Phosphorylated Twist1 and cancer

The present application relates to methods for treating cancer in a subject by modulating the phosphorylation of the Serine 42 of Twist1 by administering to said subject a therapeutically effective amount of a modulator of said phosphorylation of the Serine 42 of Twist1. Antibodies, uses methods and biomarkers based on the phosphorylation of the Serine 42 of Twist1 are also provided. 1. A method for treating cancer in a subject by modulating the phosphorylation of the Serine 42 of Twist1 by administering to said subject a therapeutically effective amount of a modulator of said phosphorylation of the Serine 42 of Twist1.2. The method of wherein the phosphorylation of the Serine 42 of Twist1 is modulated by an inhibitor which specifically binds to Twist1 and hinders the phosphorylation of its Serine 42 by PKB.3. The method of wherein the inhibitor is an antibody or a small molecule.4. The method of wherein the modulator is a peptide comprising an amino acid corresponding to the Serine 42 of Twist1 claim 1 , which fragment is recognized and phosphorylated by PKB at said amino acid corresponding to the Serine 42 of Twist1.5. The method of wherein the subject is a mammal.6. The method of wherein the epithelial-mesenchymal transition of cancer cells and/or metastasis formation is reduced.7. The method of wherein the cancer is a colorectal cancer claim 1 , a breast cancer claim 1 , a lung cancer or a prostate cancer.8. (canceled)9. A peptide comprising an amino acid corresponding to the Serine 42 of Twist1 claim 1 , which peptide is recognized and phosphorylated by PKB at said amino acid corresponding to the Serine 42 of Twist1.10. A method for the identification of a substance that modulates a PKB signaling pathway claim 1 , which method comprises the step of assessing the phosphorylation of the Serine 42 of Twist1.11. A method of diagnosing cancer comprising the step of assessing the phosphorylation of the Serine 42 of Twist1.12. The method of claim 11 , wherein an ...

METHOD OF AND SYSTEM FOR CALIBRATING GAS FLOW DILUTORS

The preferred embodiments described herein make possible to use lower cost, fixed flow components, such as critical orifices, which are fast to stabilise to a steady flow. These cannot be adjusted to achieve equal flows but are selected to be sensibly close to their desired flow values. This embodiment determines the true ratios of the flows of all of the flow controlling components. Actual flows are not measured but near equal flows are each fed to a common flow meter and the ratio of the indicated flow meter readings is taken to be the same as the ratio of the flows. Two, near equal flows are then combined and compared to a single flow of approximately the same value, and so on. The flow meter is used only to compare near equal flows so does not need to be calibrated nor linear over a wide range. 119-. (canceled)21. A method according to claim 20 , wherein at least one of said components is coupled to provide diluent gas in said dilutor and at least one other of said components is coupled to provide standard gas to be diluted.22. A method according to claim 20 , wherein said fixed flow fluid components are provided with critical orifices claim 20 , capillaries or non-critical orifices.23. A method according to claim 20 , wherein said fixed flow components have capacities of at least 1 claim 20 , 1 and 2 units of flow respectively.24. A method according to claim 20 , including the step of feeding standard fluid and diluent fluid into the dilutor through the diluent pressure regulation and the standard pressure regulator claim 20 , wherein said flow regulators are equal in capacity.25. A method according to claim 24 , including the step of measuring differential pressure between said regulators and compensating for pressure differences therebetween.26. A method according to claim 20 , including the step of calibrating the other fluid flow components on the basis of relative flow of fluid through said other components and combinations of one or more of the other ...

TREATING CANCER BY MODULATING MAMMALIAN STERILE 20-LIKE KINASE 3

The present invention relates to a method for modulating miRNA, said method being characterized in that a modulator of XRN1 is used. Also provided are uses of said method for therapeutical purposes, reagents therefore, as well as screening methods. 1. A method for modulating miRNA in a sample , said method being characterized in that the sample is contacted with a modulator of XRN1.2. (canceled)3. The method of claim 16 , wherein the method is performed to treat a disease and wherein a therapeutically effective amount of said modulator of XRN1 is administered to said subject.4. The method of claim 3 , wherein the disease is a cancer claim 3 , a metabolic disease claim 3 , a developmental disorder claim 3 , a cardiac disease or a viral infection.5. The method of claim 16 , wherein the modulator of XRN1 is a small molecule claim 16 , for instancc a RNasc inhibitor.6. The method of claim 16 , wherein the modulator of XRN1 is an antibody.7. The method of claim 16 , wherein the modulator of XRN1 is an agonist.8. The method of claim 16 , wherein the modulator of XRN1 is an inhibitor of XRN1.9. The method of wherein said inhibitor of XRN1 decreases or silences the expression of XRN1.10. The method of wherein the inhibitor is a siRNA.11. The method of claim 16 , wherein the subject is a mammal.12. (canceled)13. (canceled)14. A method for the identification of a substance that modulates the expression of XRN1 and/or its biological activity claim 16 , which method comprises the steps of:(i) contacting a XRN1 polypeptide or a fragment thereof having the biological activity of XRN1, a polynucleotide encoding such a polypeptide or polypeptide fragment, an expression vector comprising such a polynucleotide or a cell comprising such an expression vector, and a test substance under conditions that in the absence of the test substance would permit XRN1 expression and/or biological activity; and(ii) determining the amount of expression and/or biological activity of XRN1, e.g. the ...

PHOSPHORYLATED TWIST1 AND METASTASIS

The present application relates to methods for metastasis in a subject by modulating the phosphorylation of the Serine 42 of Twist1 by administering to said subject a therapeutically effective amount of a modulator of said phosphorylation of the Serine 42 of Twist1. Antibodies, uses methods and biomarkers based on the 1. A method for inhibiting metastasis in a subject by modulating the phosphorylation of the Serine 42 of Twist1 by administering to said subject a therapeutically effective amount of a modulator of said phosphorylation of the Serine 42 of Twist1.2. The method of wherein the phosphorylation of the Serine 42 of Twist1 is modulated by an inhibitor which specifically binds to Twist1 and hinders the phosphorylation of its Serine 42 by PKB.3. The method of wherein the inhibitor is an antibody or a small molecule.4. The method of wherein the modulator is a peptide comprising an amino acid corresponding to the Serine 42 of Twist1 claim 1 , which fragment is recognized and phosphorylated by PKB at said amino acid corresponding to the Serine 42 of Twist1.5. The method of wherein the subject is a mammal.6. The method of wherein the epithelial-mesenchymal transition of cancer cells is reduced.7. The method of wherein the cancer cells are from a colorectal cancer claim 6 , a breast cancer claim 6 , a lung cancer or a prostate cancer.8. (canceled)9. (canceled)10. A method for the identification of a substance that modulates the formation of metastasis claim 6 , which method comprises the step of assessing the phosphorylation of the Serine 42 of Twist1.11. A method of diagnosing metastasis comprising the step of assessing the phosphorylation of the Serine 42 of Twist1.12. The method of claim 11 , wherein an increased phosphorylation of the Serine 42 of Twist1 is indicative of metastasis formation.13. (canceled)14. The method of claim 5 , wherein the mammal is a human subject. The present invention relates to a method of treating cancer metastasis by modulating the ...

GIFT COLLABORATION SOCIAL NETWORK SERVICE

Techniques for facilitating collaboration on gift ideas for a receiver are provided. An example method according to the disclosure includes creating a group for discussing gift ideas for the receiver in response to a request from a user, receiving a gift idea from a member of the group, and providing a group collaboration interface in which members of the group can post messages discussing the gift idea. 1. A method for facilitating collaboration on gift ideas for a receiver , the method comprising:creating a group for discussing gift ideas for the receiver in response to a request from a user;receiving a gift idea from a member of the group;providing a group collaboration interface in which members of the group can post messages discussing the gift idea.2. The method of claim 1 , further comprising:receiving a gift item idea associated with the gift idea from a member of the group; andassociating the gift item idea received from the member of the group with the gift idea.3. The method of claim 2 , further comprising:displaying the gift item idea received from the member of the group in the group collaboration interface.4. The method of claim 1 , further comprising:receiving information about the receiver from one or more members of the group; andassociating the information about the receiver with the receiver.5. The method of claim 1 , further comprising:receiving information identifying a person mentioned in message discussing the gift idea, the person not being a member of the group; andinviting the person to join the group in response to receiving the message identifying the person.6. The method of claim 1 , further comprising:associating the receiver with a known receiver based on one or more attributes of the known receiver and information associated with the user, the known receiver being associated with one or more other groups for discussing gift ideas for the known receiver.7. The method of wherein associating the receiver with a known receiver further ...

