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Disc cartridge |
A disc cartridge includes a cartridge body, a first shutter, a second shutter, and a rotational member. The cartridge body includes a disc storage portion, a chucking opening and a head opening. The disc storage portion has a disc window and a bottom and stores a disc, having first and second sides, therein so that the disc is rotatable in the disc storage portion and that the disc exposes the first side inside the disc window. The first and second shutters are provided on the bottom of the disc storage portion to expose or cover the head opening. The rotational member is provided over the first and second shutters inside the disc storage portion and is engaged with the first and second shutters in such a manner as to open or close the first and second shutters when rotates inside the disc storage portion. |
1. A disc cartridge comprising: a cartridge body including a disc storage portion, a chucking opening and a head opening, wherein the disc storage portion has a disc window and a bottom and stores a disc, having first and second sides, therein so that the disc is rotatable in the disc storage portion and that the disc exposes the first side inside the disc window; the chucking opening is provided on the bottom of the disc storage portion so as to get the disc chucked externally; and the head opening is also provided on the bottom of the disc storage portion so as to allow a head, which reads and/or writes a signal from/on the second side of the disc, to access the second side of the disc; a first shutter and a second shutter, which are provided on the bottom of the disc storage portion to expose or cover the head opening; and a rotational member, which is provided over the first and second shutters inside the disc storage portion and which is engaged with the first and second shutters in such a manner as to open or close the first and second shutters when rotates inside the disc storage portion. 2. The disc cartridge of claim 1, wherein the center of rotation of the rotational member substantially matches with the center of the disc that is stored in the disc storage portion. 3. The disc cartridge of claim 2, wherein the rotational member includes: a disc supporting portion for supporting an outer edge of the second side of the disc thereon; and a notch provided for the disc supporting portion, the notch being located inside the head opening while the first and second shutters are opened. 4. The disc cartridge of claim 3, wherein while the first and second shutters are closed, the disc supporting portion contacts with the outer edge of the second side of the disc. 5. The disc cartridge of claim 1, wherein the first and second shutters each include a notch so as to define a hole in a region corresponding to a center hole of the disc while the first and second shutters are closed. 6. The disc cartridge of claim 5, wherein the first and second shutters include first and second convex portions around the notches of the first and second shutters, respectively. 7. The disc cartridge of claim 6, wherein the upper surface of the disc supporting portion of the rotational member and the upper surface of the first and second convex portions of the first and second shutters are located at substantially the same vertical levels. 8. The disc cartridge of claim 7, wherein the first and second shutters respectively include first and second protrusions that protrude into the center hole of the disc while the first and second shutters are closed. 9. The disc cartridge of claim 8, wherein the upper surface of the first and second protrusions of the first and second shutters is located at a vertical level higher than the upper surface of the first and second convex portions thereof. 10. The disc cartridge of claim 3, wherein the first and second shutters have their shafts under the disc supporting portion of the rotational member. 11. The disc cartridge of claim 10, wherein the disc supporting portion of the rotational member includes first and second protrusions that protrude toward the bottom of the disc storage portion, and wherein the first and second shutters include first and second guide grooves that respectively engage with the first and second protrusions of the rotational member. 12. The disc cartridge of claim 1, wherein the rotational member has a sidewall that covers the outer side surface of the disc, and wherein a first opener/closer is provided for the sidewall. 13. The disc cartridge of claim 12, wherein the head opening reaches a first side surface of the cartridge body, and wherein the cartridge body has an opening on a second side surface thereof that is adjacent to the first side surface, and wherein the first opener/closer is located inside the opening of the second side surface. 14. The disc cartridge of claim 13, wherein at least one of the first and second shutters includes a second opener/closer that protrudes from the head opening. 15. The disc cartridge of claim 1, wherein the first and second shutters include a number of disc holders, which contact with an outer edge and a surrounding portion of the disc and hold the disc thereon while the first and second shutters are closed. 16. The disc cartridge of claim 15, wherein each said disc holder has a downwardly tapered slope. 17. A disc cartridge comprising: a cartridge body including a disc storage portion, a chucking opening and a head opening, wherein the disc storage portion has a disc window and a bottom and stores a disc, having first and second sides, therein so that the disc is rotatable in the disc storage portion and that the disc exposes the first side inside the disc window; the chucking opening is provided on the bottom of the disc storage portion so as to get the disc chucked externally; and the head opening is also provided on the bottom of the disc storage portion so as to allow a head, which reads and/or writes a signal from/on the second side of the disc, to access the second side of the disc; a first shutter and a second shutter, which are provided on the bottom of the disc storage portion to expose or cover the head opening; and a rotational member, which is provided over the first and second shutters inside the disc storage portion and which rotates as the first and second shutters are opened or closed, wherein the rotational member includes: a disc supporting portion for supporting an outer edge of the second side of the disc thereon while the first and second shutters are closed; and a notch provided for the disc supporting portion, the notch being located inside the head opening while the first and second shutters are opened. 18. The disc cartridge of claim 17, further comprising a shielding member, which is located inside the notch of the disc supporting portion while the first and second shutters are closed and which swings in a radial direction of the disc. 19. The disc cartridge of claim 18, wherein the shielding member contacts with the outer edge of the disc while the first and second shutters are closed. 20. The disc cartridge of claim 19, wherein the shielding member has a shaft that is located over the first side of the disc and that is parallel to a tangent line defined with respect to the disc. 21. The disc cartridge of claim 20, wherein the shielding member swings as the rotational member rotates. 22. The disc cartridge of claim 21, wherein the rotational member includes a sidewall that covers the outer side surface of the disc, and wherein the shaft of the shielding member is located between an upper shell of the cartridge body and the rotational member. 23. The disc cartridge of claim 17, wherein the disc storage portion includes a sidewall along an outer periphery of the bottom, and wherein one of the first and second shutters includes a disc holder for applying an elastic force to the disc and holding the disc thereon in such a manner that the outer edge of the disc contacts with the sidewall of the disc storage portion inside the notch of the rotational member while the first and second shutters are closed. 24. A disc cartridge comprising: a cartridge body including a disc storage portion, a chucking opening and a head opening, wherein the disc storage portion has a disc window and a bottom and stores a disc, having first and second sides, therein so that the disc is rotatable in the disc storage portion and that the disc exposes the first side inside the disc window; the chucking opening is provided on the bottom of the disc storage portion so as to get the disc chucked externally; and the head opening is also provided on the bottom of the disc storage portion so as to allow a head, which reads and/or writes a signal from/on the second side of the disc, to access the second side of the disc; and at least one disc stopper, which is provided for the cartridge body so as to protrude into the disc window and thereby prevent the disc from dropping through the disc window, wherein the radius R1 of the disc and the radius R2 of a smallest circular opening, of which the center matches with the center of the disc window and which is in contact with the disc stopper, satisfy 14/15≦=R2/R1. 25. The disc cartridge of claim 24, wherein the radii R1 and R2 satisfy 14/15<R2/R1<1. 26. The disc cartridge of claim 24, further comprising another disc stopper, wherein the two disc stoppers are arranged symmetrically with respect to the center of the disc window. 27. A disc cartridge comprising: a cartridge body including a disc storage portion, a chucking opening and a head opening, wherein the disc storage portion has a disc window and a bottom and stores a disc, having first and second sides, therein so that the disc is rotatable in the disc storage portion and that the disc exposes the first side inside the disc window; the chucking opening is provided on the bottom of the disc storage portion so as to get the disc chucked externally; and the head opening is also provided on the bottom of the disc storage portion so as to allow a head, which reads and/or writes a signal from/on the second side of the disc, to access the second side of the disc; and a type recognizing region, which is provided for the cartridge body to recognize the type of the disc stored in the disc cartridge, wherein the presence and absence of a concave portion in/from the type recognizing region represent two possible types of the disc stored in the disc cartridge. 28. The disc cartridge of claim 27, wherein the cartridge body further includes a positioning hole, which is engageable with a positioning pin of a disc drive, and wherein the type recognizing region is provided near the positioning hole. 29. The disc cartridge of claim 27, wherein one of the two possible types of the disc to be stored in the disc cartridge has a single signal recording layer, while the other type of the disc has double signal recording layers, and wherein if the disc stored in the disc cartridge has a single signal recording layer, then the concave portion is absent from the type recognizing region, and wherein if the disc stored in the disc cartridge has double signal recording layers, then the concave portion is present in the type recognizing region. 30. A disc cartridge comprising: a cartridge body including a disc storage portion, a chucking opening and a head opening, wherein the disc storage portion has a disc window and a bottom and stores a disc, having first and second sides, therein so that the disc is rotatable in the disc storage portion and that the disc exposes the first side inside the disc window; the chucking opening is provided on the bottom of the disc storage portion so as to get the disc chucked externally; and the head opening is also provided on the bottom of the disc storage portion so as to allow a head, which reads and/or writes a signal from/on the second side of the disc, to access the second side of the disc; a first shutter and a second shutter, which are provided on the bottom of the disc storage portion to expose or cover the head opening; a groove, which is provided on, and extends along, a first side surface of the cartridge body; an opener/closer, which protrudes through the bottom of the groove and which moves along the groove, thereby opening or closing the first and second shutters; a first concave portion, which is provided on the first side surface of the cartridge body; and a second concave portion, which is provided on a second side surface of the cartridge body, the second side surface being opposed to the first side surface, wherein the first concave portion is continuous with the groove on the first side surface and has a bottom that is deeper than the bottom of the groove, and wherein the bottom of the first concave portion and the bottom of the groove are connected together by a sloped surface that defines a predetermined angle with the bottom of the first concave portion. 31. The disc cartridge of claim 30, wherein the first concave portion passes through the back surface of the cartridge body but does not reach the upper surface of the cartridge body. 32. The disc cartridge of claim 31, wherein a side surface of the first concave portion, which crosses the bottom of the first concave portion, is located closer to the upper surface of the cartridge body than a side surface of the groove, which crosses the bottom of the groove. 33. The disc cartridge of claim 31, wherein the predetermined angle that is defined by the sloped surface with the bottom of the first concave portion is in the range of about 20 degrees to about 40 degrees. 34. A disc cartridge comprising: a cartridge body including a disc storage portion, a chucking opening and a head opening, wherein the disc storage portion has a disc window and a bottom and stores a disc, having first and second sides, therein so that the disc is rotatable in the disc storage portion and that the disc exposes the first side inside the disc window; the chucking opening is provided on the bottom of the disc storage portion so as to get the disc chucked externally; and the head opening is also provided on the bottom of the disc storage portion so as to allow a head, which reads and/or writes a signal from/on the second side of the disc, to access the second side of the disc; a first shutter and a second shutter, which provided on the bottom of the disc storage portion to expose or cover the head opening; and a write-protect mechanism, which is provided for the cartridge body, wherein the write-protect mechanism includes: an elongated hole, which is provided on the back surface of the cartridge body and which includes a first region and a second region; and a sliding member, which has a raised portion that protrudes through the elongated hole and which is supported such that the raised portion goes back and forth inside the elongated hole, and wherein when the disc cartridge is overlapped with another disc cartridge, which complies with a different set of specifications and which also includes a first region and a second region, such that the center of the disc stored in the former disc cartridge matches with that of the disc stored in the latter disc cartridge and that insert directions of the two disc cartridges are matched with each other, the first region of the another disc cartridge for use to determine whether the disc stored therein is writable or unwritable overlaps with the first region of the disc cartridge almost completely and the second region of the another disc cartridge for use to read information unique to the disc stored therein also overlaps with the second region of the disc cartridge almost completely, the first and second regions of the another disc cartridge being arranged in a direction that is perpendicular to the direction that the front sides of the two disc cartridges face, and wherein a direction in which the elongated hole extends intersects with the direction in which the first and second regions of the another disc cartridge are arranged, and wherein the sliding member goes back and forth inside the elongated hole such that the first region of the elongated hole is selectively opened or closed. 35. The disc cartridge of claim 34, wherein the cartridge body includes a side surface having a portion that is parallel to the elongated hole. |
<SOH> BACKGROUND ART <EOH>Various disc cartridges have been proposed as protective cases for disk storage media. For example, Japanese Laid-Open Publication No. 9-153264 discloses a disc cartridge in which a disk storage medium having a single or double signal recording sides (which will be herein referred to as a “disc” simply) is completely enclosed in a disc storage portion. The disc storage portion is defined inside a cartridge body that is made up of upper and lower halves. The cartridge body includes chucking openings and a head opening. The chucking openings allow the turntable of a spindle motor and a damper to chuck a disc inserted, while the head opening allows a read/write head to read and/or write a signal from/on the disc. The lower one of the chucking openings is continuous with the head opening. Accordingly, while the user carries such a cartridge, dust easily enters the inside of the cartridge through these openings and the disc is also easily soiled with finger marks. For that reason, the disc cartridge further includes a shutter for closing these openings up. A disc cartridge having such a structure, however, has the following drawbacks. Firstly, such a disc cartridge cannot be so thin. This is because the disc storage space, defined between the upper and lower halves, should be thick enough to allow a disc drive to accurately read or write a signal (or information) from/onto the disc stored in such a disc cartridge. The reasons why the disc storage space should be relatively thick include the expected flutter or warp of the disc being rotated and an error that may occur in disposing the disc cartridge at a predetermined position inside the disc drive. Secondly, the shutter for closing up these chucking and head openings at the same time cannot be formed at a low cost, thus increasing the overall manufacturing cost of such a disc cartridge. The reason is as follows. Specifically, the lower half of the disc cartridge is provided with a chucking opening for the turntable of the spindle motor and a head opening, while the upper half thereof is provided with another chucking opening for the clamper. Thus, to close these three openings up at a time, the shutter needs to be formed in a U-shape, which is not so cheap to make. Thirdly, the disc stored inside such a disc cartridge is not fixed in many cases, thus possibly causing dust or fine particle deposition and scratching problems. Specifically, although a disc with a metal hub can be attracted and fixed in position via a magnetic force so as not to move inconstantly, an optical disc with no hub, e.g., a CD or a DVD, is normally not fixed, and movable freely, inside the disc cartridge. Accordingly, when the shutter of the disc cartridge is opened inside the disc drive, dust may enter the cartridge through its openings and be deposited on the disc easily. Also, if the disc is shaken so much as to contact with the inner walls of the disc cartridge, the signal recording side of the disc may get scratched or fine particles may be stirred up and deposited on the disc. |
<SOH> BRIEF DESCRIPTION OF DRAWINGS <EOH>FIG. 1 is a perspective view illustrating an overall configuration for a disc cartridge according to a first specific preferred embodiment of the present invention. FIG. 2 is a perspective view of the disc cartridge shown in FIG. 1 as viewed from below it. FIG. 3 is an exploded perspective view of the disc cartridge shown in FIG. 1 . FIG. 4 is a cross-sectional view illustrating a disc older and a surround portion of the disc cartridge shown in FIG. 1 . FIG. 5 is a cross-sectional view illustrating another disc holder and a surround portion of the disc cartridge shown in FIG. 1 . FIG. 6 is a perspective view illustrating a state of the disc cartridge shown in FIG. 1 in which its shutter is opened and positioning pins have been inserted into its positioning holes. FIG. 7 is a cross-sectional view illustrating a disc holder and a surround portion of the disc cartridge shown in FIG. 6 . FIG. 8 is a perspective view illustrating another disc holder and a surround portion of the disc cartridge shown in FIG. 6 . FIG. 9 is a plan view illustrating an overall configuration for a disc cartridge according to a second specific preferred embodiment of the present invention. FIG. 10 is a plan view illustrating a state of the disc cartridge shown in FIG. 9 in which the disc has been released from its disc holders. FIG. 11 is a plan view illustrating an overall configuration for a disc cartridge according to a third specific preferred embodiment of the present invention. FIG. 12 is a plan view illustrating a state of the disc cartridge shown in FIG. 11 in which the disc has been released from its disc holders. FIG. 13 is a plan view illustrating an overall configuration for a disc cartridge according to a fourth specific preferred embodiment of the present invention. FIG. 14 is a plan view illustrating a state of the disc cartridge shown in FIG. 13 in which the disc has been released from its disc holder. FIG. 15 is a plan view illustrating an overall configuration for a disc cartridge according to a fifth specific preferred embodiment of the present invention in a state where its shutter is closed. FIG. 16 is a cross-sectional view of a disc holder of the disc cartridge in the-state shown in FIG. 15 . FIG. 17 is a plan view illustrating an overall configuration for the disc cartridge shown in FIG. 15 in a state where its shutter is opened. FIG. 18 is a cross-sectional view of the disc holder of the disc cartridge in the state shown in FIG. 17 . FIG. 19 is a plan view illustrating an overall configuration for a disc cartridge according to a sixth specific preferred embodiment of the present invention in a state where its shutter is closed. FIG. 20 is a plan view illustrating an overall configuration for the disc cartridge shown in FIG. 19 in a state where its shutter is opened. FIG. 21 is a plan view illustrating an overall configuration for a disc cartridge according to a seventh specific preferred embodiment of the present invention in a state where its shutter is closed. FIG. 22 is a plan view illustrating an overall configuration for the disc cartridge shown in FIG. 21 in a state where its shutter is opened. FIG. 23 is a perspective view illustrating an overall configuration for a disc cartridge according to an eighth specific preferred embodiment of the present invention. FIG. 24 is an exploded perspective view of the disc cartridge shown in FIG. 23 . FIG. 25 is a perspective view illustrating the disc cartridge shown in FIG. 23 with its upper shell and the disc removed to show a state where its shutters are closed. FIG. 26 is a perspective view illustrating the disc cartridge shown in FIG. 23 with its upper shell and the disc removed to show a state where its shutters are opened. FIG. 27 is a perspective view illustrating the disc cartridge shown in FIG. 23 with the disc removed to show a state where its shutters are closed. FIG. 28 is a perspective view illustrating the disc cartridge shown in FIG. 23 with the disc removed to show a state where its shutters are opened. FIG. 29 is a partial cross-sectional view of the disc cartridge shown in FIG. 23 , which is viewed along a plane that passes the center of the disc. FIG. 30 is a cross-sectional view illustrating a portion of the shutter of the disc cartridge shown in FIG. 23 . FIG. 31 is a partial plan view illustrating a shutter opener/closer and its surrounding portion of the disc cartridge shown in FIG. 23 . FIG. 32 is a perspective view illustrating a disc stopper of the disc cartridge shown in FIG. 23 . FIG. 33 is a front view illustrating the insertion side of the disc cartridge shown in FIG. 23 . FIG. 34 is a perspective view illustrating an overall configuration for a disc cartridge according to a ninth specific preferred embodiment of the present invention. FIG. 35 is an exploded perspective view of the disc cartridge shown in FIG. 34 . FIG. 36 is a perspective view illustrating the disc cartridge shown in FIG. 34 with the disc removed to show a state where its shutters are closed. FIG. 37 is a perspective view illustrating the disc cartridge shown in FIG. 34 with the disc removed to show a state where its shutters are opened. FIG. 38 is a partial cross-sectional view of the disc cartridge shown in FIG. 34 , which is viewed along a plane that passes the center of the disc to show a state where its shutters are closed. FIG. 39 is a partial cross-sectional view of the disc cartridge shown in FIG. 34 , which is viewed along a plane that passes the center of the disc to show a state where its shutters are opened. FIG. 40 is a partial cross-sectional view illustrating a portion of the disc cartridge shown in FIG. 34 around the disc outer periphery, which is viewed along a plane passing the center of the disc to show a state where its shutters are closed. FIG. 41 is a partial cross-sectional view illustrating a portion of the disc cartridge shown in FIG. 34 around the disc outer periphery, which is viewed along a plane passing the center of the disc to show a state where its shutters are opened. FIG. 42 is a perspective view illustrating an overall configuration for a disc cartridge according to a tenth specific preferred embodiment of the present invention. FIG. 43 is an exploded perspective view of the disc cartridge shown in FIG. 42 . FIG. 44 is a perspective view illustrating the disc cartridge shown in FIG. 42 with the disc removed to show a state where its shutters are closed. FIG. 45 is a perspective view illustrating the disc cartridge shown in FIG. 42 with the disc removed to show a state where its shutters are opened. FIG. 46 is a partial cross-sectional view of the disc cartridge shown in FIG. 42 , which is viewed along a plane that passes the center of the disc to show a state where its shutters are closed. FIG. 47 is a partial cross-sectional view of the disc cartridge shown in FIG. 42 , which is viewed along a plane that passes the center of the disc to show a state where its shutters are opened. FIG. 48 is a partial cross-sectional view illustrating a portion of the disc cartridge shown in FIG. 42 around the disc outer periphery, which is viewed along a plane passing the center of the disc to show a state where its shutters are closed. FIG. 49 is a partial cross-sectional view illustrating a portion of the disc cartridge shown in FIG. 42 around the disc outer periphery, which is viewed along a plane passing the center of the disc to show a state where its shutters are opened. FIG. 50 is a perspective view illustrating an overall configuration for a disc cartridge according to an eleventh specific preferred embodiment of the present invention. FIG. 51 is an exploded perspective view of the disc cartridge shown in FIG. 50 . FIG. 52 is a perspective view illustrating the disc cartridge shown in FIG. 50 with the disc removed to show a state where its shutters are closed. FIG. 53 is a perspective view illustrating the disc cartridge shown in FIG. 50 with the disc removed to show a state where its shutters are opened. FIG. 54 is a partial cross-sectional view of the disc cartridge shown in FIG. 50 , which is viewed along a plane that passes the center of the disc to show a state where its shutters are closed. FIG. 55 is a partial cross-sectional view of the disc cartridge shown in FIG. 50 , which is viewed along a plane that passes the center of the disc to show a state where its shutters are opened. FIG. 56 is a cross-sectional view illustrating a portion of the shutter of the disc cartridge shown in FIG. 50 . FIG. 57 is a partial plan view illustrating a shutter opener/closer and its surrounding portion of the disc cartridge shown in FIG. 50 . FIG. 58 is a perspective view illustrating a disc cartridge according to a twelfth specific preferred embodiment of the present invention with the disc removed to show a state where its shutters are closed. FIG. 59 is a partial cross-sectional view of the disc cartridge shown in FIG. 58 , which is viewed along a plane that passes the center of the disc to show a state where its shutters are closed. FIG. 60 is a perspective view illustrating the disc cartridge shown in FIG. 58 with the disc removed to show a state where its shutters are opened. FIG. 61 is a partial cross-sectional view of the disc cartridge shown in FIG. 58 , which is viewed along a plane that passes the center of the disc to show a state where its shutters are opened. FIG. 62 is a perspective view illustrating a modified example of the disc cartridge shown in FIG. 58 with the disc removed to show a state where its shutters are closed. FIG. 63 is a perspective view illustrating a modified example of the disc cartridge shown in FIG. 58 with the disc removed to show a state where its shutters are opened. FIG. 64 is a perspective view illustrating an overall configuration for a disc cartridge according to a thirteenth specific preferred embodiment of the present invention. FIG. 65 is an exploded perspective view of the disc cartridge shown in FIG. 64 . FIG. 66 is a schematic plan view illustrating a state of the disc cartridge shown in FIG. 64 in which its shutters are closed. FIG. 67 is a schematic plan view illustrating a state of the disc cartridge shown in FIG. 64 in which its shutters are opened. FIG. 68 is a plan view illustrating the details of the shutter locking mechanism of the disc cartridge shown in FIG. 64 . FIG. 69 is a cross-sectional view illustrating the details of the disc holder of the shutter in the disc cartridge shown in FIG. 64 . FIG. 70 is a cross-sectional view illustrating the shapes of a pair of contact portions between the two shutters of the disc cartridge shown in FIG. 64 . FIG. 71 is a cross-sectional view illustrating the shapes of another pair of contact portions between the two shutters of the disc cartridge shown in FIG. 64 . FIG. 72 is a perspective view illustrating an overall configuration for a disc cartridge according to a fourteenth specific preferred embodiment of the present invention. FIG. 73 is a perspective view illustrating the shutters the disc cartridge shown in FIG. 72 . FIG. 74 is a perspective view illustrating the disc holders and their surrounding members of the disc cartridge shown in FIG. 72 to a larger scale. FIG. 75 is a perspective view illustrating the disc holder and its surrounding portion of the disc cartridge shown in FIG. 72 to a larger scale. FIG. 76 is a cross-sectional view illustrating the disc older and its surrounding members of the disc cartridge shown in FIG. 72 to a larger scale. FIG. 77 is a schematic plan view illustrating a state of the disc cartridge shown in FIG. 72 in which its shutters are closed. FIG. 78 is a schematic plan view illustrating a state of the disc cartridge shown in FIG. 72 in which its shutters are opened. FIG. 79 is a cross-sectional view of the disc cartridge shown in FIG. 72 taken along the line B-B shown in FIG. 78 . FIG. 80 is a cross-sectional view of the disc cartridge shown in FIG. 72 taken along the line C-C shown in FIG. 78 . FIG. 81 is a cross-sectional view of the disc cartridge shown in FIG. 72 taken along the line A-A shown in FIG. 77 . FIG. 82 is a cross-sectional view illustrating a modified example of the disc supporting portion. FIG. 83 is an exploded perspective view of a disc cartridge according to a fifteenth specific preferred embodiment of the present invention. FIG. 84 is a schematic plan view illustrating a state of the disc cartridge shown in FIG. 83 in which its shutters are closed. FIG. 85 is a schematic plan view illustrating a state of the disc cartridge shown in FIG. 83 in which its shutters are opened. FIG. 86 is a cross-sectional view of the disc cartridge shown in FIG. 83 taken along the line D-D shown in FIG. 84 . FIG. 87 is a cross-sectional view of the disc cartridge shown in FIG. 83 taken along the line E-E shown in FIG. 85 . FIG. 88 is a perspective view illustrating an overall configuration for a disc cartridge according to a sixteenth specific preferred embodiment of the present invention. FIG. 89 is an exploded perspective view of the disc cartridge shown in FIG. 88 . FIG. 90 is a schematic plan view illustrating a state of the disc cartridge shown in FIG. 88 in which its shutters are closed. FIG. 91 is a schematic plan view illustrating a state of the disc cartridge shown in FIG. 88 in which its shutters are opened. FIG. 92 is a schematic plan view illustrating a modified example of the disc cartridge shown in FIG. 88 in which its shutters are closed. FIG. 93 is a schematic plan view illustrating a state of the disc cartridge shown in FIG. 92 in which its shutters are opened. FIG. 94 is a perspective view illustrating an overall configuration for a disc cartridge according to a seventeenth specific preferred embodiment of the present invention. FIG. 95 is an exploded perspective view of the disc cartridge shown in FIG. 94 . FIG. 96 is a schematic plan view illustrating a state of the disc cartridge shown in FIG. 94 in which its shutters are closed. FIG. 97 is a schematic plan view illustrating a state of the disc cartridge shown in FIG. 94 in which its shutters are opened. FIG. 98 is a perspective view illustrating an overall configuration for a disc cartridge according to an eighteenth specific preferred embodiment of the present invention. FIG. 99 is an exploded perspective view of the disc cartridge shown in FIG. 98 . FIG. 100 is a schematic plan view illustrating a state of the disc cartridge shown in FIG. 98 in which its shutters are closed. FIG. 101 is a schematic plan view illustrating a state of the disc cartridge shown in FIG. 98 in which its shutters are opened. FIG. 102 is an exploded perspective view of a disc cartridge according to a nineteenth specific preferred embodiment of the present invention. FIG. 103 is a cross-sectional view illustrating a disc holder and its surrounding members of the disc cartridge shown in FIG. 102 to a larger scale. FIG. 104 is an exploded perspective view of a disc cartridge according to a twentieth specific preferred embodiment of the present invention. FIG. 105 is a plan view illustrating the disc cartridge shown in FIG. 104 with its upper shell removed. FIG. 106 is a cross-sectional view of the disc cartridge shown in FIG. 104 taken along the line F-F shown in FIG. 105 . FIG. 107 is a plan view illustrating the shutters and rotational member of the disc cartridge shown in FIG. 104 in a state where the shutters are closed. FIG. 108 is a cross-sectional view of the disc cartridge shown in FIG. 104 taken along the line G-G shown in FIG. 107 . FIG. 109 is a plan view illustrating the shutters and rotational member of the disc cartridge shown in FIG. 104 in a state where the shutters are opened. FIG. 110 is a cross-sectional view of the disc cartridge shown in FIG. 104 taken along the line H-H shown in FIG. 109 . FIG. 111 is a perspective view illustrating the shielding member of the disc cartridge shown in FIG. 104 . FIG. 112 is a cross-sectional view illustrating how the shielding member shown in FIG. 111 is supported by the upper shell. FIG. 113 is a cross-sectional view illustrating the end of the shielding member in a state where the shutters are closed. FIG. 114 is a cross-sectional view illustrating the center of the shielding member in a state where the shutters are closed. FIG. 115 is a cross-sectional view illustrating the end of the shielding member in a state where the shutters are opened. FIG. 116 is a cross-sectional view illustrating the center of the shielding member in a state where the shutters are opened. FIG. 117 is a schematic plan view illustrating a modified example of the disc cartridge shown in FIG. 104 . FIG. 118 is a schematic plan view illustrating another modified example of the disc cartridge shown in FIG. 104 . FIG. 119 is a plan view of the disc cartridge shown in FIG. 104 . FIG. 120 is a plan view illustrating the back surface of a disc cartridge according to a twenty-first specific preferred embodiment of the present invention. FIG. 121 is a side view of the disc cartridge shown in FIG. 120 as viewed in the direction indicated by the arrow 121 . FIG. 122 is a side view of the disc cartridge shown in FIG. 120 as viewed in the direction indicated by the arrow 122 . FIG. 123 is a perspective view illustrating main members of the disc cartridge shown in FIG. 120 . FIG. 124 is a plan view illustrating the write-protect mechanism and surrounding members of the disc cartridge shown in FIG. 120 on a larger scale. FIG. 125 is an exploded perspective view of the write-protect mechanism for use in the disc cartridge shown in FIG. 120 . FIG. 126 is a perspective view illustrating a situation where the write-protect mechanism indicates a writable state. FIG. 127 is a perspective view illustrating a situation where the write-protect mechanism indicates an unwritable state. detailed-description description="Detailed Description" end="lead"? |
