Abstract: A method for forming cement-based cementitious material includes: pouring a cement paste into a mold; applying an electrical current to the cement paste to perform an electro-osmotic reaction; and transferring the reacted cement paste into a water tank for curing, thereby obtaining a functionally graded cement-based cementitious material. A pair of electrodes is placed in the mold and connected to an external power source. The compressive strength of the functionally graded cement-based cementitious material in the middle is lower than that at either of both ends.

Abstract: In certain aspects, a memory device includes a non-volatile memory storing firmware, a control logic coupled to the non-volatile memory, and an array of memory cells coupled to the control logic, the array of memory cells is embedded with instructions that are executable by the control logic. The control logic is configured to perform a power-on reset (POR) initialization operation to control an initialization of the memory device based on the firmware, repair the firmware based on execution of the instructions embedded on the array of memory cells, and perform a remaining POR initialization operation based on the repaired firmware.

Abstract: The present invention relates to polypeptides which share primary sequence with human IL-2, except for several amino acids that have been mutated. A panel of IL-2 variants comprise mutations substantially reduce the ability of these polypeptides to stimulate Treg cells and make them more effective in the therapy of tumors. Also includes therapeutic uses of these mutated variants, used alone or in combination with vaccines, or TAA-targeting biologics, or immune checkpoint blocker, or as the building block in bifunctional molecule construct, for the therapy of diseases such as cancer or infections where the activity of regulatory T cells (Tregs) is undesirable. In another aspect the present invention relates to pharmaceutical compositions comprising the polypeptides disclosed.

Abstract: The present invention relates to bifunctional fusion molecules for therapy of autoimmune and various inflammatory disorders, cancer or cancer metastasis. The bifunctional fusion molecules comprise various IL-2 variants which comprise mutations that preferentially promotes the proliferation, survival, activation and/or function of immunosuppressive regulatory T cells ((T CD4+CD25+FoxP3+) over effector T cells and NK cells or IL-2 variants which comprise mutations substantially reduce the ability of these polypeptides to stimulate Treg cells and make them more effective in the therapy of tumors. The bifunctional fusion molecules further comprise a disease tissue targeting biologic or comprise a tumor associated antigen (TAA)-targeting biologic. In another aspect the present invention relates to pharmaceutical compositions comprising the polypeptides disclosed.

Abstract: The present disclosure provides novel and improved IL-15 fusion proteins for use in the treatment of cancer and other disorders. In various embodiments, the fusion proteins of the invention have two functional domains: an IL-15/IL-15R?Sushi domain (also referred to herein as an “IL-15/IL-15R?Sushi complex”) and an Fc domain, each of which can take different forms, and configured such that the IL-15 is fused to the C-terminal of the Fc domain and co-expressed and non-covalently complexed with IL-15R?Sushi. Importantly, the fusions proteins of the present invention address several of the limitations observed with the IL-15 therapeutics evaluated to date; specifically, the fusion proteins demonstrate extended the half-life of IL-15 in vivo, and demonstrate superior preclinical activity compared to rIL-15 or related cytokine therapeutics.

Abstract: The invention provides nucleic acid molecules encoding FGF21 mutant polypeptides, FGF21 mutant polypeptides, pharmaceutical compositions comprising FGF21 mutant polypeptides, and methods for treating metabolic disorders using such nucleic acids, polypeptides, or pharmaceutical compositions.

Abstract: The present invention relates to polypeptides which share primary sequence with human IL-2, except for several amino acids that have been mutated. One panel of IL-2 variants comprise mutations with impressive manufacturability that preferentially promotes the proliferation, survival, activation and/or function of immunosuppressive regulatory T cells (Treg: CD4+CD25+FoxP3+) over effector T cells and NK cells. Also includes therapeutic uses of such IL-2 selective agent, used alone, or in combination with immune modulating agents or disease-tissue targeting antibody, protein or peptide to treat Treg cell-deficiency, various autoimmune and inflammatory disorders, organ transplantation and graft-versus-host disease. In another aspect the present invention relates to pharmaceutical compositions comprising the polypeptides disclosed.

Abstract: The invention provides methods for treating non-alcoholic steatohepatitis (NASH) using FGF21 mutant polypeptides.