IgG Bispecific Antibodies and Processes for Preparation

The present invention provides fully IgG bi-specific antibodies comprising designed residues in the interface of the heavy chain-heavy chain (C3/C3) domains, processes for preparing said fully IgG bi-specific antibodies, and nucleic acids, vectors and host cells encoding the same. 133-. (canceled)34. An IgG bispecific antibody comprising:{'sub': H', 'H, 'a. a first heavy chain, wherein said first heavy chain comprises a first variable domain (V) and a first human IgG1, human IgG2 or human IgG4 constant region, wherein said first human, human IgG2 or human IgG4 IgG1 constant region comprises an alanine at residue 407 of the C3 domain;'}{'sub': L', 'L, 'b. a first light chain, wherein said first light chain comprises a first variable domain (V) and a first constant domain (C);'}{'sub': H', 'H, 'c. a second heavy chain, wherein said second heavy chain comprises a second variable domain (V) and a second human IgG1, human IgG2 or human IgG4 constant region, wherein said second human IgG1, human IgG2 or human IgG4 constant region comprises a valine or methionine at residue 366 and a valine at residue 409 of the C3 domain; and'}{'sub': L', 'L, 'd. a second light chain, wherein said second light chain comprises a second variable domain (V) and a second constant domain (C).'}35. The IgG bispecific antibody of claim 34 , wherein said second human IgG1 claim 34 , human IgG2 or human IgG4 constant region comprises a valine at residue 366 of the C3 domain.36. The IgG bispecific antibody of claim 35 , wherein said first human IgG1 claim 35 , human IgG2 or human IgG4 constant region further comprises a methionine at residue 399 of the C3 domain.37. The IgG bispecific antibody of claim 36 , wherein said first human IgG1 claim 36 , human IgG2 or human IgG4 constant region further comprises an aspartic acid at residue 360 of the C3 domain claim 36 , and said second human IgG1 claim 36 , human IgG2 or human IgG4 constant region further comprises an arginine at residues 345 and 347 of ...

METHODS FOR PRODUCING FABS AND BI-SPECIFIC ANTIBODIES

The present invention provides methods for producing Fabs and bi-specific antibodies comprising designed residues in the interfaces of the heavy chain-light chain variable (V/V) domain and the heavy chain-light chain constant (C/C] domain, Fabs and bi-specific antibodies produced according to said processes and host cells encoding the same. 150-. (canceled)51. A method for producing a first and second fragment , antigen binding (Fab) comprising: (a) a first nucleic acid encoding both a first heavy chain variable domain and a first IgG heavy chain constant CH1 domain, wherein said first heavy chain variable domain comprises a lysine substituted at residue 39 and a glutamic acid substituted at the residue which is four amino acids upstream of the first residue of HFR3 according to Kabat, and said first IgG heavy chain constant CH1 domain comprises an alanine substituted at residue 172 and a glycine substituted at residue 174;', '(b) a second nucleic acid encoding both a first light chain variable domain and a first light chain constant domain, wherein said first light chain variable domain is a kappa isotype and comprises an arginine substituted at residue 1 and an aspartic acid substituted at residue 38, and said first light chain constant domain comprises a tyrosine substituted at residue 135 and a tryptophan substituted at residue 176;', '(c) a third nucleic acid encoding both a second heavy chain variable domain and a second IgG heavy chain constant CH1 domain, wherein said second heavy chain variable domain comprises a tyrosine substituted at residue 39 and said second IgG heavy chain constant CH1 domain comprises a WT sequence; and', '(d) a fourth nucleic acid encoding both a second light chain variable domain and a second light chain constant domain, wherein said second light chain variable domain comprises an arginine substituted at residue 38 and said second light chain constant domain comprises a WT sequence, wherein each of said first heavy chain and light ...

IgG Bispecific Antibodies and Processes for Preparation

The present invention provides fully IgG bi-specific antibodies comprising designed residues in the interface of the heavy chain-heavy chain (C/C) domains, processes for preparing said fully IgG bi-specific antibodies, and nucleic acids, vectors and host cells encoding the same. 115-. (canceled)16. A process for producing an IgG bispecific antibody comprising:{'sub': H', 'H, 'a. a first heavy chain, wherein said first heavy chain comprises a first heavy chain variable domain (V) and a first human IgG heavy chain constant region, wherein said first human IgG heavy chain is a human IgG heavy chain constant region that comprises an alanine at residue 407, a methionine at residue 399, and an aspartic acid at residue 360 of the C3 domain;'}{'sub': L', 'L, 'b. a first light chain, wherein said first light chain comprises a first light chain variable domain (V) and a first light chain constant domain (C);'}{'sub': H', 'H, 'c. a second heavy chain, wherein said second heavy chain comprises a second Vand a second human IgG constant region, wherein said second human IgG heavy chain constant region is a human IgG constant region that comprises an arginine at residue 345, an arginine at residue 347, a valine at residue 366, and a valine at residue 409 of the C3 domain; and'}{'sub': L', 'L, 'claim-text': [ a. a first nucleic acid sequence encoding the first heavy chain;', 'b. a second nucleic acid sequence encoding the first light chain;', 'c. a third nucleic acid sequence encoding the second heavy chain; and', 'd. a fourth nucleic acid sequence encoding the second light chain, wherein one of said first or second heavy chain variable domains and one of said first or second light chain variable domains each comprise three complementarity determining regions (CDRs) which direct binding to a first antigen, and the other of said first or second variable domains and first or second light chain variable domains each comprise three CDRs which direct binding to a second antigen that ...

NOVEL HETEROCYCLIC CARBOXAMIDES AS MODULATORS OF KINASE ACTIVITY

The invention provides novel heterocyclic carboxamide compounds according to Formula (I) their manufacture and use for the treatment of hyperproliferative diseases, such as cancer. 113-. (canceled)15. The method according to claim 14 , wherein X is N and Y is N—R.16. The method according to claim 14 , wherein X is N; Y is N—R; and R claim 14 , Rtogether form monocyclic alkyl having 3 claim 14 , 4 claim 14 , 5 claim 14 , 6 claim 14 , or 7 ring atoms claim 14 , wherein one or two CHgroups may be replaced by an —NH— claim 14 , —NA- claim 14 , —N(L-R)— claim 14 , —CHA- claim 14 , —CA- claim 14 , CH(L-R)— or —CO— group claim 14 , and wherein monocyclic alkyl may be substituted by NH.17. The method according to claim 14 , wherein X is N; Y is N—R; and R claim 14 , Rtogether form monocyclic alkyl having 4 claim 14 , 5 or 6 ring atoms claim 14 , wherein one CHgroup is replaced by an —N(L-R)— group claim 14 , and wherein monocyclic alkyl may be substituted by NH.18. The method according to claim 14 , wherein X is N; Y is N—R; R claim 14 , Rtogether form monocyclic alkyl having 4 claim 14 , 5 or 6 ring atoms claim 14 , wherein one CHgroup is replaced by an —N(L-R)— group claim 14 , and wherein monocyclic alkyl may be substituted by NH; and Lis a bond claim 14 , —CONH— claim 14 , —NHCO— claim 14 , —CONHCH— claim 14 , or CHCONH—.19. The method according to wherein X is N; Y is N—R; R claim 14 , Rtogether form monocyclic alkyl having 4 claim 14 , 5 or 6 ring atoms claim 14 , wherein one CHgroup is replaced by an —N(L-R)— group claim 14 , and wherein monocyclic alkyl may be substituted by NH; and Ris phenyl claim 14 , which is unsubstituted claim 14 , or independently mono- claim 14 , di- or trisubstituted by Hal claim 14 , C(Hal) claim 14 , CH claim 14 , or C(Hal)O.20. The method according to claim 14 , wherein X is N; Y is N—R; R claim 14 , Rtogether form monocyclic alkyl having 4 claim 14 , 5 or 6 ring atoms claim 14 , wherein one CHgroup is replaced by an —N(L-R)— group claim ...

Universal Alignment Adapter

In a shadow mask tensioning method and apparatus, a shadow mask supported by a support frame is positioned between a shadow mask frame and a set of actuators with a portion of the shadow mask extending across a gap between the support frame and the shadow mask frame. Under the control of a programmed controller, the set of actuators is caused to simultaneously displace numerous, spaced locations of the portion of the shadow mask into the gap to align alignment apertures of the shadow mask to predetermined positons in fields of view of cameras positioned to observe the alignment apertures. The shadow mask is then affixed to the shadow mask frame. 1. A shadow mask tensioning method comprising:(a) providing a shadow mask supported by a support frame;(b) following step (a), positioning the shadow mask supported by a support frame between a shadow mask frame and a set of actuators with a portion of the shadow mask extending across a gap between the support frame and the shadow mask frame;(c) following step (b), causing the set of actuators to simultaneously displace numerous, spaced locations of the portion of the shadow mask into the gap; and(d) following step (c), affixing the shadow mask to the shadow mask frame.2. The method of claim 1 , further including:a plurality of alignment apertures in the shadow mask;providing cameras to view the plurality of alignment apertures; andstep (c) includes causing the set of actuators to displace the numerous, spaced locations of the portion of the shadow mask into the gap to align the plurality of alignment apertures to predetermined positons in fields of view, of the cameras.3. The method of claim 2 , wherein step (c) occurs automatically under the control of a programmed controller.4. The method of claim 2 , wherein each camera is positioned with at least one alignment aperture in the field of view of the camera.5. The method of claim 2 , further including providing a light source for:projecting light onto a side of the shadow ...

Shadow Mask Tensioning Method and Apparatus

In a system and method of shadow mask tensioning, an object having second set of alignment features is positioned on a side of shadow mask having a first set of alignment features such that the object and the shadow mask can move independently of each other and the first and second sets of alignment features are not in final alignment. Tension is then applied to the shadow mask to bring the first set of alignment features into final alignment with the second set of alignment features. The alignment features of the shadow mask can include at least one deposition aperture of the shadow mask.

