Bicyclic Heteroaryl Compounds

This invention relates to compounds of the general formula: 6. A compound of wherein Rings A and B are aryl.7. A compound of or wherein Ring C is an imidazole ring.9. A compound of wherein s is 0; m claim 8 , p and v are 1; Rand Rare methyl; and Ris CF.12. A compound of claim 11 , wherein Rings A and B are aryl.14. A compound of claim 13 , wherein Ring D is a piperazine ring and Lis CH.16. A compound of wherein s is 0 claim 15 , m is 1 claim 15 , p is 1 claim 15 , Ris methyl claim 15 , Ris CF claim 15 , and Ris methyl or —CHCHOH.1761012. A method for treating cancer in a mammal in need thereof claim 1 , comprising administering to the mammal a therapeutically effective amount of a compound of any of - or - or a pharmaceutically acceptable salt claim 1 , solvate or hydrate thereof.18. A method for treating cancer in a mammal in need thereof claim 7 , comprising administering to the mammal a therapeutically effective amount of a compound of or a pharmaceutically acceptable salt claim 7 , solvate or hydrate thereof.19. A method for treating cancer in a mammal in need thereof claim 13 , comprising administering to the mammal a therapeutically effective amount of a compound of or a pharmaceutically acceptable salt claim 13 , solvate or hydrate thereof.2061012. A composition comprising a compound of any of - or - or a pharmaceutically acceptable salt claim 1 , solvate or hydrate thereof and a pharmaceutical acceptable carrier claim 1 , diluent or vehicle.21. A composition comprising a compound of or a pharmaceutically acceptable salt claim 7 , solvate or hydrate thereof and a pharmaceutical acceptable carrier claim 7 , diluent or vehicle.22. A composition comprising a compound of or a pharmaceutically acceptable salt claim 13 , solvate or hydrate thereof and a pharmaceutical acceptable carrier claim 13 , diluent or vehicle. The protein kinases are a large family of proteins which play a central role in the regulation of a wide variety of cellular processes. A partial, non ...

Pixel structure

A pixel structure having an SMII (semiconductor-metal-insulator-ITO) capacitor is provided. Specifically, a partial region of a transparent electrode layer corresponding to a semiconductor layer is removed, so as to eliminate parasitic capacitance between the transparent electrode layer and the semiconductor layer, prevent defects (e.g., waterfall, image sticking, etc.) from occurring on the display frame, and improve the display quality.

Schottky diode with lowered forward voltage drop

A Schottky diode with a lowered forward voltage drop has an N− type doped drift layer formed on an N+ type doped layer. The N− type doped drift layer has a surface formed with a protection ring inside which is a P-type doped layer. The surface of the N− type doped drift layer is further formed with an oxide layer and a metal layer. The contact region between the metal layer and the N− type doped drift layer within the P-type doped layer forms a Schottky barrier. An upward extending N type doped layer is formed on the N+ type doped layer and under the Schottky barrier to reduce the thickness of the N− type doped drift layer under the Schottky barrier. This lowers the forward voltage drop of the Schottky diode.

Monocyclic Heteroaryl Compounds

This invention relates to compounds of the general formula: 4. A compound according to claim 3 , wherein Rings A and B are aryl.5. A compound of wherein Ring C is a heteroaryl ring.6. A compound of wherein Ring C is an imidazole ring.8. A compound of wherein Ris independently selected from —CH claim 7 , or —C(O)NH claim 7 , v is 1 claim 7 , n is 0 or 1 claim 7 , m is 1 claim 7 , t is 1 claim 7 , Ris —CH claim 7 , Ris CFand Ris —CH.10. A compound according to wherein Rings A and B are aryl.11. A compound of wherein Ring D is a substituted or unsubstituted piperazine ring and Lis CH.12. A compound of wherein Ring D is a substituted or unsubstituted heteroaryl.14. A compound of wherein Ris independently selected from —CHand —C(O)NH claim 13 , n is 0 or 1 claim 13 , m is 1 claim 13 , t is 1 claim 13 , Ris methyl claim 13 , Ris CF claim 13 , one of Ris selected from methyl and CHCHOH.1514. A method for treating cancer in a mammal in need thereof claims 1 , comprising administering to the mammal a therapeutically effective amount of a compound of any of - or a pharmaceutically acceptable salt claims 1 , solvate or hydrate thereof.1614. A composition comprising a compound of any of - or a pharmaceutically acceptable salt claims 1 , solvate or hydrate thereof and a pharmaceutically acceptable carrier claims 1 , diluent or vehicle. The protein kinases represent a large family of proteins, which play a central role in the regulation of a wide variety of cellular processes and maintaining control over cellular function. A partial, non limiting, list of such kinases includes abl, Akt, bcr-abl, Blk, Brk, c-kit, c-met, c-src, CDK1, CDK2, CDK3, CDK4, CDK5, CDK6, CDK7, CDK8, CDK9, CDK10, cRaf1, CSK, EGFR, ErbB2, ErbB3, ErbB4, Erk, Pak, fes, FGFR1, FGFR2, FGFR3, FGFR4, FGFR5, Fgr, flt-1, Fps, Frk, Fyn, Hck, IGF-1R, INS-R, Jak, KDR, Lck, Lyn, MEK, p38, PDGFR, PIK, PKC, PYK2, ros, tie, tie2, TRK and Zap70. Abnormal protein kinase activity has been related to several disorders, ranging ...

Acetylenic Heteroaryl Compounds

This invention relates to compounds of the general formula: 3. A compound of wherein:{'sup': 1', 't1, 'Xis CH or CR;'}{'sup': 2', 't2, 'Xis CR;'}{'sup': '3', 'Xis N.'}4. A compound of wherein:{'sup': 1', 't1, 'Xis CH or CR;'}{'sup': 2', 't2, 'Xis CR;'}{'sup': 3', 't3, 'Xis CR.'}5. A compound of wherein:{'sup': I', 't1, 'Xis CH or CR;'}{'sup': '2', 'Xis N;'}{'sup': '3', 'Xis N.'}6. A compound of wherein:{'sup': 1', 't1, 'Xis CRor N;'}{'sup': 2', 't2, 'Xis CR;'}{'sup': 3', 't3, 'Xis CRor N.'}8. A compound of in which Xis CH.9. A compound of in which Xis CRor N.11. A compound of wherein Ring C is a substituted or unsubstituted heteroaryl ring.12. A compound of wherein Ring C is a substituted or unsubstituted imidazole ring.15. A compound of wherein Xis selected from CH claim 14 , CRor N.17. A compound of wherein Ring D is a substituted or unsubstituted heteroaryl.18. A compound of wherein Ring D is a substituted or unsubstituted piperazine ring and Lis CH.21. The compound of wherein Xis selected from CH claim 21 , CRor N.22. A method for treating cancer in a mammal in need thereof claim 1 , comprising administering to the mammal a therapeutically effective amount of a compound of any of ; or a pharmaceutically acceptable salt claim 1 , solvate or hydrate thereof.23. A method for treating cancer in a mammal in need thereof claim 10 , comprising administering to the mammal a therapeutically effective amount of a compound of ; or a pharmaceutically acceptable salt claim 10 , solvate or hydrate thereof.24. A method for treating cancer in a mammal in need thereof claim 16 , comprising administering to the mammal a therapeutically effective amount of a compound of ; or a pharmaceutically acceptable salt claim 16 , solvate or hydrate thereof.25. A composition comprising a compound of ; or a pharmaceutically acceptable salt claim 1 , solvate or hydrate thereof and a pharmaceutically acceptable carrier claim 1 , diluent or vehicle.26. A composition comprising a compound of ; or ...

System and Method for Low-Latency Content Streaming

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. 1. A computer-implemented method , comprising:sequentially generating multiple data fragments; wherein each data fragment represents a distinct portion of media content generated from a live content source; wherein each data fragment includes multiple sub-portions; wherein for a given data fragment, said generating comprises sequentially generating each sub-portion of that data fragment; andresponsive 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.2. The computer-implemented method of claim 1 , wherein said multiple data fragments represent different consecutive time periods of the media content from the live content source.3. The computer-implemented method of claim 2 , wherein for a given data ...

Methods and Compositions for Treating Cancer

The invention features methods, kits, and pharmaceutical compositions for treating cancer using 3-(imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methyl-N-(4-((4-methylpiperazin-1-yl)-methyl)-3-(trifluoromethyl)phenyl)benzamide. 127-. (canceled)37. The method according to claim 36 , wherein 1-methyl-4-(4-nitro-2-(trifluoromethyl)benzyl)piperazine is formed by the method comprising reacting 1-(bromomethyl)-4-nitro-2-(trifluoromethyl)benzene with 1-methylpiperazine.38. A method according to claim 37 , wherein 1-(bromomethyl)-4-nitro-2-(trifluoromethyl)benzene is formed by the method comprising reacting 2-methyl-5-nitrobenzotrifluoride in the presence of NBS and AIBN. This invention relates to pharmaceutical compositions and therapeutic methods based on the multi-kinase inhibitor, ponatinib (“compound 1”) for the treatment of disorders associated with pathological cellular proliferation, such as neoplasms, cancer, and conditions associated with pathological angiogenesis.The protein kinases are a large family of proteins which play a central role in the regulation of a wide variety of cellular processes. A partial, non limiting, list of such kinases includes abl, Akt, BCR-ABL, Blk, Brk, c-KIT, c-met, c-src, CDK1, CDK2, CDK3, CDK4, CDK5, CDK6, CDK7, CDK8, CDK9, CDK10, cRaf1, CSK, EGFR, ErbB2, ErbB3, ErbB4, Erk, Pak, fes, FGFR1, FGFR2, FGFR3, FGFR4, FGFR5, Fgr, FLT1, FLT3, Fps, Frk, Fyn, Hck, IGF-1R, INS-R, Jak, KDR, Lck, Lyn, MEK, p38, PDGFR, PIK, PKC, PYK2, ros, tie, tie2, TRK, and Zap70. Abnormal protein kinase activity has been related to several disorders, ranging from non-life threatening diseases such as psoriasis to extremely serious diseases such as cancers.Kinase inhibitors have been developed and used therapeutically with some important successes. However, not all of the targeted patients respond to those kinase inihibitors, and some become refractory to a given inhibitor through the emergence of mutation in the kinase or by other mechanisms. Currently approved kinase ...

Power conversion device for solar energy generating system

A power conversion device includes a DC-DC converter, a DC-AC inverter and a relay. The DC-DC converter leads in a DC from an external solar panel and transforms the DC into a direct voltage. The DC-AC inverter transforms the direct voltage from the DC-DC converter into an alternating voltage and connecting to an external electric load via electric load output ends. The relay includes a coil connected to an external commercial power line via commercial power input ends, and conductive contacts actuated by the coil and serially-disposed between the commercial power input ends and the DC-AC inverter, and with the commercial power line electrifying the coils, the conduction control is formed therebetween, preventing the electric energy of the solar energy generation from inversely transmitting to the commercial power line when interrupting the commercial power service.

Bicyclic Heteroaryl Compounds

This invention relates to compounds of the general formula: 6. A compound of wherein Rings A and B are aryl.7. A compound of or wherein Ring C is an imidazole ring.9. A compound of wherein s is 0; m claim 8 , p and v are 1; Rand Rare methyl; and Ris CF.12. A compound of claim 11 , wherein Rings A and B are aryl.14. A compound of claim 13 , wherein Ring D is a piperazine ring and Lis CH.16. A compound of wherein s is 0 claim 15 , m is 1 claim 15 , p is 1 claim 15 , Ris methyl claim 15 , Ris CF claim 15 , and Ris methyl or —CHCHOH.1761012. A method for treating cancer in a mammal in need thereof claims 1 , comprising administering to the mammal a therapeutically effective amount of a compound of any of - or - or a pharmaceutically acceptable salt claims 1 , solvate or hydrate thereof.18. A method for treating cancer in a mammal in need thereof claim 7 , comprising administering to the mammal a therapeutically effective amount of a compound of or a pharmaceutically acceptable salt claim 7 , solvate or hydrate thereof.19. A method for treating cancer in a mammal in need thereof claim 13 , comprising administering to the mammal a therapeutically effective amount of a compound of or a pharmaceutically acceptable salt claim 13 , solvate or hydrate thereof.2061012. A composition comprising a compound of any of - or - or a pharmaceutically acceptable salt claims 1 , solvate or hydrate thereof and a pharmaceutical acceptable carrier claims 1 , diluent or vehicle.21. A composition comprising a compound of or a pharmaceutically acceptable salt claim 7 , solvate or hydrate thereof and a pharmaceutical acceptable carrier claim 7 , diluent or vehicle.22. A composition comprising a compound of or a pharmaceutically acceptable salt claim 13 , solvate or hydrate thereof and a pharmaceutical acceptable carrier claim 13 , diluent or vehicle. The protein kinases are a large family of proteins which play a central role in the regulation of a wide variety of cellular processes. A partial, ...

Phosphorus Derivatives as Kinase Inhibitors

The invention features compounds of the general formula: 2. The compound of in which Xis N.3. The compound of in which Xis N and Xis CR.4. The compound of in which Xis CRand Xis CR.5. The compound of in which Xis CR.6. The compound of in which Xis N and Xis CR.7. The compound of in which Xis CRand Xis CR.8. The compound of any of claim 5 , claim 5 , claim 5 , or in which Ris selected from Cl claim 5 , F claim 5 , C1-C4 alkyl claim 5 , trihaloalkyl claim 5 , cycloalkyl claim 5 , C2-C4 alkenyl claim 5 , and alkynyl.9. The compound of in which Xis CRand Xis CRwherein Rand R claim 1 , together with the atoms to which they are attached claim 1 , form a fused claim 1 , 5- claim 1 , 6- or 7-membered saturated claim 1 , partially saturated or unsaturated ring claim 1 , which contains 0-4 heteroatoms selected from N claim 1 , O and S(O)and which may bear up to four substituents.109. The compound of any of - in which s is 1 claims 1 , 2 claims 1 , 3 or 4 claims 1 , and each of the substituents Ris independently selected from halo claims 1 , —R claims 1 , —OR claims 1 , —NRRand —P(═O)(R) claims 1 , wherein each Rand Rmoiety may be further substituted or unsubstituted.11. The compound of in which at least one substituent Ris —ORand Ris selected from C1-C6 alkyl claim 10 , C2-C6 alkenyl claim 10 , and C2-C6 alkynyl.12. The compound of or in which at least one substituent Ris a 5- claim 10 , 6- or 7-membered heterocyclic or 5- or 6-membered heteroaryl moiety claim 10 , linked to Ring A either directly or by an ether bond claim 10 , and which may be further substituted with 1-3 substituents independently selected from halo claim 10 , —CN claim 10 , —NO claim 10 , —R claim 10 , —OR claim 10 , —O—NRR claim 10 , —NRR claim 10 , —NR—NRR claim 10 , —NR—OR claim 10 , —C(O)YR claim 10 , —OC(O)YR claim 10 , —NRC(O)YR claim 10 , —SC(O)YR claim 10 , —NRC(═S)YR claim 10 , —OC(═S)YR claim 10 , —C(═S)YR claim 10 , —YC(═NR)YR claim 10 , —YC(═N—OR)YR claim 10 , —YC(═N—NRR)YR claim 10 , —YP(═O)( ...

