involves administering to the subject a therapeutically effective amount of the disclosed chimeric polypeptide. Also disclosed is a method for enhance hematopoiesis in a subject, comprising administering to the subject a therapeutically effective amount of the disclosed chimeric polypeptide.

Abstract: In various implementations, a server is configured to execute instructions stored in storage that when executed perform operations that include receiving a hypertext transfer protocol (HTTP) request to stream a video segment of multimedia content to a client device. The video segment is of a video sub-stream of the multimedia content. The operations further include sending the video segment and an audio segment to the client device based on the HTTP request for the video segment. The sending pushes the video segment and/or the audio segment to the client device. The audio segment is of an audio sub-stream of the multimedia content. A plurality of segment sets may be pushed based on the HTTP request for the video segment. Each segment set can include an additional video segment and an additional audio segment that correspond to at least partially concurrent portions of the multimedia content.