COMBINATION OF A BRAFV600E INHIBITOR AND MERTK INHIBITOR TO TREAT MELANOMA

The invention relates to a pharmaceutical combination which comprises (a) a compound inhibiting BRAFand (b) a compound which inhibits MerTK activation; for simultaneous, separate or sequential use; a commercial package or product comprising such a combination as a combined preparation for simultaneous, separate or sequential use; and to a method of treatment of a warm-blooded animal, especially a human. 1. A method of treating melanoma in a subject , wherein the method comprises administering a combination of compounds , wherein the combination comprises (a) a compound which inhibits BRAFand (b) a compound which inhibits MerTK activation; wherein the compounds may be administered simultaneously , separately or sequentially.2. The method of claim 1 , wherein the compound which inhibits MerTK activation inhibits autophagy claim 1 , thereby inhibiting MerTK activation.3. The method of claim 1 ,wherein the compound which inhibits MerTK activation is selected from the group consisting of: 3-Methyladenine, Bafilomycin Al, Chloroquine, LY294002, B202190, SB203580, Hydroxychloroquine sulfate, Pifithrin-mu, Amurensis H, Hydroxychloroquine niosomes, Ribavirin/hydroxychloroquine and Wortmannin.4. The method of claim 1 ,{'sup': 'V600E', 'wherein the compound inhibiting BRAFis selected from the group consisting of PLX4032 and Dabrafenib mesylate.'}5. The method of claim 1 ,{'sup': 'V600E', 'wherein the compound which inhibits BRAFis PLX4032.'}6. The method of claim 1 ,{'sup': 'V600E', 'wherein the compound which inhibits BRAFis Dabrafenib mesylate.'}7. The method of claim 1 ,wherein the compound which inhibits MerTK activation is Chloroquine.8. The method of claim 1 ,{'sup': 'V600E', 'wherein a therapeutically effective amount of a compound which inhibits MerTK activation is administered simultaneously, separately or sequentially in combination with the BRAFinhibitor to said subject.'}9. The method of claim 4 , wherein the compounds which inhibits BRAFVemurafenib claim 4 , ...

PROTEINS COMPRISING T-CELL RECEPTOR CONSTANT DOMAINS

Provided herein are proteins comprising T-cell receptor (TCR) constant domains with one or more stabilization mutations, nucleic acids encoding such proteins, and methods of making and using such proteins. 2. The protein of claim 1 , wherein:the first polypeptide comprises a Cα comprising at least one of the following residues: phenylalanine at position 139, isoleucine at position 150, threonine at position 190 (residues numbered according to Kabat numbering); andthe second polypeptide comprises a Cβ comprising at least one of the following residues: lysine at position 134, arginine at position 139, proline at position 155, aspartic acid or glutamic acid at position 170 (residues numbered according to Kabat numbering).3. The protein of claim 2 , wherein:the first polypeptide comprises a Cα domain comprising the following residues: phenylalanine at position 139, isoleucine at position 150, threonine at position 190 (residues numbered according to Kabat numbering); andthe second polypeptide comprises a Cβ domain comprising the following residues: lysine at position 134, arginine at position 139, proline at position 155, aspartic acid at position 170 (residues numbered according to Kabat numbering).4. The protein of claim 2 , wherein:the first polypeptide comprises a Cα domain comprising the following residues: phenylalanine at position 139 and threonine at position 190 (residues numbered according to Kabat numbering); andthe second polypeptide comprises a Cβ domain comprising the following residues: lysine at position 134, arginine at position 139, proline at position 155, aspartic acid at position 170 (residues numbered according to Kabat numbering).5. The protein of claim 4 , wherein the first polypeptide is linked to the second polypeptide by an inter-chain disulfide bond.6. The protein of claim 5 , wherein:the Cα domain further comprises a cysteine residue at position 166 (residue numbered according to Kabat numbering), andthe Cβ domain further comprises a ...

Novel Heterocyclic Carboxamides as Modulators of Kinase Activity

The invention provides novel heterocyclic carboxamide compounds compounds according to Formula (I) their manufacture and use for the treatment of hyperproliferative diseases, such as cancer. 2. The compound according to claim 1 , or its stereoisomers or tautomers claim 1 , or pharmaceutically acceptable salts of each of the foregoing claim 1 , including mixtures thereof in all ratios claim 1 , wherein X is N and Y is N—R.3. The compound according to claim 1 , or its stereoisomers or tautomers claim 1 , or pharmaceutically acceptable salts of each of the foregoing claim 1 , including mixtures thereof in all ratios claim 1 , wherein X is N; Y is N—R; Rand Rtogether form a monocyclic alkyl ring having 3 claim 1 , 4 claim 1 , 5 claim 1 , 6 claim 1 , or 7 ring atoms claim 1 , wherein one or two CHgroups may be replaced by an —NH— claim 1 , —NA- claim 1 , —N(L-R)— claim 1 , —CHA- claim 1 , —CA- claim 1 , CH(L-R)— or —CO— group claim 1 , and wherein the monocyclic alkyl ring is optionally substituted by NH.4. The compound according to claim 1 , wherein the compound is selected from:5-((4-(4-(trifluoromethoxy)phenyl)pyrrolidin-3-yl)amino)quinazoline-8-carboxamide (trans_racemic),5-((4-phenylpiperidin-3-yl)amino)quinazoline-8-carboxamide (trans_racemic),5-((4-(3-fluoro-4-(trifluoromethyl)phenyl)piperidin-3-yl)amino)quinazoline-8-carboxamide (trans_racemic),5-((-4-(3-(trifluoromethoxy)phenyl)pyrrolidin-3-yl)amino)quinoline-8-carboxamide (trans_racemic)5-((4-(3-(trifluoromethyl)phenyl)pyrrolidin-3-yl)amino)quinazoline-8-carboxamide,5-((4-(4-chloro-3-fluorophenyl)piperidin-3-yl)amino)quinazoline-8-carboxamide,5-((4-(3-chloro-4-fluorophenyl)piperidin-3-yl)amino)quinazoline-8-carboxamide,5-(((3R,4R)-4-(3-chloro-4-fluorophenyl)piperidin-3-yl)amino)quinazoline-8-carboxamide, and5-((4-(4-fluorophenyl)piperidin-3-yl)amino)quinazoline-8-carboxamide,or its stereoisomers or tautomers, or pharmaceutically acceptable salts of each of the foregoing, including mixtures thereof in all ratios ...

METHODS FOR PRODUCING FABS AND BI-SPECIFIC ANTIBODIES

The present invention provides methods for producing Fabs and bi-specific antibodies comprising designed residues in the interfaces of the heavy chain-light chain variable (V/V) domain and the heavy chain-light chain constant (C/C) domain, Fabs and bi-specific antibodies produced according to said processes and host cells encoding the same. 150.-. (canceled)51. A method for producing a fragment , antigen binding (Fab) , the method comprising (all residues are numbered according to the Kabat numbering system): (a) a first nucleic acid encoding a heavy chain variable (VH) domain and a human IgG heavy chain constant CH1 (CH1) domain, wherein said VH domain comprises a tyrosine at residue 39 and an arginine at residue 105, and said CH1 domain comprises an aspartic acid at residue 228, a cysteine at position 127 and a glycine at position 230; and', '(b) a second nucleic acid encoding both a light chain variable (VL) domain and a light chain constant (CL) domain, wherein said VL domain comprises an arginine at residue 38 and an aspartic acid at residue 42, said CL domain comprises a lysine at residue 122, wherein each of said VH and VL domains comprise three complementarity determining regions (CDRs) which direct binding to an antigen;, '(1) co-expressing in a host cell(2) cultivating said host cell under conditions such that said VH and CH1 domains and said VL and CL domains are produced; and(3) recovering from said host cell a Fab wherein said Fab comprises said VH and CH1 domains and said VL and CL domains.52. A method for producing a fragment , antigen binding (Fab) , the method comprising (all residues are numbered according to the Kabat numbering system): (a) a first nucleic acid encoding a heavy chain variable (VH) domain and a human IgG heavy chain constant CH1 (CH1) domain, wherein said VH domain comprises a tyrosine at residue 39 and an arginine at residue 105, and said CH1 domain comprises an alanine at residue 172 and a glycine at residue 174; and', '(b) a ...

MULTI-MASK ALIGNMENT SYSTEM AND METHOD

In a multi-mask alignment system and method, a carrier frame is provided having a number of apertures therethrough. A number of shadow mask-frame combinations are also provided. Each shadow mask-frame combination includes a first set of alignment features and each shadow mask-frame combination is positioned on a first side of the carrier with the frame supporting the shadow mask in alignment with one of the apertures. An alignment system is provided and a control system including a programmed controller is also provided. Under the control of the controller, the alignment system is caused to adjust the position of each shadow mask-frame combination with respect to the carrier based on positions of the first set of alignment features determined by the controller. 1. A multi-shadow mask alignment system comprising: a combination frame and shadow mask positioned on a first side of the carrier with the frame supporting the shadow mask in alignment with the aperture;', 'an alignment system positioned on a second side of the carrier opposite the first side and operative for adjusting a position of the combination frame and shadow mask with respect to the carrier; and', 'a control system including a programmed controller coupled to the alignment system, the controller operative for controlling the alignment system to fine or precision align the combination frame and shadow mask based on a position determined by the control system of each of a first set of alignment features of the combination frame and shadow mask., 'a carrier including a plurality of apertures therethrough, each aperture having associated therewith2. The alignment system of claim 1 , wherein the control system includes a digital camera coupled to the controller claim 1 , the camera positioned to a side of the combination frame and shadow mask opposite the carrier claim 1 , the camera operative for acquiring and forwarding digital images including the first set of alignment features to the controller which ...

