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Device for changing the work rolls and the back-up rolls of a strip-mill |
The invention relates to a method and a device for changing the work rolls and the back-up rolls (8, 9) of a strip mill, by means of a roll-changing carriage (2) which can be transversally displaced in relation to the roll stand (1). Said roll-changing carriage receives the old sets of rolls removed, enabling them to be exchanged for new sets of rolls. |
1.-3. (canceled) 4. An apparatus for changing the work rolls and backup rolls of a roll stand in a strip mill, the strip mill defining a longitudinal path therethrough, said apparatus comprising: a roll-changing carriage movable transversely to the longitudinal path of the strip mill, said roll-changing carriage being movable from a distal standby position to a proximal position relative to the roll stand; a stationary changing cylinder mounted proximate a floor level of the strip mill and a piston movably inserted in said changing cylinder and having a forward end projecting out of said changing cylinder, said piston being movable in said changing cylinder transverse to the longitudinal path of the strip mill; an extraction carriage connected to said piston rod at said forward end and movable with said piston rod on said roll-changing carriage, said extraction carriage being selectively connectable with said roll-changing carriage such that said extraction carriage and said roll-changing carriage are movable together by said piston rod of said changing cylinder transversely to the longitudinal path of said strip mill when said extraction carriage is connected with said roll-changing carriage; a transverse shift table installed on said roll-changing carriage and movable approximately parallel to the longitudinal path of the strip mill; and a shift cylinder movable approximately parallel to the longitudinal path of said strip mill and selectively engageable with said transverse shift table for moving said transverse shift table into and out of a changing position aligned with the roll stand. 5. A process for changing work rolls in a roll stand of a strip mill using the apparatus of claim 1, comprising the steps of: arranging the roll-changing carriage at the distal standby position, wherein the transverse table holds a new set of work rolls; coupling the extraction carriage to the roll-changing carriage and moving, by the changing cylinder, the extraction carriage and the roll-changing carriage to the proximal position relative to the roll stand; connecting the extraction carriage with an old set of work rolls in the roll stand to be changed; uncoupling the extraction carriage from the roll-changing carriage and engaging the transverse shift table with the shift cylinder, which causes the roll-changing carriage to be locked in the proximal position relative to the roll stand; moving, by the changing cylinder and the extraction carriage, the old set of work rolls from the roll stand to a changing position on the transverse shift table; disconnecting the extraction carriage from the old set of work rolls; shifting the transverse shift table, by the shift cylinder, so that the old set of work rolls is moved out of the changing position and the new set of work rolls is moved into the changing position, which is aligned with the roll stand; connecting the extraction carriage with the new set of work rolls and moving, by the changing cylinder, the extraction carriage and the new set of work rolls such that the new set of work rolls are moved into the roll stand; disconnecting the extraction carriage from the new set of work rolls; disengaging the shift cylinder from the transverse shift table and coupling the extraction carriage to the roll-changing carriage; and moving the roll-changing carriage with the old set of work rolls located on the transverse shift table into the distal standby position, where the old set of work rolls is removeable. 6. A process for changing the backup rolls in a roll stand of a strip mill after removal of the work rolls using the apparatus of claim 1, comprising the steps: arranging the roll-changing carriage at the distal standby position; coupling the extraction carriage to the roll-changing carriage and moving, by the changing cylinder, the extraction carriage and the roll-changing carriage to the proximal position relative to the roll stand; connecting the extraction carriage with a lower backup roll of the old set of backup rolls in the roll stand to be changed; moving, by the changing cylinder, the extraction carriage and the roll-changing carriage together away from the roll stand such that the lower backup roll of the old set of backup rolls connected to the extraction carriage is brought into a changing position to the side of the roll stand; placing a dummy on the lower backup roll; moving, by the changing cylinder, the roll-changing carriage with the extraction carriage and the lower backup roll of the old set of backup rolls with the dummy back into the roll stand; placing the upper backup roll of the old set of backup rolls on the dummy; moving, by the changing cylinder, the roll-changing carriage with the extraction carriage and the old set of backup rolls out of the roll stand and into the changing position; disconnecting the extraction carriage from the lower backup roll of the old set of backup rolls; replacing the old set of backup rolls with a new set of backup rolls including a dummy; connecting the extraction carriage with a lower backup roll of the new set of backup rolls; moving, by the changing cylinder, the roll-changing carriage with the extraction carriage and the new set of backup rolls into the roll stand; removing the upper backup roll of the new set of backup rolls from the dummy and installing the upper backup roll of the new set of backup rolls in the roll stand; moving, by the changing cylinder, the roll-changing carriage with the extraction carriage and the lower backup roll of the new set of backup rolls with the dummy from the roll stand to the changing position; removing the dummy from the lower backup roll of the new set of backup rolls; moving, by the changing cylinder, the roll-changing carriage with the extraction carriage and the lower backup roll of the new set of backup rolls into the roll stand; disconnecting the extraction carriage from the lower backup roll of the new set of backup rolls; and moving, by the changing cylinder, the extraction carriage and the roll-changing carriage to the distal standby position. |
Demodulator and demodulation method for demodulating received signals |
The invention relates to a demodulator and also a demodulation method and enables a reliable demodulation even when the intermediate frequency range overlaps the range of the data frequencies of the signal. For this purpose, a rapidly oscillating output signal is generated from the in-phase signal and also the quadrature signal, the sign of which output signal varies in a manner dependent on the product of the signs of the in-phase signal and of the quadrature signal. Either an XOR gate or a multiplier stage may be used in order to generate an output signal of this type. |
1. A demodulator for demodulating radiofrequency signals, comprising: a mixer, which downconverts the radiofrequency signal into an intermediate frequency range, the mixer generating an in-phase signal and also a quadrature signal, a signal converter unit, which converts the in-phase signal and also the quadrature signal into an output signal of increased carrier frequency, the signal converter unit varying the sign of the output signal in a manner dependent on the product of the signs of the in-phase signal and of the quadrature signal, and means for determining the period duration or the frequency of the output signal generated by the signal converter unit. 2. The demodulator as claimed in claim 1, wherein the demodulator further comprises channel filters for the in-phase signal and the quadrature signal, which are connected downstream of the mixer and suppress, at least in part, frequencies outside the intermediate frequency range. 3. The demodulator as claimed in claim 2, wherein the channel filters comprise complex bandpass filters. 4. The demodulator as claimed in claims 1, wherein the signal converter unit comprises means for an XOR combination of the in-phase signal and of the quadrature signal. 5. The demodulator as claimed in claim 4, wherein the in-phase signal and the quadrature signal are embodied as analog signals, and in that the means for the XOR combination of the in-phase signal and of the quadrature signal are embodied using analog technology. 6. The demodulator as claimed in claim 4, wherein the signal converter unit comprises means for limiting and level matching of the in-phase signal and of the quadrature signal and in that the means for the XOR combination of the in-phase signal and of the quadrature signal are embodied using digital technology and combine the limited, level-matched signals. 7. The demodulator as claimed in claims 1, wherein the signal converter unit comprises a multiplier stage for multiplying the in-phase signal and the quadrature signal, the in-phase signal and the quadrature signal being embodied as analog signals. 8. The demodulator as claimed in claim 1, wherein the means for determining the period duration or the frequency comprises edge detectors for detecting the signal edges of the output signal of the signal converter unit. 9. The demodulator as claimed in claim 8, wherein the means for determining the period duration or the frequency comprises edge detectors for detecting the rising signal edges and edge detectors and for detecting the falling signal edges. 10. The demodulator as claimed in claim 1, wherein the means for determining the period duration or the frequency comprises at least one counting discriminator for detecting the time intervals between successive rising or falling signal edges. 11. The demodulator as claimed in claim 10, wherein the at least one counting discriminator comprises a counter whose counter reading is counted up by a counting clock, the counter being read and reset with each pulse of the edge detector. 12. The demodulator as claimed in claim 1, wherein the means for determining the period duration or the frequency comprises at least one integrator which integrates the output signal generated by the signal converter unit. 13. The demodulator as claimed in claim 1, wherein the means for determining the period duration or the frequency comprises at least one 1/x element, with which the detected period durations are converted into values proportional to the frequency. 14. A radio station, which comprises a demodulator as claimed in claim 1. 15. The radio station as claimed in claim 14, wherein the radio station is designed for data transmission in accordance with one of the standards DECT or Bluetooth. 16. A method for demodulating radiofrequency signals, comprising: a) downconverting the radiofrequency signal into an intermediate frequency range and generation of an in-phase signal and also of a quadrature signal; b) converting the in-phase signal and of the quadrature signal into an output signal of increased carrier frequency, the sign of which is varied in a manner dependent on the product of the signs of the in-phase signal and of the quadrature signal; and c) determining the period duration or of the frequency of the output signal. 17. The method as claimed in claim 16, wherein the in-phase signal and the quadrature signal are converted into the output signal by means of an XOR combination. 18. The method as claimed in claim 16, wherein the output signal is obtained by multiplication of the in-phase signal by the quadrature signal. 19. The method as claimed in claim 16, wherein signal edges of the output signal are detected in order to determine the period duration or the frequency of the output signal. 20. The method as claimed in claim 19, wherein the time intervals between successive rising or falling signal edges are detected in order to determine the period duration or the frequency of the output signal. 21. The method as claimed in claim 16, further comprising integrating the output signal in order to determine the period duration or the frequency of the output signal. 22. The method as claimed in claim 16, wherein the determined period durations are converted into values proportional to the frequency by means of a 1/x element. |
Pulp pump |
Centrifugal pumps for pumping a pulp suspension and conducting gas away from the pulp suspension are disclosed including a pump housing having an inlet and an outlet, a rotary shaft, an impeller mounted on the rotary shaft within the pump housing, the impeller including a hub and pump blades extending outwardly from the hub, a wheel disk adjacent to the impeller so that the pump blades extend outwardly along the wheel disk, a vacuum impeller within the pump housing behind the wheel disk and including a vacuum pump housing, vacuum impeller blades, a seal for sealing the vacuum pump housing to the rotary shaft, the vacuum pump housing including a suction port for drawing gas into the vacuum pump housing and an exhaust port for expelling gas therefrom. |
1-3. (canceled). 4. A centrifugal pump for pumping a pulp suspension and conducting gas away from said pulp suspension, said centrifugal pump comprising a pump housing including an inlet for said pulp suspension and an outlet for said pumped pulp suspension, a rotary shaft, an impeller mounted on said rotary shaft within said pump housing, said impeller including a hub, and a plurality of pump blades extending outwardly from said hub, a wheel disk adjacent to said impeller whereby said pump blades extend outwardly along said wheel disk, a vacuum impeller disposed within said pump housing behind said wheel disk, said vacuum impeller including a vacuum pump housing, a plurality of vacuum impeller blades disposed within said vacuum pump housing, and a seal for sealing said vacuum pump housing to said rotary shaft, said vacuum pump housing including a suction port for drawing gas into said vacuum pump housing and an exhaust port for expelling gas from said vacuum pump housing. 5. The centrifugal pump of claim 4 including a channel connecting said suction port with said exhaust port, and a valve disposed within said channel for controlling the vacuum in said vacuum pump housing. 6. The centrifugal pump of claim 4 wherein said vacuum pump housing includes a first side adjacent to said impeller and a second side distal from said impeller, said suction port and said exhaust port being disposed on said first side of said vacuum pump housing, said seal being disposed on said second side of said vacuum pump housing and including a sealed housing and a liquid inlet connected to said sealed housing, said sealed housing communicating with said vacuum pump housing to supply said liquid to said vacuum pump housing. |
<SOH> FIELD OF THE INVENTION <EOH>The present invention relates to a centrifugal pump for pulp suspensions of lignocellulosic material. More particularly, the present invention relates to a pump where gas, such as air, can be separated from the pulp in the pump. Gas following along with the pulp creates problems during pumping of pulp by centrifugal pumps. The gas in the pulp forms bubbles, which are accumulated in front of the impeller and thereby deteriorate the capacity of the pump. This problem can be overcome by evacuating the gas from the space in front of the impeller, for example by means of vacuum pumps such as the liquid-ring pump type. Such a pump can be a separate vacuum pump, the suction pipe of which is connected to the sealing space of the pulp pump, or it can be formed with a separate vacuum impeller in the form of a liquid-ring impeller, which is mounted on the shaft of the pulp pump, so that for both impellers a common operation is obtained. In cases where a separate vacuum pump is used, the pulp pump becomes relatively complicated and expensive, because the system comprises more components compared to a pulp pump, where the vacuum impeller is mounted on the shaft of the pulp pump. Swedish patent specification No. 502,127 and European patent specification No. 298,949 describe embodiments of pulp pumps where the vacuum impeller is mounted on the shaft of the pulp pump. During, for example, control of the capacity of the vacuum pump by adjustable throttling or resetting the eccentricity of the vacuum pump housing, as shown in Swedish patent specification No. 502,127, several movable parts are required in the pump housing. This requires more or less extreme designs, with the concurrent risk of faulty functioning. The maintenance will also thus be more complicated and expensive. In cases when the vacuum pump is controlled by means of additional air, as shown in European patent specification No. 298,949, a great amount of air is supplied to a pump system, with the intention being that air should be removed therefrom. The present invention implies that the aforesaid problems can be eliminated. The manufacture and maintenance costs for the pulp pump, for example, can be reduced. The need of liquid for the operation is decreased, and control and sealing of the vacuum pump can be carried out more simply. The need of air to be added to the pump can also be reduced substantially. |
<SOH> SUMMARY OF THE INVENTION <EOH>In accordance with the present invention, these and other objects have been realized by the invention of a centrifugal pump for pumping a pulp suspension and conducting gas away from the pulp suspension, the centrifugal pump comprising a pump housing including an inlet for the pulp suspension and an outlet for the pumped pulp suspension, a rotary shaft, an impeller mounted on the rotary shaft within the pump housing, the impeller including a hub, and a plurality of pump blades extending outwardly from the hub, a wheel disk adjacent to the impeller whereby the pump blades extend outwardly along the wheel disk, a vacuum impeller disposed within the pump housing behind the wheel disk, the vacuum impeller including a vacuum pump housing, a plurality of vacuum impeller blades disposed within the vacuum pump housing, and a seal for sealing the vacuum pump housing to the rotary shaft, the vacuum pump housing including a suction port for drawing gas into the vacuum pump housing and an exhaust port for expelling gas from the vacuum pump housing. In a preferred embodiment, the centrifugal pump includes a channel connecting the suction port with the exhaust port, and a valve disposed within the channel for controlling the vacuum in the vacuum pump housing. In accordance with another embodiment of the centrifugal pump of the present invention, the vacuum pump housing includes a first side adjacent to the impeller and a second side distal from the impeller, the suction port and the exhaust port being disposed on the first side of the vacuum pump housing, the seal being disposed on the second side of the vacuum pump housing and including a sealed housing and a liquid inlet connected to the sealed housing, the sealed housing communicating with the vacuum pump housing to supply the liquid to the vacuum pump housing. In accordance with the present invention, the pulp pump is formed so that the suction port and exhaust port of the vacuum pump housing are in controllable connection with each other. |
Radio communication device radio communication method, radio communication system, recording medium, and program |
The present invention relates to a radio communication apparatus and a radio communications method, a radio communication system, a recording medium, and a computer program in which a response signal to an inquiry is returned to a master only when instructions to perform radio communications are issued. A CPU 51 blinks LED 56 when an inquiry signal is received, and transmits a response to the inquiry signal when a user who has referred to lighting of the LED 56 operates a connection response button 53. The connection response button 53 is operated when the user issues radio communications instructions with respect to the inquiry signal. In other words, even when wireless headphones 2 are within an area capable of radio communications with the master, only if the connection response button 53 is operated by the user, it sends to the master a response to the inquiry, and establishes connection. The present invention may be applied to a wireless storage server, wireless headphones, and audio reproduction apparatuses. |
