1.-17. (canceled)
18. A tooling for holding a pair of preformed parts to be friction-welded together to form a generally hollow structure having at least one internal stiffener section, the tooling comprising:
a framework positioned along outer surfaces of the preformed parts and holding the pair of preformed parts inside the framework against the internal stiffener section to form the hollow structure, the framework having two generally rectangular frames formed of a pair of length members extending in an extension direction, the two frames movable with respect to each other to be joined together in an assembled position on both outer surfaces of the preformed parts and extending in the general plane in which the hollow structure extends the framework including shape-holder members which are shaped to correspond and contact an outer surface of the preformed parts;
a welding path defined between the length members of the framework, wherein a welding pin is adapted to be passed through the welding path to weld the preformed parts together,
at least one anvil installed inside the framework and extending in the extension direction, the anvil adapted for being inserted inside the pair of preformed parts laterally adjacent the internal stiffener section; and
a reversible clamp installed inside the framework and extending in the extension direction adapted for being inserted inside the pair of preformed parts laterally adjacent the anvil, wherein the clamp applies a clamping thrust in at least two directions such that thrust is applied in a lateral direction to the anvil and the clamp applies thrust in a second direction along an inside surface of each of the pair of preformed parts to oppose force applied to the outer surface of the pair of preformed parts by the shape-holder members of the framework,
wherein the pair of preformed parts is held with the clamp and framework in a welding position so that abutting edges of the pair of preformed parts is friction-welded together adjacent the internal stiffener section along the extension direction of the hollow structure.
19. The tooling according to claim 18, wherein the reversible clamp inflates to apply the clamping force.
20. The tooling according to claim 19, wherein the reversible clamp is deflated while installed in the framework inside the hollow structure, and the reversible clamp inflates to apply the clamping force.
21. The tooling according to claim 19, wherein the reversible clamp includes at least one inflatable bladder.
22. The tooling according to claim 21, wherein the reversible clamp includes a body provides for bearing against the inside face of the preformed part and for bearing against the anvil, wherein the body houses the inflatable bladder.
23. The tooling according to claim 19, wherein the reversible clamp includes at two inflatable bladders for being placed laterally on either side of the internal stiffener section.
24. The tooling according to claim 23, wherein the at least one anvil includes two anvils for being placed laterally on either side of the internal stiffener section and each anvil opposing the clamping force of one of the two inflatable bladders.
25. The tooling according to claim 18, wherein the welding path extends in the extension direction.
26. The tooling according to claim 18, wherein the shape-holder members include backing thrust members that are individually mounted on the framework with position-adjustment means to oppose the thrust applied by the reversible clamp.
27. The tooling according to claim 26, wherein the backing thrust members are distributed mounted on the length members.
28. A tooling for holding a set of preformed parts to be friction-welded together to construct a generally plane hollow structure being made up of the set of preformed parts, the tooling comprising:
a framework for receiving the preformed parts inside the framework for welding together to form the hollow structure, the framework being subdivided into two frames to be joined together in an assembled position on both outer surfaces of the preformed parts and extending in the general plane in which the hollow structure extends, the framework including shape-holder members which are shaped to correspond and contact the outer surfaces of the preformed parts;
at least one anvil disposed inside the framework; and
a reversible clamp installed inside the framework and movable into a clamping position in which the clamp inflates to apply opposing thrust in at least two directions such that thrust is applied in a lateral direction to the anvil and applied in a second direction to the inside surface of at least one preformed part disposed inside the framework,
wherein the preformed parts are held in a welding position with the clamp and framework while a welding operation is performed.
29. The tooling according to claim 28, wherein the shape-holder members includes backing thrust members that are individually mounted on one of the other of the frames via position-adjustment means.
30. The tooling according to claim 29, wherein the backing thrust members are distributed at least along a pair of length members forming part of each of the frames, the length members of the pair leaving between them a path for passing a welding tool towards the preformed parts placed in overlap on the flanges of the section.
31. The tooling according to claim 28, wherein the reversible clap is arranged as deformable members that are movable between the clamping position and an assembly position in which deformable members are suitable for being inserted inside the set of preformed parts installed inside the framework.
32. The tooling according to claim 28, wherein the reversible clamp includes at least one inflatable bladder.
33. The tooling according to claim 32, wherein the reversible clamp includes a body that is suitable for bearing against the inside face of the preformed part and that houses the bladder suitable for bearing against the anvil.
34. A tooling for holding a pair of preformed parts to be friction-welded together to form a generally hollow structure having at least one internal stiffener section, the tooling comprising:
a framework positioned along outer surfaces of the preformed parts and holding the pair of preformed parts inside the framework against the internal stiffener section to form the hollow structure, the framework having two generally rectangular frames formed of a pair of length members extending in an extension direction, the two frames movable with respect to each other to be joined together in an assembled position on both outer surfaces of the preformed parts and extending in the general plane in which the hollow structure extends the framework including shape-holder members which are shaped to correspond and contact an outer surface of the preformed parts;
a welding path defined between the length members of the framework, wherein a welding pin is adapted to be passed through the welding path to weld the preformed parts together,
two anvils installed inside the framework and extending in the extension direction and installed laterally on either side of the internal stiffener section; and
two reversible clamps installed inside the framework and extending in the extension direction for being inserted inside the pair of preformed parts, wherein each clamp applies a clamping thrust in at least two directions such that thrust is applied in a lateral direction to one of the anvils and each clamp applies thrust in a second direction along an inside surface of each of the pair of preformed parts to oppose force applied to the outer surface of the pair of preformed parts by the shape-holder members,
wherein the pair of preformed parts is held with the clamps and framework in a welding position so that abutting edges of the pair of preformed parts is friction-welded together adjacent the internal stiffener section along the extension direction of the hollow structure.