SYSTEM FOR CREATING DATA-CONNECTED APPLICATIONS

A system for building a software application may comprise a database and a hardware processor. The database may be configured to store a plurality of object definitions, each object definition being configured to cause an executing processor to perform specific processing when executed. The hardware processor may be configured to cause a user interface to be displayed; receive, from the user interface, a selection of a plurality of the object definitions and an input specifying at least one relationship between the plurality of the object definitions; create an application definition based on the selection and the input; and provide an application interpreter configured to enable the executing processor to process the application definition. The software application may include the application definition and the application interpreter. 1. A method of building a software application , the method comprising:storing, in a database, a plurality of object definitions, each object definition defining an object configured to cause an executing processor to perform specific processing when executed;causing, by a hardware processor, a user interface to be displayed;receiving, by the hardware processor from the user interface, a selection of a plurality of the object definitions and an input specifying at least one relationship between the plurality of the object definitions;creating, by the hardware processor, an application definition based on the selection and the input; andproviding, by the hardware processor, an application interpreter configured to enable the executing processor to process the application definition,wherein the software application includes the application definition and the application interpreter.2. The method of claim 1 , wherein the application comprises an application programming interface (API).3. The method of claim 1 , wherein at least one of the object definitions comprises a plurality of the object definitions assembled into a single object ...

Method and Apparatus for Tensioning a Shadow Mask for Thin Film Deposition

In a method and apparatus for shadow mask tensioning, a shadow mask frame and an anchor frame are positioned in spaced relation defining a gap therebetween and a shadow mask is positioned on the shadow mask frame and the anchor frame with an interior portion of the shadow mask extending across the gap. An edge of the shadow mask is affixed to the anchor frame and the shadow mask is tensioned by urging the interior portion of the shadow mask into the gap. Once the shadow mask has been tensioned to a desired extent, the shadow mask is affixed to the shadow mask frame. Thereafter, the combination of the shadow mask affixed to the shadow mask frame is separated from the anchor frame.

Multi-Mask Alignment System and Method

In a multi-mask alignment system and method, a carrier frame is provided having a number of apertures therethrough. A number of shadow mask-frame combinations are also provided. Each shadow mask-frame combination includes a first set of alignment features and each shadow mask-frame combination is positioned on a first side of the carrier with the frame supporting the shadow mask in alignment with one of the apertures. A single alignment stage is provided and a control system including a programmed controller is also provided. Under the control of the controller, the single alignment stage translates to each shadow mask-frame combination, one-at-a time, and adjusts the position of the shadow mask-frame combination based on positions of the first set of alignment features determined by the controller.

SYSTEM FOR CREATING DATA-CONNECTED APPLICATIONS

A system for building a software application may comprise a database and a hardware processor. The database may be configured to store a plurality of object definitions, each object definition being configured to cause an executing processor to perform specific processing when executed. The hardware processor may be configured to cause a user interface to be displayed; receive, from the user interface, a selection of a plurality of the object definitions and an input specifying at least one relationship between the plurality of the object definitions; create an application definition based on the selection and the input; and provide an application interpreter configured to enable the executing processor to process the application definition. The software application may include the application definition and the application interpreter. 1. A method of building a software application , the method comprising:storing, in a database, a plurality of object definitions, each object definition defining an object configured to cause an executing processor to perform specific processing when executed;receiving, by a hardware processor, first data specifying a second plurality of the object definitions forming a subset of the plurality of the object definitions and second data specifying at least one relationship between the plurality of the object definitions;creating, by the hardware processor, an application definition comprising the selected second plurality of object definitions and the at least one relationship of the selected second plurality of object definitions based on the first data and the second data; andproviding, by the hardware processor, an application interpreter configured to enable the executing processor to process the application definition,wherein the software application includes the application definition and the application interpreter.2. The method of claim 1 , wherein the application comprises an application programming interface (API).3. The ...

TOOL ORIENTATION SYSTEMS AND METHODS

Systems and methods for tool orientation and/or position determining system are described herein. In one example, a plurality of tool sensors can be coupled to a tool. The tool sensors can provide data to a control module or system controller. The orientation and/or position of the tool can accordingly be determined from the data. If the orientation and/or position of the tool matches a desired orientation, the tool and/or control module can provide an indication that the tool is in the desired orientation. 1. An apparatus comprising:a first tool sensor configured to be coupled to a first portion of a tool;a second tool sensor configured to be coupled to a second portion of the tool;a third tool sensor configured to be coupled to a third portion of the tool; and communicatively couple to the first tool sensor, the second tool sensor, and the third tool sensor; and', receiving, at a first timeframe, calibration data from the first tool sensor, the second tool sensor, and the third tool sensor;', 'determining a calibration orientation of a major length of the tool from the calibration data;', 'receiving, at a second timeframe, orientation data from the first tool sensor, the second tool sensor, and the third tool sensor;', 'determining, from the orientation data, whether the major length of the tool is oriented substantially similarly to the calibration orientation; and', 'providing, by the user interface, an indication of whether the major length of the tool is oriented substantially similarly to the calibration orientation., 'perform operations comprising], 'a control module comprising a user interface and configured to2. The apparatus of claim 1 , wherein the first portion claim 1 , the second portion claim 1 , and the third portion are extremities of the tool.3. The apparatus of claim 1 , wherein the first tool sensor claim 1 , the second tool sensor claim 1 , and/or the third tool sensor are configured to be adhesively claim 1 , mechanically claim 1 , and/or ...

Methods for Producing Fabs and IgG Bispecific Antibodies

The present invention provides methods for producing Fabs and IgG bi-specific antibodies comprising expressing nucleic acids encoding designed residues in C1/Cinterface, Fabs and IgG bi-specific antibodies produced according to said processes as well as nucleic acids, vectors and host cells encoding the same. 1. A method for producing a first and second fragment , antigen binding (Fab) comprising:(1) co-expressing in a host cell:{'sub': H', 'H', 'H', 'H, '(a) a first nucleic acid sequence encoding both a first heavy chain variable domain (V) and a first human IgG heavy chain constant C1 (C1) domain, wherein said first human C1 domain comprises an alanine at residue 145 (according to Kabat Numbering);'}{'sub': 'L', '(b) a second nucleic acid sequence encoding both a first light chain variable domain (V) and a first human light chain kappa constant (Ck) domain, wherein said first human Ck domain comprises an arginine at residue 131 (according to Kabat Numbering);'}{'sub': H', 'H', 'H', 'H, '(c) a third nucleic acid encoding both a second Vdomain and a second human C1 domain, wherein said second human C1 domain has the wide type human IgG C1 sequence; and'}{'sub': L', 'H', 'L', 'H', 'L, '(d) a fourth nucleic acid encoding both a second Vdomain and a second human Ck domain, wherein said second human Ck domain has the wide type human Ck sequence, wherein each of said first Vand Vdomains comprise three complementarity determining regions (CDRs) which direct binding to a first antigen and further wherein each of said second Vand Vdomains comprise three CDRs which direct binding to a second antigen that differs from said first antigen;'}{'sub': H', 'H', 'L, '(2) cultivating said host cell under conditions such that said first and second Vand human C1 domains and said first and second Vand human Ck domains are produced; and'}{'sub': H', 'H', 'L', 'H', 'H', 'L, '(3) recovering from said host cell a first and second Fabs wherein said first Fab comprises said first Vand first ...

METHODS FOR PRODUCING FABS AND BI-SPECIFIC ANTIBODIES

The present invention provides methods for producing Fabs and bi-specific antibodies comprising designed residues in the interfaces of the heavy chain light-chain variable (V/V) domain and the heavy chain-light chain constant (C/C) domain, Fabs and bi-specific antibodies produced according to said processes and host cells encoding the same. 1. A method for producing a fragment , antigen binding (Fab) comprising: (a) a first nucleic acid encoding both a heavy chain variable domain and a human IgG heavy chain constant CH1 domain, wherein said heavy chain variable domain comprises a lysine at residue 39 and a glutamic acid at residue 62, and said human IgG heavy chain constant CH1 domain comprises an alanine at residue 172 and a glycine at residue 174, wherein each of said residues are numbered according to the Kabat numbering system;', '(b) a second nucleic acid encoding both a light chain variable domain and a light chain constant domain, wherein said light chain variable domain is a kappa isotype and comprises an arginine at residue 1 and an aspartic acid at residue 38 , and said light chain constant domain comprises a tyrosine at residue 135 and a tryptophan at residue 176, wherein each of said residues are numbered according to the Kabat numbering system and wherein each of said heavy chain and light chain variable domains comprise three complementarity determining regions (CDRs) which direct binding to an antigen;, '(A) (1) co-expressing in a host cell(2) cultivating said host cell under conditions such that said heavy chain variable and human IgG CH1 constant domains and said light chain variable and constant domains are produced; and(3) recovering from said host cell a Fab wherein said Fab comprises said heavy chain variable and constant domains and said light chain variable and constant domains; (a) a first nucleic acid encoding both a heavy chain variable domain and a human IgG heavy chain constant CH1 domain, wherein said heavy chain variable domain ...