1. A radio communication apparatus capable of radio-communicating with another radio communication apparatus, characterized by comprising: receiving means for receiving an inquiry signal for asking whether or not radio communication is available from said other radio communication apparatus; first input means for receiving an operation input when a user grants communication with said other radio communication apparatus; and transmitting means for transmitting predetermined information to said other radio communication apparatus when said operation is inputted by said first input means. 2. The radio communication apparatus according to claim 1, characterized by further comprising: notice means for notifying that said inquiry signal has been received by said receiving means. 3. The radio communication apparatus according to claim 2, characterized in that said notice means further notifies that a data link with said other communication apparatus has been established. 4. The radio communication apparatus according to claim 2, characterized in that said notice means further notifies that the data link with said other communication apparatus has not been established. 5. The radio communication apparatus according to claim 2, characterized in that said notice means is constituted by an LED. 6. The radio communication apparatus according to claim 5, characterized in that said first input means is constituted by a button, and said LED is integrated with said button. 7. The radio communication apparatus according to claim 5, characterized in that said notice means notifies that said inquiry signal has been received by blinking said LED, further notifies that the data link with said other communication apparatus has been established by lighting said LED, and further notifies that the data link with said other communication apparatus has not been established by turning said LED off. 8. The radio communication apparatus according to claim 2, characterized in that said notice means carries out audio reproduction of a message notifying that said inquiry signal has been received. 9. The radio communication apparatus according to claim 2, characterized in that said first input means is operated by said user notified that said inquiry signal has been received by said notice means, and said predetermined information transmitted by said transmitting means to said other radio communication apparatus is an inquiry response signal to said inquiry signal. 10. The radio communication apparatus according to claim 2, characterized in that said first input means is operated by said user notified that said inquiry signal has been received by said notice means, and said predetermined information is a connection request signal transmitted by said transmitting means to said other radio communication apparatus. 11. The radio communication apparatus according to claim 1, characterized in that said transmitting means transmits said predetermined information to said other radio communication apparatus when said inquiry signal is received by said receiving means after said first input means received an operation input by said user. 12. The radio communication apparatus according to claim 1, characterized in that said transmitting means transmits said predetermined information to said other radio communication apparatus when said inquiry signal is received by said receiving means during a period in which said first input means receives said operation input by said user. 13. The radio communication apparatus according to claim 1, characterized in that said receiving means receives said inquiry signal only during a period in which said first input means receives said operation input by said user. 14. The radio communication apparatus according to claim 2, characterized by further comprising: generation means for generating said inquiry signal for searching for said other radio communication apparatus which can perform wireless communications; second input means for instructing transmission of said inquiry signal; and transmitting means for transmitting said inquiry signal when the instructions to transmit said inquiry signal are issued by said second input means. 15. The radio communication apparatus according to claim 14, characterized in that said notice means further notifies that said inquiry signal has been transmitted by said transmitting means. 16. The radio communication apparatus according to claim 14, characterized in that said notice means further notifies that a data link with said other communication apparatus has been established. 17. The radio communication apparatus according to claim 14, characterized in that said notice means further notifies that data link with said other communications apparatus has not been established. 18. The radio communication apparatus according to claim 14, characterized in that said first input means and said second input means are integrated as a third input means; said third input means operates as said first input means when said inquiry signal is received by said receiving means before said third input means receives the operation input by said user; and said third input means operates as said second input means when said third input means receives the operation input by said user before said inquiry signal is received by said receiving means. 19. The radio communication apparatus according to claim 18, characterized in that said third input means is constituted by a button; said notice means is constituted by an LED; and said LED is integrated with said button. 20. A wireless-communications method for a radio communication apparatus capable of communicating with another radio communication apparatus by radio, characterized by comprising: a reception control step of controlling reception of an inquiry signal for asking whether or not radio communications are available, the inquiry signal being transmitted from said other radio communication apparatus; an input control step of controlling an operation input when a user permits communicating with said other radio communication apparatus; and a transmitting control step of controlling transmission of predetermined information to said other radio communication apparatus when the input of said operation is controlled by said input control step. 21. A recording medium having recorded therein a computer program, characterized in that the computer program for a radio communication apparatus capable of communicating with another radio communication apparatus by radio, includes: a reception control step of controlling reception of an inquiry signal for asking whether or not radio communications are available, the inquiry signal being transmitted from said other radio communication apparatus; an input control step of controlling an operation input when a user permits communicating with said other radio communication apparatus; and a transmitting control step of controlling transmission of predetermined information to said other radio communication apparatus when the input of said operation is controlled by said input control step. 22. A computer program capable of being executed by a computer which controls a radio communication apparatus capable of communicating information to another radio communication apparatus by radio, characterized by comprising: a reception control step of controlling reception of an inquiry signal for asking whether or not radio communications are available, the inquiry signal being transmitted from said other radio communication apparatus; an input control step of controlling an operation input when a user permits communicating of said information to said other radio communication apparatus; and a transmitting control step of controlling transmission of predetermined information to said other radio communication apparatus when the input of said operation is controlled by said input control step. predetermined information to said other radio communication apparatus when the input of said operation is controlled by said input control step. 23. A radio communication system constituted by a first radio communication apparatus and a second radio communication apparatus which can mutually communicate by wireless communications, characterized in that said first radio communication apparatus comprises: a generation means for generating an inquiry signal for searching for said second radio communication apparatus capable of performing radio communications; a first input means for receiving an operation input when a user issues instructions to transmit said inquiry signal generated by said generation means to every apparatus capable of radio communications within a predetermined area; and a first transmitting means for transmitting said inquiry signal to said every apparatus capable of radio communications within said predetermined area when said first input means issues instructions to transmit said inquiry signal; said second radio communication apparatus comprises: a second input means for receiving the operation input when the user permits communicating of information to said first radio communication apparatus; a receiving means for receiving said inquiry signal transmitted from said first radio communication apparatus by said first transmitting means; a second transmitting means for transmitting predetermined information to said first radio communication apparatus when said second input means inputs a fact that said user permits communicating of said information to said first radio communication apparatus and said inquiry signal is received by said receiving means. 24. The radio communication system according to claim 23, characterized in that said predetermined information transmitted by said second transmitting means is an inquiry response signal to said inquiry signal. 25. The radio communication system according to claim 23, characterized in that said predetermined information transmitted by said second transmitting means is a connection request signal to said first radio communication apparatus. |
<SOH> BACKGROUND ART <EOH>In recent years, short-distance radio communication technologies, such as IrDA (InfraRed Data Association) and Bluetooth (registered trademark) communication, have spread widely. IrDA is a radio communication technology using infrared rays, permitting communication at 1.152 Mbps and 4 Mbps by only set up of software. On the other hand, the Bluetooth communication is a radio transmission system which uses a 2.4 GHz zone, and does not have directivity but high permeability, unlike a case where infrared is used. The Bluetooth communication is expected to be an interface which realizes a data exchange regardless of devices, such as a personal computer, a peripheral apparatus, a household appliance, and a portable phone. As for Bluetooth compliant devices, there are a “master” which determines a frequency hopping pattern and a “slave” which communicates with and follows the master, and a network comprises one master and a plurality of (seven sets, at most) slaves. The slaves perform communication between the master and the slaves, synchronizing with the frequency hopping pattern determined by the master. Communications between the devices are always performed through the master, so that no direct communication is performed between the slaves. When choosing a communication counterpart's device in the Bluetooth communications, it is common that the master transmits an inquiry signal (Inquiry), by broadcasting, to devices which exist around itself so as to search for a possible device to be communicated, collect responses from the slaves, display, on a display screen, a list of model names, device ID's, etc. of devices which may be communicated, and have a user to choose a communication counterpart's device out of them. However, with this method, there are many devices which allow radio communication within an area where communications are available and, even if most of the devices do not desire communication, all devices will be listed and displayed on a display section of the master. For example, when the list is displayed on the display screen by means of device ID's, it is difficult for the user to choose a desired one out of the displayed list including the plurality of apparatus ID's which cannot be grasped intuitively. Similarly, when the list on the display screen is displayed by means of model names and a plurality of more apparatuses of the same type are included in the apparatuses which can communicate, it is difficult to determine which device the user to choose. In particular as for a short-distance radio communication technology which does not have directivity, such as the Bluetooth communication, unlike the communications having the directivity such as the infrared technology etc., it is difficult to intuitively choose a communication counterpart's device from the plurality of devices which can communicate, since devices within a predetermined area can communicate in all directions. In addition, in order to determine a communication counterpart's device, a conventional method forces the user to perform operations such as referring to the display and choosing a desired device out of them, and there is a need for a technology in which the communication counterpart's device can be intuitively determined by an easy operation. |
<SOH> BRIEF DESCRIPTION OF THE DRAWINGS <EOH>FIG. 1 is a view for explaining a radio communication system to which the present invention is applied; FIG. 2 is a block diagram showing a structure of a wireless storage server to which the present invention is applied; FIG. 3 is a block diagram showing a structure of wireless headphones to which the present invention is applied; FIG. 4 is a view for explaining an example of structure of a connection response button and an LED; FIG. 5 is a view for explaining an example of structure of the connection response button and the LED; FIG. 6 is a view for explaining an example of structure of the connection response button and the LED; FIG. 7 is a flow chart for explaining a connection establishment process 1 ; FIG. 8 is a flow chart for explaining a connection establishment process 2 ; FIG. 9 is a view for explaining an inquiry packet and an inquiry response packet; FIG. 10 is a flow chart for explaining a connection establishment process 3 ; FIG. 11 is a flow chart for explaining a connection establishment process 4 ; FIG. 12 is a block diagram showing a structure of a audio reproduction apparatus applying the present invention; FIG. 13 is a flow chart for explaining a process in the audio reproduction apparatus; FIG. 14 is a flow chart for explaining a process of the audio reproduction apparatus; and FIG. 15 is a table for explaining modes of transmission and reception for an inquiry in the Bluetooth communication. detailed-description description="Detailed Description" end="lead"? |
Oral compositions for the treatment of scalp disorders |
Pharmaceutical and/or cosmetic compositions for the treatment and the prevention of scalp disorders, containing as active components extracts of Serenoa repens and of Vitis vinifera. |
1. The use of: a) extract of Serenoa repens; b) extract of Vitis vinifera in the free form and/or as phospholipid complexes; for the preparation of oral pharmaceutical and/or cosmetic compositions for the treatment and the prevention of scalp disorders. 2. The use of: a) extract of Serenoa repens; b) extract of Vitis vinifera in the free form and/or as complexes with phospholipids; in combination with additional active ingredients selected from the group consisting of oligoelements, such as zinc, copper, iron, selenium, magnesium; amino acids, such as L-lysine, L-proline, L-hydroxyproline, L-leucine, L-isoleucine, L-methionine, L-cysteine, L-cystine; vitamins, such as the vitamins B complex, vitamin E and vitamin C, for the preparation of oral pharmaceutical and/or cosmetic compositions for the treatment and the prevention of scalp disorders. 3.-11. (cancelled) |
Trench isolation having a self-adjusting surface seal and method for producing one such trench isolation |
The invention relates to a trench isolation with a self-aligning surface sealing and a fabrication method for said surface sealing. In this case, the surface sealing may have an overlap region of the substrate surface or a receded region into which extends an electrically conductive layer formed on the substrate surface. |
1. A method for fabricating a trench isolations on a semiconductor substrate, comprising: fabricating a layer stacks comprising a first, second and third layer on a surface of the semiconductor substrate; patterning the layer stacks as far as the surface of the semiconductor substrate to fabricate an opening region in the layer stack; etching the semiconductor substrate for the formation of an isolation trench in the opening region of the layer stack; depositing a first insulators for filling the isolation trench in the semiconductor substrate and the opening region in the layer stack; removing the first insulator in the opening region in the layer stacks and in the isolation trench in the semiconductor substrate as far as a level below the surface of the semiconductor substrate; depositing a second insulator on the first insulator for filling the isolation trench in the semiconductor substrate and the opening region in the layer stack, the second insulator having a higher resistance to removing and/or modifying methods than the first insulator; planarizing removal of the second insulator and of the layer stack down to a predetermined layer thickness of the second layer in the layer stack; and removing the remaining layer stack as far as the surface of the semiconductor substrate. 2. The method as claimed in claim 1, wherein removing the first insulator comprises lateral etching of the first layer of the layer stack with the aid of an isotropic etching method to undercut the second layer of the layer stack and to form a lamellar gap between the surface of the semiconductor substrate and the second layer of the layer stack at the surface of the semiconductor substrate for the second insulator that is subsequently deposited. 3. The method as claimed in claim 1, wherein patterning the layer stack comprises patterning the third and second layers of the layer stack with the aid of an anisotropic etching method to prefashion an opening region for an isolation trench on the first layer of the layer stack; lateral etching of the second layer of the layer stack with the aid of an isotropic etching method to undercut the third layer of the layer stack and to form a set-back region between the third and first layers, of the layer stack; and anisotropic etching of the first layer of the layer stack with the third layer of the layer stack as etching mask to fabricate the opening region for the isolation trench in the layer stack; and wherein removing of the first insulator further comprises: lateral etching of the first layer of the layer stack around the set-back region between the third and first layers of the layer stack form a lamellar gap between the surface of the semiconductor substrate and the third layer of the layer stack for the second insulator that is subsequently deposited. 4. The method as claimed in claim 1, wherein removing the remaining layer stack comprises: removing the second layer with the aid of a selective etching method; reducing the cross section of an upper region of the second insulator with the aid of a selective isotropic etching method; and removing the first layer with the aid of a selective etching method; and after removing the remaining layer stack: depositing an epitaxial semiconductor layer on the surface of the semiconductor substrate as far as a level below a surface of the second insulator. 5. The method as claimed in claim 1, wherein depositing a second insulating layer comprises: producing a thin separation layer on the side walls of the opening region in the layer stack and of the uncovered isolation trench above the first insulator; and depositing a second insulator on the first insulator for filling the isolation trench in the semiconductor substrate and the opening region in the layer stack; and after depositing a second insulating layer: essentially completing removal of the thin separation layer at the second insulator; and depositing an epitaxial semiconductor layers on the surface of the semiconductor substrate as far as a level below a surface of the second insulator. 6. The method as claimed in claim 1, wherein the first insulator is a silicon dioxide and the second insulator is a silicon nitride, and in the layer stack the first layer is a silicon dioxide layer, the second layer is an amorphous or polycrystalline silicon layer and the third layer is a silicon nitride layer. 7. A semiconductor structure having a trench isolation in a semiconductor substrate, comprising: an isolation trench having a first and a second insulator layer, the second insulator layer extending from a level below a surface of the semiconductor substrate as far as a level above a surface of the semiconductor substrate and being essentially planar with respect to the first insulator layer, the isolation trench and the first and second insulator layers having essentially perpendicular side walls, the second insulator layer having a higher resistance to removing and/or modifying methods than the first insulator layer, and the second insulator layer having, along a periphery of the isolation trench, a collar region directly on the surface of the semiconductor substrate with a defined lateral extent. 8. The semiconductor structure as claimed in claim 7, the collar region of the second insulator layer being formed in stepped fashion or in lamellar fashion. 9. The semiconductor structure as claimed in claim 7, the collar region of the second insulator layer having a lateral extent of 3 nm to 100 nm. 10. A semiconductor structure having a trench isolations in a semiconductor substrate, comprising: an isolation trench having a first and a second insulator layer, the second insulator layer extending from a level below a surface of the semiconductor substrate as far as a level above a surface of the semiconductor substrate and being essentially planar with respect to the first insulator layer, the isolation trench and the first and second insulator layers having essentially perpendicular side walls, the second insulator layer having a higher resistance to removing and/or modifying methods than the first insulator layer, the second insulator layer having a reduced cross section in an upper region, an electrically conductive layer being formed directly on the surface of the semiconductor substrate as far as a level below a surface of the second insulator layer, and the electrically conductive layer enclosing an upper region of the second insulator layer. 11. The semiconductor structure as claimed in claim 10, the upper region of the second insulator layer with the reduced cross section extending essentially as far as the level of the surface of the semiconductor substrate. 12. The semiconductor structure as claimed in claim 10, the upper region of the second insulator layer with the reduced cross section extending as far as a level below a surface of the semiconductor substrate, the electrically conductive layer filling a gap between the upper region of the second insulator layer and the isolation trench. 13. The semiconductor structure as claimed in claim 10, the electrically conductive layer being a semiconductor layer produced epitaxially. |