Phosphorus Derivatives as Kinase Inhibitors

The invention features compounds of the general formula: 2. The compound of in which Xis N.3. The compound of in which Xis N and Xis CR.4. The compound of in which Xis CRand Xis CR.5. The compound of in which Xis CR.6. The compound of in which Xis N and Xis CR.7. The compound of in which Xis CRand Xis CR.8. The compound of any of claim 5 , claim 5 , claim 5 , or in which Ris selected from Cl claim 5 , F claim 5 , C1-C4 alkyl claim 5 , trihaloalkyl claim 5 , cycloalkyl claim 5 , C2-C4 alkenyl claim 5 , and alkynyl.9. The compound of in which Xis CRand Xis CRwherein Rand R claim 1 , together with the atoms to which they are attached claim 1 , form a fused claim 1 , 5- claim 1 , 6- or 7-membered saturated claim 1 , partially saturated or unsaturated ring claim 1 , which contains 0-4 heteroatoms selected from N claim 1 , O and S(O)and which may bear up to four substituents.109. The compound of any of - in which s is 1 claims 1 , 2 claims 1 , 3 or 4 claims 1 , and each of the substituents Ris independently selected from halo claims 1 , —R claims 1 , —OR claims 1 , —NRRand —P(═O)(R) claims 1 , wherein each Rand Rmoiety may be further substituted or unsubstituted.11. The compound of in which at least one substituent Ris —ORand Ris selected from C1-C6 alkyl claim 10 , C2-C6 alkenyl claim 10 , and C2-C6 alkynyl.12. The compound of or in which at least one substituent Ris a 5- claim 10 , 6- or 7-membered heterocyclic or 5- or 6-membered heteroaryl moiety claim 10 , linked to Ring A either directly or by an ether bond claim 10 , and which may be further substituted with 1-3 substituents independently selected from halo claim 10 , —CN claim 10 , —NO claim 10 , —R claim 10 , —OR claim 10 , —O—NRR claim 10 , —NRR claim 10 , —NR—NRR claim 10 , —NR—OR claim 10 , —C(O)YR claim 10 , —OC(O)YR claim 10 , —NRC(O)YR claim 10 , —SC(O)YR claim 10 , —NRC(═S)YR claim 10 , —OC(═S)YR claim 10 , —C(═S)YR claim 10 , —YC(═NR)YR claim 10 , —YC(═N—OR)YR claim 10 , —YC(═N—NRR)YR claim 10 , —YP(═O)( ...

Bicyclic Heteroaryl Compounds

This invention relates to compounds of the general formula: 6. A compound of wherein Rings A and B are aryl.7. A compound of or wherein Ring C is an imidazole ring.9. A compound of wherein s is 0; m claim 8 , p and v are 1; Rand Rare methyl; and Ris CF.12. A compound of claim 11 , wherein Rings A and B are aryl.14. A compound of claim 13 , wherein Ring D is a piperazine ring and Lis CH.16. A compound of wherein s is 0 claim 15 , m is 1 claim 15 , p is 1 claim 15 , Ris methyl claim 15 , Ris CF claim 15 , and Ris methyl or —CHCHOH.1761012. A method for treating cancer in a mammal in need thereof claim 1 , comprising administering to the mammal a therapeutically effective amount of a compound of any of - or - or a pharmaceutically acceptable salt claim 1 , solvate or hydrate thereof.187. A method for treating cancer in a mammal in need thereof claim 1 , comprising administering to the mammal a therapeutically effective amount of a compound of claim or a pharmaceutically acceptable salt claim 1 , solvate or hydrate thereof.19. A method for treating cancer in a mammal in need thereof claim 13 , comprising administering to the mammal a therapeutically effective amount of a compound of or a pharmaceutically acceptable salt claim 13 , solvate or hydrate thereof.2061012. A composition comprising a compound of any of - or - or a pharmaceutically acceptable salt claim 1 , solvate or hydrate thereof and a pharmaceutical acceptable carrier claim 1 , diluent or vehicle.21. A composition comprising a compound of or a pharmaceutically acceptable salt claim 7 , solvate or hydrate thereof and a pharmaceutical acceptable carrier claim 7 , diluent or vehicle.22. A composition comprising a compound of or a pharmaceutically acceptable salt claim 13 , solvate or hydrate thereof and a pharmaceutical acceptable carrier claim 13 , diluent or vehicle.25. A method according to claim 23 , wherein the leukemia is chronic myeloid leukemia (CML).26. A method according to claim 23 , wherein the ...

SYSTEM AND METHOD FOR LOCAL GENERATION OF STREAMING CONTENT WITH A HINT TRACK

Embodiments of a system and method for local generation of streaming content with a hint track are described. Embodiments may include receiving a first version of encrypted content comprising encrypted content samples that each include media content and non-content information. Embodiments may also include receiving a hint track including packet header information for a stream of media packets from which the media content was sourced, and offset information identifying locations of encrypted media content within the encrypted content samples. Embodiments may include generating a second version of the encrypted content for streaming, which may include, based on the information of the hint track, identifying the location of media content within the encrypted content samples. Embodiments may include generating media packets within the second version of the encrypted content, each of those media packets including header information from the hint track and the identified media content from the encrypted content samples. 1. A computer-implemented method , comprising:receiving a first version of encrypted content comprising one or more encrypted content samples that each include media content and non-content information;receiving a hint track comprising: packet header information for a stream of media packets from which the media content was sourced, and offset information identifying one or more locations of encrypted media content within said encrypted content samples; and based on the information of the hint track, identifying the location of media content within the one or more encrypted content samples; and', 'generating one or more media packets within the second version of the encrypted content, each of those media packets comprising at least some of the header information from the hint track and at least some of the identified media content from the one or more encrypted content samples., 'generating a second version of the encrypted content for streaming, said ...

Phosphorus Derivatives as Kinase Inhibitors

The invention features compounds of the general formula: 2. The compound of in which Xis N.3. The compound of in which Xis N and Xis CR.4. The compound of in which Xis CRand Xis CR.5. The compound of in which Xis CR.6. The compound of in which Xis N and Xis CR.7. The compound of in which Xis CRand Xis CR.8. The compound of any of claim 5 , claim 5 , claim 5 , or in which Ris selected from Cl claim 5 , F claim 5 , C1-C4 alkyl claim 5 , trihaloalkyl claim 5 , cycloalkyl claim 5 , C2-C4 alkenyl claim 5 , and alkynyl.9. The compound of in which Xis CRand Xis CRwherein Rand R claim 1 , together with the atoms to which they are attached claim 1 , form a fused claim 1 , 5- claim 1 , 6- or 7-membered saturated claim 1 , partially saturated or unsaturated ring claim 1 , which contains 0-4 heteroatoms selected from N claim 1 , O and S(O)and which may bear up to four substituents.109. The compound of any of - in which s is 1 claims 1 , 2 claims 1 , 3 or 4 claims 1 , and each of the substituents Ris independently selected from halo claims 1 , —R claims 1 , —OR claims 1 , —NRRand —P(═O)(R) claims 1 , wherein each Rand Rmoiety may be further substituted or unsubstituted.11. The compound of in which at least one substituent Ris —ORand Ris selected from C1-C6 alkyl claim 10 , C2-C6 alkenyl claim 10 , and C2-C6 alkynyl.12. The compound of or in which at least one substituent Ris a 5- claim 10 , 6- or 7-membered heterocyclic or 5- or 6-membered heteroaryl moiety claim 10 , linked to Ring A either directly or by an ether bond claim 10 , and which may be further substituted with 1-3 substituents independently selected from halo claim 10 , —CN claim 10 , —NO claim 10 , —R claim 10 , —OR claim 10 , —O—NRR claim 10 , —NRR claim 10 , —NR—NRR claim 10 , —NR—OR claim 10 , —C(O)YR claim 10 , —OC(O)YR claim 10 , —NRC(O)YR claim 10 , —SC(O)YR claim 10 , —NRC(═S)YR claim 10 , —OC(═S)YR claim 10 , —C(═S)YR claim 10 , —YC(═NR)YR claim 10 , —YC(═N—OR)YR claim 10 , —YC(═N—NRR)YR claim 10 , —YP(═O)( ...

CD PLAYER AND METHOD FOR EJECTION CONTROL THEREOF

A compact disc (CD) player and method for ejection control thereof is provided. The CD player has: a CD tray, an eject button, a front-end module, a back-end module, and a fast response eject module, wherein the front-end module and the back-end module are coupled to each other and integrated in an integrated circuit (IC). The fast response eject module has a second tray control module for detecting a status of the eject button, and a second ejection detection module for controlling the ejecting/inserting of the CD tray according to the detected status of the eject button after the CD player is powered up and before initialization of the first ejection detection module is completed. Accordingly, the CD player of the invention may quickly respond to the status of the eject button and control ejecting/inserting of the CD tray immediately after the CD player is powered up. 1. A compact disc (CD) player , comprises:a CD tray;an eject button;a front-end module, comprising a first tray control module coupled to the CD tray;a back-end module, coupled to the front-end module, wherein the back-end module comprises a first ejection detection module coupled to the eject button, and the front-end module and the back-end module are integrated on an integrated circuit (IC); and a second tray control module, coupled to the CD tray; and', 'a second ejection detection module, coupled to the eject button and the first ejection detection module,, 'a fast response eject module, comprisingwherein the second ejection detection module detects a status of the eject button and the second tray control module controls ejecting/inserting of the CD tray according to the detected status of the eject button during a time period after the CD player is powered up and before initialization of the first ejection detection module is completed.2. The CD player as claimed in claim 1 , wherein the fast response eject module is integrated in the back-end module claim 1 , and the fast response eject module ...

TLR9-TARGETED THERAPEUTICS

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. 1. A molecule comprising a toll like receptor-9 (TLR9) targeting ligand conjugated to a cytotoxic agent via a bivalent linker , wherein the cytotoxic agent comprises a cytotoxic nanoparticle.2. The method of claim 1 , wherein the cytotoxic nanoparticle comprises a cationic polymer claim 1 , wherein said ligand is covalently conjugated to said cationic polymer via said bivalent linker.3. The molecule of claim 1 , wherein the TLR9 targeting ligand is an unmethylated CpG oligodeoxynucleotide claim 1 , or an analogue or derivative thereof that binds TLR9.4. The molecule of claim 1 , wherein the TLR9 targeting ligand comprises an unmethylated GpC oligodeoxynucleotide claim 1 , a random oligodeoxynucleotide or a combination thereof.5. The molecule of claim 1 , wherein the bivalent linker comprises a C6 amino-SMCC-Cys linker.6. The molecule of claim 1 , wherein the cytotoxic nanoparticle has a mean diameter of 1.5 to 50 nm.7. The molecule of claim 1 , wherein the cytotoxic nanoparticle comprises a symmetrical dendrimer claim 1 , an asymmetrical dendrimer claim 1 , a linear and/or branched homopolymer claim 1 , a block copolymer claim 1 , a graft copolymer claim 1 , a random copolymer claim 1 , or a combination thereof.8. The molecule of claim 1 , wherein the cytotoxic nanoparticle comprises a biodegradable polymer comprising a biodegradable polymer backbone ...

CHIMERIC TIM-3 FUSION PROTEIN

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. 1. A chimeric polypeptide , comprising a TIM3 ectodomain and an Fc portion of an immunoglobulin.2. The polypeptide of claim 1 , wherein the TIM3 ectodomain comprises at least the IgV domain.3. The polypeptide of claim 2 , wherein the TIM3 ectodomain further comprises the mucin domain claim 2 , the transmembrane domain claim 2 , the cytoplasmic domain claim 2 , or any combination thereof.4. The polypeptide of claim 1 , wherein the TIM3 ectodomain lacks the mucin domain claim 1 , the transmembrane domain claim 1 , the cytoplasmic domain claim 1 , or any combination thereof.5. The polypeptide of claim 1 , further comprising signal peptide.6. The polypeptide of claim 1 , wherein the polypeptide is defined by the formula:{'br': None, 'SP-IgV-Cyto-Fc'}wherein “SP” represents a signal peptide,wherein “IgV” represents an IgV domain of TIM3,wherein “Mucin” represents a mucin domain of TIM3,wherein “TM” represents an transmembrane domain of TIM3,wherein “Cyto” represents a cytoplasmic domain of TIM3,wherein “Fc” represents an Fc portion of an immunoglobulin, andwherein “-” represents a linker peptide or peptide bond.7. The polypeptide of claim 1 , wherein the polypeptide is defined by the formula:{'br': None, 'SP-IgV-Mucin-TM-Cyto-Fc'}wherein “SP” represents a signal peptide,wherein “IgV” represents an IgV domain of TIM3,wherein “Mucin” represents a mucin domain of TIM3,wherein “TM” represents an transmembrane domain of TIM3,wherein “Cyto” represents ...

System and Method for Detecting a Security Compromise on a Device

Embodiments of a system and method for detecting a security compromise on a device are described. Embodiments may be implemented by a content consumption application configured to protect content decryption keys on a device, such as a computer system (e.g., a desktop or notebook computer) or a mobile device (e.g., a smartphone or tablet). For instance, the content consumption application may be configured to provide decryption keys for respective content to a media component (or another component of the operating system) if multiple conditions have been met. For instance, in various embodiments, the content consumption application may pass the key to the media component after ensuring that i) one or more security mechanisms of the device operating system have not been compromised and ii) one or more executable instructions of the content consumption application have not been tampered (e.g., instructions corresponding to a function that handles the decryption key(s)). 120-. (canceled)21. A computer-implemented method comprising:receiving, via an application executing on a computer, one or more decryption keys configured to enable a media component on the computer to decrypt encrypted content;determining whether a replacement operating system or an altered operating system is present on the computer;determining that one or more security mechanisms of an operating system of the computer are not compromised in response to a replacement operating system or an altered operating system not being present on the computer; andproviding, via the application, the one or more decryption keys to the media component on the computer in response to determining that the one or more security mechanisms of the operating system of the computer are not compromised.22. The computer-implemented method of claim 21 , wherein determining whether a replacement operating system or an altered operating system is present on the computer determines whether a file indicative of a replacement ...

SUBSTITUTED ACETYLENIC PYRAZOLO[1,5-A]PYRIDINE COMPOUNDS AS KINASE INHIBITORS

This invention relates to compounds of the general formula: 122.-. (canceled)25. The compound of claim 24 , wherein Ring A and Ring B are each independently a 5- or 6-membered aryl.26. The compound of claim 25 , wherein Ring C is imidazolyl.28. The compound of claim 27 , wherein Ring A and Ring B are each independently a 5- or 6-membered aryl.29. The compound of claim 28 , wherein Ring D is piperazinyl and Lis CH.30. The compound of claim 29 , wherein s is 0 claim 29 , m is 1 claim 29 , p is 1 claim 29 , Ris —CH claim 29 , Ris CF claim 29 , and Ris —CHor —CHCHOH.31. A composition comprising a compound of or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier claim 23 , diluent or vehicle. The protein kinases are a large family of proteins which play a central role in the regulation of a wide variety of cellular processes. A partial, non limiting, list of such kinases includes abl, Akt, bcr-abl, Blk, Brk, c-kit, c-met, c-src, CDK1, CDK2, CDK3, CDK4, CDK5, CDK6, CDK7, CDK8, CDK9, CDK10, cRaf1, CSK, EGFR, ErbB2, ErbB3, ErbB4. Erk, Pak, fes, FGFR1, FGFR2, FGFR3, FGFR4, FGFR5, Fgr, flt-1, Fps, Frk, Fyn, Hck, IGF-1R, INS-R, Jak, KDR, Lck, Lyn, MEK, p38, PDGFR, PIK, PKC, PYK2, ros, tie, tie2, TRK and Zap70. Abnormal protein kinase activity has been related to several disorders, ranging from non-life threatening diseases such as psoriasis to extremely serious diseases such as cancers.In view of the large number of protein kinases and associated diseases, there is an ever-existing need for new inhibitors selective for various protein kinases which might be useful in the treatment of related diseases.This invention concerns a new family of acetylenic heteroaryl compounds and their use in treating cancers, bone disorders, metabolic disorders, inflammatory disorders and other diseases.1. General Description of Compounds of the InventionThe compounds of this invention have a broad range of useful biological and pharmacological activities, ...

