1. A method of measuring an alignment error, said method comprising:
using a first patterning structure to impart a beam of radiation with a first pattern in its cross-section;
projecting the beam having the first pattern onto a first side of a substrate to create a first mark;
subsequent to said projecting the beam having the first pattern, turning said substrate over;
aligning said substrate with respect to a reference position;
using a second patterning structure to impart a beam of radiation with a second pattern in its cross-section;
projecting the beam having the second pattern onto a second side of said substrate, said second side being substantially opposite to said first side, to create a second mark;
detecting a position of said first mark on said first side of said substrate in a plane substantially parallel to said first side; and
detecting a position of said second mark on said second side of said substrate in a plane substantially parallel to said second side,
wherein said substrate is transparent to the beams of radiation, and
wherein, between said detecting a position of said first mark and said detecting a position of said second mark, the substrate remains stationary relative to a substrate table holding said substrate.
2. The method of measuring according to claim 1, said method comprising, based on a result of said detecting a position of said first mark and a result of said detecting a position of said second mark, determining a displacement between said first mark and said second mark in a plane substantially parallel to said first side.
3. The method of measuring according to claim 1, wherein said second mark is a mirror image of said first mark.
4. The method of measuring according to claim 1, wherein said detecting a position of said first mark and said detecting a position of said second mark are performed using a detection system,
wherein during said detecting a position of said first mark, said first mark is located in a focal plane of said detection system, and
wherein during said detecting a position of said second mark, said second mark is located in the focal plane of said detection system.
5. The method of measuring according to claim 1, wherein said second mark is offset from said first mark by a known amount.
6. The method of measuring according to claim 1, wherein said first and second marks are substantially identical.
7. The method of measuring according to claim 1, wherein said aligning is performed using front to back side alignment optics.
8. The method of measuring according to claim 1, wherein said projecting the beam having the first pattern comprises projecting at least one beam having the first pattern onto the first side of said substrate to create a plurality of first marks, and
wherein said projecting the beam having the second pattern comprises projecting at least one beam having the second pattern onto the second side of said substrate to create a plurality of second marks, each of said plurality of second marks corresponding to one of the plurality of first marks.
9. A method of measuring according to claim 1, said method comprising: subsequent to said detecting a position of said first mark and said detecting a position of said second mark, rotating said substrate about an axis substantially perpendicular to said first side by substantially one-hundred-eighty degrees; and subsequent to said rotating, detecting a second position of said first mark on said first side of said substrate in a plane substantially parallel to said first side and detecting a second position of said second mark on said second side of said substrate in a plane substantially parallel to said second side.
10. The method of measuring according to claim 8, wherein said plurality of second marks is a mirror image of said plurality of first marks.
11. The method of measuring according to claim 10, wherein said turning said substrate over comprises turning said substrate about an axis parallel to an axis of symmetry of at least one of said plurality of second marks.
12. A method of measuring according to claim 9, said method comprising, based on a result of said detecting a position of said first mark and a result of said detecting a position of said second mark, determining a first displacement between said first mark and said second mark in a plane substantially parallel to said first side and based on a result of said detecting a second position of said first mark and said detecting a second position of said second mark, determining a second displacement between said first mark and said second mark in a plane substantially parallel to said first side.
13. A method of measuring according to claim 12, said method comprising calculating an overlay value based on a difference between said first and second displacements.
14. A method of measuring an alignment error, said method comprising:
using a first patterning structure to impart a beam of radiation with a first pattern in its cross-section;
projecting the beam having the first pattern onto a first side of a substrate to create a first mark;
subsequent to said projecting the beam having the first pattern, turning said substrate over;
aligning said substrate with respect to a reference position;
using a second patterning structure to impart a beam of radiation with a second pattern in its cross-section;
projecting the beam having the second pattern onto a second side of said substrate, said second side being substantially opposite to said first side, to create a second mark;
detecting from the first side a position of said first mark on said first side of said substrate in a plane substantially parallel to said first side; and
detecting from the first side, through the substrate, a position of said second mark on said second side of said substrate in a plane substantially parallel to said second side,
wherein said substrate is transparent to an alignment beam of radiation,
wherein, between said detecting a position of said first mark and said detecting a position of said second mark, the substrate remains stationary relative to a substrate table holding said substrate, and
wherein said second mark is a mirror image of said first mark.
15. The method of measuring according to claim 14, wherein said detecting a position of said first mark and said detecting a position of said second mark are performed using a detection system,
wherein during said detecting a position of said first mark, said first mark is located in a focal plane of said detection system, and
wherein during said detecting a position of said second mark, said second mark is located in the focal plane of said detection system.
