text
stringlengths 0
1.67M
|
|---|
A compound represented by the following general formula (I): (wherein R1 represents phenyl, etc. which can have substituents selected from the group consisting of C1-8 alkyl, C1-8 alkyl having halogen, halogen, hydroxyl, etc.; R2 represents C1-8 alkyl, etc.; A represents oxygen, sulfur, etc.; X represents C1-8 alkylene chain, etc.; Y represents C(═O), CH═CH, etc.; R3, R4, and R5 each represents hydrogen, C1-8 alkyl, etc.; B represents CH or nitrogen; Z represents oxygen or sulfur; R6 and R7 each represents hydrogen, C1-8 alkyl, etc.; and R8 represents hydrogen or C1-8 alkyl; provided that at least one of R3, R4, and R5 is not hydrogen) or a salt of the compound; and a PPAR-δ activator which contains the compound or salt as the active ingredient. |
1. A compound having the following formula (I) or a salt thereof: (wherein R1 is phenyl, naphthyl, pyridyl, thienyl, furyl, quinolyl or benzothienyl, any of which can have substituents selected from the group consisting of C1-8 alkyl, C1-8 alkyl having halogen, C1-8 alkoxy, C1-8 alkoxy having halogen, C2-8 alkenyl, C2-8 alkynyl, halogen, C2-7 acyl, benzoyl, hydroxyl, nitro, amino, phenyl and pyridyl; R2 is C1-8 alkyl, C1-8 alkyl having halogen, C2-8 alkenyl, C2-8 alkynyl, 3-7 membered cycloalkyl, C1-8 alkyl having 3-7 membered cycloalkyl, or C1-6 alkyl substituted with phenyl, naphthyl or pyridyl, any of which can have substituents selected from the group consisting of C1-8 alkyl, C1-8 alkyl having halogen, C1-8 alkoxy, C1-8 alkoxy having halogen, C2-8 alkenyl, C2-8 alkynyl, halogen, C2-7 acyl, benzoyl, hydroxyl, nitro, amino, phenyl and pyridyl; A is oxygen, sulfur or NR9 in which R9 is hydrogen or C1-8 alkyl; X is a C1-8 alkylene chain which can have substituents selected from the group consisting of C1-8 alkyl, C1-8 alkoxy and hydroxyl and which can contain a double bond; Y is C(═O), C(═N—OR10), CH(OR11), CH═CH, C—C, or C(═CH2) in which each of R10 and R11 is hydrogen or C1-8 alkyl; each of R3, R4 and R5 is hydrogen, C1-8 alkyl, C1-8 alkyl having halogen, C1-8 alkoxy, C1-8 alkoxy having halogen, C2-8 alkenyl, C2-8 alkynyl, halogen, C2-7 acyl, benzoyl, hydroxyl, nitro, amino, phenyl, or pyridyl; B is CH or nitrogen; Z is oxygen or sulfur; each of R6 and R7 is hydrogen, C1-8 alkyl, C1-8 alkyl having halogen; and R8 is hydrogen or C1-8 alkyl; provided that at least one of R3, R4 and R5 is not hydrogen. 2. A compound or a salt of thereof defined in claim 1, wherein R1 is phenyl which can have substituents selected from the group consisting of C1-8 alkyl, C1-8 alkyl having 1-3 halogen atoms, C1-8 alkoxy, C1-8 alkoxy having 1-3 halogen atoms, C2-8 alkenyl., C2-8 alkynyl, halogen, C2-7 acyl, benzoyl, hydroxyl, nitro, amino, phenyl and pyridyl. 3. A compound or a salt thereof defined in claim 1 or 2, wherein R2 is C2-8 alkyl. 4. A compound or a salt thereof defined in any one of claims 1 to 3, wherein R1 is attached to the 2nd position. 5. A compound or a salt thereof defined in any one of claims 1 to 4, wherein A is oxygen or sulfur. 6. A compound or a salt thereof defined in any one of claims 1 to 5, wherein X is a C1-8 alkylene chain. 7. A compound or a salt thereof defined in any one of claims 1 to 6, wherein Y is C(═O). 8. A compound or a salt thereof defined in any one of claims 1 to 7, wherein each of R3, R4 and R5 is hydrogen, C1-8 alkyl or C1-8 alkyl having halogen. 9. A compound or a salt thereof defined in any one of claims 1 to 8, wherein B is CH. 10. A compound or a salt thereof defined in any one of claims 1 to 9, wherein Z is oxygen. 11. A compound or a salt thereof defined in any one of claims 1 to 10, wherein each of R6 and R7 is hydrogen or C1-4 alkyl. 12. A compound or a salt thereof defined in any one of claims 1 to 11, wherein R8 is hydrogen. 13. A compound or a salt thereof defined in claim 1, wherein R1 is phenyl or naphthyl, each of which can have substituents selected from the group consisting of C1-8 alkyl, C1-8 alkyl having halogen, C1-8 alkoxy, C1-8 alkoxy having halogen, C2-8 alkenyl, C2-8 alkynyl, halogen, C2-7 acyl, benzoyl, hydroxyl, nitro, amino, phenyl and pyridyl; R2 is C2-8 alkyl; A is oxygen or sulfur; X is a C1-8 alkylene chain which can have a C1-8 alkyl substituent and which can contain a double bond; Y is C(═O), CH═CH, or C(═CH2); each of R3, R4 and R5 is hydrogen, C1-8 alkyl, C1-8 alkyl having halogen, C1-8 alkoxy, C1-8 alkoxy having halogen, C2-8 alkenyl, C2-8 alkynyl, halogen, C2-7 acyl, benzoyl, hydroxyl, nitro, amino, phenyl, or pyridyl; B is CH; Z is oxygen or sulfur; each of R6 and R7 is hydrogen or C1-8 alkyl; and R8 is hydrogen or C1-8 alkyl. 14. A compound or a salt thereof defined in claim 13, wherein X is a C1-8 alkylene chain. 15. A compound or a salt thereof defined in claim 13 or 14, wherein R1 is attached to the 2nd position. 16. A compound or a salt thereof defined in any one of claims 13 to 15, wherein R8 is hydrogen. 17. A compound or a salt thereof defined in any one of claims 13 to 16, wherein the substituents of R3, R4 and R5 other than hydrogens are placed at ortho-positions with respect to -Z-CR6R7CO2R8. 18. An activator of peroxisome proliferator activated receptor δ which contains as an effective component a compound or a salt thereof defined in any one of claims 1 to 17. |
<SOH> TECHNICAL FIELD <EOH>The present invention relates to an activator of peroxisome proliferator activated receptor δ. |
Navigation apparatus and navigation method |
A navigation device 10 comprises: position detecting means 11 for determining the current position of a user from the absolute position in longitude and latitude by using the electric waves coming from a plurality of artificial satellites going around the earth; storage means 14 for storing the coordinates in longitude and latitude of nodes, as obtained by setting a starting point and a final place, on a scheduled route; display means 12 for displaying the current position and the scheduled route; and control means 16 for controlling the display on the display means 12 by converting the angular data of the absolute positions and the coordinates into distance data while making corrections according to the current position, and by calculating an element between the nodes thereby to calculate whether or not the current position is on the scheduled route, in dependence upon whether or not the distance between the element and the current position is within a predetermined range. |
1. A navigation device is characterized by comprising: position detecting means for determining the current position of a user from the absolute position in longitude and latitude by using the electric waves coming from a plurality of artificial satellites going around the earth; storage means for storing the coordinates in the longitude and latitude of a starting place and a final place, and the coordinates in the longitude and latitude of nodes, as obtained by setting said starting point and said final place, on a scheduled route; display means for displaying said current position and said scheduled route; and control means for controlling the display on said display means by converting the angular data of said absolute positions and said coordinates into distance data while making corrections according to said current position, and by calculating an element between said nodes thereby to calculate whether or not said current position is on said scheduled route, in dependence upon whether or not the distance between said element and said current position is within a predetermined range. 2. A navigation device is characterized by comprising: position detecting means for determining the current position of a user from the absolute position in longitude and latitude by using the electric waves coming from a plurality of artificial satellites going around the earth; storage means for storing the coordinates in the longitude and latitude of a starting place and a final place, and the coordinates in the longitude and latitude of nodes, as obtained by setting said starting point and said final place, on a scheduled route; display means for displaying said current position and said scheduled route; control means for controlling the display on said display means by converting the angular data of said absolute positions and said coordinates into distance data while making corrections according to said current position, and by calculating an element between said nodes thereby to calculate whether or not said current position is on said scheduled route, in dependence upon whether or not the distance between said element and said current position is within a predetermined range; and interface means for interchanging data with an external auxiliary device for searching said scheduled route. 3. A navigation method characterized: in that at least one scheduled route is determined by setting a starting place and a final place, before used, with an external auxiliary device thereby to search said scheduled route; in that the coordinates in longitude and latitude of the starting place and the final place and the coordinates in longitude and latitude of nodes on said scheduled route are stored in storage means of the navigation device through interface means; in that the absolute position in longitude and latitude of the current position of a user by using electric waves coming from a plurality of artificial satellites going around the earth with position detecting means; in that the angular data of said absolute position and said coordinates while making corrections according to said current position are converted into distance data, and in that an element between said nodes is determined by calculations; in that whether or not said current position is on said scheduled route is calculated depending on whether or not the distance between said element and said current position is within a predetermined range; and in that said current position and said scheduled route are displayed by display means in accordance with the calculation results. 4. A navigation method as set forth in claim 3, characterized in that said predetermined range is made so different in values between the cases, in which said current position is approaching and leaving said scheduled route that the former value is smaller than the latter value. |
<SOH> Background Art <EOH>The navigation device to be mounted on an automobile or a two-wheeled vehicle, for example, is constructed to include: position detecting means such as a GPS (Global Positioning System) for determining the current position of the user of the vehicle by using the electric waves coming from a plurality of artificial satellites going around the earth; reproduction means for reproducing storage medium such as the CD-ROM stored with map data and accessory data associated therewith (e.g., display data to be displayed together with the map data such as place names or road names, or non-display data not to be displayed together with the map data, such as coordinates of nodes such as the intersections on roads or the points having made turns at predetermined angles (in degrees) or the distance or the like of an element indicating the segment between the nodes) associated with the map data; and control means such as a microcomputer for controlling those means. On the basis of the current position specified by the position detecting means, the reproduction means reads the map data, as stored in the storage medium, of the corresponding area, and the current position or the like is displayed by display means such as a liquid crystal display element (as referred to JP-A-10-20776 and JP-A-11-14378, for example). In another navigation device practiced, alternatively, by operating input means such as a remote-control or touch-panel type switch to set a starting place and a final place (including a routed place on the route), the control means searches a scheduled route from the map data or the like of its surrounding place, and the user is guided by using the display means on the basis of the scheduled route and the current position. This navigation device has to be mounted on the vehicle in its entirety including the position detecting means, the reproduction means (containing the storage medium), the control means, the display means and the input means, so that the system construction is large-sized to raise a problem in the retention of the mounting space. For the guidance, on the other hand, there is known a navigation device (as referred to JP-A-9-145394), in which the precision is enhanced by using the absolute position obtained by the GPS in longitude and latitude, together with the relative position determined by an self-contained navigation for measuring the movements from a reference point (e.g., the starting point) by accumulating them with a distance sensor and a direction sensor, because it is difficult for the position detecting means to determine the current position precisely merely with the GPS. This navigation device can have an enhanced location precision but is troubled by a problem that the operations of the absolute position and the relative position are complicated. There is also known a navigation device, in which the number of branches of routes, the branching directions and the positional information (in latitude, longitude and altitude) are stored as the map information in a flash memory to display those branching situations and the straight lines joining the individual branches in distance and direction, so as. to retain the portability and to reduce the capacity of storage for the map information (as referred to JP-A-2002-22480, for example). In this navigation device, the storage capacity is reduced, but the angular data in the longitude and latitude are used. Therefore, it seems that a difference appears in the distance data which are needed when the relations between the current position and the branches are measured and displayed. This is caused the earth has a spherical shape so that the point distance becomes different even for an equal angular difference. The present invention has been conceived in view of those problems and has an object to provide a navigation device and a navigation method, which can reduce the size of the system construction and can improve the precision while simplifying the operations. |
<SOH> BRIEF DESCRIPTION OF THE DRAWINGS <EOH>FIG. 1 is a block diagram for explaining a construction of a navigation device; FIG. 2 is an explanatory diagram of a scheduled route in the navigation device; FIG. 3 presents explanatory diagrams of a current position in the navigation device; and FIG. 4 presents explanatory diagrams of displays in the navigation device. detailed-description description="Detailed Description" end="lead"? |
Apparatus and method for controlling adaptive circuits |
A feed-forward amplifier having a signal cancellation loop including a cancellation node that includes a gain controller and a phase controller. Each controller provides a discrete tap steering signal and modulates the corresponding tap steering signal with a discrete tracer signal that takes on a preselected sequence of values. The sequence chosen so that the tracer signal is mutually orthogonal to each other tracer signal over a preselected period. A gain and phase adjuster connected to the outputs of the controllers provides a controlled gain change and phase shift in the signal cancellation loop, the magnitude of the gain change and phase shift controlled by the corresponding tap steering signals presented to the gain and phase adjuster by the controllers. A detector, the input of which is connected to the cancellation node and the output of which is connected to the controllers, outputs a measure of the envelope of the signal at the cancellation node. After the preselected period new values for the tap steering signals presented to the gain and phase adjuster by the controllers are obtained by multiplying detector output by the respective tracer signal, each over the respective preselected period, summing each resulting series of values, and changing the tap steering signals to be modulated and presented to the gain and phase adjuster in accordance with the values of the respective sums. |
1-42 (Cancelled) 43. A feed-forward amplifier having a signal cancellation loop including a cancellation node, comprising: a gain controller and a phase controller, each controller for providing a discrete tap steering signal and modulating the corresponding tap steering signal with a discrete tracer signal that takes on a preselected sequence of values, the sequence chosen so that the tracer signal is mutually orthogonal to each other tracer signal over a preselected period; a gain and phase adjuster connected to the outputs of the controllers for providing a controlled gain change and phase shift in the signal cancellation loop, the magnitude of the gain change and phase shift controlled by the corresponding tap steering signals presented to the gain and phase adjuster by the controllers; and a detector, the input of which is connected to the cancellation node and the output of which is connected to the controllers, the detector outputting a measure of the envelope of the signal at the cancellation node, wherein after the preselected period new values for the tap steering signals presented to the gain and phase adjuster by the controllers are obtained by multiplying detector output by the respective tracer signal, each over the respective preselected period, summing each resulting series of values, and changing the tap steering signals to be modulated and presented to the gain and phase adjuster in accordance with the values of the respective sums. 44. The feed-forward amplifier of claim 43, wherein each tap steering signal is increased or decreased depending upon the polarity of the corresponding sum. 45. The feed-forward amplifier of claim 43, wherein the tap steering signal presented to the gain and phase adjuster is left unchanged if the corresponding sum is zero or within a preselected range about zero but, if the corresponding sum is outside the preselected range about zero, is increased or decreased depending upon the polarity of the corresponding sum. 46. The feed-forward amplifier of claim 45, wherein a tap steering signal is increased if the corresponding sum is positive and decreased if the corresponding sum is negative. 47. A feed-forward amplifier, comprising: an input port; a first main path splitter, the input of which is connected to the input port so that when an input signal applied to the input port it is split by the first main path splitter into a main signal and a feed-forward signal; a main signal path gain and phase adjuster, the input of which is connected to the first output of the first main path splitter, the main signal path gain and phase adjuster having a gain-control input tap and a phase-control input tap configured so that the voltage levels on the taps control the amplitude and phase of the main signal; a main amplifier, the input of which is connected to the output of the main signal path gain and phase adjuster; a second main path splitter, the input of which is connected to the output of the main amplifier; a feed-forward signal path delay element, the input of which is connected to the second output of the first main path splitter, the delay imposed by the feed-forward signal path delay element selected to approximately match the delay in the main signal caused by the main amplifier; a feed-forward path coupler, the first input of which is connected to the output of the feed-forward signal path delay element; a connector/attenuator connecting the second output of the second main path splitter to the second input of the feed-forward path coupler, the attenuation selected so that the undistorted portion of the main signal provided to the feed-forward path coupler is approximately cancelled out by the feed-forward signal; a feed-forward path splitter, the input of which is connected to the output of the feed-forward path coupler; a detector, the input of which is connected to the second output of the feed-forward path splitter; a gain controller, the input of which is connected to the output of the detector and the output of which is connected to the gain-control input tap; and a phase controller, the input of which is connected to the output of the detector and the output of which is connected to the phase-control input tap, wherein: each of the controllers modulates the voltage level on its respective output with a discrete low level signal that takes on a preselected sequence of values, the sequence chosen so that each low level signal is mutually orthogonal to each other low level signal over a preselected period; the detector outputs a measure of the envelope of the signal at the cancellation node; and each controller multiples the signal received from the detector by the low level signal with which it modulated the tap to which it is connected, in each case over the preselected period, sums the resulting series of values over time, and changes the voltage level on its respective tap in accordance with the value of the sum. 48. The feed-forward amplifier of claim 47, wherein each voltage level is increased or decreased depending upon the polarity of the corresponding sum. 49. The feed-forward amplifier of claim 47, wherein the voltage level presented to the gain and phase adjuster is left unchanged if the corresponding sum is zero or within a preselected range about zero but, if the corresponding sum is outside the preselected range about zero, is increased or decreased depending upon the polarity of the corresponding sum. 50. The feed-forward amplifier of claim 49, wherein each voltage level is increased if the corresponding sum is positive and decreased if the corresponding sum is negative. 51. The feed-forward amplifier of claim 50, wherein the low level signals vary in polarity but not in magnitude. 52. The feed-forward amplifier of claim 51, wherein the low level signals are chosen to be pseudo noise sequences. 53. The feed-forward amplifier of claim 51, wherein the low level signals are chosen to be Walsh codes. 