Micro-organisms for the treatment of soil and process for obtaining them |
The present invention relates to product(s) containing living microorganism(s) suitable for soil treatment, microorganisms multiplying under different climatic and natural circumstances, as well as procedures for the production of the products, and procedures for the treatment of the soil and plants with the products. More particularly, the invention relates to a procedure for preparing the products from any of the microorganisms specified below, or from the mixture thereof. Furthermore, the invention relates to a procedure for the creation of the cultures of the microorganisms to be used. The subject invention also pertains to the microorganisms themselves. More particularly, the invention relates to a procedure for the treatment of the soil and the plants with a product containing at least one of the microorganisms selected from Azospirillum brasilense ssp. SW51 (NCAIM /P/ B 001293), Azotobacter vinelandii ssp. M657 (NCAIM /P/B 001292), Pseudomonas fluorescens var. SW11 (NCAIM /P/ B 001296), Bacillus polymyxa var. SW17 (NCAIM /P/ B 001295), Bacillus megaterium var. M326 (NCAIM /P/ B 001291), Micrococcus roseus ssp. A21 (NCAIM /P/B 001294), Bradyrhizobium japonicum var. PH25 (NCAIM /P/ B 001302), and Streptomyces albus var. 0003 LP (NCAIM /P/ B 001301), and furthermore the products multiplying and existing in the environment of the plant in question, containing the listed microorganisms and their production. |
1-10. (canceled). 11. A preparation suitable for treatment of soil and plant seeds, which comprises a living microorganism or microorganisms capable of propagating in different soil types in the environment of a plant, characterized by containing the culture of at least one microorganism that can propagate at low temperature and in soils with low pH. 12. The preparation according to claim 11, wherein said preparation comprises agriculturally acceptable wet or dry carriers non-toxic for said microorganism. 13. The preparation according to claim 11, wherein said preparation comprises at least one of the following compounds selected from the group consisting of water, soya flour, starch, and glucose, or a derivative of these, as carrier. 14. The preparation according to claim 11, wherein said at least one microorganism is selected from the group consisting of the strains Azospirillum brasilense ssp. SW51 (NCAIM /P/ B 001293), Azotobacter vinelandii ssp. M657 (NCAIM /P/B 001292), Pseudomonas fluorescens var. SW11 (NCAIM /P/ B 001296), Bacillus polymyxa var. SW17 (NCAIM /P/ B 001295), Bacillus megaterium var. M326 (NCAIM /P/ B 001291), Micrococcus roseus ssp. A21 (NCAIM /P/B 001294), Bradyrhizobium japonicum var. PH25 (NCAIM /P/ B 001302), and Streptomyces albus var. 0003 LP (NCAIM /P/ B 001301). 15. The preparation according to claim 11, wherein said preparation comprises 5×106 to 5×1011 cell/gm of said microorganism. 16. The preparation according to claim 11, wherein said preparation comprises 107 to 1010 cells/gram of said microorganism. 17. The preparation according to claim 11, wherein said at least one microorganism can propagate at temperature below 20° C. 18. The preparation according to claim 11, wherein said at least one microorganism can propagate in soils with a pH below 5.0. 19. A process for preparing a preparation of claim 11 suitable for the treatment of soil and plant seeds, characterized by cultivating separately or together, in a culture medium containing a carbon source and a nitrogen source and inorganic salts, at least one microorganism that can propagate at low temperature and in soils with low pH until reaching between 5×107 and 5×109 cells per milliliter. 20. The process according to claim 19, further comprising mixing the culture or cultures obtained in a specified proportion. 21. The process according to claim 19, further comprising depositing the culture or cultures obtained on the carrier or mixing therewith. 22. The process according to claim 19, further comprising freeze drying the culture or cultures obtained. 23. The process according to claim 19, wherein said carbon source is glucose; and said nitrogen source is selected from the group consisting of ammonium nitrate, ammonium sulphate, corn steep liquor, and casein-hydrolyzate; and said inorganic salt is calcium carbonate, or salts dissociating from sodium-, potassium-, magnesium-, calcium-, ferro-, nitrate-, chloride-, sulphate-, carbonate-, phosphate-ions, or trace elements. 24. A microorganism optimally propagating at a temperature below 20° C. and at a pH below 5, selected from the group consisting of microorganisms deposited in the National Collection of the Agricultural and Industrial Microorganisms (NCAIM) under the following numbers: a) Azospirillum brasilense ssp. SW51 (NCAIM /P/ B 001293); b) Azotobacter vinelandii ssp. M657 (NCAIM /P/B 001292); c) Pseudomonas fluorescens var. SW11 (NCAIM /P/ B 001296); d) Bacillus polymyxa var. SW17 (NCAIM /P/ B 001295); e) Bacillus megaterium var. M326 (NCAIM /P/ B 001291); f) Micrococcus roseus ssp. A21 (NCAIM /P/B 001294); g) Bradyrhizobium japonicum var. PH25 (NCAIM /P/B 001302); and h) Streptomyces albus var. 0003 LP (NCAIM /P/ B 001301). 25. A process for the preparation of the microorganisms according to claim 24, characterized by taking a soil sample from the environment of plants, from the upper layer of 40 cm of a given type of soil, identifying the selected microorganisms, applying a treatment to said microorganisms with mutation agents, and isolating variant microorganisms that can propagate at low temperature. 26. The process according to claim 25, wherein said variant microorganisms can propagate at a temperature below 20° C. 27. A process for soil treatment with a preparation of claim 11, comprising applying transport microorganism cells in quantities between 1010 and 1014 cells pro hectare on or in the soil, in frost-free period. 28. The process according to claim 27, wherein said quantity is between 1011 and 1012 cells pro hectare. 29. The process according to claim 27, wherein said preparation comprises at least one of the following compounds selected from the group consisting of water, soya flour, starch, and glucose, or a derivative of these, as carrier. 30. A process for the treatment of plant seeds with a preparation of claim 11, comprising treating the seeds with a liquid product comprising said at least one microorganism of said preparation or a mixture thereof. 31. The process according to claim 30, wherein said preparation comprises at least one of the following compounds selected from the group consisting of water, soya flour, starch, and glucose, or a derivative of these, as carrier. 32. A process for improving or maintaining the soil structure, characterized by transporting polysaccharides of microbiological origin. 33. The process according to claim 32, wherein said polysaccharides are from a microorganism or microorganisms that can biosynthesize succinoglucone in the soil. 34. The process according to claim 33, wherein said microorganism or microorganisms are selected from the group consisting of the strains Bacillus polymyxa var. SW17 (NCAIM /P/ B 001295), Bacillus megaterium var. M326 (NCAIM /P/ B 001291), Micrococcus roseus ssp. A21 (NCAIM /P/B 001294), and Bradyrhizobium japonicum var. PH25 (NCAIM /P/ B 001302). |
<SOH> BACKGROUND ART <EOH>The natural medium of the soil is the self-regulating ecosystem of the plants and micro-organisms, under natural circumstances, the existence of the former determines that of the other ones. When the balance developed in the course of the evolution is altered by human activities (deep ploughing, natural and artificial fertilisation, use of plant-protecting agents, etc.) in its structure and function, changes of non foreseeable effect can occur. For the development of the micro-organism populations needed for the optimal cultivation of a given cultivated plant, on the different soils and under different climatic circumstances, a selection time lasting for long years is needed. The determinant micro-organisms of the favourable micro-organism population, however, can be transported in the soil and the circumstances needed for the optimal cultivation can be created within one-two days. The result of this is the higher yield, without the harmful upsetting of the natural ecosystem. The useful and dominant micro-organisms existing in the environment of a given plant important from economic point of view can be determined by laboratory experiments and these can be individually multiplied, produced by industrial methods, and can be brought back in the soil in proper proportion. Important regularities can be discovered in the ecosystem of the soil and micro-organisms. The number of the micro-organisms is different and different species can be identified in the immediate environment of the root system of the living plants (rhysosphere) and the germinating seeds (spermatosphere) than more remote from these. The propagation of the bacteria in the environment of the root is influenced by many factors. These factors depend on the region, quality of the soil, composition of the micro-organism population, and on the climatic circumstances. The carbon source to be found in the soil comes into being primarily and in the overwhelming majority by using the solar energy, with photosynthesis. The nitrogen cycle is more complicated than that of the carbon. On the transformation of nitrogen, biological and chemical processes have an effect. In the nature, the gaseous nitrogen in a so-called inert condition is dominant, and the so-called fixed nitrogen (nitrate, nitrite, ammonia) is present in a limited quantity. For the mineralization of the nitrogen gas first of all the biological nitrogen binding is responsible. Since over one hectare the quantity of the molecular nitrogen amounts to 6-7×10 8 tons, this means an inexhaustible source for the nitrogen bound. The interest of the experts is directed towards the nitrogen binding living beings, i.e. towards the living beings, which can reduce the molecular nitrogen to ammonia since, among others, the knowledge of these micro-organisms and the adequate utilisation of their properties can ensure, in an environment friendly manner, the world-wide ceasing of the hunger. Some nitrogen binding bacteria fix the nitrogen in free living condition but numerous bacteria are capable of nitrogen fixing only combined with other, higher plants. The phosphorousous cycle, contrary to that of the nitrogen, is practically closed under natural circumstances. The input and output are identical, the flow is slight, the air won't be contaminated with phosphorousous. Finally, this element accumulates in the waters, seas, and only a slight quantity of this gets back to the land (for instance in the form of guano). In the living cells of the soil the phosphorousous accumulates in organic compounds, the mineralization of these takes place with a high speed (3-8 g/m 2 /year). The solubility—so their accessibility for the plants—of the arising phosphorousous compounds is different, merely 5% of the 400-1200 mg phosphorousous detectable in each 1 kg of the average soils is available. The turnover of certain phosphorousous compounds is 500-2000 years. By transporting some phosphonolytic micro-organism groups in the soil, the complex phosphorousous compounds, which are not accessible for the plant, can be brought in solution. If the micro-organisms brought in the soil “function”, and the mineral contents of the soil are satisfactory, the use of the fertilizers containing phosphate is not necessary or can be considerably reduced. For growth, the plants need—especially at the time of the ripening of the crop—potassium of a considerable quantity. The plant cultivators bring the potassium in the soil by feeding of fertilizer with potassium content. This fertiliser can be made available from the potassium minerals by means of the micro-organisms releasing the potassium ion. As far as the plants are concerned, the micro-organisms multiplying in the soil biosynthetize physiologically active compounds, out of these the most important compounds being: phytohormones, auxins (indole-3-acetic acid), ethylene, gibberellines, kinetins, etc. Some Pseudomonas groups, in the presence of iron of a slight quantity, produce so-called siderophores, which can collect the iron. As a consequence of this, the other, phytopathogenic bacteria and fungi, since these cannot utilize the iron from the siderophores, suffer inhibition owing to the lack of iron, on the other hand, these siderophores, in soil with lack of iron, significantly stimulate the growth of the plants, since binding the iron, these directly provide the iron for the plant. For the solution of the above, several technical versions had been elaborated; several micro-organisms are described in the special literature in full details. Hungarian inventors disclosed the preparation of powdered nitrification cultures (Hungarian patent HU 143.391), Azobacter chroococcum and Rhizobium meliloti cultures (Hungarian patent HU 188.434), alga cultures (Hungarian patent HU 195.068) and Azotobacter chroococcum cultures again, as well as the preparation of the cultures of Bacillus megaterium micro-organisms (Hungarian patent HU 207.751). The Azobacter chroococcum had been deposited under the deposit No. 00238, the Bacillus megaterium under the serial No. NCAIM /P/ B 1140. More detailed, in Hungarian patents HU 188.434 and HU 207.751, the authors describe the fermentation turning out of the mixture of the above deposited micro-organisms. According to Hungarian patent HU 213 163 the authors complete the culture of the microorganisms of HU 207.751 with carboxy-methyl-cellulose. Hungarian inventors in HU 1671/96 describe cultures containing Azospirillum lipoferum ssp., Azobacter vinelandi sp., Pseudomonas fluorescens ssp. and Bacillus megaterium ssp. micro-organisms. The application and effect of the micro-organisms applied in the mentioned procedures are limited by the fact that these, under different cultivation circumstances, in soils of various compositions, under different climatic circumstances, survive only for a short time, the environment and rhysosphere of the various plants not always create optimal conditions. |
<SOH> SUMMARY <EOH>Subject of the invention is products and procedure for the treatment of the soil with bacteria for the improvement of the growth of the plants and for increasing the yields, procedures for making the products, micro-organism stocks serving as a basis of the products, multiplying at low temperature, biosynthetizing polysacharides, and procedure for the production of these. One of the micro-organism cells according to the invention or a compound of these, will be transported to the soil or fixed the seeds of the plants. With the procedure according to the invention a product will be transported to the soil, which product contains at least one of the soil-bacterium groups transforming the nitrogen of the air into compounds available for the plants, solubilising the mineralised phosphate- and potassium compounds and biosynthetising the materials improving the vegetal development, producing polysaccharides optimally influencing the structure of the soil, isolated from various soils and altered in laboratory, so satisfactory yields will be reached, practically excluding the application of the expensive fertilizers. detailed-description description="Detailed Description" end="tail"? |
Nr1h4 nuclear receptor binding compounds |
The present invention relates to compounds according to the general formula (1) which bind to the NR1H4 receptor and act as agonists, antagonists or mixed agonists/antagonists of the NR1H4 receptor. The invention further relates to the treatment of diseases and/or conditions through binding of said nuclear receptor by said compounds and the production of medicaments using said compounds. |
1. A compound including resolved diastereoisomers and enantiomers, and tautomers of the formula (1), or pharmaceutical acceptable salts or solvates thereof, wherein: R1 in formula (1) is H, C1 to C7 acyl or C1 to C7 substituted acyl, R2 is phenyl, substituted phenyl, C5 to C6 heteroaryl, C5 to C6 substituted heteroaryl, naphthyl or substituted naphthyl, R3 is H, C1 to C8 alkyl, C1 to C8 substituted alkyl, C3 to C8 cycloalkyl, C3 to C8 substituted cycloalkyl, C7 to C12 alkylphenyl, C7 to C12 substituted phenylalkyl, or phenyl, R4 is H, C1 to C8 alkyl, C1 to C8 substituted alkyl, C3 to C8 cycloalkyl, C3 to C8 substituted cycloalkyl, C7 to C12 alkylphenyl or C7 to C12 substituted phenylalkyl, R3 and R4 may be taken together with nitrogen to form a heterocycle or substituted heterocycle, or a heteroaryl or substituted heteroaryl ring, R5 is H, C1 to C8 alkyl, halogen, hydroxy, alkoxy, in particular C1 to C8 alkoxy, carboxy, ester, amide or C1 to C8 aminoacyl, R6 is H, C1 to C8 alkyl, C1 to C8 substituted alkyl and R7 is H, F, Cl, methyl, or trifluoromethyl. 2. The compound according to claim 1, or pharmaceutical acceptable salts or solvates thereof, wherein: R1 is H, R2 is substituted phenyl, C5 to C6 heteroaryl, or substituted C5 to C6 heteroaryl, R3 is H, R4 in formula (1) is a structure according to formula (2), —CH2—R4-1—CO2R8, formula (2) wherein: R4-1 is C1 to C8 alkyl, C1 to C8 substituted alkyl, C3 to C8 cycloalkyl, C3 to C8 substituted cycloalkyl, C5 to C6 aryl, C5 to C6 substituted aryl, C5 to C6 heteroaryl, or C5 to C6 substituted heteroaryl, and the methylene and the COOR8 substituents take the [1,4]-positions in case R4-1 is cyclohexyl, substituted cyclohexyl, C6 aryl, C6 substituted aryl, C6 heteroaryl, or C6 substituted heteroaryl; or the methylene and the COOR8-substituents take the [1,3]-positions in case R4-1 is cyclopentyl, substituted cyclopentyl, or substituted C5 heteroaryl; the methylene and the COOR8 substituents can have all possible diastereomeric configurations, R5 is H, a halogen, hydroxy, alkoxy or C1 to C8 alkyl, R6 is H, R7 is H, and R8 is H, methyl or ethyl. 3. The compound according to claim 1, or pharmaceutical acceptable salts or solvates thereof, wherein: R3 is H, R4 in formula (1) is a structure according to formula (3), —R4-1—CO2R8, formula (3) wherein: R4-1 is C1 to C8 alkyl, C1 to C8 substituted alkyl, C3 to C8 cycloalkyl, C3 to C8 substituted cycloalkyl, C5 to C6 aryl, C5 to C6 substituted aryl, C5 to C6 heteroaryl, or C5 to C6 substituted heteroaryl, and the methylene and the COOR8 substituents take the [1,4]-positions in case R4-1 is cyclohexyl, substituted cyclohexyl, C6 aryl, C6 substituted aryl, C6 heteroaryl, or C6 substituted heteroaryl; or the methylene and the COOR8-substituents take the [1,3]-positions in case R4-1 is cyclopentyl, substituted cyclopentyl, or substituted C5 heteroaryl; the methylene and the COOR8 substituents can have all possible diastereomeric configurations. 4. The compound according to claim 1, or pharmaceutical acceptable salts or solvates thereof, wherein: R1 is H, R2 is substituted phenyl, R3 is H, R4 in formula (1) is a structure according to formula (4), wherein the methylene and the COOR8 substituents can have all possible diastereomeric configurations, R5 is H, a halogen, hydroxy, alkoxy or C1 to C8 alkyl, R6 is H, R7 is H, and R8 is H, methyl or ethyl. 5. The compound according to claim 1, of the formula (5), or pharmaceutical acceptable salts or solvates thereof, wherein: R1 is H, R2 is substituted phenyl, C5 to C6 heteroaryl, or C5 to C6 substituted heteroaryl, R4 is H and R3 is a structure according to formula (6) wherein the COOR8 and the methylene substituents are in double axial (a,a) positions, R5 is H, a halogen, hydroxy, alkoxy or C1 to C8 alkyl, R6 is H, R7 is H, and R8 is H, methyl or ethyl. 6. The compound according to claim 1, of the formula (7) 7. The compound according to claim 1, of the formula (8) 8. The compound according to claim 1, of the formula (9) 9. The compound according to claim 1, of the formula (10) 10. The compound according to claim 1, of the formula (11) 11. The compound according to claim 1, of the formula (12) 12. The compound according to claim 1, of the formula (13) 13. The compound according to claim 1, of the formula (14) 14. (canceled) 15. The compound according to claim 1, wherein said compound binds with the human NR1H4 receptor protein or a portion thereof or a mammalian homologue thereof according to SEQ ID NO. 1. 16-25. (canceled) 26. The method, according to claim 36, which is for the prevention or treatment of a disease or condition which is mediated or can be addressed by the NR1H4 receptor in a mammal. 27. The method, according to claim 26, which is for regulating bile flow or the bile acid transport system in a mammal. 28. The method, according to claim 36, which is for treating in a mammal a disease or condition which is affected by impaired blood levels of cholesterol, lipoproteins, phospholipids, triglycerides, or bile acids and/or impaired bile flow or impaired bile levels of cholesterol, phospholipids or bile acids. 29. The method, according to claim 36, which is for treating in a mammal cholestatic conditions. 30. A method for treating in a mammal malign proliferative diseases such as cancer which can be treated by inducing apoptosis in the affected cells or tissues comprising administering to a mammal in need of such treatment a therapeutically effective amount of a compound including resolved diastereoisomers and enantiomers, and tautomers of the formula (1), or pharmaceutical acceptable salts or solvates thereof, wherein: R1 in formula (1) is H, C1 to C7 acyl or C1 to C7 substituted acyl, R2 is phenyl, substituted phenyl, C5 to C6 heteroaryl, C5 to C6 substituted heteroaryl, naphthyl or substituted naphthyl, R3 is H, C1 to C8 alkyl, C1 to C8 substituted alkyl, C3 to C8 cycloalkyl, C3 to C8 substituted cycloalkyl, C7 to C12 alkylphenyl, C7 to C12 substituted phenylalkyl, or phenyl, R4 is H, C1 to C8 alkyl, C1 to C8 substituted alkyl, C3 to C8 cycloalkyl, C3 to C8 substituted cycloalkyl, C7 to C12 alkylphenyl or C7 to C12 substituted phenylalkyl, R3 and R4 may be taken together with nitrogen to form a heterocycle or substituted heterocycle, or a heteroaryl or substituted heteroaryl ring, R5 is H, C1 to C8 alkyl, halogen, hydroxy, alkoxy, in particular C1 to C8 alkoxy, carboxy, ester, amide or C1 to C8 aminoacyl, R6 is H, C1 to C8 alkyl, C1 to C8 substituted alkyl and R7 is H, F, Cl, methyl, or trifluoromethyl. 31. A method for treating in a mammal conditions of drug resistance that arise during drug treatment of disorders such as cancer or infectious diseases, or during continuous administration of contraceptive drugs comprising administering to a mammal in need of such treatment a therapeutically effective amount of a compound including resolved diastereoisomers and enantiomers, and tautomers of the formula (1), or pharmaceutical acceptable salts or solvates thereof, wherein: R1 in formula (1) is H, C1 to C7 acyl or C1 to C7 substituted acyl, R2 is phenyl, substituted phenyl, C5 to C6 heteroaryl, C5 to C6 substituted heteroaryl, naphthyl or substituted naphthyl, R3 is H, C1 to C8 alkyl, C1 to C8 substituted alkyl, C3 to C8 cycloalkyl, C3 to C8 substituted cycloalkyl, C7 to C12 alkylphenyl, C7 to C12 substituted phenylalkyl, or phenyl, R4 is H, C1 to C8 alkyl, C1 to C8 substituted alkyl, C3 to C8 cycloalkyl, C3 to C8 substituted cycloalkyl, C7 to C12 alkylphenyl or C7 to C12 substituted phenylalkyl, R3 and R4 may be taken together with nitrogen to form a heterocycle or substituted heterocycle, or a heteroaryl or substituted heteroaryl ring, R5 is H, C1 to C8 alkyl, halogen, hydroxy, alkoxy, in particular C1 to C8 alkoxy, carboxy, ester, amide or C1 to C8 aminoacyl, R6 is H, C1 to C8 alkyl, C1 to C8 substituted alkyl and R7 is H, F, Cl, methyl, or trifluoromethyl. 32. The method, according to claim 36, which is for blocking in a mammal the cholesterol absorption or bile acid re-absorption in the intestine of a mammal in need of such blocking. 33. A method for regulating the expression of NR1H4 responsive genes wherein said method comprises administering a therapeutically effective amount of a compound including resolved diastereoisomers and enantiomers, and tautomers of the formula (1), or pharmaceutical acceptable salts or solvates thereof, wherein: R1 in formula (1) is H, C1 to C7 acyl or C1 to C7 substituted acyl, R2 is phenyl, substituted phenyl, C5 to C6 heteroaryl, C5 to C6 substituted heteroaryl, naphthyl or substituted naphthyl, R3 is H, C1 to C8 alkyl, C1 to C8 substituted alkyl, C3 to C8 cycloalkyl, C3 to C8 substituted cycloalkyl, C7 to C12 alkylphenyl, C7 to C12 substituted phenylalkyl, or phenyl, R4 is H, C1 to C8 alkyl, C1 to C8 substituted alkyl, C3 to C8 cycloalkyl, C3 to C8 substituted cycloalkyl, C7 to C12 alkylphenyl or C7 to C12 substituted phenylalkyl, R3 and R4 may be taken together with nitrogen to form a heterocycle or substituted heterocycle, or a heteroaryl or substituted heteroaryl ring, R5 is H, C1 to C8 alkyl, halogen, hydroxy, alkoxy, in particular C1 to C8 alkoxy, carboxy, ester, amide or C1 to C8 aminoacyl, R6 is H, C1 to C8 alkyl, C1 to C8 substituted alkyl and R7 is H, F, Cl, methyl, or trifluoromethyl. 34. The method, according to claim 36, which is for modulating the expression of the intestinal bile acid binding protein (IBABP) in intestinal mucosa cells and/or cholangiocytes by the NR1H4 receptor in a mammal. 35. A method according to claim 36 where the mammal is a human. 36. A method for providing treatment to a mammal in need of one or more of the following: a) regulation of bile flow or the bile acid transport system by activating or repressing the NR1H4 receptor; b) treating a disease or condition which is affected by impaired blood levels of cholesterol, lipoproteins, phospholipids, triglycerides, or bile acids and/or impaired bile flow or impaired bile levels of cholesterol, phospholipids or bile acids; c) treating cholestatic conditions; d) blocking the cholesterol absorption or bile acid re-absorption in the intestine of the mammal; and e) modulating the expression of the intestinal bile acid binding protein (IBABP) in intestinal mucosa cells and/or cholangiocytes by the NR1H4 receptor; wherein said method comprises administering, to the mammal, a therapeutically effective amount of a compound including resolved diastereoisomers and enantiomers, and tautomers of the formula (1), or pharmaceutical acceptable salts or solvates thereof, wherein: R1 in formula (1) is H, C1 to C7 acyl or C1 to C7 substituted acyl, R2 is phenyl, substituted phenyl, C5 to C6 heteroaryl, C5 to C6 substituted heteroaryl, naphthyl or substituted naphthyl, R3 is H, C1 to C8 alkyl, C1 to C8 substituted alkyl, C3 to C8 cycloalkyl, C3 to C8 substituted cycloalkyl, C7 to C12 alkylphenyl, C7 to C12 substituted phenylalkyl, or phenyl, R4 is H, C1 to C8 alkyl, C1 to C8 substituted alkyl, C3 to C8 cycloalkyl, C3 to C8 substituted cycloalkyl, C7 to C12 alkylphenyl or C7 to C12 substituted phenylalkyl, R3 and R4 may be taken together with nitrogen to form a heterocycle or substituted heterocycle, or a heteroaryl or substituted heteroaryl ring, R5 is H, C1 to C8 alkyl, halogen, hydroxy, alkoxy, in particular C1 to C8 alkoxy, carboxy, ester, amide or C1 to C8 aminoacyl, R6 is H, C1 to C8 alkyl, C1 to C8 substituted alkyl and R7 is H, F, Cl, methyl, or trifluoromethyl. 37. The method, according to claim 29, wherein said condition is selected from the group consisting of primary biliary cirrhosis (PBC), progressive familiary cholestasis (PFIC), estrogen or drug induced cholestasis, extrahepatic cholestasis, secondary forms of cholestasis, atherosclerosis, gallstone disease, lipid disorders, obesity, and cardiovascular and metabolic disorders. 38. The method, according to claim 33, wherein said gene is selected from genes that encode cholesterol-7-alpha hydroxylase (cyp7a1), sterol-12-alpha hydroxylase (cyp8b1), small heterodimer partner (shp), phospholipid transfer protein (pltp), bile salt export pump (bsep), sodium-taurocholate co-transporter (ntcp), organic anion transport proteins 1 and 2 (oatp1 and -2), canalicular multidrug resistance protein 2 (mdr2) or other genes that are members of the cytochrom P450 family or members of the ABC-transporter family or members of the MDR class III multidrug resistance proteins or members of the MRP multidrug resistance protein family or members of the nuclear receptor gene family. 39. The method, according to claim 30, wherein said mammal is a human. 40. The method, according to claim 31, wherein said mammal is a human. 41. The method, according to claim 33, wherein said mammal is a human. |
