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1. A system to reduce nitrogen oxide emissions of an internal combustion engine having an exhaust line, the system comprising: a DeNOx catalytic converter in the exhaust line, the DeNOx catalytic converter having a reactor portion comprising a catalyst for the reduction of nitrogen oxides, and a temperature regulating portion, a hydrogen-generating reactor, and a hydrogen feed line connecting the hydrogen-generating reactor to the exhaust line upstream of the DeNOx catalytic converter. 2. The system of claim 1, further comprising a fuel tank, the fuel tank being connected to supply fuel to the hydrogen-generating reactor and the internal combustion engine. 3. The system of claim 1 wherein the internal combustion engine has a cooling system, and wherein the DeNOx catalytic converter is integrated with the engine cooling system. 4. The system of claim 1 wherein the temperature regulating portion of the DeNOx catalytic converter comprises one or more channels. 5. The system of claim 4 wherein the channels are connected to receive at least one of the intake air supplied to the internal combustion engine, an air stream supplied by a fan, and a partial exhaust stream being recirculated to the internal combustion engine. 6. The system of claim 4, further comprising a temperature sensor associated with the DeNOx catalytic converter, and a mechanism for adjusting the supply of coolant fluid to the channels in response to the temperature sensor. 7. The system of claim 6 wherein the mechanism for adjusting the supply of coolant fluid to the channels comprises a valve disposed in the coolant line and a controller associated with the valve and the temperature sensor for adjusting the supply of coolant fluid. 8. The system of claim 6 wherein the mechanism for adjusting the supply of coolant fluid to the channels comprises a controller for adjusting the speed of a device directing coolant fluid through the channels. 9. The system of claim 6 wherein the temperature sensor is disposed in the DeNOx catalytic converter. 10. The system of claim 6 wherein the temperature sensor is in the exhaust line downstream of the DeNOx catalytic converter. 11. The system of claim 1 wherein the DeNOx catalytic converter comprises at least two stages, each stage in the exhaust line, and wherein the hydrogen feed line is more than one hydrogen feed line with at least one hydrogen feed line connecting the hydrogen generating reactor to the exhaust line upstream of each stage. 12. A method of reducing nitrogen oxide emissions from an internal combustion engine, the method comprising: (a) passing exhaust from the internal combustion engine through a DeNOx catalytic converter, and (b) maintaining the temperature of the DeNOx catalytic converter within a desired temperature range by supplying a coolant fluid to a heat exchanger integrated with the DeNOx catalytic converter. 13. The method of claim 12 wherein the amount of coolant fluid supplied to the heat exchanger is adjusted based on a parameter indicative of the temperature of the DeNOx catalytic converter. 14. The method of claim 13, further comprising monitoring the temperature in the DeNOx catalytic converter. |
<SOH> FIELD OF THE INVENTION <EOH>The invention concerns a system and a method to reduce nitrogen oxides in the exhaust of an internal combustion engine. |
<SOH> BRIEF SUMMARY OF THE INVENTION <EOH>Using a heat exchanger design with active cooling of the DeNOx catalytic converter makes it possible to set a temperature level that is suitable for the reduction reaction in all operating states. This improves the selectivity of the reaction, which results in a higher level of conversion in the reduction of nitrogen oxides. At the same time, less hydrogen is needed, and thus less additional fuel, which lowers fuel consumption. Moreover, thermal control over the reaction in the DeNOx catalytic converter can be maintained even when large quantities of hydrogen are added. The use of a temperature sensor enables very simple and accurate control of the temperature in the DeNOx catalytic converter. A multi-stage design of the DeNOx catalytic converter offers advantages with respect to the level of conversion of nitrogen oxides. These and other aspects will be evident upon reference to the attached figure and following detailed description. |
Sorting device and method for flat objects |
A device for loading, conveying, and sorting substantially flat items (FLATS), in particular mail items (3), having a number of item receptacles (18) traveling along an endless path (7) between a loading area (10), where a substantially flat item (3) is fed into each item receptacles (18), and an unloading area (12), where the substantially flat items in the item receptacles (18) are released selectively. Each item receptacle (18) has an inner cavity (26) for housing the substantially flat item (3), and which communicates with the outside through at least one rectangular elongated opening (30) positioned with its major sides substantially aligned with a first traveling direction (D). The device also has a feed device (50) for feeding the substantially flat item (3) in a second direction (F) crosswise to the first direction (D), so that the substantially flat item is fed into the inner cavity (26) through the elongated opening (30), with leading edges of the substantially flat item substantially parallel to the major sides of the elongated opening (30). |
1) A device for loading, conveying, and sorting substantially flat items (FLATS), in particular mail items (3), comprising at least one loading unit (18) traveling along a path (7) between a loading area (10), where a substantially flat item (3) is fed to the loading unit (18), and an unloading area (12), where the substantially flat item in the loading unit (18) is released; said loading unit (18) defining an inner cavity (26) for receiving and housing said substantially flat item (3); and said inner cavity (26) communicating with the outside of the loading unit (18) through at least one opening (30); characterized in that said opening (30) is elongated, and is positioned with its major sides substantially aligned with a first traveling direction (D) of said loading unit when the loading unit is located at said loading area (10); said device also comprising a FLAT feed device (50) for feeding a said substantially flat item (3) in a second direction (F) crosswise-in particular, perpendicular-to the first direction (D), so that said substantially flat item (3) is fed into said inner cavity (26) through said elongated opening (30), with leading edges (LE) of said substantially flat item (3) parallel to said major sides of said elongated opening (30). 2) A device as claimed in claim 1, wherein said elongated opening (30) is rectangular. 3) A device as claimed in claim 1, wherein said loading unit (18) comprises at least a first and a second wall (20,21) spaced apart and defining opposite sides of said inner cavity (26); at least one portion each of respective facing straight edges (20b2, 21b2) of said first and second wall defining the major sides of said elongated opening (30). 4) A device as claimed in claim 1, wherein said loading unit (18) comprises at least one unloading opening (33) fitted with a lid (35) which is movable between a closed position closing the unloading opening (33), and an open position in which the unloading opening (33) is at least partly accessible; said lid (35) being set, at said unloading area (12), to said open position to enable said substantially flat item (3) to be unloaded from said inner cavity (26) through said unloading opening (33). 5) A device as claimed in claim 1, wherein a number of loading units (18) are connected to form a conveying unit (5) traveling along said path (7). 6) A device as claimed in claim 5, wherein said elongated openings (30) of said loading units (18) extend on the same side of said conveying unit (5). 7) A device as claimed in claim 1, wherein rotation means (43) are provided to rotate said loading unit (18) about an axis of rotation (45); said rotation means rotating said loading unit (18) between a first loading position, in which said elongated opening (30) is positioned with its major sides parallel to said first direction (D), and a second unloading position, in which said elongated opening (30) is positioned with its major sides crosswise-in particular, perpendicular-to said first direction (D). 8) A device as claimed in claim 7, wherein said rotation means (43): set said loading unit (18) to said first loading position at said loading area (10); set said loading unit (18) to said second unloading position at said unloading area (12) to unload said substantially flat items by force of gravity; and restore said loading unit (18) to said first loading position once said substantially flat items (3) are unloaded. 9) A device as claimed in claim 1, wherein said FLAT feed device (50) comprises at least one pair of powered rollers (53, 54) positioned with their axes parallel to the first direction (D), and which frictionally engage opposite flat surfaces (3a, 3b) of a substantially flat item (3); said rollers (53, 54) being rotated by drive means in opposite directions to accelerate the substantially flat item (3) retained between the rollers, and to hurl it in said second direction (F) towards the elongated opening of said loading unit (18). 10) A device as claimed in claim 9, wherein a number of loading units (18) are connected to form a conveying unit (5) traveling along said path (7); the position of said pair of powered rollers (53, 54) with respect to the various loading units (18) being adjustable. 11) A device as claimed in claim 10, wherein the position of said pair of powered rollers (53, 54) is fixed, and the position of said conveying unit (5) is adjustable to position a selected loading unit (18) facing said pair of powered rollers (53, 54), and to feed said substantially flat item (3) to said loading unit. 12) A device as claimed in claim 10, wherein the position of said conveying unit (5) is fixed, and the position of said pair of powered rollers (53, 54) is adjustable to position said pair of powered rollers (53, 54) facing a selected loading unit (18), and to feed said substantially flat item (3) to said loading unit. 13) A device as claimed in claim 10, wherein a number of pairs of powered rollers are provided, each pair positioned facing a respective loading unit (18) to feed said substantially flat item (3) to the loading unit. 14) A device as claimed in claim 1, wherein said path is an endless path (7) extending in a three-dimensional space. 15) A device as claimed in claim 14, wherein at least one conveying unit (5) is provided comprising a number of loading units (18) adjacent to one another in one direction; said path comprising a sloping portion (7c) extending between a start point (7-i) located at a first height (h1) with respect to a reference plane (P), and an end point (7-ii) located at a second height (h2) lower than the first height (h1); said device (1) also comprising a number of FLAT feed devices (50) spaced along said sloping portion (7c) and substantially at a third height (h3) with respect to the reference plane (P); as the conveying unit (5) travels along said sloping portion (7c), different loading units (18) are positioned at the third height (h3), so that each loading unit (18) is positioned facing a respective FLAT feed device (50) to receive from it a substantially flat item (3). 16) A device as claimed in claim 15, wherein said sloping portion (7c) terminates at a first upward portion (7a-I) which terminates at a first unloading area (12-I) where first loading units (18) are selectively opened to feed the released substantially flat items to a first conveying system; said first upward portion (7a-I) continuing, downstream from said first unloading area (12-I) into a second upward portion (7a-II) which terminates at a second unloading area (12-II) where second loading units (18) are selectively opened to feed the released substantially flat items to a second conveying system; said second upward portion (7a-II) terminating, downstream from the second unloading area, at a downward portion (7d) leading back to said sloping portion (7c). 17) A device as claimed in claim 15, wherein said sloping portion (7c) slopes downwards in steps, and comprises a number of horizontal portions (7c-h) located at different heights and connected by sloping portions (7c-s). 18) A device as claimed in claim 1, and comprising: first sensor means (60) for detecting the approach of said loading unit (18) to said FLAT feed device (50); and second sensor means (61) for detecting the position of the substantially flat item 83) fed to said FLAT feed device (50); said device also determining the position of the incoming substantially flat item (3) with respect to the incoming loading unit (18). 19) A method of loading, conveying, and sorting substantially flat items (FLATS), in particular mail items (3), comprising the steps of: feeding a substantially flat item (3) to a loading unit (18) at a loading area (10); moving said loading unit to an unloading area (12); and selectively releasing the substantially flat item from said loading unit; said loading unit (18) defining an inner cavity (26) for housing said substantially flat item (3) and which communicates with the outside of the loading unit (18) through at least one elongated opening (30); characterized in that said feeding step comprises the steps of: positioning said elongated opening with its major sides substantially aligned with a first traveling direction (D) of the loading unit (18); and |
<SOH> BACKGROUND ART <EOH>Devices for loading, conveying, and sorting substantially flat items, in particular mail items, are known in which a number of loading units travel along an endless path to convey the items between one or more loading areas, where the items are fed singly into the loading units, and one or more unloading areas, where the items in the loading units are released selectively to conveying containers and/or systems. The term “substantially flat items” is intended to mean any items (e.g. letters, postcards, enclosed documents, boxes, magazines and newspapers with or without a protective cover) having two dimensions which are predominant with respect to the third. Known loading units normally comprise a casing defining an inner cavity which communicates with the outside of the loading unit through an inlet opening through which the substantially flat item is inserted. Known sorting devices provide at best for a throughput of roughly 40,000 items/hour, which cannot be increased further without necessarily increasing the linear traveling speed of the loading units along the path. Increasing speed, however, increases the likelihood of the end edges of the substantially flat items, as they are inserted through the inlet opening, striking the parts of the loading unit defining the inlet opening, in which case, the item normally bounces off or crumples, or at any rate is not deposited inside the loading unit. |
<SOH> BRIEF DESCRIPTION OF THE DRAWINGS <EOH>A preferred, non-limiting embodiment of the invention will be described by way of example with reference to the accompanying drawings, in which: FIG. 1 shows a schematic view in perspective of a device for loading, conveying, and sorting substantially flat items (FLATS), in particular mail items, in accordance with the teachings of the present invention; FIG. 2 shows a larger-scale view of a detail of the FIG. 1 device in a first operating position; FIG. 3 shows the FIG. 2 detail in a second operating position; FIG. 4 shows a side view of a subassembly of the FIG. 1 device; FIG. 5 shows a view in perspective of a variation of the FIG. 1 device. detailed-description description="Detailed Description" end="lead"? |
Method of processing geophysical data |
A method of processing geophysical data comprises determining the azimuth of a mirror symmetry plane within the earth from the geophysical data that comprises sets of geophysical data acquired with different source-receiver azimuths. The data are processed to determine attributes of the geophysical data that are azimuth-dependent. One azimuth-dependent attribute of the geophysical data is selected, and a value of the source-receiver azimuth about which the selected attribute exhibits mirror symmetry is determined. This locates a mirror symmetry plane within the earth. The azimuth which the selected attribute exhibits mirror symmetry may be determined by generating an objective function indicative of the difference between the actual value of an attribute at one azimuth and the value predicted for that attribute at that azimuth using a trial estimate of the azimuth of a mirror symmetry plane, and finding the azimuth of a mirror symmetry plane that minimises the objective function. |
1. A method of processing geophysical data, the data comprising at least a first set of geophysical data acquired with a first source-receiver azimuth and a second set of geophysical data acquired with a second source-receiver azimuth different from the first source-receiver azimuth, the method comprising; a) selecting an attribute of the geophysical data that is dependent on the source-receiver azimuth; and b) determining a value of the source-receiver azimuth about which the selected attribute exhibits mirror symmetry. 2. A method of determining an azimuthal symmetry plane within the earth from geophysical data comprising at least a first set of geophysical data acquired with a first source-receiver azimuth and a second set of geophysical data acquired with a second source-receiver azimuth different from the first source-receiver azimuth, the method comprising the steps of: a) selecting an attribute of the geophysical data that is dependent on the source-receiver azimuth; and b) determining a value of the source-receiver azimuth about which the selected attribute exhibits mirror symmetry thereby to locate a mirror symmetry plane within the earth. 3. The method of claim 1, wherein step (b) comprises determining a respective value of the selected attribute from each set of geophysical data. 4. The method of claim 3, further comprising the step of interpolating between the value of the selected attribute determined from the first set of geophysical data and the value of the selected attribute determined from the second set of geophysical data thereby to estimate the value of the selected attribute at a source-receiver azimuth intermediate the first and second source-receiver azimuths. 5. The method of claim 1, wherein the determining step comprises c) calculating a function indicative of the variation between the value of the selected attribute at a first source-receiver azimuth (Φ−Φ0) and the value of the selected attribute at a second source-receiver azimuth (Φ0−Φ) where Φ0 is the azimuth of a mirror symmetry plane, and d) determining a value of Φ0 that minimizes the value of the function. 6. The method of claim 5 wherein step (d) comprises determining a value of Φ0 that gives a value for the function that is lower than a pre-set value. 7. The method of claim 5 wherein the function is: E = ∑ i = 1 n ( f i - f [ - ϕ + ϕ 0 ] ) 2 + ( f i - f [ 180 - ϕ + ϕ 0 ] ) 2 + ( f i - f [ 180 + ϕ - ϕ 0 ] ) 2 where fi is the value of the selected attribute at a source-receiver azimuth Φ, and f is the value of the attribute at a source-receiver azimuth α. 8. The method of claim 1 further comprising: c) selecting another attribute of the geophysical data that is dependent on the source-receiver azimuth; and d) determining a value of the source-receiver azimuth about which the another selected attribute exhibits mirror symmetry. 9. The method of claim 8, further comprising the step of determining a value of the azimuth of a mirror symmetry plane within the earth from the value of the source-receiver azimuth about which the selected attribute exhibits mirror symmetry and from the value of the source-receiver azimuth about which the another selected attribute exhibits mirror symmetry. 10. The method of claim 1, wherein the attribute is selected from the arrival time, the polarisation angle, the transverse component, the polarity, the temporal frequency, the amplitude or the linearity of acquired seismic energy. 11. The method of claim 1, further comprising: locating a mirror symmetry plane within the earth from the determined value; and controlling subsequent processing steps on the basis of the located mirror symmetry plane. 12. The method of claim 1, further comprising an initial step of acquiring at least a first set of geophysical data with a first source-receiver azimuth and a second set of geophysical data with a second source-receiver azimuth different from the first source-receiver azimuth. 13. The method of claim 1, wherein the geophysical data are seismic data. 14. An apparatus for processing geophysical data comprising at least a first set of geophysical data acquired with a first source-receiver azimuth and a second set of geophysical data acquired with a second source-receiver azimuth different from the first source-receiver azimuth, the apparatus comprising; a) means for selecting an attribute of the geophysical data that is dependent on the source-receiver azimuth; and b) means for determining a value of the source-receiver azimuth about which the selected attribute exhibits mirror symmetry. 15. An apparatus for determining an azimuthal symmetry plane within the earth from geophysical data comprising at least a first set of geophysical data acquired with a first source-receiver azimuth and a second set of geophysical data acquired with a second source-receiver azimuth different from the first source-receiver azimuth, the apparatus comprising: a) means for selecting an attribute of the geophysical data that is dependent on the source-receiver azimuth; and b) means for determining a value of the source-receiver azimuth about which the selected attribute exhibits mirror symmetry thereby to locate a mirror symmetry plane within the earth. 16. (Canceled) 17. (Canceled) 18. (Canceled) 19. The method of claim 2, wherein step (b) comprises determining a respective value of the selected attribute from each set of geophysical data. 20. The method of claim 19, further comprising the step of interpolating between the value of the selected attribute determined from the first set of geophysical data and the value of the selected attribute determined from the second set of geophysical data thereby to estimate the value of the selected attribute at a source-receiver azimuth intermediate the first and second source-receiver azimuths. 21. The method of claim 2, wherein the determining step comprises c) calculating a function indicative of the variation between the value of the selected attribute at a first source-receiver azimuth (Φ−Φ0) and the value of the selected attribute at a second source-receiver azimuth (Φ0−Φ) where Φ0 is the azimuth of a mirror symmetry plane, and d) determining a value of Φ0 that minimizes the value of the function. 22. The method of claim 21, wherein step (d) comprises determining a value of Φ0 that gives a value for the function that is lower than a pre-set value. 23. The method of claim 21, wherein the function is: E = ∑ i = 1 n ( f i - f [ - ϕ + ϕ 0 ] ) 2 + ( f i - f [ 180 - ϕ + ϕ 0 ] ) 2 + ( f i - f [ 180 + ϕ - ϕ 0 ] ) 2 where fi is the value of the selected attribute at a source-receiver azimuth Φ, and f is the value of the attribute at a source-receiver azimuth α. 24. The method of claim 2, further comprising: c) selecting another attribute of the geophysical data that is dependent on the source-receiver azimuth; and d) determining a value of the source-receiver azimuth about which the another selected attribute exhibits mirror symmetry. 25. The method of claim 24, further comprising the step of determining a value of the azimuth of a mirror symmetry plane within the earth from the value of the source-receiver azimuth about which the selected attribute exhibits mirror symmetry and from the value of the source-receiver azimuth about which the another selected attribute exhibits mirror symmetry. 26. The method of claim 2, wherein the attribute is selected from the arrival time, the polarisation angle, the transverse component, the polarity, the temporal frequency, the amplitude or the linearity of acquired seismic energy. 27. The method of claim 2, further comprising controlling subsequent processing steps on the basis of the determined mirror symmetry plane. 28. The method of claim 2, further comprising an initial step of acquiring at least a first set of geophysical data with a first source-receiver azimuth and a second set of geophysical data with a second source-receiver azimuth different from the first source-receiver azimuth. 29. The method of claim 2, wherein the geophysical data are seismic data. 30. The apparatus of claim 14, wherein the determining means comprises means for determining a respective value of the selected attribute from each set of geophysical data. 31. The apparatus of claim 14, wherein the determining means comprises c) means for calculating a function indicative of the variation between the value of the selected attribute at a first source-receiver azimuth (Φ−Φ0) and the value of the selected attribute at a second source-receiver azimuth (Φ0−Φ) where Φ0 is the azimuth of a mirror symmetry plane, and d) means for determining a value of Φ0 that minimizes the value of the function. 32. The apparatus of claim 14, further comprising: c) means for selecting another attribute of the geophysical data that is dependent on the source-receiver azimuth; and d) means for determining a value of the source-receiver azimuth about which the another selected attribute exhibits mirror symmetry. 33. The apparatus of claim 14, wherein the selecting means selects the attribute from the arrival time, the polarisation angle, the transverse component, the polarity, the temporal frequency, the amplitude or the linearity of acquired seismic energy. 34. The apparatus of claim 45, further comprising means for controlling subsequent processing steps on the basis of the determined mirror symmetry plane. 35. The apparatus of claim 14, further comprising means for acquiring at least a first set of geophysical data with a first source-receiver azimuth and a second set of geophysical data with a second source-receiver azimuth different from the first source-receiver azimuth. 36. The apparatus of claim 14, wherein the geophysical data are seismic data. 37. A storage medium encoded with instructions that, when executed by a programmable data processor, perform a method of processing geophysical data, the data comprising at least a first set of geophysical data acquired with a first source-receiver azimuth and a second set of geophysical data acquired with a second source-receiver azimuth different from the first source-receiver azimuth, the method comprising: a) selecting an attribute of the geophysical data that is dependent on the source-receiver azimuth; and b) determining a value of the source-receiver azimuth about which the selected attribute exhibits mirror symmetry. 