Abstract: The present disclosure provides a cytokine-based bioactivatable drug construct (“VitoKine”) platform that aims to reduce systemic mechanism-based toxicities and lead to broader therapeutic utility for proteins and cytokines such as IL-15 and IL-2 for the treatment of cancer, autoimmune diseases, inflammatory diseases, viral infection, transplantation and various other disorders. The novel VitoKine constructs of the present invention comprise: 1) a tissue or disease site targeting moiety D1 domain (“D1”), 2) a bioactivatable moiety D2 domain (“D2”), and a concealing moiety D3 domain (“D3”). Importantly, because the “active moiety” of the VitoKine construct will remain inert until activated locally by proteases that are upregulated in diseased tissues, this will limit binding of the active moiety to the receptors or to the targets in the peripheral or on the cell-surface of non-diseased cells and tissue to prevent over-activation of the pathway and reduce undesirable “on-target” “off tissue” toxicities.

Abstract: A method for forming cement-based cementitious material includes: pouring a cement paste into a mold; applying an electrical current to the cement paste to perform an electro-osmotic reaction; and transferring the reacted cement paste into a water tank for curing, thereby obtaining a functionally graded cement-based cementitious material. A pair of electrodes is placed in the mold and connected to an external power source. The compressive strength of the functionally graded cement-based cementitious material in the middle is lower than that at either of both ends.

Abstract: The present invention provides stabilized activin IIB receptor polypeptides and proteins capable of binding and inhibiting the activities of activin A, myostatin, or GDF-11. The present invention also provides polynucleotides, vectors and host cells capable of producing the stabilized polypeptides and proteins. Compositions and methods for treating muscle-wasting diseases and metabolic disorders are also provided.

Abstract: The present invention provides stabilized activin IIB receptor polypeptides and proteins capable of binding and inhibiting the activities of activin A, myostatin, or GDF-11. The present invention also provides polynucleotides, vectors and host cells capable of producing the stabilized polypeptides and proteins. Compositions and methods for treating muscle-wasting diseases and metabolic disorders are also provided.

Abstract: A new architecture is provided to support a precise information retrieval system on a web scale. The architecture provides algorithms to generate candidates and select the top N results via ranking models (e.g., Semantic ranking models, Aggregation ranking models) to capture term relationships between query and result contents at search-time.

Abstract: A design optimization and manufacturing approach for the creation of complex 3D curved rod structures with spatially variable material distributions that exhibit active deformation behavior is provided. The framework optimizes the cross-sectional properties of a rod structure, in particular the Young's modulus, such that under given loading conditions the rod structure may obtain one or more target shapes resulting from geometrically nonlinear deformation, from which the structure can then actively deform back to the original shape due to the shape memory effect. A novel algorithm is provided to generate physical realizations from the computational design model, which allows their direct fabrication via printing of shape memory composites with voxel-level compositional control with a multi-material 3D printer. The design and manufacture digital toolchain allows the continuous variation of multiple active materials as a route to optimize mechanical as well as active behavior of a structure.

Abstract: The present invention provides stabilized activin IIB receptor polypeptides and proteins capable of binding and inhibiting the activities of activin A, myostatin, or GDF-11. The present invention also provides polynucleotides, vectors and host cells capable of producing the stabilized polypeptides and proteins. Compositions and methods for treating muscle-wasting diseases and metabolic disorders are also provided.

Abstract: Disclosed is an isolated antigen binding protein, such as but not limited to, an antibody or antibody fragment. Also disclosed are pharmaceutical compositions and medicaments comprising the antigen binding protein, isolated nucleic acid encoding it, vectors, host cells, and hybridomas useful in methods of making it. In some embodiments the antigen binding protein comprises one to twenty-four pharmacologically active chemical moieties conjugated thereto, such as a pharmacologically active polypeptide.

Abstract: The invention provides nucleic acid molecules encoding FGF21 mutant polypeptides, FGF21 mutant polypeptides, pharmaceutical compositions comprising FGF21 mutant polypeptides, and methods for treating metabolic disorders using such nucleic acids, polypeptides, or pharmaceutical compositions.

Abstract: The invention provides methods of treating diabetes, reducing triglyceride levels, and treating obesity by administering to a subject in need there a fusion protein comprising an FGF21 mutant.

Abstract: Disclosed is an isolated antigen binding protein, such as but not limited to, an antibody or antibody fragment. Also disclosed are pharmaceutical compositions and medicaments comprising the antigen binding protein, isolated nucleic acid encoding it, vectors, host cells, and hybridomas useful in methods of making it. In some embodiments the antigen binding protein comprises one to twenty-four pharmacologically active chemical moieties conjugated thereto, such as a pharmacologically active polypeptide.

Abstract: The present invention provides stabilized activin IIB receptor polypeptides and proteins capable of binding and inhibiting the activities of activin A, myostatin, or GDF-11. The present invention also provides polynucleotides, vectors and host cells capable of producing the stabilized polypeptides and proteins. Compositions and methods for treating muscle-wasting diseases and metabolic disorders are also provided.