POST-FABRICATION FORGING TREATMENT

A method of modifying a grain structure of a metal article includes disposing at least a portion of a metal article in a molten salt bath in a pressure vessel. The molten salt bath has bath temperature that is below a melting point temperature of the metal article. The method also includes pressuring the molten salt bath in the pressure vessel to a forging pressure sufficient to cause pressure-driven grain changes in the metal article. 1. A method of modifying a grain structure of a metal article , the method comprising:disposing at least a portion of a metal article in a molten salt bath in a pressure vessel, the molten salt bath at a bath temperature that is below a melting point temperature of the metal article; andpressurizing the molten salt bath in the pressure vessel to a forging pressure sufficient to cause pressure-driven grain changes in the metal article.2. The method of claim 1 , further comprising claim 1 , after maintaining the molten salt bath at the forging pressure for a forging period claim 1 , disposing at least the portion of the metal article in a quench medium.3. The method of claim 2 , wherein disposing at least the portion of the metal article in the quench medium comprises:extracting molten salt from the pressure vessel; andintroducing the quench medium into the pressure vessel.4. The method of claim 3 , further comprising venting claim 3 , from the pressure vessel claim 3 , gases released by the quench medium.5. The method of claim 2 , further comprising claim 2 , after disposing at least the portion of the metal article in the quench medium claim 2 , heat treating the metal article in the molten salt bath at a pressure less than the forging pressure.6. The method of claim 5 , wherein heat treating the metal article in the molten salt bath comprises:extracting the quench medium from the pressure vessel; andintroducing molten salt into the pressure vessel.7. The method of claim 1 , further comprising claim 1 , before disposing at least the ...

NOVEL HETEROCYCLIC CARBOXAMIDES AS MODULATORS OF KINASE ACTIVITY

The invention provides novel heterocyclic carboxamide compounds compounds according to Formula (I) their manufacture and use for the treatment of hyperproliferative diseases, such as cancer. 2. (canceled)4. The compound according to claim 1 , wherein the compound is selected from:(S)-5-((1-(3-fluorophenyl)-2-(methylamino)ethylamino)quinoline-8-carboxamide (Example 16);5-((-4-(quinolin-7-yl)pyrrolidin-3-yl)amino)quinoline-8-carboxamide (Example 17);5-(3-phenylpiperazin-1-yl)quinoline-8-carboxamide (Example 18);5-((3-phenylazetidin-3-yl)amino)quinoline-8-carboxamide (Example 19);5-(((3-(phenylcarbarnoyl)pyrrolidin-3-yl)methyl)amino)quinoline-8-carboxamide (Example 20);5-((-4-(3-(trifluoromethoxy)phenyl)pyrrolidin-3-yl)amino)quinoline-8-carboxamide (Example 21);5-(((4S)-4-(3-trifluoromethoxy)phenyl)pyrrolidin-3-yl)amino)quinoline-8-carboxamide (Example 22);5-(((3S,4R)-4-(3-(trifluoromethoxy)phenyl)pyrrolidin-3-yl)amino)quinoline-8-carboxamide (Example 23);5-((-4-(3-(trifluoromethoxy)phenyl)pyrrolidin-3-yl)amino)quinoline-8-carboxamide (Example 24);5-((4-(3-fluorphenyl)piperidin-3-yl)amino)quinolin-8-carboxamide (Example 25);5-(((4R)-4-(3-chloro-5-fluorophenyl)pyrrolidin-3-yl)amino)quinoline-8-carboxamide (Example 26);5-((4S)-4-(3-fluorophenyl)pyrrolidine-3-carboxamide)quinoline-8-carboxamide (Example 27);5-((4S)-4-phenylpyrrolidine-2-carboxamido)quinoline-8-carboxamide (Example 28);5-(2-amino-2-phenylacetamido)quinoline-8-carboxamide (Example 29);5-((3S)-3-phenylazetidine-2-carboxamido)quinoline-8-carboxamide (Example 30);5-(4-fluorobenzylamino)-quinoline-8-carboxamide (Example 31);5-(2-Fluorobenzylamino)-quinoline-8-carboxamide (Example 32);5-(3-Fluorobenzylamino)-quinoline-8-carboxamide (Example 33);5-(3-Chlorobenzylamino)-quinoline-8-carboxamide (Example 34);5-(3,4-Difluorobenzylamino)-quinoline-8-carboxamide (Example 35);5-(3,4,5-trifluorobenzylamino)-quinoline-8-carboxamide (Example 36);5-(4-Fluoro-3-trifluoromethylbenzylamino)-quinoline-8-carboxamide (Example 37 ...

Apparatus and Method for Planarizing Multiple Shadow Masks on a Common Carrier Frame

In an apparatus and method for multi mask alignment, a carrier is provided that includes apertures therethrough. For each aperture, a combination frame and shadow mask that includes alignment features is positioned on spacers supported by the carrier with the shadow mask of the combination in coarse alignment with the aperture. Next, each combination frame and shadow mask is moved to a position spaced from the spacers whereupon the alignment system, under the control of a controller, individually aligns each combination frame and shadow mask to align the alignment features of the combination with reference alignment features associated with the combination. Each combination frame and shadow mask is then returned to a position on the spacers whereafter each combination frame and shadow mask is secured to the carrier. In an example, all of the combination frames and shadow masks can be aligned simultaneously. 1. A multi-mask alignment system comprising:a carrier including first and second sides and a plurality of apertures extending through the carrier from the first side to the second side, wherein each aperture has associated therewith a combination frame and shadow mask including alignment features, wherein the shadow mask is supported via the frame on the first side of the carrier with the shadow mask in alignment with the aperture;an alignment system positioned on the second side of the carrier;a controller operative for controlling the alignment system to individually align each combination frame and shadow mask such that the alignment features of said combination align with reference alignment features associated with said combination but not part of the carrier or said combination; andspacers positioned on the carrier and configured to support each combination frame and shadow mask above a surface of the first side of the carrier.2. The system of claim 1 , wherein the spacers are configured to planarize each combination frame and shadow mask.3. The system of ...

Filter tube

A filter tube, which filter tube comprises a mass of interrelated nonwoven glass fibers, the fibers having a diameter of from about 0.001 to about 10 microns, the fibers bonded at the junctions of the fiber crossovers with a hardened silicone resin bonding agent, the fibers interrelated to form a semirigid mass of desired porosity suitable for use as a filter for gases or liquids.

Spleen tyrosine kinase and brain cancers

The present invention relates to a method for treating cancer, for instance brain tumors, in a subject by inhibiting spleen tyrosine kinase (Syk) by administering to said subject a therapeutically effective amount of a modulator of Syk, for example a specific antibody or a siRNA. The present invention also encompasses methods of diagnosing cancer by measuring levels of Syk, as well as method of targeted therapy using anti-Syk antibodies conjugated to therapeutic agents.

Treating cancer by modulating mammalian sterile 20-like kinase 3

The present invention relates to a method for treating cancer in a subject by modulating MST3, by administering to said subject a therapeutically effective amount of a modulator of MST.

Phosphorylated twist1 and metastasis

The present application relates to methods for metastasis in a subject by modulating the phosphorylation of the Serine 42 of Twist1 by administering to said subject a therapeutically effective amount of a modulator of said phosphorylation of the Serine 42 of Twist1. Antibodies, uses methods and biomarkers based on the phosphorylation of the Serine 42 of Twist1 are also provided.

Methods for producing fabs and bi-specific antibodies

The present invention provides methods for producing Fabs and bi-specific antibodies comprising designed residues in the interfaces of the heavy chain-light chain variable (V H /V L ) domain and the heavy chain-light chain constant (C H1 /C L ] domain, Fabs and bi-specific antibodies produced according to said processes and host cells encoding the same.

BISPECIFIC IGG ANTIBODIES AND THEIR PREPARATION PROCESSES

Patent DE3037788C2

Mine gallery or tunnel driving shield loader - has ramp and arms movable together on floor from rear to front

The loading ramp has loading arms swinging reciprocally above it. It serves for loading in cutter shield forward driving, in a mine or tunnel. The ramp (15) together with its arms (16) is movable as an entity from one operative position to another. In the first position it is located on the floor area behind the cutting edge, or behind the ends of the floor cutters (11) on the face side. In the other position it lies on the floor area in front of the cutters. The unit may be movable by one or more forward-thrust cylinders (25). Thus the floor area can be cleared far enough to simplify forward drive.

IgG bispecific antibodies and processes for preparation

The present invention provides fully IgG bi-specific antibodies comprising designed residues in the interface of the heavy chain-heavy chain (C H 3/C H 3) domains, processes for preparing said fully IgG bi-specific antibodies, and nucleic acids, vectors and host cells encoding the same.

Methods for producing fabs and igg bispecific antibodies

Abstract The present invention provides methods for producing Fabs and IgG bi-specific antibodies comprising expressing nucleic acids encoding designed residues in C H 1/C L interface, Fabs and IgG bi-specific antibodies produced according to said processes as well as nucleic acids, vectors and host cells encoding the same.

Fault management system for a communications network

There is described a method of operating a fault management system for an access network which forms part of a communications network. In the access network, terminating lines in the form of pairs of copper wires extend from a local switch (10) through a series of nodes to terminal equipment provided f or user of the network. The fault management system includes a test head (104) and an access network management system (102). Each night, the test head (10 4) performs a series of tests on each of the terminating lines. The results of the tests are transmitted to the access network management (102). The test results are then analysed with respect of a set of parameter to identify characteristics that would indicate that a fault is likely to occur on the associated circuit within a predetermined period e.g. 1 year. Further analys is can then be carried out to establish the probability of the fault actually occurring and/or whether the potential fault analysed is going to occur in either the underground or the over-ground part of the network.