38. The storage medium of claim 37, wherein step (b) in the encoded method comprises determining a respective value of the selected attribute from each set of geophysical data. 39. The storage medium of claim 37, wherein the determining step in the encoded method further comprises c) calculating a function indicative of the variation between the value of the selected attribute at a first source-receiver azimuth (Φ−Φ0) and the value of the selected attribute at a second source-receiver azimuth (Φ0−Φ) where Φ0 is the azimuth of a mirror symmetry plane, and d) determining a value of Φ0 that minimizes the value of the function. 40. The storage medium of claim 37, wherein the encoded method further comprises: c) selecting another attribute of the geophysical data that is dependent on the source-receiver azimuth; and d) determining a value of the source-receiver azimuth about which the another selected attribute exhibits mirror symmetry. 41. The storage medium of claim 37, wherein the attribute is selected in the encoded method from the arrival time, the polarisation angle, the transverse component, the polarity, the temporal frequency, the amplitude or the linearity of acquired seismic energy. 42. The storage medium of claim 53, wherein the encoded method further comprises the controlling subsequent processing steps on the basis of the determined mirror symmetry plane. 43. The storage medium of claim 37, the encoded method further comprises an initial step of acquiring at least a first set of geophysical data with a first source-receiver azimuth and a second set of geophysical data with a second source-receiver azimuth different from the first source-receiver azimuth. 44. The storage medium of claim 37, wherein the geophysical data are seismic data. 45. The apparatus of claim 14, further comprising locating a mirror symmetry plane within the earth from the determined value. 46. The apparatus of claim 15, wherein the determining means comprises means for determining a respective value of the selected attribute from each set of geophysical data. 47. The apparatus of claim 15, wherein the determining means comprises c) means for calculating a function indicative of the variation between the value of the selected attribute at a first source-receiver azimuth (Φ−Φ0) and the value of the selected attribute at a second source-receiver azimuth (Φ0−Φ) where Φ0 is the azimuth of a mirror symmetry plane, and d) means for determining a value of Φ0 that minimizes the value of the function. 48. The apparatus of claim 15, further comprising: c) means for selecting another attribute of the geophysical data that is dependent on the source-receiver azimuth; and d) means for determining a value of the source-receiver azimuth about which the another selected attribute exhibits mirror symmetry. 49. The apparatus of claim 15, wherein the selecting means selects the attribute from the arrival time, the polarisation angle, the transverse component, the polarity, the temporal frequency, the amplitude or the linearity of acquired seismic energy. 50. The apparatus of claim 15, further comprising means for controlling subsequent processing steps on the basis of the determined mirror symmetry plane. 51. The apparatus of claim 15, further comprising means for acquiring at least a first set of geophysical data with a first source-receiver azimuth and a second set of geophysical data with a second source-receiver azimuth different from the first source-receiver azimuth. 52. The apparatus of claim 15, wherein the geophysical data are seismic data. 53. The storage medium of claim 42, further comprising locating a mirror symmetry plane within the earth from the determined value. 54. An apparatus, comprising: a programmable data processor; a storage accessible by the programmable data processor; and a program residing on the storage that, when executed by the programmable data processor performs a method of processing geophysical data, the data comprising at least a first set of geophysical data acquired with a first source-receiver azimuth and a second set of geophysical data acquired with a second source-receiver azimuth different from the first source-receiver azimuth, the method comprising: a) selecting an attribute of the geophysical data that is dependent on the source-receiver azimuth; and b) determining a value of the source-receiver azimuth about which the selected attribute exhibits mirror symmetry. 55. The apparatus of claim 54, wherein step (b) in the encoded method comprises determining a respective value of the selected attribute from each set of geophysical data. 56. The apparatus of claim 54, wherein the determining step in the encoded method further comprises c) calculating a function indicative of the variation between the value of the selected attribute at a first source-receiver azimuth (Φ−Φ0) and the value of the selected attribute at a second source-receiver azimuth (Φ0−Φ) where Φ0 is the azimuth of a mirror symmetry plane, and d) determining a value of Φ0 that minimizes the value of the function. 57. The apparatus of claim 54, wherein the encoded method further comprises: c) selecting another attribute of the geophysical data that is dependent on the source-receiver azimuth; and d) determining a value of the source-receiver azimuth about which the another selected attribute exhibits mirror symmetry. 58. The apparatus of claim 54, wherein the attribute is selected in the encoded method from the arrival time, the polarisation angle, the transverse component, the polarity, the temporal frequency, the amplitude or the linearity of acquired seismic energy. 59. The apparatus of claim 54, further comprising locating a mirror symmetry plane within the earth from the determined value. 60. The apparatus of claim 59, wherein the encoded method further comprises the controlling subsequent processing steps on the basis of the determined mirror symmetry plane. 61. The apparatus of claim 54, the encoded method further comprises an initial step of acquiring at least a first set of geophysical data with a first source-receiver azimuth and a second set of geophysical data with a second source-receiver azimuth different from the first source-receiver azimuth. 62. The apparatus of claim 54, wherein the geophysical data are seismic data. |
Device for stacking sheets, especially sheets of paper or cardboard transported by a stream feeder, onto pallets |
In order to stack sheets (1) of paper or cardboard transported by a stream feeder onto pallets (4), devices are known which comprise a vertically fixed transport mechanism (2) for the sheets (1), placed above the ground, above the maximum stack height, and a stacking platform (5) which can be raised and lowered, and on which the piles (3) are formed. Ejection rolls (10) and separating shoes (11) are arranged in the form of stack-forming elements, behind the transport mechanism (2), acting on the longitudinal edges of a sheet (1). According to the invention, the separating shoes (11) are formed in a cuneiform manner with a separating edge extending upwards from a tip situated on the entrance side in the displacement direction of the sheets. Said shoes are arranged in the displacement direction of the sheets, behind the ejection rolls (10), in such a way that the separating edge starts below the ejection height of the ejection rolls (10). |
1. A device for stacking sheets transported by a stream feeder onto pallets, the device comprising: (a) a vertically fixed feed mechanism situated above the ground at a height above a maximum stack height; (b) a stacking platform capable of being raised and lowered and on which a stack of sheets is formed; and, (c) at least one ejection roll and at least one separating shoe that are each arranged downstream from the feed mechanism, wherein the separating shoes are wedge-shaped with a separating edge running from an inlet-side tip upwardly in a direction of sheet travel and are arranged in the sheet-travel direction downstream from the ejection roll in such a way that the separating edge starts below an ejection height of the ejection roll. 2. The device of claim 1, wherein the separating shoes and ejection rolls are attached to a shared, crosswise adjustable holder. 3. The device of claim 1, a wherein the separating is shoes are attached to a first holding plate (18). 4. The device of claim 3, wherein the first holding plate (18) is attached to a second holding plate so as to be vibration-uncoupled. 5. The device of claim 3, wherein a separating plate is attached to the first holding plate. 6. The deadline of claim 3, further comprising a shaking drive attached to the first holding plate. 7. The device of claim 4, wherein the ejection rolls are attached to the second holding plate. |
<SOH> TECHNICAL FIELD <EOH>The invention relates to a device for stacking sheets, especially sheets of paper or cardboard transported by a stream feeder, onto pallets, with a vertically fixed feed mechanism for the sheets, situated above the ground at a height above the maximum stack height, with a stacking platform that can be raised and lowered and on which the stacks are formed, and with at least one ejection roll and at least one separating shoe that are arranged downstream from the feed mechanism. |
<SOH> BRIEF DESCRIPTION OF THE DRAWING <EOH>The drawing serves to explain the invention with respect to a simplified embodiment: FIG. 1 is a schematic representation of the side view of a stacking device. FIG. 2 is an enlarged representation of the side view of the stack-forming elements acting on the longitudinal edges of the sheet. FIG. 3 is a view of the stack-forming elements opposite from the sheet-travel direction. detailed-description description="Detailed Description" end="lead"? |
Data carrier for chemical or biochemical analyses |
The invention relates to a data carrier having memory locations to which data is written, wherein the memory locations have a number of first memory locations with erroneous data and at least one second memory location for the arrangement of analytical substances on the data carrier, wherein, when the analytical substances react with a medium that is to be investigated, the reaction product may cause a change to the data item which is written to the at least one second memory location, and the number of first memory locations is designed such that, on the one hand, when there is no reaction between the analytical substances and a medium which is to be investigated, a first data record can be determined when reading the data carrier and using a conventional error correction method, and, on the other hand, when the reaction product has caused a change to the data item which is written to the at least one second memory location, a second data record can be determined when reading the data carrier and using the conventional error correction method, with the second data record not being the same as the first data record. |
1. A carrier for application of substances for analytical purposes, characterized by: a data track corresponding to that used in known mass data stores (CD-audio, CD-ROM, CD-R, CD-RW, DVD, magnetooptical storage media, hard disks, replaceable disks, all derivatives of them as well as magnetic tapes and bar code readers), with the data track being structured into data blocks and optional structure elements thereof, data being represented by information units, and the information units being represented by a physical structures on the carrier, at least one predefined information unit within at least one data block or its subunit; the use of error correction methods, wherein parity data is used, the parity data can be calculated by solving homogeneous equation systems, the parameters of the equation systems are parity data and/or data, defined areas within a sequence of physical structures which represent at least one information unit on which sensor molecules are immobilized, with the result of a chemical or biochemical test which is carried out with the sensor molecules having these additional errors after the test in the interpretation of the physical structures as information units, and/or errors which were present before the test being corrected after the test; a determined interaction of predefined errors in information units and by means of errors which are produced or corrected after a test by interpretation of areas of physical structures which are provided with sensor modules, such that the sum of the error points and test points in information units in total exceeds the correction capability of the error correction method that is used; the possibility for a unique interpretation capability of the information units, which are supplied from the respective reader, in a data block or its subunits with regard to the test result by comparison with a previously known reference value, so that the characteristics of the reader have no influence on the interpretation in given error correction methods. 2. The data carrier as claimed in claim 1, wherein at least one defined error is inserted in at least one information unit within data blocks or subunits of data blocks as a function of the error correction methods which are used for reading the data. 3. The data carrier as claimed in claim 1, wherein a Reed-Solomon code is used for the error correction method. 4. The data carrier as claimed in claim 1, wherein a CRC (cyclic redundancy checksum) is used for the error correction method. 5. The data carrier as claimed in claim 1, wherein the data track is applied in the form of a line or a grid, in the form of concentric circles, in a spiral shape or in other linear or area patterns. 6. The data carrier as claimed in claim 1, wherein additional data ensures the protection of the test data against misinterpretation by dirt on the carrier surface, in particular, redundant repetitions of the predefined data. 7. The data carrier as claimed in claim 1, wherein predetermined statistical protection for the test validity is ensured by means of a correspondingly large number of repetitions, in particular 2 to 10 7, of the individual tests. 8. The data carrier as claimed in claim 1, wherein quality inspection and standardization of the bonding characteristics of a given test can be carried out by means of standard substances which are applied to the carrier. 9. The data carrier as claimed in claim 1, wherein information about the chemical or biochemical test which is applied to the carrier is also included in the data. 10. The data carrier as claimed in claim 1, wherein once the chemical or biochemical test has been carried out, parts of the carrier may also record the results which are produced by the test in accordance with a conventional method (magnetic or magnetooptic memory, hard disks, CD-R or CD-RW and mixed forms of them). 11. The data carrier as claimed in claim 1, in which mixed forms of at least two data memories as cited in the preceding claim may be used. 12. A carrier having locally different amounts of sensor molecules, wherein these amounts are chosen such that the number of errors which are produced by reaction with the sensor molecules can be used to deduce the concentration of substances which react with the sensor molecules. 13. The carrier as claimed in claim 1, wherein further data fields are included in addition to the data fields which are used for analytical tests and include information for the further evaluation of the tests, in particular software for creation of calibration curves, interpretation and analysis of data, recording of further data and its graphical representation and storage, and matching to external data from networks. 14. A kit, including the major substances for carrying out one or more analyses with the carrier as described in claim 1. 15. A data carrier having memory locations to which data is written, wherein the memory locations have a number of first memory locations with erroneous data and at least one second memory location for the arrangement of analytical substances on the data carrier, wherein, when the, analytical substances react with a medium that is to be investigated, a reaction product may cause a change to the data item which is written to the at least one second memory location, and the number of first memory locations is designed such that, on the one hand, when there is no reaction between the analytical substances and a medium which is to be investigated, a first data record can be determined when reading the data carrier and using a conventional error correction method, and, on the other hand, when the reaction product has caused a change to the data item which is written to the at least one second memory location, a second data record can be determined when reading the data carrier and using the conventional error correction method, with the second data record not being the same as the first data record. 16. The data carrier as claimed in claim 15, wherein the erroneous data has predetermined values, such that both the first data record and the second data record are determined. 17. The data carrier as claimed in claim 15, characterized in that the number of first memory locations with erroneous data corresponds to the maximum number of errors which can be corrected by the error correction method. 18. The data carrier as claimed in claim 15, characterized in that two or more second memory locations are provided with analytical substances, with the analytical substances reacting in different second memory locations for different concentrations of the medium that is to be investigated. |
Polymer hydrogenation process |
A process for hydrogenating unsaturations in polymers, the process comprising contacting at least one polymer having unsaturations with a catalyst comprising at least one Group Ia, Ib, IIb, VIb, VIIb or VIII metal on a support of an alkaline earth metal silicate having a surface area of at least 30 m2/g at a temperature of from 50 to 250° C. and a pressure of from 5 to 150 bar. |
1-12. (canceled) 13. A process for hydrogenating unsaturations in polymers, the process comprising contacting at least one polymer having unsaturations and hydrogen with a supported catalyst at a temperature of from 50 to 250° C. and a pressure of from 5 to 150 bars, said catalyst comprising at least one Group Ia, Ib, IIb, VIb, VIIb or VIII metal on a support formed of an alkaline earth metal silicate having a surface area of at least 30 m2/g. 14. A process according to claim 13 wherein the support comprises a crystalline calcium silicate. 15. A process according to claim 14 wherein said support has a surface area within the range of 30 to 200 m2/g. 16. A process according to claim 14 wherein said support has a surface area within the range of 40 to 90 m2/g . 17. A process according to claim 14 wherein the calcium silicate has the chemical composition Ca6Si6O17(OH)2. 18. A process according to claim 13 wherein the support is in the form of substantially spherical particles having a mean diameter of from 10 to 200 microns and comprising pores in the particles having a diameter of from 100 to 2000 Angstroms. 19. A process according to claim 13 wherein the support has a basicity corresponding to a pH of greater than 7.5 when the support is immersed in water at a concentration of 4 wt. %. 20. A process according to claim 13 wherein said catalyst comprises palladium impregnated onto the support in an amount of from 0.01 to 10 wt. % based on the weight of the supported catalyst. 21. A process according to claim 13 wherein said catalyst is contacted at a temperature within the range of 100 to 160° C. and a pressure within the range of 20 to 100 bars. 22. A process according to claim 13 wherein said at least one polymer is dissolved in a solvent to provide a feedstock having a solids content of from 1 to 75 wt. %. 23. A process according to claim 13 wherein said at least one polymer has ethylenically unsaturated regions and aromatically unsaturated regions and the ethylenically unsaturated regions are selectively hydrogenated. 24. A process according to claim 13 wherein said at least one polymer comprises a styrene-butadiene-styrene copolymer. 25. A process for selectively hydrogenating at least one unsaturated polymer having ethylenically unsaturated regions and aromatically unsaturated regions comprising contacting said at least one polymer with hydrogen in the presence of a supported catalyst comprising at least one Group Ia, Ia, IIb, VIb, VIIb or VIII metal on a crystalline calcium silicate support having a surface area of at least 30 m2/g, the support being in the form of substantially spherical particles and comprising pores in the particles having a diameter of from 100 to 2000 Angstroms. 26. A process according to claim 25 wherein said pores have a diameter within the range of 100 to 1000 Angstroms. 27. A process according to claim 25, wherein the calcium silicate has the chemical composition Ca6Si6O17(OH)2. 28. A process according to claim 25 wherein said at least one polymer comprises a styrene-butadiene-styrene block copolymer. 29. A process according to claim 28 wherein said styrene-butadiene-styrene block copolymer is passed over the catalyst at a temperature within the range of 60-200° C. and a pressure within the range of 5-150 bars. 30. The process according to claim 29 wherein said temperature is within the range of 100-160° C. and said pressure is within the range of 20-100 bars. |
Pre-fabricated structural components strengthened with tensile reinforcements and method for production thereof |
The prefabricated structural components strengthened by tensile reinforcements, preferably metal inlays, containing binders and aggregates, wherein said binder is an alkali water glass, and the aggregates have a broad grain size distribution like aggregates added to reinforced concrete. |
1. Prefabricated structural components strengthened by tensile reinforcements containing cured binders and aggregates, characterized in that said binder is an alkali water glass, and the aggregates have a grain size distribution common for aggregates in reinforced concrete, wherein the components are mixed, introduced into a mold and cured at 100 to 150° C., followed by annealing the structural components at a temperature within a range of from 500 to 700° C. 2. The structural components according to claim 1, characterized in that the metal inlays are in the form of rods, ropes and/or sheets. 3. The structural components according to claim 1, characterized by being externally coated with a waterproof and weather-resistant protection layer. 4. The structural components according to claim 3, characterized by being externally coated with a plate having a thickness of at least 2 mm and having been annealed at 500 to 700° C. and prepared from water glass and fillers selected from the group consisting of Al203, SiO2 and/or carbon. 5. A method for preparing the structural components according to claim 1, characterized in that the components are mixed, introduced into a mold and cured at 100 to 150° C., followed by bonding the annealed plates with the structural component using water glass. 6. A method for preparing the structural components according to any of claim 1, characterized by having the shape of round or polygonal tubes. |
Process and apparatus for continuously producing an elastomeric composition |
A process for continuously producing an elastomeric composition includes providing at least one extruder, metering and feeding at least one elastomer, at least one filler, and ingredients different from elastomers and fillers into the at least one extruder, mixing and dispersing the at least one filler and the ingredients different from elastomers and fillers into the at least one elastomer using the at least one extruder, and extruding a resulting elastomeric composition. The at least one extruder includes the housing and at least one screw rotatably mounted in the housing. The housing includes at least one feed opening and a discharge opening. At least one of the ingredients different from elastomers and fillers includes a subdivided product including one or more minor ingredients dispersed in at least one thermoplastic binding agent. An apparatus for continuously producing the elastomeric composition is also disclosed. |
