Abstract: A peripheral circuit of a memory device includes page buffers. Each page buffer includes a main latch, a bias latch, (N?1) data latches, and a cache latch coupled to a data path. The peripheral circuit is further configured to: in the process of programming a first physical page, disable a bit line bias function to release the bias latch to replace one of N page latches to perform a programming verification of memory states; release one of the N page latches to cache program data of one of the N logical pages of a second physical page; and in the process of programming the first physical page, store the program data of the one of the N logical pages of the second physical page in a released page latch.

Abstract: A memory device includes a memory cell array and a peripheral circuit coupled to the memory cell array. The memory cell array includes memory cells, each of which is set to one of 2N levels corresponding to a piece of N-bits data, where N is an integer greater than 1. The peripheral circuit includes a page buffer including a first latch, (N?1) second latches, and a third latch coupled to a data path. The peripheral circuit configured to perform first programming and second programming sequentially and respectively on a first physical page and a second physical page, in a process of programming the first physical page, sequentially release the third latch and the second latches, and in the process of programming the first physical page, sequentially store all programming data of N logical pages of the second physical page in the released third latch and second latches.

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: The present invention relates to polypeptides which share primary sequence with human Interleukin 2 (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 (Tregs) (Treg: CD4+CD25+FoxP3+) over effector T cells and Natural Killer Cells (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: A peripheral circuit of a memory device is configured to: in the process of programming a first physical page, perform a programming verification to a programming corresponding to the 2(N?M) th memory state; when the program verification of the 2(N?M) th memory state is passed, identifiers corresponding to the 1st to 2(N?M) th memory states stored by the main latch are made different from those corresponding to the 2(N?M)+1st to 2N th memory states; release at least one of the N page latches to cache program data of at least one logical page of the N logical pages of a second physical page; and the programming data of one logical page in the N logical pages of the second physical page is stored in a released page latch, where M is an integer greater than or equal to 1 and less than or equal to (N?2).

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 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: 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 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 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 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: In certain aspects, a memory device includes a memory cell array having rows of memory cells, word lines respectively coupled to the rows of memory cells, and a peripheral circuit coupled to the memory cell array through the word lines. Each memory cell is configured to store a piece of N-bits data in one of 2N levels, where N is an integer greater than 1. The level corresponds to one of 2N pieces of N-bits data. The peripheral circuit is configured to program, in a first pass, a row of target memory cells, such that each target memory cell is programmed into one of K intermediate levels based on the corresponding piece of N-bits data, wherein 2N-1<K<2N. The peripheral circuit is also configured to program, in a second pass after the first pass, the row of target memory cells, such that each target memory cell is programmed into one of the 2N levels based on the corresponding piece of N-bits data.

Abstract: A peripheral circuit of a memory device is configured to: in the process of programming a first physical page, perform a programming verification to a programming corresponding to the 2(N-M) th memory state; when the program verification of the 2(N-M) th memory state is passed, identifiers corresponding to the 1st to 2(N-M) th memory states stored by the main latch are made different from those corresponding to the 2(N-M)+1st to 2N th memory states; release at least one of the N page latches to cache program data of at least one logical page of the N logical pages of a second physical page; and the programming data of one logical page in the N logical pages of the second physical page is stored in a released page latch, where M is an integer greater than or equal to 1 and less than or equal to (N?2).

Abstract: A peripheral circuit of a memory device includes page buffers. Each page buffer includes a main latch, a bias latch, (N?1) data latches, and a cache latch coupled to a data path. The peripheral circuit is further configured to: in the process of programming a first physical page, disable a bit line bias function to release the bias latch to replace one of N page latches to perform a programming verification of memory states; release one of the N page latches to cache program data of one of the N logical pages of a second physical page; and in the process of programming the first physical page, store the program data of the one of the N logical pages of the second physical page in a released page latch.

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 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: 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: 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 antibody domain, each of which can take different forms, and configured such that the IL-15 is fused to the C-terminal of the antibody 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 optimized preclinical activity compared to rIL-15 or related cytokine therapeutics.

Abstract: In certain aspects, a memory device includes a memory cell array having rows of memory cells, word lines respectively coupled to the rows of memory cells, and a peripheral circuit coupled to the memory cell array through the word lines. Each memory cell is configured to store a piece of N-bits data in one of 2N levels, where N is an integer greater than 1. The level corresponds to one of 2N pieces of N-bits data. The peripheral circuit is configured to program, in a first pass, a row of target memory cells, such that each target memory cell is programmed into one of K intermediate levels based on the corresponding piece of N-bits data, wherein 2N?1<K<2N. The peripheral circuit is also configured to program, in a second pass after the first pass, the row of target memory cells, such that each target memory cell is programmed into one of the 2N levels based on the corresponding piece of N-bits data.