35. The tooling according to claim 34, wherein the reversible clamps inflate to apply the clamping forces.
36. The tooling according to claim 35, wherein the reversible clamps are deflated while installed in the framework inside the hollow structure, and the reversible clamps inflate to apply the clamping forces.
37. The tooling according to claim 35, wherein each reversible clamp includes an inflatable bladder for being placed laterally on either side of the internal stiffener section.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
1. A method for treating a cardiovascular or metabolic disorder in a mammal, comprising subcutaneously administering to the mammal a polypeptide comprising an amino acid sequence as set forth in SEQ ID NO:3, or an amino acid sequence as set forth in SEQ ID NO:3 having less than five amino acid additions, subtractions, and substitutions.
2. The method of claim 1, wherein the polypeptide comprises an amino acid sequence as set forth in SEQ ID NO:3 having less than five amino acid additions, subtractions, and substitutions.
3. The method of claim 1, wherein the polypeptide comprises an amino acid sequence as set forth in SEQ ID NO:3 having less than four amino acid additions, subtractions, and substitutions.
4. The method of claim 1, wherein the polypeptide comprises the amino acid sequence as set forth in SEQ ID NO:3.
5. The method of claim 1, wherein the polypeptide consists of the amino acid sequence set forth in SEQ ID NO:3.
6. The method of claim 1, wherein the cardiovascular disorder is selected from the group consisting of hypertension, resistant hypertension, and myocardial infarction.
7. The method of claim 1, wherein the metabolic disorder is selected from the group consisting of obesity and type II diabetes.
8. The method of claim 1, comprising administering the polypeptide via depot polymer, transdermal patch, injection, pump, microparticle, or nanoparticle.
9. The method of claim 1, further comprising administering to the mammal insulin andor an aldosterone inhibitor.
10. The method of claim 9, wherein the aldosterone inhibitor is spironolactone or eplerenone.
11. The method of claim 9, comprising administering the polypeptide and the insulin andor aldosterone inhibitor simultaneously.
12. The method of claim 9, comprising administering the polypeptide and the insulin andor aldosterone inhibitor sequentially.
13. The method of claim 1, wherein the polypeptide is coupled to a fatty acid.
14. A method for treating a cardiovascular or metabolic disorder in a mammal, comprising subcutaneously administering to the mammal a composition comprising a polypeptide comprising an amino acid sequence as set forth in SEQ ID NO:3, or an amino acid sequence as set forth in SEQ ID NO:3 having less than five amino acid additions, subtractions, and substitutions.
15. The method of claim 14, wherein the polypeptide comprises an amino acid sequence as set forth in SEQ ID NO:3 having less than five amino acid additions, subtractions, and substitutions.
16. The method of claim 14, wherein the polypeptide comprises an amino acid sequence as set forth in SEQ ID NO:3 having less than four amino acid additions, subtractions, and substitutions.
17. The method of claim 14, wherein the polypeptide comprises the amino acid sequence as set forth in SEQ ID NO:3.
18. The method of claim 14, wherein the polypeptide consists of the amino acid sequence set forth in SEQ ID NO:3.
19. The method of claim 14, wherein the cardiovascular disorder is selected from the group consisting of hypertension, resistant hypertension, and myocardial infarction.
20. The method of claim 14, wherein the metabolic disorder is selected from the group consisting of obesity and type II diabetes.
21. The method of claim 14, comprising administering the composition via depot polymer, transdermal patch, injection, pump, microparticle, or nanoparticle.
22. The method of claim 14, further comprising administering to the mammal insulin andor an aldosterone inhibitor.
23. The method of claim 22, wherein the aldosterone inhibitor is spironolactone or eplerenone.
24. The method of claim 22, wherein the composition comprises the polypeptide and the insulin andor aldosterone inhibitor.
25. The method of claim 22, comprising administering the composition separately from the insulin andor aldosterone inhibitor.
26. The method of claim 14, wherein the polypeptide is coupled to a fatty acid.
27. A method for making a conjugate comprising a polypeptide coupled to palmitic acid, comprising:
providing a polypeptide comprising an amino acid sequence as set forth in SEQ ID NO:3, or an amino acid sequence as set forth in SEQ ID NO:3 having less than five amino acid additions, subtractions, and substitutions, wherein said polypeptide is linked to a solid phase synthesis resin;
adding 1 mmol palmitic acid in 5 ml dichloromethane (DCM) to the peptide-resin;
adding 4 ml of dimethylformamide (DMF) containing 1 mmol N-hydroxybenzotriazole and 1 mmol O-benzotriazole-N,N,N\u2032,N\u2032-tetramethyl-uronium-hexafluorophosphate to the reaction mixture;
adding 2 mmol diisopropylethylamine to the reaction mixture;
incubating the reaction mixture for 18 hours at room temperature with shaking;
washing the peptide-resin with DMF;
washing the peptide-resin with DCM; and
cleaving the palmitoylated peptide from the resin.