<SOH> BACKGROUND OF THE INVENTION <EOH>Multicellular organisms are dependent on advanced mechanisms of information transfer between cells and body compartments. The information that is transmitted can be highly complex and can result in the alteration of genetic programs involved in cellular differentiation, proliferation, or reproduction. The signals, or hormones, are often simple molecules, such as peptides, fatty acid, or cholesterol derivatives. Many of these signals produce their effects by ultimately changing the transcription of specific genes. One well-studied group of proteins that mediate a cells response to a variety of signals is the family of transcription factors known as nuclear receptors, hereinafter referred to often as “NR”. Members of this group include receptors for steroid hormones, vitamin D, ecdysone, cis and trans retinoic acid, thyroid hormone, bile acids, cholesterol-derivatives, fatty acids (and other peroxisomal proliferators), as well as so-called orphan receptors, proteins that are structurally similar to other members of this group, but for which no ligands are known (Escriva, H. et al., Ligand binding was acquired during evolution of nuclear receptors, PNAS, 94, 6803-6808, 1997). Orphan receptors may be indicative of unknown signaling pathways in the cell or may be nuclear receptors that function without ligand activation. The activation of transcription by some of these orphan receptors may occur in the absence of an exogenous ligand and/or through signal transduction pathways originating from the cell surface (Mangelsdorf, D. J. et al., The nuclear receptor superfamily: the second decade, Cell 83, 835-839, 1995). In general, three functional domains have been defined in NRs. An amino terminal domain is believed to have some regulatory function. A DNA-binding domain hereinafter referred to as “DBD” usually comprises two zinc finger elements and recognizes a specific Hormone Responsive Element hereinafter referred to as “HRE” within the promoters of responsive genes. Specific amino acid residues in the “DBD” have been shown to confer DNA sequence binding specificity (Schena, M. & Yamamoto, K. R., Mammalian Glucocorticoid Receptor Derivatives Enhance Transcription in Yeast, Science, 241:965-967, 1988). A Ligand-binding-domain hereinafter referred to as “LBD” is at the carboxy-terminal region of known NRs. In the absence of hormone, the LBD of some but not all NRs appears to interfere with the interaction of the DBD with its HRE. Hormone binding seems to result in a conformational change in the NR and thus opens this interference (Brzozowski et al., Molecular basis of agonism and antagonism in the oestrogen receptor, Nature, 389, 753-758, 1997; Wagner et al., A structural role for hormone in the thyroid hormone receptor, Nature, 378, 690-697.1995). A NR without the HBD constitutively activates transcription but at a low level. Coactivators or transcriptional activators are proposed to bridge between sequence specific transcription factors and the basal transcription machinery and in addition to influence the chromatin structure of a target cell. Several proteins like SRC-1, ACTR, and Grip1 interact with NRs in a ligand enhanced manner (Heery et al., A signature motif in transcriptional coactivators mediates binding to nuclear receptors, Nature, 387, 733-736; Heinzel et al., A complex containing N-CoR, mSin3 and histone deacetylase mediates transcriptional repression, Nature 387, 43-47, 1997). Furthermore, the physical interaction with repressing receptor-interacting proteins or corepressors has been demonstrated (Xu et al., Coactivator and Corepressor complexes in nuclear receptor function, Curr Opin Genet Dev, 9 (2), 140-147, 1999). Nuclear receptor modulators like steroid hormones affect the growth and function of specific cells by binding to intracellular receptors and forming nuclear receptor-ligand complexes. Nuclear receptor-hormone complexes then interact with a hormone response element (HRE) in the control region of specific genes and alter specific gene expression. The Farnesoid X Receptor alpha (FXR; hereinafter also often referred to as NR1H4 when referring to the human receptor) is a prototypical type 2 nuclear receptor which activates genes upon binding to promoter region of target genes in a heterodimeric fashion with Retinoid X Receptor (hereinafter RXR, Forman et al., Cell, 81, 687-93, 1995). The relevant physiological ligands of NR1H4 seem to be bile acids (Makishima et al., Science, 284, 1362-65, 1999; Parks et al., Science, 284, 1365-68, 1999). The most potent is chenodeoxycholic acid, which regulates the expression of several genes that participate in bile acid homeostasis. Farnesol, originally described to activate the rat ortholog at high concentration does not activate the human or mouse receptor. FXR is expressed In the liver, small intestine, colon, ovary, adrenal gland and kidney. Like LXR-α, NR1H4 is involved in autocrine signaling. FXR is proposed to be a nuclear bile acid sensor. As a result, it modulates both, the synthetic output of bile acids from the liver and their recycling in the intestine (by regulating bile acid binding protein). Upon activation (e.g. binding of chenodeoxycholic acid) it influences the conversion of dietary cholesterol into bile acids by by inhibiting the transcription of key genes which are involved in bile acid synthesis such as CYP7A1 or in bile acid transport across the hepatocyte membranes such as the bile acid transporters BSEP (=Bile Salt Export Pump) and NTCP (Na-Taurocholate Co-Transporter). This seems to be a major mechanism of feedback regulation onto bile acid synthesis. Moreover, NR1H4 seems to be the crucial receptor for maintaining bile acid homeostasis within the hepatocyte and therefore might be an appropriate drug target to treat diseases that result from impaired bile acid production, impaired export into the bile canaliculi or impaired bile flow in general such as cholestatic conditions. Loss of function of NR1H4 results in major changes in bile acid homeostasis on the organism level (Lu, et al., Mol Cell. (2000) 6(3):507-15; Goodwin, et al., Mol Cell. (2000) 6(3):517-26; Sinai, et al., Cell (2000) 15;102(6):731-44). The synthetic compounds, 1,1-bisphosphonate esters, appear to display a number of similar activities to the two identified prototypes of natural FXR agonists, farnesol, and chenodeoxycholic acid. Like farnesol, the 1,1- bisphosphonate esters increase the rate of 3-Hydroxy-3-methylglutaryl-CoA (HMG-CoA) Reductase degradation and like bile acids they induce the expression of the Intestinal Bile Acid Binding Protein (I-BABP) and repress the cholesterol 7 α-hydroxylase gene. Certain 1,1-bisphosphonate esters also bind to FXR. (Niesor et al., Curr Pharm Des,7(4):231-59, 2001). That means that activation of FXR could lead to opposing effects (lowering the rate of cholesterol synthesis by increasing degradation of HMG-CoA Reductase and increasing the cholesterol pool by inhibition of cholesterol degradation into bile acids). The FXR agonist chenodeoxycholic acid does not change cholesterol and lipoprotein levels significantly in patients, although a repression of bile acid synthesis as well as a decreased HMG-CoA Reductase activity was observed (Einarsson et al., Hepatology, 33(5), 1189-93, 2001) confirming that cellular cholesterol synthesis and degradation are controlled by numerous regulatory loops including the coordinate regulation of HMGCoA reductase and cholesterol 7α-hydroxylase and that compounds modulating FXR acitvity might have different effects on blood lipid parameters. In the course of functional analysis of certain 1,1-bisphosphonate esters, it was shown that these compounds which are known to bind to FXR also induce apoptosis in a variety of cell types, similar to the isoprenoids farnesol and geranylgeraniol which are also known as weak FXR binders (Flach et al., Biochem Biophys Res Com, 270, 240-46, 2000). To date only very few compounds have been described which bind the NR1H4 receptor and thus show utility for treating diseases or conditions which are due to or influenced by said nuclear receptor (Maloney at al., J Med Chem, 10; 43(16):2971-4, 2000). It is currently believed that FXR agonists might be useful to treat cholestatic conditions because they result in an upregulation of bile acid transport activity across the canalicular hepatocyte membrane (Plass, et al., Hepatology. (2002) 35(3):589-96; Willson, et al., Med Res Rev. (2001) 21(6):513-22). In contrast, it is believed that compounds that act as FXR antagonists or at least as mixed agonists/antagonists might reduce total serum cholesterol (Urizar, et al., Science (2002) 31;296(5573):1703-6). It was thus an object of the present invention to provide for novel NR1H4 binding compounds. It was thus an object of the present invention to provide for compounds which by means of binding the NR1H4 receptor act as agonist or antagonist or mixed agonist/antagonist of said receptor and thus show utility for treating diseases or conditions which are due to or influenced by said nuclear receptor. It was further an object of the invention to provide for compounds which may be used for the manufacture of a medicament for the treatment of cholesterol or bile acid associated conditions or diseases. In a preferred embodiment of the invention it was an object of the invention to provide for cholesterol lowering or anti-cholestatic compounds. It was also an object of the invention to provide for compounds that may be used for the manufacture of anticancer medicaments or apoptosis-inducing medicaments in general. It was further an object of the invention to provide for compounds which are orally available and can be used for an oral treatment of the diseases mentioned afore. |
<SOH> SUMMARY OF THE INVENTION <EOH>The present invention provides, inter alia, novel NR1H4 nuclear receptor protein binding compounds according to the general formulae (1), (2), (3), (4) shown below. Said compounds are also binders of mammalian homologues of said receptor. Further the object of the invention was solved by providing for amongst the NR1H4 nuclear receptor protein binding compounds according to the general formulae (1), (2), (3), (4) such compounds which act as agonists and such compounds which act as antagonists or mixed agonists/antagonists of the human FXR receptor or a mammalian homologue thereof. The invention provides for FXR agonists which may be used for the manufacture of a medicament for the treatment of cholesterol or bile acid associated conditions or diseases or for the treatment of hyperproliferative diseases such as cancer or for the treatment of drug resistance which results from continous drug treatment of cancer or infectious diseases. In a preferred embodiment of the invention it was an object of the invention to provide for cholesterol lowering or anti-cholestatic compounds. It was also an object of the invention to provide for compounds that may be used for the manufacture of anticancer medicaments or apoptosis-inducing medicaments in general. The foregoing merely summarizes certain aspects of the present invention and is not intended, nor should it be construed, to limit the invention in any manner. All patents and other publications recited herein are hereby incorporated by reference in their entirety. |
Methods for the treatment and prevention of cancer |
The present inventions features methods for treating or preventing cancer (e.g., cancer of the central nervous system) by administering a compound that inhibits PAK kinase activity and/or merlin phosphorylation to a mammal (e.g., a human). The invention also provides screening methods for identifying additional inhibitors of PAK kinase activity and/or merlin phosphorylation. |
1. A method of treating, stabilizing, or preventing cancer in a mammal comprising administering to said mammal a compound that reduces PAK kinase activity in an amount sufficient to treat, stabilize, or prevent cancer in said mammal. 2. The method of claim 1, wherein said compound reduces PAK2 kinase activity. 3. A method of treating, stabilizing, or preventing cancer in a mammal comprising administering to said mammal a compound that reduces the phosphorylation level of merlin in an amount sufficient to treat, stabilize, or prevent cancer in said mammal. 4. The method of claim 3, wherein the amount of merlin phosphorylated at serine 518 is reduced by at least 20%. 5. A screening method for determining whether a compound is useful for treating, stabilizing, or preventing cancer in a mammal, said method comprising measuring PAK kinase activity in a cell, tissue, or mammal in the presence and absence of said compound, wherein said compound is determined to treat, stabilize, or prevent cancer if said compound decreases PAK kinase activity. 6. The method of claim 5, further comprising administering said compound to a mammal with cancer or an increased risk for cancer. 7. The method of claim 5, wherein said compound decreases the phosphorylation of merlin by a PAK kinase, the level of a PAK kinase mRNA or protein, the half-life of a PAK kinase mRNA or protein, the binding of a PAK kinase to another molecule, or the level or activity of a protein that phosphorylates a PAK kinase. 8. A screening method for determining whether a compound is useful for treating, stabilizing, or preventing cancer in a mammal, said method comprising measuring the phosphorylation level of merlin in a cell, tissue, or mammal in the presence and absence of the compound, wherein said compound is determined to treat, stabilize, or prevent cancer if said compound decreases the phosphorylation level of merlin. 9. The method of claim 8, further comprising administering said compound to a mammal with cancer or an increased risk for cancer. 10. The method of claim 8, wherein said compound decreases the percentage of merlin that is phosphorylated or the total amount of phosphorylated merlin by at least 50%. 11. The method of claim 5 or 8, wherein said compound is a member of a library of at least 5 compounds, all of which are simultaneously administered to said cell, tissue, or mammal. 12. The method of claim 1, 3, 5, or 8, wherein said compound comprises an autoinhibitory region of a PAK kinase. 13. The method of claim 1, 3, 5, or 8, wherein said compound is a PAK kinase antisense nucleic acid or double stranded RNA molecule. 14. The method of claim 1, 3, 5, or 8, wherein said compound is an antibody that specifically binds a PAK kinase. 15. The method of claim 1, 3, 5, or 8, wherein said compound is an ATP analog. 16. The method of claim 1, 3, 5, or 8, wherein said compound reduces the protein level of a PAK kinase. 17. The method of claim 1, 3, 5, or 8, wherein said compound reduces the mRNA level of a PAK kinase. 18. The method of claim 1, 3, 5, or 8, wherein said cancer is neurofibromatosis type 2. 19. A pharmaceutical composition comprising a compound that reduces PAK kinase activity and an acceptable vehicle. 20. A pharmaceutical composition comprising a compound that inhibits merlin phosphorylation and an acceptable vehicle. 21. The composition of claim 19 or 20, that treats or prevents cancer in a mammal. 22. The composition of claim 19 or 20, wherein said compound is a PAK kinase antisense nucleic acid or double stranded RNA molecule, PAK kinase antibody, merlin antibody, dominant negative PAK kinase protein, or an autoinhibitory region of a PAK kinase activity. |
<SOH> BACKGROUND OF THE INVENTION <EOH>Neurofibromatosis type 2 is an inherited disorder characterized by the development of Schwann cell tumors of the eighth cranial (auditory) nerve. Mutations and loss of heterozygosity of the NF2 locus have been detected in various familial and sporadic tumors of the nervous system, including schwannomas, meningiomas, and ependymomas. These mutations have been detected both in the germ-line of Nf2 patients and sporadically occurring tumors, indicative of a classical tumor suppressor gene pattern. Together, these tumors account for approximately 30% of central nervous system neoplasms in adults. In further support of a role for NF2 in tumor suppression, mice heterozygous for a Nf2 mutation are predisposed to a wide variety of tumors with high metastatic potential. In a separate model in which Nf2 was inactivated specifically in Schwann cells, mice developed schwannomas and Schwann cell hyperplasia. The longest and predominant splice form of the Nf2 gene codes for a 595-amino acid protein called merlin that is highly similar to the band 4.1 family of proteins. It is most closely related to the ERM proteins—ezrin, radixin, and moesin. The ERM proteins are thought to function as cell membrane-cytoskeleton linkers and are localized to cortical actin structures near the plasma membrane such as microvilli, membrane ruffles, and lamellipodia. Likewise, merlin is localized to cortical actin structures in patterns that partially overlap with the ERMs. It has been proposed that intramolecular binding of the N-terminal and C-terminal domains conformationally regulates the ERM proteins by masking binding sites for interacting proteins. The ERMs can also form homo-dimers and hetero-dimers among themselves and with merlin, adding an additional level of complexity to the regulation of these proteins. The recently solved crystal structure of moesin N/C-terminal complex strengthens this model of conformational regulation. Unfortunately, many of the current treatments that destroy cancerous cells also affect normal cells, resulting in a variety of possible side-effects, such as nausea, vomiting, low blood cell counts, increased risk of infection, hair loss, and ulcers in mucous membranes. Thus, improved methods are needed for the treatment and prevention of cancers, such as cancers of the nervous system. |
<SOH> SUMMARY OF THE INVENTION <EOH>In general, the invention provides novel methods for the treatment or prevention of cancer (e.g., cancer of the central nervous system) by administering one or more compounds that inhibit PAK kinase activity and/or phosphorylation of merlin. Exemplary diseases that can be treated or prevented using these methods include neurofibromatosis type 2 or any other disease that involves aberrations in the function of the Nf2 gene or in the function of merlin. In one aspect, the invention provides a method of treating, stabilizing, or preventing cancer in a mammal (e.g., a human) that involves reducing PAK kinase activity in the mammal. In desirable embodiments, a compound that reduces PAK kinase activity (e.g., PAK1, PAK2, PAK3, PAK4, PAK5, and/or PAK6 kinase activity) is administered to the mammal in an amount sufficient to treat, stabilize, or prevent cancer in the mammal. Desirably, an activity of a PAK kinase is reduced by at least 5, 10, 20, 30, 40, 50, 60, or 80, 90, 95, or 100%. In various embodiments, the compound is a purified or unpurified synthetic organic molecule, naturally occurring organic molecule, nucleic acid molecule, PAK kinase antisense nucleic acid or double stranded RNA molecule, biosynthetic protein or peptide, naturally occurring peptide or protein, PAK kinase antibody, or dominant negative PAK kinase protein (e.g., a mutant or fragment of a PAK kinase). In other embodiments, the compound is an autoinhibitory region of a PAK kinase, such as a protein that includes or consists of at least 25, 50, 75, 100, 125, or 150 contiguous amino acids of residues 82-146 of PAK2 or the corresponding region in another PAK kinase (e.g., residues 83-149 of PAK1). In certain embodiments, the protein includes at least 25, 50, 75, 100, 125, 150, 200, or 300 of the N-terminal amino acids of a PAK kinase. In some embodiments, the compound is staurosporine or an ATP analog. In another aspect, the invention provides a method of treating, stabilizing, or preventing cancer in a mammal (e.g., a human) that involves reducing the amount of merlin that is phosphorylated (e.g., phosphorylation on serine 518) in the mammal. In desirable embodiments, a compound that reduces the phosphorylation level of merlin (e.g., phosphorylation at serine 518) is administered to the mammal in an amount sufficient to treat, stabilize, or prevent cancer in the mammal. In other desirable embodiments, the amount of merlin that is phosphorylated at serine 518 is reduced by at least 5, 10, 20, 30, 40, 50, 60, or 80, 90, 95, or 100%. In various embodiments, at least 20, 40, 50, 60, 80, 90, or 95% of merlin is located in microvilli. Exemplary merlin proteins have an amino acid sequence that is at least 40, 50, 60, 70, 80, 90, 95, or 100% identical to the sequence of a region of human merlin or the sequence of full-length human merlin (accession number P35240). In various embodiments, the compound is a purified or unpurified synthetic organic molecule, naturally occurring organic molecule, nucleic acid molecule, PAK kinase antisense nucleic acid or double stranded RNA molecule, biosynthetic protein or peptide, naturally occurring peptide or protein, PAK kinase antibody, or dominant negative PAK kinase protein (e.g., a mutant or fragment of a PAK kinase). In other embodiments, the compound is an autoinhibitory region of a PAK kinase, such as a protein that includes or consists of at least 25, 50, 75, 100, 125, or 150 contiguous amino acids of residues 82-146 of PAK2 or the corresponding region in another PAK kinase (e.g., residues 83-149 of PAK1). In certain embodiments, the protein includes at least 25, 50, 75, 100, 125, 150, 200, or 300 of the N-terminal amino acids of a PAK kinase. In some embodiments, the compound is staurosporine or an ATP analog. In other embodiments, the compound is an anti-merlin antibody. Desirably, the amount of phosphorylated merlin that is bound by the antibody is at least 2, 5, 10, or 15-fold greater that the amount of unphosphorylated merlin that is bound. The invention also features methods for identifying or selecting compounds that decrease PAK kinase activity or decrease the level of merlin phosphorylation and thus are useful for treating or preventing cancer in a mammal (e.g., a human). Accordingly, in one aspect, the invention features a screening method for determining whether a compound is useful for treating, stabilizing, or preventing cancer in a mammal. This method involves measuring PAK kinase activity in a cell, tissue, or mammal in the presence and absence of the compound. The compound is determined to treat, stabilize, or prevent cancer if the compound decreases PAK kinase activity. In some embodiments, the method also includes administering the compound to a mammal in need of the treatment (e.g., a mammal with cancer or an increased risk for cancer). In certain embodiments, the compound is a member of a library of at least 5, 10, 15, 20, 30, 50, or more compounds, all of which are simultaneously administered to the cell, tissue, or mammal. In various embodiments, the compound is a purified or unpurified synthetic organic molecule, naturally occurring organic molecule, nucleic acid molecule, PAK kinase antisense nucleic acid or double stranded RNA molecule, biosynthetic protein or peptide, naturally occurring peptide or protein, PAK kinase antibody, or dominant negative PAK kinase protein (e.g., a mutant or fragment of a PAK kinase). In other embodiments, the compound is an autoinhibitory region of a PAK kinase, such as a protein that includes or consists of at least 25, 50, 75, 100, 125, or 150 contiguous amino acids of residues 82-146 of PAK2 or the corresponding region in another PAK kinase (e.g., residues 83-149 of PAK1). In certain embodiments, the protein includes at least 25, 50, 75, 100, 125, 150, 200, or 300 of the N-terminal amino acids of a PAK kinase. In some embodiments, the compound is staurosporine or an ATP analog. In desirable embodiments, the compound decreases an activity of a PAK kinase (e.g., the phosphorylation of merlin), the level of a PAK kinase mRNA or protein, the half-life of a PAK kinase mRNA or protein, the binding of a PAK kinase to a substrate or to another molecule, or the level or activity of a protein that phosphorylates a PAK kinase. Desirably, the level of a PAK kinase mRNA or protein, an activity of a PAK kinase, the half-life of a PAK kinase mRNA or protein, the binding of a PAK kinase to another molecule, or the level or activity of a protein that phosphorylates a PAK kinase decreases by at least 5, 10, 20, 30, 40, 50, 60, or 80, 90, 95, or 100%. In a related aspect, the invention features another screening method for determining whether a compound is useful for treating, stabilizing, or preventing cancer in a mammal. This method involves measuring the phosphorylation level of merlin (e.g., phosphorylation of serine 518) in a cell, tissue, or mammal in the presence and absence of the compound. The compound is determined to treat, stabilize, or prevent cancer if the compound decreases the phosphorylation level of merlin. In some embodiments, the method also includes administering the compound to a mammal in need of the treatment (e.g., a mammal with cancer or an increased risk for cancer). In certain embodiments, the compound is a member of a library of at least 5, 10, 15, 20, 30, 50, or more compounds, all of which are simultaneously administered to the cell, tissue, or mammal. In various embodiments, the compound is a purified or unpurified synthetic organic molecule, naturally occurring organic molecule, nucleic acid molecule, PAK kinase antisense nucleic acid or double stranded RNA molecule, biosynthetic protein or peptide, naturally occurring peptide or protein, PAK kinase antibody, or dominant negative PAK kinase protein (e.g., a mutant or fragment of a PAK kinase). In other embodiments, the compound is an autoinhibitory region of a PAK kinase, such as a protein that includes or consists of at least 25, 50, 75, 100, 125, or 150 contiguous amino acids of residues 82-146 of PAK2 or the corresponding region in another PAK kinase (e.g., residues 83-149 of PAK1). In certain embodiments, the protein includes at least 25, 50, 75, 100, 125, 150, 200, or 300 of the N-terminal amino acids of a PAK kinase. In some embodiments, the compound is staurosporine or an ATP analog. In other embodiments, the compound is an anti-merlin antibody. Desirably, the amount of phosphorylated merlin that is bound by the antibody is at least 2, 5, 10, or 15-fold greater that the amount of unphosphorylated merlin that is bound. In desirable embodiments, the compound decreases the percentage of merlin that is phosphorylation or the total amount of phosphorylated merlin by at least 5, 10, 20, 30, 40, 50, 60, 80, 90, 95, or 100%. Exemplary merlin proteins have an amino acid sequence that is at least 40, 50, 60, 70, 80, 90, 95, or 100% identical to the sequence of a region of human merlin or the sequence of full-length human merlin (accession number P35240). The invention also features pharmaceutical compositions for the treatment or prevention of cancer. In one such aspect, the invention features a pharmaceutical composition that includes one or more compounds that inhibit PAK kinase activity and/or merlin phosphorylation in an acceptable vehicle. In some embodiments, the composition contains between 10 ng and 10 mg, such as between 0.1 to 1 mg, of the compound. In various embodiments, the compound is a synthetic organic molecule, naturally occurring organic molecule, nucleic acid molecule, PAK kinase antisense nucleic acid or double stranded RNA molecule, biosynthetic protein or peptide, naturally occurring peptide or protein, PAK kinase antibody (e.g., an antibody that specifically binds a PAK kinase such as PAK2), or dominant negative PAK kinase protein (e.g., a mutant or fragment of a PAK kinase). In other embodiments, the compound is an autoinhibitory region of a PAK kinase, such as a protein that includes or consists of at least 25, 50, 75, 100, 125, or 150 contiguous amino acids of residues 82-146 of PAK2 or the corresponding region in another PAK kinase (e.g., residues 83-149 of PAK1). In certain embodiments, the protein includes at least 25, 50, 75, 100, 125, 150, 200, or 300 of the N-terminal amino acids of a PAK kinase. In some embodiments, the compound is staurosporine or an ATP analog. In other embodiments, the compound is an anti-merlin antibody. Desirably, the amount of phosphorylated merlin that is bound by the antibody is at least 2, 5, 10, or 15-fold greater that the amount of unphosphorylated merlin that is bound. In desirable embodiments, the compound decreases the percentage of merlin that is phosphorylation, the total amount of phosphorylated merlin, or an activity of a PAK kinase by at least 5, 10, 20, 30, 40, 50, 60, 80, 90, 95, or 100%. Suitable carriers include, but are not limited to, saline, buffered saline, dextrose, water, glycerol, ethanol, and combinations thereof. The composition can be adapted for the mode of administration and can be in the form of, for example, a pill, tablet, capsule, spray, powder, or liquid. In some embodiments, the pharmaceutical composition contains one or more pharmaceutically acceptable additives suitable for the selected route and mode of administration. These compositions may be administered by, without limitation, any parenteral route including intravenous, intra-arterial, intramuscular, subcutaneous, intradermal, intraperitoneal, intrathecal, as well as topically, orally, and by mucosal routes of delivery such as intranasal, inhalation, rectal, vaginal, buccal, and sublingual. In some embodiments, the pharmaceutical compositions of the invention are prepared for administration to vertebrate (e.g., mammalian) subjects in the form of liquids, including sterile, non-pyrogenic liquids for injection, emulsions, powders, aerosols, tablets, capsules, enteric coated tablets, or suppositories. Exemplary cancers that can be treated, stabilized, or prevented using the above methods include cancers of the nervous system (e.g., Schwann cell tumors or Nf2), prostate cancers, breast cancers, ovarian cancers, pancreatic cancers, gastric cancers, bladder cancers, salivary gland carcinomas, gastrointestinal cancers, lung cancers, colon cancers, melanomas, brain tumors, leukemias, lymphomas, and carcinomas. Benign tumors may also be treated or prevented using the methods and compounds of the present invention. Exemplary mammals include humans, primates such as monkeys, animals of veterinary interest (e.g., cows, sheep, goats, buffalos, and horses), and domestic pets (e.g., dogs and cats). With respect to the therapeutic methods of the invention, it is not intended that the administration of compounds to a mammal be limited to a particular mode of administration, dosage, or frequency of dosing; the present invention contemplates all modes of administration, including oral, intraperitoneal, intramuscular, intravenous, intraarticular, intralesional, subcutaneous, or any other route sufficient to provide a dose adequate to prevent or treat cancer. One or more compounds may be administered to the mammal in a single dose or multiple doses. When multiple doses are administered, the doses may be separated from one another by, for example, one week, one month, one year, or ten years. It is to be understood that, for any particular subject, specific dosage regimes should be adjusted over time according to the individual need and the professional judgment of the person administering or supervising the administration of the compositions. If desired, conventional treatments such as radiation therapy, chemotherapy, and/or surgery may be used in combination with the compounds of the present invention. In various embodiments of any of the aspects of the invention, the compound has a molecular weight contained in one of the following ranges: 100-4,000 daltons, 100-3,000 daltons; 100-2,000 daltons; 100-1,000 daltons; 100-750 daltons; 250-4,000 daltons, 250-3,000 daltons; 250-2,000 daltons; 250-1,000 daltons; 250-750 daltons; 400-4,000 daltons, 400-3,000 daltons; 400-2,000 daltons; 400-1,000 daltons; or 400-750 daltons, inclusive. By ““AK kinase” is meant a protein with an amino acid sequence that is at least 40, 50, 60, 70, 80, 90, 95, or 100% identical to the sequence