<SOH> BACKGROUND OF THE INVENTION <EOH>Trench isolations constitute lateral isolation structures of adjacent electrically active regions which are formed as trenches that are etched in a semiconductor substrate and filled with an electrically insulating material. Such isolation structures are necessary since, on account of the high packing density of contemporary integrated circuits (IC), the distances between the active components on the semiconductor wafer are so small that the components reciprocally influence one another to a great extent. In this case, it is also possible for parasitic components to arise which disturb the function of the original components. Trench isolations are possibilities for isolating the adjacent electrically active regions. Silicon dioxide (SiO 2 ) is generally used as material for filling the trenches in the case of trench isolations, and is deposited with the aid of thermal oxidation and oxide deposition into the trench structure. However, in the case of large aspect ratios of the trenches, which arise on account of the decreasing mutual distances between the components on a semiconductor substrate, it proves to be increasingly difficult to fill the isolation trenches. In particular, inner voids (shrink holes) occur in this case, and can disturb the function of the trench isolation or the further layer construction above the trench isolation. Furthermore, damage caused by degrading process steps during the post STI processing can impair the effect of trench isolations. Thus, principally the removal and the roughening of the insulator filling are responsible for defects of the trench isolation or adjoining components. Such defects can largely be avoided by elevated trench isolations and/or by restrictions to the post STI processing. In order to protect the insulator layer of the trench isolation against damage which can arise during the post STI processing, U.S. Pat. No. 6,146,970 A proposes depositing a nitride layer on the insulator layer. For this purpose, in a first step, a polysilicon layer formed on an adhesion layer above the substrate surface is oxidized. Removal of the thin oxide layer thus produced yields, along the isolation trench, a narrow region of open substrate surface, which is likewise filled during the subsequent filling of the isolation trench. In this case, the width of the overlap region of the nitride covering layer is prescribed by the thickness of the removed oxide layer. U.S. Pat. No. 6,010,947 A, U.S. Pat. No. 5,940,716 A and U.S. Pat. No. 6,143,623 A in each case describe methods for fabricating trench isolations which have regions partly overlapping the semiconductor substrate along their periphery. U.S. Pat. No. 6,143,626 A discloses a method for fabricating a trench isolation in a semiconductor substrate, wherein a two-layer isolation trench filling is provided in order to avoid voids which can usually arise during the filling of isolation trenches. |
<SOH> SUMMARY OF THE INVENTION <EOH>The present invention provides an improved trench isolation which remains resistant to removing and roughening process steps after the fabrication of the trench isolation. Furthermore, the invention provides a method for fabricating such a trench isolation. According to one embodiment of the invention, three layers are applied on a substrate surface and then an isolation trench is produced with the aid of removing process steps in the three layers and the underlying substrate. Afterward, the trench is filled with a first insulator layer and an insulating sealing layer arranged in a self-aligned manner with respect thereto, the sealing layer having a high resistance. By virtue of the invention's formation of a sealing layer, the insulator layer in the isolation trench is protected against removing or modifying post STI processes. This prevents, inter alia, the formation of shrink-hole openings, void openings and also parasitic components. Furthermore, the need for ideal filling and subsequent high densification of the first insulator layer is reduced. The use of a layer stack with a central layer arranged between the adhesion and hard mask layers makes it possible to vary the thickness of the sealing layer above the substrate surface during the fabrication of the trench isolation. The invention's fabrication of the trench isolation with the aid of a layer stack having a topmost hard mask layer makes it possible to obviate an additional photolithographic mask step during the patterning of the underlying layers. In one advantageous embodiment of the invention, in order to form the sealing layer, the second or the first layer is etched back laterally by a specific amount with the aid of isotropic etching processes. In this case, it is possible to vary the lateral extent and the configuration of the etched-back regions through a targeted choice of the process sequence. During the subsequent filling of the isolation trench with the sealing layer, the laterally etched-back regions are then also concomitantly filled and form a collar region along the periphery of the isolation trench which covers the substrate surface directly along the edge thereof. The collar region of the sealing layer, which directly overlaps the substrate surface along the periphery of the isolation trench, protects the substrate surface situated directly below the overlap region against removing or modifying post STI processes. The lateral extent and also the form of the overlap region require only little variation of the process sequence. The sealing layer can thus be optimally adapted in a simple manner to the specific requirements of the respective integrated circuit (IC). A further advantage of the preferred embodiment of the invention is that the substrate surface situated directly below the collar region is also electrically insulated toward the top. In a further advantageous embodiment of the invention, the sealing layer may have a narrowed partial section produced by the etching-back of the sealing layer or by means of a separation layer previously formed on the sidewalls of the isolation trench. A further preferred embodiment provides for an electrically conductive layer to be applied to the substrate surface. In this case, the layer, preferably formed as an epitaxial semiconductor layer, is deposited selectively onto the substrate surface and also extends into the receded regions of the sealing layer. This laterally extends the active substrate surface adjoining the isolation trenches, which brings about improved electrical properties of the active components formed within the extended active regions. |
Enzymes and enzymic processes |
A chimeric protein comprises a haem domain from a mammalian or plant cytochrome P450 and a scaffold domain generally comprising an electron transfer domain, from P450 BM3 of Bacillus megaterium. The protein does not include the membrane binding portion of the wild type mammalian or plant P450 and is hence water soluble. The protein is enzymnically active on substrates for the wild-type mammalian or plant P450 and electrons are transferred to electron transfer portions for instance part of the scaffold domain, such as FAD or FMN. The protein is useful for analysing the substrate specificity of the haem domain or for detecting substrates which are analytes of interest. |
1. A water soluble chimeric protein which comprises a scaffold domain and a monooxygenase haem containing domain, in which the scaffold domain comprises an integral electron transfer domain capable of transferring electrons to the haem domains and is derived from BM3 and the haem domain is derived from a plant or an animal P450 enzyme. 2. A protein according to claim 1 in which the electron transfer domain is a flavo protein. 3. A protein according to claim 1 in which the haem domain is derived from a human P450 enzyme. 4. A protein according to claim 3 in which the haem domain is derived from human P450 2E1. 5. A protein according to claim 3 in which the haem domain comprises at least 200 contiguous residues of the wild-type P450 enzyme or an active mono oxygenase mutant thereof in which no more than 20 residues have been deleted or altered. 6. A protein according to claim 5 in which the haem domain comprises at least 250 continuous residues including the C-terminal or a sequence commending from no more than 50 residues in-board of the C-terminal of the wild-type P450 enzyme. 7. A protein according to claim 6 in which the haem domain comprises at least 300 residues. 8. A protein according to claim 4 in which no more than 10 residues have been deleted or altered relative to the wild-type P450 enzyme. 9-17. (canceled) 18. A protein according to claim 8 in which no more than 10 residues have been deleted or altered relative to the wild-type P450 enzyme. 19. A protein according to claim 1 in which the scaffold domain comprises at least 25 residues from the N terminal of wild-type BM3 protein or mutants thereof in which no more than 10 residues have been deleted or altered. 20. A protein according to claim 19 in which the scaffold domain comprises at least 50 residues from the N-terminal of wild-type BM3 protein and mutants thereof in which no more than 10 residues have been deleted or altered. 21. A protein according to claim 7 in which the scaffold domain comprises at least 50 residues from the N-terminal of wild-type BM3 protein and mutants thereof in which no more than 10 residues have been deleted or altered. 22. An oxidation process comprising the steps: providing a water-soluble chimeric protein comprising a scaffold domain and a monooxygenase haem containing domain in which the scaffold domain comprises an integral electron transfer domain capable of transferring electrons to the haem domain is derived from BM3 and the haem domain is derived from a plant or an animal P450 enzyme and contacting the chimeric protein with a substate in a reaction mixture in the prescence of oxygen whereby the substrate is oxidised to form an oxidised product and the electron transfer domain is converted to its oxidised form transferring an electron to the haem domain. 23. A process according to claim 22 in which the electron transfer domain is converted back to its reduced from by transfer of electrons from NAD(P)H or an electrode. 24. A process according to claim 22 in which the substrate is an analyte of interest and in which the extent of the oxidation reaction is measured whereby the presence or concentration of analyte is determined in the reaction mixture. 25. A process according to claim 24 in which transfer of an electron is from NAD(P)H and in which the extent of the oxidation reaction is determined by monitoring the production of NAD(P)+. 26. A process according to claim 24 in which transfer of an electron is from NAD(P)H, oxygen is present during the process and the extent of oxidation reaction is determined by monitoring oxygen consumption. 27. A microorganism transformed to synthesise a protein according to claim 1. 28. A microorganism transformed to synthesise a protein according to claim 6. 29. A microorganism transformed to synthesize a protein which comprises a scaffold domain and a monooxygenase haem containing domain, in which the scaffold domain comprises an integral electron transfer domain capable of transferring electrons to the haem domains and is derived from BM3 and the haem domain is derived from a plant or an animal P450 enzyme, transformed to synthesise a protein in which the scaffold domain comprises at least 50 residues from the N-terminal of wild-type BM3 protein and mutants thereof in which no more than 10 residues have been deleted or altered. 30. A microorganism according to claim 27 which is E. coli. 31. A plasmid comprising a gene capable of expressing a protein according to claim 1. |
Genetic products of ashbya gossypii, associated with transmembrane transport |
The invention relates to novel polynucleotides from Ashbya gossypii; to oligonucleotides hybridizing therewith; to expression cassettes and vectors which comprise these polynucleotides; to microorganisms transformed therewith; to polypeptides encoded by these polynucleotides; and to the use of the novel polypeptides and polynucleotides as targets for improving transmembrane transport and, in particular, improving vitamin B2 production in microorganisms of the genus Asbya. |
1. An isolated polynucleotide derived from a microorganism of Ashbya gossypii that codes for a protein associated with the process of transmembrane transport of said microorganism. 2. The polynucleotide of claim 1, wherein the protein possesses a structural or functional property of a mitochondrial energy transfer protein, an ABC transport protein, a membrane-integrated mitochondrial protein, a mitochondrial inner membrane transport protein, a non-vacuolar 102 kD subunit of an H+-ATPase V0 domain, an isp4 protein, a VAC1 protein, a cystolic and peripheral membrane protein having three zinc fingers, a protein with ATPase activity, a protein with an ATPase-like function, a PHO85 protein, or a p24 protein. 3. The polynucleotide of claim 1, comprising the sequence of SEQ ID NO: 1, 5, 10, 14, 19, 23, 28, 33, 37 or 42 a sequence complementary thereto; or a sequence derived from said sequence or said complementary sequence through degeneracy of the genetic code. 4. The polynucleotide of claim 1, which comprises the sequence of SEQ ID NO: 3, 8, 12, 17, 21, 26, 31, 35, 40 or 44, or a fragment thereof. 5. An oligonucleotide that hybridizes with the polynucleotide of claim 1. 6. An isolated nucleic acid that hybridizes with the oligonucleotide of claim 5, and codes for a gene product derived from a microorganism of the genus Ashbya or a functional equivalent thereof. 7. An isolated polypeptide encoded by a the polynucleotide of claim 1 or a fragment thereof. 8. An expression cassette comprising the polynucleotide of claim 1 operatively linked to at least one regulatory nucleic acid sequence. 9. A recombinant vector comprising at least one expression cassette of claim 8. 10. A prokaryotic or eukaryotic host cell transformed with the recombinant vector of claim 9. 11. The host cell of claim 10, wherein functional expression of a gene that codes for said protein is modulated. 12. The host cell of claim 10, which is of the genus Ashbya. 13. A method for microbiological production of vitamin B2 or a precursor or derivative thereof comprising culturing a cell transformed with the vector of claim 9; and isolating there from the vitamin B2 or the precursor or derivative thereof. 14. A method for recombinant production of the polypeptide of claim 7 comprising culturing a cell transformed with said polynucleotide and isolating said polypeptide there from. 15. A method for detecting an effector target for modulating microbiological production of vitamin B2 or a precursor or derivative thereof, comprising: treating a microorganism with an effector, wherein said microorganism is capable of the microbiological production of vitamin B2 or the precursor or derivative thereof and wherein said effector target comprises the polypeptide of claim 7 or a nucleic acid sequence that encodes said polypeptide; detecting an influence of the effector on the effector target by determining a change in the amount of the microbiologically produced vitamin B2 or the precursor or derivative thereof. 16. A method for modulating microbiological production of vitamin B2 or a precursor or derivative thereof, comprising: treating a microorganism with an effector that interacts with a target, wherein said microorganism is capable of the microbiological production of vitamin B2 or the precursor or derivative thereof and contains a gene that encodes the polypeptide of claim 7, and wherein said target is said polypeptide or a nucleic acid sequence that encodes said polypeptide. 17. The method of claim 16, wherein the effector is selected from the group consisting of: antibodies or antigen-binding fragments thereof; polypeptide ligands, which are different from said antibodies or antigen-binding fragments thereof, and interact with the polypeptide; low molecular weight effectors that modulate biological activity of said polypeptide; antisense nucleic acid sequences; ribozymes; and catalytic RNA molecules. 18. A method for microbiological production of vitamin B2 or a precursor or derivative thereof, a comprising: culturing the host cell of claim 10 in a culture mixture under conditions favoring production of said vitamin B2 or a precursor or derivative thereof; and isolating a desired product from the culture mixture. 19. The method of claim 18, wherein the host cell is treated with an effector before or during culturing. 20. The method of claim 18, wherein the host cell is a microorganism of the genus Ashbya. 21. The method of claim 18, wherein the desired product is vitamin B2 or a precursor or derivative thereof. 22. A method for modulating production of vitamin B2 or a precursor or derivative thereof of a microorganism of the genus Ashbya comprising: treating a cell transformed with a polynucleotide with an effector, wherein said polynucleotide is derived from a microorganism of the genus Ashbya and codes for a protein associated with the process of transmembrane transport in said microorganism, and wherein the effector modulates the production of vitamin B2 or the precursor or derivative thereof, of said microorganism. 23. A method for modulating transmembrane transport activity of a transmembrane protein or a subsequent state associated therewith in a microorganism of the genus Ashbya comprising: culturing the microorganism, wherein said microorganism contains a sequence that encodes the polypeptide of claim 7; and treating said microorganism with an effector that interacts with said polypeptide or said sequence of the microorganism. 24. The host cell of claim 12, which has an improved cellular response to external conditions. 25. The polynucleotide of claim 1, wherein the protein is a transmembrane protein. 26. The polynucleotide of claim 2, wherein the property is derived from a protein of S. cerevisiae. 27. The polynucleotide of claim 2, wherein the property is derived from a protein of S. pombe. 28. The oligonucleotide of claim 5, wherein hybridization is under stringent hybridization conditions. 29. A polypeptide encoded by the polynucleotide of claim 6. 30. A polynucleotide that contains an amino acid sequence comprising at least ten consecutive amino acid residues of SEQ ID NO: 2, 4, 6, 7, 9, 11, 13, 15, 16, 18, 20, 22, 24, 27, 29, 30, 32, 34, 36, 38, 39, 41, 43 or SEQ ID NO: 45; or a functional equivalent thereof. 31. The polynucleotide of claim 30, which possesses a structural or functional property selected from the group consisting of said structural or functional property possessed by a mitochondrial energy transfer protein, an ABC transport protein, a membrane-integrated mitochondrial protein, a mitochondrial inner membrane transport protein, a non-vacuolar 102 kD subunit of an H+-ATPase V0 domain, an isp4 protein, a VAC1 protein, a cystolic and peripheral membrane protein having three zinc fingers, a protein with ATPase activity, a protein with an ATPase-like function, a PHO85 protein, and a p24 protein. 32. The host cell of claim 11, wherein the modulation is an increase or a decrease of an activity of said protein expressed by said gene. 33. The method of claim 15, wherein the effector binds to said effector target. 34. The method of claim 15, further comprising isolating said target. 35. The method of claim 23, further comprising isolating vitamin B2 or a precursor or derivative thereof from said culture. 36. The host cell of claim 24, wherein the improved cellular response comprises, as compared to an untransformed cell, a more efficient transmembrane transport, an increased activity of a transmembrane protein, an increased growing and multiplication, an increased viability, an increased yield of a desired product, an increased yield of vitamin B2 or a precursor or derivative there, or a combination thereof. 37. An isolated effector that interacts with an effector target, wherein the effector is selected from the group consisting of: antibodies or antigen-binding fragments thereof; polypeptide ligands that are different from said antibodies or antigen-binding fragments thereof, and that interact with the polypeptide; low molecular weight effectors that modulate biological activity of a said polypeptide; antisense nucleic acid sequences; ribozymes; and catalytic RNA molecules; and the effector target is selected from the group consisting of: a nucleic acid that encodes a polypeptide associated with the process of transmembrane transport of a microorganism of the genus Ashbya; and a polypeptide encoded by said nucleic acid. 38. The effector of claim 37, wherein the effector target is the nucleic acid and said nucleic acid encodes an amino acid sequence comprising at least ten consecutive amino acid residues of SEQ ID NO: 2, 4, 6, 7, 9, 11, 13, 15, 16, 18, 20, 22, 24, 27, 29, 30, 32, 34, 36, 38, 39, 41, 43 or SEQ ID NO: 45; or a functional equivalent thereof. 39. The effector of claim 37, wherein the effector target is the polypeptide and said polypeptide contains an amino acid sequence comprising at least ten consecutive amino acid residues of SEQ ID NO: 2, 4, 6, 7, 9, 11, 13, 15, 16, 18, 20, 22, 24, 27, 29, 30, 32, 34, 36, 38, 39, 41, 43 or SEQ ID NO: 45; or a functional equivalent thereof. 40. The method of claim 37, wherein the effector binds to said effector target. |