BENZIMIDAZOLE COMPOUNDS AS C-KIT INHIBITORS

The invention relates to c-Kit inhibitors useful in the treatment of cancers, and other serine-threonine kinase mediated diseases, having the Formula: (I) where A, L, R, R, R, and n are described herein. 2. The compound of claim 1 , wherein L is a —C(O)NR—.3. The compound of claim 1 , wherein L is a —NRC(O)—.4. The compound of any one of the preceding claims claim 1 , wherein Ris (C-C) alkyl or halogen.5. The compound of any one of the preceding claims claim 1 , wherein Ris methyl or F.6. The compound of any one of the preceding claims claim 1 , wherein Ris methyl.7. The compound of any one of the preceding claims claim 1 , wherein Ris H.8. The compound of any one of the preceding claims claim 1 , wherein A is (C-C) aryl optionally substituted with one or two R.9. The compound of any one of the preceding claims claim 1 , wherein A is 6-membered heteroaryl optionally substituted with one or two R.10. The compound of any one of the preceding claims claim 1 , wherein A is phenyl or pyridinyl optionally substituted with one or two R.11. The compound of any one of the preceding claims claim 1 , wherein A is phenyl or pyridinyl substituted with one R.12. The compound of any one of the preceding claims claim 1 , wherein A is phenyl or pyridinyl substituted with two R.13. The compound of any one of the preceding claims claim 1 , wherein Ris H.14. The compound of any one of the preceding claims claim 1 , wherein n is 0.15. The compound of any one of the preceding claims claim 1 , wherein n is 1.16. The compound of any one of the preceding claims claim 1 , wherein A is phenyl or pyridinyl substituted with one Rand Ris CFor cyclopropyl.17. The compound of any one of the preceding claims claim 1 , wherein A is phenyl or pyridinyl substituted with two Rand at least one Ris CF.21. The compound of claim 20 , wherein Ris H.22. The compound of or claim 20 , wherein n is 1 and Ris methyl.23. The compound of any one of to claim 20 , wherein Ris H.24. The compound of any one of to ...

ICARIIN DERIVATIVES

Disclosed are derivatives of icariin. Disclosed are compounds having Formula I-VIII as defined herein. Methods of using these compounds for the treatment of cancer and inflammation are also disclosed. 2. The compound of claim 1 , wherein each D is a hydroxyl group.3. The compound of any of the - claim 1 , wherein Y is COH and X is O.4. The compound of any of the - claim 1 , wherein n is 1.5. The compound of claim 4 , wherein Ris a methoxy group.11. The compound of claim 1 , wherein Y is N and X is NH.12. The compound of any of or claim 1 , wherein n is 2.15. A pharmaceutical composition comprising a compound of any of the preceding claims.18. A method of treating myelodysplastic syndrome comprising: administering to the subject a therapeutically effective amount of a compound or composition of any one of the preceding claims.19. A method of killing a tumor cell claim 1 , comprising contacting a tumor cell with an effective amount of a compound or composition of any one of -. This application claims the benefit of priority to U.S. Provisional Application 61/930,757, filed Jan. 23, 2014, and U.S. Provisional Application 61/977,985, filed Apr. 10, 2014, the disclosures of each are incorporated herein by referenced in their entireties.Inflammation is a hallmark of cancer and promotes the development and progression of cancer as well as the invasion of the immune system by tumor cells. Inflammation-induced cancer can be attributed to myeloid-derived suppressor cells (MDSCs), which accumulate in tumor bearing hosts, particularly in the local tumor microenvironment. MDSCs, characterized as Gr1CD11b in mice and HLA-DRLinCD33 in humans, were identified as the major immune creator of an immunosuppressive and tumorigenic microenvironment (Gabrilovich D I, Nagaraj S. 2009; 9(3):162-74). In healthy individuals, these cells exist as immature myeloid cells (IMC) and are part of normal myelopoiesis as they can quickly differentiate into mature monocytes, DC and neutrophils. However ...

BENZIMIDAZOLE COMPOUNDS AS C-KIT INHIBITORS

The invention relates to c-Kit inhibitors useful in the treatment of cancers, and other serine-threonine kinase mediated diseases, having the Formula: (I) where A, L, R, R, R, and n are described herein.

INFLAMMASOME ACTIVATION IN MYELODYSPLASTIC SYNDROMES

Disclosed are methods for treating a meylodysplastic syndrome (MDS) in a subject that involves administering to the subject a therapeutically effective amount of an inflammasome inhibitor. Also disclosed are methods for diagnosing a myelodysplastic syndrome (MDS) in a subject. In some embodiments, the method involves assaying a sample from the subject to detect inflammasome activation, wherein an increase in inflammasome activation in the sample compared to a control is an indication of MDS in the subject. In some embodiments, the method involves assaying a sample from the subject to detect s100A9 protein levels, wherein an increase in s100A9 protein levels in the sample compared to a control is an indication of MDS in the subject. The disclosed methods can further involve treating the subject for MDS if an increase in inflammasome activation and/or s100A9 levels are detected. 1. A method for treating a myelodysplastic syndromes (MDS) in a subject , comprising administering to the subject a therapeutically effective amount of an inflammasome inhibitor.2. The method of claim 1 , wherein the inflammasome inhibitor comprises a NLRP3 inflammasome inhibitor.4. The method of claim 2 , wherein the inflammasome inhibitor is selected from the group consisting of comprises glybenclamide (glyburide) claim 2 , 5-chloro-2-methoxy-N-[2-(4-sulfamoylphenyl)ethyl]benzamide claim 2 , and isoliquiritigenin.5. The method of claim 1 , wherein the inflammasome inhibitor comprises a caspase-1 inhibitor or a pan-caspase inhibitor.6. The method of any one of to claim 1 , wherein the MDS in the subject is non-del(5q) MDS.7. The method of any one of to claim 1 , wherein the MDS in the subject is del(5q) MDS.8. The method of claim 1 , wherein the inflammasome inhibitor comprises an S100A9 inhibitor.9. The method of claim 8 , wherein the S100A9 inhibitor is an S100A9 high-affinity chimeric (CD33-IgG) decoy receptor.10. The method of claim 5 , wherein the caspase-1 inhibitor is a shRNA targeting ...

PHOSPHOROUS DERIVATIVES AS KINASE INHIBITORS

The invention features compounds of the general formula (I) in which the variable groups are as defined herein, and to their preparation and use. 2. The compound of in which Xis N.3. The compound of in which Xis N and Xis CR.4. The compound of in which Xis CRand Xis CR.5. The compound of in which Xis CR.6. The compound of in which Xis N and Xis CR.7. The compound of in which Xis CRand Xis CR.8. The compound of any of claim 5 , claim 5 , claim 5 , or in which Ris selected from Cl claim 5 , F claim 5 , C1-C4 alkyl claim 5 , trihaloalkyl claim 5 , cycloalkyl claim 5 , C2-C4 alkenyl claim 5 , and alkynyl.9. The compound of in which Xis CRand Xis CRwherein Rand R claim 1 , together with the atoms to which they are attached claim 1 , form a fused claim 1 , 5- claim 1 , 6- or 7-membered saturated claim 1 , partially saturated or unsaturated ring claim 1 , which contains 0-4 heteroatoms selected from N claim 1 , O and S(O) claim 1 , and which may bear up to four substituents.10. The compound of any of - in which s is 1 claim 1 , 2 claim 1 , 3 or 4 claim 1 , and each of the substituents Ris independently selected from halo claim 1 , —R claim 1 , —OR claim 1 , —NRRand —P(═O)(R) claim 1 , wherein each Rand Rmoiety may be further substituted or unsubstituted.11. The compound of in which at least one substituent Ris —ORand Ris selected from C1-C6 alkyl claim 10 , C1-C6 alkenyl claim 10 , and C2-C6 alkynyl.12. The compound of or in which at least one substituent Ris a 5- claim 10 , 6- or 7-membered heterocyclic or 5- or 6-membered heteroaryl moiety claim 10 , linked to Ring A either directly or by an ether bond claim 10 , and which may be further substituted with 1-3 substituents independently selected from halo claim 10 , —CN claim 10 , —NO claim 10 , —R claim 10 , —OR claim 10 , —O—NRR claim 10 , —NRR claim 10 , —NR—NRR claim 10 , —NR—OR claim 10 , —C(O)YR claim 10 , —OC(O)YR claim 10 , —NRC(O)YR claim 10 , —SC(O)YR claim 10 , —NRC(═S)YR claim 10 , —OC(═S)YR claim 10 , —C(═S)YR ...

SOLUBLE CD33 FOR TREATING MYELODYSPLASTIC SYNDROMES (MDS)

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. 1. A recombinant fusion protein , comprising:(a) at least two S100A9-binding moieties selected from the group consisting of an extracellular domain of human CD33, an extracellular domain of toll like receptor 4 (TLR4), and an extracellular domain of Receptor for Advanced Glycation End Products (RAGE); and(b) an immunoglobulin Fc region.2. The fusion protein of claim 1 , comprising a formula selected from the group consisting of:{'br': None, 'eCD33-eTLR4-Fc,'}{'br': None, 'eCD33-eRAGE-Fc,'}{'br': None, 'eTLR4-eRAGE-Fc,'}{'br': None, 'eRAGE-eTLR4-Fc,'}{'br': None, 'eCD33-eTLR4-eRAGE-Fc,'}{'br': None, 'eCD33-eRAGE-eTLR4-Fc,'}{'br': None, 'eTLR4-eCD33-eRAGE-Fc,'}{'br': None, 'eRAGE-eCD33-eTLR4-Fc,'}{'br': None, 'eTLR4-eRAGE-eCD33-Fc, and'}{'br': None, 'eRAGE-eTLR4-eCD33-Fc,'}wherein “eCD33” comprises the extracellular domain of human CD33,wherein “eTLR4” comprises the extracellular domain of TLR4,wherein “eRAGE” comprises the extracellular domain of RAGE,wherein “Fc” comprises the immunoglobulin Fc region, andwherein “-” consists of a peptide linker or a peptide bond.3. The fusion protein of claim 1 , further comprising a biotin acceptor peptide that can be biotinylated with biotin ligase (BirA) in the presence of biotin and ATP.4. (canceled)5. The fusion protein of claim 3 , comprising a formula selected from the group consisting of:{'br': None, 'eCD33-Fc-Avi,'}{'br': None, 'eTLR4-Fc-Avi,'}{'br': None, 'eRAGE-Fc-Avi,'}{'br': None, 'eCD33-eTLR4-Fc-Avi,'}{'br': None, 'eCD33-eRAGE-Fc-Avi,'}{'br': None, 'eTLR4-eRAGE-Fc-Avi,'}{'br': None, 'eRAGE-eTLR4-Fc-Avi,'}{'br': None, 'eCD33-eTLR4-eRAGE-Fc-Avi,'}{'br': None, 'eCD33-eRAGE-eTLR4-Fc-Avi,'}{'br': None, 'eTLR4-eCD33-eRAGE-Fc-Avi,'}{'br': None, 'eRAGE-eCD33-eTLR4-Fc-Avi,'}{'br': None, 'eTLR4- ...

SUBSTITUTED ACETYLENIC PYRAZOLO[1,5-A]PYRIDINE COMPOUNDS AS KINASE INHIBITORS

This invention relates to compounds of the general formula: 6. A compound of wherein Rings A and B are aryl.7. A compound of or wherein Ring C is an imidazole ring9. A compound of wherein s is 0; m claim 8 , p and v are Rand Rare methyl; and Ris CF.11. A compound of claim 11 , wherein Rings A and B are aryl.14. A compound of claim 13 , wherein Ring D is a piperazine ring and Lis CH.16. A compound of wherein s is 0 claim 15 , m is 1 claim 15 , p is 1 claim 15 , Ris methyl claim 15 , Ris CF claim 15 , and Ris methyl or —CHCHOH.1712. A method for treating cancer in a mammal in need thereof claim 15 , comprising administering to the mammal a therapeutically effective amount of a compound of any of - or - or a pharmaceutically acceptable salt claim 15 , solvate or hydrate thereof.18. A method for treating cancer in a mammal in need thereof claim 7 , comprising administering to the mammal a therapeutically effective amount of a compound of or a pharmaceutically acceptable salt claim 7 , solvate or hydrate thereof.19. A method for treating cancer in a mammal in need thereof claim 13 , comprising administering to the mammal a therapeutically effective amount of a compound of or a pharmaceutically acceptable salt claim 13 , solvate or hydrate thereof.2012. A composition comprising a compound of any of - or - or a pharmaceutically acceptable salt claim 13 , solvate or hydrate thereof and a pharmaceutical acceptable carrier claim 13 , diluent or vehicle.21. A composition comprising a compound of or a pharmaceutically acceptable salt claim 7 , salivate or hydrate thereof and a pharmaceutical acceptable carrier claim 7 , diluent or vehicle.22. A composition comprising a compound of or a pharmaceutically acceptable salt claim 13 , solvate or hydrate thereof and a pharmaceutical acceptable carrier claim 13 , diluent or vehicle. The protein kinases are a large family of proteins which play a central role in the regulation of a wide variety of cellular processes. A partial, non ...

STREAMING MEDIA SEGMENTS

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. 1. A media streaming system comprising: receiving a hypertext transfer protocol (HTTP) request message specifying a first media segment to stream to a client device;', 'identifying a number of sets of media segments to push, starting with the first media segment, pursuant to a push strategy defined by the client device, without the client device providing identifiers for each of the media segments; and', 'streaming the sets of media segments to the client device in response to the request message., 'a server configured to execute instructions that when executed cause the server to perform operations comprising2. The media streaming system of claim 1 , wherein the HTTP request message from the client device includes a header extension claim 1 , a URL claim 1 , or a URI that specifies the number of sets of media segments to push.3. The media streaming system of claim 1 , wherein the HTTP request message from the client device specifies the number of sets of media segments for the server to push by designating the first media segment and at least one of an ending media segment or a ...

CD PLAYER AND METHOD FOR EJECTION CONTROL THEREOF

A compact disc (CD) player and method for ejection control thereof is provided. The CD player has: a CD tray, an eject button, a front-end module, a back-end module, and a fast response eject module, wherein the front-end module and the back-end module are coupled to each other and integrated in an integrated circuit (IC). The fast response eject module has a tray control module for detecting a status of the eject button, and an ejection detection module for controlling the ejecting/inserting of the CD tray according to the detected status of the eject button after the CD player is powered up and before the front-end module starts to work. The CD player of the invention may quickly respond to the status of the eject button and control ejecting/inserting of the CD tray immediately after the CD player is powered up. 1. A compact disc (CD) player , comprises:a CD tray;an eject button;a front-end module, coupled to the CD tray;a back-end module, coupled to the front-end module, wherein the front-end module and the back-end module are integrated on an integrated circuit (IC); and a tray control module, coupled to the CD tray; and', 'an ejection detection module, coupled to the eject button,, 'a fast response eject module, comprisingwherein the ejection detection module detects a status of the eject button and the tray control module controls ejecting/inserting of the CD tray according to the detected status of the eject button during a time period after the CD player is powered up and before the front-end module starts to work.2. The CD player as claimed in claim 1 , wherein the fast response eject module is integrated in the back-end module claim 1 , and the fast response eject module is configured to start detecting the status of the eject button after the back-end module is powered up.3. The CD player as claimed in claim 1 , wherein the fast response eject module is integrated on the IC and disposed on the outside of the back-end module.4. The CD player as claimed in ...

CHIMERIC ANTIGEN RECEPTORS WITH ENHANCED TUMOR INFILTRATION

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. 1. An polynucleotide comprising a nucleic acid sequence encoding a chimeric antigen receptor (CAR) polypeptide , wherein the polynucleotide further comprises:a nucleic acid sequence encoding a CX3CR1 protein;a nucleic acid sequence encoding an IL-15 protein;a nucleic acid sequence encoding an EGFR protein; or any combination thereof.2. The polynucleotide of claim 1 , wherein the CAR polypeptide comprises an NKG2D ectododomain claim 1 , a transmembrane domain claim 1 , an intracellular signaling domain claim 1 , and a co-stimulatory signaling region3. The polynucleotide of claim 2 , wherein the NKG2D ectodomain comprises an amino acid sequence having at least 65% claim 2 , 70% claim 2 , 71% claim 2 , 72% claim 2 , 73% claim 2 , 74% claim 2 , 75% claim 2 , 76% claim 2 , 77% claim 2 , 78% claim 2 , 79% claim 2 , 80% claim 2 , 81% claim 2 , 82% claim 2 , 83% claim 2 , 84% claim 2 , 85% claim 2 , 86% claim 2 , 87% claim 2 , 88% claim 2 , 89% claim 2 , 90% claim 2 , 91% claim 2 , 92% claim 2 , 93% claim 2 , 94% claim 2 , 95% claim 2 , 96% claim 2 , 97% claim 2 , 98% claim 2 , 99% claim 2 , or 100% sequence identity SEQ ID NO:9 claim 2 , or a fragment thereof of at least 100 claim 2 , 110 claim 2 , 120 claim 2 , 130 claim 2 , 135 claim 2 , 136 claim 2 , 137 claim 2 , 138 claim 2 , 139 claim 2 , 140 ...