16. The method of measuring according to claim 14, wherein said second mark is offset from said first mark by a known amount.
17. The method of measuring according to claim 14, wherein said first and second marks are substantially identical.
18. The method of measuring according to claim 14, wherein said aligning is performed using front to back side alignment optics.
19. The method of measuring according to claim 14, said method comprising, based on a result of said detecting a position of said first mark and a result of said detecting a position of said second mark, determining a first displacement between said first mark and said second mark in a plane substantially parallel to said first side.
20. The method of measuring according to claim 14, wherein said projecting the beam having the first pattern comprises projecting at least one beam having the first pattern onto the first side of said substrate to create a plurality of first marks, and
wherein said projecting the beam having the second pattern comprises projecting at least one beam having the second pattern onto the second side of said substrate to create a plurality of second marks, each of said plurality of second marks corresponding to one of the plurality of first marks.
21. A method of measuring according to claim 19, said method comprising:
subsequent to said detecting a position of said first mark and said detecting a position of said second mark, rotating said substrate about an axis substantially perpendicular to said first side by substantially one-hundred-eighty degrees; and
subsequent to said rotating, detecting a second position of said first mark on said first side of said substrate in a plane substantially parallel to said first side and detecting a second position of said second mark on said second side of said substrate in a plane substantially parallel to said second side.
22. A method of measuring according to claim 21, said method comprising, based on a result of said detecting a second position of said first mark and said detecting a second position of said second mark, determining a second displacement between said first mark and said second mark in a plane substantially parallel to said first side.
23. A method of measuring according to claim 22, said method comprising calculating an overlay value based on a difference between said first displacement and second displacements.
24. The method of measuring according to claim 20, wherein said plurality of second marks is a mirror image of said plurality of first marks.
25. The method of measuring according to claim 24, wherein said turning said substrate over comprises turning said substrate about an axis parallel to an axis of symmetry of at least one of said plurality of second marks.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
What is claimed:
1. A nucleic acid comprising a nucleotide sequence encoding a polypeptide comprising: (a) amino acid residues 27-309 of SEQ ID NO:2 (human NgR NTLRRCT domain), or amino acid residues 27-309 of SEQ ID NO:2 with 1-20 conservative amino acid substitutions; and (b) and less than a complete CTS domain, provided that a partial CTS domain, if present, consists of no more than the first 39 consecutive amino acid residues.
2. The nucleic acid of claim 1, wherein the encoded polypeptide comprises amino acid residues 27-309 of SEQ ID NO:2.
3. The nucleic acid of claim 1, wherein the encoded polypeptide comprises fewer than 50 consecutive amino acids from amino acids 310-445 of SEQ ID NO:2.
4. The nucleic acid of claim 1, wherein the encoded polypeptide does not comprise a functional GPI domain.
5. A vector comprising the nucleic acid of claim 1.
6. The vector of claim 5, wherein the nucleic acid is operably linked to an expression control sequence.
7. A cell comprising the vector of claim 5.
8. A polypeptide comprising: (a) amino acid residues 27-309 of SEQ ID NO:2 (human NgR NTLRRCT domain), or amino acid residues 27-309 of SEQ ID NO:2 with 1-20 conservative amino acid substitutions; and (b) fewer than 115 consecutive amino acids from amino acids 310-445 of SEQ ID NO:2.
9. The polypeptide of claim 8, wherein the polypeptide comprises amino acid residues 27-309 of SEQ ID NO:2.
10. The polypeptide of claim 8, wherein the polypeptide comprises fewer than 50 consecutive amino acids from amino acids 310-445 of SEQ ID NO:2.
11. The polypeptide of claim 8, wherein the encoded polypeptide does not comprise a functional GPI domain.
12. A method of producing the polypeptide of claim 8, comprising introducing a nucleic acid encoding the polypeptide into a host cell, culturing the host cell under conditions suitable for expression of said polypeptide, and recovering the polypeptide.
13. An antibody that binds to an epitope in the CTS domain of NgR.
14. A method of inhibiting binding of a Nogo polypeptide to a NgR, comprising contacting the Nogo polypeptide with an effective amount of the polypeptide of claim 8.
15. A method of inhibiting binding of a Nogo polypeptide to a NgR, comprising contacting the NgR with an antibody that binds to the amino acid sequence consisting of SEQ ID NO:2 (NgR polypeptide).
16. The method of claim 15, wherein the antibody binds to an epitope within amino acids 310-445 of SEQ ID NO:2 (CTS domain of NgR).