of a region (e.g., a region of at least 50, 100, 150, or 200 amino acids) of a p21-activted kinase (PAK) or the sequence of a full-length PAK. Exemplary PAK kinases have a sequence at least 40, 50, 60, 70, 80, 90, 95, or 100% identical to human PAK1, 2, 3, 4, 5, or 6 over its entire sequence. Examples of human PAK kinase sequences are deposited under the following accession numbers: Q13153 (PAK1), Q13177 (PAK2), O75914 (PAK3), NP — 005875 (PAK4), BAA94194 (PAK5), and NP — 064553 (PAK6). Desirably, the level of an activity of the PAK kinase (e.g., phosphorylation of merlin) is at least 30, 50, 60, 70, 80, 90, 95, or 100% of the level of the corresponding activity of human PAK1, 2, 3, 4, 5, or 6. PAK kinases belong to a larger group of the STE20-like kinases. By “compound that decreases PAK kinase activity” is meant a compound that decreases the level of a PAK kinase mRNA or protein, an activity of a PAK kinase, the half-life of a PAK kinase mRNA or protein, or the binding of a PAK kinase to another molecule (e.g., a substrate for a PAK kinase, a Rac protein, or a cdc42 protein), as measured using standard methods (see, for example, Ausubel et al., Current Protocols in Molecular Biology, Chapter 9, John Wiley & Sons, New York, 2000). For example, the compound may directly or indirectly inhibit the ability of a PAK kinase to phosphorylate merlin. In other desirable embodiments, a compound that decreases PAK kinase activity reduces or stabilizes the level of Rac or cdc42 mRNA or protein and thus reduces or stabilizes the level of an activated PAK kinase. mRNA expression levels may be determined using standard RNase protection assays or in situ hybridization assays, and the level of protein may be determined using standard Western or immunohistochemistry analysis (see, for example, Ausubel et al., supra). The phosphorylation levels of signal transduction proteins downstream of merlin acitivity may also be measured using standard assays. Desirably, the compound decreases PAK kinase activity by at least 20, 40, 60, 80, or 90%. In another desirable embodiment, the level of PAK kinase activity is at least 2, 3, 5, 10, 20, or 50-fold lower in the presence of the compound. In yet another desirable embodiment, the compound preferentially decreases the expression or kinase activity of PAK2; for example, the compound may decrease the expression or kinase activity of PAK2 by at least 50, 100, 200 or 500% more than it decreases the expression or kinase activity of another PAK kinase, such as PAK1, PAK3, PAK4, PAK5, or PAK6. Other desirable compounds decrease the expression or kinase activity of multiple PAK kinases (e.g., 2, 3, 4, 5, 6, or more PAK kinases). Desirably, the level of PAK2 mRNA, PAK2 protein, or PAK2 kinase activity in the presence of the compound is less than 80, 60, 40, or 20% of the corresponding level in the absence of the compound. Desirably, the decrease in PAK kinase activity in the central nervous system is at least 2, 3, 5, 10, 20, or 50-fold greater than the decrease in PAK kinase activity in the periphery or than the decrease in the activity of another kinase. It is also contemplated that the expression or activity of a protein having an amino acid sequence that is substantially identical to that of a PAK kinase may be inhibited. Compounds that may be tested for their ability to decrease PAK kinase activity include, but are not limited to, synthetic organic molecules, naturally occurring organic molecules, nucleic acid molecules, PAK kinase antisense nucleic acids or double stranded RNA molecules, biosynthetic proteins or peptides, naturally occurring peptides or proteins, PAK kinase antibodies, or dominant negative PAK kinase proteins. Because sequences within PAK kinases are autoinhibitory, peptides or peptide analogs based on these autoinhibitory regions may be used as inhibitors of PAK kinase activity (Maruta et al., Ann. N.Y. Acad. Sci., 886:48-57, 1999). Additionally, the autoinhibitory domain of PAK2 that is described herein may be used as an inhibitor of PAK kinase activity or may be used as an initial structure for the design of other peptides or peptide analogs that inhibit PAK kinase activity. Other exemplary PAK kinase inhibitors include staurosporine, staurosporine analogs, and pharmacuetically acceptable salts thereof (Zeng et al., J. Cell Sci. 113 (Pt 3): 471-82, 2000; Yu et al., J Biochem (Tokyo), 129(2): 243-51, 2001). Exemplary PAK kinase inhibitors which may inhibit PAK kinases indirectly include those reported by He et al. (Cancer J. 7(3): 191-202, 2001, Cancer J. 6(4):243-8, 2000). Still other preferred compounds include ATP analogs. By “antibody that specifically binds a protein” is meant an antibody that binds to a PAK kinase or merlin, but does not substantially bind to other molecules in a sample, e.g., a biological sample, that naturally includes a PAK kinase or merlin. Desirably, the amount antibody bound to a PAK kinase or merlin is at least 50%, 100%, 200%, 500%, or 1,000% greater than the amount of antibody bound to other proteins under the same conditions. In some embodiments, the amount of antibody bound to PAK2 is at least 2, 5, 10, or 20-fold more than the amount bound to another PAK kinase, such as PAK1, PAK3, PAK4, PAK5, or PAK6. Desirably, the antibody decreases the activity of a PAK kinase and/or the phosphorylation level of merlin by at least 30, 50, 60, 70, 80, 90, 95, or 100%. In various embodiments, the antibody is a modified antibody, bifunctional antibody, or antibody fragment. By “modified antibody” is meant an antibody having an altered amino acid sequence so that fewer antibodies and/or immune responses are elicited against the modified antibody when it is administered to a mammal such as a human. For example, the constant region of the antibody may be replaced with the constant region from a human antibody. For the use of the antibody in a mammal other than a human, an antibody may be converted to that species format. By “bifunctional antibody” is meant an antibody that includes an antibody or a fragment of an antibody covalently linked to a different antibody or a different fragment of an antibody. In one preferred embodiment, both antibodies or fragments bind to different epitopes expressed on a PAK kinase. Other preferred bifunctional antibodies bind to two different antigens, such as to two different PAK kinases. Standard molecular biology techniques such as those described herein may be used to operably link two nucleic acids so that the fusion nucleic acid encodes a bifunctional antibody. By “fragment” is meant a polypeptide having a region of consecutive amino acids that is identical to the corresponding region of an antibody of the invention but is less than the full-length sequence. The fragment has the ability to bind the same antigen as the corresponding antibody based on standard assays, such as those described herein. Desirably, the binding of the fragment to a PAK kinase is at least 20, 40, 60, 80, or 90% of that of the corresponding antibody. By “antisense” is meant a nucleic acid, regardless of length, that is complementary to the coding strand or mRNA of a PAK kinase. In some embodiments, the antisene molecule inhibits the expression of only one PAK kinase, and in other embodiments, the antisense molecule inhibits the expression of more than one PAK kinase. Desirably, the antisense nucleic acid decreases the expression or biological activity of a PAK kinase by at least 20, 40, 50, 60, 70, 80, 90, 95, or 100%. A antisense molecule can be introduced, e.g., to an individual cell or to whole animals, for example, it may be introduced systemically via the bloodstream. In some embodiments, the antisense molecule is less than 200, 150, 100, 75, 50, or 25 nucleotides in length. In other embodiments, the antisense molecule is less than 50,000; 10,000; 5,000; or 2,000 nucleotides in length. In certain embodiments, the antisense molecule is at least 200, 300, 500, 1000, or 5000 nucleotides in length. In some embodiments, the number of nucleotides in the antisense molecule is contained in one of the following ranges: 5-15 nucleotides, 16-20 nucleotides, 21-25 nucleotides, 26-35 nucleotides, 36-45 nucleotides, 46-60 nucleotides, 61-80 nucleotides, 81-100 nucleotides, 101-150 nucleotides, or 151-200 nucleotides, inclusive. In addition, the antisense molecule may contain a sequence that is less than a full length sequence or may contain a full-length sequence. By “double stranded RNA” is meant a nucleic acid containing a region of two or more nucleotides that are in a double stranded conformation. In various embodiments, the double stranded RNA consists entirely of ribonucleotides or consists of a mixture of ribonucleotides and deoxynucleotides. The double stranded RNA may be a single molecule with a region of self-complimentarity such that nucleotides in one segment of the molecule base pair with nucleotides in another segment of the molecule. Alternatively, the double stranded RNA may include two different strands that have a region of complimentarity to each other. Desirably, the regions of complimentarity are at least 70, 80, 90, 95, 98, or 100% complimentary. Desirably, the region of the double stranded RNA that is present in a double stranded conformation includes at least 5, 10, 20, 30, 50, 75, 100, 200, 500, 1000, 2000 or 5000 nucleotides or includes all of the nucleotides in the double stranded RNA. Desirable double stranded RNA molecules have a strand or region that is at least 70, 80, 90, 95, 98, or 100% identical to a coding region or a regulatory sequence (e.g., a transcription factor binding site, a promoter, or a 5′ or 3′ untranslated region) of a PAK kinase. In some embodiments, the double stranded RNA is less than 200, 150, 100, 75, 50, or 25 nucleotides in length. In other embodiments, the double stranded RNA is less than 50,000; 10,000; 5,000; or 2,000 nucleotides in length. In certain embodiments, the double stranded RNA is at least 200, 300, 500, 1000, or 5000 nucleotides in length. In some embodiments, the number of nucleotides in the double stranded RNA is contained in one of the following ranges: 5-15 nucleotides, 16-20 nucleotides, 21-25 nucleotides, 26-35 nucleotides, 36-45 nucleotides, 46-60 nucleotides, 61-80 nucleotides, 81-100 nucleotides, 101-150 nucleotides, or 151-200 nucleotides, inclusive. In addition, the double stranded RNA may contain a sequence that is less than a full-length sequence or may contain a full-length sequence. In some embodiments, the double stranded RNA molecule inhibits the expression of only one PAK kinase, and in other embodiments, the double stranded RNA molecule inhibits the expression of more than one PAK kinase. Desirably, the nucleic acid decreases the expression or biological activity of a PAK kinase by at least 20, 40, 50, 60, 70, 80, 90, 95, or 100%. A double stranded RNA can be introduced, e.g., to an individual cell or to whole animals, for example, it may be introduced systemically via the bloodstream. In various embodiments, the double stranded RNA or antisense molecule includes one or more modified nucleotides in which the 2′ position in the sugar contains a halogen (such as flourine group) or contains an alkoxy group (such as a methoxy group) which increases the half-life of the double stranded RNA or antisense molecule in vitro or in vivo compared to the corresponding double stranded RNA or antisense molecule in which the corresponding 2′ position contains a hydrogen or an hydroxyl group. In yet other embodiments, the double stranded RNA or antisense molecule includes one or more linkages between adjacent nucleotides other than a naturally-occurring phosphodiester linkage. Examples of such linkages include phosphoramide, phosphorothioate, and phosphorodithioate linkages. By “purified” is meant separated from other components that naturally accompany it. Typically, a factor is substantially pure when it is at least 50%, by weight, free from proteins, antibodies, and naturally-occurring organic molecules with which it is naturally associated. Desirably, the factor is at least 75%, more desirably, at least 90%, and most desirably, at least 99%, by weight, pure. A substantially pure factor may be obtained by chemical synthesis, separation of the factor from natural sources, or production of the factor in a recombinant host cell that does not naturally produce the factor. Proteins, vesicles, organelles, and small molecules may be purified by one skilled in the art using standard techniques such as those described by Ausubel et al. (Current Protocols in Molecular Biology, John Wiley & Sons, New York, 2000). The factor is desirably at least 2, 5, or 10 times as pure as the starting material, as measured using polyacrylamide gel electrophoresis, column chromatography, optical density, HPLC analysis, or western analysis (Ausubel et al., supra). Preferred methods of purification include immunoprecipitation, column chromatography such as immunoaffinity chromatography, magnetic bead immunoaffinity purification, and panning with a plate-bound antibody. By “treating, stabilizing, or preventing cancer” is meant causing a reduction in the size of a tumor, slowing or preventing an increase in the size of a tumor, increasing the disease-free survival time between the disappearance of a tumor and its reappearance, preventing an initial or subsequent occurrence of a tumor, or reducing an adverse symptom associated with a tumor. In one desirable embodiment, the number of cancerous cells surviving the treatment is at least 20, 40, 60, 80, or 100% lower than the initial number of cancerous cells, as measured using any standard assay. Desirably, the decrease in the number of cancerous cells induced by administration of a compound of the invention is at least 2, 5, 10, 20, or 50-fold greater than the decrease in the number of non-cancerous cells. In yet another desirable embodiment, the number of cancerous cells present after administration of an compound that inhibits PAK kinase activity or inhibits merlin phosphorylation is at least 2, 5, 10, 20, or 50-fold lower than the number of cancerous cells present prior to the administration of the compound or after administration of a buffer control. Desirably, the methods of the present invention result in a decrease of 20, 40, 60, 80, or 100% in the size of a tumor as determined using standard methods. Desirably, at least 20, 40, 60, 80, 90, or 95% of the treated subjects have a complete remission in which all evidence of the cancer disappears. Desirably, the cancer does not reappear or reappears after at least 5, 10, 15, or 20 years. Examples of cancers that may be treated using these methods include familial and sporadic tumors of the nervous system, such as schwannomas, meningiomas, or ependymomas. By “mutation” is meant an alteration in a naturally-occurring or reference nucleic acid sequence, such as an insertion, deletion, frameshift mutation, silent mutation, nonsense mutation, or missense mutation. Desirably, the amino acid sequence encoded by the nucleic acid sequence has at least one amino acid alteration from a naturally-occurring sequence. By “substantially identical” is meant having a sequence that is at least 60, 70, 80, 90, 95, or 100% identical to that of another sequence. Sequence identity is typically measured using sequence analysis software with the default parameters specified therein (e.g., Sequence Analysis Software Package of the Genetics Computer Group, University of Wisconsin Biotechnology Center, 1710 University Avenue, Madison, Wis. 53705). This software program matches similar sequences by assigning degrees of homology to various substitutions, deletions, and other modifications. |
Method for producing a membrane from a crosslink polymer blend, and corresponding fuel cell |
The present invention relates to a polymer blend membrane comprising a bridged polymer which is produced by a selected process. The membrane of the invention displays a significantly improved fracture toughness (elongation at break/stress) combined with virtually unchanged other properties. The membranes of the invention are suitable for producing membrane-electrode units for fuel cells. |
1. A membrane comprising a bridged polymer obtainable by a process comprising the following steps: A. preparing a solution comprising a basic polymer (polymer I) having at least one amino group per repeating unit and at least one bridging reagent and, in addition, at least one basic catalyst in at least one suitable solvent, B. casting a film using the solution obtained from step A), C. removing the solvent from step A), D. carrying out the bridging reaction in the film obtained in step C), E. doping the film obtained in step D) with a strong acid, wherein at least one further polymer based on a polysulfone (polymer II) in addition to the basic polymer (polymer I) is added in step A). 2. A membrane as claimed in claim 1, wherein the bridging reagent has at least two epoxide groups or isocyanate groups per molecule. 3. A membrane as claimed in claim 1, wherein the bridging reagent is at least one compound of the formula (II) and/or (III) where R1 is a hydrocarbon group having from 1 to 30 carbon atoms. 4. A membrane as claimed in claim 3, wherein R1 is where m, k and I are identical or different and are each an integer from 1 to 6, n is an integer from 1 to 10, preferably 1. 5. A membrane as claimed in claim 1, wherein the bridging reagent contains at least three epoxide groups per molecule. 6. A membrane as claimed in claim 5, wherein the bridging reagent is the compound 7. A membrane as claimed in claim 1, wherein the bridging reagent is bisphenol A glycidyl ether [BPAGDE] and/or 1,4-butanediol diglycidyl ether. 8. A membrane as claimed in claim 1, wherein the solution prepared in step A) contains from 0.1 to 7 mol % of the bridging reagent per unit of the basic polymer. 9. A membrane as claimed in claim 1, wherein polybenzimidazoles, polyimidazoles, polyvinylimidazoles, polybenzobisimidazoles and copolymers thereof are used as basic polymer. 10. A membrane as claimed in claim 9, wherein polybenzimidazoles used have the formula: where R is alkylene, perfluoralkylene or a substituent of one of the following formulae: and each alkylene and perfuoroalkylene group R preferably has from 1 to 10 carbon atoms, particularly preferably from 1 to 6 carbon atoms. 11. A membrane as claimed in claim 9, wherein polybenzobisimidazoles used have the formula where R is as defined in claim 10. 12. A membrane as claimed in claim 1, wherein the further polymer based on a polysulfone (polymer II) comprises one or more polysulfones comprising recurring units which have linking sulfone groups and correspond to the formulae 2A, 2B, 2C, 2D, 2E, 2F and/or 2G: where the radicals R are identical or different and are each, independently of one another, 1,2-phenylene, 1,3-phenylene, 1,4-phenylene, 4,4′-biphenyl, a divalent radical of a heteroaromatic, a divalent radical of a C10-aromatic and/or a divalent radical of a C14-aromatic, where the polysulfone preferably has no sulfonic acid groups. 13. A membrane as claimed in claim 12, wherein the number average molecular weight of the polysulfone is greater than 30,000 g/mol. 14. A membrane as claimed in claim 1, wherein the solution prepared in step A) comprises from 1 to 99 percent by weight of the basic polymer, with the bridging reagent and the basic catalyst being included, and from 99 to 1 percent by weight of the polymer based on polysulfone. 15. A membrane as claimed in claim 1, wherein bridging in step D) is carried out by heating, so that bridging (step D) and drying (step C) are carried out simultaneously in one step. 16. A membrane as claimed in claim 1, wherein drying of the film is carried out at a temperature below the reaction temperature of the bridging reagent and the film is subsequently heated further for the purpose of bridging. 17. A membrane as claimed in claim 1, wherein bridging in step D) is carried out by irradiation with electromagnetic waves (photochemical reaction). 18. A membrane as claimed in claim 1, wherein the strong acid used in step E) is phosphoric acid and/or sulfuric acid. 19. A membrane as claimed in claim 1, wherein the treatment in step E) is carried out using water or an aqueous acid and the polysulfone bears sulfonic acid groups and/or protonated sulfonic acid groups. 20. A membrane as claimed in claim 1, wherein basic catalysts used are basic oxides and hydroxides of the elements of main groups I, II and III of the Periodic Table, hybrides of the elements of main group I of the Periodic Table and organolithium compounds. 21. A membrane as claimed in claim 20, wherein basic catalysts used are KOH, LiOH, NaOH, RbOH, CsOH, Ca(OH)2, Mg(OH)2, Ba(OH)2, LiH, NaH, KH, methyllithium and/or butyllithium. 22. A membrane as claimed in claim 1, wherein the basic catalyst is added to the solution in step A) in amounts of from 0.01 to 5 mol %, based on the bridging reagent used. |
System and method for rapid heating of fluid |
Apparatus for rapidly heating fluid includes a fluid circuit having electrodes between which the fluid flows. A voltage is applied between a pair of electrodes whereby current is caused to flow through the fluid. The inlet and outlet fluid temperatures are measured and the current controlled by varying the applied voltage to produce a desired temperature rise in the fluid in accordance with measured fluid flow rate. |
1. An apparatus for heating fluid comprising passageway means defining a flow path for the fluid to be heated, upstream fluid temperature measuring means to measure the temperature of fluid to be heated, a plurality of sets of electrode means in or forming the flow path and between which said fluid passes, said sets of electrode means including at least first and second electrode sets along the fluid flow path, said first electrode set and said second electrode set both having at least one pair of electrodes between which an electric current is passed through the said fluid to heat the fluid during its passage along the flow path, first downstream temperature measuring means downstream of the second electrode set, fluid flow rate measuring means, and electrical control means to supply and control electrical power to the electrodes of each set, said control means having processing means to relate current flow and applied voltage in response to measured upstream and downstream temperatures and fluid flow rate to determine desired power input to the fluid from each electrode set to achieve a desired fluid temperature downstream of the second electrode set. 2. An apparatus according to claim 1 wherein said passageway means comprises an annular space between spaced, substantially coaxial cylindrical members. 3. An apparatus according to claim 1 wherein a second temperature measuring means measures the temperature of the fluid between the first and second electrode sets, and the control means controls power to the first and second electrode sets in accordance with the measured temperatures and a desired fluid temperature increase in the passage of the fluid between the respective electrode sets. 4. An apparatus according to claim 1 wherein said plurality of sets of electrode means includes a third electrode set positioned downstream of said second electrode set, and a third downstream temperature measuring means measures the fluid temperature downstream of the third electrode set. 5. An apparatus according to claim 1 wherein the electrode means comprises cylindrical, substantially coaxial electrodes defining separate sections of the passageway means along the flow path(s). 6. An apparatus according to claim 1 wherein said passageway means includes three sections, each passageway section having an inlet and an outlet, the sections being connected together in series such that the outlet of a first section communicates with the inlet of the second section, and the outlet of the second section communicates with the inlet of the third section, with a set of electrodes for each section. 7. An apparatus according to claim 6 wherein the outlets of each of the first second and third sections have fluid temperature measuring means, and said control means controls the power to the electrodes of each section in accordance with the sensed inlet and outlet temperatures of each section and a predetermined desired temperature difference. 8. An apparatus according to claim 6 wherein each passageway section is formed by spaced substantially coaxial cylindrical electrodes defining an annular flow path for the fluid. 9. An apparatus according to claim 1 wherein said passageway means includes more than three passageway sections, each section having an inlet and outlet, the sections being connected in series and the control means controlling power to an electrode pair of each section in accordance with measured inlet and outlet temperatures of each section, and a predetermined desired temperature difference. 10. An apparatus according to claim 7 wherein the predetermined desired temperature difference is determined in relation to applied voltage between the respective electrodes and current drawn, inlet and outlet temperatures of the sections, fluid flow and upstream and downstream measures temperatures. 11. An apparatus according to claim 1 wherein the control means supplies a varying voltage to the electrode pairs at a pulse frequency which is sub-multiple of mains supply voltage frequency, and control of the power supplied to the electrodes includes varying the number of pulses per unit time. 12. An apparatus according to claim 1 wherein said passageway means defines a plurality of parallel flow paths for said fluid, each flow path having a plurality of sets of electrode means in or forming the flow path. 13. A method for heating fluid comprising the steps of: passing fluid along a fluid path; providing at least two sets of electrodes spaced along the fluid path; applying a variable electrical voltage between the electrodes of each set to thereby pass electrical currents through the fluid between electrodes of each set; monitoring fluid path inlet fluid temperature; monitoring fluid path outlet fluid temperature; monitoring the currents passing through the fluid between electrodes of each electrode set in response to application of the variable electrical voltage; and controlling the variable electrical voltage between electrodes of each electrode set in response to the specific conductance of the fluid as determined by reference to the monitored fluid temperatures and current flows for a given fluid flow in each section of the flow path such that an amount of electrical power passed to the fluid corresponds to a predetermined temperature increase of the fluid. 14. A method for heating fluid according to claim 13 including the step of monitoring the temperature of the fluid between the electrode sets. 15. A method for heating fluid according to claim 13 including the step of controlling the electrical power passed to the fluid by a microcomputer controlled management system. 16. A method for heating fluid according to claim 13 including the step of managing and responding to changes in the electrical conductivity of the fluid as it is heated within the system in conjunction with measured fluid flow, fluid inlet temperature, and desired rate of temperature rise. 17. A method for heating fluid according to claim 13 including the step of compensating for a change in the electrical conductivity of the fluid caused by varying temperatures and varying concentrations of dissolved chemicals and salts, and through the heating of the fluid, by altering the average electrical voltage to accommodate for changes in specific conductance when increasing the fluid temperature by the desired amount. 18. A method for heating fluid according to claim 13 including the steps of providing at least three sets of electrodes in the fluid flow, applying an electrical voltage between electrodes of each pair in accordance with monitored temperatures of fluid at locations upstream and downstream of the electrode pairs. 19. A method for heating fluid according to claim 18 including the steps of monitoring the temperature of the fluid in the flow path on either side of each pair of electrodes, separately controlling the electrical power applied to the electrode pairs of each set of electrodes to maintain a required constant fluid temperature increase in that segment of fluid flow adjacent the respective electrode pairs. 20. A fluid heating system comprising at least one flow path for the fluid to be heated and having a fluid inlet, inlet fluid temperature measuring means, at least two pairs of electrodes in or defining the fluid path, the electrode pairs being spaced along the flow path, downstream fluid temperature measuring means downstream of each electrode pair, fluid flow rate measuring means, electrical control means to supply and control electrical power to the electrodes of each pair, said control means having processing means to relate current flow, applied voltage, inlet fluid temperature, respective downstream fluid temperatures, and fluid flow rate to determine desired power input to the fluid by each electrode pair to achieve a desired outlet fluid temperature in a predetermined time. 21. A fluid heating system according to claim 20 wherein said flow path comprises an annular space between spaced, substantially coaxial cylindrical members. 22. A fluid heating system according to claim 20 wherein said cylindrical members constitute said electrodes. 23. A fluid heating system according to claim 20 having a plurality of parallel flow paths for said fluid, each flow path having a plurality of sets of electrode means in or forming the flow path. 24. A fluid heating system according to claim 20 wherein said flow path includes three sections, each section having an inlet and an outlet, the sections being connected together in series such that the outlet of a first section communicates with the inlet of the second section, and the outlet of the second section communicates with the inlet of the third section, with electrodes for each section. 25. A fluid heating system according to claim 20 wherein fluid temperature measuring devices are located adjacent each set of electrodes, and said control means controls the power to the electrodes of each section in accordance with the sensed inlet and outlet temperatures of each section and a predetermined desired temperature difference in each section. 26. A fluid heating system according to claim 20 wherein the control means supplies a voltage to the electrode pairs at a pulse frequency which is sub-multiple of mains supply voltage frequency, control of the power supplied to each pair of electrodes including control by varying the number of pulses. 27. (Cancelled) 28. (Cancelled) 29. (Cancelled) |