INTEGRATED INDUCTOR STRUCTURE AND INTEGRATED CIRCUIT

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. 1. An integrated inductor structure , comprising:at least two plane inductors, which are sequentially stacked, wherein different ones of the at least two plane inductors are formed in metal layers of different functional modules; andat least one connection part, which is disposed between adjacent ones of the functional modules, wherein each two adjacent ones of the at least two plane inductors are electrically connected through a respective one of the at least one connection part.2. The integrated inductor structure of claim 1 , wherein an electrical connection mode of the at least two plane inductors is at least one of: series connection and parallel connection.3. The integrated inductor structure of claim 1 , wherein the each two adjacent ones of the at least two plane inductors have an overlapping part in a direction perpendicular to a plane in which the at least two plane inductors are located.4. The integrated inductor structure of claim 3 , wherein the overlapping part of the each two adjacent ones of the at least two plane inductors has a same current direction.5. The integrated inductor structure of claim 1 , wherein each of the at least two plane inductors is a plane spiral structure.6. The integrated inductor structure of claim 1 , wherein the connection part comprises at least one of: a solder ball and a metal pillar.7. The integrated inductor structure of claim 1 , wherein the at least two plane inductors comprise a first plane inductor and a second plane inductor claim 1 , and the functional modules ...

POWER EFFICIENT MULTIMEDIA CONTENT STREAMING BASED ON A SERVER PUSH

Techniques for influencing power consumption of a client while streaming multimedia content from a server over a network are described. For example, a server push strategy is used to push a number of media segments of the multimedia content from the server to the client in response to a single request identifying one of the media segments. Thus, instead of using multiple requests, the media segments are provided to the client by using a single request. Reducing the number of requests influences (e.g., reduces) the power consumption of the client. To optimize the power consumption given current client, server, and/or network conditions, the number of the media segments to be pushed is computed based on parameters associated with these conditions. 1. In a wireless network environment , a method for influencing power consumption of a client streaming multimedia content from a server using hypertext transfer protocol (HTTP) by controlling how many HTTP requests are used by the client , the method comprising:determining, by the client, a number of media segments of the multimedia content to request from the server per request based on a context of one or more of: the client, the server, or the wireless network environment, wherein the number is greater than one;sending, by the client to the server, a single HTTP request based on the determined number; andreceiving, by the client from the server, the number of the media segments in response to the single HTTP request.2. The method of claim 1 , further comprising:sending, by the client to the server, another single HTTP request indicative of a same or another number of media segments, the other number determined based on an updated context of the one or more of: the client, the server, or the wireless network;receiving, by the client from the server, the other number of the media segments in response to the other single HTTP request; andplaying, by the client, the number of the media segments and the other number of media ...

POWER EFFICIENT MULTIMEDIA CONTENT STREAMING BASED ON MEDIA SEGMENT DURATION

Techniques for influencing power consumption of a client while streaming multimedia content from a server over a network are described. The power consumption is influenced by controlling how many requests are used by the client to receive media segments of the multimedia content from the server. For example, the number of requests is reduced by increasing the durations of the available media segments. Thus, rather than requesting a certain number of media segments each of a particular duration, a lower number of media segments is requested where the requested media segments have longer durations. Although a longer duration generally results in a larger power saving, the length of a requested media segment is balanced against other parameters associated with current conditions of the client, server, and/or network to allow for, for example, adaptive streaming. As such an optimum duration is determined based on different parameters associated with the current conditions. 1. In a wireless network environment , a method for influencing power consumption of a client streaming multimedia content from a server by determining a media segment duration to control how many hypertext transfer protocol (HTTP) requests the client uses to request media segments of the multimedia content , the method comprising:determining, by the client, a duration for a media segment of the multimedia content based on a context of one or more of: the client, the server, or the wireless network environment;sending, by the client to the server, a HTTP request based on the determined duration; andreceiving, by the client from the server, the media segment in response to the HTTP request, the media segment having a length corresponding to the determined duration.2. The method of claim 1 , further comprising: playing claim 1 , by the client claim 1 , the media segment as a part of streaming the multimedia content.3. The method of claim 1 , wherein the context includes a battery power level of the ...

TARGETED SENSITIZATION OF NON-DEL(5q) MALIGNANT CELLS

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 PP2Acα, 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. 1. A molecule comprisingan oligonucleotide inhibitor of Cdc25C that directly inhibits gene expression of Cdc25C, an oligonucleotide inhibitor of PP2Acα that directly inhibits gene expression of PP2Acα, or a combination thereof;a toll like receptor-9 (TLR9) targeting ligand; andlenalidomide, or an synthetic lethal analogue thereof.2. The molecule of claim 1 , comprising the oligonucleotide inhibitor of Cdc25C coupled to the oligonucleotide inhibitor of PP2Acα by a bivalent linker.3. The molecule of claim 1 , wherein the TLR9 targeting ligand is coupled to the oligonucleotide inhibitor of Cdc25C or the oligonucleotide inhibitor of PP2Acα by a bivalent linker.4. The molecule of claim 1 , wherein the lenalidomide is coupled to the oligonucleotide inhibitor of Cdc25C or the oligonucleotide inhibitor of PP2Acα by a bivalent linker.5. The molecule of claim 1 , wherein the molecule is defined by the formula:{'br': None, 'TTL--IC--IP--LEN, or'}{'br': None, 'TTL--IP--IC--LEN,'}wherein “TTL” represents a TLR9 targeting ligand,wherein “IC” represents an siRNA inhibitor of Cdc25C,wherein “IP ” represents an-siRNA inhibitor of PP2Acα,wherein “LEN” represents an lenalidomide, andwherein “--” represents a bivalent linker.6. The molecule of claim 1 , wherein the TLR9 targeting ...

PRINTING HEAD DEVICE AND PRINTING METHOD

A printing method includes outputting multiple delay signals corresponding to multiple pixels by a delay latch array. The delay signals are calculated according to the largest and each resistance value corresponding to the multiple pixels in a thermal printing head respectively; and controlling the pixels to print according to the delay signals by the multiple pixel switches. 1. A printing head device , comprising:a delay latch array configured to store and output a plurality of delay signals, wherein the plurality of delay signals are calculated according to a largest resistance value and a plurality of resistance values corresponding to a plurality of pixels in the printing head device respectively; anda plurality of pixel switches corresponding to the plurality of pixels in the printing head device respectively, wherein the plurality of pixel switches are configured to control the plurality of pixels to print according to the plurality of delay signals.2. The printing head device of claim 1 , wherein the plurality of delay signals are calculated according to a plurality of heating times corresponding to the plurality of pixels in the printing head device respectively.3. The printing head device of claim 2 , wherein the plurality of heating times are obtained according to a longest heating time multiplied by a ratio between the largest resistance value and the corresponding resistance values respectively.4. The printing head device of claim 1 , comprising an integrated transmission control interface claim 1 , the integrated transmission control interface communicatively coupled to a controller of a thermal printing system claim 1 , the integrated transmission control interface configured to receive from the controller at least one of a compensation data claim 1 , a printing data claim 1 , a clock signal claim 1 , a data signal claim 1 , a latch signal or a start-heating signal.5. The printing head device of claim 4 , wherein the integrated transmission control ...

PRINTING SYSTEM

A printing system includes a controller and a thermal printing head including multiple driving elements and an integrated transmission control interface. The thermal printing head is coupled to the controller. The driving elements are configured to print. The integrated transmission control interface coupled to the controller and driving elements is configured to receive from the controller at least one of a compensation data, a printing data, a clock signal, a data signal, a latch signal or a start-heating signal, and send to driving elements the at least one of the compensation data, the printing data, the clock signal, the data signal, the latch signal or the start-heating signal. 1. A printing system , comprising:a controller; and a plurality of driving elements configured to print; and', 'an integrated transmission control interface coupled to the controller and driving elements and configured to receive from the controller at least one of a compensation data, a printing data, a clock signal, a data signal, a latch signal or a start-heating signal and send to driving elements the at least one of the compensation data, the printing data, the clock signal, the data signal, the latch signal or the start-heating signal., 'a thermal printing head coupled to the controller, the thermal printing head comprising2. The printing system of claim 1 , wherein the integrated transmission control interface comprises a high speed serial interface circuit claim 1 , the high speed serial interface circuit is configured to receive from the controller at least one of the compensation data and the printing data.3. The printing system of claim 1 , wherein the integrated transmission control interface is further configured to convert the printing data into a printing command and send the printing command to the driving elements.4. The printing system of claim 1 , wherein the integrated transmission control interface comprises a field-programmable gate array or an application-specific ...

ICARIIN AND ICARITIN DERIVATIVES

Disclosed are derivatives of icariin. Disclosed are compounds having Formula I-V as defined herein. Methods of using these compounds for the treatment of cancer and inflammation are also disclosed. 2. The compound of claim 1 , wherein each D is a hydroxyl group.3. The compound of claim 1 , wherein each D is a methoxyl group.4. (canceled)5. The compound of claim 1 , wherein n is 1.6. The compound of claim 1 , wherein Ris a methoxy group.7. The compound of claim 1 , wherein Ris hydrogen claim 1 , alkyl claim 1 , or alkenyl.9. The compound of claim 8 , wherein Ris an alkyl group claim 8 , optionally substituted with carbonyl claim 8 , alkyl claim 8 , amino claim 8 , amido claim 8 , alkoxyl claim 8 , alkylhydroxy claim 8 , cycloalkyl claim 8 , heterocycloalkyl claim 8 , aryl claim 8 , heteroaryl claim 8 , carbonyl claim 8 , halogen claim 8 , hydroxyl claim 8 , thiol claim 8 , cyano claim 8 , or nitro.10. The compound of claim 8 , wherein Ris ═CH.11. The compound of claim 8 , wherein Ris CH(CH).13. The compound of claim 12 , wherein Ris an alkyl group claim 12 , optionally substituted with carbonyl claim 12 , alkyl claim 12 , amino claim 12 , amido claim 12 , alkoxyl claim 12 , alkylhydroxy claim 12 , cycloalkyl claim 12 , heterocycloalkyl claim 12 , aryl claim 12 , heteroaryl claim 12 , carbonyl claim 12 , halogen claim 12 , hydroxyl claim 12 , thiol claim 12 , cyano claim 12 , or nitro.14. The compound of claim 12 , wherein Ris ═CH.15. The compound of claim 12 , wherein Ris CH(CH).17. (canceled)19. (canceled)20. A pharmaceutical composition comprising a therapeutically effective amount of a compound of and a pharmaceutical carrier and optional anticancer or anti-inflammatory agent.21. A method of treating myelodysplastic syndrome comprising: administering to the subject a therapeutically effective amount of a compound of .22. A method of killing a tumor cell claim 1 , comprising contacting a tumor cell with an effective amount of a compound or composition of . This ...

Scaling resistant ceramic glaze and functional overglaze for q345 hot rolled alloy steel double sided enameling

A scaling resistant ceramic glaze and a functional overglaze for Q345 hot rolled alloy steel double sided enameling. The components and the weight percentage of each component of the ground glaze of the enamel are as follows: 3-6% of Al 2 O 3 , 60-70% of SiO 2 ; 10-15% of B 2 O 3 , 10-15% of Na 2 O+K 2 O+Li 2 O, 3-6% of CaF 2 , 3-6% of ZrO 2 , 2-5% of CoO+NiO, 1-3% of BaMoO 4 +Sb 2 O 3 , 0.3-1.5 of WO 3 . The ground glaze is prepared by formulating chemical raw materials in a weight ratio converted by the described chemical composition, stirring thoroughly and mixing uniformly, melting same in a rotary furnace at 1200-1350° C., and then quenching the melt. The provided scaling resistant ceramic glaze and functional overglaze for Q345 hot rolled alloy steel double sided enameling can be applied to Q345 steel that contains C, P, S and the like which are considered harmful elements and contains a variety of common alloy elements.

HETEROARYL COMPOUNDS FOR KINASE INHIBITION

Compounds and pharmaceutical compositions that modulate kinase activity, including mutant EGFR and mutant HER2 kinase activity, and compounds, pharmaceutical compositions, and methods of treatment of diseases and conditions associated with kinase activity, including mutant EGFR and mutant HER2 activity, are described herein. 14. The compound according to claim 1 , wherein Xis CR.15. The compound according to or claim 1 , wherein Xis CH.16. The compound according to or claim 1 , wherein Xis N.17. The compound of any one of or - claim 1 , wherein Xis CR.18. The compound according to claim 1 , wherein Xis N.19. The compound of any one of or - claim 1 , wherein Xis CR.20. The compound of any one of or - claim 1 , wherein Xis N.21. The compound according to claim 1 , wherein Z claim 1 , Z claim 1 , and Zare each independently selected from CRR claim 1 , NRand O.22. The compound according to claim 21 , wherein Z claim 21 , Z claim 21 , and Zare each independently selected from CRR.23. The compound according to claim 22 , wherein Rand Rare each H.24. The compound according to claim 1 , wherein Zis CRR.25. The compound according to claim 24 , wherein Zis selected from CRR claim 24 , NR claim 24 , and O.26. The compound according to claim 25 , wherein Zis selected from CRR claim 25 , NR claim 25 , and O.27. The compound according to claim 1 , wherein Zis CH claim 1 , Zis CRR claim 1 , and Zis O.28. The compound according to claim 1 , wherein Zis CH claim 1 , Zis CH claim 1 , and Zis NR.29. The compound according to claim 1 , wherein Zis CH claim 1 , Zis CRRwhere Rand Rare taken together with the carbon atom to which they are attached to form an oxo group claim 1 , and Zis O or NR.30. The compound according to or wherein Zis NMe.31. The compound according to claim 1 , wherein Zis CRRwhere Rand Rare taken together with the carbon atom to which they are attached to form an oxo group claim 1 , Zis CH claim 1 , and Zis selected from CRR claim 1 , O and NR.32. The compound ...

TLR9 TARGETED CYTOTOXIC AGENTS

Disclosed are compositions and methods for targeted treatment of TLR9-expressing cancers. In particular, molecules containing a TLR9 targeting ligand, such as a CpG oligodeoxynucleotide, that target cytotoxic agents to TLR9-expressing malignant cells are disclosed. 1. A molecule comprising a toll like receptor-9 (TLR9) targeting ligand conjugated to a cytotoxic agent , wherein the cytotoxic agent is not a polynucleotide.2. The molecule of claim 1 , wherein the molecule is defined by the formula:{'br': None, 'TTL-CA,'}wherein “TTL” represents the TLR9 targeting ligand,wherein “CA” represents the cytotoxic agent, andwherein “-” represents a bivalent linker.3. The molecule of claim 1 , wherein the cytotoxic agent comprises a lytic peptide.4. The molecule of claim 1 , wherein the TLR9 targeting ligand is an unmethylated CpG oligodeoxynucleotide claim 1 , or an analogue or derivative thereof that binds TLR9.5. The molecule of claim 3 , wherein the lytic peptide comprises the amino acid sequence PNPNNNPNPN (SEQ ID NO:48) claim 3 , wherein “P” is any polar amino acid claim 3 , and wherein “N” is any non-polar amino acid.6. The molecule of claim 5 , wherein the lytic peptide comprises the amino acid sequence KIKMVISWKG (SEQ ID NO:1).7. (canceled)8. (canceled)9. A pharmaceutical composition comprising the molecule of in a pharmaceutically acceptable carrier.10. A method for treating a TLR9-positive cancer in a subject claim 9 , comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition of .11. The method of claim 10 , wherein the TLR9-positive cancer comprises a meylodysplastic syndrome (MDS).12. The method of claim 11 , wherein the TLR9-positive cancer comprises non-del(5q) MDS.13. The method of claim 10 , further comprising assaying a biopsy sample from the subject for TLR9 expression prior to treatment. This application is a divisional of copending application Ser. No. 15/522,956, filed Apr. 28, 2017, which is the National ...