54. The feed-forward amplifier of claim 53, wherein each output voltage level is changed in proportion to magnitude of the respective sum. 55. A feed-forward amplifier having a signal cancellation loop including a cancellation node at which a signal is to be minimized, comprising: a controller for providing a tap steering signal and modulating the tap steering signal with a tracer signal that takes on a preselected sequence of values; an adjuster connected to the output of the controller for providing a controlled change in a characteristic of the signal cancellation loop that results in a change in a measure of the envelope of the signal at the cancellation node, the magnitude of the change in the characteristic controlled by the modulated tap steering signal presented to the adjuster by the controller; and a detector, the input of which is connected to the cancellation node and the output of which is connected to the controller, the detector for outputting the measure of the envelope of the signal at the cancellation node, wherein after the preselected period a new setting for the tap steering signal is obtained by multiplying the detector output by the tracer signal, summing the resulting series of values, and changing the tap steering signal to be modulated and provided to the adjuster in accordance with the value of the sum. 56. The feed-forward amplifier of claim 55, wherein a tap steering signal is increased or decreased depending upon the polarity of the corresponding sum. 57. The feed-forward amplifier of claim 55, wherein the tap steering signal presented to the gain and phase adjuster left unchanged if the corresponding sum is zero or within a preselected range about zero but, if the corresponding sum is outside the preselected range about zero, increasing or decreasing the tap steering signal depending upon the polarity of the corresponding sum. 58. The feed-forward amplifier of claim 57, wherein a tap steering signal is increased if the corresponding sum is positive and decreased if the corresponding sum is negative. 59. The feed-forward amplifier of claim 57, wherein the tap steering signal is changed in proportion to magnitude of the sum. 60. The feed-forward amplifier of claim 59, wherein the adjuster is a gain adjuster and the characteristic is gain in the gain adjuster. 61. The feed-forward amplifier of claim 59, wherein the adjuster is a phase adjuster and the characteristic is phase change in the phase adjuster. 62. The feed-forward amplifier of claim 59, wherein the tracer signal is chosen to be a pseudo noise sequence. 63. The feed-forward amplifier of claim 59, wherein the tracer signal is chosen to be a Walsh code. 64. A circuit having a node at which a signal is adaptively minimized by the circuit, comprising: a controller providing an output voltage level, the output voltage level modulated by a low level signal that takes on a preselected sequence of values over a preselected period; an adjuster connected to the output of the controller for providing a controlled change in a characteristic of the adaptive circuit that results in a change in the envelope of the signal at the node, the magnitude of the change in the characteristic controlled by the voltage level presented to the adjuster by the controller; and a detector, the input of which is connected to the node and the output of which is connected to the controller, the detector outputting a measure of the envelope of the signal at the node, wherein after the preselected period a new setting for the voltage level presented to the adjuster by the controller is obtained by multiplying the detector output by the low level signal, summing the resulting series of values, and changing the voltage level presented to the adjuster in accordance with the value of the sum. 65. The circuit of claim 64, wherein the output voltage level is increased or decreased depending upon the polarity of the sum. 66. The circuit of claim 64, wherein the output voltage level is left unchanged if the sum is zero or within a preselected range about zero but, if the sum is outside the preselected range about zero, increasing or decreasing the output voltage level depending upon the polarity of the sum. 67. The circuit of claim 66, wherein the output voltage level is increased if the sum is positive and decreased if the sum is negative. 68. The circuit of claim 66, wherein the low level signal voltage level is changed in proportion to magnitude of the sum. 69. The circuit of claim 68, wherein the low level signal is chosen to be a Walsh code. 70. The circuit of claim 68, wherein the low level signal is chosen to be a pseudo noise sequence. 71. A method for operating an adaptive control circuit having a plurality of control input taps, the method comprising, for each control input, the steps of: detecting a signal, including a tracer signal, from the adaptive control circuit; extracting a measurement from the tracer signal in the detected signal; determining an appropriate input to be applied to the control input to improve operation of the adaptive control circuit; creating a tracer signal for the control input, the created tracer signal being orthogonal to the tracer signals created for each other control input; and combining the tracer signal and the determined input and applying the resulting signal to the control input. 72. The method according to claim 71 wherein the adaptive control circuit comprises an amplifier portion of a feed forward amplifier having a pair of input control taps for a first gain-and-phase adjuster and a second pair of control input taps for a second gain and phase adjuster. 73. The method according to claim 71 wherein the tracer signals are Walsh codes. 74. The method according to claim 71 wherein the tracer signals are pseudo noise sequences. 75. The method according to claim 71 wherein the tracer signal and the determined input are combined by applying the tracer signal to the determined input as a dither. 76. An adaptive circuit comprising: at least two adjusters, each adjuster including at least one control input to alter the operation of the circuit; at least one signal generator to create at least two tracer signals, each created tracer signal being orthogonal to each other created tracer signal; at least two controllers, each controller operable to output a control signal to at least a respective one of the control inputs of the at least two adjusters, a different orthogonal tracer signal from the at least one signal generator being applied to each respective control signal as a dither; and at least one detector operable to extract a composite signal from the circuit and to apply the composite signal to the at least two controllers, each controller being responsive to the applied signal to extract at least one orthogonal tracer and to alter the respective control signal to converge operation of the circuit to an optimal or near optimal configuration. 77. The adaptive circuit as claimed in claim 76, wherein the adaptive circuit is a feed forward amplifier. 78. The adaptive circuit as claimed in claim 77, wherein the at least two adjusters operate to adjust the phase and gain of a signal passed through them and each of the at least two adjusters includes a phase control input tap to control the phase adjustment and a gain control input tap to control the gain adjustment. 79. The adaptive circuit as claimed in claim 78, further including at least two detectors, each of the at least two detectors extracting at least two composite signals and applying the composite signals to a respective one of the at least two controllers, each controller being responsive to the applied signal to extract at least one orthogonal tracer and alter the respective control signal to converge operation of the circuit to an optimal or near optimal configuration. 80. The adaptive circuit as claimed in claim 78 wherein the orthogonal tracer signals are Walsh codes. 81. The adaptive circuit as claimed in claim 78 wherein the orthogonal tracer signals are pseudo noise sequences. |
<SOH> BACKGROUND OF THE INVENTION <EOH>Adaptive circuits are well known and used in a variety of applications. One well-known example of an adaptive circuit is the feed forward amplifier (“FFA”). In order to achieve linearity in a feed forward amplifier, careful control of the amplifier circuitry is required. In particular, in FFAs two or more gain and phase adjusters are often employed and the taps of each of these adjusters are carefully steered to achieve linearity through the amplifier. Within the art of FFAs, it is known to use detector-controller circuits, one for each gain-and-phase adjuster. Each detector-controller circuit is operable to steer the taps of its respective gain-and-phase adjuster in the FFA so that the main amplifier and correctional amplifier can properly cooperate in order to reduce error introduced by the main amplifier and, should a pilot tone be used in the FFA, to also reduce the output residue of the pilot tone injected prior to the main amplifier. In certain prior art detector-controller circuits, once the detector portion of the detector-controller circuit has indicated that the associated controller portion should make an adjustment, the controller arbitrarily steers the taps of the gain-and-phase adjuster in a direction to either increase or decrease the input to the tap, without knowing which of an increase or decrease will actually achieve the desired effect. In order to verify whether the controller steered the tap in the correct direction (e.g., to increase the signal to the tap), after the correction has been applied the detector circuit ascertains whether the direction of the variation brought about the desired effect, and, if so, instructs the controller circuit to continue steering in the same direction, if necessary. If, however, the detector circuit ascertains that the steering direction brought about an undesired result, then the detector instructs to the controller to try steering the tap in the opposite direction (e.g., to decrease the signal to the tap). In the prior art, each detector-controller circuit works independently of each other, and therefore, achieving convergence towards an optimum level for each tap of each adjuster can be difficult. For example, rapid changes in the strength of the input signal being amplified by the FFA can make it difficult for the detector-controller circuits to respond quickly enough to converge the tap levels of each gain-and-phase adjuster towards the respective optimum levels. Furthermore, the adjustment of one tap of a gain-and-phase adjuster can disrupt an optimum or near optimum input level achieved at another tap, therefore cascading disruptions through all of the taps. The inventor of the present invention also believes that a further problem is that such prior art controller circuits can sometimes result in taps being steered to levels that are levels corresponding to local minima for the input signal, missing a global optimum for the input signal. |
<SOH> SUMMARY OF THE INVENTION <EOH>It is an object of the present invention to provide a novel apparatus and method for controlling an adaptive circuit that obviates or mitigates at least one of the above-identified disadvantages of the prior art. It is a further object of the present invention to provide a novel feed forward amplifier that obviates or mitigates at least one of the above-identified disadvantages of the prior art. According to an aspect of the present invention, there is provided a feed-forward amplifier having a signal cancellation loop including a cancellation node that includes a gain controller and a phase controller. Each controller provides a discrete tap steering signal and modulates the corresponding tap steering signal with a discrete tracer signal that takes on a preselected sequence of values. The sequence chosen so that the tracer signal is mutually orthogonal to each other tracer signal over a preselected period. A gain and phase adjuster connected to the outputs of the controllers provides a controlled gain change and phase shift in the signal cancellation loop, the magnitude of the gain change and phase shift controlled by the corresponding tap steering signals presented to the gain and phase adjuster by the controllers. A detector, the input of which is connected to the cancellation node and the output of which is connected to the controllers, outputs a measure of the envelope of the signal at the cancellation node. After the preselected period new values for the tap steering signals presented to the gain and phase adjuster by the controllers are obtained by multiplying detector output by the respective tracer signal, each over the respective preselected period, summing each resulting series of values, and changing the tap steering signals to be modulated and presented to the gain and phase adjuster in accordance with the values of the respective sums. Optionally, each tap steering signal may be increased or decreased depending upon the polarity of the corresponding sum, or the tap steering signal presented to the gain and phase adjuster is left unchanged if the corresponding sum is zero or within a preselected range about zero but, if the corresponding sum is outside the preselected range about zero, is increased or decreased depending upon the polarity of the corresponding sum. Also, each tap steering signal is increased if the corresponding sum is positive and decreased if the corresponding sum is negative. In any of the embodiments discussed above, the tracer signals vary in polarity but not in magnitude and may be chosen to be pseudo noise sequences or Walsh codes. According to another aspect of the present invention, there is provided a feed-forward amplifier that includes: an input port; a first main path splitter, the input of which is connected to the input port so that when an input signal applied to the input port it is split by the first main path splitter into a main signal and a feed-forward signal; a main signal path gain and phase adjuster, the input of which is connected to the first output of the first main path splitter, the main signal path gain and phase adjuster having a gain-control input tap and a phase-control input tap configured so that the voltage levels on the taps control the amplitude and phase of the main signal; a main amplifier, the input of which is connected to the output of the main signal path gain and phase adjuster; a second main path splitter, the input of which is connected to the output of the main amplifier; a feed-forward signal path delay element, the input of which is connected to the second output of the first main path splitter, the delay imposed by the feed-forward signal path delay element selected to approximately match the delay in the main signal caused by the main amplifier; a feed-forward path coupler, the first input of which is connected to the output of the feed-forward signal path delay element; a connector/attenuator connecting the second output of the second main path splitter to the second input of the feed-forward path coupler, the attenuation selected so that the undistorted portion of the main signal provided to the feed-forward path coupler is approximately cancelled out by the feed-forward signal; a feed-forward path splitter, the input of which is connected to the output of the feed-forward path coupler; a detector, the input of which is connected to the second output of the feed-forward path splitter; a gain controller, the input of which is connected to the output of the detector and the output of which is connected to the gain-control input tap; and a phase controller, the input of which is connected to the output of the detector and the output of which is connected to the phase-control input tap, wherein: each of the controllers modulates the voltage level on its respective output with a discrete low level signal that takes on a preselected sequence of values, the sequence chosen so that each low level signal is mutually orthogonal to each other low level signal over a preselected period; the detector outputs a measure of the envelope of the signal at the cancellation node; and each controller multiples the signal received from the detector by the low level signal with which it modulated the tap to which it is connected, in each case over the preselected period, sums the resulting series of values over time, and changes the voltage level on its respective tap in accordance with the value of the sum. Optionally, each voltage level is increased or decreased depending upon the polarity of the corresponding sum or the voltage level presented to the gain and phase adjuster is left unchanged if the corresponding sum is zero or within a preselected range about zero but, if the corresponding sum is outside the preselected range about zero, is increased or decreased depending upon the polarity of the corresponding sum. Also, each voltage level may be increased if the corresponding sum is positive and decreased if the corresponding sum is negative and each output voltage level may be changed in proportion to magnitude of the respective sum. In any of the embodiments discussed above, the low level signals vary in polarity but not in magnitude and the low level signals may be chosen to be pseudo noise sequences or Walsh codes. According to yet another aspect of the present invention, there is provided a feed-forward amplifier having a signal cancellation loop including a cancellation node at which a signal is to be minimized, including: a controller for providing a tap steering signal and modulating the tap steering signal with a tracer signal that takes on a preselected sequence of values; an adjuster connected to the output of the controller for providing a controlled change in a characteristic of the signal cancellation loop that results in a change in a measure of the envelope of the signal at the cancellation node, the magnitude of the change in the characteristic controlled by the modulated tap steering signal presented to the adjuster by the controller; and a detector, the input of which is connected to the cancellation node and the output of which is connected to the controller, the detector for outputting the measure of the envelope of the signal at the cancellation node, wherein after the preselected period a new setting for the tap steering signal is obtained by multiplying the detector output by the tracer signal, summing the resulting series of values, and changing the tap steering signal to be modulated and provided to the adjuster in accordance with the value of the sum. Optionally, the tap steering signal may be increased or decreased depending upon the polarity of the corresponding sum, or the tap steering signal presented to the gain and phase adjuster is left unchanged if the corresponding sum is zero or within a preselected range about zero but, if the corresponding sum is outside the preselected range about zero, is increased or decreased depending upon the polarity of the corresponding sum. Also, the tap steering signal is increased if the corresponding sum is positive and decreased if the corresponding sum is negative. In any of the embodiments discussed above, the tracer signal vary in polarity but not in magnitude and may be chosen to be pseudo noise sequences or Walsh codes. According to yet another aspect of the present invention, there is provided a circuit having a node at which a signal is adaptively minimized by the circuit, comprising: a controller providing an output voltage level, the output voltage level modulated by a low level signal that takes on a preselected sequence of values over a preselected period; an adjuster connected to the output of the controller for providing a controlled change in a characteristic of the adaptive circuit that results in a change in a measure of the envelope of the signal at the node, the magnitude of the change in the characteristic controlled by the voltage level presented to the adjuster by the controller; and a detector, the input of which is connected to the node and the output of which is connected to the controller, the detector outputting the measure of the envelope of the signal at the node, wherein after the preselected period a new setting for the voltage level presented to the adjuster by the controller is obtained by multiplying the detector output by the low level signal, summing the resulting series of values, and changing the voltage level presented to the adjuster in accordance with the value of the sum. Optionally, each voltage level is increased or decreased depending upon the polarity of the corresponding sum or the voltage level presented to the adjuster is left unchanged if the corresponding sum is zero or within a preselected range about zero but, if the corresponding sum is outside the preselected range about zero, is increased or decreased depending upon the polarity of the corresponding sum. Also, each voltage level may be increased if the corresponding sum is positive and decreased if the corresponding sum is negative and each output voltage level may be changed in proportion to magnitude of the respective sum. According to yet another aspect of the present invention, there is provided a feed forward amplifier comprising: an amplifier portion including a coupler, first and second gain and phase adjusters, first and second delay elements, a main amplifier and a correctional amplifier, the coupler providing an input signal to said amplifier portion to a first signal path including the first gain and phase adjuster, the main amplifier and the first delay element and an output and the coupler providing the input signal to a second signal path including the second delay element, the second gain and phase adjuster and the correctional amplifier having a first signal path for carrying an input signal to a first gain-and-phase adjuster and a main-amplifier, said first gain-and-phase adjuster having a pair of taps for steering said first adjuster, said amplifier portion having a second signal path for carrying a sample of said input signal generated to a second gain-and-phase adjuster and a correctional-amplifier, said second gain-and-phase adjuster having a pair of taps for steering said adjuster; and a detector-controller portion having a first detector for receiving a detected signal from said first signal path and a second detector for receiving a detected signal from said second signal path, said detector-controller portion further comprising a first pair of controllers for receiving said detected signal from said first detector and a second pair of controllers for