<SOH> BACKGROUND OF THE INVENTION <EOH>Hot water systems of one form or another are installed in the vast majority of residential and business premises in developed countries. In some countries, the most common energy source for the heating of water is electricity. Of course, as it is generally known, the generation of electricity by the burning of fossil fuels significantly contributes to pollution and global warming. For example, in 1996, the largest electricity consuming sector in the United States were residential households, which were responsible for 20% of all carbon emissions produced. Of the total carbon emissions from this electricity-consuming sector, 63% were directly attributable to the burning of fossil fuels used to generate electricity for that sector. In developed nations, electricity is now considered a practical necessity for residential premises and with electricity consumption per household growing at approximately 1.5% per annum since 1990 the projected increase in electricity consumption for the residential sector has become a central issue in the debate regarding carbon stabilisation and meeting the goals of the Kyoto Protocol. From 1982 to 1996 the number of households in the United States increased at a rate of 1.4% per annum and residential electricity consumption increased at a rate of 2.6% per annum for the same period. Accordingly, the number of households in the United States is projected to increase by 1.1% per annum through to the year 2010 and residential electricity consumption is expected to increase at a rate of 1.6% per annum for the same period. It was estimated in 1995 that approximately 40 million households worldwide used electric water heating systems. The most common form of electric hot water heating system involves a storage tank in which water is heated slowly over time to a predetermined temperature. The water in the storage tank is maintained at the predetermined temperature as water is drawn from the storage tank and replenished with cold inlet water. Generally, storage tanks include a submerged electrical resistance-heating element connected to the mains electricity supply whose operation is controlled by a thermostat or temperature-monitoring device. Electric hot water storage systems are generally considered to be energy inefficient as they operate on the principle of storing and heating water to a predetermined temperature greater than the temperature required for usage, even though the consumer may not require hot water until some future time. As thermal energy is lost from the hot water in the storage tank, further consumption of electrical energy may be required to reheat that water to the predetermined temperature. Ultimately, a consumer may not require hot water for some considerable period of time. However, during that time, some electric hot water storage systems continue to consume energy to heat the water in preparation for a consumer requiring hot water at any time. Of course, rapid heating of water such that the water temperature reaches a predetermined level within a short period of time enables a system to avoid the inefficiencies that necessarily occur as a result of storing hot water. Rapid heating or “instant” hot water systems are currently available where both gas, such as natural gas or LPG (Liquefied Petroleum Gas) and electricity are used as the energy source. In the case of natural gas and LPG, these are fuel sources that are particularly well suited to the rapid heating of fluid as the ignition of these fuels can impart sufficient thermal energy transfer to fluid and raise the temperature of that fluid to a satisfactory level within a relatively short time under controlled conditions. However, whilst it is possible to use natural gas fuel sources for the rapid heating of water, these sources are not always readily available. In contrast, an electricity supply is readily available to most households in developed nations. There have been previous ineffective attempts to produce an electrical “instant” hot water system. These include the hot wire and the electromagnetic induction systems. The hot wire “instant” hot water system has been developed wherein a wire is located in a thermally and electrically non-conductive tube of a relatively small diameter. In operation, water passes through the tube in contact with or in very close proximity to the wire, which is energised to thereby transfer thermal energy to the water in the tube. Control is generally affected by monitoring the output temperature of water from the tube and comparing it with a predetermined temperature setting. Dependent upon the monitored output temperature of the water, a voltage is applied to the wire until the temperature of the water reaches the desired predetermined temperature setting. Whilst this type of system avoids the energy inefficiencies involved with the storage of hot water, it unfortunately suffers a number of other disadvantages. In particular, it is necessary to heat the wire to temperatures much greater than that of the surrounding water. This has the disadvantageous effect of causing the formation of crystals of dissolved salts normally present in varying concentrations in water such as calcium carbonate and calcium sulphate. Hot areas of the wire in direct contact with the water provide an excellent environment for the formation of these types of crystals which results in the wire becoming “caked” and thus reducing the efficiency of thermal transfer from the wire to the surrounding water. As the tube is generally relatively small in diameter, the formation of crystals can also reduce the flow of water through the tube. In addition, hot wire type systems require relatively high water pressures for effective operation and thus these systems are not effective for use in regions that have relatively low water pressure or frequent drops in water pressure that may occur during times of peak water usage. The electromagnetic induction system functions like a transformer. In this case currents induced into a secondary winding of the transformer cause the secondary winding to heat up. The heat generated here is dissipated by circulating water through a water jacket that surrounds the secondary winding. The heated water is then passed out of the system for usage. Control is generally affected by monitoring the output temperature of water from the water jacket and comparing it with a predetermined temperature setting. Dependent upon the monitored output temperature of the water, voltage applied to the primary winding can be varied, which varies the electric currents induces in the secondary winding until the temperature of the water reaches the desired predetermined temperature setting. Whilst this type of system avoids the energy inefficiencies involved with the storage of hot water, it also suffers a number of other disadvantages. In particular, it is necessary to heat the secondary winding to temperatures greater than that of the surrounding water. This has the same effect of causing the formation of crystals of dissolved salts as discussed above. As the gap between the secondary winding and the surrounding water jacket is generally relatively narrow, the formation of crystals can also reduce the flow of water through the jacket. In addition, the magnetic fields developed and the high currents induced in the secondary winding may result in unacceptable levels of electrical or RF noise. This electrical or RF noise can be difficult to suppress or shield, and affects other electromagnetic susceptible devices within range of the electromagnetic fields. It is therefore desirable to provide apparatus for rapid heating of fluid, particularly water, using electrical energy and which obviates at least some of the disadvantages of other systems. It is also desirable to provide an improved method for rapidly heating water using electrical energy which minimises power consumption. It is also desirable to provide an improved system for heating water using electrical energy which provides relatively rapid water heating suitable for domestic and/or commercial purposes. It is also desirable to provide an improved apparatus and method for electric fluid heating which facilitates control of the output temperature whilst minimising formation of crystals of dissolved salts. It is also desirable to provide an improved fluid heating system which uses mains power generally available in domestic and commercial buildings. It is also desirable to provide an improved heating apparatus which can be manufactured in various capacities of fluid throughput. It is also desirable to provide fluid heating apparatus which can be designed to operate with a variety of fluids or with water of varying hardness. It is also desirable to provide fluid heating apparatus which can be installed in close proximity to the hot water outlet, thereby reducing the time delay of the arrival of hot water and thereby obviating unnecessary wastage of water. It will be understood that any discussion of devices, articles or the like which has been included in this specification is solely for the purpose of providing a context for the present invention. It is not to be taken as an admission that any or all of these matters either form part of the prior art base or were common general knowledge in the field relevant to the present invention as it existed before the priority date of each claim of this application. |
<SOH> SUMMARY OF THE INVENTION <EOH>In accordance with one aspect of the invention there is provided apparatus for heating fluid comprising passageway means defining a flow path for the fluid to be heated, upstream fluid temperature measuring means to measure the temperature of fluid to be heated, a plurality of sets of electrode means in or forming the flow path and between which said fluid passes, said sets of electrode means including at least first and second electrode sets along the fluid flow path, said first electrode set and said second electrode set both having at least one pair of electrodes between which an electric current is passed through the said fluid to heat the fluid during its passage along the flow path, first downstream temperature measuring means downstream of the second electrode set, fluid flow rate determining means, and electrical control means to supply and control electrical power to the electrodes of each set, said control means having processing means to relate current flow and applied voltage in response to measured upstream and downstream temperatures and fluid flow rate to determine desired power input to the fluid from each electrode set to achieve a desired fluid temperature downstream of the second electrode set. Preferably, the passageway means comprises an annular space between spaced, substantially coaxial cylindrical members. The passageway means may define a plurality of parallel flow paths for the fluid. In one embodiment, a second temperature measuring means measures the temperature of the fluid between the first and second electrode sets, and the control means controls power to the first and second electrode sets in accordance with the measured temperatures and a desired fluid temperature increase in the passage of the fluid between the respective electrode sets. In a preferred embodiment, the electrode means comprises at least three pairs of electrodes spaced along the flow path. The electrodes of each pair are spaced across the flow path so that voltage applied between the electrodes of each pair causes current to flow through the fluid across the flow path as the fluid passes along the passageway means. In one preferred embodiment, the electrode means comprises cylindrical, substantially coaxial electrodes forming or located in a section of the passageway means. Preferably, the passageway means includes three sections, each passageway section having an inlet and an outlet, the sections being connected together in series such that the outlet of a first section comprises the inlet of the second section, and the outlet of the second section comprises the inlet of the third section, with electrodes for each of the three sections. With this arrangement, the outlets of the first and second sections have fluid temperature measuring means, and the control means controls the power to the electrodes of each section in accordance with the measured inlet and outlet temperatures of each section and a predetermined desired temperature difference. In a preferred embodiment, each passageway section is formed by spaced, substantially coaxial cylindrical electrodes defining an annular flow path for the fluid. In another embodiment, the passageway means includes more than three passageway sections, each section having an inlet and an outlet, the sections being connected in series and the control means controlling power to an electrode pair of each section in accordance with measured inlet and outlet temperatures of each section and a predetermined desired temperature difference for each section. In preferred embodiments of the invention, control of the electrical power being passed to the fluid is provided by a microcomputer controlled management system. The microcomputer controlled management system is preferably able to detect and accommodate changes in the specific conductance of the fluid itself due to the change in temperature of the fluid within the system itself, as well as variances in electrical conductivity of the incoming fluid. That is, in preferred embodiments of the present invention, the management system monitors and responds to an electrical conductivity, or specific conductance gradient between the input and output of elements of the heating system. In an instant fluid heating system in accordance with an embodiment of the present invention used for domestic water heating, fluctuations in incoming water electrical conductivity can also be caused by factors such as varying water temperatures and varying concentrations of dissolved chemicals and salts, and such variations should be managed as a matter of course. However, preferred embodiments of the present invention will also manage and respond to changes in the electrical conductivity of the fluid as it is heated within the system itself, that is, the effective management of the specific conductance gradient. According to another aspect of the invention there is provided a method for heating fluid comprising the steps of: passing fluid along a fluid path; providing at least two sets of electrodes spaced along the fluid path; applying a variable electrical voltage between the electrodes of each set to thereby pass electrical currents through the fluid between electrodes of each set; monitoring fluid path inlet fluid temperature; monitoring fluid path outlet fluid temperature; monitoring the currents passing through the fluid between electrodes of each electrode set in response to application of the variable electrical voltage; and controlling the variable electrical voltage between electrodes of each electrode set in response to the specific conductance of the fluid as determined by reference to the monitored fluid temperatures and current flows for a given fluid flow in each section of the flow path such that an amount of electrical power passed to the fluid corresponds to a predetermined temperature increase of the fluid. In preferred embodiments of the method of the present invention, additional further steps may be carried out comprising: Compensating for a change in the electrical conductivity of the fluid caused by varying temperatures and varying concentrations of dissolved chemicals and salts, and through the heating of the fluid, by altering the variable electrical voltage to accommodate for changes in specific conductance when increasing the fluid temperature by the desired amount. Such a step may be performed by controlling the electrical power applied to the electrode sets to maintain the required constant fluid temperature increase in that electrode segment. The variable electrical voltage may then be adjusted to compensate for changes in specific conductance of the fluid within the segment of the flow path associated with each electrode pair, which will affect the current drawn by the fluid in that segment. The changes in specific conductance of the fluid passing through the separate electrode segments can be managed separately in this manner. Therefore the system is able to effectively control and manage the resulting specific conductance gradient across the whole system. Similarly, the system of the present invention preferably further comprises means to manage the changes in specific conductance of the fluid caused by heating of the fluid. Such means may comprise a temperature sensor for measuring the system output fluid temperature for comparison to the input fluid temperature of each section in order to determine whether a desired temperature increase of the fluid has been achieved. In preferred embodiments, a temperature sensor is placed upstream from the electrode segments to supply a signal representative of the temperature of the fluid prior to its passage between the electrode segments. With the temperature sensor placed upstream of the electrode segments, a temperature difference may be determined between the inlet fluid and a desired temperature of the outlet fluid. The desired temperature of the outlet fluid may be adjusted by a user via an adjustable control means. The volume of fluid passing between any set of electrodes may be accurately determined by measuring the dimensions of the passage within which the fluid is exposed to the electrodes taken in conjunction with fluid flow. Similarly, the time for which a given volume of fluid will receive electrical power from the electrodes may be determined by measuring the flow rate of fluid through the passage. The temperature increase of the fluid is proportional to the amount of electrical power applied to the fluid. The amount of electrical power required to raise the temperature of the fluid a known amount, is proportional to the mass (volume) of the fluid being heated and the fluid flow rate through the passage. The measurement of electrical current flowing through the fluid can be used as a measure of the electrical conductivity, or the specific conductance of that fluid and hence allows determination of the required change in applied voltage required to keep the applied electrical power constant. The electrical conductivity, and hence the specific conductance of the fluid being heated will change with rising temperature, thus causing a specific conductance gradient along the path of fluid flow. The energy required to increase the temperature of a body of fluid may be determined by combining two relationships: in-line-formulae description="In-line Formulae" end="lead"? Energy=Specific Heat Capacity×Density×Volume×Temp-Change Relationship (1) in-line-formulae description="In-line Formulae" end="tail"? or The energy per unit of time required to increase the temperature of a body of fluid may be determined by the relationship: Power ( P ) = Specific Heat Capacity ( SHC ) × Density × Vol ( V ) × Temp - Change ( Dt ) Time ( T ) For analysis purposes, the specific heat capacity of water may be considered as a constant between the temperatures of 0 degC and 100 degC. The density of water being equal to 1, may also be considered constant. Therefore, the amount of energy required to change the temperature of a unit mass of water, 1 degc in 1 second is considered as a constant and can be labelled “k”. Volume/Time is the equivalent of flow rate (Fr). Thus: The energy per unit of time required to increase the temperature of a body of fluid may be determined by the relationship: Power ( P ) = k × Flow rate ( Fr ) × Temp - Change ( Dt ) Time ( T ) Thus if the required temperature change is known, the flow rate can be determined and the power required can be calculated. In preferred embodiments of the present invention, the electrodes are segmented and input and output temperatures are measured. Measurement of the temperature allows the computing means of the microcomputer controlled management system to determine the voltage required to be applied to the electrodes in an electrode segment in order to supply a necessary amount of electrical power to the fluid in order to provide the necessary management of changes in the specific conductance of the fluid so as to increase the temperature of the fluid by a desired amount. Typically, when a user requires heated water, a hot water tap is operated thus causing water to flow. This flow of water may be detected by a flow meter and cause the initiation of a heating sequence. The temperature of incoming water may be measured and compared with a preset desired temperature for water emitting from the system. From these two values, the required change in water temperature from inlet to outlet may be determined. Of course, the temperature of the inlet water to the electrode segments may be repeatedly measured over time and as the value for the measured inlet water temperature changes, the calculated value for the required temperature change from inlet to outlet of the electrode segments can be adjusted accordingly. Similarly, with changing temperature, mineral content and the like, changes in electrical conductivity and therefore specific conductance of the fluid may occur over time. Accordingly, the current passing through the fluid will change causing the resulting power applied to the water to change. Repeatedly measuring the temperature outputs of the electrode segments over time and comparing these with the required output temperature values will enable repeated calculations to correct the voltage applied to the electrode segments. In one preferred embodiment, a computing means provided by the microcomputer controlled management system is used to determine the electrical power that should be applied to the fluid passing between the electrodes, by determining the value of electrical power that will effect the desired temperature change between the electrode segment inlet and outlet, measuring the effect of changes to the specific conductance of the water and the thereby calculate the voltage that needs to be applied for a given flow rate. |
Chuck for tools, especially screwdriver bits |
The invention relates to a chuck (1) for tools, especially screwdriver bits with a polygonal section (2), having a polygonal cavity (3) for the insertion of the polygonal section (2), the wall (4) of the polygonal cavity (3) having a window (5) in which is disposed a pressure-piece (6) which can be displaced in the insertion direction (E) and which, in order to secure the inserted polygonal section (2) against being drawn out, is forced against the polygonal section (2), in a direction transverse to the insertion direction (E), by a sloping inner wall (9) of an actuating element which is outside the window and is retained in a clamping position by a restoring spring (10), and which, in a release position of the actuating element (7), can move aside out of the polygonal cavity (3) in order for the polygonal section (2) to be drawn out, and proposes to achieve a further development of the generic type in that the pressure-piece (6) is subjected to the action of a compression spring (8) acting counter to the insertion direction (E) and, upon displacement counter to the direction of spring action, can move aside out of the polygonal cavity (3). |
1-10. (cancelled) 11. Chuck (1) for tools, especially screwdriver bits with a polygonal section (2), the chuck comprising: a polygonal cavity (3) for the insertion of the polygonal section (2), a wall (4) of the polygonal cavity (3) having a window (5) in which is disposed a pressure-piece (6) which is displaceable in an insertion direction (E); wherein, in order to secure the inserted polygonal section (2) against being drawn out, the pressure-piece (6) is forced against the polygonal section (2), in a direction transverse to the insertion direction (E), by a sloping inner wall (9) of an actuating element; wherein the actuating element is outside the window and is retained in a clamping position by a restoring spring (10), and which, in a release position of the actuating element (7), can move aside out of the polygonal cavity (3) in order for the polygonal section (2) to be drawn out; and wherein the pressure-piece (6) is subjected to the action of a compression spring (8) acting counter to the insertion direction (E) and, upon a displacement counter to the direction of spring action of the compression spring, the pressure-piece (6) can move aside out of the polygonal cavity (3). 12. Chuck according to claim 11, wherein the pressure-piece (6) is a round piece. 13. Chuck according to claim 11, wherein the pressure-piece (6) is a ball. 14. Chuck according to claim 11, wherein the pressure-piece (6) is subjected to the action of a sloping inner wall (9) of an actuating sleeve which forms the actuating element (7). 15. Chuck according to claim 11, wherein the window (5) is associated with one of the edges of the polygon of the cavity (3). 16. Chuck according to claim 11, wherein the actuating element (7) is displaceable from the clamping position into the release position counter to the force of the restoring spring (10). 17. Chuck according to claim 11, wherein the restoring spring (10) and the compression spring (8) act in the same direction. 18. Chuck according to claim 11, wherein the pressure-piece (6) can penetrate, through the window (5), into a corner cutout (11) of the polygonal section (2). 19. Chuck according to claim 11, wherein the window (5) is configured as a slot extending in the insertion direction (E). 20. Chuck according to claim 11, wherein the window (5) is located level with a corner cutout (11) provided in at least one of the edges of the polygon of the polygonal section (2). |
Method for controlling the operation of a transport system for containers, operating devices and transport system thus controlled |
A transport system for containers comprises an operating device with linear guide means for the transformation of a uniform circular motion of a motor into a linear harmonic motion with a substantially sinusoidal velocity in a longitudinal direction. The operating device is controlled so as to vary the rotational speed of the motor and to obtain a substantially bell-shaped velocity profile, for gradually accelerating and decelerating the containers so as to obtain a precise advance and positioning thereof without the need for further means for centring the containers. |
1. A method for controlling the operation of a transport system for containers, of the type comprising a support structure (10) with at least one fixed portion (11) and a movable portion (14), the containers (13) being disposed in a line on the fixed portion (11), spaced from one another at a predetermined pitch (P), the method comprising the following steps: raising the movable portion (14) parallel to a first direction (Z) in order to raise the containers (13) from the fixed portion (11); advancing the movable portion (14) parallel to a second direction X for a predetermined distance (P)′, with gradual acceleration and deceleration at the beginning and the end of the forward travel, respectively; lowering the movable portion (14) parallel to the first direction (Z) in order to place the containers (13) on the fixed portion (11) again; retracting the movable portion (14). 2. A method according to claim 1, wherein the first direction (Z) is substantially vertical, and the second direction (X) is substantially horizontal. 3. A method according to claim 1, wherein the predetermined distance of advance of the movable portion (14) is substantially equal to the pitch (P) between one container (13) and another. 4. A method according to claim 1, wherein the velocity (Vx) of the movable portion (14) over time (t), at least in the phase of advance parallel to the second direction (X), is substantially representable by the curve V1, of FIG. 6. 5. An operating device for a transport system for containers, comprising a device (18) movable in a longitudinal direction (X), adapted to be connected to the movable portion (14) of the transport system, a motor (23) with an output shaft being operably connected to the movable device by means of operating members (20, 21, 22) adapted to transform a uniform circular motion of the output shaft of the motor (23) into a harmonic reciprocating motion of the movable device (18), at a velocity which is substantially sinusoidal in the longitudinal direction (X). 6. An operating device according to claim 5, comprising a support structure (16) with first linear guide means (17) for the movable device (18), second linear guide means (20, 21) being arranged on the movable device (18) in a substantially orthogonal direction with respect to the first linear guide means (17), crank means (22) being connected on one side to the second linear guide means (20, 21), and on the other side to the motor (23). 7. An operating device according to claim 5, wherein the motor (23) is an electric motor controlled by an inverter. 8. A transport system for containers, comprising a support structure (10) with a fixed portion (11) and a movable portion (14), the movable portion being controlled by at least two separate operating means in two different directions (X, Z), the second direction X being substantially parallel to a predetermined direction of advance (A) of the containers (13), the operating means (15) for the control of the movable portion (14) in the second direction X being adjustable in velocity. 9. A transport system according to claim 8, wherein the operating means (15) comprise an electric motor (23) controlled by an inverter. 10. A transport system according to claim 8, wherein the operating means (15) are connected to the movable portion (14) and are formed in such a manner that constant rotation of the electric motor (23) results in a movement of the movable portion (14) at a substantially sinusoidal velocity in the second direction (X), the electric motor (23) being operated, in use, so that its rotation speed is constant at least in the state of operation of the movable portion (14) in the second direction (X) 11-12. (Cancelled) 13. A transport system according to claim 8, comprising an operating device comprising a device (18) movable in a longitudinal direction (X), adapted to be connected to the movable portion (14) of the transport system, a motor (23) with an output shaft being operably connected to the movable device by means of operating members (20, 21, 22) adapted to transform a uniform circular motion of the output shaft of the motor (23) into a harmonic reciprocating motion of the movable device (18), at a velocity which is substantially sinusoidal in the longitudinal direction (X). 14. A transport system according to claim 13, comprising a support structure (16) with first linear guide means (17) for the movable device (18), second linear guide means (20, 21) being arranged on the movable device (18) in a substantially orthogonal direction with respect to the first linear guide means (17), crank means (22) being connected on one side to the second linear guide means (20, 21), and on the other side to the motor (23). 15. A transport system according to claim 14, wherein the motor (23) is an electric motor controlled by an inverter. |
Correction of the temperature error during a measurement conducted by a coordinate measuring device |
The discovered temperature of the feeler is regularly determined and is recorded together with the associated calibrating data at this temperature. Temperature correction data for the feeler are established from this historic collection consisting of temperature values and of calibrating data. This temperature correction data can be used during a measurement at the respective temperature. This method avoids a separate and complicated setting of the temperature of the feeler or of the entire coordinate measuring device for the calibration. |
1. A method for correcting the temperature error during a measurement with the aid of a coordinate measuring machine, having the following steps: a) determining and recording the temperature found for at least one part of the coordinate measuring machine and determining and recording calibration data of the at least one part of the coordinate measuring machine at the temperature found; a1) at least one feeler or a feeler combination being selected as the at least one part of the coordinate measuring machine; a2) the determination and recording of the temperature found and/or of the calibration data being carried out by the coordinate measuring machine; a3) the calibration data being calculated from machine coordinates; b) repeating step a) at least once at a later instant, and recording the new temperature, found at the later instant, and associated calibration data; c) determining temperature correction data for the at least one part of the coordinate measuring machine from the recorded temperatures and associated calibration data; d) determining the temperature of the at least one part of the coordinate measuring machine during the measurement; and e) selecting suitable temperature correction data for the at least one part of the coordinate measuring machine on the basis of the temperature, determined during the measurement, of the at least one part of the coordinate measuring machine. 2. The method as claimed in claim 1, characterized in that the temperature correction data are determined individually for each individual feeler. 3. The method as claimed in claim 1, characterized in that the determined calibration data are weighted during the determination of the temperature correction data in accordance with the difference between the temperature belonging to the calibration data and a reference temperature. 4. A coordinate measuring machine f) having means for determining and recording the temperature found for at least one part of the coordinate measuring machine, and having means for determining and recording calibration data of the at least one part of the coordinate measuring machine at the temperature found; f1) at least one feeler or a feeler combination being the at least one part of the coordinate measuring machine; f3) having means for calculating the calibration data from machine coordinates; g) having means for repeating at least once the determination of temperature and calibration data at a later instant, and having means for recording the new temperature, found at the later instant, and associated calibration data; h) having means for determining temperature correction data for the at least one part of the coordinate measuring machine from the recorded temperatures and associated calibration data; i) having means for determining the temperature of the at least one part of the coordinate measuring machine during a measurement; and j) having means for selecting suitable temperature correction data for the at least one part of the coordinate measuring machine on the basis of the temperature, determined during the measurement, of the at least one part of the coordinate measuring machine. |