REDUCING REQUESTS FOR MEDIA SEGMENTS IN STREAMING OF MULTIMEDIA CONTENT

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. 1. A media streaming system comprising: receiving a hypertext transfer protocol (HTTP) request to stream a video segment of multimedia content, the video segment being of a video sub-stream of the multimedia content; and', 'sending the video segment and an audio segment based on the HTTP request for the video segment, the sending pushing the audio segment without requiring a separate HTTP request for the audio segment, the audio segment being of an audio sub-stream of the multimedia content., 'a server configured to execute instructions stored in storage that when executed perform operations comprising2. The system of further comprising: sending the HTTP request to stream the video segment;', 'receiving the video segment and the audio segment sent by the server; and', 'playing back the multimedia content using the received video segment and the received audio segment., 'a client device configured to execute instructions stored in storage that when executed perform operations comprising3. The system of claim 2 , wherein the client device plays back the received video segment and ...

Encapsulation structure and solar cell module

An encapsulation structure and a solar cell module are provided, wherein the encapsulation structure is disposed on the light incident surface of the solar cell module and is consisted of a thermoplastic protective layer, a transparent water-barrier layer, and an adhesive layer. The thermoplastic protective layer is disposed on the outermost layer of the light incident surface, and the material thereof includes thermoplastic polyurethane (TPU), thermoplastic polyolefin (TPO), or thermoplastic elastomer (TPE). The transparent water-barrier layer is disposed between the adhesive layer and the thermoplastic protective layer.

HETEROARYL COMPOUNDS FOR KINASE INHIBITION

Compounds and pharmaceutical compositions that modulate kinase activity, including mutant EGFR and mutant HER2 kinase activity, and compounds, pharmaceutical compositions, and methods of treatment of diseases and conditions associated with kinase activity, including mutant EGFR and mutant HER2 activity, are described herein. 36.-. (canceled)7. The method according to claim 1 , wherein Xis CRand/or Xis N.863.-. (canceled)6567.-. (canceled)68. The method according to claim 1 , wherein{'sub': '1', 'Ris selected from amido, ester, CN, and heteroaryl; or'}{'sub': '3', 'Ris selected from H, alkyl, alkoxy, and halo; or'}{'sub': 5', '10', '11', '10', '11', '12', '12, 'Ris —NRR, Ris alkyl, Ris alkyl substituted with 1 or 2 R, and Ris amino or heterocyclyl; or'}{'sub': 6', '12, 'Ris selected from H and alkyl substituted with one R.'}7080.-. (canceled)8290.-. (canceled)9293.-. (canceled)94. The method according to claim 1 , wherein the compound of Formula I is a compound selected from:N-(3-((5-chloro-4-(6-(2-(pyrrolidin-1-yl)ethoxy)-1H-indol-3-yl)pyrimidin-2-yl)amino)-4-methoxyphenyl)acrylamide;N-(5-((5-chloro-4-(pyrazolo[1,5-a]pyridin-3-yl)pyrimidin-2-yl)amino)-2-(2-(dimethylamino)ethoxy)-4-methoxyphenyl)acrylamide;N-(3-((5-cyano-4-(1-methyl-6-(2-(1-methylpyrrolidin-2-yl)ethoxy)-1H-indol-3-yl)pyrimidin-2-yl)amino)-4-methoxyphenyl)acrylamide;N-(3-((5-cyano-4-(1-methyl-6-(2-(pyrrolidin-1-yl)ethoxy)-1H-indol-3-yl)pyrimidin-2-yl)amino)-4-methoxyphenyl)acrylamide;N-(2-((2-(dimethylamino)ethyl)(methyl)-amino)-4-methoxy-5-((4-(1-methyl-1H-indol-3-yl)-5-(N-methylisobutyramido)-pyrimidin-2-yl)amino)phenyl)acrylamide;N-(3-((5-cyano-4-(6-(3-(dimethylamino)propoxy)-1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-4-methoxyphenyl)acrylamide;N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)acrylamide;N-(4-methoxy-2-(methyl(2-(methylamino)ethyl)amino)-5-((4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)acrylamide;N-(2-((2-( ...

Bicyclic Heteroaryl Compounds

This invention relates to compounds of the general formula: 6. A compound of wherein Rings A and B are aryl.7. A compound of or wherein Ring C is an imidazole ring.9. A compound of wherein s is 0; m claim 8 , p and v are 1; Rand Rare methyl; and Ris CF.12. A compound of claim 11 , wherein Rings A and B are aryl.14. A compound of claim 13 , wherein Ring D is a piperazine ring and Lis CH.16. A compound of wherein s is 0 claim 15 , m is 1 claim 15 , p is 1 claim 15 , Ris methyl claim 15 , Ris CF claim 15 , and Ris methyl or —CHCHOH.1761012. A method for treating cancer in a mammal in need thereof claims 1 , comprising administering to the mammal a therapeutically effective amount of a compound of any of - or - or a pharmaceutically acceptable salt claims 1 , solvate or hydrate thereof.18. A method for treating cancer in a mammal in need thereof claim 7 , comprising administering to the mammal a therapeutically effective amount of a compound of or a pharmaceutically acceptable salt claim 7 , solvate or hydrate thereof.19. A method for treating cancer in a mammal in need thereof claim 13 , comprising administering to the mammal a therapeutically effective amount of a compound of or a pharmaceutically acceptable salt claim 13 , solvate or hydrate thereof.2061012. A composition comprising a compound of any of - or - or a pharmaceutically acceptable salt claims 1 , solvate or hydrate thereof and a pharmaceutical acceptable carrier claims 1 , diluent or vehicle.21. A composition comprising a compound of or a pharmaceutically acceptable salt claim 7 , solvate or hydrate thereof and a pharmaceutical acceptable carrier claim 7 , diluent or vehicle.22. A composition comprising a compound of or a pharmaceutically acceptable salt claim 13 , solvate or hydrate thereof and a pharmaceutical acceptable carrier claim 13 , diluent or vehicle. The protein kinases are a large family of proteins which play a central role in the regulation of a wide variety of cellular processes. A partial, ...

TLR9 TARGETED THERAPEUTICS

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. 1. A molecule comprising a toll like receptor-9 (TLR9) targeting ligand conjugated to a lytic peptide via a bivalent linker , wherein the lytic peptide comprises the amino acid sequence PHHPPHHPHHPPHHPHHP (SEQ ID NO:2) , where P is a positively charged amino acid and H is a hydrophobic amino acid.2. The molecule of claim 1 , wherein the lytic peptide comprises the amino acid sequence SEQ ID NO:1.3. The molecule of claim 1 , wherein the TLR9 targeting ligand is an unmethylated CpG oligodeoxynucleotide claim 1 , or an analogue or derivative thereof that binds TLR9.4. The molecule of claim 1 , wherein the bivalent linker comprises a C6 amino-SMCC-Cys linker.5. A molecule comprising cancer targeting agent conjugated to a cytotoxic agent via a bivalent linker claim 1 , wherein the bivalent linker comprises a C6 amino-SMCC-Cys linker.6. The molecule of claim 5 , wherein the cytotoxic agent comprises a lytic peptide.7. The molecule of claim 5 , wherein the cancer targeting agent comprises a TLR9 targeting ligand.8. The molecule of claim 7 , wherein the TLR9 targeting ligand is an unmethylated CpG oligodeoxynucleotide claim 7 , or an analogue or derivative thereof that binds TLR9.9. A pharmaceutical composition comprising the molecule of in a pharmaceutically acceptable carrier.10. A method for treating a cancer in a subject claim 9 , comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition of .11. The method of claim 10 , wherein the cancer comprises a meylodysplastic syndrome (MDS).12. The method of claim 10 , wherein the cancer comprises a hepatic cancer.13. The method of claim 10 , further comprising assaying a biopsy sample from the subject ...

SOLUBLE CD33 FOR TREATING MYELODYSPLASTIC SYNDROMES (MDS)

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. 1. A recombinant fusion protein , comprising:(a) at least two S100A9-binding moieties selected from the group consisting of an extracellular domain of human CD33, an extracellular domain of toll like receptor 4 (TLR4), and an extracellular domain of Receptor for Advanced Glycation End Products (RAGE); and(b) an immunoglobulin Fc region.2. The fusion protein of claim 1 , comprising a formula selected from the group consisting of:eCD33-eTLR4-Fc,eCD33-eRAGE-Fc,eTLR4-eRAGE-Fc,eRAGE-eTLR4-Fc,eCD33-eTLR4-eRAGE-Fc,eCD33-eRAGE-eTLR4-Fc,eTLR4-eCD33-eRAGE-Fc,eRAGE-eCD33-eTLR4-Fc,eTLR4-eRAGE-eCD33-Fc, andeRAGE-eTLR4-eCD33-Fc,wherein “eCD33” comprises the extracellular domain of human CD33,wherein “eTLR4” comprises the extracellular domain of TLR4,wherein “eRAGE” comprises the extracellular domain of RAGE,wherein “Fc” comprises the immunoglobulin Fc region, andwherein “-” consists of a peptide linker or a peptide bond.3. The fusion protein of claim 1 , further comprising a biotin acceptor peptide that can be biotinylated with biotin ligase (BirA) in the presence of biotin and ATP.4. A recombinant fusion protein claim 1 , comprising:(a) an S100A9-binding moiety selected from the group consisting of an extracellular domain of human CD33, an extracellular domain of toll like receptor 4 (TLR4), and an extracellular domain of Receptor for Advanced Glycation End Products (RAGE);(b) a biotin acceptor peptide that can be biotinylated with biotin ligase (BirA) in the presence of biotin and ATP; and(c) an immunoglobulin Fc region.5. The fusion protein of claim 4 , comprising a formula selected from the group consisting of:eCD33-Fc-Avi,eTLR4-Fc-Avi,eRAGE-Fc-Avi,eCD33-eTLR4-Fc-Avi,eCD33-eRAGE-Fc-Avi,eTLR4-eRAGE-Fc-Avi,eRAGE-eTLR4-Fc-Avi,eCD33-eTLR4-eRAGE-Fc- ...

PHOSPHOROUS DERIVATIVES AS KINASE INHIBITORS

The invention features compounds of the general formula: 2. The compound of in which Xis N.3. The compound of in which Xis N and Xis CRC.4. The compound of in which Xis CRand Xis CRC.5. The compound of in which Xis CR.6. The compound of in which Xis N and Xis CRC.7. The compound of in which Xis CRand Xis CRC.8. The compound of any of claim 5 , claim 5 , claim 5 , or in which Ris selected from Cl claim 5 , F claim 5 , C1-C4 alkyl claim 5 , trihaloalkyl claim 5 , cycloalkyl claim 5 , C2-C4 alkenyl claim 5 , and alkynyl.9. The compound of in which Xis CRand Xis CRwherein Rand R claim 1 , together with the atoms to which they are attached claim 1 , form a fused claim 1 , 5- claim 1 , 6- or 7-membered saturated claim 1 , partially saturated or unsaturated ring claim 1 , which contains 0-4 heteroatoms selected from N claim 1 , O and S(O)and which may bear up to four substituents.109. The compound of any of - in which s is 1 claims 1 , 2 claims 1 , 3 or 4 claims 1 , and each of the substituents W is independently selected from halo claims 1 , —R claims 1 , —OR claims 1 , —NRRand —P(═O)(R) claims 1 , wherein each Rand Rmoiety may be further substituted or unsubstituted.11. The compound of in which at least one substituent Ris —ORand Ris selected from C1-C6 alkyl claim 10 , C2-C6 alkenyl claim 10 , and C2-C6 alkynyl.12. The compound of or in which at least one substituent Ris a 5- claim 10 , 6- or 7-membered heterocyclic or 5- or 6-membered heteroaryl moiety claim 10 , linked to Ring A either directly or by an ether bond claim 10 , and which may be further substituted with 1-3 substituents independently selected from halo claim 10 , —CN claim 10 , —NO claim 10 , —OR claim 10 , —NRR claim 10 , —NR—NRR claim 10 , —C(O)YR claim 10 , —OC(O)YR claim 10 , —NRC(O)YR claim 10 , —SC(O)YR claim 10 , —NRC(═S)YR claim 10 , —OC(═S)YR claim 10 , —C(═S)YR claim 10 , —YC(═NR)YR claim 10 , —YC(═N—OR)YR claim 10 , —YC(═N—NRR)YR claim 10 , —YP(═O)(YR)(YR) claim 10 , —NRSOR claim 10 , —S(O)R ...

PHOSPHOROUS DERIVATIVES AS KINASE INHIBITORS

The invention features compounds of the general formula (I) in which the variable groups are as defined herein, and to their preparation and use. 2. The compound of in which Xis N.3. The compound of in which Xis N and Xis CR.4. The compound of in which Xis CRand Xis CR.5. The compound of in which Xis CR.6. The compound of in which Xis N and Xis CR.7. The compound of in which Xis CRand Xis CR.8. The compound of any of claim 5 , claim 5 , claim 5 , or in which Ris selected from Cl claim 5 , F claim 5 , C1-C4 alkyl claim 5 , trihaloalkyl claim 5 , cycloalkyl claim 5 , C2-C4 alkenyl claim 5 , and alkynyl.9. The compound of in which Xis CRand Xis CRwherein Rand R claim 1 , together with the atoms to which they are attached claim 1 , form a fused claim 1 , 5- claim 1 , 6- or 7-membered saturated claim 1 , partially saturated or unsaturated ring claim 1 , which contains 0-4 heteroatoms selected from N claim 1 , O and S(O)and which may bear up to four substituents.10. The compound of any of - in which s is 1 claim 1 , 2 claim 1 , 3 or 4 claim 1 , and each of the substituents Ris independently selected from halo claim 1 , —R claim 1 , —OR claim 1 , —NRRand —P(═O)(R) claim 1 , wherein each Rand Rmoiety may be further substituted or unsubstituted.11. The compound of in which at least one substituent Ris —ORand Ris selected from C1-C6 alkyl claim 10 , C2-C6 alkenyl claim 10 , and C2-C6 alkynyl.12. The compound of or in which at least one substituent Ris a 5- claim 10 , 6- or 7-membered heterocyclic or 5- or 6-membered heteroaryl moiety claim 10 , linked to Ring A either directly or by an ether bond claim 10 , and which may be further substituted with 1-3 substituents independently selected from halo claim 10 , —CN claim 10 , —NO claim 10 , —R claim 10 , —OR claim 10 , —O—NRR claim 10 , —NRR claim 10 , —NR—NRR claim 10 , —NR—OR claim 10 , —C(O)YR claim 10 , —OC(O)YR claim 10 , —NRC(O)YR claim 10 , —SC(O)YR claim 10 , —NRC(═S)YR claim 10 , —OC(═S)YR claim 10 , —C(═S)YR claim 10 , ...

Pixel structure

A pixel structure including a scan line, a data line, an active device, a pixel electrode, a capacitor electrode line, a semi-conductive pattern layer and at least one dielectric layer is provided. The active device is electrically connected to the scan line and the data line. The pixel electrode is electrically connected to the active device. The capacitor electrode line is located under the pixel electrode. A first storage capacitor is formed between the capacitor electrode line and the pixel electrode. The semi-conductive pattern layer is disposed between the capacitor electrode line and the pixel electrode, the pixel electrode is electrically connected to the semi-conductive pattern layer. A second storage capacitor is formed between the semi-conductive pattern layer and the capacitor electrode line. The dielectric layer is disposed between the capacitor electrode line and the pixel electrode and located between the semi-conductive pattern layer and the capacitor electrode line.

DRM PROTECTED VIDEO STREAMING ON GAME CONSOLE WITH SECRET-LESS APPLICATION

Techniques are disclosed for secure playback of protected multimedia content on a game console using a secret-less application. An SSO model can be used for client authentication at a key server, which eliminates the need of storing or using any secret information in the client application. Further, an encrypted content key generated by a content packager using a public key can be deployed in the key URI of a playlist file, which is sent to the key server. The key server can be configured to decrypt the content key using a corresponding private key. Further, the content key and unencrypted samples are protected in the game console client application from debugging and replay attacks by using additional security checks at both the client and key server. By storing secret information remotely from the game console and using the SSO model, DRM policies can be enforced on an untrusted client application. 1. A computer-implemented method comprising:receiving, from a client computing device via a communications network using a secure communications protocol, an access control credential and an encrypted content key associated with protected multimedia content;determining that the client computing device is authenticated based on the access control credential;in response to the determination, decrypting the encrypted content key using a private cryptographic key; andsending the decrypted content key to the client computing device via the communications network using the secure communications protocol, the decrypted content key being configured for use by the client computing device for accessing the protected multimedia content.2. The method of claim 1 , wherein the encrypted content key is encoded within a security token signed by a multimedia content server associated with the protected multimedia content.3. The method of claim 2 , further comprising receiving claim 2 , from the client computing device via the communications network using the secure communications ...