receiving said detected signal from said second detector, said controllers each operable to steer a respective one of said taps based on said received detected signals, each of said controllers further operable to inject tracer-signals into its respective tap, said tracer-signals for carrying through said amplifier portion and modulating said detected signals, said controllers each operable to extract from its respective detected signals a tap-signal by using its respective said tracer-signal, said controllers each further operable to utilize said extracted tap-signal to determine a desired direction for steering its respective tap and to output, substantially simultaneously with each other controller, a signal to steer said respective tap. According to yet another aspect of the present invention, there is provided a feed forward amplifier comprising: an amplifier portion including: (a) a first signal path having a first gain and phase adjuster, a main amplifier and a delay element; and (b) a second signal path having a delay element, a second gain and phase adjuster and a correctional amplifier, each gain and phase adjuster including a control input tap to accept an input to alter the phase response of the gain and phase adjuster and a control input tap to accept an input to alter the gain response of the gain and phase adjuster, the first and second signal paths having a common signal input and a common signal output; and a detector portion including: (c) a first detector to receive a signal from the common signal output and to provide the received signal to a first controller operable to create an input to the gain tap of the second gain and phase adjuster and to provide the received signal to a second controller operable to create an input to the phase tap of the second gain and phase adjuster; and (d) a second detector to receive a signal from the second signal path before the second gain and phase adjuster and to provide the received signal to a first controller operable to create an input to the gain tap of the first gain and phase adjuster and to provide the received signal to a second controller operable to create an input to the phase tap of the first gain and phase adjuster, each controller responsive to a component in said received signals which is orthogonal to the components to which each other controller are responsive to and all the created inputs being applied to the taps substantially simultaneously and altering the operation of said feed forward amplifier to linearize the amplification of the input signal through the feed forward amplifier. According to yet another aspect of the present invention, there is provided a method for operating an adaptive control circuit having a plurality of control input taps, said method comprising, for each said control input, the steps of: detecting a signal, including a tracer signal, from said circuit; extracting a measurement from the tracer signal in said detected signal; determining an appropriate input to be applied to said control input to improve operation of said adaptive circuit; creating a tracer signal for said control input, said created tracer signal being orthogonal to the tracer signals created for each other control input; and combining said tracer signal and said determined input and applying the resulting signal to said control input. An apparatus and method for operating an adaptive circuit includes injecting a set of orthogonal tracer signals into the circuit. The tracers' signals are extracted after modification during operation of at least a portion of the circuit and are examined by respective controllers to modify operation of the circuit. In one embodiment, the invention is incorporated into a feed forward amplifier in which a set of orthogonal tracer signals is applied to the amplifier. A detector controller detects a signal including as components the orthogonal tracer signals as modified by portions of the amplifier. Each controller portion of the detector controller extracts a measurement relative to its respective tracer signal from the detected signal and modifies its output to control a portion of the amplifier accordingly. The controllers apply their outputs to the respective portions of the amplifier at substantially the same time, leading to quick convergence of the operating point of the amplifier to an optimal, or near-optimal, configuration. Injection of the tracer signals into the amplifier is accomplished by dithering the controller outputs by the respective orthogonal tracer signals. According to yet another aspect of the present invention, there is provided an adaptive circuit comprising: at least two adjusters, each adjuster including at least one control input to alter the operation of the circuit; at least one signal generator to create at least one tracer signal, each created tracer signal being orthogonal to each other created tracer signal; at least two controllers, each controller operable to output a control signal to at least a respective one of the control inputs of the at least two adjusters, a different orthogonal tracer signal from said at least one signal generator being applied to each respective control signal as a dither; and at least one detector operable to extract a composite signal from the circuit and to apply the composite signal to the at least two controllers, each controller being responsive to the applied signal to extract at least one orthogonal tracer and alter the respective control signal to converge operation of the circuit to an optimal or near optimal configuration. |
Method of forming tungsten film |
A method of forming a tungsten film, capable of restricting voids and volcanoes as large as adversely affecting characteristics despite the small diameter of a buried hole, and providing good burying characteristics. When forming a tungsten film on the surface of an object of treating (W) in a vacuumizing-enabled treating vessel (22), a reduction gas supplying process 70 and a tungsten gas supplying process 72 for supplying a tungsten-containing gas are alternately repeated with a purge process 74, for supplying an inert gas while vacuumizing, intervened therebetween to thereby form an initial tungsten film 76. Therefore, an initial tungsten film can be formed as a nucleation layer high in film thickness uniformity; and, accordingly, when main tungsten films are subsequently deposited, it is possible to restrict voids and volcanoes as large as adversely affecting characteristics despite the small diameter of a buried hole, and provide good burying characteristics. |
1. A method of forming a tungsten film on a surface of an object to be processed in a vessel capable of being vacuumized, the method comprising the step of: forming an initial tungsten film by alternately repeating a reduction gas supplying process for supplying a reduction gas and a tungsten gas supplying process for supplying a tungsten-containing gas with an intervening purge process therebetween for supplying an inert gas while vacuumizing the vessel. 2. The method of claim 1, wherein the initial tungsten film is formed by alternately repeating the reduction gas supplying process for supplying the reduction gas and the tungsten gas supplying process for supplying the tungsten-containing gas while controlling the total pressure of the gases to be constant throughout the step of forming the initial tungsten film. 3. The method of claim 1, wherein a parameter, which is obtained by multiplying a partial pressure of the reduction gas by the supplying time thereof in an initial reduction gas supplying process among the repeated reduction gas supplying processes, is set to be greater than that in the remaining reduction gas supplying processes. 4. The method of claim 1, wherein a reduction gas supplying period of in an initial reduction gas supplying process among the repeated reduction gas supplying processes is set to be longer than that of the remaining reduction gas supplying processes. 5. (deletion) 6. (deletion) 7. (deletion) 8. (deletion) 9. The method of claim 1, wherein the tungsten-containing gas is WF6 gas or an organic tungsten source gas. 10. The method of claim 1, wherein the reduction gas is selected from the group consisting of H2 gas, silane (SiH4), disilane (Si2H6), dichlororosilane (SiH2Cl2), diboran (B2H6) and phospine (PH3). 11. (deletion) 12. (deletion) 13. (deletion) 14. (deletion) 15. (deletion) 16. (deletion) 17. (deletion) 18. (deletion) 19. (deletion) 20. A method of forming a tungsten film on a surface of an object to be processed in a vacuum vessel, the method comprising the steps of; forming an initial tungsten film by alternately repeating a reduction gas supplying process for supplying a reduction gas and a tungsten gas supplying process for supplying a tungsten-containing gas with an intervening purge process therebetween for supplying an inert gas while vacuumizing the vessel; and forming a main tungsten film by simultaneously supplying the tungsten-containing gas and the reduction gas after the initial tungsten film is formed. 21. The method of claim 20, wherein during the step of forming the initial tungsten film, the initial tungsten film is formed by alternately repeating the reduction gas supplying process for supplying the reduction gas and the tungsten gas supplying process for supplying the tungsten-containing gas while controlling the total pressure of the gases to be constant throughout the step of forming the initial tungsten film. 22. The method of claim 20, wherein during the step of forming the initial tungsten film, a parameter, which is obtained by multiplying a partial pressure of a reduction gas by a supplying time thereof, in an initial reduction gas supplying process among the repeated reduction gas supplying processes is set to be greater than that in the remaining reduction gas supplying processes. 23. The method of claim 20, wherein during the step of forming the initial tungsten film, a reduction gas supplying period of an initial reduction gas supplying process among the repeated reduction gas supplying processed is set to be longer than that of the remaining reduction gas supplying processes. 24. The method of claim 20, wherein the tungsten-containing gas is WF6 gas or an organic tungsten source gas. 25. The method of claim 20, wherein the reduction gas is selected from the group consisting of H2 gas, silane (SiH4), disilane (Si2H6), dichlororosilane (SiH2Cl2), diboran (B2H6) and phospine (PH3). 26. A method of forming a tungsten film on a surface of an object to be processed in a vacuum vessel, the method comprising the steps of: forming an initial tungsten film by alternately repeating a reduction gas supplying process for supplying a reduction gas and a tungsten gas supplying process for supplying a tungsten-containing gas with an intervening purge process theretween for supplying an inert gas while vacuumizing the vessel; performing a main tungsten film forming step by simultaneously supplying the tungsten-containing gas and the reduction gas after the initial tungsten film is formed; and performing a passivation tungsten film forming step between the initial tungsten film forming step and the main tungsten film forming step, for forming a passivation tungsten film by simultaneously supplying the tungsten-containing gas and the reduction gas while controlling the flow ratio of the tungsten-containing gas to be smaller than that in the main tungsten film forming step. 27. The method of claim 26, wherein during the step of forming the initial tungsten film, the initial tungsten film is formed by alternately repeating the reduction gas supplying process for supplying the reduction gas and the tungsten gas supplying process for supplying the tungsten-containing gas while controlling the total pressure of the gases to be constant throughout the step of forming the initial tungsten film. 28. The method of claim 26, wherein during the step of forming the initial tungsten film, a parameter, which is obtained by multiplying a partial pressure of a reduction gas by a supplying time thereof, in an initial reduction gas supplying process among the repeated reduction gas supplying processes is set to be greater than that in the remaining reduction gas supplying processes. 29. The method of claim 26, wherein during the step of forming the initial tungsten film, a reduction gas supplying period of an initial reduction gas supplying process among the repeated reduction gas supplying processes is set to be longer than that of the remaining reduction gas supplying processes. 30. The method of claim 26, wherein the initial tungsten film forming step and the passivation tungsten film forming step have at least either a process pressure or a process temperature substantially equal. 31. The method of claim 26, wherein the main tungsten film forming step has at least either a process pressure or a process temperature substantially higher than the passivation tungsten film forming step. 32. The method of claim 26, wherein the tungsten-containing gas is WF6 gas or an organic tungsten source gas. 33. The method of claim 26, wherein the reduction gas is selected from the group consisting of H2 gas, silane (SiH4), disilane (Si2R6), dichlororosilane (SiH2Cl2), diboran (B2H6) and phospine (PH3). 34. The method of claim 26, wherein the tungsten-containing gas is WF6 gas, and the reduction gas is SiH4 gas in the initial tungsten film forming step and H2 gas in the passivation tungsten film forming step and the main tungsten film forming step. |
<SOH> BACKGROUND OF THE INVENTION <EOH>Generally, in order to form a wiring pattern on a surface of a semiconductor wafer serving as an object to be processed or bury recesses between wiring or contact holes during a semiconductor integrated circuit manufacturing process, a metal or a metalic compound such as W(tungsten), WSi(tungsten silicide), Ti(titanium), TiN(titanium nitride), TiSi(titanium silicide), Cu(copper) or Ta 2 O 5 (tantalum oxide) is deposited to form a thin film. In such a case, a tungsten film is widely uses since it has a small resistivity and requires a low film adhesion temperature. In order to form such a tungsten film, tungsten hexafluoride (WF 6 ) is used as a source gas and is reduced by hydrogen, silane, dichlorosilane or the like, thereby depositing the tungsten film. In case of forming such a tungsten film, a Ti film, a TiN film, or a stack of both of those films is thinly and uniformly formed first on a wafer surface as a barrier layer serving as an under film for the purpose of improving the adhesivity and then suppressing a reaction with an underlying silicon layer and the tungsten film is deposited thereon. When burying or remedying the recesses or the like, hydrogen gas having a weaker reducing power than silane is mainly used to enhance the burying characteristics. At this time, the barrier layer may be attacked by unreacted WFs to react with fluorine and then be expanded in volume, thereby generating an upwardly protruded volcano or a void in a buried hole. The above phenomenon will be explained with reference to FIG. 13 . FIG. 13 is a cross sectional view of a buried hole having a volcano and a void. A buried hole 2 such as a contact hole or the like is formed on a surface of a semiconductor wafer W. A barrier layer 4 formed of, e.g., a Ti/TiN film, is formed in advance on the surface including an inner surface of the buried hole 2 . In case of performing a burying process on the structure described above by depositing a tungsten film 6 by way of simultaneously supplying WFg gas and H 2 gas, fluorine of the WF 6 gas is diffused into the barrier layer 4 . Especially, the fluorine reacts with Ti in the barrier layer 4 on the inner surface, leading to a protruded deposition of the tungsten film 6 starting at the buried hole 2 . As a result, a volcano 8 can be generated at an end portion of the protrusion by a stress of the tungsten film 6 or a void 10 having a cavity shape can also be generated inside the buried hole 2 . In order to prevent the generation of the volcano 8 or the like, silane having a stronger reducing power than that of the hydrogen gas was also used for forming a nucleation layer of the tungsten film 6 with a small thickness of, e.g., about 300 to 500 Å. Thereafter, deposition of a main tungsten film was carried out starting at the nucleation layer by using H 2 gas and WF 6 gas. In this case, however, the nucleation layer may not be Uniformly formed due to, e.g., a contamination of a surface of the barrier layer 4 serving as a base film. Thus, prior to the formation of the nucleation layer, only silane is provided for a certain time period to allow reaction intermediates of the silane (SiHx:x<4) to be absorbed on a wafer surface at a low temperature, e.g., 400° C. at which a part of the silane can be decomposed. Then, the nucleation layer is grown starting at that portion. FIGS. 14A to 14 F illustrate the processes for charging a buried hole with tungsten by using the above-described method. As shown in FIG. 14A , an initiation process of adhering reaction intermediates 12 , i.e., SiHx discussed above, on a surface of a wafer W is performed on the wafer W having a barrier layer 4 formed on its entire surface including an inner surface of a buried hole 2 ( FIGS. 14A and 14B ). Next, as described above, by simultaneously supplying the WF 6 gas and the SiH 4 gas for a certain time period as illustrated in FIG. 14C , a tungsten film is deposited starting at the reaction intermediates 12 , thereby forming a nucleation layer 14 ( FIG. 14D ). Subsequently, by simultaneously supplying the WF 6 gas and the H 2 gas as shown in FIG. 14E , a main tungsten film 16 is deposited so as to fill the buried hole as illustrated in FIG. 14F . In case of forming the barrier layer 4 formed on the wafer surface, an organic compound source of Ti is normally used in order to increase a step coverage. However, a carbon component in the organic compound source is included in the barrier layer 4 and, thus, adhesion of the reaction intermediates to the barrier layer 4 becomes irregular despite the initiation process due to the exposure of the carbon component on a surface of the barrier layer 4 . Consequently, the nucleation layer 14 is irregularly formed thereon, and the step coverage thereof is also deteriorated, resulting in deteriorated burying characteristics of a main tungsten film, causing voids, volcanoes or the like. Such a problem does not occur in a case where the ratio between the thickness of the nucleation layer 14 and that of the entire tungsten film including the main tungsten deterioration of the step coverage of the nucleation layer 14 . The above problem becomes aggravated as a serious issue especially when an inner diameter of a buried hole becomes smaller than or same to, e.g., 0.2 μm as a result of the manufacturing requirement for a further scaling down and a thinner film. |
<SOH> SUMMARY OF THE INVENTION <EOH>It is, therefore, a primary object of the present invention to provide a method of forming a tungsten film of satisfactory burying characteristics by preventing the generation of voids and volcanoes as large as adversely affecting the characteristics, even in a buried hole having a small diameter. In accordance with a preferred embodiment of the present invention, there is provided a method of forming a tungsten film on a surface of an object to be processed in a vacuum vessel, the method including the step of: forming an initial tungsten film by alternately repeating a reduction gas supplying process for supplying a reduction gas and a tungsten gas supplying process for supplying a tungsten-containing gas with an intervening purge process therebetween for supplying an inert gas while vacumizing the vessel. Accordingly, an initial tungsten film having a uniform thickness can be formed as a nucleation layer. Therefore, when a main tungsten film is subsequently deposited thereon, it is possible to restrict the generation of voids or volcanoes in sizes capable of adversely affecting the burying characteristics, e.g., even in a buried hole having a small diameter. In accordance with another preferred embodiment of the present invention, there is provided a method of forming a tungsten film on a surface of an object to be processed in a processing vessel capable of being vacuumized, the method including the step of: forming an initial tungsten film by, in repetition, supplying a reduction gas and a tungsten-containing gas with an intervening purge process therebetween for supplying an inert gas while vacuumizing the vessel, wherein the total pressure of the reduction gas, the tungsten-containing gas and the inert gas is controlled to be constant. In accordance with the present invention, by controlling the total pressure of the reduction gas, the tungsten-containing gas and the inert gas throughout the step of forming the initial tungsten film, the temperature of a wafer (an object to be processed) and the amount of gas to be absorbed can be maintained regularly. In the method of forming the tungsten film in accordance with the present invention, a parameter, which is obtained by multiplying a partial pressure of the reduction gas by the supplying time thereof in an initial reduction gas supplying process among the repeated reduction gas supplying processes, may be set to be greater than that in the subsequent reduction gas supplying processes. In accordance with the present invention, by performing a substantially same function as the initiation process of the conventional method, a reaction intermediate may be adhered to a surface of an object to be processed so that the surface can be activated. In accordance with still another preferred embodiment of the present invention, an initial tungsten film is formed by repeatedly supplying a reduction gas and a tungsten-containing gas with an intervening purge process for supplying an inert gas, while setting the supplying time of a reduction gas in an initial reduction gas supplying process among the repeated reduction gas supplying processes to be longer than that of the subsequent reduction gas supplying processes and controlling the total pressure of the reduction gas, the tungsten-containing gas, and the inert gas to be constant throughout the step of forming the initial tungsten film. In accordance with the present invention, the initial reduction gas supplying process functions in a same way as in the initiation process of the conventional method, and a temperature of a wafer (an object to be processed) and the amount of gas to be absorbed thereon can be maintained regularly by controlling the total pressure of the reduction gas, the tungsten-containing gas and the inert gas. In accordance with the method of the present invention, after the initial tungsten film is formed, a main tungsten film is formed by simultaneously supplying the tungsten-containing gas and the reduction gas. In accordance with the present invention, it is possible to prevent the generation of voids or volcanoes having sizes capable of adversely affecting the burying characteristics even in a buried hole having a small diameter, thereby providing satisfactory burying characteristics. In accordance with the method of the present invention, a process for forming a passivation tungsten film is performed between the initial tungsten film forming process and the main tungsten film forming process by simultaneously supplying the tungsten-containing gas and the reduction gas while setting the flow ratio of the tungsten-containing gas to be smaller than that supplied in the main tungsten film forming process. In case the thickness of an initial tungsten film is thin, when the main tungsten film is formed, volcanoes may be generated by an attack of the WF 6 gas. However, in accordance with the present invention, by forming a passivation tungsten film functioning as a so-called passivation film, the initial tungsten film can be protected, thereby further improving the burying characteristics. In accordance with the method of the present invention, the initial tungsten film forming process and the passivation tungsten film forming process are carried out in a substantially equal condition with respect to the process pressure and/or the process temperature. In accordance with the method of the present invention, the main tungsten film forming process has at least either the process pressure or the process temperature substantially higher in comparison with the passivation tungsten film forming process. In the method of the present invention, the tungsten-containing gas may be WF 6 gas or an organic tungsten source gas. Further, in the method of the present invention, the reduction gas may be selected from the group consisting of H 2 , silane (SiH 4 ), disilane (Si 2 H 6 ), dichlororosilane (SiH 2 Cl 2 ), diboran (B 2 H 6 ) and phospine (PH 3 ) Further, in the method of the present invention, the tungsten-containing gas may preferably be WF 6 gas, and the reduction gas may preferably be SiH 4 gas in the initial tungsten film forming process and H 2 gas in the passivation tungsten film forming process. |