Non-Endocrine Disrupting Cytoprotective UV Radiation Resistant Substance |
Compositions for enhanced UV-protective agents that increase immuno-responsiveness by providing cytoprotective additives for mammalian skin by ensuring avoidance from endocrine disrupting agents are described. A composition comprising: (a) at least one inorganic non-endocrine disrupting sun-blocking agent or organic non-endocrine disrupting sunscreen agent, (b) at least one non-endocrine disrupting emollient or mixtures thereof and (c) an optional oil component comprising a carrier oil, preferably an essential oil of a naturally occuring substance and a method of making this and other embodiments of similar compositions of the same invention is detailed. Inorganic component (a) is titanium dioxide, zinc oxide, silica or silicon dioxide, fluoropolymers or mixtures thereof. Organic component (a) is butylmethoxy dibenzoylmethane. The non-endocrine disrupting component (b) is cold-processed Aloe barbadensis Miller, which contains a glucose-rich mannose-containing oligosaccharide or oligosaccharides, or a fatty acid salt such as sodium stearate. The compositions are shown to be capable of protecting skin and mammalian health from the harmful effects of radiation including ultraviolet light or sunlight by inhibiting the loss of skin immunocompetency and eliminating any known or suspected endocrine disrupting agents normally utilized as sun protective agents. |
1. A composition comprising: (a) at least one inorganic, non-endocrine disrupting sun-blocking agent; (b) at least one non-endocrine disrupting emollient or mixtures thereof; and optionally; (c) an oil component, said composition capable of protecting skin from harmful effects of radiation including sunlight and ultraviolet light. 2. The composition according to claim 1 wherein said oil is a carrier oil, or an essential oil, or both, derived from an earth grown substance comprising no known endocrine disrupting agents. 3. A composition according to claim 1, wherein said emollient is aloe barbadensis Miller. 4. A composition according to claim 3, wherein said emollient includes oligosaccharides of aloe barbadensis Miller that inhibit loss of skin immuno-competency. 5. A composition according to claim 1, wherein active sun-block agents, emollients, and carrier or essential oils or both include other non-endocrine disruptive agents comprising a sunless tanning agent, an anti-microbial agent, a de-pigmentation agent, an anti-aging agent, an anti-fungal agent, and an insect repellent or any combination thereof, and wherein one or more of said agents are topically active. 6. A sun-block composition according to claim 1, wherein said inorganic sun-block agent is titanium dioxide, zinc oxide, silica or silicon dioxide, fluoropolymers, or mixtures thereof. 7. A sun-block composition according to claim 6 wherein said inorganic sun-block agent is zinc oxide. 8. A sun-block composition according to claim 7 wherein said zinc oxide has a primary particle size of less than about 30 nm. 9. A sun-block composition according to claims 1, wherein said emollient is a salt of a fatty acid, where said salt of said fatty acid has been determined to be non-endocrine disrupting. 10. A sun-block composition according to claims 1 wherein said composition has a pH of at least of 5. 11. A sun-block composition according to claim 10 wherein said pH is from about 6.5 to about 8.5. 12. A sun-block composition according to claims 1 having a Sun Protection Factor (SPF) of at least 10, and preferably an immuno-responsiveness factor (IRF) of greater than zero, and preferably a non-endocrine disrupter (NED) factor not greater than zero. 13. A composition comprising: (a) at least one organic, non-endocrine disrupting sunscreen agent; (b) at least one non-endocrine disrupting emollient or mixtures thereof; and; (c) a not essential inorganic, non-endocrine disrupting sun-block agent and; (d) a not essential oil component comprising a carrier oil or an essential oil or both derived from an earth grown substance comprising no known endocrine disruptive agents; said composition capable of protecting skin from harmful effects of radiation including ultraviolet light or sunlight. 14. The composition according to claim 13, wherein said sunscreen agent is butylmethoxydibenzoylmethane. 15. The composition according to claim 14, wherein said emollient is aloe barbadensis Miller. 16. The composition according to claim 15, wherein said emollient includes oligosaccharides of aloe barbadensis Miller that inhibit loss of skin immunocompetency. 17. The composition according to claim 13, wherein active sunscreen agents, emollients, and carrier oils may include other non-endocrine disruptive agents comprising a sunless tanning agent, an anti-microbial agent, a de-pigmentation agent, an anti-aging agent, an anti-fungal agent, and an insect repellent or any combination thereof, and wherein one or more of said agents are topically active. 18. A sunscreen composition according to claim 13 wherein said inorganic sun-block agent is titanium dioxide, zinc oxide, silica or silicon dioxide or mixtures thereof. 19. A sunscreen composition according to claim 18 wherein said inorganic sun-block agent is zinc oxide. 20. A sunscreen composition according to claim 19 wherein said zinc oxide has a primary particle size of less than or equal to 30 nannometers. 21. A sunscreen composition according to claim 20 wherein said emollient is a salt of a fatty acid, where said salt of said fatty acid has been determined to be non-endocrine disrupting. 22. A sunscreen composition according to claim 13, wherein said composition has a pH of at least of 5. 23. A sunscreen composition according to claim 22, wherein said pH is from about 6.5 to about 8.5. 24. A sunscreen composition according to claim 13 having a Sun Protection Factor (SPF) of at least 10, and preferably an immuno-responsiveness factor (IRF) of greater than zero, and preferably a non-endocrine disrupter (NED) factor not greater than zero. 25. A sun-block composition according to claim 1, comprising; aloe vera, deionized water, micronized zinc oxide, glycerin, beeswax, ascorbyl vitamin C palmitate, an enzyme concentrate, rose oil, tocopheryl vitamin E acetate, retinyl vitamin A palmitate, ergocalciferol (vitamin D), xanthan gum, magnesium silicate, grapefruit seed extract, rosemary extract, cinnamon extract, and bearberry extract. 26. A sun-block composition consisting of; aloe vera, deionized water, micronized zinc oxide, glycerin, beeswax, ascorbyl vitamin C palmitate, an enzyme concentrate, rose oil, tocopheryl vitamin E acetate, retinyl vitamin A palmitate, ergocalciferol (vitamin D), xanthan gum, magnesium silicate, grapefruit seed extract, rosemary extract, cinnamon extract, and bearberry extract. 27. The composition of claim 1, wherein said composition contains between 2% and about 25% of an inorganic sun-block or sunscreen agent, from between 0.5% and about 10% of an emollient and from between 0.5% and about 10% of an oil component comprising a carrier oil where said carrier oil is a desirable essential oil derived from earth grown substances. 28. The composition of claim 13, wherein said composition contains between 2% and about 25% of an inorganic sun-block or sunscreen agent, from between 0.5% and about 10% of an emollient and from between 0.5% and about 10% of an oil component comprising a carrier oil where said carrier oil is a desirable essential oil derived from earth grown substances. 29. The composition of claims 27 or 28, wherein the ratio of inorganic sun-block agent to oil component is from between 0:3 to about 1:1, or ratio of organic sunscreen agent to oil component is from between 0:3 to about 1:1 or ratio of the combination of both sun-block and sunscreen is from between 0:3 to about 1:1. 30. The composition of claims 1 or 13, wherein said compositions comprise any enzyme or enzyme mixture. 31. The composition of claim 27, wherein said composition comprises; (a) a cyto-protective agent deriving from an earth grown substance; and a composition containing at least one or more of the following additional substances; (b) sunflower oil, vegetable glycerin, coconut oil, stearic acid as extracted from vegetable fat, beeswax, orange wax, tocopheryl acetate, buttermilk powder, sodium borate, xanthan gum, honey, sucrose stearate, glucose, glucose oxidase, lactoperoxidase, and rosemary extract and an essential oil containing fragrance. 32. The composition of claim 28, wherein said composition comprises; (a) a cyto-protective agent deriving from an earth grown substance; and a composition containing at least one or more of the following additional substances; (b) sunflower oil, vegetable glycerin, coconut oil, stearic acid as extracted from vegetable fat, beeswax, orange wax, tocopheryl acetate, buttermilk powder, sodium borate, xanthan gum, honey, sucrose stearate, glucose, glucose oxidase, lactoperoxidase, and rosemary extract and an essential oil containing fragrance. 33. A method of protecting mammalian skin from harmful effects of ultraviolet-A and ultraviolet-B radiation and enhancing skin immunocompetency comprising topically applying to said skin an effective amount of a UV-protective composition, said composition comprising; (a) at least one non-endocrine disrupting sun-block or sunscreen active agent in an amount effective to protect said skin against actinic radiation from sunlight; wherein said sun-block agents include zinc oxide or titanium dioxide and said sunscreen agents include butyl-methoxydibenzoylmethane; (b) non-endocrine disruptive and cytoprotective mixtures made of substances that are grown from the earth, at least one of said mixtures comprising a glucose-rich mannose-containing oligosaccharide or oligosaccharides obtained from cold processed aloe barbadensis Miller and not essential components including; (c) sunflower oil, vegetable glycerin, coconut oil, stearic acid as extracted from vegetable fat, beeswax, orange wax, tocopheryl acetate, buttermilk powder, sodium borate, xanthan gum, sucrose stearate, glucose, glucose oxidase, lactoperoxidase, and rosemary extract and an essential oil containing fragrance; and; (d) sufficient filtered water to form an emulsion. 34. A method of protecting mammalian skin from harmful effects of ultraviolet-A and ultraviolet-B radiation and enhancing skin immunocompetency comprising topically applying to said skin an effective amount of a UV-protective composition, said composition comprising; (e) at least one non-endocrine disrupting sun-block or sunscreen active agent in an amount effective to protect said skin against actinic radiation from sunlight; wherein said sun-block agents include zinc oxide or titanium dioxide and said sunscreen agents include butyl-methoxydibenzoylmethane; (f) non-endocrine disruptive and cytoprotective mixtures made of substances that are grown from the earth, at least one of said mixtures comprising a glucose-rich mannose-containing oligosaccharide or oligosaccharides obtained from cold processed aloe barbadensis Miller and required components including; (g) sunflower oil, vegetable glycerin, coconut oil, stearic acid as extracted from vegetable fat, beeswax, orange wax, tocopheryl acetate, buttermilk powder, sodium borate, xanthan gum, sucrose stearate, glucose, glucose oxidase, lactoperoxidase, and rosemary extract and an essential oil containing fragrance; and; (h) sufficient filtered water to form an emulsion. 35. The method of claims 33 or 34, wherein said composition comprises any enzyme or enzyme mixture. 36. The method of claims 33 or 34, wherein said composition comprises from about 0.0001% to about 10% (w/w) of said non-endocrine disrupting agents and said cytoprotective agents. 37. The method of claims 33 or 34, wherein said composition comprises about 0.01% to about 1% (w/w) of said non-endocrine disrupting agents and said cytoprotective agents. 38. The method of claims 33 or 34, wherein said composition comprises about 0.1% to about 0.5% (w/w) of said non-endocrine disrupting agents and said cytoprotective agents. 39. The method of claims 33-38, wherein said composition is formulated into a solid, a liquid, an aerosol, a cream, a lotion, an ointment, a microemulsion, a solution, or a gel form. 40. The method of claims 33 or 34, wherein said sunscreen agent comprises non-endocrine disrupting agents consisting of butyl-methoxydibenzoylmethane and other dibenzoyl etheric. 41. The method of claim 40, wherein any or all said agents are immunoenhancing. 42. The method of claim 41, wherein any or all said agents are cytoprotecting. 43. The method of claims 33 or 34, wherein said sun-block agent is selected from the group consisting of; zinc oxide and titanium dioxide or zinc oxide or titanium dioxide individually. 44. A method of protecting mammalian skin from harmful effects of ultraviolet-A and ultraviolet-B radiation and enhancing skin immunocompetency comprising topically applying to said skin an effective amount of a UV-protective composition, said composition comprising; (a) at least one sun-block or sunscreen active agent in an amount effective to protect said skin against actinic radiation from sunlight; (b) agents of said UV-protective compositions free of any known or suspected endocrine disrupters; (c) a non-endocrine disruptive, cytoprotective mixture made of earth grown substances, said mixture comprising glucose-rich mannose-containing oligosaccharide or oligosaccharides obtained from and used with aloe barbadensis Miller processed at or below room temperature within 45 minutes of harvesting, and; not essential components including; (d) aminoacids, vitamins or provitamins, nucleoderivatives, and vegetable extracts, wherein said aminoacids comprise tryptophan, histidine, phenylalanine, tyrosine, said vitamins and provitamins comprise vitamin B6, vitamin A, vitamin E, tocopherols, betacarotene, bioflavonoids, nucleotides and polymers thereof, cascara, frangula, camomile, hyperic, calendula, elicriso, licorice or essential oils thereof, and; (e) enough water to form a well mixed emulsion. 45. A method of protecting mammalian skin from harmful effects of ultraviolet-A and ultraviolet-B radiation and enhancing skin immunocompetency comprising topically applying to said skin an effective amount of a UV-protective composition, said composition comprising; (a) at least one sunscreen or sun-block active agent in an amount effective to protect said skin against actinic radiation from sunlight; (b) agents of said UV-protective compositions free of any known or suspected endocrine disrupters; (c) a non-endocrine disruptive, cytoprotective mixture made of earth grown substances, said mixture comprising a glucose-rich mannose-containing oligosaccharide or oligosaccharides obtained from and used with aloe barbadensis Miller that can function as the at least one emollient, and; (d) enough water to form a well mixed emulsion. 46. The method of claims 44 or 45, wherein said compositions comprise any enzyme or enzyme mixture. 47. A method of making a UV-protective composition comprising; (a) adding de-ionized water, cold pressed aloe, and zinc oxide or titanium dioxide or both in combination to a vessel; (b) then, adding a carrier oil; (c) then, mixing said resultant composition in said vessel. 48. The method of claim 47, comprising the steps of; (a) adding de-ionized water, cold pressed aloe, and zinc oxide or titanium dioxide or both in combination to a vessel; (b) then, adding a carrier oil and an emollient other than cold pressed aloe to said vessel; (c) then, mixing said resultant composition; (d) maintaining (a)-(c) at or below 80 F, then, maintaining or adjusting the pH of said composition to above 5. 49. The method of claim 48, comprising the steps of; (a) adding de-ionized water, cold pressed aloe, and zinc oxide or titanium dioxide or both in combination to a vessel; (b) then, adding a carrier oil and an emollient other than cold pressed aloe, and a thickener to said vessel; (c) then, mixing said resultant composition; (d) maintaining (a)-(c) at or below 80 F, then, maintaining or adjusting the pH of said composition to above 5. 50. The method of claim 50, wherein said UV-protective composition is also non-endocrine disrupting, cytoprotecting, and immuno-enhancing. |