HETEROARYL COMPOUNDS FOR KINASE INHIBITION

Compounds and pharmaceutical compositions that modulate kinase activity, including mutant EGFR and mutant HER2 kinase activity, and compounds, pharmaceutical compositions, and methods of treatment of diseases and conditions associated with kinase activity, including mutant EGFR and mutant HER2 activity, are described herein. 1213.-. (canceled)220. The method according to claim 219 , wherein the compound of Formula V-1 is combined with the compound of Formula V-2 to form the compound of Formula I.221. The method according to claim 219 , wherein the compound of Formula V-1 is combined with the compound of Formula V-3 to form the compound of Formula I.222. The method according to claim 214 , wherein step a) is performed in the presence of AlClor FeCl.223. The method according to claim 222 , wherein step a) is performed in the presence of AlCl.224. The method according to claim 215 , wherein step b) is performed in the presence of a palladium catalyst and a base.225. The method according to claim 224 , wherein the Pd-catalyst is selected from Pd(OAc)and XantPhos claim 224 , Pddbaand XantPhos claim 224 , and PdCl(dppf); and the base is selected from CsCO claim 224 , NaOBu claim 224 , LiHMDS claim 224 , KPO claim 224 , KCO claim 224 , NaOMe and KOH.226. The method according to claim 225 , wherein the palladium catalyst is Pd(OAc)and XantPhos claim 225 , and the base is CsCO.227. The method according to claim 215 , wherein step b) is performed in the presence of an acid catalyst.228. The method according to claim 227 , wherein the acid catalyst is selected from TFA claim 227 , PTSA and HCl.229. The method according to claim 228 , wherein the acid catalyst is TFA.230. The method according to claim 215 , wherein step b) is performed in the presence of a base.231. The method according to claim 230 , wherein the base is selected from potassium carbonate claim 230 , sodium carbonate claim 230 , cesium carbonate claim 230 , and potassium carbonate.232. The method according to ...

TLR9 LIGAND TRAP

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. 1. A fusion protein , comprising a TLR9 extracellular domain peptide , and an IgG Fc domain.2. The fusion protein of claim 1 , defined by the formula:{'br': None, 'i': '−Fc,', 'TLR9'}wherein “TLR9” represents the TLR9 extracellular domain peptide,wherein “Fc” represents an IgG Fc domain, andwherein “-” represents a linker or hinge domain.3. The fusion protein of claim 1 , wherein the TLR9 extracellular domain peptide comprises the amino acid sequence SEQ ID NO:1 claim 1 , or a variant thereof having at least 90% sequence identity to SEQ ID NO:1.4. The fusion protein of claim 1 , wherein the IgG Fc domain is an IgG4 Fc domain.5. The fusion protein of claim 1 , comprising the amino acid sequence SEQ ID NO:7 claim 1 , or a variant thereof having at least 90% sequence identity to SEQ ID NO:7.6. A composition claim 1 , comprising the fusion protein of in a pharmaceutically acceptable excipient.7. A method of treating myelodysplastic syndrome (MDS) in a subject claim 6 , comprising ...

Compounds for Inhibiting Cell Proliferation in EGFR-Driven Cancers

The invention features compounds, pharmaceutical compositions and methods for treating patients who have an EGFR-driven cancer of Formula I: 11. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris H claim 1 , halo claim 1 , —CH claim 1 , —CF claim 1 , —CHCH claim 1 , —OCH claim 1 , —OCF claim 1 , —OCHCH claim 1 , —OCHCHN(CH)or —O-heterocyclyl.12. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris H claim 1 , Cl claim 1 , F claim 1 , Br claim 1 , I claim 1 , CN claim 1 , CH claim 1 , CF claim 1 , —CHCH═CH claim 1 , or cyclopropyl.13. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris H.1419-. (canceled)21. (canceled)2324-. (canceled)27. (canceled)29. (canceled)3041-. (canceled)42. A method for treating an EGFR-driven cancer in a subject claim 1 , said method comprising administering to said subject a therapeutically effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof.4351-. (canceled)52. A pharmaceutical composition comprising a compound of . This invention relates to pharmaceutical compositions and methods for inhibiting the proliferation of cells.In human clinical studies with non-small cell lung cancer (NSCLC) patients, the kinase inhibitors, erlotinib and gefitinib have been found to be effective, but in only a subset of patients. It was later determined that the responsive patients had certain mutations in the gene for epidermal growth factor receptor (EGFR). The mutant forms of EGFR are enzymatically active without the need for ligand stimulation. They are also particularly sensitive to kinase inhibitors like erlotinib and gefitinib, which competitively bind to the ATP binding site of the EGFR kinase domain. Those mutations have been cataloged and described at length in the scientific literature. They include small deletions or point mutations in the kinase domain as has previously been written ...

Bicyclic Heteroaryl Compounds

This invention relates to compounds of the general formula: 122.-. (canceled)25. The compound of claim 24 , wherein Ring A and Ring B are each independently a 5- or 6-membered aryl.26. The compound of claim 25 , wherein Ring C is imidazolyl.28. The compound of claim 27 , wherein Ring A and Ring B are each independently a 5- or 6-membered aryl.29. The compound of claim 28 , wherein Ring D is piperazinyl and Lis CH.30. The compound of claim 29 , wherein s is 0 claim 29 , m is 1 claim 29 , p is 1 claim 29 , Ris —CH claim 29 , Ris CF claim 29 , and Ris —CHor —CHCHOH.31. A pharmaceutical composition comprising a compound of or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier claim 23 , diluent or vehicle. The protein kinases are a large family of proteins which play a central role in the regulation of a wide variety of cellular processes. A partial, non limiting, list of such kinases includes abl, Akt, bcr-abl, Blk, Brk, c-kit, c-met, c-src, CDK1, CDK2, CDK3, CDK4, CDK5, CDK6, CDK7, CDK8, CDK9, CDK10, cRaf1, CSK, EGFR, ErbB2, ErbB3, ErbB4, Erk, Pak, fes, FGFR1, FGFR2, FGFR3, FGFR4, FGFR5, Fgr, flt-1, Fps, Frk, Fyn, Hck, IGF-1R, INS-R, Jak, KDR, Lck, Lyn, MEK, p38, PDGFR, PIK, PKC, PYK2, ros, tie, tie2, TRK and Zap70. Abnormal protein kinase activity has been related to several disorders, ranging from non-life threatening diseases such as psoriasis to extremely serious diseases such as cancers.In view of the large number of protein kinases and associated diseases, there is an ever-existing need for new inhibitors selective for various protein kinases which might be useful in the treatment of related diseases.This invention concerns a new family of acetylenic heteroaryl compounds and their use in treating cancers, bone disorders, metabolic disorders, inflammatory disorders and other diseases.The compounds of this invention have a broad range of useful biological and pharmacological activities, permitting their use in pharmaceutical ...

System and Method for Local Generation of Streaming Content with a Hint Track

Embodiments of a system and method for local generation of streaming content with a hint track are described. Embodiments may include receiving a first version of encrypted content comprising encrypted content samples that each include media content and non-content information. Embodiments may also include receiving a hint track including packet header information for a stream of media packets from which the media content was sourced, and offset information identifying locations of encrypted media content within the encrypted content samples. Embodiments may include generating a second version of the encrypted content for streaming, which may include, based on the information of the hint track, identifying the location of media content within the encrypted content samples. Embodiments may include generating media packets within the second version of the encrypted content, each of those media packets including header information from the hint track and the identified media content from the encrypted content samples. 1. A method , comprising:receiving a first version of encrypted content by a computing device comprising one or more encrypted content samples that each include media content and header information; packet header information for a stream of media packets from which the media content was sourced; and', 'offset information identifying one or more locations of encrypted media content within the encrypted content samples; and, 'receiving, by the computing device, a hint track comprisinggenerating, based on the hint track information by the computing device, a second version of the encrypted content formatted differently than the first version of encrypted content.2. The method of claim 1 , wherein the generating the second version of the encrypted content comprises identifying the one or more locations of media content within the one or more encrypted content samples and generating one or more media packets within the second version of the encrypted content ...

Low Latency Live Video Streaming

Techniques are disclosed for low latency live video streaming. A client can be configured to send a single HTTP request for live video streaming to a server. The server can be configured to push one or more video segments to the client in response to the request, following a pre-defined push strategy. For example, using a so-called all-push strategy, the client sends only one request to the server, and in response, the server sends all of the video segments to the client as soon as each segment is complete. The HTTP 2.0 protocol may be used for pushing the video from the server to the client. This technique eliminates the request explosion problem when small segments are used. Further, the number of segments pushed with each request can be varied, which is to facilitate adaptive bitrate switching. 1. A computer-implemented method comprising:generating a plurality of video segments, each segment representing a portion of multimedia content, as the respective portions of the multimedia content are received from a live content source;receiving, from a client computing device, only one HTTP request for at least two of the video segments; andpushing, from a server computer to the client computing device, the at least two video segments in accordance with a predefined push strategy without requiring separate HTTP requests from the client for each of the video segments.2. The method of claim 1 , wherein the pushing of the at least two video segments is performed using a stateless communication protocol.3. The method of claim 1 , wherein the request includes an HTTP GET request that indicates start and end segments within the plurality of video segments to be pushed to the client computing device.4. The method of claim 3 , wherein the predefined push strategy is an all-push strategy and the end segment is a last segment of the plurality of video segments.5. The method of claim 3 , wherein the predefined push strategy is a k-push strategy and the end segment is any segment ...

Pyrazinopyrazines and Derivatives as Kinase Inhibitors

This invention relates to compounds of the general formula: 2. A compound of in which n is 1.3. A compound of in which n is 2.4. A compound of any of to in which Q is N.5. A compound of any of to in which Q is CR.6. A compound of in which Ris an alkyl.7. A compound of in which Ris halo.8. A compound of any of to in which Lis a bond.9. A compound of any of to in which Lis C(O)Calkyl.10. A compound of any of to in which Lis C(O)NHCalkyl1110. A compound of any of to and to in which Wis aryl.1210. A compound of any of to and to in which Wis 5- or 6-membered heteroaryl.1310. A compound of any of to and to in which Wis a 5- claim 5 , 6- or 7-membered heterocyclyl.1410. A compound of any of to and to in which Wis a 3- to 8-membered carbocyclyl.15. A compound of any of to in which Lis CHor CH(CH).16. A compound of in which Lis CH.20. A compound of in which Q is N.21. A compound of in which Q is CR.22. A compound of in which Ris a lower alkyl or halo.23. A compound of in which n is 1.24. A compound of in which n is 2.25. A compound of in which Wand Ware aryl optionally substituted with 1-5 Rand 1-5 Rrespectively; and R is H.26. A compound of in which Wis a 5- or 6-membered heteroaryl optionally substituted with 1-5 Rand Wis an aryl optionally substituted with 1-5 Rrespectively; and R is H.27. A compound of any of to in which Lis C(O)Calkyl.28. A compound of in which Lis C(O).29. A compound of in which Lis C(O)CH.31. A compound of in which Wand Ware aryl optionally substituted with 1-5 Rand 1-5 Rrespectively.32. A compound of in which Wis a 5- or 6-membered heteroaryl optionally substituted with 1-5 R claim 30 , Wis an aryl optionally substituted with 1-5 R.33. A compound of in which Q is N.34. A compound of in which Q is CR.35. A compound of in which Ris a lower alkyl or halo.36. A compound of in which n is 1.37. A compound of in which n is 2.38. A method for treating cancer in a mammal in need thereof claim 30 , comprising administering to the mammal a therapeutically ...

Shower structure with hot air function

A shower structure with a hot air function includes a fixed base with a watertight switch, a shower head, and a hot air structure. The fixed base has a water supply end and a water outlet, and an end of the shower head is coupled to the water outlet, and the hot air structure includes one or more pipe members, one or more fans, and one or more electrical heating pipes, and plural air inlet holes and an air outlet are formed at the external periphery of the pipe member, and the fan and electrical heating pipe are installed in the pipe member, and the fan and electrical heating pipe are electrically connected to the switch of the fixed base. The shower structure facilitates users to blow dry their hair directly after taking a shower.

TLR9-BINDING CHIMERIC ANTIGEN RECEPTORS

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. 1. A chimeric antigen receptor (CAR) polypeptide , comprising a TLR9-binding region , a transmembrane domain , a signaling domain , and a co-stimulatory signaling region.2. The polypeptide of claim 1 , wherein the costimulatory signaling region comprises the cytoplasmic domain of a costimulatory molecule selected from the group consisting of CD27 claim 1 , CD28 claim 1 , CD7 claim 1 , 4-1BB claim 1 , OX40 claim 1 , CD30 claim 1 , CD40 claim 1 , PD-1 claim 1 , ICOS claim 1 , lymphocyte function-associated antigen-1 (LFA-1) claim 1 , CD2 claim 1 , CD7 claim 1 , LIGHT claim 1 , NKG2C claim 1 , B7-H3 claim 1 , a ligand that specifically binds with CD83 claim 1 , and any combination thereof.4. The polypeptide of claim 3 , wherein the spacer linking the TLR9-binding domain to the hinge domain comprises the amino acid sequence SEQ ID NO:11 or SEQ ID NO:12.5. The polypeptide of claim 3 , or wherein the spacer linking the transmembrane domain to the signal domain comprises an LCK-binding region of CD8alpha.6. The polypeptide of claim 5 , wherein the LCK-binding site has the amino acid sequence SEQ ID NO:31.7. The polypeptide of claim 1 , wherein the signaling domain comprises a CD3 zeta (CD3ζ) signaling domain.8. The polypeptide of claim 1 , wherein the TLR9-binding region comprises an amino acid sequence selected from the group consisting of SEQ ID NO:18 claim 1 , SEQ ID NO:19 claim 1 , SEQ ID NO:20 claim 1 , SEQ ID NO:21 claim 1 , SEQ ID NO:22 ...

SUPPORT STAND

A support stand includes a housing, a first limiting member, a linkage bar, a first elastic positioning device, and a first supporting arm. The housing defines a receiving groove and a first hollow portion. The receiving groove is configured to receive an electronic device. The first limiting member is fixed in the first hollow portion. The first limiting member defines a first limiting groove. The linkage bar and the first elastic positioning device are movably received in the first hollow portion. The first elastic positioning device is configured to partially limit the first limiting groove, thus the linkage bar is fixed to the housing. The first supporting arm is slidably and rotatably connected to the linkage bar. The first supporting arm is configured to form a desired angle with the housing, whereby the first supporting arm cooperates with the housing to support the housing and the electronic device. 1. A support stand comprising:a housing defining a receiving groove and a first hollow portion, wherein the receiving groove is configured to receive an electronic device;a first limiting member fixed in the first hollow portion and defining a first limiting groove;a linkage bar movably received in the first hollow portion, wherein the linkage bar comprises a first shaft, the first shaft passes through the housing to be exterior to the housing;a first elastic positioning device movably received in the first hollow portion and configured to be partially deformed by the first limiting groove and to partially resist and limit the first limiting groove, thereby the linkage bar being fixed to the housing, wherein the first elastic positioning device comprises a first washer and a first elastic member, the first washer is fixed to the first shaft, the first washer is configured to be deformed by the first limiting groove and to resist and limit the first limiting groove, the first elastic member is arranged between the housing and the first shaft, the first elastic ...

Photovoltaic module

A PV module includes a transparent substrate, a first solar cell unit, a crystalline silicon solar cell, and a spacer. The first solar cell unit is between the transparent substrate and the crystalline silicon solar cell, and the first solar cell unit includes a first electrode, a second electrode, and a I-III-VI semiconductor layer between the first electrode and the second electrode. The I-III-VI semiconductor layer includes at least gallium (Ga) and sulfur (S), and the energy gap thereof is more than that of crystalline silicon. Moreover, the crystalline silicon solar cell and the first solar cell unit are separated by the spacer.