Synthesis of triphenylphosphonium quinols and quinones |
The methods of preparing quinols and quinones typified by mitoquinol and mitoquinone where a compound typified by idebenone is reacted with Ph3PHX and Ph3P, where X is a halogen atom. |
1. A method of synthesis of a compound with a moiety or the moiety of the formula (and/or its quinone form) where n is an integer from 6 to 40 which comprises or includes the preparation or obtaining of a compound of formula (and/or its quinol form) and its subsequent reaction in the presence of Ph3PHX and Ph3P, where X is a halogen atom selected from Br, I and Cl. 2. A method of claims 1 wherein X is Br. 3. A method of claim 1 wherein the product compound includes Br. 4. A method of claim 1 wherein n is up to 25. 5. A method of claim 1 wherein n is 10. 6. A method of claim 1 wherein the ratio of the compound of Formula 1 to Ph3P and the ratio of the Ph3PHX to Ph3P are each substantially stoichiometric. 7. A method of claim 6 wherein X is Br. 8. A method of claim 1 wherein the reaction(s) is (are) maintained below 80° C. 9. A method of claim 1 wherein the compound of Formula I is largely or exclusively in its quinone form. 10. A method of claim 1 wherein the compound with a moiety of Formula II is largely or exclusively in its quinol form. 11. A method of claim 1 followed by a purification process. 12. A method of claim 10 followed by a reduction of any quinone form material to its quinol form. 13. A compound with a moiety of Formula II when produced by a process of claim 1. 14. A compound of a moiety of Formula II when produced by a process of claim 2. 15. A compound of claim 13 which is mitoquinol and/or mitoquinone. |
Device and method of recognising at least one individual, the corresponding access control device and system and applications thereof |
The invention relates to a device and method for the recognition of at least one individual and to the corresponding access control device and system and application thereof. The inventive recognition device comprises a one-piece integrated circuit which is produced by integrating the following elements on a silicon substrate: at least one biometric information sensor; means of processing said biometric information; cryptographic means which deliver at least one piece of encrypted data that is representative of at least one part of said biometric information and/or a corresponding piece of recognition information; and protection means that block access to data in transit, stored and/or processed in said one-piece integrated circuit in order to create a secure perimeter. In this way, the data exchanged by said sensor(s), processing means and cryptographic means, and particularly the aforementioned biometric information, are only saved in the one-piece integrated circuit and cannot be accessed from outside. Moreover, only encrypted data are delivered to the outside from said one-piece integrated circuit. |
1. Device for recognising at least one individual, characterised in that it comprises in a monolithic integrated circuit obtained via the integration on a same silicon substrate of: at least one biometric information sensor; means of processing the said biometric information; cryptographic means, transmitting at least one piece of encrypted data representing at least one part of the said biometric information and/or one piece of corresponding recognition information; and means of protection, denying access to the flowing data, stored and/or processed in the said monolithic integrated circuit, to create a secured perimeter, so that the data exchanged by the said sensor(s), the said means of processing and the said cryptographic means, and notably the said biometric information, is solely kept in the said monolithic integrated circuit, remaining inaccessible from the outside, and that only the encrypted data is transmitted to the outside of the said monolithic integrated circuit. 2. Device for recognising at least one individual according to claim 1, characterised in that the said means of protection deny access to data comprising at least one of the means belonging to the group comprising: means of monitoring the mains supply of the said monolithic integrated circuit; means of monitoring the characteristics of a clock synchronising the operating of the said device; means of controlling the temperature of the said monolithic integrated circuit; means of scrambling the electromagnetic interference induced by the internal processing of the device; means of anti-radiation protection; means of electromagnetic field shielding; means of physical shielding intended to prevent and/or detect any physical and/or electric attempt at interfering with the device; means of scrambling flowing information, processed and/or stored in the device. 3. Device for recognising at least one individual according to any one of claims 1 or 2, characterised in that the said biometric information belongs to the group comprising: fingerprints; voiceprints; eye imprints; morphologic characteristics; behavioural characteristics 4. Device for recognising at least one individual according to any one of claims 1 to 3, characterised in that the said sensor(s) belong to the group comprising: heat sensors; pressure sensors; light sensors; movement detectors; radiation detectors; electric characteristic sensors; physical entity sensors. 5. Device for recognising at least one individual according to any one of claims 1 to 4, characterised in that the said means of processing comprise means of formatting at least one signal transmitted by at least one of the said sensors and means of extracting the said formatting signal of at least one pertinent character, creating a digital signature making it possible to identify an individual in a unique manner. 6. Device for recognising at least one individual according to any one of claims 1 to 5, characterised in that the said cryptographic means provide a cryptographic signature, calculated with the help of at least one key stored in a storage unit of the said monolithic integrated circuit. 7. Device for recognising at least one individual according to claim 8, characterised in that the said cryptographic signature also takes into account at least one random parameter generated and communicated by means independent of the said monolithic integrated circuit. 8. Device for recognising at least one individual according to any one of claims 1 to 7, characterised in that it comprises means of recognising at least one individual, according to the reference data stored in the said monolithic integrated circuit. 9. Device for recognising at least one individual according to claim 8, characterised in that the said means of recognition transmit a piece of recognition information, indicating if an individual is or is not recognised, the said recognition information being encrypted before being transmitted to the outside of the said monolithic integrated circuit. 10. Device for recognising at least one individual according to any one of claims 1 to 9, characterised in that the said monolithic integrated circuit comprises a storage unit comprising at least one of the elements belonging to the group comprising: at least one cryptographic key; at least one secured processing mechanism of cryptographic keys; at least one piece of reference data representative of an individual; data and/or programmes necessary for the implementation of the means present in the said monolithic integrated circuit. 11. Device for recognising at least one individual according to claim 10, characterised in that the said storage unit comprises at least one digital data memory. 12. Device for recognising at least one individual according to claim 11, characterised in that the said digital data memory(ies) belong to the group comprising the flash, the EEPROM, the EPROM, the ROM, the RAM, the FERAM, the MRAM and the magnetic memories. 13. Device for recognising at least one individual according to any one of claims 1 to 12, characterised in that the said monolithic integrated circuit comprises a fingerprint sensor, transmitting an imprint image, means of processing the generated image and means of extracting details on the processed image. 14. Device for recognising at least one individual according to any one of claims 1 to 13, characterised in that the said cryptographic means implement at least one equipment calculation booster. 15. Method of recognising at least one individual, characterised in that it comprises the following stages, integrally implemented on the inside of a monolithic integrated circuit: obtaining biometric information of the said individual, with the help of at least one sensor integrated into the said monolithic integrated circuit; processing the said biometric information; encrypting at least a part of the said biometric information and/or a piece of corresponding recognition information; transmitting the encrypted data to the outside, so that the data exchanged by the said sensor(s), the said means of processing and the said cryptographic means, and notably the said biometric information, is solely kept in the said monolithic integrated circuit, remaining inaccessible from the outside, and that only encrypted data is transmitted to the outside of the said monolithic integrated circuit. 16. Method of recognising at least one individual according to claim 15, characterised in that the said monolithic integrated circuit defines a secured perimeter, by implementing means of protection denying access to the flowing data, stored or processed in the said monolithic integrated circuit. 17. Method of recognising at least one individual according to any one of claims 15 or 16, characterised in that it implements at least one recognition device comprising the said monolithic integrated circuit and at least one access monitoring device linked up to the said recognition device, capable of receiving and processing encrypted data transmitted by the said recognition device(s), and consequently of authorising or refusing access to at least one piece of data, at least one object and/or at least one site. 18. Access monitoring device comprising means of access authorisation or refusal to at least one piece of data, at least one object and/or at least one site, characterised in that it comprises means for receiving and processing encrypted data provided by at least one device for recognising at least one individual according to any one of claims 1 to 14. 19. System for monitoring access to at least one piece of data, at least one object and/or at least one site, characterised in that it comprises at least one device for recognising at least one individual according to any one of claims 1 to 14 and at least one access monitoring device according to claim 18. 20. Application of a device for recognising at least one individual according to any one of claims 1 to 14 and/or a method of recognising at least one individual according to any one of claims 15 to 17 to at least one of the fields belonging to the group comprising: physical access monitoring; computer data access monitoring; identifying of the holder of the said device; implementing of mobile objects; banking services; electronic signatures. |
Electronic writing device and method for generating an electronic signature |
The invention is an electronic writing device (50) and a method for creating an electronic signature, the device comprising a sensor (S1, S2, S2) for producing an output signal by detecting a dynamic parameter of a signature, and means for calculating a detected signature pattern on the basis of the output signal of the sensor (S1, S2, S2), comparing the detected signature pattern with a signature pattern stored in a memory and generating an enabling signal on the basis of the comparison, wherein the device also comprises a communication unit for implementing communication with a host system on the basis of the enabling signal. The device comprises a private key for the electronic signature and means for generating the electronic signature by means of the private key, wherein the communication unit is capable of receiving a data flow from the host system and supplying to the host system the electronic signature generated by means of the private key from the data flow. |
1. An electronic writing device for creating an electronic signature, the device comprising a sensor for producing an output signal by detecting a dynamic parameter of a signature, means for calculating a detected signature pattern on the basis of the output of the sensor, comparing the detected signature pattern with a signature pattern stored in a memory and generating an enabling signal on the basis of the comparison, a communication unit for implementing communication with a host system on the basis of the enabling signal, a private key for the electronic signature and means for generating the electronic signature by means of the private key, wherein the communication unit is capable of receiving a hash produced from a document in the host system and supplying to the host system the electronic signature generated by means of the private key from the hash. 2. The writing device according to claim 1, wherein the means for calculating and comparing the detected signature pattern and generating the enabling signal, as well as the means for generating the electronic signature are implemented in a microprocessor-based central unit, to which a non-volatile memory comprising the stored signature pattern and the private key is connected. 3. The writing device according to claim 2, wherein depending on the enabling signal, the communication unit is instructed by the central unit to receive the hash. 4. The writing device according to claim 3, wherein the non-volatile memory further comprises a force-associated signature pattern corresponding to a signature under compulsion and a force-associated private key for an electronic signature implying compulsion, wherein the electronic signature is generated by the force-associated private key when a force-associated signature pattern is detected. 5. The writing device according to claim 4, wherein the central unit and the non-volatile memory have a design protected against read-out. 6. The writing device according to claim 5, wherein it comprises several types of sensors, preferably an optical sensor, a pressure sensor, an acceleration sensor and/or a tilting sensor, and the detected signature pattern is calculated on the basis of the output signals of the sensors. 7. The writing device according to claim 6, wherein the sensors are analog sensors, the output signals of which are supplied via an amplifier/signal conditioner unit to a multiplexer/digitizer unit, the output of which is connected to the microprocessor in the central unit. 8. The writing device according to claim 7, wherein the communication unit has a cable, infrared or radio frequency data transmission contact with the host system. 9. The writing device according to claim 8, wherein it comprises a conventional pen refill. 10. A method for generating an electronic signature by means of an electronic writing device, comprising the steps of detecting a dynamic parameter of a signature and on the basis of the detection calculating a detected signature pattern, comparing the detected signature pattern with the signature pattern stored in the writing device and producing an enabling signal on the basis of the result of the comparison, wherein the method comprises the further step of generating a hash in a host system from a document to be signed electronically, supplying the hash to the writing device, the writing device comprising a private key, generating the electronic signature by means of the private key in the writing device from the hash, and transferring the electronic signature from the writing device to the host system for further processing, wherein at least one of the supplying, generating or transferring steps is carried out depending on the enabling signal. 11. The method according to claim 10, wherein the supply of the hash from the host system to the writing device by the enabling signal. 12. The method according to claim 11, wherein the writing device further comprises a force-associated signature pattern corresponding to a signature wider compulsion, and a force-associated private key associated with an electronic signature implying compulsion, wherein the electronic signature is generated by the force-associated private key when the force-associated signature pattern is detected. 13. The method according to claim 12, wherein more than one sensor, preferably an optical sensor, a pressure sensor, an acceleration sensor and/or a tilting sensor is applied, and the detected signature pattern is calculated on the basis of the output signals of the sensors. 14. The method according to claim 13, wherein the communication between the host system and the writing device is implemented by a cable, infrared or radio frequency data transmission. 15. The method according to claim 14, wherein the stored signature pattern in the writing device is adjusted by self-learning during use. 16. The method according to claim 15, wherein a writing device comprising a conventional pen refill and giving instructions to the writing device by writing down the instructions, which writing is detected by the writing device similarly to the detection of the signature. |