17. A method of decreasing inhibition of axonal growth by a CNS neuron, comprising contacting the neuron with an effective amount of a molecule selected from the group consisting of: (a) a polypeptide of claim 8; and (b) an antibody that binds to the amino acid sequence consisting of SEQ ID NO:2 (NgR).
18. The method of claim 17, wherein the antibody binds to an epitope within the amino acid sequence consisting of amino acids 310-445 of SEQ ID NO:2 (CTS domain of NgR).
19. A method of treating a central nervous system disease, disorder or injury, comprising administering to a mammal an effective amount of an agent selected from the group consisting of (a) an agent that inhibits binding of a Nogo polypeptide to a NgR; and (b) an agent that inhibits NgR-dependent signal transduction in a central nervous system neuron.
20. The method of claim 19, wherein the agent that inhibits binding of a Nogo polypeptide to a NgR is selected from the group consisting of: (a) a polypeptide of claim 8; (b) an antibody that binds to a polypeptide consisting of SEQ ID NO:2.
21. The method of claim 20 wherein the antibody binds to an epitope within the amino acid sequence consisting of amino acids 310-445 of SEQ ID NO:2 (CTS domain of NgR).
22. The method of claim 19, wherein the central nervous system disease, disorder or injury is a spinal cord injury.
23. A method for identifying a molecule that decreases Nogo-dependent inhibition of axonal growth, the method comprising:
(a) providing a NgR polypeptide;
(b) contacting the NgR polypeptide with a candidate molecule; and
(c) detecting a decrease in binding of the Nogo polypeptide to the NgR in the presence of the candidate molecule, as compared to the binding of the Nogo polypeptide to the NgR in the absence of the candidate molecule.
24. A composition comprising a polypeptide of claim 8 and a pharmaceutically acceptable carrier.
25. A composition comprising an antibody of claim 13 and a pharmaceutically acceptable carrier.
26. A nucleic acid comprising a nucleotide sequence encoding a polypeptide comprising an amino acid sequence selected from the group consisting of: (a) IYKGVIQAI and (b) EELV, the polypeptide comprising 40 amino acids or fewer.
27. The nucleic acid of claim 26, wherein the polypeptide comprises the amino acid sequences IYKGVIQAI and EELV.
28. The nucleic acid of claim 26, wherein the polypeptide comprises fewer than 40 amino acids.
29. The nucleic acid of claim 28, wherein the polypeptide comprises amino acid residues 2 to 34 of SEQ ID NO:21.
30. The nucleic acid of claim 26, wherein the polypeptide encoded further comprises a heterologous amino acid sequence not present in NogoA, the heterologous amino acid sequence comprising at least five amino acid residues.
31. A polypeptide comprising an amino acid sequence selected from the group consisting of: (a) IYKGVIQAI and (b) EELV, the polypeptide comprising 40 amino acids or fewer.
32. The polypeptide of claim 31, wherein the polypeptide comprises the amino acid sequences IYKGVIQAI and EELV.
33. The polypeptide of claim 32, wherein the polypeptide comprises fewer than 40 amino acids.
34. The polypeptide of claim 33, wherein the polypeptide comprises amino acid residues 2 to 34 of SEQ ID NO:21.
35. The polypeptide of claim 31, wherein the polypeptide further comprises a heterologous amino acid sequence not present in NogoA, the heterologous amino acid sequence comprising at least five amino acid residues.
36. An antibody that binds to a polypeptide of claim 31.
37. A composition comprising a polypeptide of claim 31 or an antibody according to claim 36 and a pharmaceutically acceptable carrier.
38. A method of inhibiting binding of a Nogo polypeptide to a NgR, comprising contacting the NgR with an effective amount of the polypeptide of claim 31.
39. A method of inhibiting binding of a Nogo polypeptide to a NgR, comprising contacting the Nogo polypeptide with an effective amount of the antibody according to claim 36.
40. A method of decreasing inhibition of axonal growth by a CNS neuron, comprising contacting the neuron with an effective amount of a polypeptide of claim 31 or an antibody of claim 36.
41. A method of treating a central nervous system disease, disorder or injury, comprising administering to a mammal an effective amount of a polypeptide of claim 31 or an antibody of claim 36.
42. The method of claim 41, wherein the central nervous system disease, disorder or injury is a spinal cord injury.
43. A method of identifying a molecule that decreases axonal Nogo-dependent inhibition of axonal growth, the method comprising:
(a) providing a polypeptide comprising a target sequence consisting of an amino acid sequence selected from the group consisting of IYKGVIQAI and EELV;
(b) contacting the polypeptide with a candidate molecule; and
(c) detecting binding of the candidate molecule to a target sequence in the polypeptide.