TARGETED SENSITIZATION OF NON-DEL(5q) MALIGNANT CELLS

Disclosed are molecules for treating non-del(5q) MDS that mimic allelic deficiency in del5q MDS to sensitize the malignant clones of patient without del(5q). The disclosed molecule contains an inhibitor of Cdc25C, an inhibitor of PP2Acα, 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) meylodysplastic syndrome (MDS) in a subject by administering to the subject a therapeutically effective amount of the disclosed pharmaceutical composition. 1. A molecule comprisinga nucleic acid inhibitor of Cdc25C, a nucleic acid inhibitor of PP2Acα, or a combination thereof;a toll like receptor-9 (TLR9) targeting ligand; andlenalidomide, or an analogue or derivative thereof.2. The molecule of claim 1 , comprising the nucleic acid inhibitor of Cdc25C coupled to the nucleic acid inhibitor of PP2Acα by a bivalent linker.3. The molecule of claim 1 , wherein the TLR9 targeting ligand is coupled to the nucleic acid inhibitor of Cdc25C or the nucleic acid inhibitor of PP2Acα by a bivalent linker.4. The molecule of claim 1 , wherein the lenalidomide is coupled to the nucleic acid inhibitor of Cdc25C or the nucleic acid inhibitor of PP2Acα by a bivalent linker.5. The molecule of claim 1 , wherein the molecule is defined by the formula:{'br': None, 'TTL--IC--IP--LEN, or'}{'br': None, 'TTL--IP--IC--LEN,'}wherein “TTL ” represents a TLR9 targeting ligand,wherein “IC” represents an inhibitor of Cdc25C,wherein “IP ” represents an inhibitor of PP2Acα,wherein “LEN” represents an lenalidomide, or an analogue or derivative thereof, andwherein “--” represents a bivalent linker.6. The molecule of claim 1 , wherein the TLR9 targeting ligand is an unmethylated CpG oligodeoxynucleotide claim 1 , or an analogue or derivative thereof that ...

PHOSPHOROUS DERIVATIVES AS KINASE INHIBITORS

The invention features compounds of the general formula (I) in which the variable groups are as defined herein, and to their preparation and use. 222-. (canceled) The protein kinases represent a large family of proteins which play a central role in the regulation of a wide variety of cellular processes and maintain control over cellular function. A partial, non limiting, list of such kinases includes ALK, abl, Akt, bcr-abl, Blk, Brk, c-kit, c-met, c-src, CDK1, CDK2, CDK3, CDK4, CDK5, CDK6, CDK7, CDK8, CDK9, CDK10, bRaf, cRaf1, CSK, EGFR, ErbB2, ErbB3, ErbB4, Erk, Pak, fes, FGFR1, FGFR2, FGFR3, FGFR4, FGFR5, Fgr, fit-1, fit-3, Fps, Frk, Fyn, Hck, IGF-1R, INS-R, Jak1, Jak2, Jak3, KDR, Lck, Lyn, FAK, MEK, p38, PDGFR, PIK, PKC, PYK2, ros, tie, tie2, Pim-1, P13k, TRK and Zap70. Abnormal protein kinase activity has been related to several disorders, ranging from non-life threatening diseases such as psoriasis to extremely serious diseases such as cancers.In view of this large number of protein kinases and the multitude of protein kinase-related diseases, there is an ever-existing need to provide new classes of compounds with increased selectivity that are useful as protein kinase inhibitors and therefore useful in the treatment of protein tyrosine-kinase related diseases.The invention concerns a new family of phosphorous compounds and their use in treating cancers and other diseases.Compounds of the invention can have a broad range of useful biological and pharmacological activities, permitting their use in pharmaceutical compositions and methods for treating cancer (including lymphoma, solid tumors and leukemia among other cancers), including, also among others, advanced cases and cases which are resistant or refractory to one or more other treatments.Included are compounds of Formula I, and tautomers and pharmaceutically acceptable salts and solvate thereof:whereinXis NRor CR;Xis NRor CR;Xis NRor CR;Xis NRor CR;Ring A is an aryl, a 5- or a 6-membered heteroaryl ring ...

TLR9 TARGETED CYTOTOXIC AGENTS

Disclosed are compositions and methods for targeted treatment of TLR9-expressing cancers. In particular, molecules containing a TLR9 targeting ligand, such as a CpG oligodeoxynucleotide, that target cytotoxic agents to TLR9-expressing malignant cells are disclosed. Compositions and methods are disclosed for targeted treatment of cancer or cancer-stem cells with extracellular TLR9 expression, such as primary human MDS progenitors and hematopoietic stem cell (HSC). In particular, molecules containing TLR9 targeting ligands that target cytotoxic agents to TLR9-expressing malignant cells are disclosed. 1. A molecule comprising a toll like receptor-9 (TLR9) targeting ligand conjugated to a cytotoxic agent.2. The molecule of claim 1 , wherein the molecule is defined by the formula:{'br': None, 'TTL-CA,'}wherein “TTL” represents the TLR9 targeting ligand,wherein “CA” represents cytotoxic agent, andwherein “-” represents a bivalent linker.3. The molecule of claim 1 , wherein the cytotoxic agent comprises a lytic peptide.4. The molecule of claim 1 , wherein the TLR9 targeting ligand is an unmethylated CpG oligodeoxynucleotide claim 1 , or an analogue or derivative thereof that binds TLR9.5. The molecule of claim 3 , wherein the lytic peptide comprises the amino acid sequence PNPNNNPNPN (SEQ ID NO:48) claim 3 , wherein “P” is any polar amino acid claim 3 , and wherein “N” is any non-polar amino acid.6. The molecule of claim 5 , wherein the lytic peptide comprises the amino acid sequence KIKMVISWKG (SEQ ID NO:1).7. The molecule of claim 1 , wherein the cytotoxic agent comprises a functional nucleic acid that inhibits an anti-apoptotic gene target.8. The molecule of claim 7 , wherein the anti-apoptotic gene target comprises Bcl-2 claim 7 , Bcl-xL claim 7 , Mcl-1 claim 7 , or a combination thereof.9. A pharmaceutical composition comprising the molecule of in a pharmaceutically acceptable carrier.10. A method for treating a TLR9-positive cancer in a subject claim 9 , comprising ...

Tandem solar cell module

A tandem solar cell module includes a transparent substrate, a first solar cell unit, and a second solar cell unit disposed between the transparent substrate and the first solar cell unit. The first solar cell unit includes a first electrode, a second electrode, and a first absorption layer disposed between the first electrode and the second electrode, and the second solar cell unit includes a third electrode, a fourth electrode, and a second absorption layer disposed between the third electrode and the fourth electrode, wherein the second electrode is located adjacent to the third electrode, and the positions of the second electrode, the third electrode, and the fourth electrode are corresponding to each other.

AMINOTHIAZOLE COMPOUNDS AS C-KIT INHIBITORS

The invention relates to c-Kit inhibitors useful in the treatment of cancers, and other -threonine kinase mediated diseases, having the Formula: (I) wherein A, L, R, R, R, and n are described herein. 2. The compound of claim 1 , wherein L is a —C(O)NR—.3. The compound of claim 1 , wherein L is a —NRC(O)—.4. The compound of any one of the preceding claims claim 1 , wherein Ris (C-C) alkyl or halogen.5. The compound of any one of the preceding claims claim 1 , wherein n is 1 and Ris methyl or F.6. The compound of any one of the preceding claims claim 1 , wherein n is 1 and Ris methyl.7. The compound of any one of the preceding claims claim 1 , wherein A is (C-C) aryl optionally substituted with one or more R.8. The compound of any one of the preceding claims claim 1 , wherein A is 6-membered heteroaryl optionally substituted with one or more R;9. The compound of any one of the preceding claims claim 1 , wherein A is phenyl or pyridinyl optionally substituted with one or more R.10. The compound of any one of the preceding claims claim 1 , wherein A is phenyl or pyridinyl substituted with one or more R.11. The compound of any one of the preceding claims claim 1 , wherein Ris H.12. The compound of any one of the preceding claims claim 1 , wherein n is 0.13. The compound of any one of the preceding claims claim 1 , wherein n is 1.14. The compound of any one of the preceding claims claim 1 , wherein n is 1 and Ris ortho to the alkyne.15. The compound of any one of the preceding claims claim 1 , wherein Ris H claim 1 , —C(O)N(CH)or —CHCHC(O)OH.16. The compound of any one of the preceding claims claim 1 , wherein Ris H.20. The compound of claim 19 , wherein Ris H.21. The compound of or claim 19 , wherein one Ris (C-C) haloalkyl and the other Ris (C-C) alkoxy claim 19 , CN claim 19 , or —(C(R))-heterocycloalkyl wherein the heterocycloalkyl comprises a 4- to 7-membered ring and 1 to 3 heteroatoms selected from N claim 19 , O claim 19 , and S.22. The compound of any one of to ...

Phosphorous Derivatives as Kinase Inhibitors

The invention features compounds of the general formula: 142-. (canceled)46. The compound of in which Xis N.47. The compound of in which Xis N and Xis CR.48. The compound of in which Xis CRand Xis CR.49. The compound of in which Xis CR.50. The compound of in which Xis N and Xis CR.51. The compound of in which Xis CRand Xis CR.52. The compound of in which Ris selected from Cl claim 43 , F claim 43 , C-Calkyl claim 43 , trihaloalkyl claim 43 , cycloalkyl claim 43 , C-Calkenyl claim 43 , and alkynyl.53. The compound of in which Xis CRand Xis CRwherein Rand R claim 43 , together with the atoms to which they are attached claim 43 , form a fused claim 43 , 5- claim 43 , 6- or 7-membered saturated claim 43 , partially saturated or unsaturated ring claim 43 , which contains 0-4 heteroatoms selected from N claim 43 , O and S(O)and which may bear up to four substituents.54. The compound of in which s is 1 claim 43 , 2 claim 43 , 3 or 4 claim 43 , and each of the substituents Ris independently selected from halo claim 43 , —R claim 43 , —OR claim 43 , —NRRand —P(═O)(R) claim 43 , wherein each Rand Rmoiety may be further substituted or unsubstituted.55. The compound of in which at least one substituent Ris —ORand Ris selected from C-Calkyl claim 54 , C-Calkenyl claim 54 , and C-Calkynyl.56. The compound of in which at least one substituent Ris a 5- claim 54 , 6- or 7-membered heterocyclic or 5- or 6-membered heteroaryl moiety claim 54 , linked to Ring A either directly or by an ether bond claim 54 , and which may be further substituted with 1-3 substituents independently selected from halo claim 54 , —CN claim 54 , —NO claim 54 , —R claim 54 , —OR claim 54 , —O—NRR claim 54 , —NRR claim 54 , —NR—NRR claim 54 , —NR—OR claim 54 , —C(O)YR claim 54 , —OC(O)YR claim 54 , —NRC(O)YR claim 54 , —SC(O)YR claim 54 , —NRC(═S)YR claim 54 , —OC(═S)YR claim 54 , —C(═S)YR claim 54 , —YC(═NR)YR claim 54 , —YC(═N—OR)YR claim 54 , —YC(═N—NRR)YR claim 54 , —YP(═O)(YR)(YR) claim 54 , —Si(R) claim ...

MONOCYCLIC HETEROARYL COMPOUNDS

This invention relates to compounds of the general formula: 4. A compound according to claim 3 , wherein Rings A and B are aryl.5. A compound of wherein Ring C is a heteroaryl ring.6. A compound of wherein Ring C is an imidazole ring.8. A compound of wherein Ris independently selected from —CH claim 7 , or —C(O)NH claim 7 , v is 1 claim 7 , n is 0 or 1 claim 7 , m is 1 claim 7 , t is 1 claim 7 , Ris —CH claim 7 , Ris CFand Ris —CH.10. A compound according to wherein Rings A and B are aryl.11. A compound of wherein Ring D is a substituted or unsubstituted piperazine ring and Lis CH.12. A compound of wherein Ring D is a substituted or unsubstituted heteroaryl.14. A compound of wherein Ris independently selected from —CHand —C(O)NH claim 13 , n is 0 or 1 claim 13 , m is 1 claim 13 , t is 1 claim 13 , Ris methyl claim 13 , Ris CF claim 13 , one of Ris selected from methyl and CHCHOH.15. A method for treating cancer in a mammal in need thereof claim 13 , comprising administering to the mammal a therapeutically effective amount of a compound of any of - or a pharmaceutically acceptable salt claim 13 , solvate or hydrate thereof.16. A composition comprising a compound of any of - or a pharmaceutically acceptable salt claim 13 , solvate or hydrate thereof and a pharmaceutically acceptable carrier claim 13 , diluent or vehicle. The protein kinases represent a large family of proteins, which play a central role in the regulation of a wide variety of cellular processes and maintaining control over cellular function. A partial, non limiting, list of such kinases includes abl, Akt, bcr-abl, Blk, Brk, c-kit, c-met, c-src, CDK1, CDK2, CDK3, CDK4, CDK5, CDK6, CDK7, CDK8, CDK9, CDK10, cRaf1, CSK, EGFR, ErbB2, ErbB3, ErbB4, Erk, Pak, fes, FGFR1, FGFR2, FGFR3, FGFR4, FGFR5, Fgr, flt-1, Fps, Frk, Fyn, Hck, IGF-1R, INS-R, Jak, KDR, Lck, Lyn, MEK, p38, PDGFR, PIK, PKC, PYK2, ros, tie, tie2, TRK and Zap70. Abnormal protein kinase activity has been related to several disorders, ranging ...

ICARIIN DERIVATIVES

Disclosed are derivatives of icariin. Disclosed are compounds having Formula I-VIII as defined herein. Methods of using these compounds for the treatment of cancer and inflammation are also disclosed. 119-. (canceled)22. The method of claim 20 , wherein the compound decreases the accumulation and activation of myeloid derived suppressor cells. This application is a continuation of U.S. application Ser. No. 15/113,500, filed Jul. 22, 2016, which is a § 371 U.S. National phase of PCT/US2015/012749, filed Jan. 23, 2015, and which claims the benefit of priority to U.S. Provisional Application 61/930,757, filed Jan. 23, 2014, and U.S. Provisional Application 61/977,985, filed Apr. 10, 2014, the disclosures of each are incorporated herein by referenced in their entireties.Inflammation is a hallmark of cancer and promotes the development and progression of cancer as well as the invasion of the immune system by tumor cells. Inflammation-induced cancer can be attributed to myeloid-derived suppressor cells (MDSCs), which accumulate in tumor bearing hosts, particularly in the local tumor microenvironment. MDSCs, characterized as Gr1 CD11b in mice and HLA-DRLin CD33 in humans, were identified as the major immune creator of an immunosuppressive and tumorigenic microenvironment (Gabrilovich D I, Nagaraj S. 2009; 9(3):162-74). In healthy individuals, these cells exist as immature myeloid cells (IMC) and are part of normal myelopoiesis as they can quickly differentiate into mature monocytes, DC and neutrophils. However, under certain pathological situations, including inflammation and cancer, these IMCs are activated and accumulate in local tissues where they act both as tumor promoting and immunosuppressive cells through the release of soluble angiogenic and suppressive factors, such as VEGF, TGFβ, IL-6, or IL-10. They can also directly suppress tumor-specific CD4 and CD8 T-cell responses and induce CD4 CD25FOXP3 regulatory T cells (Tregs). Moreover, they can also contribute ...