<SOH> BACKGROUND ART <EOH>The development of the information society —with special regard to electronic business transactions and electronic public administration —made it inevitable to elaborate and introduce a process that provides an opportunity for making authentic electronic statements and data-transmission. A solution to do so is provided by the so-called electronic signature. An electronic signature has to meet the same requirements as a conventional paper based signature (hereinafter signature): only one person is able to create a signature characterizing him/her, consequently the signature cannot be forged or disowned; the signature can be made and verified easily; if a signatory acts under compulsion, he/she can sabotage the signature in a way which cannot be detected by the person imposing the compulsion; the signed document can not be modified undetectably after signing. The method of electronic signature is based on the principle of Public Key Infrastructure (PKI) elaborated by several international standards organizations. The UN organization UNCITRAL described the related information in its document published under the title Model Law on Electronic Signatures with Guide to Enactment (2001, United Nations, New York, 2002 United Nations Publication Sales No. E.02.V.8 ISBN 92-1-133653-8). The essence of Public Key Infrastructure is an encrypting method, in which two different keys are required for coding and decoding a message. These keys represent a supplementing pair, and yet it is practically impossible to derive a private key from the public key. A person signing an electronic document must have a private key not known to others as well as a public key. The signatory ‘signs’ the electronic document with his/her own private key by generating first a hash of the electronic document by means of an algorithm, an encoding algorithm encodes this hash by means of the private key, and the data series so generated is the electronic signature. The signatory sends the electronic document together with the electronic signature to the receiving party, which also makes a hash of the document, using the same method as the signatory. By means of the public key, the receiving party decodes another hash from the electronic signature. The two matching hashes indicate the authenticity of the electronic document. The description above shows that an electronic signature is bound to a document logically and not physically, and yet if a document is altered after signing, the hash will not be identical with the hash that can be decoded from the electronic signature, consequently the signature will not be authentic. Currently, the private key required for an electronic signature is mostly stored in a chip card, which is able to carry out the required coding activities as well. The possibility of causing damage by theft or any opportunities for abuse can be reduced by means of a password or PIN code in a way that the card would not generate a signature until enabled by an appropriate password. In this case the identification of the user is performed in a combined way on the basis of an asset (card) and knowledge (PIN code), but even so it cannot be guaranteed that it is the proper person who makes use of the card. Practice unfortunately proves that in many cases the users are misled, and they unsuspectingly or unknowingly disclose secret particulars like their signature key, password or PIN code. To eliminate these disadvantages, a requirement has emerged to generate the electronic signature through the application of a biometric identification method instead of the ‘asset’ and ‘knowledge’ factors. It is known from the prior art that a signature in the conventional sense is a biometric parameter of the signatory, which parameter is suitable for such identification. By measuring dynamic parameters of a signature, like the change in time of the pen's tilting angle, the change in time of the pressure between the writing surface and the pen, the change in time of the pen's position, the line-drawing velocity, acceleration and twisting etc., a so-called dynamic signature detection can be carried out, by which appropriate biometric identification can be obtained. An electronic writing device/writing surface unit and a method are described for such identification for example in WO 98/12661. This known unit and method, however, are only suitable for identifying the user and fail to enable the generation of a digital signature in a simple and efficient way. A further disadvantage of this known approach is that an electronic unit comprising a special writing surface is necessary for identification, and this does not enable the creation of a simple, portable and widely applicable system. Furthermore, in U.S. Pat. No. 5,892,824 a method and an apparatus is described for reading in the pattern of a conventional signature on a special sensing writing surface, in addition to enabling identification based thereon. This known approach also has the disadvantages mentioned above. |
<SOH> BRIEF DESCRIPTION OF DRAWINGS <EOH>The invention will hereinafter be described on the basis of preferred embodiments depicted by the drawings, where FIG. 1 is a schematic diagram of a writing device according to the invention, FIG. 2 is a detailed schematic diagram of the writing device shown in FIG. 1 , FIG. 3 is a schematic cross sectional structural view of the writing device shown in FIG. 2 , FIG. 4 is a schematic view of the writing device shown in FIG. 3 and placed into a holding module, FIG. 5 is a diagram depicting the steps related to an electronic signature, FIG. 6A is a simplified flow diagram of digitizing a signature, FIG. 6B is a simplified flow diagram of communication related to an electronic signature, FIG. 6C is a simplified flow diagram of communication related to a force-associated electronic signature and FIG. 7 is a flow diagram of the program operating in the writing device. detailed-description description="Detailed Description" end="lead"? |
Fluid-assisted medical devices, systems and methods |
Adaptors for electrically coupling between an electrosurgical generator and a bipolar electrosurgical device are provided. In one preferred embodiment, the adaptor comprises a power input connector for coupling the adaptor with a monopolar mode power output connector of the electrosurgical generator, a ground connector for coupling the adaptor with a ground connector of the electrosurgical generator, a first and a second power output connector, each for coupling the adaptor with a first and a second bipolar mode power input connector of the bipolar electrosurgical device, respectively, a transformer coupled between the power input connector and the first and second power output connectors, a monopolar hand switch connector for coupling the adaptor with a monopolar mode hand switch connector of the electrosurgical generator, and at least one bipolar mode hand switch connector for coupling the adaptor with a bipolar mode hand switch connector of the electrosurgical device. |
1-27. (Cancelled) 28. An adaptor for electrically coupling between an electrosurgical generator and a bipolar electrosurgical device, the adaptor comprising: a power input connector for coupling the adaptor with a monopolar mode power output connector of the electrosurgical generator; a ground connector for coupling the adaptor with a ground connector of the electrosurgical generator; a first and a second power output connector, each for coupling the adaptor with a first and a second bipolar mode power input connector of the bipolar electrosurgical device, respectively; a transformer coupled between the power input connector and the first and second power output connectors; a monopolar hand switch connector for coupling the adaptor with a monopolar mode hand switch connector of the electrosurgical generator; and at least one bipolar mode hand switch connector for coupling the adaptor with a bipolar mode hand switch connector of the electrosurgical device. 29. The adaptor according to claim 28 wherein: the transformer comprises a first coil and a second coil; the first coil adapted to be coupled to the generator; and the second coil adapted to be coupled to the bipolar electrosurgical device. 30. The adaptor according to claim 29 wherein: the first coil comprises a plurality of windings; the second coil comprises a plurality of windings; and the number of first coil windings is greater then the number of second coil windings. 31. The adaptor according to claim 28 wherein: the transformer comprises a first coil and a second coil; the first coil is coupled at a first end to the power input connector of the adaptor; the first coil is coupled at a second end to the ground connector of the adaptor; the second coil is coupled at a first end to the first power output connector of the adaptor; and the second coil is coupled at a second end to the second power output connector of the adaptor. 32. The adaptor according to claim 28 further comprising: a first and a second bipolar mode hand switch connector for coupling the adaptor with a first and a second bipolar mode hand switch connector of the electrosurgical device, respectively. 33. The adaptor according to claim 32 wherein: the first bipolar mode hand switch connector of the adaptor is coupled to the monopolar hand switch connector of the adaptor; and the second bipolar mode hand switch connector of the adaptor is coupled to the power input connector of the adaptor in parallel with the transformer. 34-39. (Cancelled) |
<SOH> BACKGROUND <EOH>Electrosurgical devices configured for use with a dry tip use electrical energy, often radio frequency (RF) energy, to cut tissue or to cauterize blood vessels. During use, a voltage gradient is created at the tip of the device, thereby inducing current flow and related heat generation in the tissue. With sufficiently high levels of electrical power, the heat generated is sufficient to cut the tissue and, advantageously, to stop the bleeding from severed blood vessels. Current dry tip electrosurgical devices can cause the temperature of tissue being treated to rise significantly higher than 100° C., resulting in tissue desiccation, tissue sticking to the electrodes, tissue perforation, char formation and smoke generation. Desiccation occurs when tissue temperature exceeds 100° C. and all of the intracellular water boils away, leaving the tissue extremely dry and much less electrically conductive. Peak temperatures of target tissue as a result of dry RF treatment can be as high as 320° C., and such high temperatures can be transmitted to adjacent tissue via thermal diffusion. Consequently, this may result in undesirable desiccation and thermal damage to the adjacent tissue. The use of saline inhibits undesirable effects such as tissue desiccation, electrode sticking, smoke production and char formation. However, an uncontrolled or abundant flow rate of saline can provide too much electrical dispersion and cooling at the electrode/tissue interface. This reduces the temperature of the target tissue being treated, and, in turn, can result in longer treatment time to achieve the desired tissue temperature for treatment of the tissue. Long treatment times are undesirable for surgeons since it is in the best interest of the patient, physician and hospital, to perform surgical procedures as quickly as possible. RF power delivered to tissue can be less than optimal when using general-purpose generators. Most general-purpose RF generators have modes for different waveforms (e.g., cut, coagulation, or blend) and device types (e.g., monopolar, bipolar), as well as power levels that can be set in watts. However, once these settings are chosen, the actual power delivered to tissue and associated heat generated can vary dramatically over time as tissue impedance changes during the course of RF treatment. This is because the power delivered by most generators is a function of tissue impedance, with the power ramping down as impedance either decreases toward zero or increases significantly to several thousand ohms. Current dry tip electrosurgical devices are not configured to address a change in power provided by the generator as tissue impedance changes or the associated effect on tissue, and rely on the surgeon's expertise to overcome this limitation. The patent application is related to U.S. provisional application Ser. No.______, filed Mar. 6, 2003 (having attorney docket number 13045.40USP1) and also to U.S. provisional application Ser. No. 60/368,177, filed Mar. 27, 2002, now pending. This patent application is also related to U.S. patent application Ser. No. 09/947,658, filed Sep. 5, 2001, now pending, which is a continuation-in-part of U.S. patent application Ser. No. 09/797,049, filed Mar. 1, 2001, now pending, which claimed priority to U.S. provisional application Ser. No. 60/187,114, filed Mar. 6, 2000. This patent application is also related to U.S. patent application Ser. No. 09/668,403, filed Sep. 22, 2000, now pending. This patent application is also related to PCT patent application serial No. PCT/US02/28488, filed Sep. 6, 2002, now pending. The entire disclosure of each of these patent applications is incorporated herein by reference to the extent it is consistent. |
<SOH> SUMMARY OF THE INVENTION <EOH>The invention is directed to various embodiments of electrosurgical devices, systems and methods. In one preferred embodiment, an electrosurgical device has a handle, a shaft extending from the handle having a distal end, and an electrode tip having an electrode surface with at least a portion of the electrode tip extending distally beyond the distal end of the shaft. In one embodiment, preferably the portion of the electrode tip extending distally beyond the distal end of the shaft comprises a cone shaped portion. The device also has a fluid passage being connectable to a fluid source and at least one fluid outlet opening in fluid communication with the fluid passage. In another preferred embodiment, the electrode tip extending distally beyond the distal end of the shaft has a neck portion and an enlarged end portion with the enlarged end portion located distal to the neck portion and comprising the cone shaped portion. In another preferred embodiment, the fluid outlet opening is arranged to provide a fluid from the fluid source to the neck portion of the electrode tip. In yet another preferred embodiment, the fluid outlet opening is arranged to provide a fluid from the fluid source towards the enlarged end portion of the electrode tip. In another preferred embodiment, an electrosurgical device has a handle, and an electrode tip having an electrode surface with the electrode surface and comprising a cone shaped portion. The device also has a fluid passage being connectable to a fluid source and at least one fluid outlet opening in fluid communication with the fluid passage and arranged to provide a fluid from the fluid source to the cone shaped portion of the electrode tip. The invention is also directed to a surgical method for treating tissue. The method includes providing tissue having a tissue surface, providing radio frequency power at a power level, providing an electrically conductive fluid at a fluid flow rate, providing an surgical device configured to simultaneously provide the radio frequency electrical power and the electrically conductive fluid to tissue, providing the electrically conductive fluid to the tissue at the tissue surface, forming a fluid coupling comprising the electrically conductive fluid which couples the tissue and the surgical device, providing the radio frequency power to the tissue at the tissue surface and below the tissue surface into the tissue through the fluid coupling, coagulating the tissue without cutting the tissue, and dissecting the tissue after coagulating the tissue. Preferably, the device comprises an electrode tip having an electrode surface, and comprising a cone shaped portion and a distal end. Also preferably, coagulating the tissue is performed with the cone shaped portion and dissecting is performed with the distal end of the device. In various embodiments, the dissection may be blunt as where the distal end of the device is blunt, or sharp as where the distal end of the device is pointed. The invention is also directed to various embodiments of an adaptor for electrically coupling between an electrosurgical generator and a bipolar electrosurgical device. In one preferred embodiment, the adaptor comprises a power input connector for coupling the adaptor with a monopolar mode power output connector of the electrosurgical generator, a ground connector for coupling the adaptor with a ground connector of the electrosurgical generator, a first and a second power output connector, each for coupling the adaptor with a first and a second bipolar mode power input connector of the bipolar electrosurgical device, respectively, a transformer coupled between the power input connector and the first and second power output connectors, a monopolar hand switch connector for coupling the adaptor with a monopolar mode hand switch connector of the electrosurgical generator, and at least one bipolar mode hand switch connector for coupling the adaptor with a bipolar mode hand switch connector of the electrosurgical device. The invention is also directed to various embodiments of a bipolar electrosurgical device. In one preferred embodiment, the device comprises a first electrode tip and a second electrode tip with the electrode tips coupled to an impedance transformer provided with the electrosurgical device, at least one fluid delivery passage being connectable to a fluid source, at least one fluid outlet opening in fluid communication with the at least one fluid delivery passage, the electrode tips configured to paint along a tissue surface in the presence of fluid from the fluid outlet opening as the tips are moved along the tissue surface whereby the tissue surface can be coagulated without cutting upon the application of radio frequency energy from the electrodes simultaneously with fluid from the fluid outlet opening while the tips are coupled with the fluid adjacent the tissue surface and moved along the tissue surface. The invention is also directed to various embodiments of medical kits. In one preferred embodiment, the kit has an electrosurgical device configured to provide radio frequency power and a fluid to a tissue treatment site, and a transformer. In various embodiments, the electrosurgical device and transformer may be provided as separate connectable components, or integrally as a single piece. |
Thiopyrane-4-ones as dna protein kinase inhibitors |
The present invention provides compounds of formula (I) and isomers, salts, solvates, chemically protected forms, and prodrugs thereof, wherein R1 and R2 are independently hydrogen, an option ally substituted C1-7 alkyl group, C3-20 heterocyclyl group, or C5-20 aryl group, or may together form, along with the nitrogen atom to which they are attached, an optionally substituted heterocyclic ring having from 4 to 8 ring atoms; and R3 is an optionally substituted C3-20 heterocyclyl or C5-20 aryl group, and their use as pharmaceuticals, particularly in treating diseases which are retroviral mediated or ameliorated by the inhibition of DNA-PK, |
1. A compound of formula I: and isomers, salts, solvates, chemically protected forms, and prodrugs thereof, wherein: R1 and R2 are independently hydrogen, an optionally substituted C1-7 alkyl group, C3-20 heterocyclyl group, or C5-20 aryl group, or may together form, along with the nitrogen atom to which they are attached, an optionally substituted heterocyclic ring having from 4 to 8 ring atoms; and R3 is an optionally substituted C5-20 aryl group. 2. A compound according to claim 1, wherein R1 and R2 form, along with the nitrogen atom to which they are attached, a heterocyclic ring having 5, 6 or 7 ring atoms. 3. A compound according to claim 2, wherein the heterocyclic ring formed by R1,R2 and the nitrogen atom to which they are attached, has 6 ring atoms. 4. A compound according to claim 2, wherein said heterocyclic ring contains one further ring heteroatom in addition to the nitrogen atom. 5. A compound according to claim 1, wherein R3 is a C5-20 carboaryl group. 6. A compound according to claim 5, wherein R3 is a phenyl group with one or more substituents selected from hydroxy, halo, carboxy, amino, amido, formyl, cyano, C5-20 aryl, C1-7 alkyl, acyl, acylamido, ester and ether. 7. A composition comprising a compound according to claim 1 and a pharmaceutically acceptable carrier or diluent. 8. canceled 9. canceled 10. canceled 11. A method for the treatment of a retroviral mediated disease or a disease ameliorated by the inhibition of DNA-PK comprising administering to a subject suffering from a retroviral mediated disease or a disease ameliorated by the inhibition of DNA-PK a therapeutically-effective amount of a compound according to claim 1. 12. A method for the treatment of tumours comprising administering to a subject suffering from tumour growth a therapeutically-effective amount of a compound according to claim 1 in combination with ionising radiation or one or more chemotherapeutic agents. 13. A method of inhibiting DNA-PK in vitro or in vivo, comprising contacting a cell with an effective amount of a compound according to claim 1. |
<SOH> BRIEF DESCRIPTION OF THE DRAWINGS <EOH>FIG. 1 shows the structure of selected compounds of formula I. detailed-description description="Detailed Description" end="lead"? |
Device and method for monitoring the connection of an electrical supply unit |
The invention relates to a device and a method for monitoring the connection of an electrical supply unit comprising voltage detection (32) detecting phase voltage (14), current detection (32) detecting phase voltages (38), a transformation unit (66) transforming the phase voltages (38) after conducting field-oriented regulation in at least one cross current (62), wherein a monitoring device (34) is provided to monitor at least one supply connection (28, 36) by means of which an electrical supply unit (32) is supplied, said monitoring unit evaluating the variation of the cross current (62) in order to monitor the connection. |
1. A device for monitoring the connection of an electrical supply unit, having a voltage detector (32), which ascertains the phase-voltages (14), having a current detector (32), which ascertains the phase currents (38), having a transformation unit (66), which converts the phase currents (38), by field-oriented regulation, into at least one transverse current (62), characterized in that for monitoring at least one supply connection (28, 36), by way of which an electrical supply unit (32) is supplied, a monitoring device (34) is provided, which evaluates the course of the transverse current (62) for the monitoring the connection. 2. The device of claim 1, characterized in that a faulty connection is found if the transverse current (62) exceeds a predeterminable limit value (I=0). 3. The device of claim 1, characterized in that the monitoring device (34) for monitoring the connection ascertains the respective phase power (pU, pV, pW) from the phase voltage (14) and phase current (38) and evaluates it. 4. The device of claim 1, characterized in that the monitoring device (34) compares the phase power (pU, pV, pW) with a limit value. 5. The device of one of claim 1, characterized in that the monitoring device (34) evaluates the longitudinal current (64) for monitoring the connection. 6. The device of claim 1, characterized in that the course of the phase currents (38) and/or voltages (14) is detected upon activation of the network voltage for a certain time interval. 7. The device of claim 1, characterized in that in the case of a faulty connection, countermeasures and/or triggering of a display is initiated. 8. The device of claim 1, characterized in that an intermediate circuit voltage (46) of a direct voltage intermediate circuit is detected for recognizing whether at least one intermediate circuit capacitor (44) is discharged, and in the case of a non-discharging intermediate circuit capacitor (44), an intentional short circuit is brought about via at least some transistors of the power stage (60) of the supply unit (32). 9. The device of claim 1, characterized in that the voltage detection (32) is effected on the side of the network connection and the current detection (32) is effected on the side of the supply unit. 10. The device of claim 1, characterized in that the transverse current (62) is a component that influences the effective power. 11. A method for monitoring the connection of an electrical supply unit, characterized by the following steps: charging at least one intermediate circuit capacitor (44); detecting the courses of the phase currents (38) and phase voltages (14) for a defined length of time during the charging phase of the intermediate circuit capacitor; ascertaining a course of the transverse current (62) and/or longitudinal current (64) from the phase currents (38) and/or the phase voltages (14) by field-oriented regulation; comparison of the course of the transverse current (62) and/or longitudinal current (64) with a limit value, wherein a fault of the connection of the supply unit (32) is recognized if the limit value is exceeded or undershot. 12. The method of claim 11, characterized in that in a further step, from the courses of the phase currents (38) and the phase voltages (14), the phase-related powers are ascertained and compared with a limit value, and a fault of the connection of the supply unit (32) is recognized if the limit value is exceeded or undershot. |