<SOH> BACKGROUND OF THE INVENTION <EOH>Although a tan has long been considered a symbol indicative of good health and the ability to secure sufficient leisure time to enjoy many and numerous outdoor activities, it has become very evident that excessive exposure of the human skin to sunlight is harmful. It is well documented that human skin and most likely most mammalian skin, is sensitive to sunlight and artificial light containing radiation of wavelengths between about 290 nanometers (nm) and 400 nm. Ultraviolet radiation of wavelengths between about 290 nm and 320 nm (UV-B region) has been known to rapidly produce damaging effects on the skin including reddening or erythema, edema, blistering or other skin eruptions in more severe cases. Prolonged or chronic exposure to radiation in this wavelength range has been associated with serious skin conditions such as actinic keratoses and carcinomas. In recent years, concern has also been expressed regarding ultraviolet radiation of wavelengths above 320 nm (UV-A region) and the adverse effects of such radiation on human skin. The radiation between 320 and 400 nm also contributes to the premature aging of the skin. In addition, recent studies indicate that chronic sun exposure limits the immuno-response of the skin. There is some evidence that a tan will offer some protection against burning but that the tan is quite ineffectual against many other types of solar damage and there is no evidence that a tan increases immuno-responsive function in human skin. Growing public awareness that the enjoyment of outdoor activities includes the need for adequate sun protection has led to an unprecedented growth in the area of sun-block and sunscreen products. A very recent study by Margaret Schlumph from the Institute of Pharmacology and Toxicology at the University of Zurich (reported in Chemical Week in May 2001) supports earlier health concerns regarding the use of endocrine disrupting organic substances in nearly all UV screening chemicals used in sunscreen or sun-block. Additionally, the use of Aloe, or more specifically aloe barbadensis Miller has heretofore been known as a useful agent for the formulation of sun-block and sunscreen as well as a substance that can both reduce UV damage to human skin that is inflamed and also promote healing. What was not well documented until recent publications and a subsequent U.S. Pat. No. 5,824,659 by Strickland and coworkers is that an extract found in all Aloe plants that is normally removed during carbon adsorptive processing, is capable of providing cytoprotection to the mammalian skin. This extract boosts the immune system response of the skin, thereby significantly reducing the risk to various forms of skin cancer. There is strong evidence to suggest that this beneficial effect translates to skin in most mammals, thereby the present invention provides a possible preventative formulation for animals in zoos or other habitats where UV exposure could be hazardous to the animals' health. Cold processed aloe has more than 250 biologically active substances prior to processing. Many of these substances have been found to be immuno-enhancing and cyctoprotective, but many of the same substances are removed during conventional “hot” processing or adsortion/absorption to produce the commonly used resulting gel. It is therefore desirable to provide a UV protective product that has the following attributes: protection in the UV-A and UV-B long range and short range ultraviolet radiation ranges; maintenance of coverage, i.e., waterproof and perspiration proof; application and use convenience, i.e., ease of application, invisibility, non-staining and non-greasy; and freedom from irritation as a result of its ingredients, in particular, its active sun-block or sunscreen ingredients should also be void of any known or suspected endocrine disrupters. Recent interest in this area includes some concerns over the irritancy and sensitization problems in addition to the endocrine disruptive nature that may occur in some individuals utilizing sunscreen products with high SPF values containing organic sunscreen agents. In addition, the UV protective product could also include known cytoprotective oligosaccharides from aloe barbadensis Miller preventing damage to the skin immune system caused by harmful UV radiation. “Cold-pressed” Aloe which contains the beneficial oligosaccharides and provides an emollient base for the UV protective formulation is possibly the best known choice as a cytoprotective agent that inhibits the loss of skin immunocompetency induced by ultraviolet radiation, as this agent is readily available and comparably inexpensive. Other such inhibitors are not yet well known but it is believed that amino-acids, vitamins or pro-vitamins, nucleo-derivatives, and vegetable extracts, wherein said aminoacids comprise tryptophan, histidine, phenylalanine, tyrosine, said vitamins and provitamins comprise vitamin B6, vitamin A, vitamin E, tocopherols, betacarotene, bioflavonoids, nucleotides and polymers thereof, cascara, frangula, camomile, hyperic, calendula, elicriso, licorice or essential oils thereof all may have similar cytoprotective or immune boosting effects on mammalian skin. The essential oils of frankincense and rosemary have been found to work effectively and synergistically in strengthening the neuromuscular response of patients who are exposed to its scent in combination with compositions of the present invention. One current measure of effectiveness of a sun protective product is indicated by its sun protection factor (SPF). The sun protection factor is the ratio of the amount of exposure (dose) required to produce a minimal erythema reaction in protected skin to the amount required to produce the same reaction in unprotected skin. The absolute dose differs for each human and for each mammal, and is largely dependent on genetic predisposition and ethnic origin of the human. If a human or other mammal would normally require ten-minute exposure to sunlight to develop a minimal erythema reaction, then using an SPF 15 sun-block should allow for tolerance of up to 150 minutes of sunlight before developing a minimal erythema. Relatively recent public awareness of the problems of exposure to sunlight has led to a demand for sun-block products with high SPF values, i.e., at or above SPF 8. What has not been well considered in the sun protection and cosmetics industry heretofore, is the possibility of enhancing the immuno-responsiveness of skin cells to UV light by the proper topical application such as described above by the use of extracts of aloe or similar naturally occurring substances. Such substances would preferably not be processed, but if the beneficial effects are not lost during processing, then either the processed or non-processed substance may be used. The importance of processing within a short time period after harvesting the aloe plant as well as keeping the plant and subsequent plant extract cool (at or below room temperature) during processing is now well understood. Essential oils frankincense and rosemary have been shown to possibly have immuno-enhancing properties, as determined by Kineseologist—Dr. John Schmidt of Triangle Wellness Center in Raleigh N.C. This was determined by a strengthening in neuromuscular response using scent (aroma) testing of these essential oils. The testing was performed both together with compositions of the present invention and alone. A more complete rating mechanism than the SPF rating method is suggested here. The immuno-response rating system could be a simple 0-10 value, with 10 applying to a substance within the UV-protective composition that is most beneficial to boosting skin cell immune responsiveness to carcinoma, melanoma, etc. (for instance). What has also not been well considered by the same industry is the effect that certain agents, recently determined to be endocrine disrupters, may have on certain mammals, particularly humans, regarding the immune system response to UV radiation. Endocrines are essentially excretions from organs or glands. The organs or glands continually function by discharging waste or at the least exchanging fluids from an inlet side to an outlet side. Any disruption in the natural behavior of an organ or gland could have a deleterious effect on the ability of that organ or gland to continue to function normally. In a systems approach to health, the abnormal function of any organ or gland could lead to immune system disruptions (and immune system deficiencies) that may lead to serious health related complications. Certainly, there appears to be much evidence supporting the fact that immune suppression response occurs when organ or gland discharge is interrupted. Changes in endocrine exposure has recently been linked to hormonal imbalances seen in young and especially adolescent or pubescent children, as well as in the global food chain where hermaphroditic insects and other animals have been discovered. A UV-protective formulation or composition that may inhibit normal endocrine function(s) is at least undesirable, and at most a potential health threat to millions who continue to apply such a formulation or composition directly to their skin. Although the SPF value may be high, the potential for endocrine disruption may also be high and again this poses the possibility of another ranking system. In ranking potential endocrine disruption substances, again the 0-10 rating has appeal, with 0 being the desired criteria that a consumer would want to purchase to ensure consumption of a quality product that is also completely safe in terms of potential adverse health effects. Therefore, as part of the present invention, a new rating system for UV-protective compositions is proposed that includes; SPF value—greater than 15 desired Immuno-responsiveness factor (IRF)—5 or higher desired (greater than 0) Non-endocrine disrupter factor (NED)—0 desired Therefore the ultimate UV-protective formulation would safely block or screen UV light, enhance the immune responsiveness of the skin in the absence or presence of UV, and ensure the user that there is no endocrine disrupting substance present. Ease of application and cosmetic appeal, on the other hand, are important in formulating sun protective compositions. These characteristics rely on subjective evaluations such as visual and tactile impression by the user. Softening compounds such as emollients provide an excellent basis for a soothing compound to add to the cosmetic appeal, so long as those emollients used don't contain endocrine disrupting agents. One emollient of the present invention is cold processed aloe. Consumer research studies indicate that a sun-block formulation should rub in easily, leave the skin non-sticky and, above all should be invisible on the skin after application. Sun protective compositions containing organic sunscreen agents have been found, in some cases, to irritate the skin. Additionally, recent studies have confirmed the suspicion that endocrine disrupting agents exist in currently available sunscreen formulations including; benzophenone-s, homosalate, 4-methylbenzylidene camphor, octyl methoxycinnamate, and octyl-dimethyl-PABA. All of these substances, in fact, made cancer cells grow more rapidly and three caused developmental effects in animals. Therefore a non-endocrine disrupting UV protective formulation should include the use of inorganic sun-block agents, such as titanium dioxide and/or zinc oxide. A recent development in the reduction of particle sizes of ZnO has resulted in micro-fine, essentially clear ZnO, when applied to the skin. One such formulation is known as Z-Cote which is a trademarked composition sold by BASF. In addition, the need for an acceptable emollient that reduces the negative affects associated with abrasive inorganics and that also includes the benefit of providing cytoprotection and healing of the skin is necessary. Allowing for the reduction of irritation or sensitization of the skin suggests that “cold-pressed” Aloe is a useful and necessary ingredient for such a UV-protective formulation. Our review of the prior art in this field includes the following pertinent information; For example, Japanese Patent Application No. 1981-161, 881, describes cosmetics containing 0.1-40% of ultrafine divided titanium oxide with a particle size of 10-30 nm which has been rendered hydrophobic. It indicates that when hydrophobically treated titanium dioxide with a particle size of 1030 nm is blended into cosmetic base materials, it transmits visible light but reflects and scatters the harmful ultraviolet rays. It has been found that when these titanium dioxide compositions are utilized as a sun-block agent in sun-block compositions, it may result in the loss of one of the most desired properties of such compositions, i.e., invisibility. U.S. Pat. No. 5,028,417, issued Jul. 2, 1991, describes sun-block compositions containing microfine titanium dioxide. The particle size of the titanium dioxide is required to be less than 10 nm. It also states that other sun-block agent can be utilized with the titanium dioxide. U.S. Pat. No. 5,340,567, issued Aug. 23, 1994 describes a sun-block composition comprising a synergistic combination of titanium dioxide having a particle size of less than about 35 nm and zinc oxide having a particle size of less than about 50 nm with titanium dioxide and zinc oxide being present at given ratios. German Patent No. 3642794 (1987) describes a cosmetic composition for preventing sunburn which contains 1-25% zinc oxide of a particle size of 70-300 microns. It further indicates that the composition may also contain titanium dioxide of a particle size of 30-70 microns. This composition is undesirably due to its unaesthetic whiteness characteristics at high SPF levels. U.S. Pat. No. 5,188,831, issued Feb. 23, 1993, describes sun-block compositions wherein the sun-block effect is obtained from a blended of oil-dispersible ultrafine titanium dioxide and water dispersible titanium dioxide. However, the SPF level obtained is only of 10 with a total concentration of titanium dioxide of 5.0% w/w. World Patent Application WO 90/06103, published Jun. 14, 1990, describes titanium dioxide sun-block where the microfine titanium dioxide particles are coated with a phospholipid, either through the use of a powder mill or through the making of a dispersion in an oil phase containing the phospholipid with a high shear mixer. The phospholipid coated titanium dioxide is the incorporated into sun-block compositions. A high efficiency is claimed: the data presented shows SPF values of up to 11 for a 3.75% titanium dioxide concentration and up to 25 for a for a 7.5% concentration of titanium dioxide. The use of high shear mixer or a powder mill is complicated and energy intensive process. EP 535372 A1, published Apr. 7, 1993 describes a method of preparing sun-block in which a dispersion of zinc oxide and/or titanium dioxide particles in an oil are formed by milling. EP 619999 A2, published Oct. 19, 1994 describes an aqueous dispersion of particulate metallic oxide of particle size less than 200 nm mixed with an emulsifier and an oil phase and also an organic hydrophobic sunscreen to form an o/w emulsion. The resulting sun protection composition has a higher SPF than would be expected if there was only an additive effect. However, the titanium dioxide alone at 4% yielded a SPF of only 7 to about 11. EP 628303, published Oct. 19, 1994 describes a process for preparing a sun-block composition. It consists of mixing sun-block particles of metallic oxide less than 200 nm dispersed in an oil with one or more emulsifier and/or organic sun-block. The resulting sun-block composition is claimed to have a SPF value considerably higher than expected. The high SPF is only obtained when a metallic oxide is blended with an organic sun-block. In fact, when no organic sun-block is used, the SPF value is only about 7. WO 93/11742 describes sun-block compositions comprising titanium dioxide and iron oxide of particle size less than 200 nm preferably coated with a phospholipid. An article published in DCI in September 1992 by Tioxide Specialties Ltd. describes ways of incorporating oil or water dispersions of titanium dioxide in emulsions. However, no data is given on the resulting SPF values. An article published in Cosmetics and Toiletries, Vol. 107, October 1992, describes various ways of formulating with a physical sun-block. The discussion focuses on using titanium dioxide in a dispersion or using an emulsifier which is also an effective dispersing agent for titanium dioxide. It states that SPF's far above 20 can be achieved. However, no examples are given, nor does the article mention the specific sun-block components or their composition. A brochure published by the Tioxide Company on Mar. 15, 1994, discloses inorganic sun-block of high SPF values obtained without the addition of any organic sunscreen. When measured, the SPF of the sun-block compositions was indeed that described. However, when the titanium dioxide concentration was measured, it was at least twice what was claimed. U.S. Pat. No. 5,498,406 describes sun-block compositions in an oil-in-water emulsion containing both organic and inorganic sun protective ingredients and comprising long chain (C25-45) alcohols for stabilization of the emulsion. This composition relies predominately on the organic sunscreen active components. While the authors mention the use of stearic acid as a part of the oil in water composition, they teach against the use of stearic acid in stabilizing the titanium dioxide with C 22-45 alcohols. U.S. Pat. No. 6,099,825 describes sun-block having disappearing color which is extremely useful when combined with titanium dioxide or zinc oxide. It was unexpectedly found that although the inclusion of particulate pigments in a sun-block emulsion can render the sun-block visually colored as it is being spread onto the skin and that the coloration will substantially disappear when the sun-block emulsion is rubbed into the skin. U.S. Pat. No. 6,042,813 also describes sun-block having disappearing color indicator. The sun-block includes at least one active sun-block agent, at least one emulsifier, sufficient amounts of water to create the colored emulsion, and at least one oil-soluble dye that imparts color to the emulsion. U.S. Pat. No. 6,048,517, issued Apr. 11, 2000, describes low-cost sunscreen compositions with high SPF values of at least 40. The ingredients in the sunscreen include mixtures of homosalate, octyl salicylate, oxybenzone, octyl methoxycinnamate, or avobenzone. U.S. Pat. No. 5,770,183, issued Jun. 23, 1998, describes an emulsion that contains a water phase and an oil phase that includes active sun-block ingredients and skin conditioning agents. The sun-block provides an SPF greater than 30, and the particle size in the oil phase averages 2.0 microns, providing high levels of protection from the sun while using minimum amounts of active sun-block agents. U.S. Pat. No. 5,492,690, issued Feb. 20, 1996, describes a method for preventing skin damage by applying a substance that includes a benzolyacetate ester and seems to describe a potential non-endocrine disrupting benzoylacetate ester that would require testing prior to use in the present inventive composition(s). U.S. Pat. No. 5,747,010, issued May 5, 1998, describes means and methods of protecting skin from the oxidative effects of UVA radiation using a substance that contains a lipophilic anti-oxidant. Such an anti-oxidant, if proven to be non-endocrine disruptive and not to interfere with the cytoprotective qualities of the present inventive composition(s) could also be useful and beneficial. WO 99/11236 published first in Germany and then as a WO document dated Mar. 11, 1999, describes a transparent sun-block gel that contains methlyvinyl ether and maleic acid copolymers cross-linked with decadiene. EP 0834301, published Mar. 8, 1998, describes compositions that include glutathione liposomes combined with at least one emulsifier and are topically applied to the skin to prevent the damaging effects of UV radiation. U.S. Pat. No. 5,914,102, issued Jun. 22, 1999, describes an oil-in-water sun protective emulsion comprised of at least one ultraviolet-absorbing organic compound and hydrophobically-treated silica particles. The concentration of the organic compounds is at least 30 times the concentration of the silica U.S. Pat. No. 5,916,542, issued Jun. 29, 1999, describes a mixture comprised of natural substances that effectively protect against skin damage caused by UVA and UVB light. U.S. Pat. No. 5,945,090, issued Aug. 31, 1999, describes a high-SPF sun-block comprised of an algae extract, aloe vera, and tapioca powder that protects against UVA and UVB light. U.S. Pat. No. 5,980,871, issued Nov. 9, 1999 to Johnson and Johnson, and apparently licensed to Neutrogena, describes a sun-block composition that includes inorganic sun-block agents, such as titanium dioxide or zinc oxide, anionic emulsifiers, and an oil component. The composition allows for SPF greater than 10 with a titanium dioxide concentration of about 4%. This U.S. Pat. No. 5,980,871 further describes the method required to make the sun-block. This patented composition and method most closely resembles the present invention. There is no mention, however, of the use of any cytoprotective agents or the importance of providing only non-endocrine disruptive agents to the composition. In our review of commercially available products, this composition would appear to pose the least risk in terms of both short and longer-term health effects. The product itself, however, is somewhat undesirable as it leaves a very white appearance on the skin for long periods of time, is difficult to spread, and somewhat abrasive to sensitive skin. In addition, the composition allows for the use of parabens as inactive ingredients, also recently found to be suspected endocrine disrupters as cited in the reference EPA website as an appendage to this specification. Thus, in one possible embodiment, the present invention is directed toward a colored sun-block emulsion comprising: (a) at least one ultramarine pigment that imparts a color other than white to the emulsion with a titanium dioxide or zinc oxide or possibly fumed or fused silica or even silicon dioxide so that when the emulsion is rubbed into the skin, the color substantially disappears; (b) at least one sun-block active agent in an amount effective to protect skin against the actinic radiation of the sun—this preferably being ZnO or Z-Cote; (c) no known or suspected endocrine disrupting organic substances; (d) a cytoprotective substance such as a glucose-rich mannose-containing oligosaccharide obtained from and used with aloe barbadensis Miller as the at least one emulsifier; and (e) sufficient water to form the other than a white colored emulsion. The amount of the ultramarine pigment in the composition can range form about 0.5 to about 10 weight percent of the composition, preferably form about 1 to about 5 weight percent of the final formulation. This pigment is for cosmetic appeal only and is not required in the present invention. Optionally, the colored sun-block emulsion can contain one or more additional ingredients, including emollients, waterproofing agents, dry-feel modifiers, insect repellants, antimicrobial preservatives and/or fragrances. In another embodiment, the present invention is directed towards a method for protecting the skin against sunburn while increasing mammalian skin cell immunoresponse to cancerous skin cells while eliminating possible endocrine disruption response of human organs comprising topically applying the sun-block formulation as described above to the skin. An advantage of the present invention is that it provides a sun-block and a method for protecting against sunburn that enables the user to apply the sun-block more completely and uniformly to the skin, thus providing more effective protection against skin damage and homogenously enhancing cytoprotection while eliminating endocrine disruptive organics, thus providing for long term health and safety in the presence of UV light. Another advantage of the present invention is that it provides a sun-block with a color indicator which has a low fabric staining potential, and for which those stains that form can easily be removed from fabrics. Still yet another advantage of the present invention is that it provides an optionally colored sun-block and a method for protecting against sunburn that is more enjoyable for human use because of the attractiveness and appealing nature of the color indicator. For domesticated animals, the use of matching colors may also be appealing. The invention allows for the use of ultrafine ZnO particles that are invisible when applied to human skin. This “invisible” ZnO would be the primary and perhaps only sun-block “active” ingredient. |