TETRAVALENT TLR9 BISPECIFIC ANTIBODY

Disclosed are compositions and methods for targeted treatment of TLR9-expressing cancers, such as primary human MDS progenitors and hematopoietic stem cell (HSC), as well as lung and breast cancers. In particular, multispecific, multivalent antibodies are disclosed that are able to engage T-cells to destroy TLR9-expressing malignant cells. 1. A fusion polypeptide comprising the following formula:{'br': None, 'sub': L', 'H', 'L', 'H, 'VI-VT-VT-VI, or'}{'br': None, 'sub': H', 'L', 'H', 'L, 'VT-VI-VI-VT,'}{'sub': 'L', 'wherein “VI” is a light chain variable domain specific for an immune cell antigen;'}{'sub': 'H', 'wherein “VT” is a heavy chain variable domain specific for TLR9;'}{'sub': 'L', 'wherein “VT” is a light chain variable domain specific for TLR9;'}{'sub': 'H', 'wherein “VI” is a heavy chain variable domain specific for the immune cell antigen;'}wherein “-” consists of a peptide linker or a peptide bond.2. The fusion polypeptide of claim 1 , wherein the immune cell antigen is CD3.3. A tetravalent bi-specific antigen binding molecule claim 1 , comprising a dimer formed from a first fusion polypeptide of and a second fusion polypeptide of claim 1 ,{'sub': L', 'H, 'wherein the VI of the first polypeptide is in association with the VI of the second polypeptide to form an antigen binding site for the immune cell antigen;'}{'sub': H', 'L, 'wherein the VT of the first polypeptide is in association with the VT of the second polypeptide to form an antigen binding site for TLR9;'}{'sub': L', 'H, 'wherein the VT of the first polypeptide is in association with the VT of the second polypeptide to form an antigen binding site for TLR9; and'}{'sub': H', 'L, 'wherein the VI of the first polypeptide is in association with the VI of the second polypeptide to form an antigen binding site for the immune cell antigen.'}4. (canceled)5. The antigen binding molecule of claim 2 , wherein the first and second polypeptide are non-covalently associated.6. A pharmaceutical composition ...

TARGETED SENSITIZATION OF NON-DEL(5q) MALIGNANT CELLS

Disclosed are molecules for treating non-del(5q) MDS that mimic allelic deficiency in del5q MDS to sensitize the malignant clones of patient without del(5q). The disclosed molecule contains an inhibitor of Cdc25C, an inhibitor of PP2Acα, 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) meylodysplastic syndrome (MDS) in a subject by administering to the subject a therapeutically effective amount of the disclosed pharmaceutical composition. 1. A molecule comprisinga nucleic acid inhibitor of Cdc25C, a nucleic acid inhibitor of PP2Acα, or a combination thereof;a toll Like receptor-9 (TLR9) targeting ligand; andlenalidomide, or an analogue or derivative thereof.2. The molecule of claim 1 , comprising the nucleic acid inhibitor of Cdc25C coupled to the nucleic acid inhibitor of PP2Acα by a bivalent linker.3. The molecule of claim 1 , wherein the TLR9 targeting ligand is coupled to the nucleic acid inhibitor of Cdc25C or the nucleic acid inhibitor of PP2Acα by a bivalent linker.4. The molecule of claim 1 , wherein the lenalidomide is coupled to the nucleic acid inhibitor of Cdc25C or the nucleic acid inhibitor of PP2Acα by a bivalent linker.5. The molecule of claim 1 , wherein the molecule is defined by the formula:{'br': None, 'TTL-IC-IP-LEN, or'}{'br': None, 'TTL-IP-IC-LEN,'}wherein “TTL ” represents a TLR9 targeting ligand,wherein “IC” represents an inhibitor of Cdc25C,wherein “IP” represents an inhibitor of PP2Acα,wherein “LEN” represents an lenalidomide, or an analogue or derivative thereof, andwherein “-” represents a bivalent linker.6. The molecule of claim 1 , wherein the TLR9 targeting ligand is an unmethylated CpG oligodeoxynucleotide claim 1 , or an analogue or derivative thereof that binds TLR9 ...

ANILINOPYRIMIDINES AS HAEMATOPOIETIC PROGENITOR KINASE 1 (HPK1) INHIBITORS

The invention relates to HPK inhibitors useful in the treatment of cancers, and other serine-threonine kinase mediated diseases, having the Formula: where A, R, R, R, R, R, R, R, R, X, X, X, X, m, and n are described herein. 2. The compound of claim 1 , wherein Xis N.3. The compound of claim 1 , wherein Xis CH.4. The compound of or claim 1 , wherein Xis CH.5. The compound of or claim 1 , wherein Xis N.6. The compound of any one of - claim 1 , wherein Xis CRR.7. The compound of any one of - claim 1 , wherein A is Caryl.8. The compound of any one of - claim 1 , wherein A is phenyl.9. The compound of any one of - claim 1 , wherein A is 5- or 6-membered heteroaryl.10. The compound of any one of - claim 1 , wherein Rand Rare Calkyl.11. The compound of claim 10 , wherein Rand Rare each —CH.12. The compound of claim 10 , wherein Rand Rare each —CHCH.13. The compound of any one of - claim 10 , wherein Ris selected from the group consisting of halogen claim 10 , Calkyl claim 10 , and Calkoxy.14. The compound of claim 13 , wherein Ris methoxy claim 13 , ethoxy claim 13 , ethyl claim 13 , fluoro or chloro.15. The compound of claim 14 , wherein Ris methoxy.16. The compound of any one of - claim 14 , wherein Ris selected from the group consisting of H claim 14 , halogen claim 14 , Calkyl claim 14 , Chaloalkyl claim 14 , and Calkenyl.17. The compound of claim 16 , wherein Ris fluoro claim 16 , chloro claim 16 , CF claim 16 , ethyl or ethenyl.18. The compound of claim 17 , wherein Ris fluoro or chloro.19. The compound of claim 18 , wherein Ris chloro.20. The compound of any one of - claim 18 , wherein Ris methoxy and Ris chloro.21. The compound of any one of - claim 18 , wherein m+n=0.22. The compound of any one of - claim 18 , wherein m+n=1.23. The compound of any one of - claim 18 , wherein m+n=2.24. The compound of claim 22 , wherein m is 0 and n is 1.25. The compound of claim 22 , wherein m is 1 and n is 0.26. The compound of claim 23 , wherein m is 0 and n is 2.27. The ...

soluble cd33 to treat myelodysplastic syndromes (mds)

são reveladas composições e métodos para o tratamento de doença ou condição causada ou exacerbada pela atividade de s100a9, como as síndromes mielodisplásicas (mds), utilizando uma composição que compreende uma quantidade eficaz de um inibidor de cd33/s100a9. Compositions and methods for treating disease or condition caused or exacerbated by s100a9 activity, such as myelodysplastic syndromes (mds), are disclosed using a composition comprising an effective amount of a cd33 / s100a9 inhibitor.

Granular fertilizer and method of producing the same

【課題】粒状肥料及びその製造方法の提供。【解決手段】本発明の粒状肥料及びその製造方法は、造粒原料を押し出すか、或いは捏ねて原料顆粒を形成する工程と、少なくとも１つの表面材料を油剤に散布し、スプレー液を製作する工程と、該スプレー液を霧化した後、該原料顆粒に噴き付けて表面コーティングを形成し、該原料顆粒の表面を覆う工程と、該原料顆粒を乾燥させて粒状肥料を形成する工程と、を含む。【選択図】図１

Wwan printed circuit antenna with three monopole antennas disposed on a same plane

A WWAN printed circuit antenna includes three monopole antennas in the printed circuit board. Signals are fed in from the feed monopole antenna. The first and second radiating monopole antennas are actuated by the feed monopole antenna in an electromagnetic coupling way. Therefore, a three-dimensional structure derived from the planar inverted-F antenna can be replaced, and the limitation of space usage can be overcome.

Improvement of solar power generation system inverter

Method and device for writing blockchain data in parallel, computer equipment and storage medium thereof

The present invention makes public a method of writing blockchain data in parallel, corresponding device and computer equipment. The method comprises: employing a first thread to write received current block into structure file of blockchain, employing a second thread to verify transaction endorsement of current block, and obtaining verification result; employing, if verification of transaction endorsement is passed, second thread to write verification result into structure file, and employing a third thread to update status database of blockchain according to current block; if execution results of threads all exhibit successful, employing third thread to update history database of blockchain according to current block. Through coordination of threads, one correct ledger writing-in achieved only when all threads have successfully executed, so ledgers of various nodes are maintained consistent, while enhancing overall transaction performance of blockchain network, reducing transaction delay, flexibly allocating computational tasks, and avoiding waste of computational resources.

Head structure of electronic card connector

Granular fertilizer and method of manufacturing thereof

A granular fertilizer and a method of manufacturing the granular fertilizer are provided. The method comprises a step of molding or rolling a material into a granule, a step of preparing a solution by mixing at least one surface additive with an oil, a step of spraying the solution on the granule to form a layer on the surface of the granule, and a step of drying the granule to form the granular fertilizer.

Method for acquiring cross-domain separation paths, path computation element and related storage medium

Heteroaryl compounds for kinase inhibition.

En la presente se describen compuestos y composiciones farmacéuticas que modulan la actividad de cinasa, incluyendo la actividad de cinasa de EGFR mutante y HER2 mutante, y compuestos, composiciones farmacéuticas y métodos de tratamiento de enfermedades y afecciones asociadas con la actividad de cinasa, incluyendo actividad de EGFR mutante y HER2 mutante.

Drawer slide locating system

A drawer slide locating system includes an outer rail having a bracket at its front end, an inner rail, and a bearing carrier disposed between the inner rail and the outer rail. The bracket contains a locking piece toward the bearing carrier. Two wings extend from both sides of the locking piece to define a leverage axis. A slot is disposed on the outer rail. The locking piece having one lower end adapted with a hooking portion and another end being held against by the bearing carrier. The hooking portion raises to hold against the bottom of the bearing carrier and secure the bearing carrier in place.

Electrolytic device

Slide assembly for a rack

Compound animation showing user interactions

An online system presents a content item to users and receives selections of reaction icons from the users. The online system generates a background animation with the selected reaction icons and a foreground animation to be layered on top of the background animation. The online system sends the background and foreground animations to a client device to be cached. Further, the online system presents the content item to a viewing user associated with the client device and receives a selection of a reaction icon from the viewing user. The online system selects a subset of the users based on the viewing user's affinity to the users, retrieves images of the selected users, and send the images to the client device. The client device customizes the background and foreground animations based on the images and the viewing user's reaction icon to generate a compound animation for display to the viewing user.

Method for improving color tone of reclaimed bis(2-hydroxyethyl)terephthalate with ionic liquid

【課題】本発明は、高効率で不純物を除去する効果を果たせる、イオン液体で再生ビス（２－ヒドロキシエチル）テレフタラートの色合いを改良する方法を提供する。【解決手段】イオン液体で再生ビス（２－ヒドロキシエチル）テレフタラートの色合いを改良する方法は、再生すべきポリエステル織物を提供することと、化学解重合液で前記再生すべきポリエステル織物に化学解重合を行うことにより、解重合物を形成することと、前記解重合物と水とを混合することで、水相液体を形成することと、イオン液体不純物吸着材料を前記水相液体に分散させることで、前記再生すべきポリエステル織物に存在した不純物を吸着することと、を含む。【選択図】図１

Consortium-blockchain-based method and system for movable-collateral supervision

A method and an apparatus for supervising chattel collateral based on a consortium blockchain, the method comprising: a first node uploads acquired collateral information and/or warning information to a blockchain, the collateral information comprising a chattel serial number and an ID of a monitoring device monitoring the collateral (S1); after the successful settlement of the collateral information and/or warning information, triggering a corresponding monitoring event to push the collateral information and/or the warning information to a second node (S2); after storing the received collateral information and/or warning information, the second node checks whether the collateral information is complete and, if incomplete, then post-uploads the missing information to the blockchain (S3). By means of storing the collateral information in the blockchain, the present method ensures that the collateral information cannot be tampered with or forged once on the blockchain, and ensures that the collateral information looked up by financing parties, financial institutions, and warehousing parties is consistent; using a combined blockchain and Internet of Things method, warning information is uploaded to the blockchain and then pushed to a financial institution, ensuring the authenticity, reliability and traceability of the warning information.

Trapping and counting system for prsts

Photomask, manufacturing method of conducting wiring of flat display panel and wiring structure of flat display panel

Thin film transistor array substrate and method for fabricating the same

Heteroaryl compounds for kinase inhibition.

Burada, mutant EGFR ve mutant HER2 kinaz aktivitesi dahil olmak üzere kinaz aktivitesini modüle eden bileşikler ve farmasötik bileşimler ve mutant EGFR ve mutant HER2 aktivitesi de dahil olmak üzere kinaz aktivitesi ile ilişkili hastalıkların ve durumların tedavisi için bileşikler, farmasötik bileşimler ve yöntemler tarif edilmektedir. Described herein are compounds and pharmaceutical compositions that modulate kinase activity, including mutant EGFR and mutant HER2 kinase activity, and compounds, pharmaceutical compositions, and methods for treating diseases and conditions associated with kinase activity, including mutant EGFR and mutant HER2 activity.

Locating structure for a slide assembly

A locating structure for a slide assembly includes a first track, a second track, a releasing member, and a locating member; a locating tab is provided at a front end of the first track; the second track is inserted and connected onto the first track to slide thereon; the second track is provided with a locating portion; the releasing member is mounted to an inner side of the second track; one end of the releasing member is provided with an operation button; the locating member is located on one side of the operation button and has a propped portion and a plunged portion; the locating member provides resilience for the propped portion to hold against the locating portion of the second track; and the locating member drives the propped portion to disengage from the locating portion by means of the plunged portion.

Complementary deep-sea multi-energy integration platform for power generation, production, living and exploration

【課題】発電・生産・生活・探査のための補完式深海マルチエネルギー統合プラットフォームを提供する。【解決手段】支柱キャビン、プラットフォーム上部ハウジング、プラットフォーム下部ハウジングおよびガイドコラムを含み、支柱キャビン、ガイドコラム、プラットフォーム下部ハウジングとプラットフォーム上部ハウジングが相互に接続されて中空キャビンを有する三角形プラットフォームを構成し、中空キャビン内に網が設けられて海洋養殖ゾーンを形成するプラットフォーム本体と、プラットフォーム上部ハウジングの頂面端部に設けられた風力発電機、プラットフォーム上部ハウジングの頂面中央部の上方に設けられたソーラーパネル、ガイドコラムに設けられた波力発電装置、プラットフォーム下部ハウジングの頂面に設けられたいくつかの潮流エネルギー発電装置を含む持続可能な電力供給システムと、を含む。【選択図】図１

Method and device for writing blockchain data in parallel, computer equipment and storage medium thereof

The present invention makes public a method of writing blockchain data in parallel, corresponding device and computer equipment. The method comprises: employing a first thread to write received current block into structure file of blockchain, employing a second thread to verify transaction endorsement of current block, and obtaining verification result; employing, if verification of transaction endorsement is passed, second thread to write verification result into structure file, and employing a third thread to update status database of blockchain according to current block; if execution results of threads all exhibit successful, employing third thread to update history database of blockchain according to current block. Through coordination of threads, one correct ledger writing-in achieved only when all threads have successfully executed, so ledgers of various nodes are maintained consistent, while enhancing overall transaction performance of blockchain network, reducing transaction delay, flexibly allocating computational tasks, and avoiding waste of computational resources.

Three-dimensional printing method and three-dimensional printing apparatus

A three-dimensional printing apparatus and a three-dimensional printing method are provided. The method includes following step. An extending path associated with a first feeding path is obtained according to a feeding endpoint and at least one feeding point of the first feeding path. A printing head is controlled to move along the first feeding path according to a printing speed and to feed a forming material. The printing head is controlled to move along the extending path to an extending point according to a first speed, and to stop feeding the forming material, wherein the first speed is less than the printing speed. The printing head is controlled to move along a direction away from the extending point according to a second speed, wherein the second speed is greater than the printing speed.

Concrete containing rice hull ash

Structure of artificial implant

Wireless communication system with the device that detect transmission mode of communication signal

Pixel structure of active matrix organic light-emitting display, and method for manufacturing the same

【目的】スパッタリングによる有機発光層へのダメージを最小限にし、より優れた高い光透過率および開口率を備えたＡＭＯＬＥＤディスプレイの画素構造を提供する。 【解決手段】アクティブマトリックス有機発光ディスプレイの画素構造とその製造方法が提供され、その方法中、透明電極と有機発光ダイオードと反射電極とが基板上に形成された後、少なくとも１つのスイッチング薄膜トランジスターと、少なくとも１つの駆動薄膜トランジスターと、走査線と、データ線と、蓄積キャパシターとが基板上に形成される。 【選択図】図４

Phosphorous derivatives as kinase inhibitors

Heteroaryl compounds for kinase inhibition

Compounds and pharmaceutical compositions that modulate kinase activity, including mutant EGFR and mutant HER2 kinase activity, and compounds, pharmaceutical compositions, and methods of treatment of diseases and conditions associated with kinase activity, including mutant EGFRand mutant HER2 activity, are described herein.