Method and device for identifying motion in an image |
The invention relates to a method for identifying moving areas of an image that contains pixels, said image having been produced by an interlacing method. A first half-image corresponds to the even lines of an image and the second half-image corresponds to the uneven lines of the image. According to the inventive method, which can be used for a multitude of different video materials, a motion can be easily identified in an image, when at least three subsequent pixels of the same column, one of the pixels being derived from the half-image and the other two being derived from the other half-image, are evaluated with respect to a pixel parameter. Depending on the result of said evaluation, a motion in a section of the image that comprises at least one of the three pixels can be indentified. |
1. A method for identifying moving areas of an image having pixels, which image has been generated according to the line interlacing method, the image having two fields, a first field having the even-numbered lines of the image and the second field having the odd-numbered lines of the image, the method comprising: for at least three successive pixels of the same column, one of the pixels originating from one field and the other two pixels originating from the other field, performing an evaluation of the at least three pixels with regard to a pixel parameter; and depending on the result of the evaluation, identifying motion in an area of the image which has at least one of the three pixels. 2. The method as claimed in claim 1, wherein the evaluation is a comparison, two jumps in the pixel parameter values of the successive pixels indicating that motion is present in the area, while one or no jump in the pixel parameter values indicates that there is no motion present in the area. 3. The method as claimed in claim 1 wherein the pixel parameter value is one or more parameters of a color space. 4. The method as claimed in claim 3, wherein the color space is the YCbCr color space. 5. The method as claimed in claim 4, that wherein the pixel parameter is the luma (Y). 6. The method as claimed in claims 1, wherein the image is a video frame. 7. The method as claimed in claims 1, wherein a Fourier transformation is applied to the pixel parameters of the at least three pixels, from which corresponding Fourier coefficients are obtained, motion being identified if at least one of the Fourier coefficients fulfills a predetermined criterion. 8. The method as claimed in claims 1, wherein four pixels (xm, m=0,1,2,3) are used. 9. The method as claimed in claim 8, wherein the Fourier coefficients are determined by the following formula Yn=Σm=0,3xme−iωmn, where ω=2π/4, |Y2|: |Y1|≧S being used as a criterion for identifying motion, and S being a predetermined threshold value. 10. The method as claimed in claim 8, wherein |Y2|: |Y1|≧S is used as a criterion for identifying motion, where Y1=X−02+iX−13 and Y2=X+02−X+13 where X+02=x0+x2, X+13=x1+x3, X−02=0−x2 and X−13=x1−x3 hold true, and S being a predetermined threshold value. 11. The method as claimed in claim 9 wherein the magnitude |Y2|: |Y1| represents a measure of the degree of motion. 12. The method as claimed in claim 11, wherein a plurality of threshold values are predetermined, the degree of motion being determined depending on the highest threshold value for which the assessment magnitude |Y2|: |Y1| is greater than or equal to this threshold value. 13. The method as claimed in claims 9, wherein the threshold value S lies in a range of values from approximately 5 to approximately 15. 14. The method as claimed in claims 1, wherein at least part of the image is scanned columnwise, from left to right, with, in each case, a group of at least three pixels of the same column that lie one above the other, in which case, after passing through essentially all the columns, the scanning is repeated in a manner displaced by essentially one line. 15. The method as claimed in claim 14, wherein the area of the image in which motion is identified is an individual pixel. 16. The method as claimed in claim 15, wherein the individual pixel is one of the inner pixels with regard to the group of pixels. 17. The method as claimed in claims 8, wherein the individual pixel is the pixel having the second lowest line number. 18. The method as claimed in claims 1, wherein an alarm is triggered in response to the identification of motion in the image. 19. A method for processing an image in which motion has been identified in accordance with a method of claims 1, wherein the image is accepted unchanged in areas in which there is no motion present, while only pixel information from one field is used for representing areas of the image in which motion has been identified. 20. The method as claimed in claims 15, wherein, for a location of the image in which motion has been identified, only the pixel value from one field is used for the representation, in which case, at respective locations of the other field at which motion has likewise been identified and which are adjacent to the location, use is made of substitute values obtained by an interpolation of pixel values of said one field from surroundings of the location. 21. The method as claimed in claim 20, wherein the surroundings of the location reach approximately as far as the third successive pixel of said one field. 22. The method as claimed in claim 1, wherein the method is implemented as a software program. 23. (Canceled) 24. A device for identifying moving areas of an image having pixels, which image has been generated according to the line interlacing method, the image having two fields, a first field having the even-numbered lines of the image and the second field having the odd-numbered lines of the image, wherein the device has evaluation means in order, for at least three successive pixels of the same column, one of the pixels originating from one field and the other two pixels originating from the other field, to carry out an evaluation of the at least three pixels with regard to a pixel parameter, in which case, depending on the result of the evaluation, motion is identified in an area of the image which has at least one of the three pixels. 25. The device as claimed in claim 24, wherein the evaluation means are comparison means, two jumps in the pixel parameter values of the successive pixels indicating that motion is present in the area, while one or no jump in the pixel parameter values indicates that there is no motion present in the area. 26. The device as claimed in claim 24, wherein the pixel parameter value is one or more parameters of a color space. 27. The device as claimed in claim 26, wherein the color space is the YCbCr color space. 28. The device as claimed in claim 27, wherein the pixel parameter is the luma (Y). 29. The device as claimed in claims 24 wherein the image is a video frame. 30. The device as claimed in claims 24, wherein a Fourier transformation is applied to the pixel parameters of the at least three pixels, from which corresponding Fourier coefficients are obtained, motion being identified if at least one of the Fourier coefficients fulfills a predetermined criterion. 31. The device as claimed in claims 24, wherein four pixels (xm, m=0,1,2,3) are used. 32. The device as claimed in claim 31, wherein the Fourier coefficients are determined by the following formula Yn=Σm=0,3xme−iωmn, where ω=2π/4, |Y2|: |Y1|≧S being used as a criterion for identifying motion, and S being a predetermined threshold value. 33. The device as claimed in claim 31, wherein |Y2|: |Y1≧S is used as a criterion for identifying motion, where Y1=X−02+iX−13 and Y2=X+02−X+13 where X+02=x0+x2, X+13=x1+x3, X−02=x0−x2 and X−13=x1−x3 hold true, and S being a predetermined threshold value. 34. The device as claimed in claim 32 in that wherein the magnitude |Y2|: |Y1| represents a measure of the degree of motion. 35. The device as claimed in claim 34, wherein a plurality of threshold values are predetermined, the degree of motion being determined depending on the highest threshold value for which the assessment magnitude |Y2|: |Y1| is greater than or equal to this threshold value. 36. The device as claimed in claims 32, wherein the threshold value S lies in a range of values from approximately 5 to approximately 15. 37. The device as claimed in claims 24 wherein at least part of the image is scanned columnwise, from left to right, with, in each case, a group of at least three pixels of the same column that lie one above the other, in which case, after passing through essentially all the columns, the scanning is repeated in a manner displaced by essentially one line. 38. The device as claimed in claim 37, wherein the area of the image in which motion is identified is an individual pixel. 39. The device as claimed in claim 38, wherein the individual pixel is one of the inner pixels with regard to the group of pixels. 40. The device as claimed in claims 31, wherein the individual pixel is the pixel having the second lowest line number. 41. The device as claimed in any of claims 21, wherein the device has an alarm device, the alarm device being actuated and an alarm being triggered in response to the identification of motion in the image. 42. The device as claimed in claims 24, wherein the device furthermore has a device for processing the image, which accepts the image unchanged in areas in which no motion has been identified, while it performs a processing in areas of the image in which motion has been identified, only pixel information from one field being used. 43. The device as claimed in claims 38, wherein for a location of the image in which motion has been identified, only the pixel value from one field is used for the representation, in which case, at respective locations of the other field at which motion has likewise been identified and which are adjacent to the location, use is made of substitute values obtained by an interpolation of pixel values of said one field from surroundings of the location. 44. The device as claimed in claim 43, wherein the surroundings of the location reach approximately as far as the third successive pixel of said one field. 45. The device as claimed in claims 24, wherein the device is a microchip, a camera, a camcorder, a television set, a video recorder, or a DVD player. |
Process for preparation of piperidin-2-ylacetic acid |
Piperidin-2-ylacetic acid (II) is efficiently and safely produced in industrial scale by treating piperidin-2-ylethanol (I) with 2,2,6,6-tetramethylpiperidin-1-oxyl, sodium hypochlorite and sodium chlorite in a two phase solvent comprising an organic solvent and water without using strongly toxic chromium trioxide. |
1. A process for preparing piperidin-2-ylacetic acid of the formula (II): wherein piperidin-2-ylethanol of the formula (I): or its salt is treated with 2,2,6,6-tetramethylpiperidin-1-oxyl, sodium hypochlorite and sodium chlorite in a two phase solvent comprising an organic solvent and water to give piperidin-2-ylacetic acid. 2. The process for preparing piperidin-2-ylacetic acid of the formula (II): according to claim 1; wherein piperidin-2-ylethanol of the formula (I): or its salt is treated with sodium hypochlorite in the presence of 2,2,6,6-tetramethylpiperidin-1-oxyl under a neutral to basic condition and then treated with sodium chlorite under an acidic condition to give the piperidin-2-ylacetic acid. 3. The process according to claim 1, wherein the organic solvent is ethyl acetate, toluene, acetonitrile or methylene chloride. 4. The process according to claim 2 wherein the treatment with sodium hypochlorite in the presence of 2,2,6,6-tetramethylpiperadin-1-oxyl is carried out at about pH 7-10. 5. The process according to claims 2, wherein the treatment with sodium chlorite is carried out at about pH 3-6. 6. The process according to claim 2, wherein the organic solvent is ethyl acetate, toluene, acetonitrile or methylene chloride. 7. The process according to claim 3, wherein the treatment with sodium hypochlorite in the presence of 2,2,6,6-tetramethylpiperadin-1-oxyl is carried out at about pH 7-10. 8. The process according to claim 3, wherein the treatment with sodium chlorite is carried out at about pH 3-6. 9. The process according to claim 4, wherein the treatment with sodium chlorite is carried out at about pH 3-6. |
<SOH> BACKGROUND ART <EOH>A method for preparing piperidin-2-ylacetic acid (II) by subjecting piperidin-2-ylethanol (I) having the formula (I): to Jones oxidation is known [Knight D. W, et al., J. Chem. Soc. Perkin Trans. I, 1994, 2903]. According to the above oxidation, there gives an advantage that ethyl alcohol moiety at the side chain is selectively oxidized to acetic acid without oxidation of the nitrogen atom in the piperidine ring. To the contrary, it is unsuitable for industrial-scale production, because the oxidation reaction requires to use strongly toxic chromium trioxide as an oxidizing agent, and further gives a waste liquid containing chromium after the reaction. Meanwhile, a method is known, in which a primary alcohol is oxidized to a carboxylic acid by treating the alcohol in acetonitrile with sodium hypochlorite (NaOCl) in the presence of 2,2,6,6-tetramethylpiperidin-1-oxyl (TEMPO) [Nooy, A. E., et al., Synthesis, 1996, 1153]. However, this method is unsatisfactory for reaction efficacy, because it requires a largely excessive amount of sodium hypochlorite. In addition, a two-step reaction is known, in which a primary alcohol is oxidized by the Swern oxidation using dimethyl sulfoxide and oxalyl chloride to yield an aldehyde, followed by oxidation of the resulting aldehyde to the carboxylic acid by using sodium chlorite (NaClO 2 ) [Lindgren, B. O., et al., Acta Chem. Scand., 1973, 2, 888]. However, this method is complicate in post-processing, and is difficult to apply it to large-scale synthesis. Furthermore, a method is also known, in which a primary alcohol substituted with an aromatic hydrocarbon ring, a hetero ring or an alkynyl group is oxidized to the corresponding carboxylic acid by treating the alcohol with sodium hypochlorite and sodium chlorite in the presence of TEMPO in a two phase solvent comprising acetonitrile and a low pH range buffer solution [Mangzhu Zhao, et al., J. Org. Chem., 1999, 64, 2564]. According to this method, the alcohol is efficiently oxidized to the carboxylic acid, but careful attention must be paid during operation for adding sodium hypochlorite and sodium chlorite, because they must be added simultaneously notwithstanding the danger of furious reaction of sodium hypochlorite with sodium chlorite. Moreover, keeping the reaction liquid under an acidic condition is required to proceed the reaction, and accordingly a large amount of an acidic buffer solution is necessary. Therefore, it is difficult to apply this method to large-scale synthesis. |
Medicinal use of histone deacetylase inhibitor and method of evaluating antitumor effect thereof |
A therapeutic agent for prostate cancer and malignant lymphoma containing FK228 or a salt thereof as an active ingredient, and a method for evaluating an antitumor effect of a histone deacetylase inhibitor which includes at least a step of treating a test cell with a histone deacetylase inhibitor, a step of measuring change in the expression amount of a specific gene in the test cell before and, after the treatment with the inhibitor, comparing the both expression amounts. |
1-34. (canceled) 35. An agent for treating prostate cancer, which comprises a compound represented by the formula (I) or a salt thereof as an active ingredient. 36. The agent of claim 35, wherein the compound represented by the formula (I) is a compound represented by the formula (II) 37. The agent of claim 35, which has an antitumor action in vivo. 38. An agent for treating malignant lymphoma other than T cell lymphoma, which comprises a compound represented by the formula (I) or a salt thereof as an active ingredient. 39. The agent of claim 38, wherein the compound represented by the formula (I) is a compound represented by the formula (II) 40. The agent of claim 38, which has an antitumor action in vivo. 41. A pharmaceutical composition for treating prostate cancer, which comprises a compound represented by the formula (I) or a salt thereof, and a pharmaceutically acceptable carrier. 42. The pharmaceutical composition of claim 41, wherein the compound represented by the formula (I) is a compound represented by the formula (II) 43. A pharmaceutical composition for treating malignant lymphoma other than T cell lymphoma, which comprises a compound represented by the formula (I) or a salt thereof, and a pharmaceutically acceptable carrier. 44. The pharmaceutical composition of claim 43, wherein the compound represented by the formula (I) is a compound represented by the formula (II) 45. A method for treating prostate cancer, which comprises administering an effective amount of a compound represented by the formula (I) or a salt thereof to a patient. 46. A method for treating malignant lymphoma other than T cell lymphoma, which comprises administering an effective amount of a compound represented by the formula (I) or a salt thereof to a patient. 47. A commercial package comprising the pharmaceutical composition of claim 41 and a written description stating that the pharmaceutical composition can or should be used for treating prostate cancer. 48. A commercial package comprising the pharmaceutical composition of claim 43 and a written description stating that the pharmaceutical composition can or should be used for treating malignant lymphoma other than T cell lymphoma. 49. A method for evaluating an antitumor effect of a histone deacetylase inhibitor, which comprises at least a step of treating a test cell with a histone deacetylase inhibitor, and a step of measuring change in the expression of a specific gene in the test cell before and after the treatment with said inhibitor, and comparing the both expression amounts. 50. The method of claim 49, wherein the specific gene is a p21 gene and/or c-myc gene. 51. The method of claim 49, wherein the histone deacetylase inhibitor is a compound represented by the formula (I) or a salt thereof. 52. The method of claim 50, wherein the histone deacetylase inhibitor is a compound represented by the formula (I) or a salt thereof. 53. A method for evaluating an antitumor effect of a histone deacetylase inhibitor, which comprises at least a step of treating a test cell with a histone deacetylase inhibitor, and a step of measuring change in the expression of a specific protein in the test cell before and after the treatment with said inhibitor, and comparing both expression amounts. 54. The method of claim 53, wherein the specific protein is p21 and/or c-myc. 55. The method of claim 53, wherein the histone deacetylase inhibitor is a compound represented by the formula (I) or a salt thereof. 56. The method of claim 54, wherein the histone deacetylase inhibitor is a compound represented by the formula (I) or a salt thereof. 57. A method for screening a histone deacetylase inhibitor having a site-specific antitumor activity, which comprises at least a step of treating a test cell with a histone deacetylase inhibitor, and a step of measuring change in the expression of a specific gene in the test cell before and after the treatment with said inhibitor, and comparing both expression amounts. 58. A method for screening a histone deacetylase inhibitor having a site-specific antitumor activity, which comprises at least a step of treating a test cell with a histone deacetylase inhibitor, and a step of measuring change in the expression of a specific protein in the test cell before and after the treatment with said inhibitor, and comparing the both expression amounts. 59. A method for obtaining a gene capable of being an index for predicting the efficacy of FK228, which comprises at least (1) a step of treating an FK228 sensitive tumor cell and an FK228 resistant tumor cell with FK228, (2) a step of selecting genes that show increased or decreased expression in step (1) above, and (3) a step of selecting, from the genes selected in step (2) above, (i) a gene that shows increased expression due to the treatment with FK228, higher expression in the FK228 sensitive tumor cell and lower expression in the FK228 resistant tumor cell, (ii) a gene that shows increased expression due to the treatment with FK228, lower expression in the FK228 sensitive tumor cell and higher expression in the FK228 resistant tumor cell, (iii) a gene that shows decreased expression due to the treatment with FK228, higher expression in the FK228 sensitive tumor cell and lower expression in the FK228 resistant tumor cell, or (iv) a gene that shows decreased expression due to the treatment with FK228, lower expression in the FK228 sensitive tumor cell and higher expression in the FK228 resistant tumor cell. |