1-25. (canceled) 26. A process for continuously producing an elastomeric composition, comprising: providing at least one extruder; metering and feeding at least one elastomer and at least one filler into the at least one extruder; metering and feeding ingredients different from elastomers and fillers into the at least one extruder; mixing and dispersing the at least one filler and the ingredients different from elastomers and fillers into the at least one elastomer using the at least one extruder; and extruding a resulting elastomeric composition through a discharge opening of a housing of the at least one extruder; wherein the at least one extruder comprises: the housing; and at least one screw rotatably mounted in the housing; wherein the housing comprises: at least one feed opening; and the discharge opening; wherein at least one of the ingredients different from elastomers and fillers comprises a subdivided product comprising one or more minor ingredients dispersed in at least one thermoplastic binding agent, and wherein the subdivided product is conveyed, before metering and feeding into the at least one extruder, by at least one pneumatic conveying line. 27. The process of claim 26, further comprising: metering and feeding at least one plasticizing agent into the at least one extruder. 28. The process of claim 26, wherein the subdivided product is metered and fed using a gravimetric feeder. 29. The process of claim 26, wherein the subdivided product comprises greater than 40%-by-weight and less than 98%-by-weight of the one or more minor ingredients with respect to a total weight of the subdivided product. 30. The process of claim 26, wherein the subdivided product comprises greater than 50%-by-weight and less than 95%-by-weight of the one or more minor ingredients with respect to a total weight of the subdivided product. 31. The process of claim 26, wherein the subdivided product comprises greater than 70%-by-weight and less than 85%-by-weight of the one or more minor ingredients with respect to a total weight of the subdivided product. 32. The process of claim 26, wherein the subdivided product comprises a Shore A hardness greater than or equal to 45 and a Shore D hardness less than or equal to 65. 33. The process of claim 32, wherein the subdivided product comprises a Shore D hardness greater than 20 and less than 60. 34. The process of claim 26, wherein the one or more minor ingredients comprise one or more: crosslinking agents; crosslinking accelerators; synthetic resins; crosslinking activators; crosslinking retardants; adhesion promoters; protective agents; coupling agents; and/or condensation catalysts. 35. The process of claim 26, further comprising: providing first and second extruders; wherein the first extruder extrudes an intermediate rubber mixture devoid of temperature sensitive minor ingredients, and wherein the second extruder extrudes a complete rubber mixture comprising the temperature sensitive minor ingredients. 36. The process of claim 35, wherein the temperature sensitive minor ingredients comprise one or more: crosslinking agents; crosslinking accelerators; crosslinking retardants; and/or crosslinking activators. 37. The process of claim 26, wherein the at least one thermoplastic binding agent comprises a melting temperature (Tm) greater than or equal to 40° C. 38. The process of claim 26, wherein the at least one thermoplastic binding agent comprises a melting temperature (Tm) greater than 50° C. and less than 120° C. 39. The process of claim 26, wherein the at least one thermoplastic binding agent comprises one or more: ethylene homopolymers or copolymers of ethylene with at least one aliphatic or aromatic alpha-olefin and, optionally, with at least one polyene; copolymers of ethylene with at least one ethylenically unsaturated ester; and/or polymers obtained by methatesis reaction of at least one cycloalkene. 40. The process of claim 26, wherein the at least one thermoplastic binding agent comprises: a copolymer of ethylene with at least one aliphatic or aromatic alpha-olefin and, optionally, with at least one polyene; and a molecular weight distribution index (MWD) less than 5. 41. The process of claim 26, wherein the at least one thermoplastic binding agent comprises: a copolymer of ethylene with at least one aliphatic or aromatic alpha-olefin and, optionally, with at least one polyene; and a molecular weight distribution index (MWD) greater than 1.5 and less than 3.5. 42. The process of claim 40 or 41, wherein the copolymer is obtained by copolymerization of ethylene with an aliphatic or aromatic alpha-olefin and optionally, a polyene, in a presence of a single-site catalyst. 43. The process of claim 26, wherein the at least one thermoplastic binding agent is in admixture with at least one elastomeric polymer comprising a glass transition temperature (Tg) less than 20° C. 44. The process of claim 26, wherein the at least one thermoplastic binding agent is in admixture with at least one reinforcing filler. 45. The process of claim 26, wherein the at least one thermoplastic binding agent is in admixture with at least one plasticizing agent. 46. An apparatus for continuously producing an elastomeric composition, comprising: at least one extruder; at least one first metering device; at least one second metering device; and at least one pneumatic conveying line; wherein the at least one extruder comprises: a housing; and at least one screw rotatably mounted in the housing; wherein the housing comprises: at least one feed opening; and a discharge opening; wherein the at least one first metering device meters and feeds at least one elastomer and at least one filler through the at least one feed opening into the at least one extruder, wherein the at least one second metering device meters and feeds ingredients different from elastomers and fillers into the at least one extruder, wherein at least one of the ingredients different from elastomers and fillers comprises a subdivided product comprising one or more minor ingredients dispersed in at least one thermoplastic binding agent, and wherein the at least one pneumatic conveying line conveys the subdivided product from a storage bin to the at least one second metering device. 47. The apparatus of claim 46, further comprising: a first extruder; and a second extruder; wherein the first extruder extrudes an intermediate rubber mixture devoid of temperature sensitive minor ingredients, and wherein the second extruder extrudes a complete rubber mixture comprising the temperature sensitive minor ingredients. 48. The apparatus of claim 46, wherein one or more of the at least one first metering device and the at least one second metering device is a gravimetric feeder. 49. The apparatus of claim 46, further comprising: a rubber grinder; wherein the rubber grinder comminutes the at least one elastomer before metering and feeding the at least one elastomer into the at least one extruder. 50. The apparatus of claim 46, further comprising: at least one filtering body; wherein the at least one filtering body filters an elastomeric composition discharged from the at least one extruder. |
Remedies for diseases with bone mass loss having ep4 agonist as the active ingredient |
A pharmaceutical composition for topical administration for prevention and/or treatment of diseases associated with decrease in bone mass comprising an EP4 agonist as an active ingredient. An EP4 agonist, in which includes a compound possessing prostaglandin skeleton as a representative, possesses promoting action on bone formation, so it is useful for prevention and/or treatment of diseases associated with decrease in bone mass (bone diseases such as primary osteoporosis, secondary osteoporosis, bone metastasis of cancer, hypercalcemia, Paget's disease, bone loss and bone necrosis, postoperative osteogenesis, alternative therapy for bone grafting). |
1. A pharmaceutical composition for topical administration for prevention and/or treatment of diseases associated with decrease in bone mass comprising an EP4 agonist as an active ingredient. 2. The pharmaceutical composition for prevention and/or treatment according to claim 1, wherein the disease associated with decrease in bone mass is primary osteoporosis, secondary osteoporosis, bone metastasis of cancer, hypercalcemia, Paget's disease, bone loss and bone necrosis, postoperative osteogenesis, or alternative therapy for bone grafting. 3. A sustained release formulation comprising an EP4 agonist as an active ingredient. 4. The formulation according to claim 3, wherein the sustained release formulation is a microsphere, a microcapsule, a nanosphere or a film. 5. A pharmaceutical composition for prevention and/or treatment of diseases associated with decrease in bone mass, comprising the formulation described in claim 3 which is topically administered. 6. The pharmaceutical composition for prevention and/or treatment of diseases associated with decrease in bone mass according to claim 1, wherein the EP4 agonist is a compound possessing prostaglandin skeleton. 7. The sustained release formulation according to claim 3, wherein the EP4 agonist is a compound possessing prostaglandin skeleton. 8. The pharmaceutical composition for treatment and/or prevention according to claim 1, wherein the compound possessing prostaglandin skeleton is a compound selected from the group of formula (I-1) wherein R1-1 is hydroxy, C1-6 alkyloxy, or NR6-1R7-1, wherein R6-1 and R7-1 are each independently, hydrogen atom or C1-4 alkyl, R2-1 is oxo, halogen, or O—COR8-1, wherein R8-1 is C1-4 alkyl, phenyl or phenyl(C1-4 alkyl), R3-1 is hydrogen atom or hydroxy, R4a-1 and R4b-1 are each independently, hydrogen atom or C1-4 alkyl, R5-1 is phenyl substituted by the group listed below: (i) 1 to 3 of C1-4 alkyloxy-C1-4 alkyl, C2-4 alkenyloxy-C1-4 alkyl, C2-4 alkynyloxy-C1-4 alkyl, C3-7 cycloalkyloxy-C1-4 alkyl, C3-7 cycloalkyl(C1-4 alkyloxy)-C1-4 alkyl, phenyloxy-C1-4 alkyl, phenyl-C1-4 alkyloxy-C1-4 alkyl, C1-4 alkylthio-C1-4 alkyl, C2-4 alkenylthio-C1-4 alkyl, C2-4 alkynylthio-C1-4 alkyl, C3-7 cycloalkylthio-C1-4 alkyl, C3-7 cycloalkyl(C1-4 alkylthio)-C1-4 alkyl or phenylthio-C1-4 alkyl or phenyl-C1-4 alkylthio-C1-4 alkyl, (ii) C1-4 alkyloxy-C1-4 alkyl and C1-4 alkyl, C1-4 alkyloxy-C1-4 alkyl and C1-4 alkyloxy, C1-4 alkyloxy-C1-4 alkyl and hydroxy, C1-4 alkyloxy-C1-4 alkyl and halogen, C1-4 alkylthio-C1-4 alkyl and C1-4 alkyl, C1-4 alkylthio-C1-4 alkyl and C1-4 alkyloxy, C1-4 alkylthio-C1-4 alkyl and hydroxy or C1-4 alkylthio-C1-4 alkyl and halogen, (iii) haloalkyl or hydroxy-C1-4 alkyl, or (iv) C1-4 alkyl and hydroxy; is single bond or double bond, wherein when R2-1 is O—COR8-1, C8-9 position is double bond, or a non-toxic salt thereof, or a cyclodextrin clathrate thereof. 9. The sustained release formulation according to claim 3, wherein the compound possessing prostaglandin skeleton is a compound selected from the group of formula (I-1) described in claim 8, or a non-toxic salt thereof, or a cyclodextrin clathrate thereof. 10. The pharmaceutical composition for treatment and/or prevention according to claim 1, wherein the compound possessing prostaglandin skeleton is a compound selected from the group of formula (I-2) wherein R1-2 is (1) —CO—(NH-amino acid residue-CO)m-2—OH, (2) —COO—Y2—R9-2, (3) —COO—Z1-2—Z2-2—Z3-2, wherein Y2 is bond or C1-10 alkylene, R9-2 is (1) phenyl or (2) biphenyl optionally substituted by 1-3 C1-10 alkyl, C1-10 alkoxy or halogen atom, Z1-2 is (1) C1-15 alkylene, (2) C2-15 alkenylene or (3) C2-15 alkynylene, Z2-2 is (1) —CO—, (2) —OCO—, (3) —COO—, (4) —CONR11-2—, (5) —NR12-2CO—, (6) —O—, (7) —S—, (8) —SO—, (9) —SO2—, (10) —NR13-2—, (11) —NR14-2CONR15-2—, (12) —NR16-2COO—, (13) —OCONR17-2— or (14) —OCOO—, Z3-2 is (1) hydrogen atom, (2) C1-15 alkyl, (3) C2-15 alkenyl, (4) C2-15 alkynyl, (5) ring12 or (6) C1-10 alkyl substituted by C1-10 alkoxy, C1-10 alkylthio, C1-10 alkyl-NR18-2— or ring12, ring12 is (1) C3-15 mono-, bi- or tri-carbocyclic aryl which may be partially or fully saturated or (2) 3 to 15 membered mono-, bi- or tri-heterocyclic aryl containing 1 to 4 hetero atom selected from oxygen, nitrogen and sulfur atom(s) which may be partially or fully saturated, R11-2, R12-2, R13-2, R14-2, R15-2, R16-2, R17-2 and R18-2 are each independently, hydrogen atom or C1-15 alkyl, R11-2 and Z3-2 may be taken together with the nitrogen atom to which they are attached to form 5 to 7 membered saturated monoheterocyclic ring, and the heterocyclic ring may contain another one hetero atom selected from oxygen, nitrogen and sulfur atom, ring12 and saturated monoheterocyclic ring formed by R11-2, Z3-2 and the nitrogen atom to which Z3-2 is attached may be substituted by 1-3 group(s) selected from (1) C1-15 alkyl, (2) C2-15 alkenyl, (3) C2-15 alkynyl and (4) C1-10 alkyl substituted with C1-10 alkoxy, C1-10 alkylthio or C1-10 alkyl-NR19-2, R19-2 is hydrogen atom or C1-10 alkyl, m-2 is 1 or 2, other symbols are same meaning as defined in claim 8, or a non-toxic salt thereof, or cyclodextrin clathrate thereof. 11. The sustained release formulation according to claim 3, wherein the compound possessing prostaglandin skeleton is a compound selected from the group of formula (I-2) described in claim 10, or a non-toxic salt thereof, or a cyclodextrin clathrate thereof. 12. The pharmaceutical composition for treatment and/or prevention according to claim 1, wherein the compound possessing prostaglandin skeleton is a compound selected from the group of formula (I-3) wherein is (1) single bond or (2) double bond, R19-3 and R20-3 are each independently, (1) hydrogen atom, (2) C1-10 alkyl or (3) halogen atom, T3 is (1) oxygen atom or (2) sulfur atom, X3 is (1) —CH2—, (2) —O— or (3) —S—, A3 is A1-3or A2-3, A1-3 is (1) C2-8 straight-chain alkylene optionally substituted by 1-2 C1-4 alkyl, (2) C2-8 straight-chain alkenylene optionally substituted by 1-2 C1-4 alkyl or (3) C2-8 straight-chain alkynylene optionally substituted by 1-2 C1-4 alkyl, A2-3 is -G1-3-G2-3-G3-3-, G1-3 is (1) C1-4 straight-chain alkylene optionally substituted by 1-2 C1-4 alkyl, (2) C2-4 straight-chain alkenylene optionally substituted by 1-2 C1-4 alkyl or (3) C2-4 straight-chain alkynylene optionally substituted by 1-2 C1-4 alkyl, G2-3 is (1) —Y3—, (2) -(ring 13)-, (3) —Y3-(ring13)-, (4) -(ring13)-Y3— or (5) —Y3—(C1-4 alkylene)-(ring13)-, Y3 is (1) —S—, (2) —SO—, (3) —SO2—, (4) —O— or (5) —NR—1-3—, R1-3 is (1) hydrogen atom, (2) C1-10 alkyl or (3) C2-10 acyl, G3-3 is (1) bond, (2) C1-4 straight-chain alkylene optionally substituted by 1-2 C1-4 alkyl, (3) C2-4 straight-chain alkenylene optionally substituted by 1-2 C1-4 alkyl or (4) C2-4 straight-chain alkynylene optionally substituted by 1-2 C1-4 alkyl, D3 is D1-3 or D2-3, D1-3 is (1) —COOH, (2) —COOR2-3, (3) tetrazol-5-yl or (4) CONR3-3SO2R4-3, R2-3 is (1) C1-10 alkyl, (2) phenyl, (3) C1-10 alkyl substituted by phenyl or (4) biphenyl, R3-3 is (1) hydrogen atom or (2) C1-10 alkyl, R4-3 is (1) C1-10 alkyl or (2) phenyl, D2-3 is (1) —CH2OH, (2) —CH2OR5-3, (3) hydroxy, (4) —OR5-3, (5) formyl, (6) —CONR6-3R7-3, (7) —CONR6-3SO2R8-3, (8) —CO—(NH-amino acid residue-CO)m-3—OH, (9) —O—(CO-amino acid residue-NH)m-3—H, (10) —COOR9-3, (11) —OCO—R10-3, (12) —COO—Z1-3—Z2-3—Z3-3, (13) R5-3 is C1-10 alkyl, R6-3 and R7-3 are each independently, (1) hydrogen atom or (2) C1-10 alkyl, R8-3 is C1-10 alkyl substituted by phenyl, R9-3 is (1) C1-10 alkyl substituted by biphenyl optionally substituted by 1-3 C1-10 alkyl, C1-10 alkoxy or halogen atom or (2) biphenyl substituted by 1-3 C1-10 alkyl, C1-10 alkoxy or halogen atom, R10-3 is (1) phenyl or (2) C1-10 alkyl, m-3 is 1 or 2, Z1-3 is (1) C1-15 alkylene, (2) C2-15 alkenylene or (3) C2-15 alkynylene, Z2-3 is (1) —CO—, (2) —OCO—, (3) —COO—, (4) —CONR11-3—, (5) —NR12-3CO—, (6) —O—, (7) —S—, (8) —SO—, (9) —SO2—, (10) —NR13-3—, (11) —NR14-3CONR15-3—, (12) —NR16-3COO—, (13) —OCONR17-3— or (14) —OCOO—, Z3-3 is (1) hydrogen atom, (2) C1-15 alkyl, (3) C2-15 alkenyl, (4) C2-15 alkynyl; (5) ring23 or (6) C1-10 alkyl substituted by C1-10 alkoxy, C1-10 alkylthio, C1-10 alkyl-NR18-3— or ring23, R11-3, R12-3, R13-3, R14-3, R15-3, R16-3, R17-3 and R18-3 are each independently, (1) hydrogen atom or (2) C1-15 alkyl, R11-3 and Z3-3 may be taken together with the nitrogen atom to which they are attached to form 5 to 7 membered saturated monoheterocyclic ring, and the heterocyclic ring may contain other one hetero atom selected from oxygen, nitrogen and sulfur atom, E3 is E1-3 or E2-3, E1-3 is (1) C3-7 cycloalkyl or (2) ring33, E2-3 is (1) C3-7 cycloalkyl, (2) ring43 or (3) ring53, ring13 and ring53are optionally substituted by 1-3 R21-3 and/or R22-3, ring33 is optionally substituted by 1-2 R21-3, C3-7 cycloalkyl represented by E2-3 is substituted by one of R21-3 or R22-3, and optionally substituted by another 1-2 R21-3 and/or R22-3, ring43 is substituted by one of R22-3, optionally substituted by another 1-2 R21-3 and/or R22-3, and optionally substituted by heterocyclic ring formed by R11-3, Z3-3 and the nitrogen to which Z3-3 is attached or ring23 may be substituted by R23-3, R21-3 is (1) C1-10 alkyl, (2) C1-10 alkoxy, (3) halogen atom, (4) nitro, (5) C1-10 alkyl substituted by 1-3 halogen atom(s) or (6) phenyl, R22-3 is (1) C2-10 alkenyl, (2) C2-10 alkynyl, (3) C1-10 alkylthio, (4) hydroxy, (5) —NR24-3R25-3, (6) C1-10 alkyl substituted by C1-10 alkoxy, (7) C1-10 alkyl substitute 10 alkoxy substituted by 1-3 halogen atom(s), (8) C1-10 alkyl substituted by —NR24-3R25-3, (9) ring63, (10)-O-ring73, (11) C1-10 alkyl substituted by ring73, (12) C2-10 alkeny substituted by ring73, (13) C2-10 alkynyl substituted by ring73, (14) C1-10 alkoxy substituted by ring 73, (15) C1-10 alkyl substituted by —O-ring73, (16) —COOR26-3 or (17) C1-10 alkoxy substituted by 1-3 halogen atom(s)(s), R24-3, R25-3 and R26-3 are each independently, (1) hydrogen atom or (2) Cl-10 alkyl, R23-3 is (1) C1-15 alkyl, (2) C2-15 alkenyl, (3) C2-15 alkynyl or (4) C1-10 alkyl substituted by C1-10 alkoxy, C1-10 alkylthio or C1-10 alkyl-NR27-3—, R27-3 is (1) hydrogen atom or (2) C1-10 alkyl, ring13, ring23, ring53, ring63 and ring73 are (1) C3-15 mono-, bi- or tri-carbocyclic aryl which may be partially or fully saturated or (2) 3 to 15 membered mono-, bi- or tri-heterocyclic aryl containing 1 to 4 hetero atom selected from oxygen, nitrogen and sulfur atom(s) which may be partially or fully saturated, ring33 and ring43 are (1) thienyl, (2) phenyl or (3) furyl, ring63 and ring73 may be substituted by 1-3 R28-3, R21-3 is (1) C1-10 alkyl, (2) C2-10 alkenyl, (3) C2-10 alkynyl, (4) C1-10 akloxy, (5) C1-10 alkyl substituted by C1-10 alkoxy, (6) halogen atom, (7) hydroxy, (8) C1-10 alkyl substituted by 1-3 halogen atom(s) or (9) C1-10 alkyl substituted by C1-10 alkoxy substituted by 1-3 halogen atom(s), and wherein (1) when T3 is oxygen atom, X3 is CH2—, A3 is A1-3, and D3 is D1-3, E3 is E2-3 (2) ring53 is not C3-7 cycloalkyl, phenyl, thienyl nor furyl, (3) ring63 is phenyl, then phenyl have at least one R28-3, or a non-toxic salt thereof, or a cyclodextrin clathrate thereof 13. The sustained release formulation according to claim 3, wherein the compound possessing prostaglandin skeleton is a compound selected from the group of formula (1-3) described in claim 12, or a non-toxic salt thereof, or a cyclodextrin clathrate thereof 14. A prostaglandin derivative of formula (I-2) wherein all symbols have the same meaning as defined in claim 10, or a non-toxic salt thereof, or a cyclodextrin clathrate thereof 15. A compound selected from the group of formula (I-3) wherein all symbols have the same meaning as defined in claim 12, or a non-toxic salt thereof, or a cyclodextrin clathrate thereof. 16. A compound selected from the group consisting of (1) (15α,13E)-9-oxo-15-hydroxy-16-(3-chlorophenyl)-17,18,19,20-tetranor-8-azaprost-13-enoic acid, (2) (15α,13E)-9-oxo-15-hydroxy-16-(3-phenylphenyl)-17,18,19,20-tetranor-8-azaprost-13-enoic acid, (3) (15α,13E)-9-oxo-15-hydroxy-16-(3-methylphenyl)-17,18,19,20-tetranor-8-azaprost-13-enoic acid, (4) (15α,13E)-9-oxo-15-hydroxy-16-(3-fluorophenyl)-17,18,19,20-tetranor-8-azaprost-13-enoic acid, (5) (15α,13E)-9-oxo-15-hydroxy-16-(4-fluorophenyl)-17,18,19,20-tetranor-8-azaprost-13-enoic acid, (6) (15α,13E)-9-oxo-15-hydroxy-16-(4-methylphenyl)-17,18,19,20-tetranor-8-azaprost-13-enoic acid, (7) (15α,13E)-9-oxo-15-hydroxy-16-(2-methylphenyl)-17,18,19,20-tetranor-8-azaprost-13-enoic acid, (8) (15α,13E)-9-oxo-15-hydroxy-16-(2-fluorophenyl)-17,18,19,20-tetranor-8-azaprost-13-enoic acid, (9) (15α,13E)-9-oxo-15-hydroxy-16-(3-trifluoromethylphenyl)-17,18,19,20-tetranor-8-azaprost-13-enoic acid, (10) (15α,13E)-9-oxo-15-hydroxy-16-(3-methoxyphenyl)-17,18,19,20-tetranor-8-azaprost-13-enoic acid, (11) (15α,13E)-9-oxo-15-hydroxy-16-(3-ethylphenyl)-17,18,19,20-tetranor-8-azaprost-13-enoic acid, (12) (15α,13E)-9-oxo-15-hydroxy-16-(3,4-difluorophenyl)-17,18,19,20-tetranor-8-azaprost-13-enoic acid, (13) (15α,13E)-9-oxo-15-hydroxy-16-(3,5-difluorophenyl)-17,18,19,20-tetranor-8-azaprost-13-enoic acid, (14) (15α,13E)-9-oxo-15-hydroxy-16-(3-propylphenyl)-17,18,19,20-tetranor-8-azaprost-13-enoic acid, (15) (15α,13E)-9-oxo-15-hydroxy-16-(3-ethoxyphenyl)-17,18,19,20-tetranor-8-azaprost-13-enoic acid, (16) (15α,13E)-9-oxo-15-hydroxy-16-(3-isopropyloxyphenyl)-17,18,19,20-tetranor-8-azaprost-13-enoic acid, (17) (15α,5Z,13E)-9-oxo-15-hydroxy-16-(3-trifluoromethylphenyl)-17,18,19,20-tetranor-8-azaprost-5,13-dienoic acid, (18) (15α,5Z,13E)-9-oxo-15-hydroxy-16-(3-methylphenyl)-17,18,19,20-tetranor-8-azaprost-5,13-dienoic acid, (19) (15α,13E)-9-oxo-15-hydroxy-16-(3,5-dimethylphenyl)-17,18,19,20-tetranor-8-azaprost-13-enoic acid, (20) (15α,5Z,13E)-9-oxo-15-hydroxy-16-(3-chlorophenyl)-17,18,19,20-tetranor-8-azaprost-5,13-dienoic acid, (21) (15α,13E)-9-oxo-15-hydroxy-16-(3,4-difluorophenyl)-17,18,19,20-tetranor-8-azaprost-5,13-dienoic acid, (22) (15α,5Z,13E)-9-oxo-15-hydroxy-16-(3-fluorophenyl)-17,18,19,20-tetranor-8-azaprost-5,13-dienoic acid, (23) (15α,5Z,13E)-9-oxo-15-hydroxy-16-(4-fluorophenyl)-17,18,19,20-tetranor-8-azaprost-5,13-dienoic acid, (24) (15α)-9-oxo-15-hydroxy-16-(3-methylphenyl)-17,18,19,20-tetranor-8-azaprostanoic acid, and (25) (15α,13E)-9-oxo-15-hydroxy-16-phenyl-17,18,19,20-tetranor-8-azaprost-13-enoic acid 3-phenylphenyl ester, or a non-toxic salt thereof, or a cyclodextrin clathrate thereof. 17. The compound according to claim 15, wherein —Y3— group in A3 group of a compound of formula (I-3) is —S— group. 18. The compound according to claim 14, which is a compound selected from the group consisting of (1) (11α,15α,13E)-9-oxo-11,15-dihydroxy-16-(3-methoxymethylphenyl)-17,18,19,20-tetranor-5-thiaprost-13-enoic acid 2-nonanoyloxyethyl ester, (2) (11α,15α,13E)-9-oxo-11,15-dihydroxy-16-(3-methoxymethylphenyl)-17,18,19,20-tetranor-5-thiaprost-13-enoic acid pivaloyloxymethyl ester, (3) (11α,15α,13E)-9-oxo-11,15-dihydroxy-16-(3-methoxymethylphenyl)-17,18,19,20-tetranor-5-thiaprost-13-enoic acid 1-cyclohexyloxycarbonyloxyethyl ester, (4) (11α,15α,13E)-9-oxo-11,15-dihydroxy-16-(3-methoxymethylphenyl)-17,18,19,20-tetranor-5-thiaprost-13-enoic acid N,N-diethylaminocarbonylmethyl ester, (5) (11α,15α,13E)-9-oxo-11,15-dihydroxy-16-(3-methoxymethylphenyl)-17,18,19,20-tetranor-5-thiaprost-13-enoic acid 2-acetyloxyethyl ester, (6) (11α,15α,13E)-9-oxo-11,15-dihydroxy-16-(3-methoxymethylphenyl)-17,18,19,20-tetranor-5-thiaprost-13-enoic acid benzoylmethyl ester, (7) (11α,15α,13E)-9-oxo-11,15-dihydroxy-16-(3-methoxymethylphenyl)-17,18,19,20-tetranor-5-thiaprost-13-enoic acid isopropyloxycarbonylmethyl ester, (8) (11α,15α,13E)-9-oxo-11,15-dihydroxy-16-(3-methoxymethylphenyl)-17,18,19,20-tetranor-5-thiaprost-13-enoic acid N,N-diethylaminocarbonyloxymethyl ester, (9) (11α,15α,13E)-9-oxo-11,15-dihydroxy-16-(3-methoxymethylphenyl)-17,18,19,20-tetranor-5-thiaprost-13-enoic acid t-butyloxycarbonylmethyl ester, (10) (11α,15α,13E)-9-oxo-11,15-dihydroxy-16-(3-methoxymethylphenyl)-17,18,19,20-tetranor-5-thiaprost-13-enoic acid 1-isopropyloxycarbonylethyl ester, (11) (11α,15α,13E)-9-oxo-11,15-dihydroxy-16-(3-methoxymethylphenyl)-17,18,19,20-tetranor-5-thiaprost-13-enoic acid 1-benzoylethyl ester, (12) (11α,15α,13E)-9-oxo-11,15-dihydroxy-16-(3-methoxymethylphenyl)-17,18,19,20-tetranor-5-thiaprost-13-enoic acid methoxycarbonylmethyl ester, (13) (11α,15α,13E)-9-oxo-11,15-dihydroxy-16-(3-methoxymethylphenyl)-17,18,19,20-tetranor-5-thiaprost-13-enoic acid 2-tridecanoyloxyethyl ester, (14) (11α,15α,13E)-9-oxo-11,15-dihydroxy-16-(3-methoxymethylphenyl)-17,18,19,20-tetranor-5-thiaprost-13-enoic acid 2-heptanoyloxyethyl ester, (15) (11α,15α,13E)-9-oxo-11,15-dihydroxy-16-(3-methoxymethylphenyl)-17,18,19,20-tetranor-5-thiaprost-13-enoic acid 2-octanoyloxyethyl ester, (16) (11α,15α,13E)-9-oxo-11,15-dihydroxy-16-(3-methoxymethylphenyl)-17,18,19,20-tetranor-5-thiaprost-13-enoic acid 2-decanoyloxyethyl ester, (17) (11α,15α,13E)-9-oxo-11,15-dihydroxy-16-(3-methoxymethylphenyl)-17,18,19,20-tetranor-5-thiaprost-13-enoic acid allyloxycarbonylmethyl ester, (18) (11α,15α,13E)-9-oxo-11,15-dihydroxy-16-(3-methoxymethylphenyl)-17,18,19,20-tetranor-5-thiaprost-13-enoic acid nonanoyloxymethyl ester, (19) (11α,15α,13E)-9-oxo-11,15-dihydroxy-16-(3-methoxymethylphenyl)-17,18,19,20-tetranor-5-thiaprost-13-enoic acid 2-hydroxyethyl ester, (20) (11α,15α,13E)-9-oxo-11,15-dihydroxy-16-(3-methoxymethylphenyl)-17,18,19,20-tetranor-5-thiaprost-13-enoic acid phenyl ester, (21) (11α,15α,13E)-9-oxo-11,15-dihydroxy-16-(3-methoxymethylphenyl)-17,18,19,20-tetranor-5-thiaprost-13-enoic acid carboxymethyl ester, (22) (11α,15α,13E)-9-oxo-11,15-dihydroxy-16-(3-methoxymethylphenyl)-17,18,19,20-tetranor-5-thiaprost-13-enoic acid dipropylcarbamoylmethyl ester, (23) (11α,15α,13E)-9-oxo-11,15-dihydroxy-16-(3-methoxymethylphenyl)-17,18,19,20-tetranor-5-thiaprost-13-enoic acid dibutylcarbamoylmethyl ester, (24) (11α,15α,13E)-9-oxo-11,15-dihydroxy-16-(3-methoxymethylphenyl)-17,18,19,20-tetranor-5-thiaprost-13-enoic acid 4-pentylbenzoylmethyl ester, (25) (11α,15α,13E)-9-oxo-11,15-dihydroxy-16-(3-methoxymethylphenyl)-17,18,19,20-tetranor-5-thiaprost-13-enoic acid 1,1-dimethylheptyloxycarbonylmethyl ester, (26) (11α,15α,13E)-9-oxo-11,15-dihydroxy-16-(3-methoxymethylphenyl)-17,18,19,20-tetranor-5-thiaprost-13-enoic acid dipentylcarbamoylmethyl ester, (27) (11α,15α,13E)-9-oxo-11,15-dihydroxy-16-(3-methoxymethylphenyl)-17,18,19,20-tetranor-5-thiaprost-13-enoic acid 2-octyloxyethyl ester, (28) (11α,15α,13E)-9-oxo-11,15-dihydroxy-16-(3-methoxymethylphenyl)-17,18,19,20-tetranor-5-thiaprost-13-enoic acid 2-(2,2-dimethylpentanoyloxy)ethyl ester, (29) (11α,15α,13E)-9-oxo-11,15-dihydroxy-16-(3-methoxymethylphenyl)-17,18,19,20-tetranor-5-thiaprost-13-enoic acid 3-butoxypropyl ester, (30) (11α,15α,13E)-9-oxo-11,15-dihydroxy-16-(3-methoxymethylphenyl)-17,18,19,20-tetranor-5-thiaprost-13-enoic acid 2-butoxyethyl ester, (31) (11α,15α,13E)-9-oxo-11,15-dihydroxy-16-(3-methoxymethylphenyl)-17,18,19,20-tetranor-5-thiaprost-13-enoic acid 2-pentyloxyethyl ester, (32) (11α,15α,13E)-9-oxo-11,15-dihydroxy-16-(3-methoxymethylphenyl)-17,18,19,20-tetranor-5-thiaprost-13-enoic acid 2-hexyloxyethyl ester, (33) (11α,15α,13E)-9-oxo-11,15-dihydroxy-16-(3-methoxymethylphenyl)-17,18,19,20-tetranor-5-thiaprost-13-enoic acid 2-(2,2-dimethyloctanoyloxy)ethyl ester, (34) (11α,15α,13E)-9-oxo-11,15-dihydroxy-16-(3-methoxymethylphenyl)-17,18,19,20-tetranor-5-thiaprost-13-enoic acid 2-(2,2-diethylpentanoyloxy)ethyl ester, (35) (11α,15α,13E)-9-oxo-11,15-dihydroxy-16-(3-methoxymethylphenyl)-17,18,19,20-tetranor-5-thiaprost-13-enoic acid 4-(4-chlorophenyl)phenyl ester, (36) (11α,15α,13E)-9-oxo-11,15-dihydroxy-16-(3-methoxymethylphenyl)-17,18,19,20-tetranor-5-thiaprost-13-enoic acid 2-(adamantan-1-ylcarbonyloxy)ethyl ester, and (37) (11α,15α,13E)-9-oxo-11,15-dihydroxy-16-(3-methoxymethylphenyl)-17,18,19,20-tetranor-5-thiaprost-13-enoic acid 2-(2,2-dipropylpentanoyloxy)ethyl ester, or a non-toxic salt thereof, or a cyclodextrin clathrate thereof. 