<SOH> SUMMARY OF THE INVENTION <EOH>The foregoing objects and other features and advantages of the present invention are achieved by primarily sun-blocking compositions containing inorganic sun-blocking agents or known non-endocrine disruptive sun-block agents as the active ingredients. More particularly, the present invention relates to sun-blocking compositions containing zinc oxide and, optionally, titanium dioxide of preferred particle size ranges, and in preferred amounts and ratios. These sun-blocking agents together with specifically cold-pressed aloe that contains an oligosaccharide of molecular weight of approximately 1-5,000 daltons that is glucose rich and also contains mannose which inhibits the loss of skin immuno-competency form the basis of a novel protective UV formulation. It has become evident that cold-processed aloe that is processed within 45 minutes of harvesting contains about 250 biologically active agents. The synergistic effect of all of these agents is desirable to further enhance the cytoprotective and immuno enhancing abilities inherent in aloe plant extract. These specific compositions permit the use of much lower amounts of the sun-block active ingredients than previously achievable while still achieving desired and very high SPF values for the compositions and without the unsightly whiteness which occurs in prior sun-block compositions at concentrations above about 5%. In the sun-block compositions of this invention, considerably higher concentrations of zinc oxide and possibly titanium dioxide may also be used without incurring a whitening effect, e.g., even up to 15% with acceptable appearance, or possibly higher. Furthermore, our invention does not rely upon the use of hydrophilic titanium dioxide preparations as required in the above noted patents, nor are energy intensive processes such as powder milling, nor are organic active sun-block required for high efficacy. A method of mixing either zinc or titanium dioxide with cold processed aloe initially, before mixing any of the other ingredients for the sun-block is an embodiment of the present invention. The purpose of this primary mixing step is that wetting of the oxide is necessary and important and occurs well in combination with the aloe. The compositions of this invention are primarily oil-in-water emulsions containing at least the following components: (a) an inorganic sun-blocking agent and/or a non-endocrine disruptive sun-block agent; (b) a non-endocrine disrupting and cytoprotective emulsifier or mixtures thereof; (c) an optional oil component comprising a carrier oil, preferably an essential oil any of which are also non-endocrine disruptive and immuno-enhancing and; (d) at least one emollient, where said emollient may be the cytoprotective emulsifier of (b) above. An emollient is preferably aloe as it is “Cold processed” or an extract of aloe that is currently removed during normal processing and recovered by some means. The aloe or its extract may not provide sufficient emulsification based on the remaining ingredients of the composition. The compositions of this invention provide formulations having an SPF of at least 10 with a concentration level of titanium dioxide of about 4%. The compositions of this invention exhibit extremely efficient uses of sun-block components, particularly zinc oxide. The compositions of this invention therefore may be formulated so as to contain relatively smaller amounts of zinc oxide than used heretofore at a given SPF level. Alternatively, higher levels of titanium dioxide or zinc oxide can be used if ultramarine pigments are added to the composition. These pigments are known to eliminate the whiteness and poor spreadability of currently available compositions. For the purposes of this invention, however, these pigments must be known to be non-endocrine disruptive as well as to not interfere with the cytoprotective influence of the oligosaccharide aloe extract. Essentially, the compositions of this invention are easily made by simple mixing and provide an excellent dispersion of the inorganic based sun-block/sunscreen agent throughout the composition, thus ensuring even skin coverage. With the use of ultramarine pigments, after initial coloring effects, the compositions are substantially invisible upon application to the skin. The embodiments of the present invention include three main characteristics required for any and all agents, which must be either one of or all of: a known non-endocrine disrupting agent; an immuno-enhancing agent; and a cytoprotective agent. A combination of agents containing all the above properties is an embodiment of the present invention, and all compounds fitting within the above characteristics are part of the same inventive entity. More specifically, the ultimate sun-block composition of the present invention must have at least one cytoprotective agent and no endocrine disrupting agents. In addition, the present invention will include at least one immuno-enhancing agent if such cytoprotective agent is not itself an immuno-enhancing agent. Another embodiment of the present invention is that such a compound may also be a sunscreen and not simply a sun-block. The difference being in that a sunscreen acts as a filter to certain UV rays, while a sun-block acts as a complete barrier to those UV rays. Such a sunscreen agent, in keeping with the inventive concepts of the present invention, must also exhibit only non-endocrine disrupting agents. Only one known organic UVA protector, butyl-methoxydibenzoylmethane has been shown to be benign regarding activity in cells or developmental effects on animals. This compound is of the type to act as such a sunscreen for the purposes of the present invention. detailed-description description="Detailed Description" end="lead"? |
Method and device for active radial control of wheel pairs or wheel sets on vehicles |
The invention relates to a method for active radial control of the wheels (11, 53, 103, 108, 115) of at last one wheel unit (8, 9, 10, 51, 52) on a chassis, in particular a bogie on a tracked vehicle, whereby control movements are applied to the wheel unit (8, 9, 10, 51, 52) and an integrated regulation with control movements in at least two non-identical frequency ranges are carried out. First control movements in a first frequency range and second control movements in a second frequency range, different form the first frequency range are superimposed and applied to the wheel unit (8, 9, 10, 51, 52). The invention also relates to a device for carrying out said method. |
1. A method for active radial control of the wheels of at least one wheel unit of a running gear of a vehicle, the method comprising applying control movements to said wheel unit, wherein an integrated control with control movements in at least two non-identical frequency ranges is carried out, and wherein first control movements in a first frequency range, and second control movements in a second frequency range, different from said first frequency range, are superimposed and applied to said wheel unit. 2. The method according to claim 1, wherein the vehicle has a carriage body and said running gear comprises a bogie and wherein said integrated control is arranged to be effective within the running gear, without any mechanical effective connection to the carriage body. 3. The method according to claim 1, wherein when travelling through a curve, said control movements in said first frequency range result in a quasi-static setting of said wheels of said wheel unit such that equalisation of the sums of the transverse forces acting on said wheels of said wheel units of the running gear takes place. 4. The method according to claim 1, wherein when travelling through a curve, said control movements in said first frequency range result in a quasi-static setting of said wheels of said wheel unit such that distribution of the sums of the transverse forces acting on said wheels of said wheel units of said running gear results, wherein the running behaviour is matched to specifiable operating and maintenance conditions. 5. The method according to claim 1, wherein a control of the running stability of said vehicle takes place as a result of said control movements in said second frequency range. 6. The method according to claim 1, wherein said second frequency range comprises frequencies which are, at least in part, higher than frequencies from said first frequency range. 7. The method according to claim 1, wherein said second frequency range is arranged above said first frequency range. 8. The method according to claim 1, wherein said second frequency range continues from said first frequency range. 9. The method according to claim 1, wherein said first frequency range is arranged between 0 Hz and 3 Hz. 10. The method according to claim 1, wherein said second frequency range is arranged between 0 Hz and 10 Hz, preferably between 3 Hz and 10 Hz. 11. The method according to claim 1, wherein said control controls at least one fast-reacting actuating device which sets an angular position of said wheel unit relative to a frame of said running gear or a carriage body. 12. The method according to claim 1, wherein the vehicle comprises at least two wheel units and by means of said control movements, a relative angle between outer wheel units of said at least two wheel units is controlled. 13. The method according to claim 1, wherein by way of said control movements, an absolute angle of at least one wheel unit is controlled in relation to a frame of said running gear or a carriage body. 14. The method according to claim 1, wherein the vehicle is a rail vehicle traveling along rails and control of the position of said wheel unit takes place depending on a radius of rail curvature or a travelling speed or an unbalanced transverse acceleration, or a coefficient of friction or profile parameters between said wheels and the rails. 15. The method according to claim 1, wherein at least one of the following is used for said control method: a determined transverse travel of at least one wheel unit relative to a bogie frame or a carriage body; a determined yaw angle of at least one wheel unit relative to a bogie frame or a carriage body; a determined actuating distance or actuating angle of at least one actuating device a determined actuating force of at least one actuating device a determined travelling speed; a determined speed or acceleration of said wheel unit in a transverse direction; a determined yaw speed or yaw acceleration of said wheel unit; a radius of curvature of a travel path. 16. A device for active radial control of at least one wheel unit of a vehicle, comprising: at least one actuating device connected to said wheel unit for applying control movements to said wheel unit; and a control device connected to said actuating device for controlling said actuating device, wherein said control device is arranged for controlling said actuating device in such a way that said actuating device: in a first frequency range, applies to said wheel unit first control movements for generating quasi-static excursions of said wheel unit corresponding to a radius of curvature of a track segment to be currently travelled along; and in a second frequency range, which differs from said first frequency range, applies to said wheel unit second control movements which are superimposed on said first control movements, said second control movements serving to generate excursions of said wheel unit for stabilising the running characteristics of said vehicle. 17. The device according to claim 16, wherein said actuating device is an electric, hydraulic or pneumatic actuating drive. 18. The device according to claim 16, wherein the vehicle comprises a plurality of wheels or couplings of wheels and a plurality of wheel bearings and wherein at least one actuating device is provided per wheel of said wheel unit or per each wheel bearing of said wheel unit or per each coupling of wheels of said wheel unit. 19. The device according to claim 16, wherein the vehicle comprises a plurality of wheels and at least two wheels are coupled to each other. 20. The device according to claim 19, wherein at least two coupled wheels belong to a wheel unit or two coupled wheels belong to different wheel units, and wherein said coupled wheels are arranged on the same side of said vehicle or on opposite sides of said vehicle. 21. The device according to claim 18, wherein a gear arrangement is provided between said actuating device and said wheel or said wheel bearing of said wheel unit. 22. The device according to claim 16, wherein said actuating device has a linear effective movement. 23. The device according to claim 16, wherein said actuating device has a rotary effective movement. 24. The device according to claim 18, wherein said actuating device is arranged between wheels on different sides of said vehicle. 25. The device according to claim 18, wherein one actuating device is arranged on one side of said vehicle. 26. The device according to claim 16, wherein for the purpose of creating redundancy, several actuating devices are combined. |
Screening methods and sequences relating thereto |
A screening method for identifying an individual having a pre-disposition towards having a cancer is disclosed, which screening method comprises the steps of: (a) obtaining a test sample comprising a nucleotide sequence comprised in a gene in a gene in a base excision repair (BER) pathway of the individual or an amino acid sequence of a polypeptide expressed thereby; and (b) comparing a region of the test sample sequence with the corresponding region of the wild type sequence, whereby a difference between the test sample sequence and the wild type sequence signifies that the individual is pre-disposed to having the cancer; and wherein the difference comprises a specified variation. The specified variation can be the known mutation in the human MYH protein, G382D-hMYH or a nucleotide sequence encoding it, or it can be one or more novel variations, namely, Y165C, E466X, and Y90X, or the respective corresponding nucleotide sequences. The method is particularly suitable for determining a pre-disposition towards bowel cancer. |
1-33. (canceled). 34. A screening method for identifying an individual having a pre-disposition towards having a cancer, which screening method comprises the steps of: (a) obtaining a test sample comprising a nucleotide sequence comprised in a gene in a base excision repair (BER) pathway of the individual or an amino acid sequence of a polypeptide expressed thereby; and (b) comparing a region of the test sample sequence with the corresponding region of the wild type sequence, whereby a difference between the test sample sequence and the wild type sequence signifies that the individual is pre-disposed to having the cancer; wherein the difference comprises a variant of hMYH, said variant comprising a polypeptide variant selected from the group consisting of: (a) Y165C [SEQ ID NO:1]; (b) E466X [SEQ ID NO:3]; (c) Y9OX [SEQ ID NO:4]; (d) a nucleotide sequence encoding Y165C, E466X, or Y90X; (e) a sequence substantially homologous to or that hybridises to Y165C, E466X, or Y90X under stringent conditions; (f) a sequence substantially homologous to or that hybridizes under stringent conditions to the sequence (d) or (e) but for the degeneracy of the genetic code; (g) an oligonucleotide specific for any of the sequences (d), (e) or (f); and (h) G382D-hMYH or a nucleotide sequence encoding it. 35. The method according to claim 34, wherein the test sample comprises a nucleotide sequence comprised in the HMYH gene of the individual or an amino acid sequence of a polypeptide expressed thereby. 36. The method according to claim 34, wherein the BER pathway gene is involved in the repair of a second gene and protects against G:C→T:A transverse mutations therein. 37. The method according to claim 36, wherein the second gene is a known marker for the cancer. 38. The method according to claim 37, wherein the second gene is APC. 39. The method according to claim 34, wherein the cancer is bowel cancer. 40. The method according to claim 39, wherein the BER pathway gene is hMYH. 41. The method according to claim 35, wherein the difference between the test sample sequence and the wild type sequence is Y165C-hMYH [SEQ ID NO:1] or a nucleotide sequence encoding therefor. 42. The method according to claim 35, wherein the difference between the test sample sequence and the wild type sequence is E466X-hMYH [SEQ ID NO:3] or a nucleotide sequence encoding therefor. 43. The method according to claim 35, wherein the difference between the test sample sequence and the wild type sequence is Y90X-hMYH [SEQ ID NO:4] or a nucleotide sequence encoding therefor. 44. The method according to claim 35, wherein the difference between the test sample sequence and the wild type sequence is G382D-hMYH or a nucleotide sequence encoding therefor. 45. The method according to claim 34, wherein the test sample comprises genomic DNA or mRNA, or a polypeptide expressed thereby. 46. The method according to claim 34, wherein the step (b) comprises a protein or polypeptide sequencing method. 47. A variant of hMYH, suitable for use in a screening method according to claim 34, comprising a polypeptide variant selected from the group consisting of Y165C [SEQ ID NO:1], E466X [SEQ ID NO:3], Y90X [SEQ ID NO:4], a nucleotide sequence encoding Y165C, a nucleotide sequence encoding E466X, or a nucleotide sequence encoding Y90X, and any combination thereof. 48. A nucleotide sequence: (a) encoding the polypeptide variant according to claim 47; (b) a sequence substantially homologous to or that hybridises to sequence (a) under stringent conditions; or (c) a sequence substantially homologous to or that hybridizes under stringent conditions to the sequence (a) or (b) but for the degeneracy of the genetic code; or (d) an oligonucleotide specific for any of the sequences (a), (b) or (c). 