Processing device and method for an automatic perception system |
The invention relates to a processing device for an automatic perception system that involves the use of STN calculation units (1) which receive data from a data bus (7) and which are interconnected by a backannotation bus (6). According to the invention, the units are grouped together in hierarchical sets, in which the set of the order of 0 is formed by a single unit, the set of the order of 1 is formed by the combination of several order 0 set, the sets of the order of P greater than 1 are formed by a combination of lower P−1 order sets, the hierarchised sets of a given order P sharing a backannotation bus. The backannotation buses between a lower order P and a greater order P+1 are interconnected by means of a connection unit. The invention also relates to the method of using the device. |
1. A processing device for an automatic perception system utilizing STN calculation modules (1) receiving data from a data bus (7) and interconnected by a backannotation bus (6), characterized in that the modules are grouped into hierarchized sets comprising the order 0 set formed by one single module, the order 1 set formed by the combining of a plurality of order 0 sets, the order P sets greater than 1, formed by the combination of the lower order P−1 sets, the hierarchized sets of a given order P sharing a backannotation bus and in that the interconnection of the backannotation bus between a lower order P and a greater order P+1 is done by means of an interconnection module according to an interconnection configuration, a function of selection parameters. 2. The device according to claim 1, wherein the interconnection module comprises: a first compound term generator (30) receiving on input at least one lower order bus backannotation signal and producing on output a decision-making signal (31) as a function of selection parameters; at least one second compound term generator (32) receiving on input the greater order backannotation bus (36) and producing on output a signal (33) sent via the lower order backannotation bus as a function of selection parameters; a third compound term generator (34) receiving on input, on the one hand, the greater order backannotation bus (36) and, on the other hand, the decision-making signal (31) and producing on output a backannotation signal (37) sent via the greater order backannotation bus as a function of selection parameters; 3. The device according to claim 2, wherein in the case of a lower order backannotation bus of dimension I, the first compound term generator (30) receives on input I−1 backannotation signals, the backannotation signal produced by the second compound term generator (32) being excluded. 4. The device according to claim 2 or 3, wherein in the case of a greater order backannotation bus of dimension S, the second compound term generator (32) receives on input S backannotation signals and the third compound term generator (34) receives on input S−1 backannotation signals, the backannotation signal produced by the third compound term generator (34) being excluded. 5. The device according to any one of claims 2 to 4, wherein in the case of an interconnection module, whose lower order is 0; that is, interconnecting a STN calculating module (1) to an order 1 backannotation bus, the STN calculating module (1) comprises an histogram calculating unit (2) performing a calculation as a factor of a parameter selected in a data selection unit (5) arranged between a data bus and the calculating unit (2), said parameter being further taken into account by a classification unit (3) intended to produce a decision-making signal (9), the calculation of the calculating unit (2) is validated by the signal (8) coming from the second compound term generator (32) and wherein the first compound term generator (30) is virtual and produces an output signal equal to the input signal, the decision-making signal being sent directly over the third compound term generator. 6. The device according to any one of claims 2 to 5, wherein the compound term generator comprises: parameterizable inversion means of input signals E0, E1, . . . En and producing signals E′0, E′1, . . . E′n; and AND combination means (101) making it possible to produce on output an outand signal as a function of the parameters; outand=({overscore (Re g0)}+E′0).({overscore (Re g1)}+E′1) . . . ({overscore (Re gn)}+E′n)(Re g0+Re g1+ . . . Re gn) Reg0, Reg1, . . . , Regn corresponding to the parameters. 7. The device according to claim 6, wherein for the AND combination, the parameters are stored in two groups of n+1 registers, a first register group controlling a first input of a series of n+1 OR EXCLUSIVE gates, whose second input receives the corresponding input signal, a second register group controlling, after inversion (11), a first input of a series of n+1 OR gates, whose second input receives the output signal of the corresponding OR EXCLUSIVE gates, the outputs of the OR gates being combined in an AND gates at n+2 inputs, the AND NOT combination of the inverted outputs of the second group of registers being likewise sent via the AND element, to produces an output signal. 8. The device according to any one of claims 2 to 5, wherein the compound term generator comprises: parameterizable inversion means of input signals E0, E1, . . . En and producing signals E′0, E′1, . . . E′n; OR combination means (102) making it possible to produce on output an outOR signal as a function of parameters; outOR=(Re g0·E′0)+(Re g1·E′1)+ . . . (Re gn·E′n) Reg0, Reg1, . . . , Regn corresponding to the parameters. 9. The device according to claim 8, wherein for the OR combination, the parameters are stored in two groups of n+1 registers, a first register group controlling a first input of a series of n+1 OR EXCLUSIVE gates, whose second input receives the corresponding input signal, a second register group controlling a first input of a series of n+1 AND gates whose second input receives the output signal from the corresponding OR EXCLUSIVE gates, the outputs of the AND gates being combined in an OR gates having n+1 inputs for producing an output signal. 10. The device according to any one of claims 2 to 5, wherein the compound term generator comprises parameterizable inversion means of input signals E0, E1, . . . En and producing signals E′0, E′1, . . . E′n, and means making it possible to produce as a function of parameters an output signal out resulting either from an AND combination with: out=({overscore (Re g0)}+E′0).({overscore (Re g1)}+E′1) . . . ({overscore (Re gn)}+E′n)(Re g0+Re g1+ . . . Re gn) or an OR combination with: out=(Re g0·E′0)+(Re g1·E′1)+ . . . +(Re gnE′) Reg0, Reg1, . . . , Regn corresponding to the respective parameters of the combination under consideration. 11. The device according to claim 10, wherein for the AND combination, the parameters are stored in two groups of n+1 registers, a first register group controlling a first input of a series of n+1 OR EXCLUSIVE gates, whose second input receives the corresponding input signal, a second register group controlling, after inversion, a first input of a series of n+1 OR gates, whose second input receives the output signal of the corresponding OR EXCLUSIVE gates, the outputs of the OR gates being combined in an AND gate having n+2 inputs, the AND NOT combination of the inverted outputs of the second group of registers being likewise sent via the AND gate, to produces a first signal and, wherein for the OR combination, the parameters are stored in two groups of n+1 registers, a third register group controlling a first input and a second series of n+1 OR EXCLUSIVE gates, whose second input receives the corresponding input signal, a fourth register group controlling a first input of a series of n+1 AND gates, whose second input receives the output signal from the corresponding OR EXCLUSIVE gates, the outputs of the AND gates being combined in one OR gate having n+1 inputs for producing a second signal, the first signal and the second signal being selected by a multiplexer in order to produce the output signal. 12. The device according to claim 11, wherein the first and third registers as well as the first and second series of OR EXCLUSIVE gates are grouped, respectively, in one single register and one single series of gates, the outputs of the OR EXCLUSIVE gates being sent, on the one hand, via the inputs of the OR gates for the AND combination and, on the other hand, via the inputs of the AND gate for the combination OR. 13. The device according to any one of the above claims, wherein an hierarchized set of modules forms an hierarchized memory of an element of a perception environment and which is defined by the configuration of the selection parameters of the interconnection modules of the set. 14. A processing method for an automatic perception system utilizing STN calculation modules (1) receiving data from a data bus (7) and interconnected by a backannotation bus (6), characterized in that using a device according to any one of the above claims, the modules are grouped into hierarchized sets comprising the entirety of order 0 formed by a single module, the set of order 1 formed by the combination of a plurality of order 0 sets, the order P sets greater than 1 formed by the combination of lower order P−1 sets, the hierarchized sets of a given order P sharing a backannotation bus and, wherein the backannotation buses are interconnected between a lower order P and a greater order P+1 by means of an interconnection module according to an interconnection configuration, a function of selection parameters. |
Method for the translation of programs for reconfigurable architectures |
Data processing using multidimensional fields is described along with methods for advantageously using high-level language codes. |
1-20. (canceled). 21. A method for translating high-level languages onto a reconfigurable architecture, comprising: constructing a finite automaton for computation in such a way that a complex combinatory network of individual functions is formed; and assigning memories to the network for storage of operands and results. 22. A method for data processing having a multidimensional field using reconfigurable ALUs, comprising: providing a high-level language code; translating the high-level language code in such a way as to construct a finite automaton for the computation, a complex combinatory network being formed from individual functions and memories being assigned to the network for storage of at least one of operands and results. 23. The method as recited in claim 21 wherein the complex combinatory network is at least one of constructed and broken down, in such a way that reconfigurable architecture is operated for a longest possible period of time without reconfiguration. 24. The method as recited in claim 22 wherein the complex combinatory network is at least one of constructed and broken down, in such a way that reconfigurable architecture is operated for a longest possible period of time without reconfiguration. 25. The method as recited in claim 21, further comprising: determining complex instructions to one of construct and break down the complex combinatory network in such a way that the reconfigurable architecture is operated for the longest possible period of time without reconfiguration. 26. The method as recited in claim 22, further comprising: determining complex instructions to one of construct and break down the complex combinatory network in such a way that the reconfigurable architecture is operated for the longest possible period of time without reconfiguration. 27. The method as recited in claim 21, wherein the finite automaton is constructed directly from imperative source text. 28. The method as recited in claim 22, wherein the finite automaton is constructed directly from imperative source text. 29. The method as recited in claim 21, wherein the finite automaton is constructed from operations adapted to at least one of coarse-grained logic circuits and existing fine-grained elements. 30. The method as recited in claim 29, wherein the fine-grained element include at least one of FPGA cells and state machines. 31. The method as recited in claim 21, further comprising: breaking down the finite automaton into configurations. 32. The method as recited in claim 22, further comprising: breaking down the finite automaton into configuration. 33. The method as recited in claim 31, further comprising: successively mapping generated configurations onto the reconfigurable architecture; and filing at least one of operating data and states that are to be transmitted among the configurations in a memory. 34. The method as recited in claim 32, further comprising: successively mapping generated configurations onto the reconfigurable architecture; and filing at least one of operating data and states that are to be transmitted among the configurations in a memory. 35. The method as recited in claim 33, wherein the memory is at least one of provided and determined by the compiler. 36. The method as recited in claim 33, wherein during a configuration, data from at least one of a VPU-external source and an internal memory is processed and written to at least one of an external source and an internal memory. 37. The method as recited in claim 21, further comprising: providing a memory for an entire data record which is more extensive than a single data word. 38. The method as recited in claim 37, wherein data is filed in the memory as determined by the compiler during processing of a running configuration. 39. The method as recited in claim 21, further comprising: providing a memory for operands, a memory for results and a network of at least one of assignments and comparison instructions, with the automaton. 40. The method as recited in claim 39, wherein the comparison instructions include at least one of IF, CASE, WHILE, FOR, and REPEAT. 41. The method according to claim 39, further comprising: providing with the automaton an address generator for triggering the memory. 42. The method as recited in claim 21, wherein states are assigned to memories, a distinction being made between algorithmically relevant and irrelevant states, the relevant states including those states which are necessary within an algorithm to describe its correct function, and the irrelevant states including those which occur due to at least one of hardware used, a selected mapping, and other secondary reasons. 43. The method as recited in claim 21, further comprising: providing LOAD/STORE operations including data transfers with external modules, and data transfers between PAEs of the reconfigurable architecture. 44. The method as recited in claim 43, wherein the LOAD/STORE operations include data transfers between RAM PAEs and ALU PAES. 45. The method as recited in claim 21, further comprising: removing a first configuration during data processing, wherein data to be saved remains in corresponding memories. 46. The method as recited in claim 45, further comprising: reloading the first configuration and accessing previously saved data assigned to it. 47. The method as recited in claim 45, further comprising: loading a second configuration for access to previously saved data, the second configuration connecting registers to at least one global memories to access the global memory using address generators, the address generator generating addresses for the global memory, so that memory areas may be unambiguously assigned to the first configuration removed. 48. The method as recited in claim 21, further comprising: automatically performing a transformation to represent at least one of a parallelizability and a vectorizability of the configurable architecture. 49. The method as recited in claim 21, wherein arithmetic/logic instructions are mapped directly into the combinatory network. 50. The method as recited in claim 21, wherein jump instructions are rolled out directly into the combinatory network. 51. The method as recited in claim 21, wherein jump instructions are implemented by reconfiguration. 52. The method as recited in claim 21, wherein condition and control flow instructions are completely resolved in the combinatory network. 53. The method as recited in claim 21, wherein condition and control flow instructions are processed in the combinatory network. 54. The method as recited in claim 21, wherein condition and control flow instructions are relayed to a higher-level configuration unit which performs a reconfiguration accounting to a resulting status. 55. The method as recited in claim 21, wherein LOAD/STORE instructions are mapped into separate configurations. 56. The method as recited in claim 21, wherein LOAD/STORE instructions are implemented by address generators which write data from internal memories to external memories via address generator. 57. The method as recited in claim 21, wherein LOAD/STORE operations are implemented by address generators which load internal memories from at least one of external memories, and an external peripheral device. 58. The method as recited in claim 21, wherein register move operations are implemented in the combinatory network by buses between internal memories. 59. The method as recited in claim 21, wherein PUSH/POP operations are implemented by separate configurations which write to internal registers in the combinatory network. 60. The method as recited in claim 21, wherein PUSH/POP operations are implemented by separate configurations which write data for internal memories to external memories via address generators. |
<SOH> BACKGROUND INFORMATION <EOH>To implement execution of instructions for handling data (programs) that are written in high-level languages in a particular architecture used for data handling, there are conventional compilers which translate the instructions of the high-level language into instructions that are better adapted to the architecture used. Compilers which support highly parallel architectures in particular are thus parallelizing compilers. Conventional parallelizing compilers normally use special constructs such as semaphores and/or other methods for synchronization. Technology-specific methods are typically used. Conventional methods are not suitable for combining functionally specified architectures with the particular dynamic response and imperatively specified algorithms. The methods used therefore yield satisfactory results only in special cases. Compilers for reconfigurable architectures, in particular for reconfigurable processors, generally use macros created specifically for the intended reconfigurable hardware, mostly using hardware description languages such as Verilog, VHDL, or System C to create the macros. These macros are then called up from the program flow (instantiated) by an ordinary high-level language (e.g., C, C++). There are conventional compilers for parallel computers which map program parts onto multiple processors on a coarse-grained structure, mostly based on complete functions or threads. In addition, there are conventional vectorizing compilers which convert extensive linear data processing, such as computations of large expressions, into a vectorized form and thus permit computation on superscalar processors and vector processors (e.g., Pentium, Cray). A method for automatic mapping of functionally or imperatively formulated computation procedures onto different target technologies is described here, in particular on ASICs, reconfigurable modules (FPGAs, DPGAs, VPUs, chess array, kress array, Chameleon, etc.; hereinafter combined under the term VPU), sequential processors (CISC/RISC CPUs, DSPs, etc.; hereinafter summarized by the term CPU) and parallel computer systems (SMP, MMP, etc.). In this connection, reference is made in particular to the following patents and patent applications by the present applicant: P 44 16 881.0-53, DE 197 81 412.3, DE 197 81 483.2, DE 196 54 846.2-53, DE 196 54 593.5-53, DE 197 04 044.6-53, DE 198 80 129.7, DE 198 61 088.2-53, DE 199 80 312.9, PCT/DE 00/01869, DE 100 36 627.9-33, DE 100 28 397.7, DE 101 10 530.4, DE 101 11 014.6, PCT/EP 00/10516, EP 01 102 674.7, PACT13, PACT17, PACT18, PACT22, PACT24, PACT25, PACT26US, PACT02, PACT04, PACT08, PACT10, PACT15, PACT18(a), PACT27, PACT19. Each of these are hereby fully incorporated herein by reference for disclosure purposes. VPUs are basically composed of a multidimensional, homogeneous or inhomogeneous, flat or hierarchical array (PA) of cells (PAEs) which are capable of executing any functions, in particular logic functions and/or arithmetic functions and/or memory functions and/or network functions. PAEs are typically assigned a loading unit (CT) which determines the function of the PAEs by configuration and optionally reconfiguration. This method is based on an abstract parallel machine model which in addition to the finite automaton also integrates imperative problem specifications and permits an efficient algorithmic derivation of an implementation on different technologies. The following compiler classes are conventional: Classical compilers, which often generate stack machine code and are suitable for very simple processors, which are essentially designed as normal sequencers (see N. Wirth, Compilerbau [ Compiler Design ], Teubner Verlag). Vectorizing compilers construct mostly linear code which is intended for special vector computers or for highly pipelined processors. These compilers were originally available for vector computers such as the Cray. Modern processors such as Pentium processors require similar methods because of the long pipeline structure. Since the individual computation steps are performed as vectorized (pipelined) steps, the code is much more efficient. However, the conditional jump means problems for the pipeline. Therefore, a jump prediction which assumes a jump destination is appropriate. If this assumption is incorrect, however, the entire processing pipeline must be deleted. In other words, each jump for these compilers is problematical and actually there is no parallel processing. Jump predictions and similar mechanisms require a considerable extra complexity in terms of hardware. There are hardly any coarse-grained parallel compilers in the actual sense, parallelism typically being marked and managed by the programmer or the operating system, e.g., it is usually performed on a thread level in MMP computer systems such as various IBM architectures, ASCI Red, etc. A thread is a largely independent program block or even a separate program. Therefore, threads are easily parallelized on a coarse-grained level. Synchronization and data consistency must be ensured by the programmer or the operating system. This is complex to program and requires a significant portion of the computation power of a parallel computer. In addition, only a fragment of the parallelism which is actually possible is in fact usable due to this coarse parallelization. Fine-grained parallel compilers (e.g., VLIW) attempt to map the parallelism in a fine-grained form into VLIW arithmetic means that are capable of executing a plurality of computation operations in one clock cycle but may have a common register set. This limited register set is a significant problem because it must provide the data for all the computation operations. In addition, the data dependencies and inconsistent read/write operations (LOAD/STORE) make parallelization difficult. Reconfigurable processors have a large number of independent arithmetic units, typically located in a field. These are typically interconnected by buses instead of by a common register set. Therefore, vector arithmetic units are easily constructed, while it is also possible to perform simple parallel operations. In contrast with traditional register concepts, data dependencies are resolved by the bus connections. |
<SOH> SUMMARY <EOH>According to an example embodiment of the present invention, concepts of vectorizing compilers and parallelizing compilers (e.g., VLIW) are used at the same time for a compiler for reconfigurable processors and thus vectorization and parallelization are performed on a fine-grained level. An advantage is that the compiler need not map onto a fixedly predetermined hardware structure, but instead the hardware structure may be configured using an example method according to the present invention so that it is optimally suitable for mapping the particular compiled algorithm. |
Continuous polymerization process for the manufacture of superabsorbent polymers |
A continuous process for producing water-insoluble, water-swellable polymers comprises subjecting a monomer and initiator to polymerization conditions in a reactor system having at least 3 zones. |
1. A process for the preparation of water-absorbent, water-insoluble polymers, the process comprising: continuously polymerizing a monomer in a reactor system comprising at least 3 zones; wherein the first zone is an initiation zone to which there is continuously fed a monomer, an initiator and water under conditions such that the polymerization of the monomer is initiated; wherein the second zone is a gel-phase zone; wherein the third zone is a granulation zone; wherein the reactor system has at least two rotating shafts in the second and third zones; wherein the peak temperature in the second and third zones is from 50° C. to 100° C.; and wherein at least a portion of the water fed to the first zone optionally is in the form of steam. 2. The process of claim 1 wherein the monomer comprises from 25 to 50 weight percent partially neutralized acrylic acid having a degree of neutralization in the range of 50 to 80 mole percent. 3. The process of claim 1 wherein the temperature of the initiation zone is from 40 to 85° C. 4. The process of claim 1 wherein the peak-temperature in the reactor is maintained in a temperature range of 60 to 85° C. by reducing the pressure, evaporating water, and condensing the water under reflux conditions such that the condensate is sent back to the third zone. 5. The process of claim 1 wherein the combined average residence time in the three zones is from 4 to 80 minutes. 6. The process of claim 3 wherein 50 to 90 percent of the total energy input into the first zone is supplied by the heat of the polymerization reaction, 10 to 40 percent is supplied by injected steam, and 0 to 15 percent is supplied by heating the walls of the reaction vessel. 7. The process of claim 1 wherein the polymer discharged from the reactor has a weight average particle size of from 0.2 to 50 mm. 8. The process of claim 1 wherein the feed rate to the first zone is from 0.5 to 5 kg per liter of reactor volume per hour. 9. The process of claim 1 wherein the feed rate to the first zone is from 1.3 to 3.3 kg per liter of reactor volume per hour. 10. The process of claim 1 wherein a persulfate is introduced into the third zone, the discharge stream, or both. 11. The process of claim 1 wherein the monomer is in an aqueous mixture, and wherein the mixture is deoxygenated by countercurrent flow of an inert gas prior to being fed to the first zone. 12. The process of claim 1 wherein the combined residence time in the three zones is from 7 to 20 minutes. 13. The process of claim 1 wherein the three zones are contained in one reactor vessel. 14. The process of claim 1 wherein at least the second and third zone are contained in one reactor vessel. 15. The process of claim 1 wherein the first zone is in a vessel separate from the second and third zones. 16. The process of claim 1 wherein the monomer concentration in the feed to the first zone is at least 45 weight percent based on the weight of the feed. 17. The process of claim 1 wherein the wherein at least 2 of the shafts in the reactor system have overlapping radii and rotate in opposite directions. 18. The process of claim 17 wherein at least 2 shafts rotate at different speeds. 19. The process of claim 1 wherein the feed to the first zone comprises a solution of monomer, initiator, and water. 20. The process of claim 1 wherein the monomer comprises acrylic acid. 21. The process of claim 1 wherein polymer fines are recycled. 22. A process for the preparation of water-absorbent, water-insoluble polymers, the process comprising: continuously polymerizing a monomer in a reactor system comprising at least 3 zones; wherein the first zone is an initiation zone to which there is continuously fed a monomer, an initiator and water under conditions such that the polymerization of the monomer is initiated; wherein the second zone is a highly viscous gel-phase zone; wherein the third zone is a granulation zone; wherein the reactor system has at least two rotating shafts in the second and third zones; wherein the pressure in at least the second and third zones of the reactor system is subatmospheric; and wherein at least a portion of the water fed to the first zone optionally is in the form of steam. |
Process to manufacture polyurethane products using polymer polyols in which the carrier polyol is a tertiary amone based polyol |
The present invention pertains to a copolymer polyols based on tertiary amine based polyols and to polyurethane products made therefrom. The use oof such copolymer polyols reduces the amount of amine catalysts needed for the production of polyurethane foam. |
1. A process for the production of polyurethane products by reaction of a mixture of (a) at least one organic polyisocyanate with (b) a polyol composition comprising (b 1) from 0 to 99 percent by weight of a polyol compound having a functionality of 2 to 8 and a hydroxyl number of from 20 to 800 and (b2) from 100 to 1 percent by weight of at least one polyol compound having a functionality of 1 to 8 and a hydroxyl number of from 15 to 200, wherein the weight percent is based on the total amount of polyol component (b), and (b2) is a copolymer polyol composition comprising solids (b2i) dispersed in a carrier polyol (b2ii) wherein (b2) contains at least 2 percent and up to 60 percent solids (b2i) dispersion and at least 2 percent of the carrier polyol (b2ii) is a tertiary amine based polyol (b2iii); (c) optionally in the presence of a blowing agent; and (d) optionally additives or auxiliary agents known se for the production of polyurethane products. 2. The process of claim 1 wherein the carrier polyol (b2iii) has a functionality of from 2 to 6. 3. The process of claim 2 wherein the carrier polyol (b2iii) has an equivalent weight from 500 to 3000. 4. The process of claim 3 wherein the carrier polyol has an equivalent weight from 1000 to 2000. 5. The process of claim 1 wherein the amine based carrier polyol (b2iii) is made from a tertiary amine initiator which contains at least one N-methyl amino group or N,N-dimethylamino group. 6. The process of claim 1 wherein the amine based carrier polyol (biii) is initiated with a molecule containing 2 to 8 active hydrogen atoms and is subsequently capped with a tertiary amine or contains a tertiary amine in the polyol chain. 7. The process of claim 1 wherein the solids content (b2i) in the copolymer polyol is from 10 to 60 percent preferably from 10 to 50 percent. 8. The process of claim 1 wherein the solids (b2i) of (b2) are either based on polymers of styrene and/or acrylonitrile, polyurea, polyisocyanate polyadditon product, epoxide or a mixture thereof. 9. The process of claim 1 wherein the mixture further contains flame retardant agents. 10. The process of claim 1 wherein the foam hardness and reactivity of the polyurethane foaming systems is adjusted by varying the ratio between copolymer polyol (b2) and polyol (b2iii) by using (b2iii) as part of (b 1) in the formulation. 11. A polyurethane product prepared by the process of claim 1. 12. A polymer polyol composition produced by a free radical polymerization comprising: (a) a polyol (b) at least one ethylenically unsaturated monomer; (c) a free radical polymerization initiator and (d) a chain transfer agent wherein the chain transfer agent is polyol produced from a tertiary amine initiator having at least one N-methyl amino group, or N,N-dimethyl amino group, or a polyol initiated with a molecule containing 2 to 8 active hydrogen atoms wherein the polyol is capped with a tertiary amine or a polyol which contains a tertiary amine in the polyol chain. |