19. The compound according to claim 15, which is a compound selected from the group consisting of (1) (15α,13E)-9-oxo-15-hydroxy-16-(3-methoxymethylphenyl)-17,18,19,20-tetranor-8-azaprost-13-enoic acid ethyl ester, (2) (15α,13E)-9-oxo-15-hydroxy-16-(3-methoxymethylphenyl)-17,18,19,20-tetranor-8-azaprost-13-enoic acid, (3) (5S,15α,13E)-5-methyl-9-oxo-15-hydroxy-16-(3-methoxymethylphenyl)-17,18,19,20-tetranor-8-azaprost-13-enoic acid, (4) (15α,13E)-5,5-dimethyl-9-oxo-15-hydroxy-16-(3-methoxymethylphenyl)-17,18,19,20-tetranor-8-azaprost-13-enoic acid, (5) (15α,13E)-5,5-ethano-9-oxo-15-hydroxy-16-(3-methoxymethylphenyl)-17,18,19,20-tetranor-8-azaprost-13-enoic acid, (6) (5R, 15α,13E)-5-methyl-9-oxo-15-hydroxy-16-(3-methoxymethylphenyl)-17,18,19,20-tetranor-8-azaprost-13-enoic acid, (7) (15α,13E)-9-oxo-15-hydroxy-16-(3-(2,2,2-trifluoroethoxymethyl)phenyl)-17,18,19,20-tetranor-8-azaprost-13-enoic acid, (8) (15α,13E)-9-oxo-15-hydroxy-16-(3-methoxymethylphenyl)-2,3,4,17,18,19,20-heptanor-1,5-(2,5-interthienylene)-8-azaprost-13-enoic acid, (9) (15α,13E)-9-oxo-15-hydroxy-16-(3-chloro-4-hydroxyphenyl)-17,18,19,20-tetranor-8-azaprost-13-enoic acid, (10) (15α,13E)-9-oxo-15-hydroxy-16-((E)-1-propenylphenyl)-17,18,19,20-tetranor-8-azaprost-13-enoic acid, (11) (15α,13E)-9-oxo-15-hydroxy-16-(3-(2-fluorophenyl)phenyl)-17,18,19,20-tetranor-8-azaprost-13-enoic acid, (12) (15α,13E)-9-oxo-15-hydroxy-16-(3-(4-fluorophenyl)phenyl)-17,18,19,20-tetranor-8-azaprost-13-enoic acid, (13) (15α,13E)-9-oxo-15-hydroxy-16-(3-(5-methylfuran-2-yl)phenyl)-17,18,19,20-tetranor-8-azaprost-13-enoic acid, (14) (15α,13E)-9-oxo-15-hydroxy-16-(naphthalen-2-yl)-17,18,19,20-tetranor-8-azaprost-13-enoic acid, (15) (15α,13E)-9-oxo-15-hydroxy-16-(3-(2-methoxyphenyl)phenyl)-17,18,19,20-tetranor-8-azaprost-13-enoic acid, (16) (15α,13E)-9-oxo-15-hydroxy-16-(3-(2-hydroxyphenyl)phenyl)-17,18,19,20-tetranor-8-azaprost-13-enoic acid, (17) (15α,13E)-9-oxo-15-hydroxy-16-(3-(3-hydroxyphenyl)phenyl)-17,18,19,20-tetranor-8-azaprost-13-enoic acid, (18) (15α,13E)-1,5-(2,5-interthienylene)-9-oxo-15-hydroxy-16-(3-chlorophenyl)-2,3,4,17,18,19,20-heptanor-8-azaprost-13-enoic acid, (19) (15α,13E)-9-oxo-15-hydroxy-16-(3-cyclopropylphenyl)-17,18,19,20-tetranor-8-azaprost-13-enoic acid, (20) (13E)-9-oxo-15-hydroxy-16,16-difluoro-16-(3-methoxymethylphenyl)-17,18,19,20-tetranor-8-azaprost-13-enoic acid, (21) (15α,13E)-9-oxo-15-hydroxy-16-(3-benzyloxyphenyl)-17,18,19,20-tetranor-8-azaprost-13-enoic acid, (22) (15α,5Z,13E)-9-oxo-15-hydroxy-16-(3-methoxymethylphenyl)-17,18,19,20-tetranor-8-azaprost-5,13-dienoic acid, (23) (15α,13E)-9-oxo-15-hydroxy-16-(3-(benzofuran-2-yl)phenyl)-17,18,19,20-tetranor-8-azaprost-13-enoic acid, (24) (15α,13E)-2,7-(1,3-interphenylene)-9-oxo-15-hydroxy-16-(3-methylphenyl)-3,4,5,6,17,18,19,20-octanor-8-azaprost-13-enoic acid, (25) (15α,13E)-9-oxo-15-hydroxy-16-(3-(2-phenylethynyl)phenyl)-17,18,19,20-tetranor-8-azaprost-13-enoic acid, (26) (15α,13E)-2,7-(1,4-interphenylene)-9-oxo-15-hydroxy-16-(3-methylphenyl)-3,4,5,6,17,18,19,20-octanor-8-azaprost-13-enoic acid, (27) (15α,5Z,13E)-9-oxo-15-hydroxy-16-(3-chlorophenyl)-2,6-(1,3-interphenylene)-3,4,5,17,18,19,20-heptanor-8-azaprost-13-enoic acid, (28) (15α,13E)-9-oxo-15-hydroxy-16-(3-methylphenyl)-1,5-(2,5-interthienylene)-2,3,4,17,18,19,20-heptanor-8-azaprost-13-enoic acid, (29) (15α,13E)-9-oxo-15-hydroxy-16-(4-fluorophenyl)-5-(5-(5-oxo-1,2,4-oxadiazol-3-yl)thiophen-2-yl)-1,2,3,4,17,18,19,20-octanor-8-azaprost-13-ene, (30) (15α,13E)-9-oxo-15-hydroxy-16-(4-fluorophenyl)-1,5-(2,5-interfurylene)-2,3,4,17,18,19,20-heptanor-8-azaprost-13-enoic acid, (31) (15α,13E)-9-oxo-15-hydroxy-16-(4-fluorophenyl)-3,7-(2,5-interthienylene)-4,5,6,17,18,19,20-heptanor-8-azaprost-13-enoic acid, (32) (15α,13E)-9-oxo-15-hydroxy-16-(4-fluorophenyl)-5-(5-(tetrazol-5-yl)thiophen-2-yl)-1,2,3,4,17,18,19,20-octanor-8-azaprost-13-ene, (33) (15α,13E)-9-oxo-15-hydroxy-16-(naphthalen-1-yl)-17,18,19,20-tetranor-8-azaprost-13-enoic acid, (34) (15α,13E)-9-oxo-15-hydroxy-16-(3-methoxymethylphenyl)-17,18,19,20-tetranor-5-thia-8-azaprost-13-enoic acid, (35) (15α,13E)-9-oxo-15-hydroxy-16-(3-chlorophenyl)-17,18,19,20-tetranor-5-thia-8-azaprost-13-enoic acid, (36) (15α,13E)-9-oxo-15-hydroxy-16-(3-cyclopropyloxymethylphenyl)-17,18,19,20-tetranor-5-thia-8-azaprost-13-enoic acid, (37) (15α,13E)-9-oxo-15-hydroxy-16-(3-(2,2,2-trifluoroethoxymethyl)phenyl)-17,18,19,20-tetranor-5-thia-8-azaprost-13-enoic acid, (38) (15α,13E)-9-oxo-15-hydroxy-16-(3-propylphenyl)-17,18,19,20-tetranor-5-thia-8-azaprost-13-enoic acid, (39) (15α,13E)-9-oxo-15-hydroxy-16-cyclopentyl-17,18,19,20-tetranor-5-thia-8-azaprost-13-enoic acid, (40) (15α,13E)-9-oxo-15-hydroxy-16-(thiophen-2-yl)-17,18,19,20-tetranor-5-thia-8-azaprost-13-enoic acid, (41) (15α,13E)-9-oxo-15-hydroxy-16-(3-trifluoromethylphenyl)-17,18,19,20-tetranor-5-thia-8-azaprost-13-enoic acid, (42) (15α,13E)-9-oxo-15-hydroxy-16-phenyl-17,18,19,20-tetranor-5-thia-8-azaprost-13-enoic acid, (43) (15α,13E)-9-oxo-15-hydroxy-16-(3-methylphenyl)-17,18,19,20-tetranor-5-thia-8-azaprost-13-enoic acid, (44) (15α,13E)-9-oxo-15-hydroxy-16-(3-fluorophenyl)-17,18,19,20-tetranor-5-thia-8-azaprost-13-enoic acid, (45) (15α,13E)-9-oxo-15-hydroxy-16-(4-fluorophenyl)-17,18,19,20-tetranor-5-thia-8-azaprost-13-enoic acid, (46) (15α,13E)-9-oxo-15-hydroxy-16-(3,4-difluorophenyl)-17,18,19,20-tetranor-5-thia-8-azaprost-13-enoic acid, (47) (15α,13E)-9-oxo-15-hydroxy-16-(naphthalen-2-yl)-17,18,19,20-tetranor-5-thia-8-azaprost-13-enoic acid, (48) (15α,13E)-2,3-methano-9-oxo-15-hydroxy-16-(3-chlorophenyl)-17,18,19,20-tetranor-5-thia-8-azaprost-13-enoic acid, (49) (15α,13E)-9-oxo-15-hydroxy-16-(3-t-butylphenyl)-17,18,19,20-tetranor-5-thia-8-azaprost-13-enoic acid, (50) (13E)-9-oxo-15-hydroxy-16α-methyl-16-phenyl-17,18,19,20-tetranor-5-thia-8-azaprost-13-enoic acid, (51) (13E)-9-oxo-15-hydroxy-16β-methyl-16-phenyl-17,18,19,20-tetranor-5-thia-8-azaprost-13-enoic acid, (52) (15α,13E)-9-oxo-15-hydroxy-16-(3-ethylphenyl)-17,18,19,20-tetranor-5-thia-8-azaprost-13-enoic acid, (53) (15α,13E)-9-oxo-15-hydroxy-16-(4-fluoro-3-trifluoromethylphenyl)-17,18,19,20-8-tetranor-5-thia-8-azaprost-13-enoic acid, (54) (15α,13E)-9-oxo-15-hydroxy-16-(4-fluoro-3-methylphenyl)-17,18,19,20-tetranor-5-thia-8-azaprost-13-enoic acid, (55) (15α,13E)-9-oxo-15-hydroxy-16-(3-chloro-4-fluorophenyl)-17,18,19,20-tetranor-5-thia-8-azaprost-13-enoic acid, (56) (15β,13E)-9-oxo-15-hydroxy-16-(3-chlorophenyl)-17,18,19,20-tetranor-5-thia-8-azaprost-13-enoic acid, (57) (15α,13E)-9-oxo-15-hydroxy-16-(3-methylphenyl)-5-(5-carboxythiazol-2-yl)-1,2,3,4,17,18,19,20-octanor-5-thia-8-azaprost-13-ene, (58) (15α,13E)-9-oxo-15-hydroxy-16-(3-chlorophenyl)-4-(3-hydroxyisoxazol-5-yl)-1,2,3,17,18,19,20-heptanor-5-thia-8-azaprost-13-ene, (59) (15α,13E)-9-oxo-15-hydroxy-16-(3-chlorophenyl)-2-(5-oxo-1,2,4-oxadiazol-3-yl)-1,17,18,19,20-pentanor-5-thia-8-azaprost-13-ene, (60) (15α,13E)-9-oxo-15-hydroxy-16-(3-chlorophenyl)-2-(5-oxo-1,2,4-thiadiazol-3-yl)-1,17,18,19,20-pentanor-5-thia-8-azaprost-13-ene, (61) (15α,13E)-1-methoxy-9-oxo-15-hydroxy-16-(3-chlorophenyl)-17,18,19,20-tetranor-5-thia-8-azaprost-13-ene, (62) (15α,13E)-9-oxo-15-hydroxy-16-(4-fluorophenyl)-5-(4-carboxythiazol-2-yl)-1,2,3,4,17,18,19,20-octanor-5-thia-8-azaprost-13-ene, (63) (15α,13E)-1-methoxy-9-oxo-15-hydroxy-16-(4-fluorophenyl)-17,18,19,20-tetranor-5-thia-8-azaprost-13-ene, (64) (15α,13E)-9-oxo-15-hydroxy-16-(4-fluorophenyl)-5-(5-(5-oxo-1,2,4-oxadiazol-3-yl)thiazol-2-yl)-1,2,3,4,17,18,19,20-octanor-5-thia-8-azaprost-13-ene, (65) (15α,13E)-9-oxo-15-hydroxy-16-(3-chlorophenyl)-17,18,19,20-tetranor-5-thia-5-thia-8-aza-10-oxaprost-13-enoic acid, (66) (15α,13E)-9-oxo-15-hydroxy-16-(4-fluorophenyl)-17,18,19,20-tetranor-5-thia-8-aza-10-oxaprost-13-enoic acid, (67) (15α,13E)-9-oxo-15-hydroxy-16-(3-methylphenyl)-17,18,19,20-tetranor-5-thia-8-aza-10-oxaprost-13-enoic acid, (68) (15α,13E)-9-oxo-15-hydroxy-16-(3-methylaminomethylphenyl)-17,18,19,20-tetranor-5-thia-8-azaprost-13-enoic acid hydrochloride, (69) (15α,13E)-9-oxo-15-hydroxy-16-(3-ethyl-4-fluorophenyl)-17,18,19,20-tetranor-5-thia-8-azaprost-13-enoic acid, (70) (15α,13E)-9-oxo-15-hydroxy-16-(5-methylfuran-2-yl)-17,18,19,20-tetranor-5-thia-8-azaprost-13-enoic acid, (71) (15α,13E)-9-oxo-15-hydroxy-16-(2-methyloxazol-5-yl)-17,18,19,20-tetranor-5-thia-8-azaprost-13-enoic acid, (72) (15α,13E)-9-oxo-15-hydroxy-16-(benzofuran-2-yl)-17,18,19,20-tetranor-5-thia-8-azaprost-13-enoic acid, (73) (15α,13E)-9-oxo-15-hydroxy-16-(5-ethylfuran-2-yl)-17,18,19,20-tetranor-5-thia-8-azaprost-13-enoic acid, (74) (15α,13E)-9-oxo-15-hydroxy-16-(4,5-dimethylfuran-2-yl)-17,18,19,20-tetranor-5-thia-8-azaprost-13-enoic acid, (75) (15α,13E)-9-oxo-15-hydroxy-16-(3-methylfuran-2-yl)-17,18,19,20-tetranor-5-thia-8-azaprost-13-enoic acid, (76) (15α,13E)-9-oxo-15-hydroxy-16-(3-nitrophenyl)-17,18,19,20-tetranor-5-thia-8-azaprost-13-enoic acid, (77) (15α,13E)-9-oxo-15-hydroxy-16-(3-methylisoxazol-5-yl)-17,18,19,20-tetranor-5-thia-8-azaprost-13-enoic acid, (78) (15α,13E)-9-oxo-15-hydroxy-16-(3-methoxymethylphenyl)-17,18,19,20-tetranor-8-azaprost-13-en-1-ol, (79) (15α,13E)-9-oxo-15-hydroxy-16-(3-methoxymethylphenyl)-17,18,19,20-tetranor-5-thia-8-azaprost-13-en-1-ol, (80) (15α,13E)-9-oxo-15-hydroxy-16-(3,4-difluorophenyl)-17,18,19,20-tetranor-8-azaprost-13-en-1-ol, (81) (15α,13E)-9-oxo-15-hydroxy-16-(3-chlorophenyl)-17,18,19,20-tetranor-8-azaprost-13-en-1-ol, (82) (15α,13E)-9-oxo-15-hydroxy-16-(3-chlorophenyl)-17,18,19,20-tetranor-5-thia-8-azaprost-13-en-1-ol, (83) (15α,13E)-9-oxo-15-hydroxy-16-phenyl-17,18,19,20-tetranor-5-thia-8-azaprost-13-en-1-ol, (84) (15α,13E)-9-oxo-15-hydroxy-16-(3-methylphenyl)-17,18,19,20-tetranor-5-thia-8-azaprost-13-en-1-ol, (85) (15α,13E)-9-oxo-15-hydroxy-16-(3-fluorophenyl)-17,18,19,20-tetranor-5-thia-8-azaprost-13-en-1-ol, (86) (15α,13E)-9-oxo-15-hydroxy-16-(4-fluorophenyl)-17,18,19,20-tetranor-5-thia-8-azaprost-13-en-1-ol, (87) (15α,13E)-9-oxo-15-hydroxy-16-(3-propylphenyl)-17,18,19,20-tetranor-5-thia-8-azaprost-13-en-1-ol, (88) (15α,13E)-9-oxo-15-hydroxy-16-(3-trifluoromethylphenyl)-17,18,19,20-tetranor-5-thia-8-azaprost-13-en-1-ol, (89) (15α,13E)-9-oxo-15-hydroxy-16-(3-ethylphenyl)-17,18,19,20-tetranor-5-thia-8-azaprost-13-en-1-ol, (90) (15α,13E)-9-oxo-15-hydroxy-16-(3,4-difluorophenyl)-17,18,19,20-tetranor-5-thia-8-azaprost-13-en-1-ol, (91) (15α,13E)-9-oxo-15-hydroxy-16-(4-fluoro-3-trifluoromethylphenyl)-17,18,19,20-tetranor-5-thia-8-azaprost-13-en-1-ol, (92) (15α,13E)-9-oxo-15-hydroxy-16-(4-fluoro-3-methylphenyl)-17,18,19,20-tetranor-5-thia-8-azaprost-13-en-1-ol, (93) (15α,13E)-9-oxo-15-hydroxy-16-(3-chloro-4-fluorophenyl)-17,18,19,20-tetranor-5-thia-8-azaprost-13-en-1-ol, (94) (15α,13E)-9-oxo-15-hydroxy-16-(3-methylphenyl)-1,5-(2,5-interthienylene)-2,3,4,17,18,19,20-heptanor-8-azaprost-13-en-1-ol, (95) (15α,13E)-9-oxo-15-hydroxy-16-(3-methylphenyl)-5-(5-hydroxymethylthiazol-2-yl)-1,2,3,4,17,18,19,20-octanor-5-thia-8-azaprost-13-ene, (96) (15α,13E)-9-oxo-15-hydroxy-16-(3-chlorophenyl)-17,18,19,20-tetranor-5-thia-8-aza-10-oxaprost-13-en-1-ol, (97) (15α,13E)-9-oxo-15-hydroxy-16-(4-fluorophenyl)-17,18,19,20-tetranor-5-thia-8-aza-10-oxaprost-13-en-1-ol, (98) (15α,13E)-9-oxo-15-hydroxy-16-(4-fluorophenyl)-3,7-(2,5-interthienylene)-4,5,6,17,18,19,20-heptanor-8-azaprost-13-en-1-ol, (99) (15α,13E)-9-oxo-15-hydroxy-16-(3-ethyl-4-fluorophenyl)-17,18,19,20-tetranor-5-thia-8-azaprost-13-en-1-ol, (100) (15α,13E)-9-oxo-15-hydroxy-16-(5-methylfuran-2-yl)-17,18,19,20-tetranor-5-thia-8-azaprost-13-en-1-ol, (101) (15α,13E)-9-oxo-15-hydroxy-16-(5-ethylfuran-2-yl)-17,18,19,20-tetranor-5-thia-8-azaprost-13-en-1-ol, (102) (15α)-9-oxo-15-hydroxy-16-(3-methoxymethylphenyl)-17,18,19,20-tetranor-8-azaprostanoic acid ethyl ester, (103) (15α)-9-oxo-15-hydroxy-16-(3-methoxymethylphenyl)-17,18,19,20-tetranor-8-azaprostanoic acid, (104) (15α)-9-oxo-15-hydroxy-16-(3-methylphenyl)-17,18,19,20-tetranor-5-thia-8-azaprostanoic acid, (105) (15α)-9-oxo-15-hydroxy-16-(3-trifluoromethylphenyl)-17,18,19,20-tetranor-5-thia-8-azaprostanoic acid, (106) (15α,13E)-9-oxo-15-hydroxy-16-(3-methoxymethylphenyl)-17,18,19,20-tetranor-8-azaprost-13-enoic acid N-mesylarmide, (107) (15α,13E)-9-oxo-15-hydroxy-16-(3-methoxymethylphenyl)-17,18,19,20-tetranor-8-azaprost-13-enoic acid N-phenylsulfonylamide, (108) (15α,13E)-9-oxo-15-hydroxy-16-(3-methoxymethylphenyl)-17,18,19,20-tetranor-8-azaprost-13-enoic acid N-benzylsulfonylamide, (109) (15α,13E)-9-oxo-15-hydroxy-16-(4-fluorophenyl)-1,5-(2,5-interthienylene)-2,3,4,17,18,19,20-heptanor-8-azaprost-13-enoic acid N-benzylsulfonylamide, (110) (15α,13E)-9-oxo-15-hydroxy-16-(4-fluorophenyl)-5-(5-benzylsulfonylcarbamoylthiazol-2-yl)-1,2,3,4,17,18,19,20-octanor-5-thia-8-azaprost-13-ene, (111) (15α,13E)-9-thioxo-15-hydroxy-16-(3-methylphenyl)-17,18,19,20-tetranor-5-thia-8-azaprost-13-enoic acid butyl ester, (112) (15α,13E)-9-thioxo-15-hydroxy-16-(3-methylphenyl)-17,18,19,20-tetranor-5-thia-8-azaprost-13-enoic acid, (113) (15α,13E)-9-thioxo-15-hydroxy-16-(3-methoxymethylphenyl)-17,18,19,20-tetranor-8-azaprost-13-enoic acid, (114) (15α,13E)-9-oxo-15-hydroxy-16-(3-methylphenyl)-17,18,19,20-tetranor-5-thia-8-azaprost-13-en-1-yl t-butoxycarbonylglycylglycinate, (115) (15α,13E)-9-oxo-15-hydroxy-16-(3-methylphenyl)-17,18,19,20-tetranor-5-thia-8-azaprost-13-en-1-yl glycylglycinate monohydrochloride, (116) (15α,13E)-9-oxo-15-hydroxy-16-(3-methylphenyl)-17,18,19,20-tetranor-5-thia-8-azaprost-13-en-1-yl glycinate methanesulfonic acid salt, (117) (15α,13E)-9-oxo-15-hydroxy-16-(3-methylphenyl)-17,18,19,20-tetranor-5-thia-8-azaprost-13-en-1-yl tryptophanate bis-trifluoroacetic acid salt, (118) (15α,13E)-9-oxo-15-hydroxy-16-(3-methylphenyl)-17,18,19,20-tetranor-5-thia-8-azaprost-13-en-1-yl tyrosinate trifluoroacetic acid salt, (119) (15α,13E)-9-oxo-15-hydroxy-16-(3-chlorophenyl)-17,18,19,20-tetranor-5-thia-8-azaprost-13-enoic acid isopropyloxycarbonylmethyl ester, (120) (15α,13E)-9-oxo-15-hydroxy-16-(3-chlorophenyl)-17,18,19,20-tetranor-5-thia-8-azaprost-13-enoic acid dimethylaminocarbonylmethyl ester, (121) (15α,13E)-9-oxo-15-hydroxy-16-(4-fluorophenyl)-17,18,19,20-tetranor-5-thia-8-azaprost-13-enoic acid ethyl ester, (122) (15α,13E)-9-oxo-15-hydroxy-16-(4-fluorophenyl)-17,18,19,20-tetranor-5-thia-8-azaprost-13-enoic acid butyl ester, (123) (15α,13E)-9-oxo-15-hydroxy-16-(3-methylphenyl)-1,5-(2,5-interthienylene)-2,3,4,17,18,19,20-heptanor-8-azaprost-13-en-1-al, (124) (15α,13E)-9-oxo-15-hydroxy-16-(3-chlorophenyl)-17,18,19,20-tetranor-5-thia-8-azaprost-13-en-1-al, (125) (15α,13E)-9-oxo-15-hydroxy-16-(3-aminophenyl)-17,18,19,20-tetranor-5-thia-8-azaprost-13-enoic acid, (126) (15α,13E)-1-benzoyloxy-9-oxo-15-hydroxy-16-phenyl-17,18,19,20-tetranor-8-azaprost-13-ene, (127) (15α,13E)-1-butanoyloxy-9-oxo-15-hydroxy-16-phenyl-17,18,19,20-tetranor-8-azaprost-13-ene, (128) (15α,13E)-1-(2-aminoacetyloxy)-9-oxo-15-hydroxy-16-phenyl-17,18,19,20-tetranor-8-azaprost-13-ene trifluoromethanesulfonic acid salt, (129) (15α,13E)-9-oxo-15-hydroxy-16-(4-fluorophenyl)-17,18,19,20-tetranor-5-thia-8-azaprost-13-enoic acid 2-pentanoyloxyethyl ester, (130) (15α,13E)-9-oxo-15-hydroxy-16-phenyl-17,18,19,20-tetranor-8-azaprost-13-enoic acid 4-phenylbenzyl ester, (131) (15α,13E)-9-oxo-15-hydroxy-16-phenyl-17,18,19,20-tetranor-8-azaprost-13-enoic acid 2-dimethylaminoethyl ester hydrochloride, (132) (15α,13E)-9-oxo-15-hydroxy-16-(4-fluorophenyl)-17,18,19,20-tetranor-5-thia-8-azaprost-13-enoic acid 2-hexanoyloxyethyl ester, (133) (15α,13E)-9-oxo-15-hydroxy-16-(4-fluorophenyl)-17,18,19,20-tetranor-5-thia-8-azaprost-13-enoic acid 2-heptanoyloxyethyl ester, (134) (15α,13E)-9-oxo-15-hydroxy-16-(4-fluorophenyl)-17,18,19,20-tetranor-5-thia-8-azaprost-13-enoic acid 2-octanoyloxyethyl ester, (135) (15α,13E)-9-oxo-15-hydroxy-16-(4-fluorophenyl)-17,18,19,20-tetranor-5-thia-8-azaprost-13-enoic acid N-heptanoyl-N-methylcarbamoylmethyl ester, (136) (15α,13E)-9-oxo-15-hydroxy-16-(4-fluorophenyl)-17,18,19,20-tetranor-5-thia-8-azaprost-13-enoic acid (4-hexylpiperazin-1-yl)carbonylmethyl ester, (137) (15α,13E)-9-oxo-15-hydroxy-16-(4-fluorophenyl)-17,18,19,20-tetranor-5-thia-8-azaprost-13-enoic acid N-ethyl-N-(2-diethylaminoethyl)carbamoylmethyl ester, (138) (15α,13E)-9-oxo-15-hydroxy-16-(4-fluorophenyl)-17,18,19,20-tetranor-5-thia-8-azaprost-13-enoic acid 2-(2-(dipropylamino)acetyloxy)ethyl ester, (139) (15α,13E)-9-oxo-15-hydroxy-16-(4-fluorophenyl)-17,18,19,20-tetranor-5-thia-8-azaprost-13-enoic acid 2-(2-(diethylamino)acetyloxy)ethyl ester, (140) (15α,13E)-9-oxo-15-hydroxy-16-(4-fluorophenyl)-17,18,19,20-tetranor-5-thia-8-azaprost-13-enoic acid nonanoyloxymethyl ester, (141) (15α,13E)-9-oxo-15-hydroxy-16-(4-aminophenyl)-17,18,19,20-tetranor-5-thia-8-azaprost-13-enoic acid, (142) (15α,13E)-1,5-(2,5-interthienylene)-9-oxo-15-hydroxy-16-(4-fluorophenyl)-2,3,4,17,18,19,20-heptanor-5-thia-8-azaprost-13-enoic acid, (143) (15α,13E)-1,5-(2,5-interthienylene)-9-oxo-15-hydroxy-16-(3-chloro-4-fluorophenyl)-2,3,4,17,18,19,20-heptanor-5-thia-8-azaprost-13-enoic acid, (144) (15α,13E)-1,5-(2,5-interthienylene)-9-oxo-15-hydroxy-16-(4-fluoro-3-trifluoromethylphenyl)-2,3,4,17,18,19,20-heptanor-5-thia-8-azaprost-13-enoic acid, (145) (15α,13E)-9-oxo-15-hydroxy-16-(4-fluorophenyl)-17,18,19,20-tetranor-5-thia-8-azaprost-13-enoic acid ethyl ester, (146) (15α,13E)-9-oxo-15-hydroxy-16-(4-fluorophenyl)-17,18,19,20-tetranor-5-thia-8-azaprost-13-enoic acid, (147) (15α,13E)-9-oxo-15-hydroxy-16-(3-(benzofuran-2-yl)phenyl)-17,18,19,20-tetranor-5-thia-8-azaprost-13-enoic acid, (148) (15α)-9-oxo-15-hydroxy-16-(3-methylphenyl)-5-(4-carboxythiazol-2-yl)-1,2,3,4,17,18,19,20-octanor-5-thia-8-azaprostane, (149) (15α,13E)-1,6-(1,4-interphenylene)-9-oxo-15-hydroxy-16-(3-methylphenyl)-2,3,4,5,17,18,19,20-octanor-8-azaprost-13-enoic acid, (150) (15α,13E)-7-(6-carboxyindol-3-yl)-9-oxo-15-hydroxy-16-(3-methylphenyl)-1,2,3,4,5,6,17,18,19,20-decanor-8-azaprost-13-ene, (151) (15α,13E)-9-oxo-15-hydroxy-16-(3-methylphenyl)-5-(4-carboxythiazol-2-yl)-1,2,3,4,17,18,19,20-octanor-8-azaprost-13-ene, (152) (15α,13E)-9-oxo-15-hydroxy-16-(3-methylphenyl)-5-(4-carboxyoxazol-2-yl)-1,2,3,4,17,18,19,20-octanor-8-azaprost-13-ene, (153) (15α,13E)-1,7-(2,5-interthienylene)-9-oxo-15-hydroxy-16-(3-methylphenyl)-2,3,4,5,6,17,18,19,20-nonanor-8-azaprost-13-enoic acid, (154) (15α,13E)-1,6-(1,4-interphenylene)-9-oxo-15-hydroxy-16-(3-(benzofuran-2-yl)phenyl)-2,3,4,5,17,18,19,20-octanor-8-azaprost-13-enoic acid, (155) (15α,13E)-1,5-(2,5-interthienylene)-9-oxo-15-hydroxy-16-(3-(benzofuran-2-yl)phenyl)-2,3,4,17,18,19,20-heptanor-8-azaprost-13-enoic acid, (156) (15α,13E)-3,3-Ethano-9-oxo-15-hydroxy-16-(4-fluorophenyl)-17,18,19,20-tetranor-5-thia-8-azaprost-13-enoic acid, (157) (15α,13E)-1,5-(1,4-interphenylene)-9-oxo-15-hydroxy-16-(4-fluorophenyl)-2,3,4,17,18,19,20-heptanor-5-thia-8-azaprost-13-enoic acid, (158) (15α,13E)-1,5-(1,3-interphenylene)-9-oxo-15-hydroxy-16-(4-fluorophenyl)-2,3,4,17,18,19,20-heptanor-5-thia-8-azaprost-13-enoic acid, (159) (15α,13E)-9-oxo-15-hydroxy-16-(3-(4-fluoromethylbenzyloxy)phenyl)-17,18,19,20-tetranor-5-thia-8-azaprost-13-enoic acid, (160) (15α,13E)-9-oxo-15-hydroxy-16-(3-(pyridin-3-ylmethoxy)phenyl)-17,18,19,20-tetranor-5-thia-8-azaprost-13-enoic acid, (161) (15α,13E)-9-oxo-15-hydroxy-16-cyclopropyl-17,18,19,20-tetranor-5-thia-8-azaprost-13-enoic acid, (162) (15α,13E)-9-oxo-15-hydroxy-16-phenyl-5-(4-carboxythiazol-2-yl)-1,2,3,4,17,18,19,20-octanor-5-thia-8-azaprost-13-ene, (163) (15α,13E)-9-oxo-15-hydroxy-16-(3-methylphenyl)-5-(4-carboxythiazol-2-yl-1,2,3,4,17,18,19,20-octanor-5-thia-8-azaprost-13-ene, (164) (15α,13E)-9-oxo-15-hydroxy-16-(3-(pyridin-2-ylmethoxy)phenyl)-17,18,19,20-tetranor-5-thia-8-azaprost-13-enoic acid, (165) (15α,13E)-9-oxo-15-hydroxy-16-(3-(pyridin-4-ylmethoxy)phenyl)-17,18,19,20-tetranor-5-thia-8-azaprost-13-enoic acid, (166) (15α,13E)-9-oxo-15-hydroxy-16-(3-(pyridin-2-yl)phenyl)-17,18,19,20-tetranor-5-thia-8-azaprost-13-enoic acid, (167) (15α,13E)-9-oxo-15-hydroxy-16-cyclopentyl-5-(4-carboxythiazol-2-yl)-1,2,3,4,17,18,19,20-octanor-5-thia-8-azaprost-13-ene, (168) (15α,13E)-9-oxo-15-hydroxy-16-(3-(2,2,2-trifluoroethoxymethyl)phenyl)-5-(4-carboxythiazol-2-yl)-1,2,3,4,17,18,19,20-octanor-5-thia-8-azaprost-13-ene, (169) (15α,13E)-9-oxo-15-hydroxy-16-(3-(benzofuran-2-yl)phenyl)-5-(4-carboxythiazol-2-yl)-1,2,3,4,17,18,19,20-octanor-5-thia-8-azaprost-13-ene, (170) (15α,13E)-9-oxo-15-hydroxy-16-(5-methylfuran-2-yl)-5-(4-carboxythiazol-2-yl)-1,2,3,4,17,18,19,20-octanor-5-thia-8-azaprost-13-ene, (171) (15α,13E)-9-oxo-15-hydroxy-16-(4-fluorophenyl)-5-(6-carboxypyridin-2-yl)-1,2,3,4,17,18,19,20-octanor-5-thia-8-azaprost-13-ene, (172) (15α,13E)-9-oxo-15-hydroxy-16-(4-fluorophenyl)-17,18,19,20-tetranor-5-thia-8-azaprost-13-enoic acid dibutylcarbamoylmethyl ester, (173) (15α,13E)-9-oxo-15-hydroxy-16-(4-fluorophenyl)-17,18,19,20-tetranor-5-thia-8-azaprost-13-enoic acid 2-(2,2-diethylpentanoyloxy)ethyl ester, (174) (15α,13E)-9-oxo-15-hydroxy-16-(4-fluorophenyl)-17,18,19,20-tetranor-5-thia-8-azaprost-13-enoic acid 2-(adamantan-1-ylcarbonyloxy)ethyl ester, (175) (15α,13E)-9-oxo-15-hydroxy-16-(4-fluorophenyl)-17,18,19,20-tetranor-5-thia-8-azaprost-13-enoic acid 2-(1-ethyl-1-methylbutanoyloxy)ethyl ester, (176) (15α,13E)-9-oxo-15-hydroxy-16-(3-methylphenyl)-5-(4-(2-(1-ethyl-1-methylbutanoyloxy)ethoxycarbonyl)thiazol-2-yl)-1,2,3,4,17,18,19,20-octanor-5-thia-8-azaprost-13-ene, (177) (15α,13E)-9-oxo-15-hydroxy-16-(3,4-dihydroxyphenyl)-17,18,19,20-tetranor-5-thia-8-azaprost-13-enoic acid, (178) (15α,13E)-1,6-(1,4-interphenylene)-9-oxo-15-hydroxy-16-(3-(2-methylphenyl)phenyl)-2,3,4,5,17,18,19,20-octanor-8-azaprost-13-enoic acid, (179) (15α,13E)-1,6-(1,4-interphenylene)-9-oxo-15-hydroxy-16-(3-(3-methylphenyl)phenyl)-2,3,4,5,17,18,19,20-octanor-8-azaprost-13-enoic acid, (180) (15α,13E)-1,6-(1,4-interphenylene)-9-oxo-15-hydroxy-16-(3-(4-methylphenyl)phenyl)-2,3,4,5,17,18,19,20-octanor-8-azaprost-13-enoic acid, (181) (15α,13E)-1,6-(1,4-interphenylene)-9-oxo-15-hydroxy-16-(3-(4-trifluoromethylphenyl)phenyl)-2,3,4,5,17,18,19,20-octanor-8-azaprost-13-enoic acid, (182) (15α,13E)-1,6-(1,4-interphenylene)-9-oxo-15-hydroxy-16-(3-(3,5-ditrifluoromethylphenyl)phenyl)-2,3,4,5,17,18,19,20-octanor-8-azaprost-13-enoic acid, (183) (15α,13E)-1,6-(1,4-interphenylene)-9-oxo-15-hydroxy-16-(3-(4-t-butylphenyl)phenyl)-2,3,4,5,17,18,19,20-octanor-8-azaprost-13-enoic acid, (184) (15α)-9-oxo-15-hydroxy-16-(3-phenylphenyl)-5-(4-carboxythiazol-2-yl)-1,2,3,4,17,18,19,20-octanor-5-thia-8-azaprostane, (185) (15α)-9-oxo-15-hydroxy-16-(3-(4-methylphenyl)phenyl)-5-(4-carboxythiazol-2-yl)-1,2,3,4,17,18,19,20-octanor-5-thia-8-azaprostane, (186) (15α)-9-oxo-15-hydroxy-16-(3-(4-chlorophenyl)phenyl)-5-(4-carboxythiazol-2-yl)-1,2,3,4,17,18,19,20-octanor-5-thia-8-azaprostane, (187) (15α)-9-oxo-15-hydroxy-16-(3-(4-methoxyphenyl)phenyl)-5-(4-carboxythiazol-2-yl)-1,2,3,4,17,18,19,20-octanor-5-thia-8-azaprostane, (188) (15α,13E)-9-oxo-15-hydroxy-16-(3-(naphthalen-2-yl)phenyl)-17,18,19,20-tetranor-5-thia-8-azaprost-13-enoic acid, (189) (15α,13E)-9-oxo-15-hydroxy-16-(3-(benzoxazol-2-yl)phenyl)-17,18,19,20-tetranor-5-thia-8-azaprost-13-enoic acid, (190) (15α,13E)-9-oxo-15-hydroxy-16-(3-(benzothiazol-2-yl)phenyl)-17,18,19,20-tetranor-5-thia-8-azaprost-13-enoic acid, (191) (15α)-9-oxo-15-hydroxy-16-(3-(naphthalen-2-yl)phenyl)-5-(4-carboxythiazol-2-yl)-1,2,3,4,17,18,19,20-octanor-5-thia-8-azaprostane, (192) (15α)-9-oxo-15-hydroxy-16-(3-(benzoxazol-2-yl)phenyl)-5-(4-carboxythiazol-2-yl)-1,2,3,4,17,18,19,20-octanor-5-thia-8-azaprostane, (193) (15α)-9-oxo-15-hydroxy-16-(3-(benzothiazol-2-yl)phenyl)-5-(4-carboxythiazol-2-yl)-1,2,3,4,17,18,19,20-octanor-5-thia-8-azaprostane, (194) (15α,13E)-9-oxo-15-hydroxy-16-(3-(isoindolin-2-yl)phenyl)-17,18,19,20-tetranor-5-thia-8-azaprost-13-enoic acid, (195) (15α,13E)-9-oxo-15-hydroxy-16-(3-(indol-5-yl)phenyl)-17,18,19,20-tetranor-5-thia-8-azaprost-13-enoic acid, (196) (15α)-9-oxo-15-hydroxy-16-(3-(isoindolin-2-yl)phenyl)-5-(4-carboxythiazol-2-yl)-1,2,3,4,17,18,19,20-octanor-5-thia-8-azaprostane, and (197) (15α)-9-oxo-15-hydroxy-16-(3-(indol-5-yl)phenyl)-5-(4-carboxythiazol-2-yl)-1,2,3,4,17,18,19,20-octanor-5-thia-8-azaprostane, or a non-toxic salt thereof, or a cyclodextrin clathrate thereof |
<SOH> BACKGROUND ART <EOH>Prostaglandin E 2 (abbreviated as PGE 2 ) has been known as a metabolite in the arachidonate cascade. It has been known that PGE 2 possesses cyto-protective activity, uterine contractive activity, a pain-inducing effect, a promoting effect on digestive peristalsis, an awakening effect, a suppressive effect on gastric acid secretion, hypotensive activity and diuretic activity and so on. A recent study has proved existence of various PGE subtype receptors possessing a different physical role from each other. At present, four receptor subtypes are known and they are called EP 1 , EP 2 , EP 3 , and EP 4 (Negishi M., et al., J. Lipid Mediators Cell Signaling, 12, 379-391 (1995)). It is thought that EP 4 subtype receptor relates to inhibition of producing TNF-α and acceleration of producing IL-10. Therefore, the compounds which can bind on EP 4 subtype receptor are expected to be useful for the prevention and/or treatment of immunological diseases (autoimmune diseases such as amyotrophic lateral sclerosis (ALS), multiple sclerosis, Sjoegren's syndrome, chronic rheumarthrosis and systemic lupus erythematosus etc., and rejection after organ transplantation etc.), asthma, neuronal cell death, arthritis, lung failure, pulmonary fibrosis, pulmonary emphysema, bronchitis, chronic obstructive pulmonary disease, liver damage, acute hepatitis, nephritis (acute nephritis, chronic nephritis), renal insufficiency, hypertension, myocardiac ischemia, systemic inflammatory response syndrome, sepsis, hemophagous syndrome, macrophage activation syndrome, Still's disease, Kawasaki disease, burn, systemic granulomatosis, ulcerative colitis, Crohn's disease, hypercytokinemia at dialysis, multiple organ failure, and shock etc. It is also thought that EP 4 subtype receptor relates to protecting of mucosa. Therefore, the compounds which can bind on EP 4 subtype receptor are expected to be useful for the prevention and/or treatment of ulcer of gastrointestinal tract such as gastric ulcer and duodenal ulcer etc. and stomatitis. It is also thought that EP 4 subtype receptor relates to hair growth function. Therefore, the compounds which can bind on EP 4 subtype receptor are expected to be useful for the prevention and/or treatment of hair-disadvantaged and alopecia. Furthermore, it is also thought that EP 4 subtype receptor relates to maturation of cervix. Therefore, the compounds which can bind on EP 4 subtype receptor are expected to be useful for the promoter of maturation of cervix. Furthermore, the compounds which can bind on EP 4 subtype receptor also have an action of accelerating bone formation, so it is expected to be useful for the prevention and/or treatment of diseases associated with decrease in bone mass, for example, 1) primary osteoporosis (e.g., primary osteoporosis followed by aging, postmenopausal primary osteoporosis, primary osteoporosis followed by ovariectomy etc.), 2) secondary osteoporosis (e.g., glucocorticoid-induced osteoporosis, hyperthyroidism-induced osteoporosis, immobilization-induced osteoporosis, heparin-induced osteoporosis, immunosuppressive-induced osteoporosis, osteoporosis due to renal failure, inflammatory osteoporosis, osteoporosis followed by Cushing's syndrome, rheumatoid osteoporosis etc.), 3) bone diseases such as bone metastasis of cancer, hypercalcemia, Paget's disease, bone loss (alveolar bone loss, mandibular bone loss, childhood idiopathic bone loss etc.), osteonecrosis etc. Besides treatment of the above diseases, the present invention also includes a pharmaceutical composition for accelerating bone formation after bone operation (e.g., bone formation after fractures, bone formation after bone grafting, bone formation after operation of artificial joint, bone formation after spinal fusion and bone formation after the other operation for bone regeneration etc.), or promoting treatment thereof, or alternative treatment for bone grafting. It is also thought that EP 4 subtype receptor relates to induction of physiological sleeping and suppression of blood platelet aggregation, so such compounds are expected to be useful for the prevention and/or treatment of sleep disorder and thrombosis The compound which can bind an EP 4 receptor