49. Use of a nucleotide sequence in a therapeutic, diagnostic or detection method, wherein the nucleotide sequence is selected from the group consisting of: (a) a BER gene variant, or a polypeptide encoded thereby, (b) a sequence substantially homologous to or that hybridises to a nucleotide sequence (a) under stringent conditions, (c) a sequence substantially homologous to or that hybridizes under stringent conditions to the nucleotide sequence (a) or (b) but for the degeneracy of the genetic code, and (d) an oligonucleotide specific for any of the nucleotide sequences (a), (b) or (c); wherein the variant is (i) Y165C [SEQ ID NO:1], (ii) E466X [SEQ ID NO:3], (iii) Y90X [SEQ ID NO:4], (iv) a nucleotide sequence encoding Y165C, E466X, or Y90X, or (v) G382D-hMYH or a nucleotide sequence encoding it. 50. The use according to claim 49 in the diagnosis or detection of a variation in hMYH and/or a condition of the APC gene. 51. The use according to claim 50, for the determination of pre-disposition or susceptibility to a disease, such as cancer. 52. The use according to claim 51, wherein the corresponding wild type BER pathway gene or wild type hMYH gene acts to protect against G:C→T:A transverse mutations in a cancer marker gene, including APC. 53. A kit suitable for use in carrying out a screening method according to claim 34, which kit comprises at least one of: (a) an oligo- or poly-nucleotide having a nucleic acid sequence corresponding to a variant hMYH, or an amino acid sequence encoded thereby, which region incorporates at least one variation from the corresponding wild-type sequence, said variation being selected from the group consisting of Y165C [SEQ ID NO:1], E466X [SEQ ID NO:3], Y90X [SEQ ID NO:4], a nucleotide sequence encoding Y165C, E466X, or Y90X, and any combination thereof; (b) a nucleotide or amino acid sequence corresponding to the wild-type sequence in the region specified in (a); (c) one or more reagents suitable for carrying out PCR for amplifying desired regions of the patient's DNA; and (d) a surrogate marker that is indicative of or correlated to the presence of a variant of HMYH gene or the polypeptide encoded thereby. 54. A kit according to claim 53, wherein component (c) comprises at least one of: a PCR primer corresponding to an exon of the hMYH gene, a primer as defined herein in the Examples, and Taq DNA polymerase. 55. A kit according to claim 53, wherein the surrogate marker is selected from the group consisting of: (a) any biomolecule, including nucleotides, proteins, antibodies, sugars, and lipids; (b) a chemical compound, including drugs and metabolites thereof; (c) a physical characteristic, whose absence, presence, or quantity in an individual is measurable and correlated with the presence of an hMYH gene variant, or a protein encoded thereby; and (d) any combination thereof. 56. Use of an hMYH gene, a variant thereof, or a polypeptide encoded thereby, according to claims 47 or 48, or G382D-hMYH or a nucleotide sequence encoding it, for the preparation of a therapeutic composition, diagnostics composition or kit, or detection kit. 57. A screening method for identifying an individual having an inherited defect in a BER gene, an individual having an inherited defect in hMYH, or an individual who is pre-disposed to having a cancer, comprising the steps of: (a) obtaining a test sample comprising a nucleotide sequence comprised in a marker gene of the individual or an amino acid sequence of a polypeptide expressed thereby, the marker gene being a marker for a disease or condition correlated with the presence of a defect in a BER gene and/or hMYH or cancer; and (b) comparing a region of the test sample sequence with the diagnostic sequence 5′-X-X1-A-A-X2-A-A-3′ or a peptide encoded thereby, wherein X is A or T; X1 is G or T; and X2 is G or A; whereby identity between the region of the test sample gene sequence and the diagnostic sequence signifies that the individual has an inherited defect in a BER gene and/or hMYH and/or is pre-disposed to having the cancer. 58. The method according to claim 57, wherein the marker gene is APC. 59. A diagnostic sequence suitable for use in a screening method according to claim 57, comprising at least one of: (a) 5′-X-X1-A-A-X2-A-A-3′, wherein X is A or T; X1 is G or T; and X2 is G or A; (b) a sequence substantially homologous to or that hybridises to sequence (a) under stringent conditions; (c) a sequence substantially homologous to or that hybridizes under stringent conditions to the sequence (a) or (b) but for the degeneracy of the genetic code; or (d) an oligonucleotide specific for any of the sequences (a), (b) or (c). 60. Use of: (a) a diagnostic sequence according to claim 59, or a polypeptide encoded thereby, (b) a sequence substantially homologous to or that hybridises to nucleotide sequence (a) under stringent conditions; or (c) a sequence substantially homologous to or that hybridizes under stringent conditions to the nucleotide sequence (a) or (b) but for the degeneracy of the genetic code; or (d) an oligonucleotide specific for any of the nucleotide sequences (a), (b) or (c) in a therapeutic, diagnostic or detection method. 61. The use according to claim 60, for the determination of susceptibility to a disease, including cancer. 62. The use according to claim 61, wherein the diagnostic sequence is for detecting a cancer marker gene, including APC. 63. A kit suitable for use in carrying out a screening method according to claim 57 or claim 58, which kit comprises at least one of: (a) an oligo- or poly-nucleotide comprising a diagnostic sequence comprising at least one of: (i) 5′-X-X1-A-A-X2-A-A-3′, wherein X is A or T; X1 is G or T; and X2 is G or A; (ii) a sequence substantially homologous to or that hybridises to sequence (i) under stringent conditions; (iii) a sequence substantially homologous to or that hybridizes under stringent conditions to the sequence (i) or (ii) but for the degeneracy of the genetic code; or (iv) an oligonucleotide specific for any of the sequences (i), (ii) or (iii); or (v) an amino acid sequence encoded by (i), (ii), (iii), or (iv); (b) one or more reagents suitable for carrying out PCR for amplifying desired regions of the patient's DNA; and/or (c) a surrogate marker that is indicative of or correlated to the presence of a variant of sequence (a). |
Device for arching out a roller sun vizor awning |
A roller-blind arrangement has an unrollable roller blind which is moveable on a guide device, a roller-blind shaft arranged under a covering and a slotted opening located in the covering. The arrangement also has a mimic for arching out the roller blind, with the mimic being adjustable into an active position and by way of which a corresponding part acts directly on the roller blind. |
1-9. canceled. 10. A roller-blind arrangement, comprising an unrollable roller blind which is moveable on a guide device, a roller-blind shaft arranged below a covering having a slotted opening, and a mimic for arching out the roller blind, arranged to be adjusted into an active position. 11. The arrangement as claimed in claim 10, wherein the mimic is arranged to be actuatable independently of movement of the roller blind. 12. The arrangement as claimed in claim 10, characterized in that the mimic is arranged below the covering. 13. The arrangement as claimed in claim 12, wherein the mimic is arranged to be actuatable independently of movement of the roller blind. 14. The arrangement as claimed in claim 10, wherein the adjustable mimic is a pivoting lever. 15. The arrangement as claimed in claim 10, wherein the adjustable mimic is a slide which is arranged parallel to and adjustable along the covering. 16. The arrangement as claimed in claim 10, wherein the mimic is a curved device acting directly on the roller blind. 17. The arrangement as claimed in claim 11, wherein the mimic has a deflector. 18. The arrangement as claimed in claim 17, wherein the deflector is a roller. 19. The arrangement as claimed in claim 10, wherein the mimic is arranged in the region of the slotted opening. 20. A method for selectively covering an area of a vehicle comprising unrolling a roller blind movable on a guide device through an opening in a cover, and activating a mimic to arch out the roller blend so as to conform to a profile of the covered area. |
<SOH> BACKGROUND OF THE INVENTION <EOH>The present invention relates to a roller-blind arrangement having an unrollable roller blind which is moveable on a guide device, a roller-blind shaft arranged under a covering and having a slotted opening located in the covering. The arrangement also has a device for arching out the roller blind. A roller-blind arrangement of this type is suitable, for example, for covering a rear window of a motor vehicle against the incidence of light or as a way of protecting against looking in. In this case, a linear slot through which the roller blind is guided via a deflection mechanism is provided in the rear parcel shelf. If a window is arched, the distance between the window and the roller-blind outlet at the linear slotted opening changes with the profile of the arching of the window. This gives rise to dead spaces and also to visual impairments which are undesirable, for example, in a superior class of vehicle. DE 19803129 A1 shows, for a motor vehicle, a slotted opening in the rear parcel shelf. The opening has a profile which follows the arching of the window. One of the edges of the slotted opening is designed as a guide edge over which the roller blind is guided and by means of which it is arched in the direction of the window. A disadvantage of this design is the load to which the roller blind is subjected. Since the roller blind is under tensile stress, it is pressed with the corresponding force against the guide edge. This leads to considerable friction during its extension and retraction, and consequently to the blind and its coating being subject to an abrasive load. This causes problems in long-term operation and, moreover, the appearance of the blind also suffers. |
<SOH> SUMMARY OF THE INVENTION <EOH>An object of the present invention is to enable a roller blind to arch out with the above-mentioned disadvantages being avoided. To achieve this object, the device for arching out the roller blind is a “mimic” which can be adjusted into an active position. The ability of the mimic which arches out the roller blind to be adjusted between an active and an inactive position enables this mimic to act on the roller blind only when required instead of permanently. In an advantageous embodiment, the mimic can be actuated independently of the movement of the roller blind, thus avoiding the movement of the roller blind during its retraction or extension being coupled to the actuation of the mimic for arching the roller blind. In this case, the mimic is advantageously arranged below the covering in order to be able to ensure an arrangement which is protected from external influences and is largely invisible. The adjustable mimic can be configured as a pivoting lever which can be pivoted in a simple manner between an active position acting on the roller blind and an inactive position. In an alternative embodiment, the adjustable mimic is a slide arranged parallel to the covering and adjustable along the latter. The slide can act, on one hand, on the roller blind and can be used, on the other hand, to cover the slotted opening. In one expedient configuration, the adjustable mimic has an arched mechanism directly on the roller blind, which mechanism can be used to bring about a predetermined arching of the roller blind, at least in a subregion thereof. In the case of the two alterative embodiments with a pivoting lever or a slide, it is furthermore expedient to provide a deflector for the roller blind on the adjustable mimic in order to be able to extend and retract the roller blind even in the arched state under the action of the mimic without a relatively large stress being exerted on the material. In one advantageous development, the deflector is a roller. The adjustable mimic can be arranged in the region of the slotted opening. The necessary structural space is available in this region, and the roller blind can be arched out in a largely imperceptible manner. |
Contact with a rigidly welded spring cage |
A plug device having an electrical plug connector. Within the plug connector, quick-connect receptacles are situated in contact chambers, which make an electrical connection to mating connectors. In order to protect the quick-connect receptacles from possible failure due to excessively great vibration loads or other forces, it is provided that a spring basket be positioned in the region of the contact part of the quick-connect receptacle, which, besides form-locking connections, such as crimps, also has a force-locking connection to the remaining part of the quick-connect receptacle. This force locking connection is implemented by a welded connection, especially a laser weld pointing. |
1.-5. (Canceled) 6. An electrical plug connector, comprising: a quick-connect receptacle; a contact carrier made of an insulating material and including at least one row of contact chambers closed off against one another and situated parallel to one another, in each of which the quick-connect receptacle is positioned; a fastening section for a stripped end of an electric line; a middle section; a contact section including a contact part; a waist-like section lying between the fastening section and the middle section; a buckle situated on the quick-connect receptacle on a side pointing to a mating plug, the buckle extending over a part of the contact part and located adjacent to the contact part, wherein: the contact part and the buckle have a form locking connection and have at least one force connection in the form of a welded connection. 7. The electrical plug connector as recited in claim 6, wherein: the buckle is situated in a region of the contact section. 8. The electrical plug connector as recited in claim 6, wherein: the buckle is situated at least in a region of the fastening section. 9. The electrical plug connector as recited in claim 6, wherein: the welded connection is implementable using laser weld pointing. 10. The electrical plug connector as recited in claim 6, wherein: the welded connection is situated directly in a region of a transition from the middle section into the waist-like section. |
<SOH> BACKGROUND INFORMATION <EOH>Many plug connectors of the above-mentioned species are known. They include a contact carrier and several parallel contact chambers arranged in series, so-called quick-connect receptacles being situated in the contact chambers. These quick-connect receptacles have several functional sections, namely a fastening section, to which a stripped cable or an electrical line may be attached by so-called crimping and connected electrically using a quick-connect receptacle, and a center section as well as a contact section, the contact section being provided to accommodate a pin, which is situated in a mating connector, so that an electrical connection may be brought about between the plug connector and the mating connector. The quick-connect receptacle itself is positioned in a contact chamber within the plug connector in such a way that it is firmly held in this chamber, or fixed. It is known from the related art that, by bringing about a locking in the region of the waist-shaped section, one may bring about a fixing of the quick-connect receptacle within the chamber. In this context, the quick-connect receptacle is at a very small distance from the wall of the contact chamber. For the firm fixing of the quick-connect receptacle within a contact chamber, other devices are also provided. For example, a locking slide is known from German Published Patent Application No. 37 25 688 which clamps the waist shape of the quick-connect receptacle inside the contact chamber. The aforesaid locking mechanism assumes the task of directly absorbing or dissipating the forces appearing on the contact section during the plug-in process of the plug connector to the mating connector, so that almost no forces act on the fastening section or on the waist-like section. The decoupling of the vibration stress appearing during the application of the plug and the mating plug is performed inside the contact part by an elastic design, particularly by a suitable shaping of the middle section. A disadvantage of the fixing and locking mechanisms known up to now is that unacceptably large forces appear particularly in the case of a clamping connection that is not completely executed, or in the case of a loose connection, especially between a spring element and a contact part, for example, coming about by shaking motions, which excessively stress individual elements, particularly the connection between the spring element and the contact part, but also the middle section, so that their function is not ensured. A further disadvantage is that a spring element provided at the quick-connect receptacle releases a form locking that is provided between the two parts. This, in turn, leads to the elastic zone of the contact part being stretched too much, so that particularly powerful motions damage the contact point. It is an object of the present invention to create a connection of a quick-connect receptacle to a mating connector within a contact chamber that is simple and protected from shaking movements. The attainment of the object is that, at the quick-connect receptacle, on the side pointing to the mating connector, a buckle is positioned, which extends over a part of the contact part and is adjacent to it, the contact part and the buckle, besides the form locking connection having at least one force locking connection in the form of a welded connection. |
<SOH> SUMMARY OF THE INVENTION <EOH>According to the present invention, it is provided that one should slide onto an embodiment of a quick-connect receptacle known from the related art a so-called spring basket in the vicinity of the contact part and the middle section. This spring basket is predominantly a stamped part, which is then bent. The spring basket is clipped on owing to a corresponding fit, and is held to the quick-connect receptacle by so-called crimps. Additional bending processes lead to the spring basket's being connected in a form-locking way to the quick-connect receptacle. Preferably, the spring basket extends exclusively in the contact region of the quick-connect receptacle. It is further conceivable that the spring basket may also extend all the way to the waist-shaped section. The spring basket itself also has cutting devices pointing towards the outside. These are used so that the spring basket can dig its claws in, into a contact chamber of a plug contact. In order to compensate for the forces appearing during the process of clipping on or also the forces that are created especially in response to shaking movements by the plug connector and the mating connector, it is provided that one should connect the spring basket in a force locking manner, in addition to the form locking connection, as has been described. This force locking connection is achieved, for example, by a welded connection between the spring basket and the remaining part of the quick-connect receptacle. Preferably it is provided that the connection shall be made with the aid of a laser weld point. Preferably, the laser weld point is positioned in such a way that it is positioned in the region where the forces appear to a maximum. This is the region at which the spring basket ends, and at which the quick-connect receptacle has a waist-like form. It has also proven advantageous that, because of the use of a laser for producing the weld point, different types of material, such as steel and copper, can be used. By this inventive embodiment of a quick-connect receptacle together with a spring basket, it is achieved that failure of the plug connection will be avoided. |
System and method in a spreadsheet for exporting-importing the content of input cells from a scalable template instance to another |
The present invention is directed to a method, system and program for exporting-importing the content of input cells from a source scalable template instance in a source multi-dimensional spreadsheet to a destination scalable template instance in a destination multidimensional spreadsheet; a multi-dimensional spreadsheet comprising a plurality of cells identified by a cell address along each dimension; a scalable template instance comprising a variable number of contiguous elements of same size ordered and aligned along a given spreadsheet dimension and structured according to information defined in an associated scalable template; an element being defined as a range of cells; a range of cells comprising one or a plurality of cells; said scalable template comprising an element profile; an element profile defining a cell content and a cell destination for each cell within each element; said cell destination specifying whether the cell is an input cell for receiving an entry or an output cell for producing a result. The method comprises the steps of: detecting a command for exporting-importing input cells from a source scalable template instance in a source spreadsheet to a destination scalable template instance in a destination spreadsheet; identifying the source scalable template associated with the source scalable template instance; identifying cells, if there are any, defined as input cells in the element profile of the source scalable template; identifying the destination scalable template associated with the destination scalable template instance; Identifying cells, if there are any, defined as input cells in the element profile of the destination scalable template; copying cell per cell, the content of each input cell of the source scalable 36 template instance in each input cell of the destination scalable template instance. |