Magnetic roller table

HAVING HEAD FOR MINE MACHINE

L'INVENTION CONCERNE LES TETES ROTATIVES DE HAVAGE. ELLE SE RAPPORTE A UNE TETE DE HAVAGE DANS LAQUELLE UN DEFLECTEUR 50 RENVOIE UNE PARTIE D'UN COURANT D'AIR ASPIRE VERS L'INTERIEUR DU TAMBOUR 5 VERS L'EXTERIEUR DE CELUI-CI AFIN QU'IL RETOURNE VERS LE FRONT DE TAILLE, LORSQU'UN OBTURATEUR 60 BOUCHE DES OUVERTURES 49. LORSQUE L'OBTURATEUR NE BOUCHE PAS LES OUVERTURES, L'AIR PEUT ETRE EVACUE VERS LA MACHINE DE MINE. APPLICATION AUX MACHINES D'EXPLOITATION DES MINES DE CHARBON. THE INVENTION RELATES TO ROTATING HEADS FOR CHASING. IT RELATES TO A HAVING HEAD IN WHICH A BAFFLE 50 RETURNS PART OF A CURRENT OF AIR SUCTION TOWARDS THE INSIDE OF DRUM 5 TOWARDS THE EXTERIOR OF THE latter SO THAT IT RETURNS TO THE WAIST FRONT, WHEN A SHUTTER 60 BLOCKS THE OPENINGS 49. WHEN THE SHUTTER DOES NOT BLOCK THE OPENINGS, AIR MAY BE EVACUATED TO THE MINE MACHINE. APPLICATION TO COAL MINING MACHINES.

Advanced knitting machine

Improvements in and to combine harvesters

The invention is directed to an improved method and means of achieving the separation of relatively heavy threshed grain from lighter chaff/straw during the threshing operation in a combine harvester, wherein the crop materialbeing threshed by the threshing unit (12, 16) of the harvester is sujected to a jet of air which is directed between the underside of the concave (16) of the threshing unit (12) and the grain transfer means (18) which conveys threshed grain from the threshing unit (12) to an intake of a cleaning mechanism (22), the jet of air being effective to assist the delivery of the threshed material away from the threshing unit and to pre-clean the threshed grain by urging the chaff and strew into an airborne state prior to reaching the cleaning mechanism.

Process for the manufacture of urethanes

Urethanes are made by reacting an organic compound containing at least one hydroxyl group with carbon monoxide and with a nitrogenous compound containing at least one non-cyclic group in which a nitrogen atom is directly attached to a single carbon atom and through a double bond to an oxygen or another nitrogen. The hydroxy compounds have the formula R(OH)n or P(OH)n where n is 1 or more, preferably 1 to 3, R is an optionally substituted aliphatic, cycloaliphatic, or araliphatic group, P is an aromatic group containing one or more benzenoid rings which may be fused or joined by single valency bonds, directly or through bridging groups such as oxygen or sulphur atoms, sulphoxide, sulphone or carbonyl groups, or alkylene groups in which the chain may be interrupted by oxygen, or sulphur atoms, sulphoxide, sulphone or carbonyl groups. Many suitable hydroxy compounds are specified. Suitable nitrogenous compounds are organic nitro, nitroso, azo and azoxy compounds or mixtures thereof. The process may be effected at super-atmospheric pressure, e.g. 50-500 atm., at temperatures up to 250 DEG C. Suitable catalysts are metal carbonyls such as a carbonyl, hydrogen carbonyl, halogen carbonyl, hydrocarbon carbonyl, hydrocarbon halogen carbonyl, nitrose carbonyl or cyanocarbonyl of an element in Group VIa, VIIa and VIIIa of the Periodic Table such as Cr, Mo, W, Mn, Fe, Co, Ni, Ru, Rh, Ds and Ir.ALSO:Polyurethane polymers are made by reacting polynitro, polynitroso or nitro-substituted azo or azoxy compounds with organic polyhydroxy compounds and carbon monoxide. Linear polyurethanes may be made from diols, dinitro compounds and carbon monoxide or from hydroxynitro compounds and carbon monoxide, whilst cross-linked polyurethane polymers may be obtained directly from di- or poly-nitro compounds, diols or polyols and carbon monoxide. The hydroxy compounds may be optionally substituted aliphatic, cycloaliphatic or araliphatic or aromatic compounds containing one or more benzenoid ...

Patent DE2918473C2

Pharmaceutical antifungal composition

A valuable alternative antifungal antibiotic, for treatment especially of candidiasis, particularly vaginal candidiasis, is proposed. The antibiotic is a bile acid or simple derivative (salt or conjugate) thereof. Cholic, deoxycholic, chenodeoxycholic and lithocholic acid are preferred bile acids. The antibiotic is formulated for topical application. It can be used in association with an anti-inflammatory steroid for the treatment of fungal infections of the skin. It is also proposed to inhibit fungal growth in a variety of pharmaceutical compositions (containing some other active ingredient) by including in the composition, or coating a tablet, pill or capsule with, the bile acid component.

A sealing composition and a mineral insulated electric cable termination employing such composition

This invention relates to a sealing composition for a mineral insulated electric cable termination. The sealing composition includes an inert filler such as silica flour, a low vapour pressure organic material such as a polyphenyl ether and an aerosil. This composition has improved slump resistance at high temperatures with little run out and no tendency to crack at 250°C.

Tumour suppressor and uses thereof

A human protein (designated Carboxy-terminal Modulating protein, CTMP) is described and is identified as having tumour suppressor properties. CTMP has been shown to interact with protein kinase B and inhibit protein kinase B activity, establishing its importance in the protein kinase B signalling pathway.

Device for erecting a tubular structure or the like in an open trench sheeting

Fault management system for a communications network

There is described a method of operating a fault management system for an access network which forms part of a communications network. In the access network, terminating lines in the form of pairs of copper wires extend from a local switch (10) through a series of nodes to terminal equipment provided for user of the network. The fault management system includes a test head (104) and an access network management system (102). Each night, the test head (104) performs a series of tests on each of the terminating lines. The results of the tests are transmitted to the access network management (102). The test results are then analysed with respect of a set of parameter to identify characteristics that would indicate that a fault is likely to occur on the associated circuit within a predetermined period e.g. 1 year. Further analysis can then be carried out to establish the probability of the fault actually occurring and/or whether the potential fault analysed is going to occur in either the underground or the over-ground part of the network.

Method of corrosion protection at pipe junctions

A method for providing protection against corrosion of a pipe joint (1) formed by the mating of complementary ends (4, 5) of two pipes comprising the steps of: (a) applying controlled heating to a pipe body which is to be joined to an adjacent pipe, (b) applying to the ends (4,5) of each pipe a protective layer or coating of material (2) to the pipe body by a time/temperature func-tion process, (c) allowing the pipe to cool, (d) bevelling the terminations of the protective layer or coating (2), (e) mating comple-mentary ends (4,5) of the pipes together to form a seated and corrosion resistant joint (1).

Method of making filter tubes

A filter tube, which filter tube comprises a mass of interrelated nonwoven glass fibers, the fibers having a diameter of from about 0.001 to about 10 microns, the fibers bonded at the junctions of the fiber crossovers with a hardened silicone resin bonding agent, the fibers interrelated to form a semirigid mass of desired porosity suitable for use as a filter for gases or liquids.

PROTECTION DEVICE

Dispositivo de protección (10) para su utilización en la protección de por lo menos una porción de un artículo alargado (50), incluyendo el dispositivo de protección (10) un cuerpo principal (12), que incluye partes primera y segunda (22, 27) que son conectables entre sí de manera que, en una posición ensamblada, el cuerpo principal (12) tiene una cámara (14) en el mismo, con extremos opuestos, y un eje de longitudinal central que se extiende entre los extremos opuestos, teniendo cada una de las partes primera y segunda (22, 27) dos porciones de borde lateral (23, 28) que se extienden longitudinalmente, estando adaptadas las respectivas porciones de borde lateral (23) de la primera parte (22) para cooperar con respectivas porciones de borde lateral (28) de la segunda parte (27) con el objeto de conectar entre sí las dos partes en la posición ensamblada, en el que dichas partes primera y segunda (22, 27) solapan cuando están en la posición ensamblada y son conectadas entre sí mediante un movimiento relativo en la dirección axial con el objeto de adoptar la posición ensamblada, siendo dichas partes primera y segunda (22, 27) parcialmente circulares vistas en sección transversal, caracterizado porque la primera parte (22) comprende un segmento mayor de un círculo y la segunda parte (27) forma un segmento menor de un círculo, y dichas porciones de borde lateral (28) de una de las partes (22, 27) incluyen una sección (29) de borde lateral escalonada hacia dentro, que forma una sección rebajada (30) y un hombro (31) que se extiende sustancialmente desde un extremo de la misma hasta el otro, para recibir la porción del borde lateral de la otra parte (22, 27) de manera que, en la posición ensamblada, hay un espacio entre una superficie interior de la pared del cuerpo principal (12) y el artículo alargado (50). Protection device (10) for use in the protection of at least a portion of an elongated article (50), including the protection device (10) a main body (12), which ...

Active transducer system

Multi-mask alignment system and method

In a multi-mask alignment system and method, a carrier frame is provided having a number of apertures therethrough. A number of shadow mask - frame combinations are also provided. Each shadow mask - frame combination includes a first set of alignment features and each shadow mask - frame combination is positioned on a first side of the carrier with the frame supporting the shadow mask in alignment with one of the apertures. An alignment system is provided and a control system including a programmed controller is also provided. Under the control of the controller, the alignment system is caused to adjust the position of each shadow mask - frame combination with respect to the carrier based on positions of the first set of alignment features determined by the controller.