selectively do not have inducing pain which may be caused by EP 1 , uterine relaxation which may be caused by EP 2 and uterine contraction which may be caused by EP 3 , so they are thought to be agents having no effect on the above actions. In the specification of U.S. Pat. No. 4,177,346, it is disclosed that the compound of formula (A) (wherein Q A is selected from the group consisting of —COOR 3A , tetrazol-5-yl and —CONH 4A ; A A is single bond or cis-double bond; B A is single bond or trans-double bond; U A is R 2A is selected from the group consisting of α-thienyl, phenyl, phenoxy, mono-substituted phenyl and mono-substituted phenoxy, and the substituent is selected from the group consisting of chloro, fluoro, phenyl, methoxy, trifluoromethyl and C1-3 alkyl; R 3A is selected from the group consisting of hydrogen, C1-5 alkyl, phenyl and p-biphenyl; R 4A is selected from the group consisting of —COR and —SO 2 R 5A ; R 5A is selected from the group consisting of phenyl and C1-5 alkyl), and a C5 epimer thereof, the salt of alkali metal and alkaline earth metals and ammounium salt of the compound which have carboxylate or tetrazol-5-yl. And in the specification of JP-A-2001-181210, it is disclosed that the selective EP 4 receptor agonist of formula (A) is useful for the treatment of osteoporosis. And in the specification of United Kingdom Patent No. 1,553,595, the pyrrolidone derivatives of formula (B) (wherein R 1B is a straight- or branched-chain, saturated or unsaturated, aliphatic hydrocarbon radical having up to 10 carbon atoms, or a cycloaliphatic hydrocarbon radical having 3 to 7 carbon atoms, which radicals may be unsubstituted or substituted by one or more of the following: e) a cycloalkyl group of 3 to 7 carbon atoms, f) a phenyl, thienyl or furyl group which may carry one or two substituents selected from optionally halogenated alkyl group of 1 to 3 carbon atoms, halogen atoms and alkoxy group of 1 to 4 carbon atoms, R 2 B is a straight- or branched-chain, saturated or unsaturated, aliphatic or cycloaliphatic hydrocarbon radical having up to 6 carbon atoms, or an araliphatic hydrocarbon radical having 7 or 8 carbon atoms, and nB is the integer 2,3 or 4, the definitions of the symbols are excerpt), and a corresponding acid, a salt, especially the physiologically acceptable e.g. metal or amine, a salt thereof is disclosed. In the specifications of United Kingdom Patent No.1,569,982, and United Kingdom Patent No.1,583,163, the compound close to the compound of formula (B) is disclosed. In the specification of U.S. Pat. No. 4,320,136, the compound of formula (C) (wherein A C is CH═CH (cis or trans), C≡C or CH 2 CH 2 ; R C is H, C1-C12 n-alkyl, branched alkyl or cycloalkyl etc.; R 1C is H, CH 3 or C 2 H 5 ; R 2C is phenyl or mono- or di-substituted phenyl, the substituent is selected from is selected from the group consisting of, F, Cl, CH 3 , OCH 3 , NO 2 or CF 3 ; when R 2C is phenyl or substituted phenyl,nC is 0-2, the definitions of the symbols are excerpt) is disclosed. In the specification of WO00/03980, it is disclosed that the compound of formula (I-1) is useful as EP 4 receptor binding agent. In the specification of WO01/37877, it is disclosed that the EP 4 receptor agonist of formula (I-1) is useful for treatment of diseases associated with decrease in bone mass. It is disclosed that the EP 4 receptor agonist of formulae (A) and (I-1) is useful for treatment of diseases associated with bone, there is a general description about topical administration. Therefore it is unproved that topical administration of the EP 4 receptor agonist is useful for treatment of diseases associated with bone experimentally. Four PGE 2 subtype receptors possessing a different physical role from each other exist, and each subtype is called EP 1 , EP 2 , EP 3 , and EP 4 and has a different pharmacological action. So the compounds which can bind on EP 4 subtype receptor selectively and binds on the other subtype receptors weakly may be the drug with less side effect, because they show no any other activities. Therefore it is in need of finding the drug like this. On the other hand, a lot of compounds which have the EP 4 agonistic activity are found until now. However, all of them have a prostanoid skeleton, so it is thought that they influence circulatory system (e.g. blood pressure lowered or increasing of the heart rate), or cause side-effect such as diarrhea when they are administered by systemic administration such as oral administration or intravenous infusion. Therefore, they have significant problem that there is a limitation of the dose that can be administered safely. As a disease associated with EP 4 agonist, a lot of studies of diseases associated with decrease in bone mass have been done. It is also thought that systemic administration causes side-effects, so development of the drug with less side effects is expected. Finding a long-acting pharmaceutical which can be administrated topically is also expected. |
Etching method and apparatus |
An etching apparatus comprises a workpiece holder (21) for holding a workpiece (X), a plasma generator (10, 20) for generating a plasma (30) in a vacuum chamber (3), an orifice electrode (4) disposed between the workpiece holder (21) and the plasma generator (10, 20), and a grid electrode (5) disposed upstream of the orifice electrode (4) in the vacuum chamber (3). The orifice electrode (4) has orifices (4a) defined therein. The etching apparatus further comprises a voltage applying unit (25, 26) for applying a voltage between the orifice electrode (4) and the grid electrode (5) to accelerate ions from the plasma (30) generated by the plasma generator (10, 20) and to pass the extracted ions through the orifices (4a) in the orifice electrode (4), for generating a collimated neutral particle beam having an energy ranging from 10 eV to 50 eV. |
1. An etching method comprising.: generating a collimated neutral particle beam having an energy ranging from 10 eV to 50 eV from a gas; and applying said neutral particle beam to a surface of a workpiece comprising Si and SiO2, which is masked by a resist having a pattern smaller than 0.1 μm, to etch the surface of the workpiece. 2. An etching method according to claim 1, wherein said generating comprises neutralizing negative ions to generate said neutral particle beam. 3. An etching method according to claim 1, wherein said neutral particle beam includes fluorine atoms or chlorine atoms. 4. An etching method according to claim 1, wherein said gas does not include an additive gas for forming a sidewall passivation layer. 5. An etching method according to claim 1, wherein said collimated neutral particle beam is generated through an orifice plate having orifices defined therein. 6. An etching method according to claim 5, wherein a distance between said orifice plate and said workpiece is set to be in the range from 2 mm to 50 mm. 7. An etching method according to claim 1, further comprising: separating a beam generating chamber for generating said neutral particle beam from a process chamber in which said workpiece is disposed; and setting the pressure of said process chamber to be lower than the pressure of said beam generating chamber. 8. An etching method according to claim 7, wherein the pressure of said process chamber is set to be not more than 0.1 Pa. 9. An etching apparatus comprising: a workpiece holder for holding a workpiece comprising Si and SiO2, which is masked by a resist having a pattern smaller than 0.1 μm; a plasma generator for generating a plasma in a vacuum chamber; a first electrode disposed between said workpiece holder and said plasma generator, said first electrode having orifices defined therein; a second electrode disposed upstream of said first electrode in said vacuum chamber; and a voltage applying unit for applying a voltage between said first electrode and said second electrode to accelerate ions from the plasma generated by said plasma generator and to pass the extracted ions through said orifices in said first electrode, for generating a collimated neutral particle beam having an energy ranging from 10 eV to 50 eV. 10. An etching apparatus according to claim 9, wherein a distance between said first electrode and said workpiece is set to be in the range from 2 mm to 50 mm. 11. An etching apparatus according to claim 9, wherein the pressure of said process chamber is set to be not more than 0.1 Pa. |
<SOH> BACKGROUND ART <EOH>In recent years, semiconductor integrated circuits, micromachines, and the like have been processed in highly fine patterns. Therefore, a highly accurate process and a process to form a high aspect ratio pattern are required. In the fields of such processing, there has widely been used a plasma etching apparatus. As a plasma etching apparatus, there has been known a reactive ion etching (RIE) apparatus which generates various kinds of particles including positive ions and radicals. The positive ions or the radicals are applied to a workpiece to etch the workpiece. In an etching process utilizing such an RIE apparatus, there have been problems that high accuracy and high selectivity cannot be achieved simultaneously and etching profile irregularities are caused by charge build-up. The selectivity is a ratio of the etched depth in a workpiece to the etched depth in a mask or an underlying material. Specifically, when a workpiece is etched by x μm and a mask protecting the workpiece is etched by y μm, the selectivity s is expressed by s=x/y. In the case of a higher selectivity, the mask is less damaged and the workpiece can be etched to form a pattern having a high aspect ratio. In order to enhance the selectivity, a combination of gases which can deposit on the mask or the underlying material but can etch the workpiece has been used in the conventional etching process. Further, radicals deposit onto the surface of the workpiece to form a sidewall passivation layer. If the sidewall passivation layer is excessively formed on the surface of the workpiece, then the surface of the workpiece is processed into a tapered shape, so that dimensional accuracy is lowered in the etching process. When a combination of Cl 2 gas and O 2 gas is used in the conventional etching process, the selectivity of Si/SiO 2 is at most about 100. Thus, this combination of gases can achieve a higher selectivity than other combinations of gases. However, devices having a pattern smaller than 0.1 μm have been required to be processed with high accuracy and a selectivity higher than 300. Particularly, it will be the future task to simultaneously achieve a higher selectivity over an underlying layer of a gate oxide film and no residue at step portions for isolation. The etching profile irregularities are caused by the difference between the behavior of electrons and that of positive ions. Specifically, the etching profile irregularities, i.e., notches, are produced at sidewalls defining stripes of a fine pattern. When the etching process is performed with a low energy ion beam, electrons are decelerated within the fine pattern by a negative self-bias potential on the substrate, and trapped near a resist. On the other hand, ions are accelerated and delivered to the underlying layer of the oxide film to develop positive charge build-up on the substrate. However, at the outside of the fine pattern, charge build-up doesn't occur because the same amounts of electrons and ions are delivered thereto. Thus, a potential difference is produced between the inside and outside of the fine pattern, so that the trajectories of the ions are curved to produce the notches. |
<SOH> BRIEF DESCRIPTION OF DRAWINGS <EOH>FIG. 1 is a vertical cross-sectional view explanatory of a distance between an orifice plate and a workpiece in an etching apparatus according to the present invention; FIG. 2 is a schematic view showing a whole arrangement of an etching apparatus according to an embodiment of the present invention; FIG. 3A is a perspective view showing an orifice electrode in the etching apparatus shown in FIG. 2 ; FIG. 3B is a vertical cross-sectional view partially showing the orifice electrode shown in FIG. 3A ; and FIG. 4 is a graph showing an energy distribution of a neutral particle beam according to an example of the present invention. detailed-description description="Detailed Description" end="lead"? |
Bldc motor for washing machine |
The present invention prevents peak noise caused by a resonance frequency, and reduces an overall noise of the system by binding core teeth of a stator of a BLDC motor with a vibration prevention member. To do this, the present invention provides a brushless DC motor for a washing machine including a stator including a frame, a core in the frame, and a plurality of core teeth each extended outward from the frame and having a coil wound thereon, a rotor mounted to surround the core teeth, and rotatable when power is provided to the stator, and a vibration prevention member connected between the core teeth to bind the core teeth to each other, for prevention of vibration of the core teeth. |
1. A brushless DC motor for a washing machine comprising: a stator including a frame, a core in the frame, and a plurality of core teeth each extended outward from the frame and having a coil wound thereon; a rotor mounted to surround the core teeth, and rotatable when power is provided to the stator; and a vibration prevention member connected between the core teeth to bind the core teeth to each other, for prevention of vibration of the core teeth. 2. The brushless DC motor as claimed in claim 1, wherein the vibration prevention member binds outer ends of the core teeth. 3. The brushless DC motor as claimed in claim 1, wherein the vibration prevention member encloses each of outer ends of the core teeth at least once. 4. The brushless DC motor as claimed in claim 1, wherein the vibration prevention member binds outer ends of the core teeth in succession. 5. The brushless DC motor as claimed in claim 1, wherein the vibration prevention member includes one member for binding all the core teeth continuously. 6. The brushless DC motor as claimed in claim 1, wherein the vibration prevention member is a lacing thread for binding the core teeth. 7. The brushless DC motor as claimed in claim 6, wherein the lacing thread binds outer ends of the core teeth. 8. The brushless DC motor as claimed in claim 6, wherein the lacing thread winds each of outer ends of the core teeth at least once. 9. The brushless DC motor as claimed in claim 6, wherein the lacing thread binds the core teeth continuously, without disconnection. 10. The brushless DC motor as claimed in claim 6, wherein the lacing thread is formed of polyester. 11. The brushless DC motor as claimed in claim 6, wherein the vibration prevention member is a tape with a width for binding the core teeth. 12. The brushless DC motor as claimed in claim 6, wherein the vibration prevention member is formed of a non-magnetic material. 13. The brushless DC motor as claimed in claim 12, wherein the vibration prevention member is formed of plastic. 14. The brushless DC motor as claimed in claim 13, wherein the vibration prevention member is formed of polyester. |
<SOH> BACKGROUND ART <EOH>In general, the washing machine progresses washing, rinsing, and spinning cycles for removing dirt from laundry by using actions of detergent and water. In the washing machines, there are circulating type (pulsating type), agitating type (washing pole type), and drum type washing machines. Each of above types of washing machines requires a motor for driving the washing machine, most of which is the BLDC motor. The BLDC motor, provided with a stator having a coil wound thereon and a rotor around the stator, for generating a rotating power when power is provided to the stator. A related art BLDC motor will be described based on the drum type washing machine, briefly. FIG. 1 illustrates a section of a related art drum type washing machine, and FIG. 2 illustrates an enlarged view of ‘A’ part in FIG. 1 . Referring to FIGS. 1 and 2 , there are a tub 3 inside of a cabinet for holding washing water, and a drum 9 inside of the tub 3 for introduction of laundry. There is a drum shaft 7 for transmission of a driving power from a BLDC motor 20 to the drum 9 . There are bearings 11 in front, and rear parts of the drum shaft 17 , and a bearing housing 15 in a center part of a rear wall of the tub 3 for supporting the bearings 11 . There are a supporting bracket 16 mounted on the tub 3 rear wall, and a stator 30 of the BLDC motor 20 mounted on the supporting bracket 16 with a plurality of bolts 19 . There is the rotor 40 of the BLDC motor 20 mounted on a rear end part of the drum shaft 17 with a fastening bolt 18 . In the meantime, there are a door 1 in a front part of the cabinet 5 , and a gasket 2 between the door 1 and the tub 3 . There are hanging springs 4 between an inside of an upper part of the cabinet 5 and an upper part of an outside circumference of the tub 3 , and a friction damper 10 between an inside bottom of the cabinet 5 and a lower part of the outside circumference of the tub 3 , for attenuating vibration of the tub occurred during spinning. FIG. 3 illustrates a perspective view showing the stator in FIG. 1 or 2 separately, and FIG. 4 illustrates a perspective view showing the rotor in FIG. 1 or 2 , separately. Referring to FIG. 3 , the stator 30 is provided with an annular frame 31 , and a plurality of core teeth 33 each extended outward from the frame 31 having a coil wound thereon. There are fastening ribs 32 each formed as a unit with the frame 31 projected toward an inside of the frame 31 having a fastening hole 32 a for mounting the stator 30 on a rear wall of the tub 3 . Referring to FIG. 4 , the rotor 40 is provided with permanent magnets 41 attached to an inside, and mounted to the rear end part of the drum shaft 17 with the fastening bolt 18 . According to this, the drum 9 , connected to the rotor 40 directly, is rotated as the drum 9 receives the rotating power from the rotor 40 when the BLDC motor 20 is in operation. In the drum type washing machine, the rotor 40 is rotated as a power is provided to the stator 30 to form an electric magnet which interacts with the permanent magnets 41 attached to the inside of the rotor 40 , and the power transmitted to the drum shaft 17 through the rotor 40 rotates the drum 9 , to carry out washing and spinning. However, the related art drum type washing machine has a problem in that the fast alternation of polarities of the core teeth 33 in driving the BLDC motor 20 causes resonance at a certain rotation speed. Of course, the problem is occurred at other washing machines having the BLDC motor applied thereto. FIG. 5 illustrates a graph showing a result of sound power level test (PWL test) of the related art BLDC motor for the washing machine. That is, referring to FIG. 5 , the washing machine having the related art BLDC motor 20 applied thereto shows peak noises in a range of 76 dB caused by resonance at 1360 RPM and 1550 RPM. Moreover, the high overall noise, a mean value of the noises between the peak noises, in a range of 74 dB also drops a reliability of the product. |
<SOH> BRIEF DESCRIPTION OF DRAWINGS <EOH>The accompanying drawings, which are included to provide a further understanding of the invention, illustrate embodiment(s) of the invention and together with the description serve to explain the principle of the invention. In the drawings; FIG. 1 illustrates a section of a related art drum type washing machine; FIG. 2 illustrates an enlarged view of ‘A’ part in FIG. 1 ; FIG. 3 illustrates a perspective view showing the stator in FIG. 1 or 2 separately; FIG. 4 illustrates a perspective view showing the rotor in FIG. 1 or 2 , separately; FIG. 5 illustrates a graph showing a result of sound power level test (PWL test) of a related art BLDC motor for the washing machine; FIG. 6 illustrates a perspective view showing a stator in accordance with a preferred embodiment of the present invention; FIG. 7 illustrates a perspective view showing a rotor in accordance with a preferred embodiment of the present invention; and FIG. 8 illustrates a graph showing a result of sound power level test (PWL test) of a BLDC motor in accordance with a preferred embodiment of the present invention. detailed-description description="Detailed Description" end="lead"? |
Copying apparatus for copying a recoding medium, a method thereof and a computer program thereof |
A Copying Apparatus for copying a recoding medium, a method thereof and a computer program thereof is provided, wherein the recording medium is copy-protected by a predetermined method. |
1. A recording medium copying apparatus for copying a recording medium which comprises an overlap zone where addresses overlap, comprising: a file reading unit for reading and managing a file in a forward and/or reverse direction, said file recorded on an original recording medium to be copied; a file comparing and identifying unit for comparing said files read from said original recording medium and identifying whether said files are identical to each other or not; an address processing unit for collecting addresses of said files with regard to said original recording medium and generating and assigning an address at which said file is recorded on a duplicate recording medium; and a file recording unit for recording said file on said duplicate recording medium at said address assigned by said address processing unit in order that an address structure of said duplicate recording medium can be the same as that of said original recording medium. 2. A recording medium copying apparatus as claimed in claim 1, wherein said file reading unit reads said original recording medium in a forward direction which is from a head of said original recording medium at which an address is smallest to an end of said original recording medium at which an address is largest and retrieves said file recorded on said original recording medium, and uniquely identifies said file read in said forward direction according to an address thereof and/or an retrieved order and stores and manages said file in a memory. 3. A recording medium copying apparatus as claimed in claim 2, wherein said file reading unit reads said original recording medium in a reverse direction which is from said end to said head of said original recording medium and retrieves said file recorded on said original recording medium, and uniquely identifies said file read in said reverse direction according to an address thereof and/or an order opposite to said retrieved order and stores and manages said file in a memory. 4. A recording medium copying apparatus as claimed in claim 3, wherein said file reading unit comprises: a forward direction file reading unit for reading said original recording medium in said forward direction, retrieving said file recorded on said original recording medium, uniquely identifying said file read in said forward direction according to said address thereof and/or said retrieved order and storing and managing said file in said memory; and a reverse direction file reading unit for reading said original recording medium in said reverse direction, retrieving said file recorded on said original recording medium, uniquely identifying said file read in said reverse direction according to said address thereof and/or said order opposite to said retrieved order and storing and managing said file in said memory. 5. A recording medium copying apparatus as claimed in claim 1, wherein said file reading unit reads said original recording medium in said forward and reverse directions in parallel. 6. A recording medium copying apparatus as claimed in claim 1, wherein said address processing unit assigns said address at which said file read from said original recording medium is recorded on said duplicate recording medium in order that said address structure of said duplicate recording medium is the same as that of said original recording medium. 7. A recording medium copying apparatus as claimed in claim 6, wherein said address processing unit assigns said address with regard to said duplicate recording medium in order that a forward direction file and a reverse direction file which are judged not to be identical to each other by said file comparing and identifying unit have the same address, said forward and reverse direction files corresponding to each other. 8. A recording medium copying apparatus as claimed in claim 1, wherein said file recording unit records either said forward or reverse direction file judged to be identical to each other on said duplicate recording medium, while recording said forward direction file judged not to be identical on said duplicate recording medium in advance and then recording said reverse direction file judged not to be identical at an corresponding address of said duplicate recording medium. 9. A recording medium copying apparatus as claimed in claim 1, wherein a set of data divided in a predetermined unit per which a process is performed is taken as said file. 10. A recording medium copying method for copying a recording medium which comprises an overlap zone where addresses overlap, comprising the steps of: reading an original recording medium in a forward or reverse direction and retrieving a file; allowing said file read in said forward direction to be identified in a retrieved order; allowing said file read in said reverse direction to be identified in an order opposite to said retrieved order; and recording said file read in said forward or reverse direction on a duplicate recording medium in order that an address structure of said duplicate recording medium can be the same as that of said original recording medium. 11. A recording medium copying method as claimed in claim 10 further comprising a step of storing an address of said file with regard to said original recording medium to correspond to said file read from said original recording medium. 12. A recording medium copying method as claimed in claim 10, wherein said file read in said forward direction is assigned with an identification number sequentially increasing according to an order in which said file is retrieved. 13. A recording medium copying method as claimed in claim 10, wherein said file read in said reverse direction is assigned with an identification number sequentially decreasing according to an order in which said file is retrieved. 14. A recording medium copying method as claimed in claim 10, wherein said original recording medium is read in said forward and reverse directions in parallel in said step of reading. 15. A recording medium copying method as claimed in claim 10, wherein a set of data divided in a predetermined unit per which a process is performed is taken as said file. 16. A computer program for copying a recording medium which comprises an overlap zone where addresses overlap, comprising: a file reading module for reading and managing a file in a forward and/or reverse direction, said file recorded on an original recording medium to be copied; a file comparing and identifying module for comparing said files read from said original recording medium and identifying whether said files are identical to each other or not; an address processing module for collecting addresses of said files with regard to said original recording medium and generating and assigning an address at which said file is recorded on a duplicate recording medium; and a file recording module for recording said file on said duplicate recording medium at said address assigned by said address processing module in order that an address structure of said duplicate recording medium can be the same as that of said original recording medium. 17. A computer program as claimed in claim 16, wherein said address processing module stores an address of said file with regard to said original recording medium to correspond to said file read from said original recording medium. 18. A computer program as claimed in claim 16, wherein said file read in said forward direction is assigned with an identification number sequentially increasing according to an order in which said file is retrieved. 19. A computer program as claimed in claim 16, wherein said file read in said reverse direction is assigned with an identification number sequentially decreasing according to an order in which said file is retrieved. 20. A computer program as claimed in claim 16, wherein said original recording medium is read in said forward and reverse directions in parallel. 21. A computer program as claimed in claim 16, wherein a set of data divided in a predetermined unit per which a process is performed is taken as said file. |