<SOH> BACKGROUND ART <EOH>In recent years, “tailor made medicine” is gaining recognition, which takes into consideration individual differences between patients, and a search for a marker to distinguish a cancer against which a pharmaceutical agent is effective from a cancer against which the pharmaceutical agent is ineffective is considered to be necessary. It is an attempt to ethically and medically improve cost performance of medication treatment by administering a pharmaceutical agent to patients after verification in advance of the probability of effect thereof, thereby to enhance efficacy as well as avoid toxicity of the pharmaceutical agent, and to reduce insignificant use of the pharmaceutical agent. In cancer treatment, the development of a method for predicting the efficacy of anticancer agents has been desired, because it can be an important means to bridge the gap between basic study and clinical application. In addition, it has been pointed out with regard to a substance or a compound generally reported to have an antitumor activity that, when the report is based solely on in vitro results, such results do not directly lead to the prediction of in vivo results. In other words, it is a problem that a substance showing an antitumor activity in vitro does not necessarily show an antitumor activity in vivo, and application of a substance showing an antitumor activity in vitro directly as an anticancer agent is difficult. For example, a compound represented by the formula (II) has been reported to introduce a potent antitumor activity by selectively inhibiting histone deacetylase (this substance has been also reported to cause high acetylation of histone in a cell treated with this substance, and as a result, induces transcriptional control activity of various genes, cell cycle inhibitory activity and apoptosis inhibitory activity (JP-B-7-64872, H. Nakajima et al, Exp. Cell Res. 241, 126-133 (1998))). However, no report has established a factor capable of predicting an antitumor effect of this compound, and as the situation stands, many problems are yet to be solved, such as whether or not in vitro results directly apply in vivo, whether or not the compound shows a practical effect in vivo in any tumor and the like. Histone deacetylase is a metallo-deacetylated enzyme wherein Zn is coordinated at the active center (M. S. Finnin et al, Nature, 401, 188-193 (1999)). This enzyme is considered to change the affinity for DNA of various acetylated histones. A direct biological phenomenon this brings about is changes in the chromatin structure. The minimum unit of the chromatin structure is a nucleosome wherein 146 bp DNA is wound 1.8 times anticlockwise around a histone octamer (H2A, H2B, H3 and H4, each 2 molecules, core histone). The core histone stabilizes the nucleosome structure as the positive charge at the N-terminal of each histone protein interacts with DNA. Acetylation of histone is controlled by the balance between the acetylation reaction in which histone acetyl transferase is involved and the deacetylation reaction in which histone deacetylase is involved. The acetylation of histone occurs in an evolutionarily well-preserved lysine residue at the N-terminal of histone protein, whereby, it is considered, the core histone protein loses the charge at the N-terminal, the interaction with DNA is attenuated, and the nucleosome structure becomes instable. Accordingly, the deacetylation of histone is considered to proceed in reverse, namely, toward the stabilization of the nucleosome structure. However, there still remain many unclear aspects such as the degree the acetylation changes the chromatin structure, and how it relates to the secondarily induced transcriptional control and the like. |
<SOH> BRIEF DESCRIPTION OF THE DRAWINGS <EOH>FIG. 1 is a graph showing an antitumor effect of FR901228 on human prostate cancer, wherein the vertical axis shows a tumor growth rate, the transverse axis shows the number of days lapsed from the initial administration, and the tumor growth rate is expressed in a relative proportion of tumor volume after day 0 relative to the tumor volume on day 0 taken as 1. FIG. 2 includes graphs showing an antitumor effect of FR901228 on human lymphoma, wherein the vertical axis shows the proportion of survived mice, and the transverse axis shows the number of days lapsed after tumor cell implantation. FIG. 3 includes graphs showing an antitumor effect of FR901228 on human prostate cancer ((a); PC-3) and kidney cancer ((b); ACHN), wherein the vertical axis shows a tumor growth rate, the transverse axis shows the number of days lapsed after the initial administration, and the tumor growth rate is expressed in a relative proportion of tumor volume after day 0 relative to the tumor volume on day 0 taken as 1. FIG. 4 includes graphs showing an action of FR901228 on p21 gene expression in vitro (PC-3 cell, ACHN cell). (a),(b); The vertical axis shows a relative amount of p21 gene expression, and the transverse axis shows contact time (hr) with FR901228. (c); The vertical axis shows a relative amount of p21 gene expression. FIG. 5 includes graphs showing an action of FR901228 on p21 gene expression and c-myc gene expression in vivo (PC-3 cell, ACHN cell), wherein the vertical axis shows a relative amount of p21 or c-myc gene expression, and the transverse axis shows the number of days lapsed after administration of FR901228. detailed-description description="Detailed Description" end="lead"? |
Biological sequence information reading method and storing method |
A method of reading biological sequence information comprising a step of judging similarity between biological sequence information as a target of reading and biological sequence information registered in a user side database, and a step of displaying the former information together with the biological sequence information registered in the user side database which is judged to have a similar sequence, and optionally comprising a step of registering the biological information as a target of reading in the user side database. |
1. A method of reading biological sequence information which comprises: (a) a step of designating one or more biological sequence information to be a target of reading as a reading sequence, (b) a step of judging similarity between the reading sequence and one or more biological sequence information registered in a user side database, and (c) when the reading sequence is similar to one or more biological sequence information in the user side database, a step of displaying the biological sequence information in the user side database as a similar sequence together with the reading sequence. 2. The method of claim 1, wherein the reading sequence is designated in step (a) based on information displayed on the terminal. 3. The method of claim 2 that uses documents in HTML format, XHTML format, or XML format as the information displayed on the terminal. 4. The method of claim 1, wherein the judgment of similarity in step (b) is carried out by a sequence alignment method. 5. The method of claim 1, wherein the judgment of similarity in step (b) is carried out by the method described in PCT International Publication WO 01/13268 (“Eigen ID”). 6. The method of claim 1, wherein a sequence alignment between the reading sequence and the similar sequence is displayed in step (c). 7. The method of claim 1, wherein the relation between the reading sequence and the similar sequence is displayed as a group or with hierarchy in step (c). 8. The method of claim 1, characterized by merging and displaying respective annotation information on the reading sequence and the similar sequence in step (c). 9. The method of claim 1, wherein a steric structure of the protein corresponding to either one or both of the reading sequence and the similar sequence is displayed in step (c). 10. The method of claim 1, which further comprises the following step: (d) a step of storing the reading sequence in the user side database. 11. The method of claim 10, characterized by storing the reading sequence and the similar sequence as a group or with hierarchy in step (d). 12. The method of claim 10, wherein respective annotation information on the reading sequence and the similar sequence are merged and stored in step (d). 13. The method of claim 10, which further comprises the following step: (e) a step of obtaining information from a server computer using a data item in the user side database as a query and setting the information as the reading sequence in step (a). 14. The method of claim 13 which comprises a step of generating an information source specification that corresponds to a data item in the user side database using an auxiliary database storing information sources for respective types of data items. 15. A method of obtaining information from a server computer using a data item in the user side database generated by the method of claim 10 as a query. |
<SOH> BACKGROUND ART <EOH>Due to the progress of genome study, proteome study and others, information on genome that is a body of genomic information on organisms and information on proteins that are expressed based on genome are rapidly accumulating. Such biological sequence information is accumulated in server computers in public organizations and companies as databases and is utilized. As examples of databases collecting information on nucleic acid base sequences, GenBank (NCBI, USA), EMBL nucleotide sequence database (EMBL-EBI, Europe), DDBJ (National Institute of Genetics, Japan) and others are open to the public and utilized. Furthermore, there exists a nucleic acid sequence database developed by a company that conducts genomic analysis as a business. As examples of databases collecting information on amino acid sequences of proteins, SwissProt, TrEMBL (both by Swiss Institute of Bioinformatics), GenPept, RefSeq (both by NCBI, USA), PIR (NBRF, USA), PRF (Protein Research Foundation, Osaka) and others are open to the public and utilized. As an example of database collecting information on steric structures of proteins, Protein Data Bank (RCSB, USA) is known which contains information on amino acid sequence in addition to the information on the three dimensional coordinates of each atom of the protein. As an example of database collecting information on diseases arising from abnormality of genes, OMIM (NCBI, USA) is known. Among the aforementioned biological sequence information databases, there are those retaining relational information to entries in other database as data. For example, each entry of the SwissProt database retains IDs of entries in EMBL nucleotide sequence database, PIR database, Protein Data Bank, OMIM database and others, that correspond to the amino acid sequence of said entry, as relational information. Moreover, it retains IDs in the PubMed (NCBI, USA) database for literatures reporting basic data regarding said entry. By using such relational information, it is possible to display link information for displaying an entry of other related database by a URL, when a certain entry of SwissProt is displayed on the World Wide Web (WWW) browser for example, so that a user can read the entry of other database easily. Generally, most of the biological sequence information databases are made public through WWW server, and a user can use from a terminal such as a personal computer through a communication line such as the internet or local area network. On the user side terminal, it is a general practice to search databases and read information obtained by the search using a WWW browser such as the Internet Explorer or the Netscape Navigator. Furthermore, there is a system like GCG Wisconsin Package (Accekrys, USA) wherein the user searches biological sequence information database and read the information from a character display terminal. As examples of search methods for a biological sequence information database, there are methods such as BLAST (Altschul S. F. et al., J. Mol. Biol. vol.215, pp.403-410, 1990) and FASTA (Pearson W. R. and Lipman D. J., Proc. Natl. Acad. Sci. USA, vol.85, pp.2444-2448, 1988) wherein the search is carried out based on the identity or similarity of nucleic acid base sequences or amino acid sequences, as well as a general search method based on the match or partial match of a keyword in the database. Furthermore, “sequence alignment method” is also used frequently, which searches the correspondence between sequences for multiple data with similar sequences. Examples of the sequence alignment method include Smith-Waterman algorithm (Smith T. F. and Waterman M. S., J. Mol. Biol., vol.147, pp.195-197, 1981) and Clustal-W (Thompson J. D. et al., Nucleic Acids Res., vol.22, pp.4673-4680, 1994). |
Waterproofing air and vapor barrier membrane |
An integrated waterproofing and air/vapor barrier membrane is provided which comprises a preformed waterproofing or sealing material layer (1) covered on one face with adherent impervious material (1), and on the other major face with an adherent porous support sheet (16). The waterproofing or sealing material layer can be covered on both sides with adherent support sheets. Heating of the barrier membrane allows self-adhesion to a surface on which it is applied after transudation of fusion of the sealing material through the support sheets. |
1. (canceled) 2. (canceled) 3. (canceled) 4. (canceled) 5. (canceled) 6. (canceled) 7. (canceled) 8. (canceled) 9. (canceled) 10. (canceled) 11. A barrier membrane substantially impervious to atmospheric air and vapor for covering a construction surface or an area comprising a sealing material layer having opposite first and second sides, said first and second sides being coated with a support sheet composed of material allowing transudation or fusion of said sealing material through said support sheet to allow self-adhesion of the first side of said barrier membrane on said construction surface, and to a second surface on the second side. 12. The barrier membrane of claim 11, wherein said sealing material is composed of air- and water-repellant material selected from the group consisting of a bitumen, a polymer, a resin, and a mixture thereof. 13. The barrier membrane of claim 12, wherein said bitumen is a polymer-modified asphalt. 14. The barrier membrane of claim 11, wherein said sealing material further comprises up to 40% by weight of filler. 15. The barrier membrane of claim 11, wherein said support sheet is composed of material selected from the group consisting of a polymer, a resin, a plastic, a polyester, a polypropylene, a polybutyrene, a polyimide, a polycarbonate, a polyamide, a polyethylene, a polystyrene, a polyvinylchloride, a fluoroplastic, a sulfone polymer, and a polyvinylidene chloride. 16. The barrier membrane of claim 11, wherein said sealing material comprises between 50 to 100% of bitumen, and up to 50% by weight of at least one copolymer, wherein combination of said bitumen and said copolymer forms 100% of said sealing material. 17. The barrier membrane of claim 16, wherein said copolymer is styrene-butanediene-styrene, ethylene, propylene, butene, a derivative or a mixture thereof. 18. The barrier membrane of claim 11, wherein said sealing material transudes or fuses through support sheet on at least one side after heating of said barrier membrane. 19. A laminated panel used for construction covered at least partially with a barrier membrane as defined in claim 1. 20. A laminated panel used for construction covered at least partially with a barrier membrane as defined in claim 11. 21. The laminated panel of claim 20, wherein said panel is a board of wood, concrete, gypsum, perlite, kraft, foam, wood fiber or plywood. 22. A method for protecting a construction surface against atmospheric air and vapor comprising the steps of: applying a construction surface with a barrier membrane as defined in claim 1; and heating said barrier membrane applied on said construction surface for a time and to a temperature allowing said sealing material to transude or fuse through one side of said support sheet and adhere to said construction surface. 23. The method of claim 22, wherein a structural panel is adhered to the second side of said barrier membrane before or after adhesion to said construction surface. 24. The method of claim 23, wherein said structural panel is a board of insulating material, a paper sheet, or a metallic sheet. |
<SOH> BACKGROUND ART <EOH>Many related art water devices exist for covering or protecting surfaces from water penetration. These include waterproof coverings different surfaces and coatings. Similarly there are numerous protective courses which are applied over the waterproof surface to protect it On the other hand, it is known that bitumen-based membranes are used for waterproofing in construction. Such membranes normally feature a reinforcement made of non-woven polyester cloth or of a layer of reinforced glass such as fiberglass. One of the membrane surfaces is coated with small slate flakes of various colors, similar to granules, for protection against ultraviolet rays. The users of these types of membranes currently face serious problems when trying to seal together contiguous membranes because of the relatively complex steps that must be carried out to connect the two contiguous or adjacent ends. Of course, if an effective seal is not attained, the membrane system will leak and not achieve its very purpose. Most of membranes known in the art for sealing a structure or a surface need the release of one part, such as a non-adherent sheet on one face of a impervious layer before application on the surface. Waterproofing barrier membranes are generally obtained in sheets of 3, 4 or 5 mm thickness and, if total or partial adhesion to the support is required, they can be applied either by means of a propane-gas torch, which by liquefying the bituminous mass makes it adherent to the support, or by using hot air-blown bitumen which acts as an adhesive. However, while membranes based on bitumen modified with styrene-butanediene-styrene (SBS) as known in the art, yield good results with both methods (with preference for the air-blown bitumen method, due to some limitations of the SBS membrane with the torch method, such as excessive softening which almost always prevents rapid and easy application of the membrane, especially in summer), it is recognized that polyolefin-based membranes generally yield the best results only with the flame method; this especially because otherwise, in the course of time, adhesion tends to decrease due to the forming of an oily layer between the air-blown bitumen and the membrane which causes its separation in the course of time. On another aspect in building construction requirements, air leakage can account for an important part of the total heat loss in home because warm air leaks out while cold air leaks in. Along with the air, moisture (vapor) escapes and can condense inside the walls or attic that could cause serious structural damage when mold, mildew and rot occurs. A good seal ensures less air infiltration as well as drier insulation and building interior. To avoid air and vapor transfers, new-building manufacturers use state of the art products to create an air/vapor barrier envelope. The most important property of an air-vapor barrier is the ability to resist airflow and air pressure. A continuous air/vapor barrier completely encloses air within a building, keeping moisture from entering insulated cavities where it can condense into water. At the opposite, a vapor retarder inhibits vapor diffusion, but remains partially permeable to air and humidity. Bitumen-based layers are often applied to masonry or sheathing material to create an air barrier system. These membranes are relatively impermeable to water, and thus constitute vapor barriers. The problems of hardening the handling during application of waterproofing barrier membranes because of the release of paper or because of the use of a torch demonstrate that there is still an important need in the art for new waterproofing and air/vapor barrier membranes. |