Thermoconductive composition |
In a thermoconductive composition containing wax, a substantially spherical boron nitride is added as a filler. The average particle size of the substantially spherical boron nitride is preferably from 20 to 100 μm and the filling ratio is preferably from 10 to 30% by volume. |
1-9. (canceled) 10. A thermoconductive composition comprising wax and spherical boron nitride, optionally wherein said spherical boron nitride has an average particle size of 20 to 100 μm. 11. The thermoconductive composition as claimed in claim 10, wherein said spherical boron nitride is contained in an amount of 10 to 30% by volume based on the entire composition. 12. The thermoconductive composition of claim 10, which further comprises from 10 to 1,000 parts by weight of a compound represented by the following formula (I): wherein R1 and R2 each independently represent an alkyl group having from 1 to 3 carbon atoms and n represents a value of 100 to 100,000, per 100 parts by weight of wax. 13. The thermoconductive composition as claimed in claim 12, wherein said compound represented by formula (I) is polyisobutylene. 14. The thermoconductive composition of claim 10, which is formed into a film or a sheet. 15. The thermoconductive composition as claimed in claim 14, wherein said film or sheet has a thickness of 0.02 to 2.0 mm. 16. The thermoconductive composition as claimed in claim 10, wherein said wax is selected from natural wax, synthetic wax, and blends thereof. 17. The thermoconductive composition as claimed in claim 10, wherein said wax is paraffin wax. |
Nucleic acids and proteins of insect or83b odorant receptor genes and uses thereof |
The present invention relates to insect odorant receptor genes and methods for identifying odorant receptor genes. The invention provides nucleotide sequences of insect odorant receptor genes Or83b, amino acid sequences of their encoded proteins (including peptides or polypeptides), and related products and methods. The nucleic acids of the invention may be operatively linked to promoter sequences and transformed into host cells. Methods of production of an Or83b odorant receptor protein (e.g., by recombinant means), and derivatives and analogs thereof, are provided. Antibodies to an Or83b odorant receptor protein, and derivatives and analogs thereof, are provided. Methods for identifying molecules that bind or modulate the activity of these Or83b odorant receptor genes are provided. Molecules found to bind or modulate the activity of Or83b genes may be formulated into pest control agents by providing a carrier. In a preferred embodiment, molecules that bind or modulate the activity of an Or83b gene form one species but not others is desired. Methods to modify the insect behaviour by modifying an insect Or83b odorant are also provided. |
1. An isolated nucleic acid molecule comprising a nucleotide sequence which encodes a polypeptide molecule comprising a first motif comprising the amino acid sequences of SEQ ID NO: 12, or a fragment thereof of at least 10 amino acids, wherein said polypeptide molecule is an insect Or83b polypeptide or a fragment thereof, with the proviso that the sequence of said polypeptide molecule is not found in SEQ ID NO: 10. 2. The isolated nucleic acid molecule of claim 1, wherein the polypeptide molecule further comprises a second motif comprising the amino acid sequence of SEQ ID NO: 13, or fragment thereof of at least 10 amino acids. 3. The isolated nucleic acid molecule of claim 1, wherein the polypeptide molecule further comprises a second motif comprising the amino acid sequence of SEQ ID NO: 14, or fragment thereof of at least 10 amino acids. 4. The isolated nucleic acid molecule of claim 3, wherein said fragment of SEQ ID NO: 14 is at least 15 amino acids. 5. The isolated nucleic acid molecule of claim 3, wherein said fragment of SEQ ID NO: 14 is at least 20 amino acids. 6. The isolated nucleic acid molecule of claim 3, wherein the second motif comprises an amino acid sequence selected from the group consisting of SEQ ID NOS: 15, 16, and 17. 7. The isolated nucleic acid molecule of claim 1, wherein the polypeptide molecule further comprises a second motif comprising the amino acid sequence of SEQ ID NO: 18, or a fragment thereof of at least 10 amino acids. 8. The isolated nucleic acid molecule of claim 7, wherein said fragment of SEQ ID NO: 18 is at least 15 amino acids. 9. The isolated nucleic acid molecule of claim 7, wherein said fragment of SEQ ID NO: 18 is at least 20 amino acids. 10. The isolated nucleic acid molecule comprising a nucleotide sequence which encodes a polypeptide molecule comprising a first motif comprising the amino acid sequence of SEQ ID NO: 13, or a fragment thereof of at least 10 amino acids, wherein said polypeptide molecule is an insect Or83b polypeptide or a fragment thereof, with the proviso that the sequence of said polypeptide molecule is not found in SEQ ID NO: 10. 11. The isolated nucleic acid molecule of claim 10, wherein the polypeptide molecule further comprises a second motif comprising the amino acid sequence of SEQ ID NO: 14, or a fragment thereof of at least 10 amino acids. 12. The isolated nucleic acid molecule of claim 11, wherein said fragment of SEQ ID NO: 14 is at least 15 amino acids. 13. The isolated nucleic acid molecule of claim 11, wherein said fragment of SEQ ID NO: 14 is at least 20 amino acids. 14. The isolated nucleic acid molecule of claim 11, wherein said second motif comprises an amino acid sequence selected from the group consisting of SEQ ID NOS: 15, 16, and 17. 15. The isolated nucleic acid molecule of claim 10, wherein the polypeptide molecule further comprises a second motif comprising the amino acid sequence of SEQ ID NO: 18, or a fragment thereof of at least 10 amino acids. 16. The isolated nucleic acid molecule of claim 15, wherein said fragment of SEQ ID NO: 18 is at least 15 amino acids. 17. The isolated nucleic acid molecule of claim 15, wherein said fragment of SEQ ID NO: 18 is at least 20 amino acids. 18. An isolated nucleic molecule comprising a nucleotide sequence which encodes a polypeptide molecule comprising a first motif comprising the amino acid sequence of SEQ ID NO: 14, or a fragment thereof of at least 10 amino acids, wherein said polypeptide molecule is an insect Or83b polypeptide or a fragment thereof, with the proviso that the sequence of said polypeptide molecule is not found in SEQ ID NO: 10. 19. The isolated nucleic acid molecule of claim 18, wherein said fragment of SEQ ID NO: 14 is at least 15 amino acids. 20. The isolated nucleic acid molecule of claim 18, wherein said fragment of SEQ ID NO: 14 is at least 20 amino acids. 21. The isolated nucleic acid molecule of claim 18, wherein said first motif comprises an amino acid sequence selected from the group consisting of SEQ ID NOS: 15, 16, and 17. 22. The isolated nucleic acid molecule of claim 18, wherein the polypeptide molecule further comprises a second motif comprising the amino acid sequence of SEQ ID NO: 18, or a fragment thereof of at least 10 amino acids. 23. The isolated nucleic acid molecule of claim 22, wherein said fragment of SEQ ID NO: 18 is at least 15 amino acids. 24. The isolated nucleic acid molecule of claim 22, wherein said fragment of SEQ ID NO: 18 is at least 20 amino acids. 25. An isolated nucleic acid molecule comprising a nucleotide sequence which encodes a polypeptide molecule comprising the amino acid sequence of three or more of SEQ ID NOS: 12, 13, 14, and 18, or a fragment of at least 10 amino acids of three or more of SEQ ID NOS: 12, 13, 14, and 18, wherein said polypeptide molecule is an insect Or83b polypeptide or a fragment thereof, with the proviso that the sequence of said polypeptide molecule is not found in SEQ ID NO: 10. 26. The isolated nucleic acid molecule of claim 25, wherein the sequence of SEQ ID NO: 14 is selected from the group consisting of SEQ ID NOS: 15, 16, and 17. 27. The isolated nucleic acid molecule comprising a nucleotide sequence which encodes a polypeptide molecule comprising the amino acid sequence of SEQ ID NOS: 12, 13, 14, and 18, or a fragment of at least 10 amino acids of each of SEQ ID NOS: 12, 13, 14, and 18, wherein said polypeptide molecule is an insect Or83b polypeptide or a fragment thereof, with the proviso that the sequence of said polypeptide molecule is not found in SEQ ID NO: 10. 28. The isolated nucleic acid molecule of claim 27, wherein the sequence of SEQ ID NO: 14 is selected from the group consisting of SEQ ID NOS: 15, 16, and 17. 29-50. (Cancelled). 51. An isolated nucleic acid molecule comprising a nucleotide sequence encoding a polypeptide with an amino acid sequence having at least 80% identity to at least 20 contiguous amino acids of the amino acid sequence of SEQ ID NO: 11 with the proviso that said amino acid sequence is not found in SEQ ID NO: 10. 52. The isolated nucleic acid molecule of claim 51, which further comprises an origin of replication. 53. (Canceled). 54. (Canceled). 55. The isolated nucleic acid molecule of claim 51, in which the nucleotide sequence is operatively linked to a promoter. 56. (Canceled). 57. A host cell transformed or transfected with the nucleic acid molecule of claim 52. 58-105. (Canceled). |
<SOH> 2. BACKGROUND OF THE INVENTION <EOH>Insects have a profound impact upon agriculture and human health throughout the world. Damage and destruction due to insect activity represents, on average, a loss of 10-20% of agricultural crops, stored agricultural products, timber and livestock worldwide. In addition, quarantines imposed to control the spread of insect pests severely impinge on world trade and the import and export of agricultural products. Many of the most significant and devastating infectious diseases are transmitted to man by blood-feeding insects such as mosquitoes, flies and ticks. Fatalities associated with insect-borne disease far exceed one million annually, with associated illnesses surpassing 300 million (see, e.g., WHO Weekly Epidemiological Record, 1999, 74:265-270). Presently, the spread and activity of agricultural product pests is chiefly controlled by the widespread application of potent, broad-spectrum chemical pesticides over agricultural fields, greenhouses, and storage facilities. Pests posing a danger to human health are targeted with the widespread spraying of insecticides in or near residential areas. The use of conventional pesticides, however, is associated with significant hazards to the environment, human health, and non-renewable natural resources. As a result, governments throughout the world are placing increasingly severe restrictions and bans on the use of chemical pesticides. Moreover, insects develop resistance to pesticides after prolonged use, necessitating the spraying of increased levels of pesticide, or the development of new, more potent, pesticide formulations. Thus while chemical insecticides are designed to kill insects, their non-selective effects on human health, the environment and other animal species make them damaging and controversial. As a result, there is a critical need to develop safe and effective tools to manage populations of insects that are a threat to food, resources and human health. One potential approach is to exploit knowledge of insect behavior and recent exciting advances in the molecular neurobiology of insect olfaction to develop novel strategies for insect control. 2.1. Insect Olfactory Behavior The behavior of all animals, including humans, involves the perception of events in the environment by visual, auditory and other sensory systems and the translation of these sensory stimuli into appropriate muscle responses. In simpler organisms such as insects, the recognition of sensory stimuli results in very stereotyped or “hard-wired” behaviors. Thus, by modifying or blocking the perception of environmental cues, it is possible to alter the behavior of such animals in a predictable way. Such alterations afford a powerful means to interfere with or divert innate behaviors that have a destructive effect on human health and welfare, such as the host-finding behavior of biting insects and agricultural pests. Many insect behaviors, such as the location and selection of mating partners, food sources and suitable places for egg laying, are driven by the recognition of specific odors in the environment. For example, the male hawkworm moth, Manduca sexta , can detect extremely low concentrations of an attractive odor, called a pheromone, produced by females of the same species, and uses this sense to pursue females over large distances (Hildebrand, 1995, Proc. Nat'l Acad. Sci. U.S.A. 92:67-74). Female navel orangeworm moths, Amyelois transitella , a pest of almonds in California, are attracted to and lay eggs on their preferred host plant in response to volatile odors emitted by almond fruits and by larvae feeding on the almonds (Curtis and Clark, 1979, Environ. Entomol. 8:330-333; Phelan et al, 1991, J. Chem. Ecol. 17:599-614). Social insects, such as ants, make extensive use of chemical cues in communication, for example in the recognition and attack of intruder ants from other colonies (Hölldobler and Wilson, 1990 , The Ants , Belknap Press of Harvard University Press, Cambridge, Mass.). Finally, female mosquitoes of many species, including Anopheles gambiae , the principal malaria carrier, orient toward and locate human hosts by detecting human-specific scents (Takken and Knols, 1999, Annu. Rev. Entomol. 44:131-157; Bock and Cardew, eds., 1996 , Olfaction in Mosquito - Host Interactions , (Ciba Foundation Symposium 200), Wiley, Chichester). Recent progress in the understanding of the molecular basis of the sense of smell provides important new insight into the mechanisms by which these odor cues elicit specific behaviors. These advances provide an exciting opportunity to develop new tools for the behavior-based control of destructive insect species. 2.2. The Molecular Biology of Insect Olfaction Insects recognize odors in the environment using specialized olfactory organs, namely the antenna and the maxillary palps. The antenna is a highly evolved structure that extends from the head and can attain a size equivalent to the length of the organism. The maxillary palps are a pair of club-shaped structures adjacent to the proboscis. The antenna and maxillary palps are covered with tiny sensory hairs that contain nerve cells with specialized machinery that can detect odorants often at vanishingly low concentrations. The initial step in the detection of odors requires the binding of odorants to specific receptor molecules that reside on the surface of these nerve cells. Recently, a family of roughly 60 genes encoding odorant receptors has been identified in the genome of the model insect, the fruit fly Drosophila melanogaster (Vosshall et al., 1999, Cell, 96:725-736; Clyne et al., 1999, Neuron 22:327-338; Gao and Chess, 1999, Genomics 60:31-39; Vosshall et al, 2000, Cell, 102:147-159). These odorant receptors have seven predicted transmembrane domains and belong to the large superfamily of proteins termed G-protein coupled receptors (GPCRs). The expression of 42 of these receptor genes has been detected in small, non-overlapping subsets of olfactory neurons in the antenna or maxillary palp (Vosshall et al., 2000, Cell 102:147-159). The large size of this gene family, their predicted identity as seven transmembrane domain-containing GPCRS, and their selective expression in olfactory neurons strongly implicate them in the process of olfactory recognition in the fly. More recently, functional studies (Wetzel et al, 2001, Proc. Natl. Acad. Sci. USA 98:9377-9380; Störtkuhl and Kettler, 2001, Proc. Natl. Acad. Sci. USA 98:9381-9385) have identified a candidate ligand for one of these Drosophila odorant receptor gene products, confirming their identity as receptors for behaviorally relevant odorants. One striking exception to the rule that an individual olfactory neuron expresses a single odorant receptor gene is the odorant receptor Or83b (previously known as A45; Vosshall et al., 1999, Cell, 96:725-736), which is expressed by most, if not all, olfactory neurons in the antenna and maxillary palp. Thus, it appears that olfactory neurons actually express two odorant receptor genes: the “ubiquitous” odorant receptor gene Or83b, and one of the other “classical” odorant receptor genes. Further molecular genetic studies in Drosophila have provided additional insight into the logic of olfactory processing in insects. How does the insect brain know what the antenna is smelling? Expression studies have revealed that individual olfactory neurons are functionally distinct in that each nerve cell expresses only one of the odorant receptor genes (Vosshall et al., 1999, Cell, 96:725-736). Olfactory neurons expressing the same receptor and therefore responsive to the same odor extend axons that converge on a fixed point in the brain (Vosshall et a., 2000, Cell 102:147-159). Different neurons converge on different points. It immediately follows that a given odor will activate a small group of neurons in the antenna that in turn will activate distinct spatial patterns in the insect brain. The quality of a perceived odor is therefore determined by spatial patterns of activation in the brain. These patterns are then interpreted to elicit appropriate behavioral responses such as attraction, repulsion, flight, mating and feeding. Odorants that modulate such behaviors in harmful or destructive insect species will be of great value in managing populations of these harmful and destructive insects. Citation of a reference herein shall not be construed as an admission that such reference is prior art to the present invention. |
<SOH> 3. SUMMARY OF THE INVENTION <EOH>The present inventor has identified homologs of the “ubiquitous” Drosophila odorant receptor gene Or83b in several dipteran, lepidopteran and orthopteran species, including species that have a significant impact on agricultural production and human health. Or83b is highly conserved among insect species, suggesting an essential role for this gene in insect olfactory function. Widespread expression of Or83b was detected in olfactory neurons in the agricultural pest Helicoverpa zea , in the malaria mosquito Anopheles gambiae , in the locust Schistocerca americana , and in the medfly Ceratitis capitata . These data therefore lend support to the notion that compounds targeting Or83b activity will have utility in the control of numerous insect species injurious to human health and welfare. Natural or synthetic compounds that stimulate or block Or83b activity will disrupt olfactory-driven behaviors and will be useful as novel tools for the control and management of pest insect species. The identification of Or83b homologs in pest insect species by the present inventor permits the following strategy for the development of safe and effective insect control products: First, functional odorant receptor molecules are produced in cultured cells or in Xenopus laevis oocytes, or overexpressed in transgenic insects. Cells expressing Or83b receptors can be used as a screening tool for the rapid, efficient discovery of novel compounds that interact with pest insect odorant receptors. This screening methodology can be used to identify compounds act as “super-agonists”, that is, compounds that bind to receptors with higher affinity than the natural agonists. In addition, similar screening techniques can be used to isolate compounds that inactivate or antagonize receptor function, providing potent and selective chemicals to interfere with olfactory-driven behaviors. The compounds identified in such screens may be used for attracting insects to traps or to localized toxins, for monitoring pests, for repelling insects from individuals or from residential areas, or for interfering with the function of the olfactory system such that insects are unable to locate food and hosts. Since different species of insects have highly specialized food and host preferences and the odorant receptors that mediate these behaviors are extremely variable between species, control strategies that target olfaction offer powerful and selective approaches to combat pest insects. In contrast to non-selective pesticides, such products have broad applicability as pest control agents. Whether used for pesticides, repellants or attractants, these agents selectively target disease vectors and can be expected to be harmless to beneficial species of insects, insect predators and other animals. Moreover, as behaviorally-based strategies present less selective pressure than chemical pesticides and genetically engineered crops, these strategies are expected to help reduce the appearance of pesticide-resistant insect vectors. Thus, the compounds identified using this methodology will offer novel approaches to control insect damage and the spread of disease, and will significantly reduce dependence on toxic pesticides, having a direct and immediate impact on coordinated insect management programs. In one aspect, the present invention provides nucleic acids encoding insect Or83b receptors or fragments or motifs of insect Or83b receptors. In certain embodiments, the present invention provides an isolated nucleic acid comprising a nucleotide sequence which encodes a polypeptide molecule comprising a first motif comprising the amino acid sequence of SEQ ID NO:12, or a fragment thereof of at least 10, 15 or 20 amino acids, wherein said polypeptide molecule is an insect Or83b polypeptide or a fragment thereof. In one embodiment, the sequence of said polypeptide molecule is not found in SEQ ID NO:10. In another embodiment, the sequence of said polypeptide molecule is not SEQ ID NO:10. The present invention further provides an isolated nucleic acid comprising a nucleotide sequence which encodes a polypeptide molecule comprising a first insect Or83b motif comprising the amino acid sequence of SEQ ID NO:12, or a fragment thereof of at least 10, 15 or 20 amino acids, wherein said polypeptide molecule is an insect Or83b polypeptide or a fragment thereof, said polypeptide molecule further comprising a second motif comprising the amino acid sequence of SEQ ID NO:13, or fragment of SEQ ID NO:13 of 10 amino acids. The present invention further provides an isolated nucleic acid comprising a nucleotide sequence which encodes a polypeptide molecule comprising a first insect Or83b motif comprising the amino acid sequence of SEQ ID NO:12, or a fragment thereof of at least 10, 15 or 20 amino acids, wherein said polypeptide molecule is an insect Or83b polypeptide or a fragment thereof, said polypeptide molecule further comprising a second motif comprising the amino acid sequence of SEQ ID NO:14, or a fragment of SEQ ID NO:14 of at least 10 amino acids. In certain specific embodiments, the fragment of SEQ ID NO:14 is at least 15 or 20 amino acids. In other specific embodiments, the motif of SEQ ID NO:14 comprises SEQ ID NO: 15, 16 or 17. The present invention further provides an isolated nucleic acid comprising a nucleotide sequence which encodes a polypeptide molecule comprising a first insect Or83b motif comprising the amino acid sequence of SEQ ID NO:12, or a fragment thereof of at least 10, 15 or 20 amino acids, wherein said polypeptide molecule is an insect Or83b polypeptide or a fragment thereof, said polypeptide molecule further comprising a second motif comprising the amino acid sequence of SEQ ID NO:18, or fragment of SEQ ID NO:18 of at least 10 amino acids. In certain specific embodiments, the fragment of SEQ ID NO:18 is at least 15 or 20 amino acids. The present invention yet further provides an isolated nucleic acid comprising a nucleotide sequence which encodes a polypeptide molecule comprising a first motif comprising the amino acid sequence of SEQ ID NO:13, or a fragment thereof of 10 amino acids, wherein said polypeptide molecule is an insect Or83b polypeptide or a fragment thereof. In one embodiment, the sequence of said polypeptide molecule is not found in SEQ ID NO:10. In another embodiment, the sequence of said polypeptide molecule is not SEQ ID NO:10. The present invention further provides an isolated nucleic acid comprising a nucleotide sequence which encodes a polypeptide molecule comprising a first insect Or83b motif comprising the amino acid sequence of SEQ ID NO:13, or a fragment thereof of 10 amino acids, wherein said polypeptide molecule is an insect Or83b polypeptide or a fragment thereof, said polypeptide molecule further comprising a second motif comprising the amino acid sequence of SEQ ID NO:14, or fragment of SEQ ID NO:14 of at least 10 amino acids. In certain specific embodiments, the fragment of SEQ ID NO:14 is at least 15 or 20 amino acids. In other specific embodiments, the motif of SEQ ID NO:14 comprises SEQ ID NO:15, 16 or 17. The present invention further provides an isolated nucleic acid comprising a nucleotide sequence which encodes a polypeptide molecule comprising a first insect Or83b motif comprising the amino acid sequence of SEQ ID NO:13, or a fragment thereof of 10 amino acids, wherein said polypeptide molecule is an insect Or83b polypeptide or a fragment thereof, said polypeptide molecule further comprising a second motif comprising the amino acid sequence of SEQ ID NO:18 or fragment of SEQ ID NO:18 of at least 10 amino acids. In certain specific embodiments, the fragment of SEQ ID NO:18 is at least 15 or 20 amino acids. Thus, the present invention provides an isolated nucleic acid comprising a nucleotide sequence which encodes a polypeptide molecule comprising a first insect Or83b motif comprising the amino acid sequence of SEQ ID NO:14, or a fragment thereof of at least 10, 15 or 20 amino acids, wherein said polypeptide molecule is an insect Or83b polypeptide or a fragment thereof. In one embodiment, the sequence of said polypeptide molecule is not found in SEQ ID NO:10. In another embodiment, the sequence of said polypeptide molecule is not SEQ ID NO:10. In certain specific embodiments, the motif of SEQ ID NO:14 comprises SEQ ID NOS: 15, 16, or 17. The present invention further provides an isolated nucleic acid comprising a nucleotide sequence which encodes a polypeptide molecule comprising a first insect Or83b motif comprising the amino acid sequence of SEQ ID NO:14, or a fragment thereof of at least 10, 15 or 20 amino acids, wherein said polypeptide molecule is an insect Or83b polypeptide or a fragment thereof, said polypeptide molecule further comprising a second motif comprising the amino acid sequence of SEQ ID NO:18, or a fragment of SEQ ID NO:18 of at least 10 amino acids. In certain specific embodiments, the fragment of SEQ ID NO:18 is at least 15 or 20 amino acids. The present invention yet further provides isolated nucleic acid comprising a nucleotide sequence which encodes a polypeptide molecule comprising the amino acid sequence of three or more of SEQ ID NOS:12, 13, 14, or 18, or a fragment of at least 10 amino acids of SEQ ID NOS:12, 13, 14, or 18, wherein said polypeptide molecule is an insect Or83b polypeptide or a fragment thereof. Alternatively, the present invention provides an isolated nucleic acid comprising a nucleotide sequence which encodes a polypeptide molecule comprising the amino acid sequence of SEQ ID NOS:12, 13, 14, and 18, or a fragment of at least 10 amino acids of SEQ ID NOS:12, 13, 14, and 18, wherein said polypeptide molecule is an insect Or83b polypeptide or a fragment thereof. In one embodiment, the sequence of said polypeptide molecule is not found in SEQ ID NO:10. In another embodiment, the sequence of said polypeptide molecule is not SEQ ID NO:10. In certain specific embodiments, SEQ ID NO:14 comprises SEQ ID NOS:15, 16, or 17. In another aspect of the present invention, methods of identifying a nucleic acid encoding an insect Or83b polypeptide are provided. In one embodiment, a method of identifying a nucleic acid encoded an insect Or83 polypeptide comprises PCR amplification of insect genomic DNA or cDNA with a forward primer comprising a degenerate oligonucleotide encoding at least six amino acids of SEQ ID NOS: 12, 13 or 14, or its complement, and a reverse primer comprising a degenerate oligonucleotide encoding at least six amino acids of SEQ ID NOS:13, 14 or 18, or its complement; then detection of a PCR amplification product, thereby identifying a nucleic acid encoding an insect Or83b polypeptide. The reverse primer corresponds to a nucleic acid sequence downstream of the forward primer. In a preferred mode of the embodiment, PCR amplification results in a product of at least 150 nucleotides. In yet other aspects of the present invention, insect Or83b polypeptides and insect Or83b polypeptide fragments are provided. In certain embodiments, the invention provides a purified polypeptide comprising an amino acid sequence having at least 80%, 90%, or 95% identity to at least 20 contiguous amino acids of the sequence set forth in SEQ ID NO:11. In one embodiment, amino acid sequence is not found in SEQ ID NO:10. In another embodiment, the amino acid sequence does not comprise SEQ ID NO:10. In a preferred embodiment, the polypeptide is capable of being bound by an antibody that also binds to a polypeptide defined by an amino acid sequence selected from the group consisting of SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, and SEQ ID NO:8. In a specific embodiment, the present invention provides a purified polypeptide comprising the amino acid sequence set forth in SEQ ID NO:11, or a fragment thereof of at least 20 contiguous amino acids. In one embodiment, amino acid sequence is not found in SEQ ID NO:10. In another embodiment, the amino acid sequence does not comprise SEQ ID NO:10. In other specific embodiments, the present invention provides a purified polypeptide comprising an amino acid sequence having at least 80%, 90%, or 95% identity to at least 20 contiguous amino acids of the sequence set forth in SEQ ID NO:11, wherein said polypeptide comprises at least 20, 30 or 50 contiguous amino acids of the sequence as set forth in SEQ ID NO:2, or encoded by the insert of the plasmid deposited at the ATCC and assigned ATCC Accession No. PTA-3573. In a certain specific embodiment, the present invention provides a purified polypeptide comprising an amino acid sequence as set forth in SEQ ID NO:2, or encoded by the insert of the plasmid deposited at the ATCC and assigned ATCC Accession No. PTA-3573. In other specific embodiments, the present invention provides a purified polypeptide comprising an amino acid sequence having at least 80%, 90%, or 95% identity to at least 20 contiguous amino acids of the sequence set forth in SEQ ID NO:11, wherein said polypeptide comprises at least 20, 30 or 50 contiguous amino acids of the sequence as set forth in SEQ ID NO:4, or encoded by the insert of the plasmid deposited at the ATCC and assigned ATCC Accession No. PTA-3574. In a certain specific embodiment, the present invention provides a purified polypeptide comprising an amino acid sequence as set forth in SEQ ID NO:4, or encoded by the insert of the plasmid deposited at the ATCC and assigned ATCC Accession No. PTA-3574. In yet other specific embodiments, the present invention provides a purified polypeptide comprising an amino acid sequence having at least 80%, 90%, or 95% identity to at least 20 contiguous amino acids of the sequence set forth in SEQ ID NO:11, wherein said polypeptide comprises at least 20, 30 or 50 contiguous amino acids of the sequence as set forth in SEQ ID NO:6, or encoded by the insert of the plasmid deposited at the ATCC and assigned ATCC Accession No. PTA-3575. In a certain specific embodiment, the present invention provides a purified polypeptide comprising an amino acid sequence as set forth in SEQ ID NO:6, or encoded by the insert of the plasmid deposited at the ATCC and assigned ATCC Accession No. PTA-3575. In yet other specific embodiments, the present invention provides a purified polypeptide comprising an amino acid sequence having at least 80%, 90%, or 95% identity to at least 20 contiguous amino acids of the sequence set forth in SEQ ID NO:11, wherein said polypeptide comprises at least 20, 30 or 50 contiguous amino acids of the sequence as set forth in SEQ ID NO:8, or encoded by the insert of the plasmid deposited at the ATCC and assigned ATCC Accession No. PTA-3576. In a certain specific embodiment, the present invention