<SOH> BACKGROUND ART <EOH>Generally, for example, in order to retrieve the information recorded on a recording medium by controlling the medium to a reproducing apparatus, it is necessary to obtain the address information indicating where the information is recorded. The recording type of the information needed to record the address information, the content information and/or the like on the recording medium and the information structure of the recording medium are widely known in the art of the present invention. FIG. 1 shows an example of the structure of information recorded on a general DVD. As shown in FIG. 1 , the information recorded on the DVD constitutes a ‘(information) sector’ with a predetermined amount of the information per unit. 17 information sectors are formed in total as shown in FIG. 1 . Each of the information sectors includes the content information of 172 bytes and horizontally error correcting parity data of 10 bytes. And, the 17-th sector includes vertically error correcting parity data of 10 bytes. FIG. 1 shows merely an example of the information structure of a general DVD, so it does not limit the scope of the present invention. In the recording medium with the information structure as above, the address data represents which position on the recording medium certain information is stored at, and thus a part of the address data may serve as the information indicating the position of the sector. The reproducing apparatus generates required control signals by using this address data and performs reproducing operations. For example, when the reproducing apparatus moves over the recording medium or reproduces the medium from a certain position, it can control an operation of searching the information recorded on the medium by referring to the address data. Recently, however, it is possible to read the information recorded on an optical recording medium easily by using a general personal computer. Consequently, illegal copying which is very easy and diverse has become common and widely accepted. Thus, the protection for the copyright of contents recorded on a medium has become an urgent issue. Accordingly, the applicant of the present invention has disclosed a copy-protected optical recording medium capable of being reproduced by a general reproducing apparatus, comprising at least one overlapping zone whose address values allocated to information recorded on the recording medium overlap address values of another area in the recording medium and driving information for controlling the reproducing apparatus to read information on the overlapping zone in “a copy-protected optical recording medium capable of being reproduced by a general reproducing apparatus and a method for manufacturing thereof”, International Application No. PCT/KR02/00490 filed on 22 Mar. 2002. The copy-protected optical recording medium, International Application No. PCT/KR02/00490, will be described in detail referring to FIGS. 2 a and 2 b. FIG. 2 a shows a series of pieces of information, hypothetically arranged in a row, recorded on from an innermost track to an outermost track of a general optical recording medium and address values allocated to the series of pieces of the information. And, FIG. 2 b shows a series of pieces of information, hypothetically arranged in a row, recorded on from the innermost track to the outermost track of the copy-protected optical recording medium according to the International Application No. PCT/KR02/00490 and address values allocated to the series of pieces of the information. As shown in FIG. 2 a, the address values of the information on the general optical recording medium are allocated in order to linearly increase from the inner tracks to the outer tracks of the medium sequentially. A linearly increased graph is shown at the bottom of the series of pieces of the information. The address values may also linearly decrease from the inner tracks to the outer tracks. Moreover, in another optical recording medium already known, the information may be chaotically placed on the medium by scrambling the address data. In this way, the reproduction ratio can be increased by correcting errors, even if any physical damage occurs at a certain area on the medium. Even In this case, however, supposing a state where retrieved information is arranged in a row as shown in FIG. 2 a, we can understand that the address values linearly increase (or decrease) conceptually. Meanwhile, as shown in FIG. 2 b, the copy-protected optical recording medium according to the International Application No. PCT/KR02/00490 includes at least one overlapping zone whose address values allocated to the information on the medium overlap each other. The address values may be either physical or logical addresses. In FIG. 3 a, it is shown that the address values in the overlapping zone and those in a previous zone (referred to as “zone B) overlap each other. Moreover, the copy-protected optical recording medium according to the International Application No. PCT/KR02/00490 further includes driving information at a predetermined area for controlling the reproducing apparatus in order to read the information recorded on the overlapping zone. The data on the zone B has the same address values as those of the corresponding data on the overlapping zone, so that the driving information is for driving the reproducing apparatus to access the addresses respectively. In order to copy the information recorded on a recording medium according to the International Application No. PCT/KR02/00490 in an already known method, it is necessary to use the address data allocated to the above zones for recording information from the zone B and the overlapping zone on a recording medium as a duplicate. Consequently, only one of the pieces of the information on the zone B and the overlapping zone is recorded on a zone with a corresponding address value of the copied medium. Therefore, when reproducing the copied medium recorded in this way, it is impossible to retrieve one of the pieces of the information on the zone B and the overlapping zone of the original medium from the copied medium. Accordingly, some pieces of the information on the original medium remain not capable of being copied. Therefore, in case of the duplicated medium, the data retrieved from a position to which a certain address is allocated is the same regardless of the reproduction progress direction. Since that result is different from a case of the original medium where pieces of data on a position to which the same address is allocated can be different from one another depending on the progress direction, it is possible to discriminate the copied medium from the original medium. Accordingly, by that point an original medium can be protected against duplication or at least can be prevented from reproducing the duplicate of it. In case of the copy-protected recording medium as above, however, the method causes a problem that a lawful owner also cannot copy any recording medium even within a permitted scope under a law. |
<SOH> BRIEF DESCRIPTION OF DRAWINGS <EOH>FIG. 1 shows an example of the structure of information recorded on a general DVD. FIG. 2 a shows a series of pieces of the information, hypothetically arranged in a row, recorded on from an innermost track to an outermost track of a general optical recording medium and address values allocated to the series of pieces of the information. FIG. 2 b shows a series of pieces of the information, hypothetically arranged in a row, recorded on from the innermost track to the outermost track of the copy-protected optical recording medium according to the prior art and address values allocated to the series of pieces of the information. FIG. 3 is a functional block diagram schematically showing an exemplary embodiment of a recording medium copying apparatus 100 according to the present invention. FIG. 4 is a flowchart showing an exemplary embodiment of the operation of a copying apparatus according to the present invention. FIG. 5 shows a file structure of an original recording medium and a result of judging whether correspondingly forward and reverse direction files retrieved from the medium are identical to each other or not. FIG. 6 shows a file structure of an original recording medium according to another exemplary embodiment and a result of judging whether correspondingly forward and reverse direction files retrieved from the medium are identical to each other or not. FIG. 7 a shows a file structure of an original recording medium according to another embodiment of the present invention. FIG. 7 b shows a result of judging whether correspondingly forward and reverse direction files retrieved from the medium are identical to each other or not. detailed-description description="Detailed Description" end="lead"? |
Isolation and mobilization of stem cells expressing vegfr-1 |
The present invention is directed to methods of isolating mammalian stem cells expressing the VEGF receptor VEGFR-1 and compositions thereof. The present invention is also directed to methods of using such isolated mammalian stem cells expressing VEGFR-1 to treat various conditions, which can involve inducing hematopoiesis, vasculogenesis and/or angiogenesis, myogenesis, and neurogenesis to treat the various condition. Finally, the present invention is directed to therapeutic methods using a molecule that binds and activates or stimulates VEGFR-1, for example, P1GF, to stimulate proliferation and/or differentiation and mobilization, i.e., motogenesis, of stem cells. |
1. A method for isolation of mammalian stem cells comprising providing a population of cells; contacting the population of cells with a molecule that specifically binds VEGFR-1; and isolating cells that bind the molecule that specifically binds VEGFR-1. 2. The method of claim 1, wherein the population of cells is isolated from a fetal liver, umbilical cord blood, a yolk sac, a mature spinal cord, bone marrow, or an adult peripheral blood sample. 3. The method of claim 1, wherein the population of cells is isolated from central nervous system. 4. The method of claim 1, wherein the molecule that specifically binds VEGFR-1 is an antibody. 5. The method of claim 1, wherein the molecule that specifically binds VEGFR-1 is a ligand. 6. The method of claim 5, wherein the ligand is PlGF. 7. The method of claim 1, wherein the method further comprises contacting the cells with one or more positive selection markers and isolating cells that bind the one or more positive selection markers. 8. The method of claim 7, wherein the positive selection marker is CD34 or AC133. 9. The method of claim 1, wherein the method further comprises contacting the cells with one or more negative selection markers and isolating cells that do not bind the one or more negative selection markers. 10. The method of claim 9, wherein the negative selection marker is CD38 or Lin. 11. The method of claim 1, wherein the cells isolated are human stem cells. 12. The method of claim 11, wherein the human stem cells are hematopoietic stem cells. 13. The method of claim 11, wherein the human stem cells are endothelial, muscle, or neural stem cells. 14. A composition comprising a molecule that specifically binds VEGFR-1. 15. The composition of claim 14, wherein the molecule that specifically binds VEGFR-1 is an antibody. 16. The composition of claim 15, wherein the molecule that specifically binds VEGFR-1 is a ligand. 17. The composition of claim 16, wherein the ligand is PlGF. 18. A composition comprising a cell expressing VEGFR-1, wherein the cell expressing VEGFR-1 is isolating using the method of claim 1. 19. A method of treating a mammal comprising administering to the mammal a composition of claim 1. 20. The method of claim 19, wherein the treatment involves induction of hematopoiesis, vasculogenesis and/or angiogenesis, or myogenesis and/or neurogenesis. 21. The method of claim 19, wherein the treatment involves mobilization of stem cells to the area of administration. 22. The method of claim 19, wherein the treatment involves stimulation of stem cells to proliferate or differentiate. 23. The method of claim 19, wherein the treatment is useful to reconstitute pancreatic islet cells or regenerate damaged neurons. 24. The method of claim 19, wherein the method is useful to treat cardiac or peripheral ischemia. |
<SOH> BACKGROUND OF THE INVENTION <EOH>Stem cells are unique cell populations with the ability to undergo both self-renewal and differentiation. In mammalian embryos, hemangioblasts are believed to be the precursors of angioblasts and totipotent or pluripotent hematopoietic stem cells. Angioblasts and other embryonic totipotent and/or pluripotent stem cells are believed to be the precursors of postnatal endothelial cells, muscle cells, and neural cells. The mammalian hematopoietic system comprises erythrocytes (red blood cells) and white blood cells that mature from more primitive lineages. See, e.g. U.S. Pat. Nos. 5,747,651 and 5,912,133 (referencing Dexter and Spooncer, Ann. Rev. Cell Biol., 3: 423-441 (1987)). The erythrocytes result from primitive cells called erythroid burst-forming units, whose immediate progeny are called erythroid colony-forming units. The white blood cells contain the mature cells of the lymphoid and myeloid systems. The lymphoid cells include B lymphocytes and T lymphocytes, both of which result from earlier progenitor cells (Dexter and Spooncer). The myeloid system comprises a number of cells including granulocytes, platelets, monocytes, macrophages and megakaryocytes. The granulocytes are further divided into neutrophils, eosinophils, basophils, and mast cells. Each of the mature hematopoietic cells is specialized for specific functions. The development of the initial blood vessel system in embryos is generally believed to occur from the adhesion to each other and modeling of primitive endothelial precursor cells, such as angioblasts. This process is generally known as vasculogenesis. Postnatal development of new blood vessels is generally believed to occur from the proliferation, migration, and remodeling of the mature endothelial cells of pre-existing, blood vessels. This process is generally known as angiogenesis. One or more totipotent stem cells can undergo a series of differentiation steps leading to increasingly lineage-restricted progenitor cells. For example, a totipotent stem cell of a certain cell type, e.g. a hematopoietic stem cell, an endothelial stem cell, a muscle stem cell or a neural stem cell, is capable of reconstituting all cells of that cell type in vivo. The more mature stem cells have limited proliferative capacity and are generally capable of giving rise to only one or two lineages in vitro or in vivo. Stem cell-base therapies have a broad variety of applications. For example, stem cell induction of hematopoiesis, vasculogenesis and/or angiogenesis, myogenesis and neurogenesis can be employed to treat various conditions. Thus, stem cells can be used to treat diseases that result from the destruction and/or dysfunction of a limited number of cell types, such as diabetes mellitus, in which pancreatic islet cells have been selectively destroyed, or Parkinson's disease, which results from the destruction of dopaminergic neurons within a particular region of the brain. Other applications include treatment of, for example, peripheral ischemia, sickle cell anemia, thalassemia, muscular dystrophy, Alzheimer's disease, traumatic spinal cord injury, Purkinje cell degeneration, liver failure, cardiac ischemia, Duchenne's muscular dystrophy, and osteogenesis imperfecta, as well as in combination with chemotherapy or radiation treatments. A human stem cell-based strategy could also be employed to generate an unlimited supply of cells or tissue from an abundant, renewable, and readily accessible source for use in organ transplants. Moreover, by virtue of their permissiveness for stable genetic modification, stem cells could be engineered to escape or inhibit host immune responses. Moreover, stem cells have various applications in basic research, including studies relating to developmental biology. Although stem cell-based therapy holds great promise to successfully treat a variety of diseases, many barriers remain. One such barrier involves the isolation of purified populations of stem cells. In this regard, efforts have been made to use various surface markers to obtain purified populations of stem cells. For example, a purified population of CD34+ hematopoietic stem cells was described by Civin in U.S. Pat. No. 5,035,994 and U.S. Pat. No. 5,130,144. A more highly purified population of hematopoietic stem cells that are CD34+, Class II HLA+, and Thy-1+ was described by Tsukamoto et al. in U.S. Pat. No. 5,061,620. The Tsukamoto patent further explains that stem cells lack certain markers that are characteristic of more mature, lineage-committed (Lin+) cells. Such markers include CD3, CD8, CD10, CD19, CD20, and CD33. Cells that lack these markers are said to be lineage negative (Lin−). In addition, it is known that growth factors play an important role in the development and operation of mammalian stem cells. The role of these growth factors is complex. For example, hematopoiesis can be established in the absence of growth factors, provided that marrow stromal cells are added to the medium. Hematopoietic growth factors exhibit a spectrum of activities. For instance, erythropoietin is believed to promote proliferation of only mature erythroid progenitor cells. IL-3, which is believed to facilitate the growth and development of early stem cells as well as of numerous progenitor cells, including those restricted to the granulocyte/macrophage, eosinophil, megakaryocyte, erythrocyte and mast cell lineages. Another hematopoietic growth factor whose receptor is the product of the W locus, c-kit, is a member of the class of receptor protein tyrosine kinases (pTK). See, e.g., Anderson et al., Cell , 63(1): 235-43 (1990); Huang et al., Cell , 63(1): 225-33 (1990); Zsebo et al., Cell , 63(1): 213-24 (1990); Zsebo et al., Cell, 63(1): 195-201 (1990); Flanagan & Leder, Cell, 63(1): 195-94 (1990); Copeland et al., Cell, 63(1): 175-85 (1990); Williams et al., Cell, 63(1): 164-74 (1990). The ligand for c-kit, referred to by various names, e.g. stem cell factor (SCF) and mast cell growth factor (MGF) is believed to be essential for the development of early hematopoietic stem cells and cells restricted to the erythroid and mast cell lineages in mice. Id. It is becoming increasingly apparent that these protein tyrosine kinases (pTK) also play an important role as cellular receptors for stem cell growth factors. The pTK family has several conserved amino acid regions in the catalytic domain (see e.g. Hanks et al., Science, 241:42-52 9 (1988); Wilks, PNAS USA, 86:1603-1607 (1989)). Other specific examples of protein tyrosine kinases include the vascular endothelial growth factor (VEGF) receptors. There are two such receptors, fms-like tyrosine kinase (FLT-1), also known as VEGFR-1, which was sequenced by Shibuya et al., Oncogene, 5: 519-524 (1990), and kinase insert domain-containing receptor/fetal liver kinase (KDR/flk-1), also known as VEGFR-2, which was described in WO 92/14248, filed Feb. 20, 1992, and Terman et al., Oncogene, 6: 1677-1683 (1991), and sequenced by Matthews et al., PNAS USA, 88: 9026-9030 (1991). It is generally believed that VEGFR-2 is the main signal transducer for VEGF, resulting in endothelial cell proliferation, migration, differentiation, tube formation, increase of vascular permeability, and maintenance of vascular integrity. VEGFR-1 possesses a much weaker kinase activity, and is unable to generate a mitogenic response when stimulated by VEGF—although it binds to VEGF with an affinity that is approximately 10-fold higher than VEGFR-2. VEGFR-1 has also been implicated in VEGF and placenta growth factor (PlGF)—induced migration of monocytes and macrophages, and production of tissue factors. The VEGF homologue PlGF is also a natural specific ligand for VEGFR-1. PlGF, a dimeric secreted factor, is produced in large amounts by villous cytotrophoblast, sincytiotrophoblast and extravillous trophoblast and has close amino acid homology to VEGF. Three isoforms exist in humans, PlGF-1, PlGF-2, and PlGF-3. Studies with PlGF-deficient mice demonstrate that this growth factor is not involved in angiogenesis per se, but rather, specifically modulates the angiogenic and permeability effects of VEGF during pathological situations. |
<SOH> SUMMARY OF THE INVENTION <EOH>The present invention provides methods of isolating mammalian stem cells expressing the VEGF receptor VEGFR-1. Also provided are compositions of isolated mammalian stem cells expressing VEGFR-1. The isolated cells preferably include hematopoietic stem cells, endothelial stem cells, muscle stem cells and neural stem cells, which are preferably human stem cells. In a preferred embodiment, the present invention provides methods of further positively and/or negatively selecting for stem cells, as well as compositions thereof. Also provided are methods of using such isolated mammalian stem cells expressing VEGFR-1 to treat various conditions, which can involve inducing hematopoiesis, vasculogenesis and/or angiogenesis, myogenesis, and neurogenesis to treat the various condition. Finally, the present invention provides therapeutic methods using a molecule that binds and activates or stimulates VEGFR-1, which is particularly a ligand, a preferred example of which is PlGF. Such molecules can stimulate proliferation and/or differentiation and mobilization, i.e., motogenesis, of stem cells, which can then be employed to treat various conditions. This technology also allows for mobilizing a large number of stem cells to the peripheral circulation. The enriched population of the stem cells in the peripheral circulation facilitates isolation of large numbers of stem cells expressing VEGFR-1 that can be used for gene therapy or bone marrow transplantation. In addition, these stem cells can directly or intravenously be used for restoring function to the ischemic myocardium, reconstitute pancreatic islet cells, or regenerate damaged neurons. |
Analytical technique |
Radionuclides are determined by adding a combined carrier and a tracer to a sample to be analysed. The sample is mineralized by pyrolysizing and/or pyrohydrolysizing the sample. The resulting analyte is isolated and the analyte is analyzed. |
1-35. (Canceled) 36. A method for the determination of specified radionuclides, comprising the steps of: adding a combined carrier and a tracer to a sample to be analysed; mineralizing the sample comprising pyrolysizing and/or pyrohydrolysizing the sample; isolating a resulting analyte; and analyzing the analyte. 37. A method according to claim 36, wherein mineralizing the sample comprises pyrohydrolysizing the sample. 38. A method according to claim 37, wherein pyrohydrolysizing the sample comprises converting all chemical and physical forms of the analyte into soluble, inorganic forms. 39. A method according to claim 37, wherein analyzing the analyte is based upon pyrohydrolysis of both C-14 and I-129 in a single sample aliquot. 40. A method according to claim 37, wherein mineralizing the sample comprises remotely pyrohydrolysizing the sample in a shielded facility. 41. A method according to claim 40, further comprising processing the sample in the shielded facility to allow export to the radio-bench. 42. A method according to claim 40, further comprising purifying the sample and preparing a source at the radio-bench. 43. A method according to claim 42, further comprising diluting the sample in a shielded facility to determine I-129 and/or C-14. 44. A method according to claim 43, wherein diluting the sample comprises calibrating using isotope dilution methodologies. 45. A method according to claim 43, wherein pyrohydrolysizing the sample, purifying the sample, preparing the source are performed in a low-level protection environment. 46. A method according to claim 36, further comprising: absorbing and/or adsorbing evolved gases onto and/or into a substrate after mineralizing the sample. 47. A method according to claim 36, wherein isolating the resulting analyte comprises purifying the analyte. 48. A method according to claim 36, wherein analyzing the analyte comprises determining analytes of interest by classical radiometric techniques and/or by inorganic mass spectrometry 49. A method according to claim 48, wherein analyzing the analyte comprises determining analytes of interest by inorganic mass spectrometry. 50. A method according to claim 49, wherein the inorganic mass spectrometry is inductively coupled plasma mass spectrometry. 51. A method according to claim 50, wherein the analyte is I-129 or Tc-99. 52. A method according to claim 49, wherein the inorganic mass spectrometry is accelerator mass spectrometry. 53. A method according to claim 52, wherein the analyte is I-129, C-14, Tc-99 or Cl-36. 54. A method according to claim 48, wherein analyzing the analyte comprises determining analytes of interest by classical radiometric techniques. 55. A method according to claim 54, wherein the analyte is I-129, C-14, Tc-99, S-35, Ru-106 or Cl-36. 56. A method according to claim 36, wherein the analyte comprises at least one of C-14, I-129, Cl-36, Tc-99, S-35 and Ru-106. 57. A method according to claim 36, wherein the sample comprises process streams or materials, process wastes, and/or waste forms of interest in the nuclear fuel cycle. 58. A method according to claim 57, wherein the sample may be in a range from highly radioactive to non-radioactive. 59. A method according to claim 36, wherein the sample is of environmental concern and interest. 60. A method according to claim 36, wherein mineralizing the sample comprises: pyrohydrolysizing the sample in a first zone in a furnace; and oxidizing the sample in a second zone in the furnace. 61. A method according to claim 60, wherein the first zone is maintained at a substantially constant temperature and the second zone is temperature programmed. 62. A method according to claim 36, wherein the sample comprises iodine, and mineralization of the sample comprises using a catalyst to aid conversion of iodine to hydrogen iodide. 63. A method according to claim 62, wherein the catalyst is a metal oxide. 64. A method according to claim 63, wherein the catalyst is vanadium pentoxide. 65. A method according to claim 36, wherein mineralization of the sample comprises using an oxidation catalyst to aid conversion of any carbon monoxide and/or volatile organic compounds to carbon dioxide. 66. A method according to claim 65, wherein the oxidation catalyst is platinum or alumina. 67. A method according to claim 36, wherein the carrier is a quaternary alkyl ammonium iodide. 68. A method according to claim 67, wherein the carrier is tetra-butyl ammonium iodide. |