Seat stick

A seat stick comprises an extendable shaft 10 having at its upper end a seat 11 which may be opened from a folded position, where it lies along the axis of the shaft, into a position where it extends across the top of the shaft. Folding support struts 23 extend between the underside of the seat 11 and the shaft 10 when the seat is opened. At the lower end of the shaft are two folding stabilisers 34 which may be swung outwards and locked to engage the ground on each side of the shaft. The folding seat 11 is formed with hand grips 28 at its opposite side edges, and the overall width of the seat, when in the open position, is greater than 280 mm. These features make the seat stick particularly stable for disabled or infirm users, who may more easily rise from the seat by holding the handgrips and using their arms to push themselves up.

Morphine and codeine derivatives for use in therapy

A compound of formula (I) wherein R1 = H (morphine analogue), CH3 (codeine analogue), R2 = H, alkyl group of 1 to 4 carbon atoms, allyl, cyclopropylmethyl, R3 = a group (A), -O-CH2-R4 (ether), -O-COCH = CHR4 (cinnamate), R4 = (B), wherein X1, X2, X3, X4 and X5 which may be the same or different are separately selected from H, alkyl of 1 to 4 carbon atoms, NH2, NO2, alkoxy group of 1 to 4 carbon atoms, hydroxy, halogen, N-alkyl, group of 1 to 4 carbon atoms, morpholine, or a group COR5 wherein R5 is H, OH, O-alkyl where alkyl is from 1 to 4 carbon atoms, or one of X1 and X2, X2 and X3, X3 and X4 or X4 and X5 together with an alkylene group optionally interrupted by O, S or N of up to 5 atoms in length complete a ring and a pharmaceutically acceptable salt thereof for use in therapy.

Airfoil shape

Anti-fungal bile acid derivatives

Compounds of general formula (7), wherein X is a hydrogen atom or a hydroxyl group, Y is a hydrogen atom or a hydroxyl group and at least one of X and Y is a hydroxyl group and Z is a hydroxyl group or a methylol (-CH2OH) group, have anti-fungal activity, especially against organisms selected from Candida spp. and the athlete's foot/ringworm organisms Trichophyton mentagrophytes) and Microsporum audonii. Compounds in which Z is a methylol (-CH2OH) group are claimed perse.

Nuclear protein serine/threonine kinases

The current invention describes the identification of a novel widely-expressed human and D. melanogasterserine/threonine protein kinase (designated nuclear, Dbf2-related kinase, or Ndr; previously referred to as Ndr) and the use of this kinase for the identification of agonists and antagonists. The kinase is a nuclear protein and contains a short basic peptide, KRKAETWKRNRR, responsible for the nuclear accumulation.

Copolymeric plasticisers for vinyl chloride polymers

Novel copolymers having an average molecular weight of from 300-1500 comprise units of a conjugated diolefin having 4 to 6 carbon atoms, an isoalkene of 4 to 8 carbon atoms and acrylonitrile or an alpha-substituted derivative thereof, the proportion of nitrile being at most 40% by weight of the copolymer. Suitable diolefins include piperylene, isoprene, 2,3-dimethylbutadiene and butadiene. Isoalkenes specified are isobutene and 3-methylbutene-1, and methacrylonitrile is an example of a suitable acrylonitrile derivative. The copolymers may be prepared by polymerizing the appropriate monomers in solution in an inert solvent, e.g. toluene or cumene, using a peroxide initiator, e.g. di-t-butyl peroxide or cumene hydroperoxide, and a chain transfer agent such as ethyl or isopropyl mercaptan or hydrogen sulphide. When such sulphur-containing agents are used, the polymer products may be treated with an adsorbent such as activated alumina or charcoal to remove odours and discoloration. The mobile copolymer products are suitable as plasticizers for polymers comprising at least 90% by weight of vinyl chloride units, e.g. polyvinyl chloride and vinyl chloride-vinyl acetate copolymers. In examples, white lead and calcium stearate are included in the plasticized compositions.

Novel heterocyclic carboxamides as modulators of kinase activity

Flat twin bed knitting machines

Thermally compensated laser

DRIVING DEVICE FOR OPENING TUNNELS, UNDERGROUND CHANNELS OR THE LIKE.

Such an apparatus has a cutter shield (1), followed by a trailing shield (11) with end formwork (3) for in-situ concrete lining. The trailing shield (11) consists of shield segments (12) which are arranged so as to be displaceable in the driving direction by cylinders (15) connected between them and the end formwork (3) or the cutter shield (1) so that the shield segments (12) can be advanced individually and smaller forces are required when drawing up the end formwork (3). In addition, better release of the trailing shield (11) from the in-situ concrete is obtained by advancing individual segments. <IMAGE>

Cable repair

Stable memory protection using capability tables

A stable memory circuit includes a capability circuit 10 which has an object capability table 14 and a process capability table 15 each of which are stored within stable memory banks. The object capability table 14 stores a capability entry 16 for each page of the stable memory banks and the process capability table 15 stores a list of the object capabilities for those pages that a process may validly access. Since control and access of the capability tables takes place within the stable memory circuit the host processor is unaware of their values and thus it is impossible to modify any capabilities deliberately or accidently. The capabilities may also be used to provide central update logging and central dependency logging. A cache circuit incorporating a stable memory circuit which serves both the data and tags for the cache is disclosed. Further, stable memory circuits may also include disk and network interfaces and may be arranged in fully or partially instantiated N-dimensional configurations. <IMAGE>

METHOD OF PROTECTION AGAINST CORROSION IN TUBE JOINTS.

UN METODO PARA PROTEGER CONTRA LA CORROSION UNA JUNTA DE TUBERIA (1) FORMADA POR LA UNION DE LOS EXTREMOS COMPLEMENTARIOS (4, 5) DE DOS TUBERIAS QUE INCLUYE LOS PASOS DE: (A) APLICAR UN CALENTAMIENTO CONTROLADO AL CUERPO DE UNA TUBERIA QUE VA A UNIRSE CON LA TUBERIA SIGUIENTE, (B) APLICAR A LOS EXTREMOS (4, 5) DE CADA TUBERIA UNA CAPA O REVESTIMIENTO PROTECTOR DE MATERIAL (2) AL CUERPO DE TUBERIA MEDIANTE UN PROCESO DE FUNCION TIEMPO/TEMPERATURA, (C) DEJAR QUE SE ENFRIE LA TUBERIA, (D) NIVELAR LAS TERMINACIONES DE LA CAPA O REVESTIMIENTO PROTECTOR (2), (E) UNIR LOS EXTREMOS COMPLEMENTARIOS (4, 5) DE LAS TUBERIAS PARA FORMAR UNA JUNTA SELLADA Y RESISTENTE A LA CORROSION (1). A METHOD TO PROTECT AGAINST CORROSION A PIPING JOINT (1) FORMED BY THE JOINT OF COMPLEMENTARY END (4, 5) OF TWO PIPES INCLUDING THE STEPS OF: (A) APPLYING CONTROLLED HEATING TO THE BODY OF A PIPE THAT IS TO JOIN WITH THE FOLLOWING PIPE, (B) APPLY TO THE END (4, 5) OF EACH PIPE A LAYER OR PROTECTIVE COATING OF MATERIAL (2) TO THE PIPE BODY THROUGH A TIME / TEMPERATURE FUNCTION PROCESS, (C) LET IT THE PIPE COOLS, (D) LEVELING THE LAYER TERMINATIONS OR PROTECTIVE COATING (2), (E) JOINING THE COMPLEMENTARY END (4, 5) OF THE PIPES TO FORM A SEALED AND CORROSION RESISTANT JOINT (1).

Method for inserting a concrete lining when driving tunnels, galleries and the like, in particular when driving a knife blade, as well as tools for carrying out the method

Devices for coupling or locating pipes

827,484. Pipe couplings. LUCAS (INDUSTRIES) Ltd., J. May 15, 1958 [May 17, 1957], No. 15713/57. Class 99(1). A means for coupling pipes or for connecting a circular burner or tube into a sheet metal combustion chamber, comprises an annular component a, Fig. 1, inserted on or into a pipe, having a flange e which has lateral freedom of movement in the annular groove formed between two interconnected members i and f. In Fig. 1 for coupling two pipes b, g, the member i is secured, e.g. by welding, to a flange h on the member f and may be positioned by a spacer h<SP>1</SP>. The spigot a fits into or over pipe b and the member f is integral with the second pipe g. In another embodiment the annular component k, Fig. 2, fits over a burner tube m and has a flange n which has free lateral movement in the groove. formed between members p and q secured to the. combustion chamber wall o. Slots S and the annular passage t allow cooling air to pass from the chamber enclosed by jacket r.

Macrocyclics pyrimidines as aurora kinase inhibitors

Macrocyclic derivative compounds that inhibit protein kinase enzymes are disclosed along with pharmaceutical compositions comprising these compounds and methods for synthesizing the same. Such compounds have utility in the treatment of proliferative diseases resulting from unregulated and/or disturbed kinase activity such as cancers, psoriasis, viral and bacterial infections, inflammatory and autoimmune diseases.

Respirator

Nucleic acids encoding nuclear Dbf2-related (Ndr) kinases

The current invention describes the identification of a novel widely-expressed human and D. melanogaster serine/threonine protein kinase (designated nuclear, Dbf2-related kinase, or Ndr; previously referred to as Ndr) and the use of this kinase for the identification of agonists and antagonists. The kinase is a nuclear protein and contains a short basic peptide, KRKAETWKRNRR, responsible for the nuclear accumulation.