provides a purified polypeptide comprising an amino acid sequence as set forth in SEQ ID NO:8, or encoded by the insert of the plasmid deposited at the ATCC and assigned ATCC Accession No. PTA-3576. The present invention yet further provides an isolated nucleic acid comprising a nucleotide sequence encoding any of the foregoing polypeptides. In certain embodiments, the nucleotide sequence is operatively linked to a promoter. The present invention yet further provides vectors comprising a nucleotide sequence encoding any of the foregoing polypeptides. The present invention yet further provides a host cell transformed with a nucleic acid comprising a nucleotide sequence encoding any of the foregoing polypeptides. A table indicating to which Or83b-related sequence each SEQ ID NO corresponds is presented below: NUCLEOTIDE OR SEQ ID MOLECULE AMINO ACID NO Ceratitis capitata Or83b Nucleotide 1 Ceratitis capitata Or83b Amino Acid 2 Helicoverpa zea Or83b Nucleotide 3 Helicoverpa zea Or83b Amino Acid 4 Anopheles gambiae Or83b Nucleotide 5 Anopheles gambiae Or83b Amino Acid 6 Schistocerca americana Or83b Nucleotide 7 Schistocerca americana Or83b Amino Acid 8 Drosophila melanogaster Or83b Nucleotide 9 Drosophila melanogaster Or83b Amino Acid 10 Consensus Or83b Amino Acid 11 Or83b Motif I (AAs 347-362 of Amino Acid 12 SEQ ID NO: 11) Or83b Motif II (AAs 386-396 of SEQ ID Amino Acid 13 NO: 11) Or83b Motif III (AAs 420-462 of SEQ ID Amino Acid 14 NO: 11, with partial degeneracy where the corresponding residue is not identical in SEQ ID NO. 2, 4, 6 and 8) Motif III (from Ceratitis and Anopheles ) Amino Acid 15 Motif III (from Helicoverpa ) Amino Acid 16 Motif III (from Locust) Amino Acid 17 Or83b Motif IV (AAs 466-498 of SEQ ID Amino Acid 18 NO: 11) Or83b Forward Primer I Nucleotide 19 Or83b Reverse Primer II Nucleotide 20 In yet other aspects of the present invention, screening methods for identifying molecules, e.g., odorants, that bind to and/or modulate (i.e., agonize or antagonize) the activity of insect Or83b receptors are provided. Generally, an Or83b receptor comprises an amino acid sequence having at least 80% identity to at least 20 contiguous amino acids of the sequence set forth in SEQ ID NO:11. Most preferably, the insect Or83b receptor employed in the screening methods is not or does not comprise the Drosophila melanogaster Or83b receptor, as encoded by SEQ ID NO:10. In other preferred embodiments, the insect Or83b receptor employed in the screening methods comprises an amino acid sequence that is not present in the Drosophila melanogaster Or83b receptor, as encoded by SEQ ID NO:10. In one embodiment, the invention provides a method of identifying a molecule that binds to an Or83b receptor, said method comprising: (a) contacting a first cell and a second cell with a test molecule under conditions conducive to binding between the Or83b receptor and the test molecule, wherein the first cell expresses the Or83b receptor, preferably on the cell surface, and the second cell does not express the Or83b receptor, and wherein the first cell and the second cell are of the same cell type; and (b) determining whether the test molecule binds to the first cell or the second cell; wherein a molecule that binds to the first cell but not the second cell is a molecule that binds to the Or83b receptor. The present invention further provides a method for identifying a modulator of an Or83b receptor, said method comprising: (a) contacting a first cell and a second cell with a test molecule under conditions conducive to binding between the Or83b receptor and the test molecule, wherein the first cell expresses the Or83b receptor, preferably on the cell surface, and the second cell does not express the Or83b receptor, and wherein the first cell and the second cell are of the same cell type; and (b) determining whether the test molecule modulates G-protein activity in said first cell or second cell, wherein a molecule that modulates G-protein activity in the first cell but not in the second cell is an Or83b modulator. In certain preferred embodiments, G-protein activity is determined by measuring calcium ion or cyclic AMP concentration in the cell. The present invention further provides a method for identifying a molecule that binds to an Or83b receptor from a first species but not from a second species, said method comprising: (a) contacting a first cell that expresses a first Or83b receptor, preferably on the cell surface, from said first species with a test molecule under conditions conducive to binding between said first receptor and the test molecule; (b) determining whether the test molecule binds to said first cell; (c) contacting a second cell that expresses a second Or83b receptor from said second species with the test molecule under conditions conducive to binding between said second receptor and the test molecule, wherein said second cell is of the same cell type as the first cell; and (d) determining whether said test molecule binds to said second cell, wherein a test molecule that binds to the first cell but not to the second cell binds to the Or83b receptor from the first species but not from the second species. The present invention yet further provides a method of identifying a modulator of an Or83b receptor from a first species but not from a second species, said method comprising: (a) contacting a first cell that expresses a first Or83b receptor, preferably on the cell surface, from said first species with a test molecule under conditions conducive to binding between said first receptor and the test molecule; (b) determining whether the test molecule modulates G-protein activity in said first cell; (c) contacting a second cell that expresses a second Or83b receptor from said second species with the test molecule under conditions conducive to binding between said second receptor and the test molecule, wherein said second cell is of the same cell type as the first cell; and (d) determining whether the test molecule modulates G-protein activity in said second cell, wherein a test molecule that modulates G-protein activity in the first cell but not in the second cell modulates the Or83b receptor from the first species but not from the second species. The present invention yet further provides a method of identifying an odorant that binds to an insect olfactory receptor, said method comprising: (a) contacting a first cell and a second cell with a test molecule under conditions conducive to binding between the insect olfactory receptor and the test molecule, wherein the first cell expresses an the insect olfactory receptor and the Or83b receptor, preferably on the cell surface, and the second cell does not express either receptor, or expresses only the odorant receptor, or expreseses only the Or83b receptor, wherein the first cell and the second cell are of the same cell type; and (b) determining whether the test molecule binds to the first or the second cell; wherein a molecule that binds to the first cell but not the second cell is an odorant that binds to the insect olfactory receptor. The present invention yet further provides a method of identifying an odorant that modulates the activity of an insect olfactory receptor, said method comprising: (a) contacting a first cell and a second cell with a test molecule under conditions conducive to binding between the insect olfactory receptor and the test molecule, wherein the first cell expresses an the insect olfactory receptor and the Or83b receptor, preferably on the cell surface, and the second cell does not express either receptor, or expresses only the odorant receptor, or expreseses only the Or83b receptor, wherein the first cell and the second cell are of the same cell type; and (b) determining whether the test molecule modulates G-protein activity in said first cell or second cell, wherein a molecule that modulates G-protein activity in the first cell but not the second cell is an odorant that modulates the activity of the insect olfactory receptor. In certain preferred embodiments, the G-protein activity is determined by measuring calcium ion or cyclic AMP concentration in the cell. The present invention yet further provides a method of identifying an odorant that binds to a first insect olfactory receptor but not a second insect olfactory receptor, said method comprising: (a) contacting a first cell that expresses an Or83b receptor, preferably on the cell surface, and the first insect olfactory receptor, preferably on the cell surface, with a test molecule under conditions conducive to binding between the first receptor and the test molecule; (b) determining whether the test molecule binds to said first cell; (c) contacting a second cell that expresses the Or83b receptor and the second insect olfactory receptor under conditions conducive to binding between the second receptor and the test molecule, wherein said second cell is of the same cell type as the first cell; and (d) determining whether the test molecule binds to said second cell, wherein a test molecule that binds to the first cell but not to the second cell is an odorant that binds to the first insect olfactory receptor but not to the second insect olfactory receptor. The present invention yet further provides a method of identifying an odorant that modulates the activity of a first insect olfactory receptor but not the activity of a second insect olfactory receptor, said method comprising: (a) contacting a first cell that expresses an Or83b receptor, preferably on the cell surface, and the first insect olfactory receptor, preferably on the cell surface, with a test molecule under conditions conducive to binding between the receptors and the test molecule; (b) determining whether the test molecule binds to said first cell; (c) contacting a second cell that expresses the Or83b receptor and the second insect olfactory receptor under conditions conducive to binding between the receptors and the test molecule, wherein said second cell is of the same cell type as the first cell; and (d) determining whether said test molecule binds to said second cell, wherein a test molecule that binds to the first cell but not the second cell is an odorant that binds to the first insect olfactory receptor but not the second insect olfactory receptor. The present invention yet further provides a method of identifying a molecule that binds to an insect Or83b receptor but not an insect gustatory receptor, said method comprising: (a) contacting a first cell that expresses the Or83b receptor, preferably on the cell surface, with a test molecule under conditions conducive to binding between the receptor and the test molecule; (b) determining whether the test molecule binds to said first cell; (c) contacting a second cell that expresses the insect gustatory receptor, preferably on the cell surface, under conditions conducive to binding between the receptor and the test molecule, wherein said second cell is of the same cell type as the first cell; and (d) determining whether the test molecule binds to said second cell, wherein a test molecule that binds to the first cell but not to the second cell is a molecule that binds to the insect Or83b receptor but not to the insect gustatory receptor. The present invention yet further provides a method of identifying a molecule that modulates an insect Or83b receptor but not an insect gustatory receptor, said method comprising: (a) contacting a first cell that expresses the Or83b receptor, preferably on the cell surface, with a test molecule under conditions conducive to binding between the receptor and the test molecule; (b) determining whether the test molecule modulates G-protein activity in said first cell; (c) contacting a second cell that expresses the insect gustatory receptor, preferably on the cell surface, under conditions conducive to binding between the receptor and the test molecule, wherein said second cell is of the same cell type as the first cell; and (d) determining whether the test molecule modulates G-protein activity in said second cell, wherein a test molecule that modulates G-protein activity in the first cell but not in the second cell is a molecule that modulates the activity the insect Or83b receptor but not the activity of the insect gustatory receptor. In yet other aspects of the present invention, insect control agent formulations, comprising one or more of the foregoing Or83b binding molecules or modulators and a suitable carrier are provided. In one embodiment, the insect control agent is an insect repellent. In another embodiment, the insect control agent is an insect attractant. The carrier can be a solid carrier or a liquid carrier. Examples of suitable carriers are described in Section 5.9, infra. |
Flat structure |
A flat article (4) comprises bars (6) extending parallel to one another in spaced-apart fashion, which are joined together by connecting means (7). The connecting means (7) can be designed such that they extend over the full length of the flat article (4), or alternatively they can each join together only two immediately adjacent bars (6). |
1. A flat article (5), having a plurality of bars (6), located parallel next to one another, of metal or plastic, which at least in some portions are hollow and which are held together to form a flat article by means of connecting means (7), wherein each two adjacent bars (6) are spaced apart from one another, forming a gap, and the flat article (5) is flexible about axes parallel to the bars (6). 2. The flat article of claim 1, characterized in that the connecting means (7) are formed by at least two at least approximately linear connecting elements (8) of metal or plastic, by way of which the bars (6) are flexibly connected to one another, and each bar (6) is connected to the adjacent bar (6) via at least two connecting elements (8). 3. The flat article of claim 1, characterized in that the bars (6) are continuously hollow. 4. The flat article of claim 1, characterized in that the bars (6) have a continuously constant cross section. 5. The flat article of claim 1, characterized in that the bars (6) are roll-formed. 6. The flat article of claim 1, characterized in that the bars (6) comprise a material that does not oxidize in the normal environment or are coated in nonoxidizing fashion. 7. The flat article of claim 1, characterized in that the bars (6) have a circular cross section. 8. The flat article of claim 1, characterized in that the bars (6) have a cross section that deviates from the circular. 9. The flat article of claim 1, characterized in that the bars (6), with respect to a plane defined by the flat article (4), are flattened in cross section on one side (38), pointing toward the side of the flat article (4). 10. The flat article of claim 1, characterized in that the bars (6) are flattened on at least one side (44, 45), viewed in the direction parallel to the connecting means (7). 11. The flat article of claim 1, characterized in that the bars (6), viewed in the direction parallel to the connecting means (7), are concave on at least one side (48, 54), in such a way that each bar (6) presents a concave side to at least one adjacent bar (6). 12. The flat article of claim 1, characterized in that the bars (6) are embodied in concave form on both sides (48, 54) that are adjacent to respective other bars (6) in the flat article (4). 13. The flat article of claim 1, characterized in that the diameter of the bars (6) or of the enveloping circle around the cross-sectional profile of the bars (6) is between 2 and 50 mm, preferably between 2 and 5 mm, or any other value between a mm and h mm, in which a or h stand for any integer between 2 mm and 50 mm. 14. The flat article of claim 1, characterized in that the diameter of the bars (6) at the widest point of its cross section is between 2 and 50 mm, preferably between 2 and 5 mm, or any other value between a mm and h mm, in which a or h stand for any integer between 2 mm and 50 mm. 15. The flat article of claim 1, characterized in that the ratio of the diameter of the bars (6) between the smallest diameter and the largest diameter is between 1:1.5 and 1:10. 16. The flat article of claim 1, characterized in that the wall thickness of the bars (6) is between 0.1 and 2.0 mm, and preferably between 0.2 and 0.4 mm. 17. The flat article of claim 1, characterized in that the bars (6) are straight. 18. The flat article of claim 1, characterized in that the bars (6) have a shiny or matte surface on the outside. 19. The flat article of claim 1, characterized in that the bars (6) are connected to the connecting elements (8) in a secured manner such that the bars (6) are not displaceable in their longitudinal direction relative to the connecting elements (8). 20. The flat article of claim 1, characterized in that the nondisplaceable connection is formed by a taper at the point where the bars (6) are connected to the connecting elements (8). 21. The flat article of claim 1, characterized in that the bars (6) are connected to the connecting elements (8) in a secured manner such that the bars (6) are nondisplaceable in at least one direction relative to the connecting elements (8) parallel to their longitudinal direction. 22. The flat article of claim 1, characterized in that the connection point is formed by at least one opening (14), through which the applicable connecting element (8) passes. 23. The flat article of claim 1, characterized in that the bars (6) are kept spaced apart by spacer elements (11). 24. The flat article of claim 1, characterized in that the spacer elements (11) are short tubular elements, through which the connecting elements (8) pass. 25. The flat article of claim 1, characterized in that the connecting elements (8) extend uninterruptedly through, over the length of the flat article (4). 26. The flat article of claim 1, characterized in that each connecting element (8) joins only two bars (6) each to one another. 27. The flat article of claim 1, characterized in that the spacer elements (11) are an integral component of the bars (6). 28. The flat article of claim 1, characterized in that the spacer elements (11) are an integral component of the respective connecting element (8). 29. The flat article of claim 1, characterized in that the linear connecting elements (8) have a round or flattened cross section. 30. The flat article of claim 1, characterized in that the connecting elements (8) comprise a special-steel wire. 31. The flat article of claim 1, characterized in that it has at least two regions, viewed in the direction parallel to the connecting elements (8), and in one region the spacing of the bars is less than or greater than the spacing of the bars (6) in the other region. 32. The flat article of claim 1, characterized in that the spacing between adjacent bars in the direction parallel to the connecting elements (8) varies continuously from a minimum value to a maximum value. 33. The flat article of claim 1, characterized in that the connecting element (8) has a head (16) and a cylindrical shank (15), which is bent over in spaced-apart fashion from the head (16). 34. The flat article of claim 1, characterized in that the connecting element (8) has a U-shaped form, comprising a back portion (19) and two legs (21) extending axially parallel to one another, which on their ends remote from the back (19) are bent away toward opposite sides, in such a way that extensions (22) are created whose length is less than the inside diameter of a bar (6). 35. The flat article of claim 1, characterized in that the connecting element (8) is formed by a wire, which at spacings corresponding to the spacings of the bars (6) is provided with flat-pressed points (23) which form shoulders (24, 25), on which a bar (6) rests. 36. The flat article of claim 1, characterized in that the connecting element (6) is formed by a wire, which is twisted at spacings, forming a loop (26). 37. The flat article of claim 1, characterized in that the connecting element (8), with respect to the longitudinal extent is provided with undulations (7), which are located in the same plane, and that the spacing of the centers of the undulations from one another is equivalent to the spacing of the bars (6). 38. The flat article of claim 1, characterized in that the connecting element (8) is formed by a wire which is bent in a zigzag fashion. 39. The flat article of claim 1, characterized in that the connecting element (8) is formed by a band, out of which tabs (32) are bent at a spacing corresponding to that of the bars (6). 40. The flat article of claim 1, characterized in that the connecting element (8) is bandlike, and that with respect to its longitudinal extent, it has many outward-bulging portions (34). 41. The flat article of claim 1, characterized in that at least some of the bars bar (6) have a cross-sectional profile which is designed such that each bar (6) forms a continuous surface on its outside, which surface points upward in the direction of between 25° and 80°, and preferably 50°, relative to a plane defined by the vertically deployed flat article (5). 42. The flat article of claim 1, characterized in that at least some of the bars (6) have a cross-sectional profile which is designed such that each bar (6) forms a continuous groove (66, 68) on its outside, which surface points upward in the direction of between 10° and 40°, and preferably 26°, relative to a plane defined by the vertically deployed flat article (5). 43. The flat article of claim 2, characterized in that the groove is defined by two substantially flat faces (66, 68), which form an angle of between 165° and 120°, preferably approximately 137°, with one another. 44. The flat article of claim 3, characterized in that the bisector of the angle that the two faces (66, 68) of the groove form with one another extends at an angle of approximately 26° relative to a plane defined by the deployed flat article (5). 45. The flat article of claim 1 or 2, characterized in that the cross-sectional profile is pentagonal. 46. The flat article of claim 5, characterized in that two edges (62, 64) of the cross-sectional profile extend parallel to one another. 47. The flat article of claim 5, characterized in that one edge (60), located between the edges (62, 64) that are parallel to one another, forms an angle of 86° with the longer edge (62) of the parallel edges. 48. The flat article of claims 3 and 6, characterized in that the two edges that correspond to the faces (66, 68) of the groove are located between the two edges (62, 64) that are parallel to one another. 49. The flat article of claim 1, characterized in that the bar (6) is edge-rolled, and that the bar (6) forms two straight flanges (64, 71), which overlap one another flatly. 50. The flat article of claim 8, characterized in that one of the flanges (71) forms an edge located on the outside, which protrudes past the adjacent side (60) of the bar (6). 51. The flat article of claim 1, characterized in that the connecting elements (8) are connected by material engagement to the bars (6) by means of laser welding or adhesive bonding. 52. The flat article of claim 1, characterized in that it is part of a shading device, such as Venetian blinds or an awning. 53. The flat article of claim 1, characterized in that it forms a wall covering. 54. The flat article of claim 1, characterized in that it is part of a piece of furniture. 55. The flat article of claim 1, characterized in that it is part of a light fixture. |
<SOH> BACKGROUND OF THE INVENTION <EOH>For regulating the light that enters through windows, it is known to use slatted shades. A slatted shade comprises many individual slats extending parallel to one another and as a rule horizontally. The slats are curved cylindrically about an axis extending parallel to the slat axis in order to provide adequate stability against kinking. The individual slats are kept spaced apart, creating a light gap between adjacent slats. The spacers for the slats are structures similar to a rope ladder, on the rungs of which the slats rest. With the aid of two tapes extending through all the slats, the length of the thus-formed slatted rollup shade can be varied. The entry of light also can be varied by means of positioning the slats more or less obliquely. It is also known to vary the acoustical properties in a room and the appearance of the room with the aid of wall coverings and ceiling coverings. |
<SOH> OBJECTS AND SUMMARY OF THE INVENTION <EOH>The object of the invention is to create a multi-purpose novel flat article. In a further aspect of the invention, a flat article is provided in which the passage of light through it, observed from reflection, is further reduced. In carrying out the invention, a novel flat article is provided that comprises plurality of bars extending parallel to one another, which are joined together by connecting means, specifically in such a way that at least in the position for use, a gap is produced between each two adjacent bars. The connecting means furthermore make flexibility of the flat article possible about axes that extend parallel to the bars. The novel flat article can not only be used for window shades, awnings and the like, that is, to regulate the passage of light through them, but also for wall coverings or ceiling coverings, and particularly for varying the acoustics of a room. Because of the gaps between the bars, the sound absorption in the room can be varied. To join the individual bars to one another, various alternative connecting means can be used. The connecting means can be formed by at least two connecting elements that are at least approximately linear or bandlike, and the individual bars are joined together in a way to make the flat article. The linear connecting means can either pass through openings in the bars or extend over circumferential surfaces of the bars and be connected to the outer circumferential surface. The latter option is possible if there are two linear elements per connecting point which are twisted together in the region of the gap are used. The other kind of connecting means resides in the use of individual members that each join together only two bars. Their shape depends on the type of bars involved. The bars of the flat article are preferably predominantly hollow in order to minimize weight. Depending on the intended use, it is expedient if the bars have a constant cross section over their length. The bars can have the shape of tubes that are completely closed in the circumferential direction, or they can be tubelike articles with a gap extending lengthwise on one side. Using the gap makes production substantially simpler. In the case of individual connecting elements, they can be provided with a shank and a head, with the head resting on the edges of the slit and the shank extending to the outside through the gap. At an appropriate spacing, the shank into a corresponding opening in the adjacent bar and is anchored in that opening. The simplest form of anchoring is to bend the shank over 90° in the next bar. Insertable individual connecting elements can simplify assembly. The linear connecting element need only be threaded through one hole, while on the opposite side of the tubular bar it can emerge through the gap. The bars of the flat article preferably are produced by roll forming, by means of which bars with a longitudinal slit in particular can be easily produced in endless form. The bars expediently comprise a material that does not oxidize in the particular environment in use, such as aluminum or special steel, preferably with a satin-finished surface. The wall thickness of the bars in window shade applications is between 0.1 and 0.5 mm, and preferably between 0.2 and 0.4 mm. The latter range is a good comprise between weight, deformability in the roll forming, and stability in later use. Plastic can also be used. The joining technique in each case depends on the material as well as the weight and the resultant force that may occur at the most heavily loaded point. If the flat article is used to control the entry of light, the bars preferably have a substantially elliptical or kidney-shaped form in such case, even when the sun is low in the sky, good shading still is possible without the bars having to be placed too close together. The diameter of the bars can be between 2 mm and 15 mm, preferably between 2 and 5 mm. The spacing range preferably is between 0.5 and 5 mm, and the wall thickness of the bars is between 0.1 mm and 0.5 mm. The bars may be straight so they can be rolled up onto a winding roller, but alternatively can be curved. Securing means prevent the bars from being displaceable counter to one another in the longitudinal direction. To keep the bars spaced apart, spacer elements in the form of short tubular portions can be used, or the spacer elements can be an integral component of the bars or of the connecting elements. In the case of a linear connecting element of spring steel wire, the steel wire can be bent in zigzag fashion, with one bar disposed at each sharp bend. The linear connecting means can be monofilaments of plastic or metal and preferably spring steel. The connecting elements preferably should be UV-resistant and should also not oxidize. The spacing between the bars can be constant over the width of the flat article, that is, in the direction transverse to the length, or it can vary in that direction. The variation can be intermittent or continuous. Depending on the geometry of the individual bars, on the side of the flat article remote from the light source a very brightly lighted, almost glaringly bright strip can be observed, which has the width of the light source and spreads over the entire vertical or horizontal extent of the flat article. The direction of propagation of the bright strip depends on whether the bars are disposed horizontally or vertically. With horizontal bars, a vertical strip results. In the flat article of the invention, the bars form a circumferentially closed tube. The bars all have the same cross-sectional profile. By design, each bar forms a continuous groove on its outside, that is, on the side facing away from the light source. The groove points upward at an angle of approximately 26° relative to a plane defined by the deployed flat article. Because of this groove, incident light is reflected toward the underside of the bar above it at an angle such that no reflection occurs, and the light is cast onto the other side of the flat article. Especially favorable conditions result if the groove is defined by two substantially flat faces which form an angle of between 165° and 120° with one another, preferably an angle of 137°. In this case, the direction of the groove means that the bisector of the angle between the two faces that define the groove extends at an angle of approximately 26° to a plane that is defined by the deployed flat article. Especially favorable reflection conditions, that is, the least possible passage of light through, result if the cross-sectional profile is pentagonal. With the pentagonal cross-sectional profile, two edges of the cross-sectional profile can extend parallel to one another. An edge extending between the edges parallel to one another forms an angle of 86° with the longer of the two parallel edges. When the flat article is deployed, this means that the underside of the applicable bar is no longer perpendicular to the plane or the two-dimensional outline defined by the deployed flat article. The orientation is selected such that the front edge of the bar is toward the light source and somewhat higher than the edge of the bar that faces away from the light source. Production becomes especially simple if the bar is edge-rolled from a sheet-metal strip. The rolled profile can be formed embodied as overlapping one side. This has the advantage on the one hand of an improved appearance, and on the other, given a suitable location of the overlap, a defined sharp edge is created in the region of the underside of the applicable bar, and hence more-favorable conditions when light shines through, or in other words better shading action. To hold the bars firmly to the connecting elements, laser welding also can be used, which is relatively simple in production because it makes threading or insertion operations unnecessary. The pentagonal profile is quite suitable for laser welding because a plane face is already available. Other objects and advantages of the invention will become apparent upon reading the following detailed description and upon reference to the drawings, in which: |
Activator of peroxisome proliferator-activated receptor |
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