Galectin-14 therapeutic molecule and uses thereof |
The present invention relates generally to a novel galectin and to derivatives, homologues, analogues, chemical equivalents and mimetics thereof capable of modulating an immune response and, in particularly, an inflammatory response. More particularly, the present invention relates to ecalectin-like galectin (herein referred to as “galectin-14”) and to derivatives, homologues, analogues, chemical equivalents and mimetics of said protein sequence. The present invention also contemplates genetic sequences encoding said galectin and derivatives, homologues, analogues, chemical equivalents and mimetics thereof. The molecules of the present invention are useful in a range of therapeutic, prophylactic and diagnostic applications. |
1. An isolated nucleic acid molecule or derivative, homologue or analogue thereof comprising a nucleotide sequence encoding or complementary to a sequence encoding a novel galectin-14 protein or a derivative, homologue or mimetic thereof wherein said galectin-14 comprises one carbohydrate recognition domain. 2. An isolated nucleic acid molecule or derivative, homologue or analogue thereof comprising a nucleotide sequence encoding, or a nucleotide sequence complementary to a nucleotide sequence encoding, an amino acid sequence substantially as set forth in SEQ ID NO:2 or a derivative, homologue or mimetic thereof or having at least about 45% or greater similarity to at least 10 contiguous amino acids in SEQ ID NO:2. 3. An isolated nucleic acid molecule or derivative, homologue or analogue thereof comprising a nucleotide sequence substantially as set forth in SEQ ID NO:1 or a derivative, homologue or analogue thereof or capable of hybridising to SEQ ID NO:1 under low stringency conditions. 4. An isolated nucleic acid molecule according to claim 3 which further encodes an amino acid sequence corresponding to an amino acid sequence set forth in SEQ ID NO:2 or a sequence having at least about 45% similarity to at least 10 contiguous amino acids in SEQ ID NO:2. 5. An isolated nucleic acid molecule according to claim 3 substantially as set forth in SEQ ID NO:1. 6. An isolated novel galectin-14 protein or derivative, homologue, analogue, chemical equivalent or mimetic thereof wherein said galectin-14 comprises one carbohydrate recognition domain. 7. An isolated protein comprising an amino acid sequence substantially as set forth in SEQ ID NO:2 or a derivative, homologue or mimetic thereof or a sequence having at least about 45% similarity to at least 10 contiguous amino acids in SEQ ID NO:2 or a derivative, analogue, chemical equivalent or mimetic of said protein. 8. An isolated protein according to claim 7 encoded by a nucleotide sequence substantially as set forth in SEQ ID NO:1 or a derivative, homologue or analogue thereof or capable of hybridising to SEQ ID NO:1 under low stringency conditions or a derivative, homologue, analogue, chemical equivalent or mimetic of said protein. 9. An isolated protein according to claim 7 substantially as set forth in SEQ ID NO:2. 10. A method of modulating expression of galectin-14, in a mammal, said method comprising contacting the galectin-14 gene with an effective amount of an agent for a time and under conditions sufficient to increase or decrease expression of galectin-14. 11. A method of modulating the functional activity of galectin-14 in a mammal, said method comprising administering to said mammal a modulating effective amount of an agent for a time and under conditions sufficient to increase or decrease galectin-14 activity. 12. The method according to claim 11 wherein said modulation is down-regulation and said agent is an anti-galectin-14 antibody. 13. A method of treating a mammal said method comprising administering to said mammal an effective amount of an agent for a time and under conditions sufficient to modulate the expression of galectin-14 wherein said modulation results in modulation of immune functioning and/or cellular apoptosis. 14. A method of treating a mammal said method comprising administering to said mammal an effective amount of an agent for a time and under conditions sufficient to modulate the activity of galectin-14 wherein said modulation results in modulation of immune functioning and/or cellular apoptosis. 15. The method according to claim 14 wherein said modulation is down-regulation of inflammation and said agent is an anti-galectin-14 antibody. 16. A method of treating a mammal said method comprising administering to said mammal an effective amount of a protein according to claim 6 or a derivative, homologue, analogue, chemical equivalent or mimetic thereof for a time and under conditions sufficient to modulate immune functioning and/or cellular apoptosis. 17. A method of treating a mammal said method comprising administering to said mammal an effective amount of a nucleic acid molecule according to claim 1 or a derivative, homologue, analogue, chemical equivalent or mimetic thereof for a time and under conditions sufficient to modulate immune functioning and/or cellular apoptosis. 18. The method according to claim 14 wherein said immune functioning is inflammation. 19. A method for the treatment and/or prophylaxis of a condition characterised by an aberrant, unwanted or otherwise inappropriate inflammatory response in a mammal said method comprising administering to said mammal an effective amount of an agent for a time and under conditions sufficient to modulate the expression of galectin-14 or sufficient to modulate the activity of galectin-14 wherein up-regulating said expression or activity up-regulates said inflammatory response and down-regulating said expression or activity down-regulates said inflammatory response. 20. A method for the treatment and/or prophylaxis of a condition characterised by an aberrant, unwanted or otherwise inappropriate inflammatory response in a mammal said method comprising administering to said mammal an effective amount of galectin-14 or galectin-14 for a time and under conditions sufficient to up-regulate said inflammatory response. 21. A method of treatment and/or prophylaxis according to claim 19 wherein said condition is an allergic condition and its inflammatory response is a Th2 type inflammatory response which is down-regulated by down-regulation of galectin-14 or functional activity or galectin-14 expression. 22. The method according to claim 20 wherein said agent is an anti-galectin-14 antibody. 23. A method for the treatment and/or prophylaxis of a condition characterised by aberrant, unwanted or otherwise inappropriate cellular apoptosis in a mammal said method comprising administering to said mammal an effective amount of an agent for a time and under conditions sufficient to modulate the expression of galectin-14 or sufficient to modulate the activity of galectin-14 wherein up-regulating said expression or activity down-regulates said apoptosis and down regulating said expression or activity up-regulates said apoptosis. 24. A method for the treatment and/or prophylaxis of a condition characterised by aberrant, unwanted or otherwise inappropriate cellular apoptosis in a manual said method comprising administering to said mammal an effective amount of galectin-14 or galectin-14 for a time and under conditions sufficient to down-regulate said apoptosis. 25. Use of an agent capable of modulating the expression galectin-14 or a derivative, homologue, analogue, chemical equivalent or mimetic thereof in the manufacture of a medicament for the modulation of immune functioning and/or cellular apoptosis. 26. Use of an agent capable of modulating the activity of galectin-14 or a derivative, homologue, analogue, chemical equivalent or mimetic thereof in the manufacture of a medicament for the modulation of immune functioning and/or cellular apoptosis. 27. Use according to claim 26 wherein said immune functioning is an inflammatory response. 28. Use according to claim 26 wherein said modulation is down-regulation of inflammation and said agent is an anti-galectin-14 antibody. 29. Use of galectin-14 or galectin-14 or a derivative, homologue, analogue, chemical equivalent or mimetic thereof in the manufacture of a medicament for the treatment of a condition characterised by aberrant, unwanted or otherwise inappropriate inflammatory response and/or cellular apoptosis. 30. An agent for use in modulating galectin-14 activity or a derivative, analogue chemical equivalent or mimetic thereof wherein modulating said galectin-14 activity modulates immune, functioning and/or cellular apoptosis. 31. An agent according to claim 30 wherein said modulation is down-regulation of inflammation and said agent is an anti-galectin-14 antibody. 32. An agent for use in modulating galectin-14 expression or a derivative, homologue, analogue, chemical equivalent or mimetic thereof wherein modulating expression of said galectin-14 modulates immune functioning and/or cellular apoptosis. 33. An agent according to claim 30 wherein said immune functioning is an inflammatory response. 34. Galeotin-14 or galectin-14 or a derivative, homologue, analogue, chemical equivalent or mimetic thereof for use in modulating immune functioning and/or cellular apoptosis. 35. A pharmaceutical composition comprising galectin-14, galectin-14 or an agent capable of modulating galectin-14 or galectin-14 or derivative, homologue, analogue, chemical equivalent or mimetic thereof together with one or more pharmaceutically acceptable carriers and/or diluents. 36. The pharmaceutical composition according to claim 35 wherein said agent is an anti-galectin-14 antibody. 37. An isolated antibody directed to the protein according to claim 6. 38. An isolated antibody directed to the nucleic acid molecule according to claim 1. 39. An isolated antibody according to claim 37 wherein said antibody is derived from hybridoma clone 1.2 or a derivative, homologue, analogue, chemical equivalent or mimetic of said antibody. 40. The antibody according to claim 37 wherein said antibody is a monoclonal antibody. 41. The antibody according to claim 31 wherein said antibody is a polyclonal antibody. 42. A method for detecting an agent capable of modulating the functioning of galectin-14 or its functional equivalent or derivative thereof or galectin-14 expression said method comprising contacting a cell or extract thereof containing said galectin-14 or its functional equivalent or derivative or galectin-14 with a putative agent and detecting an altered expression phenotype associated with said galectin-14 or its functional equivalent or derivative or galectin-14. 43. A method for detecting an agent capable of binding or otherwise associated with a galectin-14 or galectin-14 binding site or functional equivalent or derivative of said galectin-14 or galectin-14 said method comprising contacting a cell containing said galectin-14 or galectin-14 binding site or functional equivalent or derivative thereof with a putative agent and detecting an altered expression phenotype associated with modulation of the function of galectin-14 or galectin-14 or its functional equivalent or derivative thereof. 44. A method for analyzing, designing and/or modifying an agent capable of interacting with the carbohydrate, protein kinase C and/or casein kinase II binding site of galectin-14 or derivative thereof and modulating at least one functional activity associated with said galectin-14 said method comprising contacting said galectin-14 or derivative thereof with a putative agent and assessing the degree of interactive complementarity of said agent with said binding site. 45. The method according to claim 43 wherein said binding site is defined by one or more of: (i) the amino acids H74, N76, R78, N88, W95 and E98 of SEQ ID NO:1; (ii) the amino acid sequence SGHE (position numbers 5-8 of SEQ ID NO:1), STDE (position numbers 51-54 of SEQ ID NO:1), or SLFE (position numbers 110-113 of SEQ ID NO:1); (iii) the amino acid sequence TGR (position numbers 30-32 of SEQ ID NO:1) or SFK (position numbers 122-124 of SEQ ID NO:1). 46. Agents identified utilising method of claim 43. 47. A method of diagnosing or monitoring a mammalian disease condition said method comprising screening for galectin-14 or galecetin-14 in a biological sample isolated from said mammal. 48. The method according to claim 13 wherein said modulation is down-regulation of inflammation and said agent is an anti-galectin-14 antibody. 49. The method according to claims 19 wherein said agent is an anti-galectin-14 antibody. 50. Use according to claim 25 wherein said immune functioning is an inflammatory response. |
<SOH> BACKGROUND OF THE INVENTION <EOH>Bibliographic details of the publications referred to by author in this specification are collected alphabetically at the end of the description. The reference to any prior art in this specification is not, and should not be taken as, an acknowledgment or any form of suggestion that that prior art forms part of the common general knowledge in Australia. The immune response of mammals to multicellular parasite infections and allergens often involves recruitment of eosinophils (Balic et al., 2000; Kay, A. B., Barata, L., Meng, Q., Durham, S. R. and Ying, S. (1997) Int. Allergy Immunol. 113:196-199). However, the effects of eosinophilia in TH2 allergic-type immune responses remains controversial. Little is known of the putative role eosinophil constituents play in combating multicellular parasites and exacerbating allergic responses, including the role of major constituents such as galectin-10, also known as the Charcot-Leyden crystal (Ackerman, S. J., Corette, S. E., Rosenberg, H. F., Bennett, J. C., Mastrianni, D. M., Nicholson-Weller, A., Weller, P. F., Chin, D. T., and Tennen, D. G. (1993) J. Immunol. 150:456-468; Giembycz and Lindsay, 1999). Accordingly, there is an ongoing need to identify, and elucidate the functional activity of novel eosinophil-related molecules in order to facilitate the progression towards the more sensitive control of immune responses, such as those involving an inflammatory response. Sheep have been used successfully in many immunological studies to help define the immune response of large animals, including humans. The advantages of using this animal model are the comparable size and close physiological and phylogenetic relationship with humans compared to rodent models. Haenzonchus contortus is a natural nematode parasite of sheep, which inhabits the abomasum (true stomach). H. contortus challenge infection of immunised sheep can result in massive infiltration of eosinophils within abomasal tissue (Balic et al., 2000 supra), indicating that this tissue may be a good source of inflammatory molecules associated with eosinophil recruitment. The isolation of the inflammatory cells from the abomasal tissue is however problematic and requires tissue digestion. Previous studies have shown that infusion of H. contortus larvae or lipopolysaccharide (LPS) into the mammary gland provides a ready supply of eosinophils and neutrophils, respectively after subsequent “milking” of the gland, without invasive techniques and little discomfort to the animal (Greenhalgh, C. J., Jacobs, H. J. and Meeusen, E. N. T. (1996) Immun. Cell Biol. 74:497-503, Rainbird, M. A., Macmillan, D., and Meeusen, E. N. (1998) Parasite Immunol. 20(2):93-103). This model allows the study of leukocyte populations before and after challenge with allergens, with minimal cell manipulation (Adams and Colditz, 1991, Greenhalgh et al., 1996 supra). In work leading up to the present invention the inventors have identified a novel galectin that is expressed by circulating eosinophils, or eosinophils migrating into the mammary lavage (MAL), bronchoalveolar lavage (BAL), lung or gastro-intestinal tissue in response to helminth infection or allergen challenge. |
<SOH> SUMMARY OF THE INVENTION <EOH>Throughout this specification and the claims which follow, unless the context requires otherwise, the word “comprise”, and variations such as “comprises” and “comprising”, will be understood to imply the inclusion of a stated integer or step or group of integers or steps but not the exclusion of any other integer or step or group of integers or steps. The subject specification contains nucleotide and amino acid sequence information prepared using the programme PatentIn Version 3.1, presented herein after the bibliography. Each nucleotide or amino acid sequence is identified in the sequence listing by the numeric indicator <210> followed by the sequence identifier (e.g. <210>1, <210>2, etc). The length, type of sequence (DNA, protein (PRT), etc) and source organism for each nucleotide or amino sequence are indicated by information provided in the numeric indicator fields <211), <212> and <213>, respectively. Nucleotide and amino acid sequences referred to in the specification are defined by the information provided in numeric indicator field <400> followed by the sequence identifier (e.g. <400>1, <400>2, etc). One aspect of the present invention provides an isolated nucleic acid molecule or derivative, homologue or analogue thereof comprising a nucleotide sequence encoding a novel galectin protein or a derivative, homologue or mimetic thereof wherein said galectin comprises one carbohydrate recognition domain. Another aspect of the present invention provides a nucleic acid molecule or derivative, homologue or analogue thereof comprising a nucleotide sequence encoding, or a nucleotide sequence complementary to a nucleotide sequence encoding, an amino acid sequence substantially as set forth in <400>2 or a derivative, homologue or mimetic thereof or having at least about 45% or greater similarity to at least 10 contiguous amino acids in <400>2. In another aspect the present invention contemplates a nucleic acid molecule or derivative, homologue or analogue thereof comprising a nucleotide sequence substantially as set forth in <400>1 or a derivative, homologue or analogue thereof, or capable of hybridising to <400>1 under low stringency conditions. A further aspect of the present invention contemplates a nucleic acid molecule or derivative, homologue or analogue thereof comprising a nucleotide sequence substantially as set forth in <400>1 or a derivative thereof or capable of hybridising to <400>1 under low stringency conditions and which encodes an amino acid sequence corresponding to an amino acid sequence set forth in <400>2 or a sequence having at least about 45% similarity to at least 10 contiguous amino acids in <400>2. Yet another aspect of the present invention contemplates a nucleic acid molecule comprising a sequence of nucleotides substantially as set forth in <400>1. Still another aspect of the present invention is directed to an isolated protein selected from the list consisting of: (i) A novel galectin protein or a derivative, homologue, analogue, chemical equivalent or mimetic thereof wherein said galectin comprises one carbohydrate recognition domain. (ii) A protein having an amino acid sequence substantially as set forth in <400>2 or a derivative, homologue or mimetic thereof or a sequence having at least about 45% similarity to at least 10 contiguous amino acids in <400>2 or a derivative, homologue, analogue, chemical equivalent or mimetic of said protein. (iii) A protein encoded by a nucleotide sequence substantially as set forth in <400>1 or a derivative, homologue or analogue thereof or a sequence encoding an amino acid sequence having at least about 45% similarity to at least 10 contiguous amino acids in <400>2 or a derivative, homologue, analogue, chemical equivalent or mimetic of said protein. (iv) A protein encoded by a nucleic acid molecule capable of hybridising to the nucleotide sequence as set forth in <400>1 or a derivative, homologue or analogue thereof under low stringency conditions and which encodes an amino acid sequence substantially as set forth in <400>2 or a derivative, homologue or mimetic thereof or an amino acid sequence having at least about 45% similarity to at least 10 contiguous amino acids in <400>2. (v) A protein as defined in paragraphs (i) or (ii) or (iii) or (iv) in a homodimeric form. (vi) A protein as defined in paragraphs (i) or (ii) or (iii) or (iv) in a heterodimeric form. Still yet another aspect of the present invention provides a method for modulating expression of galectin-14 in a subject, said method comprising contacting the galectin-14 gene with an effective amount of an agent for a time and under conditions sufficient to up-regulate or down-regulate or otherwise modulate expression of galectin-14. Another aspect of the present invention contemplates a method of modulating activity of galectin-14 in a mammal, said method comprising administering to said mammal a modulating effective amount of an agent for a time and under conditions sufficient to increase or decrease galectin-14 functional activity. In another aspect there is provided a method of treating a mammal said method comprising administering to said mammal an effective amount of an agent for a time and under conditions sufficient to modulate the expression of galectin-14 or sufficient to modulate the activity of galectin-14 wherein said modulation results in modulation of immune functioning. In yet another aspect the present invention relates to a method of treating a mammal said method comprising administering to said mammal an effective amount of galectin-14 or galectin-14 for a time and under conditions sufficient to modulate immune functioning. A further aspect of the present invention relates to a method for treatment and/or prophylaxis of a condition characterised by an aberrant, unwanted or otherwise inappropriate inflammatory response in a mammal said method comprising administering to said mammal an effective amount of an agent for a time and under conditions sufficient to modulate the expression of galectin-14 or sufficient to modulate the activity of galectin-14 wherein said modulation results in modulation of said inflammatory response. In another aspect the present invention relates to a method for the treatment and/or prophylaxis of a condition characterised by an aberrant, unwanted or otherwise inappropriate inflammatory response in a mammal said method comprising administering to said mammal an effective amount of galectin-14 or galectin-14 for a time and under conditions sufficient to modulate said inflammatory response. In yet another aspect, the present invention provides a method for the treatment and/or prophylaxis of an allergic condition, said method comprising administering to said mammal an effective amount of an agent for a time and under conditions sufficient to modulate the expression of galectin-14 or sufficient to modulate the activity of galectin-14 for a time and under conditions sufficient to down-regulate a Th-2 type inflammatory response. In still yet another aspect there is provided a method for the treatment and/or prophylaxis of an allergic condition, said method comprising administering to said mammal an effective amount of galectin-14 or galectin-14 for a time and under conditions sufficient to up-regulate a Th-2 type inflammatory response. Yet another aspect of the present invention relates to the use of an agent capable of modulating the expression of galectin-14 or modulating the activity of galectin-14 in the manufacture of a medicament for the modulation of an inflammatory response. A further aspect of the present invention relates to the use of galectin-14 or galectin-14 in the manufacture of a medicament for the modulation of an inflammatory response. Still yet another aspect of the present invention relates to agents for use in modulating galectin-14 expression or galectin-14 activity wherein said modulation results in modulation of an inflammatory response. Another aspect of the present invention relates to galectin-14 or galectin-14 for use in modulating an inflammatory response. In yet another further aspect the present invention contemplates a pharmaceutical composition comprising galectin-14, galectin-14 or an agent capable of modulating galectin-14 expression or galectin-14 activity together with one or more pharmaceutically acceptable carriers and/or diluents. Galectin-14, galectin-14 or said agent are referred to as the active ingredients. Another aspect of the present invention provides a method for detecting an agent capable of modulating the function of galectin-14 or its functional equivalent or derivative thereof said method comprising contacting a cell or extract thereof containing said galectin-14 or its functional equivalent or derivative with a putative agent and detecting an altered expression phenotype associated with said galectin-14 or its functional equivalent or derivative. In yet another aspect the present invention provides a method for detecting an agent capable of binding or otherwise associating with a galectin-14 binding site or functional equivalent or derivative thereof said method comprising contacting a cell containing said galectin-14 binding site or functional equivalent or derivative thereof with a putative agent and detecting an altered expression phenotype associated with modulation of the function of galectin-14 or its functional equivalent or derivative. Still another aspect of the present invention is directed to antibodies to galectin-14 including catalytic antibodies. In another aspect of the present invention, the molecules of the present invention are also useful as screening targets for use in applications such as the diagnosis of disorders which are regulated by galectin-14. Single and three letter abbreviations used throughout the specification are defined in Table 1. TABLE 1 Single and three letter amino acid abbreviations Three-letter One-letter Amino Acid Abbreviation Symbol Alanine Ala A Arginine Arg R Asparagine Asn N Aspartic acid Asp D Cysteine Cys C Glutamine Gln Q Glutamic acid Glu E Glycine Gly G Histidine His H Isoleucine Ile I Leucine Leu L Lysine Lys K Methionine Met M Phenylalanine Phe F Proline Pro P Serine Ser S Threonine Thr T Tryptophan Trp W Tyrosine Tyr Y Valine Val V Any residue Xaa |