Improvements to flat knitting machines

Fire escape system

Methods and apparatus for providing visible indication of an escape route through an enclosed smoke obscured area are disclosed. In preferred embodiments one or preferably two laser beams are directed into the system from an exit and are housed in shrouding. The shrouding has windows through which the beam can be seen when smoke particles are present in the air. Preferably the two beams are housed in juxtaposed shrouds one of which has large holes for access of smoke, giving early warning of a smoke condition. The early warning shroud communicates with the other shroud via restricted access so that smoke only penetrates into this shroud and reveals its beam in severe smoke conditions but the beam in this shroud is not extinguished until much later than the early warning beam.

Porous element and the preparation thereof

A porous tubular element of uniform density and porosity is formed by uniformly depositing binder and crushable fibers selected from the group consisting essentially of polycrystalline, alumina, zirconia, aluminum silicate and potassium polytitanate fibers from an aqueous dispersion onto a cylindrical mold. The tubular element is then compressed with sufficient pressure to crush and rearrange the fibers to obtain uniform density and porosity.

KNIFE BLADE WITH CHANGEABLE CROSS-SECTION

System and method for automatic design of components in libraries

Embodiments of the present invention introduce a novel recursive assembly process to automatically create a library of components. It starts with simple components used as building blocks and proceeds by repeatedly combining these randomly into more complex ones. The utility and quality of these random combinations of components are measured against a set of functional goals. Useful combinations then become new components in the library that can be used as building blocks for further random combination. This description is not intended to be a complete description of, or limit the scope of, the invention. Other features, aspects, and objects of the invention can be obtained from a review of the specification, the figures, and the claims.

FLUID SUPPLY CIRCUIT FOR ROTARY HEADS OF HAVAGE

Fixing method for optical fibres to walls of enclosures - uses cylindrical sleeve between conductor core and sheath to clamp cable into bushes inserted in enclosure wall

The method of fixing for an insulated conductor, typically an optical fibre, is aimed at reducing the tensile stress on the conductor to improve reliability, and comprises the following steps: insertion between the core (7) and the sleeve (9) of the conductor (8) of a rigid cylinder (13), and binding or clamping (10) the conductor through this cylindrical insert. The inner diameter of the cylinder is slightly greater than the overall diameter of the core (7) of the conductor (8), and the thermoplastic sleeve (9) of the conductor (8) is heat softened from the core end prior to the insertion of the cylindrical element. The clamping ring (10) is fitted into a flanged insert (1) pressed into a hole (2) in the wall (3) of the enclosure the cable is entering, and two cylindrical pieces (11,15) are fitted over the cable end and press fitted into the main insert (1) from the opposite side of the wall (3).

Pharmaceutical anti-fungal use of cholane derivatives

Methods for producing fabs and bi-specific antibodies

The present invention provides methods for producing Fabs and bi-specific antibodies comprising designed residues in the interfaces of the heavy chain-light chain variable (V H /V L ) domain and the heavy chain-light chain constant (C H1 /C L ] domain, Fabs and bi-specific antibodies produced according to said processes and host cells encoding the same.

A key cylinder

Driving arrangement for the drive elements for threading the upper thread into the eye of the needle of a sewing machine

A drive arrangement for the drive elements for the threading of the upper thread into the eye of a sewing machine needle is provided. Instead of individual drives for lowering the threading device and rotating it as well as threading the thread regulator to deflect the upper thread around the thread brake, drives not used at that time for the needle rod, the presser foot pressure, and the thread brake are utilized. In this way, two to three additional electric drives can be omitted and thus the controlling expense can be reduced.

SPREAD SHIELD, ESPECIALLY FOR THE ROAD DRIVING IN MINING UNDERGROUND

Fluid supply systems for rotary cutter heads for mining machines

Patent DE2937826C2

Article of furniture

A "knock-down" article of furniture, e.g. a desk, is made of a desk top 10, secured to a supporting structure made up primarily of two perpendicularly oriented base frames 12 by means of spaced connecting means each comprising a male resiliently deformable circular part 28 attached to the lower surface of the desk top 10 which is received in the open end of a square tubular frame portion 42, 43. The supporting structure may also include side frames 14 and a back panel 16. Each desk unit may be connected with similar units to form a composite desk for a plurality of people. Screens may be provided between adjacent desk tops. <IMAGE>

Ndr phosphokinase

The present invention relates to the phosphorylated form of nuclear serine/threonine protein kinase, designated n uclear, D bf2- r elated kinase (Ndr), and provides assays and materials for identifying modulators thereof. The invention relates to the fields of molecular biology, chemistry, pharmacology, and screening technology. Normal text

Multi-head flat knitting machine

Nuclear protein serine/threonine kinases

The current invention describes the identification of a novel widely-express ed human and D. melanogasterserine/threonine protein kinase (designated nuclear, Dbf2-relate d kinase, or Ndr; previously referred to as Ndr) and the use of this kinase for the identification of agonists and antagonists. The kinase is a nuclear protein and contains a sho rt basic peptide, KRKAETWKRNRR, responsible for the nuclear accumulation.

A key operable locking mechanism

Thrust reverser for fan type jet propulsion engines

In a gas turbine jet propulsion fan engine, the fan duct outer wall is provided with primary and secondary fan air blocker flaps. In the nonoperative position, both sets of flaps cooperate to provide a continuous duct outer wall and in the operative position, the primary flaps fold upon themselves across the duct so as to block it and the secondary flaps translate rearwards, the effect being to provide a radial outlet for the fan air, which outlet is substantially clear of structure.

A hinge

Abstract A method for making a hinge wherein the process involves welding, soldering, brazing or employing a like heat process for mounting a flap (101) to a first member (100) of the hinge; wherein, a second member (103) of the hinge includes a longitudinal projection (111) that is at least a portion of a pin, bar, stump, post or the like; and wherein, welding of the flap (101) to the first member (100) is completed prior to the formation of a longitudinal hole (102) in the first member (100) of a size sufficient to accommodate the at least a portion (111); and the first member is pivotable about the at least a portion when the hinge is assembled. too Jlo I - /0 1 iio2

A lock mechanism

Fault management system for a communications network

There is described a method of operating a fault management system for an access network which forms part of a communications network. In the access network, terminating lines in the form of pairs of copper wires extend from a local switch (10) through a series of nodes to terminal equipment provided for user of the network. The fault management system includes a test head (104) and an access network management system (102). Each night, the test head (104) performs a series of tests on each of the terminating lines. The results of the tests are transmitted to the access network management (102). The test results are then analysed with respect of a set of parameter to identify characteristics that would indicate that a fault is likely to occur on the associated circuit within a predetermined period e.g. 1 year. Further analysis can then be carried out to establish the probability of the fault actually occurring and/or whether the potential fault analysed is going to occur in either the underground or the over-ground part of the network.

Ball

Platform for integrating disparate ecosystems within a vehicle

A system for integrating disparate ecosystems including smart home and internet-of-things (IoT) ecosystems. The system including a vehicle assistant that executes within the context of a cloud-based application and that retrieves sensor data and utterances from a vehicle and forwards the sensor data and passenger-spoken utterances to a cloud-based application. Using the sensor data and utterances, the cloud-based application selects and executes a predetermined routine that includes at least one action to be completed in vehicle, on mobile phone or Smart Home/IoT ecosystem. The action is then complete by issuing the command to the vehicle head-unit, specified mobile phone or target ecosystem selected from a group of disparate ecosystems.

Tumour suppressor and uses thereof

A human protein (designated Carboxy-terminal Modulating protein, CTMP) is described and is identified as having tumour suppressor properties. CTMP has been shown to interact with protein kinase B and inhibit protein kinase B activity, establishing its importance in the protein kinase B signalling pathway.

Morphine and codeine derivatives for use in therapy

A compound of formula (I) wherein R1 = H (morphine analogue), CH3 (codeine analogue), R2 = H, alkyl group of 1 to 4 carbon atoms, allyl, cyclopropylmethyl, R3 = a group (A), -O-CH2-R4 (ether), -O-COCH = CHR4 (cinnamate), R4 = (B), wherein X1, X2, X3, X4 and X5 which may be the same or different are separately selected from H, alkyl of 1 to 4 carbon atoms, NH2, NO2, alkoxy group of 1 to 4 carbon atoms, hydroxy, halogen, N-alkyl, group of 1 to 4 carbon atoms, morpholine, or a group COR5 wherein R5 is H, OH, O-alkyl where alkyl is from 1 to 4 carbon atoms, or one of X1 and X2, X2 and X3, X3 and X4 or X4 and X5 together with an alkylene group optionally interrupted by O, S or N of up to 5 atoms in length complete a ring and a pharmaceutically acceptable salt thereof for use in therapy.

Platform for integrating disparate ecosystems within a vehicle

A system for integrating disparate ecosystems including smart home and internet-of-things (IoT) ecosystems. The system including a vehicle assistant that executes within the context of a cloud-based application and that retrieves sensor data and utterances from a vehicle and forwards the sensor data and passenger-spoken utterances to a cloud-based application. Using the sensor data and utterances, the cloud-based application selects and executes a predetermined routine that includes at least one action to be completed in vehicle, on mobile phone or Smart Home/IoT ecosystem. The action is then complete by issuing the command to the vehicle head-unit, specified mobile phone or target ecosystem selected from a group of disparate ecosystems.

Macrocyclic pyrimidines as protein kinase inhibitors

Macrocyclic derivative compounds that inhibit protein kinase enzymes are disclosed along with pharmaceutical compositions comprising these compounds and methods for synthesizing the same. Such compounds have utility in the treatment of proliferative diseases resulting from unregulated and/or disturbed kinase activity such as cancers, psoriasis, viral and bacterial infections, inflammatory and autoimmune diseases.