<SOH> SUMMARY OF THE INVENTION <EOH>One object of the present invention is to provide an integrated waterproofing membrane comprising a waterproofing material layer capable to transude through a sheet of fibers or a sheet of paper, having opposite first and second sides, the first side being coated with a non transudent impervious surfacing material which is adherent to the waterproofing material and the second side being coated with an adherent support sheet composed of material allowing passage of the waterproofing material through the adherent support sheet to enter in contact with a surface on which the integrated waterproofing membrane is applied, the adherent support sheet being capable also of allowing passage there through of an adhesive material previously applied thereon or on a surface on which the integrated waterproofing membrane is to be applied. The waterproofing material layer may be composed of transuding material selected from the group consisting of bitumen, a polymer, and a resin, wherein the bitumen can be polymer-modified asphalt. The thickness waterproofing material layer may be between 0.1 to 8 mm. In accordance with the present invention there is provided an waterproofing membrane in which an impervious surfacing material is composed a non transudent material that may be selected from the group consisting of a polymer, a resin, a plastic, a metal, a polyester, a polypropylene, a polybutyrene, a polyimide, a polycarbonate, a polyamide, a polyethylene, a polystyrene, a polyvinylchloride, a fluoroplastic, a sulfone polymer, and a polyvinylidene chloride. Also, the support sheet may be composed of paper, fabric, fiber network, or mixture thereof. The waterproofing material may further comprise up to 50% by weight of filler. The waterproofing material may comprise between 50 to 100% of bitumen, and up to 50% by weight of at least one copolymer. The mixture of the bitumen and a copolymer generally forms 100% of the waterproofing material. The copolymer can be composed of ethylene, propylene, butene, derivative or mixture thereof. Another object of the present invention is to provide a paneling material covered, at least partially, with the air/vapor barrier membrane of the present invention. In accordance with the present invention, there is provided a barrier membrane substantially impervious to atmospheric air and vapor for covering a construction surface or an area comprising a sealing material layer having opposite first and second sides, the first and second sides being coated with a support sheet composed of material allowing transudation or fusion of the sealing material through the support sheet to allow self-adhesion of the first side of the barrier membrane on the construction surface, and to a second surface on the second side. The sealing material can be composed of air- and water-repellant material selected from the group consisting of bitumen, a polymer, a resin, and a mixture thereof, where the bitumen can be a polymer-modified asphalt. The sealing material may further comprises up to 40% by weight of filler. The support sheet can be composed of material selected from the group consisting of a polymer, a resin, a plastic, polyester, a polypropylene, a polybutyrene, a polyimide, a polycarbonate, a polyamide, a polyethylene, polystyrene, a polyvinylchloride, a fluoroplastic, a sulfone polymer, and a polyvinylidene chloride. The sealing material may comprise between 50 to 100% of bitumen, and up to 50% by weight of at least one copolymer, wherein combination of the bitumen and the copolymer forms 100% of said sealing material. The copolymer can be styrene-butanediene-styrene, ethylene, propylene, butene, a derivative or a mixture thereof. The sealing material is capable to transude or fuse through support sheet on at least one side after heating of the barrier membrane. Another object of the present invention is to provide a laminated panel used for construction and covered at least partially with an integrated and air/vapor barrier membrane as described herein. The laminated panel can be a board of wood, concrete, gypsum, perlite, kraft, foam, wood fiber or plywood. Another object of the present invention is to provide a method for protecting a construction surface against atmospheric air and vapor comprising: a) applying a construction surface with a waterproofing and air/vapor barrier membrane as defined herein; and b) heating the barrier membrane applied on the construction surface for a time and to a temperature allowing the sealing material to transude or fuse through one side of the support sheet and adhere to the construction surface. A structural panel can additionally adhered to the second side of the barrier membrane before or after adhesion to a construction surface. The structural panel can be a board of insulating material, a paper sheet, or a metallic sheet. For the purpose of the present invention the following terms are defined below. The term “bitumen” as used herein is intended to mean residue from atmospheric distillation of crude oil or of a mixture thereof with a slightly oxidized product. The softening point of the various types varies from 36° C. to 140° C., and the penetration number is generally comprised between 40 to 350 dmm; bitumen which have a penetration number comprised between 60 to 220 dmm and a softening point comprised between 60° C. and 120° C. are preferably used for modification with polymers. It is furthermore possible to use mixture of various types of bitumen, and the properties of the bitumen can be modified by adding mineral oils, fatty substances, chemical agents which make it impenetrable to roots, and others. The term “copolymer” as used herein is intended to mean an elastic polymer which may be formed with ethylene, polyester, polypropylene, polybutyrene, polyimide, polycarbonate, polyamide, polyethylene, polystyrene, polyvinylchloride, fluoroplastics, sulfone polymers, polyvinylidene chloride, butene, derivatives or mixtures thereof. The ratios of polymers used in preparing a mixture may vary depending of the physical and chemical properties needed in a waterproofing or sealing material. For example, a waterproofing or sealing material according to the present invention may comprise between 5 to 15% by weight of copolymers. Also, for example, one type of mixture of copolymers, which can be used in the waterproofing or sealing material, may comprises between 25 to 70% propylene, 20 to 70% butene and 0 to 15% ethylene. The terms “sealing” or “sealed” as used herein are intended to mean the capacity or property of a matter to significantly prevent the passage of a gas or a liquid through a material or a structure. The terms “transudent” or “transuding” as used herein is intended to mean the capacity or property of a matter to transude, to exude, to excrete, to fuse, to transpire, to diffuse, or to pass through pores or interstices of a layer, as a sheet of paper for example. A matter capable to transude, slowly or rapidly, may be liquid, viscous, or pasty, and may have a physical state, meaning that the transuding matter may be more or less viscous for example, depending of the ambient temperature. The support sheets on both sides of the barrier membrane of the present invention can be either transuding of non-transuding. A non-transuding matter is relatively solid, and does not transude, exude, excrete, transpire, diffuse, or pass through pores or interstice. |
Method for dressing and animating dressed characters |
A method of dressing 3D virtual beings and animating the dressed beings for visualisation, the method comprising the steps of: positioning one or more garment pattern around a body of a 3D virtual being; applying, iteratively, to the pattern elastic forces in order to scam the garment; and once the garment is scanned, causing the body to carry out one or more movements, wherein the overstretching of cloth within the garment is prevented by the modification of the velocity, in the direction of cloth stretch, of one or more points within the garment. The present invention provides a fast method for dressing virtual beings and for visualising and animating the dressed bodies, and a system for carrying out the method. |
1. A method of dressing 3D virtual beings and animating the dressed beings for visualisation, the method comprising the steps of: positioning one or more garment pattern around a body of a 3D virtual being; applying, iteratively, to the pattern elastic forces in order to seam the garment; and once the garment is seamed, causing the body to carry out one or more movements, wherein overstretching of cloth within the garment is prevented by the modification of the velocity, in the direction of cloth stretch, of one or more points within the garment. 2. A method as claimed in claim 1, further including the step of determining, after each application of elastic forces to the pattern, whether the garment is correctly seamed. 3. A method as claimed in claim 1 or claim 2, wherein gravitational forces are applied to the garment prior to the body upon which it is fitted being caused to carry out movement. 4. A method as claimed in any preceding claim, wherein the cloth of the garment is modelled using a masses and springs model. 5. A method as claimed in any preceding claim, wherein the virtual body is caused to move by the production and presentation of consecutive images of the body, the images differing in positioning such that when presented consecutively the body carries out a movement sequence. 6. A method as claimed in claim 5, wherein the prevention of overstretching includes the steps of: after the generation of each image, determining for each spring within the garment whether the spring has exceeded its natural length by a pre-defined threshold; and for each spring that has exceeded its natural length, adjusting the directional velocity of the mass point at one or both ends of the spring. 7. A method as claimed in claim 6, wherein velocity adjustments are calculated by: calculating a directional vector for the garment by determining the sum of the velocity of the object which the garment is covering and the velocity due to gravity of the garment; calculating a spring directional vector; and determining an angle between the two vectors; wherein, if the spring is perpendicular to the directional vector, the velocity components at each end and parallel to the spring are modified, such that they are each set to their mean value; otherwise the velocity component, parallel to the spring, of the rearmost end of the spring with regard to the calculated directional vector is set equal to that of the frontmost end. 8. A method as claimed in claim 7, wherein the spring directional vector is calculated by determining the difference between the positions of the end parts of the spring. 9. A method as claimed in any preceding claim, further including the steps of: after the generation of each image, determining for each of a plurality of vertices or faces within the garment, whether a collision has occurred between the cloth and the body; and if a collision has occurred, generating and applying to the vertex or face the cloth's reaction to the collision. 10. A method as claimed in claim 9, wherein a face comprises a quadrangle on cloth, and the face midpoint and velocity are an average of those values for the four surrounding vertices. 11. A method as claimed in claim 9 or 10, wherein the body is represented by a depth map in image-space, and collisions are determined by comparing the depth value of a garment point with the corresponding body depth information from the map. 12. A method as claimed in any of claims 9 to 11, wherein generating the cloth's reaction includes the steps of: generating one or more normal map for the virtual body; generating one or more velocity map for the virtual body; and determining the relative velocity between garment and object. 13. A method as claimed in claim 12, wherein the cloth's reaction is determined by the relationship: vres=Cfric·vt−Crefl·vn+Vobject wherein Cfric and Crefl are friction and reflection coefficients which depend upon the materials of the colliding cloth and object, and vt and vn are the tangent and normal components of the relative velocity. 14. A method as claimed in claim 12, further including, prior to the determination of the relative velocity, the steps of: determining a reaction force for the cloth vertex; and adding the reaction force to the forces apparent upon the cloth vertex. 15. A method as claimed in claim 14, wherein the reaction force is given by: freaction=−Cfricft−fn, wherein Cfric is a frictional coefficient dependent upon the material of the cloth and ft and fn are the tangential and normal components of the force acting on the cloth vertex. 16. A method as claimed in either claim 12 or claim 13, wherein a normal map is generated by substituting a [Red, Green, Blue] depth map value of each vertex of the body with co-ordinates of its corresponding normal vector, and interpolating between points to produce a smooth normal map. 17. A method as claimed in any of claims 12 to 16, wherein a velocity map is generated by substituting [Red, Green Blue] depth map value of each vertex within the mapped body with the co-ordinates of its velocity, and interpolating the velocities for all intermediate points. 18. A method as claimed in either of claims 16 or 17, wherein substitution comprises representing the substituted coordinates as colour values. 19. A method of dressing 3D virtual beings and animating the dressed beings for visualisation, the method comprising the steps of: positioning one or more garment pattern around a body of a 3D virtual being; applying, iteratively, to the pattern elastic forces in order to seam the garment; and once the garment is seamed, causing the body to carry out one or more movements, wherein collisions between the garment and body are detected and compensated for in image-space, vector co-ordinates of the body being represented by colour values to enable body normal and velocity vectors to be generated by graphics hardware. 20. A method substantially as hereinbefore described with reference to and as shown in the accompanying drawings. 21. A system configured to carry out the method of any preceding claim. 22. A system as claimed in claim 21, wherein visualisation of the dressed and animated body takes place at a terminal remote from a server carrying out the method. 23. A system as claimed in claim 22, wherein communication between the terminal and the server is via the internet, or other analogous means. 24. A system substantially as hereinbefore described with reference to and as shown in the accompanying drawings. 25. A computer program product comprising a computer readable medium having stored thereon computer program means for causing a computer to carry out the method of any of claims 1 to 20. |
Molecular characterists of non-small cell lung cancer |
We used hierarchical clustering to examine gene expression profiles generated by serial analysis of gene expression (SAGE) in a total of nine normal lung epithelial cells and non-small cell lung cancers (NSCLC). Separation of normal and tumor samples, as well as histopathological subtypes, was evident using the 3,921 most abundant transcript tags. This distinction remained when just 115 highly differentially expressed transcript tags were used. Furthermore, these 115 transcript tags clustered into groups that were suggestive of the unique biological and pathological features of the different tissues examined. Adenocarcinomas were characterized by high-level expression of small airway-associated or immunologically related proteins, while squamous cell carcinomas overexpressed genes involved in cellular detoxification or antioxidation. The messages of two p53-regulated genes, p21WAF1/CIP1 and 14-3-3σ, were consistently under-expressed in the adenocarcinomas, suggesting that the p53 pathway itself might be compromised in this cancer type. Gene expression observed by SAGE were consistent with the results obtained by quantitative real-time PCR or cDNA array analyses using 43 additional lung tumor and normal samples. Thus, although derived from only a few tissue libraries, molecular signatures of non-small cell lung cancer derived from SAGE most likely represent an unbiased yet distinctive molecular signature for human lung cancer. |
1. A method of identifying a lung cancer as squamous cell carcinoma comprising: determining an amount of a gene product of a gene in a lung cancer sample, said gene selected from the group consisting of: glutathione peroxidase (GPX;; NM—002083), glutathione S-transferase M3 (GSTM3; NM—000849), aldoketoreductase family 1, member B 10 (NM—020299), peroxiredoxin 1 (PRDX1; NM—002574), small proline-rich protein 3 (SPRR3; NM—005416), and TNF receptor superfamily member 18 (TNFRSF18; NM004195); comparing the amount of the gene product to the amount determined in a lung tissue sample which is non-pathological, wherein an increased amount of the gene product in the lung cancer sample relative to the lung tissue sample which is non-pathological identifies the lung cancer as a squamous cell carcinoma. 2. The method of claim 1 further comprising the step of using the determined comparative gene product information to formulate a diagnosis. 3. The method of claim 1 further comprising the step of using the determined comparative gene product information to formulate a prognosis. 4. The method of claim 1 further comprising the step of using the determined comparative gene product information to formulate a treatment plan. 5. The method of claim 1 wherein the gene product of GPX is determined. 6. The method of claim 1 wherein the gene product of GSTM3 is determined. 7. The method of claim 1 wherein the gene product of aldoketoreductase is determined. 8. The method of claim 1 wherein the gene product of PRDX1 is determined. 9. The method of claim 1 wherein the gene product of SPRR3 is determined. 10. The method of claim 1 wherein the gene product of TNF receptor 18 is determined. 11. The method of claim 1 wherein the gene product is mRNA. 12. The method of claim 1 wherein the gene product is protein. 13. The method of claim 1 wherein the lung tissue sample which is non-pathological comprises normal lung small airway epithelial cells. 14. The method of claim 1 wherein the lung tissue sample which is non-pathological comprises normal bronchial/tracheal epithelial cells. 15. The method of claim 1 wherein the amount of the gene product is determined using a microarray. 16. The method of claim 15 wherein cRNA is hybridized to probes on the microarray to determine the amount of the gene product. 17. A method of identifying a lung cancer as adenocarcinoma, comprising: determining an amount of a gene product of a small proline-rich protein 3 (SPRR3; NM—005416) gene in a lung cancer sample; comparing the amount of the gene product to the amount determined in a lung tissue sample which is non-pathological, wherein a decreased amount of the gene product in the lung cancer sample relative to the lung tissue sample which is non-pathological identifies the lung cancer as adenocarcinoma. 18. The method of claim 17 further comprising the step of using the determined comparative gene product information to formulate a diagnosis. 19. The method of claim 17 further comprising the step of using the determined comparative gene product information to formulate a prognosis. 20. The method of claim 17 further comprising the step of using the determined comparative gene product information to formulate a treatment plan. 21. The method of claim 17 wherein the gene product is mRNA. 22. The method of claim 17 wherein the gene product is protein. 23. The method of claim 17 wherein the lung tissue sample which is non-pathological comprises normal lung small airway epithelial cells. 24. The method of claim 17 wherein the lung tissue sample which is non-pathological comprises normal bronchial/tracheal epithelial cells. 25. The method of claim 17 wherein the amount of the gene product is determined using a microarray. 26. The method of claim 25 wherein cRNA is hybridized to probes on the microarray to determine the amount of the gene product. |
<SOH> BACKGROUND OF THE INVENTION <EOH>Lung cancer is the leading cause of cancer death worldwide and NSCLC accounts for nearly 80% of the disease (1). Based on cell morphology, adenocarcinoma and squamous are the most common types of NSCLC (2). Although the clinical courses of these tumors are similar, adenocarcinomas are characterized by peripheral location in the lung and often have activating mutations in the K-ras oncogene (3, 4). In contrast, squamous cell carcinomas are usually centrally located and more frequently carry p53 gene mutations (5). Furthermore, the etiology of squamous cell carcinoma is closely associated with tobacco smoking while the cause of adenocarcinoma remains unclear (6, 7). Although many molecular changes associated with NSCLC have been reported (8, 9), the global gene expression pattern associated with these two most common types of lung cancer has not be described. Understanding gene expression patterns in these major tumor types will uncover novel markers for disease detection as well as potential targets for rational therapy of lung cancer. Several technologies are currently being utilized for gene expression profiling in human cancer (10). SAGE (11) is an open system that rapidly identifies any expressed transcript in a tissue of interest, including transcripts that had not been identified. This highly quantitative method can accurately identify the degree of expression for each transcript. Comparing SAGE profiles between the tumor and the corresponding normal tissues can readily identify genes differentially expressed in the two populations. Using this method, novel transcripts and molecular pathways have been discovered (12-14). In contrast, cDNA arrays represent a closed system that analyze relative expression levels of previously known genes or transcripts (15, 16). Because many thousands of genes can be placed on a single membrane or slide for rapid screening, studies have recently demonstrated molecular profiles of several human cancers (17-20). Hierarchical clustering is a systematic method widely used in cDNA array data analysis where the difference between the expression patterns of many genes is generally within a few fold (21). We reasoned that because SAGE is highly quantitative, hierarchical clustering might be used to organize gene expression data generated by SAGE from just a few tissue libraries. To test this, SAGE tags from two of each libraries derived from primary adenocarcinomas, primary squamous cell carcinomas, normal lung small airway epithelial cells (SAEC), or normal bronchial/tracheal epithelial (NHBE) cells, and a lung adenocarcinoma cell line were used. SAGE tags showing the highest abundance were subjected to clustering analysis. Although each library was derived from a different individual, normal and tumor samples clustered in two separate branches while tissues of different cell types clustered together. Furthermore, SAGE tags clustered into biologically meaningful groups revealing the important molecular characteristics of these two most common NSCLC subtypes. |
<SOH> BRIEF SUMMARY OF THE INVENTION <EOH>The present invention provides a method of identifying a lung cancer as squamous cell carcinoma. According to the method an amount of a gene product of a gene in a lung cancer sample is determined. The gene is selected from the group consisting of: glutathione peroxidase (GPX; NM — 002083), glutathione S-transferase M3 (GSTM3; NM — 000849), aldoketoreductase family 1, member B 10 (NM — 020299), peroxiredoxin 1 (PRDX1; NM — 002574), small proline-rich protein 3 (SPRR3; NM — 005416), and TNF receptor superfamily member 18 (TNFRSF18; NM004195). The amount of the gene product in the lung cancer sample is compared to the amount determined in a lung tissue sample which is non-pathological. An increased amount of the gene product in the lung cancer sample relative to the lung tissue sample which is non-pathological identifies the lung cancer as a squamous cell carcinoma. The present invention provides a method of identifying a lung cancer as adenocarcinoma. According to the method an amount of a gene product of a small proline-rich protein 3 (SPRR3; NM — 005416) gene in a lung cancer sample is determined. The amount of the gene product in the lung cancer sample is compared to the amount determined in a lung tissue sample which is non-pathological. A decreased amount of the gene product in the lung cancer sample relative to the lung tissue sample which is non-pathological identifies the lung cancer as adenocarcinoma. The invention thus provides the art with a molecular diagnostic to supplement or replace histological features and/or clinical behavior. |
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.