System and method for transmitting digital multimedia data with analog broadcast data |
A method and system for the transmission of digital data (210) over existing analog radio frequencies (230) is presented, wherein the digital data may include audio data, visual data or audio-visual data for presentation either with analog broadcast data or at a selectable time. The digital data may be transmitted over a plurality of sub-channels that have varying degrees or reliability (250). A “quality-of-service” process manages the transmission of digital data over various sub-channels based on the reliability of the sub-channel, the amount of digital data and the type of digital data to be transmitted. The digital data may further be encrypted and authenticated. |
1-133. (canceled) 134. A system of transmitting digital data on at least one RF carrier of an audio broadcast, comprising: means to identify digital data corresponding to a set of broadcast data; means to determine synchronization data corresponding to a broadcast event; means to assemble a data packet including the digital data and the synchronization data; and means transmit the data packet to a receiver before the broadcast event. 135. The system of claim 134, wherein the digital data corresponds to multimedia information for display on a receiver. 136. The system of claim 134, wherein the multimedia information may be stored on a receiver for re-call by a user at a desired time. 137. The system of claim 134, wherein said transmitting further comprises: means to transmit the data packet in a digital format on at least one RF carrier of a central analog frequency on which the broadcast data is transmitted. 138. The system of claim 134, further comprising: means to transmit the broadcast data on a central analog frequency. 139. The system of claim 134, further comprising: means to determine authentication data for allowing a receiver to authenticate the data packet. 140. The system of claim 139, wherein said assembling further comprises: means to include the authentication data in the data packet for allowing the receiver to authenticate the source of the data packet. 141. The system of claim 139, wherein said authentication data includes at least one of: a time stamp and nonce information. 142. The system of claim 134, wherein said assembling further comprises: means to encrypt the data packet with a public key. 143. The system of claim 134, further comprising: means to determine a file size of the data packet. 144. The system of claim 143, wherein said transmitting further comprises: means to select at least one RF carrier of a central analog frequency based on the file size. 145. The system of claim 144, wherein said transmitting further comprises: means to transmit the data packet on the selected RF carrier. 146. The system of claim 134, wherein said synchronization data comprises an indication that the data may be stored by the receiver for recall by a user at a desired time. 147. The system of claim 134, wherein said central analog frequency corresponds to a single frequency on one of an amplitude-modulated band and a frequency-modulated band. 148. The system of claim 134, wherein said data packet comprises data in an extensible mark-up language format. 149. The system of claim 134, wherein the broadcast data is analog data. 150. The system of claim 134, wherein the broadcast data is non-analog data. 151. The system of claim 134, wherein the broadcast data is digital data. 152. The system of claim 134, wherein the broadcast data is multimedia. 153. A system of transmitting digital data on at least one RF carrier of an audio broadcast, comprising: means to identify digital data corresponding to a set of broadcast data; means to determine synchronization data corresponding to a broadcast event; means to assemble a data packet including the digital data and the synchronization data; means to transmit the data packet to a receiver before the broadcast event; and means to determine receiver information corresponding to a receiver type that is allowed to receive the data packet. 154. (canceled) 155. A system of transmitting digital data on at least one RF carrier of an audio broadcast, comprising: means to identify digital data corresponding to broadcast data; means to determine synchronization data corresponding to a broadcast event; means to assemble a data packet including the digital data and the synchronization data; and means to transmit the data packet to a receiver before the broadcast event. 156-159. (canceled) 160. A system of transmitting digital data on at least one RF carrier of an audio broadcast, comprising: means to identify digital data including multimedia information that may be recalled by a user of a receiver at a desired time; means to determine synchronization data corresponding to an instruction to the receiver to store the digital data in a memory; means to assemble a data packet including the digital data and the synchronization data; and means to transmit the data packet to a receiver. 161-178. (canceled) 179. The system of claim 134, wherein said data packet comprises data in an extensible mark-up language format. 180-184. (canceled) 185. A system of transmitting digital data on at least one RF carrier of an audio broadcast, comprising: means to identify digital data including multimedia information that may be recalled by a user of a receiver at a desired time; means to determine synchronization data corresponding to an instruction to the receiver to store the digital data in a memory; means to assemble a data packet including the digital data and the synchronization data; and means to transmit the data packet to a receiver. 186. A system for transmitting digital data on at least one RF carrier of an audio broadcast, comprising: means to identify digital data corresponding to live broadcast data; means to determine synchronization data indicating that the digital data is to be displayed upon receipt; means to assemble a data packet including the digital data and the synchronization data; means to transmit the live broadcast data on a central analog frequency; and means to transmit the data packet to a receiver on at least one RF carrier of the central analog frequency. 187-208. (canceled) 209. A system of transmitting digital data on at least one RF carrier of RF radio broadcast, comprising: means to identify digital data corresponding to a set of broadcast data: means to determine synchronization data corresponding to a broadcast event; means to assemble a data packet including the digital data and the synchronization data; and means to transmit the data packet to a receiver before the broadcast event. 210-213. (canceled) 214. A system of transmitting digital data on at least one RF carrier of RF radio broadcast, comprising: means to identify digital data corresponding to a set of broadcast data, wherein the broadcast data is audio; means to determine synchronization data corresponding to a broadcast event; means to assemble a data packet including the digital data and the synchronization data; and means to transmit the data packet to a receive before the broadcast event. 215-218. (canceled) 219. A system of transmitting digital data on at least one RF carrier of RF radio broadcast, comprising: means to identify digital data corresponding to a set of broadcast data, wherein the set of broadcast data is digital data; means to determine synchronization data corresponding to a broadcast event; assemble a data packet including the digital data and the synchronization data; and means to transmit the data packet to a receiver before the broadcast event. 220-223. (canceled) 224. A system of transmitting digital data on at least one RF carrier of RF radio. broadcast, comprising: means to identify digital data corresponding to a set of broadcast data, wherein the set of broadcast data is digital data, wherein the digital data is audio; means to determine synchronization data corresponding to a broadcast event; means to assemble a data packet including the digital data and the synchronization data; and means to transmit the data packet to a receiver before the broadcast event. 225-228. (canceled) 229. A system of transmitting digital data on at least one RF carrier of RF radio broadcast, comprising: means to identify digital data corresponding to a set of broadcast data; means to determine synchronization data corresponding to a broadcast event, wherein the broadcast event is the time that digital broadcast data will be broadcast on one or more RF carriers of a central frequency; means to assemble a data packet including the digital data and the synchronization data; and means to transmit the data packet to a receiver before the broadcast event. 230-233. (canceled) 234. A system of transmitting digital data on at least one RF carrier RF radio broadcast, comprising: means to identify digital data corresponding to a set of broadcast data; means to determine synchronization data corresponding to a broadcast event, wherein the broadcast event is a period of time that has elapsed since a given starting time; means to assemble a data packet including the digital data and the synchronization data; and means to transmit the data packet to a receiver before the broadcast event. 235-240. (canceled) 241. A system of transmitting broadcast data on one or more RF carriers of a broadcast, comprising: means to assemble a data packet including filtering information; means to transmit the data packet on one or more RF carriers of a broadcast. 242-247. (canceled) 248. A system of receiving broadcast data on one or more RF carriers of a broadcast on a receiving device, comprising: means to receive broadcast data on one or more RF carriers of a broadcast; means to extract a data packet from the received broadcast data; means to obtain filtering information from the data packet. 249-259. (canceled) 260. A system of transmitting digital data on at least one RF carrier of a broadcast, comprising: means to determine a priority for digital data; means to assemble a data packet including the digital data; means to prioritize the data packet; means to select at least one RF carrier of a central analog frequency for transmission with broadcast data of the data packet based on its priority; means to transmit the data packet with the broadcast data. 261. The system of claim 260, wherein the selection of the RF carrier is closer to the central analog frequency for higher priority data packets. 262. The system of claim 260, wherein the selection of the RF carrier is further from the central analog frequency for lower priority data packets for a temporal instant of the transmission. 263. The system of claim 260 further comprising: means to determine a file size of the data packet. 264. The system of claim 263, wherein the selection of the RF carrier is based on the file size. 265. The system of claim 260, wherein the transmission of the data packet occurs on the selected RF carrier. 266. The system of claim 264, wherein the central analog frequency corresponds to a single frequency on one of an amplitude-modulated band and a frequency-modulated band. 267-532. (canceled) |
<SOH> BACKGROUND OF THE INVENTION <EOH>In-Band On-Channel (IBOC) broadcasting is an emerging Digital Audio Broadcasting (DAB) technology, developed by IBIQUITY DIGITAL, INC., that enables existing radio broadcasters to transmit digital data over current analog transmission frequencies. Such radio broadcasters commonly employ amplitude-modulated (AM) and frequency-modulated (FM) bands for the transmission of audio broadcast data. IBOC technology has the ability to create a “hybrid” signal that can simultaneously send both the analog and digital data. U.S. Pat. No. 5,757,854, incorporated in its entirety herein by reference, discusses these capabilities in greater detail. Digital data may be digitally-formatted data or digitally compressed analog data. Digital data may include processing instructions for rendering visual and/or audio components on, for example, an IBOC receiver. Such processing instructions may be used to render synchronized visual components, such as text and images describing artist or song title information for currently-broadcast songs on the analog band, news headlines, traffic reports or other information that would be of interest to a radio listener. The digital data may include audio components for presenting selectable audio data. In an IBOC network, IBOC receivers recognize analog and digital data broadcast by IBOC transmitters, and present such data to a user through a display and/or an audio output. The user may interact with the data and provide a response via the IBOC receiver to either a party operating the IBOC transmitter or a third party. Additional examples of digital data and its uses are described in co-pending U.S. patent application Ser. No. 09/839,451, assigned to the assignee of the present invention. In order to accommodate these various IBOC network functionalities, a protocol for the assembly, transmission and synchronization of such digital data is described. |
<SOH> SUMMARY OF THE INVENTION <EOH>The present invention relates to the data formats used to transmit digital data over traditional analog bands and other features enabled by IBOC technology. One aspect of the present invention relates to the transmission of digital data, such as digital audio data, over pre-defined channels, such as AM or FM channels using known radio broadcast equipment. Another aspect of the present invention relates to the successful transmission of digital data over analog bands using various synchronization protocols between the sender and the receiver. Still another aspect of the present invention relates to providing sufficient security for the digital transmission so to prevent the tampering or corruption of data by an outside source. The security process involves various encryption protocols and authentication procedures. Yet another aspect of the present invention relates to the transmission of a response from an IBOC receiver to an appropriate operation handler. Such operation handler may be a native handler, wherein an embedded module or procedure exists to service the request. In another embodiment the appropriate operation handler may be a non-native handler, wherein the service request is transmitted to another device for handling. Still another aspect of the present invention relates to the creation of a Quality-of-Service (QOS) system, wherein a group of RF carrier bands is created around each central frequency available for broadcast. Since the reliability of data transmission decreases with RF carriers further from the central frequency, these RF carriers may be grouped according to the volume of data that can be successfully accommodated within a predetermined time. For example, digital data corresponding to a real-time sporting event (which may require continuous updates of digital data) may be transmitted over a more-reliable, high-volume RF carrier or set of RF carriers, while digital data corresponding to a weather report that is updated only every hour may be repeatedly transmitted over a less-reliable, low-volume or set of RF carriers to insure reception of all required digital data. |
Crash-protected vacuum brake booster for motor vehicles |
In order to improve the deformation behavior of a vacuum brake booster provided with force transmission pins that are used to transmit forces onto a body splashboard of a motor vehicle, the invention discloses that the force transmission pins are made up of two sections having different strength. To achieve a sufficiently low strength when a fastening screw is used for a first section, the first section is embodied as a hollow body, and the fastening screw extends only over the length of a second section of the pin. Because the first section is configured as a hollow body, the screw arranged in the second section can be actuated through the first section. |
1-7. (canceled) 8. Vacuum brake booster for motor vehicles with a booster housing including two opposed housing shells, with at least one movable wall subdividing the interior of the booster housing into two chambers, as well as with at least one force transmission pin that extends in parallel to the longitudinal axis of the vacuum brake booster from a first housing shell to the second housing shell arranged on the opposite side of the movable wall and is sealed in relation to the movable wall, and at the end of which force transmission pin fastening elements for a vehicle body wall or a master brake cylinder connected downstream of the vacuum brake booster are designed, with the force transmission pin including at least one first section and one second section, wherein the material cross-section of the first section is chosen to be small compared to the material cross-section of the second section to such an extent that it decreases its length extending in the longitudinal direction of the pin when a predetermined force is exceeded. 9. Vacuum brake booster as claimed in claim 8, wherein the first section is configured as a hollow cylinder, whose wall thickness is chosen so be so thin that the first section will reduce its length extending in the longitudinal direction of the pin when a predetermined force is exceeded. 10. Vacuum brake booster as claimed in claim 9, wherein the pin comprises a second section designed as a hollow cylinder, and in that a fastening screw extends through the second section and is supported with its screw head at least indirectly on the end surface of the section that forms the second cylinder and, with its threaded other end projects through the second housing shell close to the body wall. 11. Vacuum brake booster as claimed in claim 10, wherein the first and the second section are integrally formed or non-detachably interconnected. 12. Vacuum brake booster as claimed in claim 11, wherein the first section is provided with a projection made by deformation, with pressure forces that act on the first housing shell being supported on said projection. 13. Vacuum brake booster for motor vehicles with a booster housing including two opposed housing shells, with at least one movable wall subdividing the interior of the booster housing into two chambers, as well as with at least one force transmission pin that extends in parallel to the longitudinal axis of the vacuum brake booster from a first housing shell to the second housing shell arranged on the opposite side of the movable wall and is sealed in relation to the movable wall, and at the end of which force transmission pin fastening elements for a vehicle body wall or a master brake cylinder connected downstream of the vacuum brake booster are designed, with the force transmission pin including at least one first section and one second section, wherein the first section and the second section are formed of hollow cylinders, that the first and the second section are fixed in position to each other in the longitudinal direction of the pin by a holding connection, that the holding connection is disengaged when a predefined force that acts in the longitudinal direction of the pin is exceeded and the two sections are telescopically displaced into each other, and that a fastening screw projects through the second section and is supported with its screw head on the end face of the cylinder that forms the second section and with its threaded, other end projects through the second housing shell close to the body wall. 14. Vacuum brake booster as claimed in claim 13, wherein the first section is provided with a projection that is formed by deformation and on which pressure forces that act on the first housing shell are supported. |
<SOH> BACKGROUND OF THE INVENTION <EOH>A vacuum brake booster of this type is disclosed in German patent DE 28 45 794. A disadvantage of this prior art vacuum brake booster is its unfavorable deformation behavior in accidents, causing deformations of the front part of the motor vehicle. The cause for this are the force transmission pins that increase the rigidity of the booster housing, have a comparatively large diameter and, in an accident, exert an excessive resistance against deformation of the booster. Consequently, the splashboard of the vehicle is deformed, whereby the position of the bearing for the pedal will change so that the pedal can injure the driver in an accident. Details on this feature are described in DE 19524492. DE 19523021 A1 discloses a vacuum brake booster for motor vehicles with a force transmission pin, said force transmission pin changing its length when a predetermined longitudinal force is exceeded. |
<SOH> BRIEF SUMMARY OF THE INVENTION <EOH>In view of the above, an object of the present invention is to disclose novel measures for a vacuum brake booster for motor vehicles with a booster housing including two opposed housing shells, with at least one movable wall subdividing the interior of the booster housing into two chambers, as well as with at least one force transmission pin that extends in parallel to the longitudinal axis of the vacuum brake booster from a first housing shell to the second housing shell arranged on the opposite side of the movable wall and is sealed in relation to the movable wall, and at the end of which force transmission pin preferably fastening elements for a vehicle body wall or a master brake cylinder connected downstream of the vacuum brake booster are designed, with the force transmission pin including at least one first section and one second section enabling further improvement of the booster's deformation behavior in accidents. A first solution of this object involves that the force transmission pin includes at least one first section and one second section, and that the material cross-section of the first section is chosen to be small compared to the material cross-section of the second section to such an extent that it decreases its length extending in the longitudinal direction of the pin when a predetermined force is exceeded. A very simple construction is achieved thereby, and the separate provision of special predetermined breaking points is avoided. The first section is shortened alone by its reduced strength or its strength reduced compared to the second section. On the other hand, the position of the shortened length that results from bulging or buckling is fixed by the position of the first section. In a preferred aspect of the invention, it is advisable that the first section is configured as a hollow cylinder, whose wall thickness is chosen so be so thin that the first section will reduce its length extending in the longitudinal direction of the pin when a predetermined force is exceeded. This provides an option in particular for the case that it is desired to screw the booster from the tandem master cylinder to the splashboard by means of a screw that projects through the booster. In this case, the screw can be introduced through the hollow cylinder of the first section, the outside peripheral surface of which is sealed in relation to the interior of the housing. It is preferred according to a favorable aspect of the invention that the pin comprises a second section designed as a hollow cylinder, and in that a fastening screw extends through the second section and is supported with its screw head at least indirectly on the end surface of the section that forms the second cylinder and, with its threaded other end projects through the second housing shell close to the body wall. Thus, a sealed passage is achieved through which the screw can extend for attachment. The difficulty is that the screw shall be rigid enough to anchor the booster at the splashboard. On the other hand, a screw disposed in the first section would considerably reinforce the section's strength. Buckling or bulging of the first section when subjected to a sufficient amount of longitudinal force would therefore be no longer ensured. Further features of claim 3 provide a remedy in this respect. More specifically, the screw is lowered so deeply into the hollow cylinder of the first section that the screw can no longer contribute to reinforcement of the first section. Nevertheless, it is still possible to fasten the booster, coming from the master cylinder, by means of a screw that extends through the housing. In an improvement of the invention, the first and the second section are integrally formed or non-detachably interconnected. The non-detachable connection may e.g. be made by means of welding, soldering, cementing, form-lock or similar connection methods. A simple possibility of supporting forces that act on the second section can be achieved because the first section is provided with a projection preferably made by deformation, with pressure forces that act on the first housing shell or, as the case may be, tension forces being supported on said projection. A second solution of the object underlying the invention involves that the force transmission pin includes at least one first section and one second section, that the first section and the second section are configured as hollow cylinders, that the first and the second section are fixed in relation to each other by a holding connection in the longitudinal direction of the pin, that the holding connection is disengaged and the two sections are telescoped into each other when a predetermined force that acts in the longitudinal direction of the pin is exceeded, and that a fastening screw extends through the second section and is supported with its screw head on the end face of the cylinder forming the second section and with its other, threaded end projects through the second housing shell close to the body wall. This obviates the need for different strength or material thickness of the two sections. The second section is rather reinforced by the screw that extends only through it, yet does not contribute to reinforcing the first section. |
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