1. A method for exporting-importing the content of input cells from a source scalable template instance in a source multi-dimensional spreadsheet to a destination scalable template instance in a destination multi-dimensional spreadsheet, said method comprising the steps of: detecting a command for exporting-importing input cells from a source scalable template instance in a source spreadsheet to a destination scalable template instance in a destination spreadsheet; identifying a source scalable template associated with the source scalable template instance; identifying cells, defined as input cells in an element profile of the source scalable template; identifying a destination scalable template associated with the destination scalable template instance; identifying cells, defined as input cells in an element profile of the destination scalable template; and copying, cell per cell, the content of each input cell of the source scalable template instance in each input cell of the destination scalable template instance. 2. The method of claim 1 wherein the content of each input cell of the source scalable template instance is copied within each input cell of the destination scalable template instance input cell per input cell starting with the first input cell of the first element of both source and destination scalable template instance. 3. The method of claim 1 wherein the source spreadsheet and the destination spreadsheet are the same spreadsheet. 4. The method of claim 1 wherein copying cell per cell, the content of each input cell of the source scalable template instance in each input cell of the destination scalable template instance, further comprises: determining whether the number of elements in the source scalable template instance is greater than the number of elements in the destination scalable template instance and if the number of elements in the source scalable template instance is greater than the number of elements in the destination scalable template instance; selecting, in the source scalable template, a number of elements equal to the number of elements of the destination scalable template instance; and copying, cell per cell, the content of each input cell of each selected element of the source scalable template instance, in each input cell of each element of the destination scalable template instance. 5. The method of claim 1 wherein selecting in the source scalable template, a number of elements equal to the number of elements of the destination scalable template instance, comprises: selecting the elements in the source scalable template instance by starting with the first element. 6. The method of claim 1 wherein copying cell per cell, the content of each input cell of the source scalable template instance in each input cell of the destination scalable template instance, further comprises: determining whether the number of input cells in each element of the source scalable template instance is greater than the number of input cells in each element of the destination scalable template instance and if the number of input cells in each element of the source scalable template instance is greater than the number of input cells in each element of the destination scalable template instance: selecting in each element of the source scalable template, a number of input cells equal to the number of input cells in each element of the destination scalable template instance; and copying, cell per cell, the content of each selected input cell of each element of the source scalable template instance, in each input cell of each element of the destination scalable template instance. 7. The method of claim 1 wherein selecting in the source scalable template, a number of input cells in each element equal to the number of input cells in each element of the destination scalable template instance comprises the step of selecting the input cells in each element of the source scalable template instance by starting with the first input cell in each element. 8. The method of claim 1 wherein copying cell per cell, the content of each input cell of the source scalable template instance in each input cell of the destination scalable template instance, further comprises: storing the content of input cells of the source scalable template in a temporary file. 9. The method of claim 1 wherein an element profile defines for each cell of an element at least one of a formula, said formula referring to one or a plurality of cells, or a default value. 10. The method of claim 1 wherein each element profile comprises a profile illustrative range of cells and, for each cell belonging to said profile illustrative range of cells, a cell content and a cell destination. 11. The method of claim 1 wherein a scalable template further comprises an element format; an element format defining for each cell within an element, one or a plurality of format attributes. 12. The method of claim 1 wherein a scalable template further comprises an element format and wherein an element format defines for each cell of an element one or a plurality of: Background attributes; and/or Alignment attributes; and/or Font attributes; and/or Line attributes; and/or Protection attributes. 13. The method of claim 1 wherein a scalable template further comprises an element format and wherein each element format comprises a format illustrative range of cells and, for each cell belonging to said format illustrative range of cells, one or a plurality of format attributes. 14. A system for exporting-importing the content of input cells from a source scalable template instance in a source multi-dimensional spreadsheet to a destination scalable template instance in a destination multi-dimensional spreadsheet, the system comprising: means for detecting a command for exporting-importing input cells from a source scalable template instance in a source spreadsheet to a destination scalable template instance in a destination spreadsheet; means for identifying a source scalable template associated with the source scalable template instance; means for identifying cells defined as input cells in an element profile of the source scalable template; means for identifying a destination scalable template associated with the destination scalable template instance; means for identifying cells defined as input cells in an element profile of the destination scalable template; and means for copying, cell per cell, the content of each input cell of the source scalable template instance in each input cell of the destination scalable template instance. 15. (Canceled). 16. The method of claim 1 wherein a multi-dimensional spreadsheet comprises a plurality of cells identified by a cell address along each dimension and wherein a scalable template instance comprises a variable number of contiguous elements of same size ordered and aligned along a given spreadsheet dimension and structured according to information defined in an associated scalable template, an element being defined as a range of cells, a range of cells comprising at least one cell; and wherein said scalable template comprises an element profile, an element profile defining a cell content and a cell destination for each cell within each element, said cell destination specifying whether the cell is an input cell for receiving an entry or an output cell for producing a result. 17. A computer program product for exporting-importing the content of input cells from a source scalable template instance in a source multi-dimensional spreadsheet to a destination scalable template instance in a destination multi-dimensional spreadsheet, the computer program product comprising: a computer-readable storage medium having computer-readable program code embodied in said medium, said computer-readable program code comprising: computer-readable program code that detects a command for exporting-importing input cells from a source scalable template instance in a source spreadsheet to a destination scalable template instance in a destination spreadsheet; computer-readable program code that identifies a source scalable template associated with the source scalable template instance; computer-readable program code that identifies cells defined as input cells in an element profile of the source scalable template; computer-readable program code that identifies a destination scalable template associated with the destination scalable template instance; computer-readable program code that identifies cells defined as input cells in an element profile of the destination scalable template; and computer-readable program code that copies, cell per cell, the content of each input cell of the source scalable template instance in each input cell of the destination scalable template instance. |
<SOH> BACKGROUND ART <EOH>Before computers, numerical analyses, particularly financial ones, were usually prepared on an accountant's columnar pad or spreadsheet, with pencil and calculator in hand. By organizing data into columns and rows, spreadsheets afford the rapid assimilation of information by a reader. The task of preparing a spreadsheet on paper, however, is not quite so fast. Instead, the process tends to be very slow, as each entry must be tediously calculated and entered into the spreadsheet. Since all calculations are the responsibility of the preparer, manually prepared spreadsheets are also prone to errors. Hence, preparation of spreadsheets by hand is slow, tedious, and unreliable. With the advent of microcomputers, a solution was forthcoming in the form of “electronic spreadsheets.” Better known simply as “spreadsheets,” these software programs provide a computerized replacement for the traditional financial modelling tools: the accountant's columnar pad, pencil, and calculator. In some regards, spreadsheet programs are to those tools what word processors are to typewriters. Spreadsheets offer dramatic improvements in ease of creating, editing, and using financial models. A typical spreadsheet program configures the memory of a computer to resemble the column/row or grid format of an accountant's columnar pad, thus providing a visible calculator for a user. Because this “pad” exists dynamically in the computer's memory, however, it differs from paper pads in several important ways. Locations in the electronic spreadsheet, for example, must be communicated to the computer in a format which it can understand. A common scheme for accomplishing this is to assign a number to each row in a spreadsheet, and a letter to each column. To reference a location at column A and row 1 (i.e., the upper-left hand corner), for example, the user types in “A1”. In this manner, the spreadsheet defines an addressable storage location or “cell” at each intersection of a row with a column. Data entry into an electronic spreadsheet occurs in much the same manner that information would be entered on an accountant's pad. After a screen cursor is positioned at a desired location, the user can enter alphanumeric information. Besides holding text and numeric information, however, spreadsheet cells can store special instructions or “formulas” specifying calculations to be performed on the numbers stored in spreadsheet cells. In this fashion, cell references can serve as variables in an equation, thereby allowing precise mathematical relationships to be defined between cells. The structure and operation of a spreadsheet program, including advanced functions such as functions and macros, are documented in the technical, trade, and patent literature. For an overview, see e.g., Cobb, S., Using Quattro Pro 2, Borland-OsbornelMcGraw-MII, 1990; and LeBlond, G. and Cobb, D., Using 1-2-3, Que corp., 1985. The disclosures of each of the foregoing are hereby incorporated by reference. Electronic spreadsheets offer many advantages over their paper counterparts. For one, electronic spreadsheets are much larger (i.e., hold more information) than their paper counterparts; electronic spreadsheets having thousands or even millions of cells are not uncommon. Spreadsheet programs also allow users to perform “what-if” scenarios. After a set of computational relationships has been entered into a worksheet, thanks to imbedded formulas and/or built-in functions for instance, the spread of information can be recalculated using different sets of assumptions, with the results of each recalculation appearing almost instantaneously. Performing this operation manually, with paper and pencil, would require recalculating every relationship in the model with each change made. Thus, electronic spreadsheet systems were invented to solve “what-if” problems, that is, changing an input and seeing what happens to an output. As exposed above, one essential value of an electronic spreadsheet is to organize data into columns and rows, while automating tedious calculations. A typical, common, and valuable example of such a set of data organized into columns and rows is a range of cells. Even if a range of cells receives a formal and strict definition within electronic spreadsheet environments, it is flexible enough so that information can be included in either a single range of cells or in a set of several ranges of cells. Ranges of cells therefore are quite useful objects. A range of cell can be defined and processed as a whole entity. For example it can be copied from one place to another place within the spreadsheet or from one spreadsheet file to another spreadsheet file. Ranges of cells are widely used in applications developed in the field of electronic spreadsheets. Most often, the ranges of cells are arranged according to some kind of structure, thus becoming structured ranges of cells. The contents of each cell is defined within an element, where an element is defined as a row of a structured range of cells, and then the same kind of element is repeated a certain number of times, to store/process a variable number of information pieces. Most of the time, several instances of similar structured ranges of cells are used. In the current context where no other tool is really available, instances of such similar structured ranges of cells are frequently created through cut/copy and paste operations. Creating a new instance of a structured range of cells is complex and lengthy, particularly because a conventional range of cells shows strong limitations: (i) structure information (such as number of columns, number of rows), format information (such as font style, color or border), and contents information (such as formulas or raw- or informative-data) are mixed, (ii) the size of the range of cell is fixed at a given instant. Therefore, when a spreadsheet user wants to create another range of cells with an identical structure, he/she needs to perform successively several operations. He/she needs to: 1. copy-paste an existing structured range of cells, 2. distinguish between areas containing raw- or informative-data and areas containing generic content such as formulas, 3. empty the copied structured range of cells of the copied raw data while trying to keep the structure, format and generic contents, 4. adjust the size of the structured copied range of cells to his new needs. 5. eventually, fill the raw data area with default values, in order to ease subsequent data entry. Furthermore, before copying and pasting a structured range of cells, the user must prepare the place for the copied structured range of cells, with the risk of overwriting, and therefore loosing the preexisting information at the destination location. This chain of operations rapidly becomes tedious, lengthy and prone to error, especially when manipulated structured ranges of cells increase in size and complexity. Updating a structured range of cells is also very often complex, lengthy and prone to error. Such updates include additions of new elements and modifications of existing elements. Several types of modifications can be performed without any specific problem in an electronic spreadsheet environment. However, this is not the case for some modifications, for instance for insertions. For example, if a row is added by means of a conventional function such as the spreadsheet row insertion method, the created row will be empty. This means that the value for every cell of every element needs to be entered. Entering data or executing copy/paste operations represents an important workload for the user, while the content of each element is known to a certain extent, and should follow the general structure of the structured range of cells. Moreover, normal spreadsheet functions such as the row insertion function may jeopardize the contents of some neighbour elements. A good exemple of an insertion jeopardising neighbour elements is the insertion of a row in a range of cells in which, on every row, a cell such as C17 or more generally (Cn), is pointing to a cell in the previous row, through a formula such as C16+B17, or more generally (Cn−1)+(Bn). After row insertion between rows 16 and 17, the formula in cell C18 becomes C16+B18 instead of the generic formula C17+B18, or more generally after row insertion between rows (n−1) and (n), the formula in cell (Cn+1) becomes (Cn−1)+(Bn+1) instead of the generic formula (Cn)+(Bn+1). As a second exemple, there are cases where modifications must be done consistently throughout the structured range of cells. Today, this can only be done using specific copy-paste operations applied to the exact area to be modified. This may prove to be very difficult, especially when manipulated structured ranges of cells increase in size and complexity. Deleting an element of a structured range of cells is an operation prone to error. As a matter of fact, normal spreadsheet functions such as the row deletion function may jeopardize the contents of some neighbour elements, leading to unresolved references (#REF results) or, even worse to wrong formulas that may be difficult to identify. Solving this problem requires additional “context intelligence”, taking into account the structure of the structured range of cells in which the element deletion occurs. Another need appears at the time the user invokes the conventional Delete function after selection in the spreadsheet of one or a plurality of cells. If the selection belongs to a structured range of cells, calling the Delete function by means of a menu or by pressing the “Delete” key, leaves room to ambiguity as to what the user wants to perform. Removing this ambiguity can only be done today by selecting the exact area to be deleted, which may prove to be very difficult, especially as manipulated structured ranges of cells increase in size and complexity. Solving this problem requires additional “context intelligence” to detect this situation, take advantage of the structure of the structured range of cells and offer the relevant choice to the user. The amount of storage that is necessary to save a structured range of cells may become prohibitive when such a structured range of cells grows in size. On another hand, an important portion of each element of such a structured range of cells may be constituted of OUT fields containing formulas, without any user provided data. Those fields are similar from element to element, and comprise redundant information. This information is not redundant from an end user standpoint, since it is certainly useful, but is redundant because it can be recreated from the base structure of the structured range of cells. Storing and/or conveying this redundant information is a waste that could be avoided if a mechanism would allow to only store/convey the informative data and the information related to the base structure of the structured range of cells. Sorting data within a selected range of cells introduces the risk of jeopardizing any neighbouring structured range of cells. This risk exists because the selected range of cells is sorted, regardless of the existence of any neighbouring structured range of cells and regardless of the respective positions of the selected range of cells versus any neighbouring structured range of cells. The risk can be avoided only by a careful and precise selection of the range to sort. This selection is prone to error, especially when structured ranges of cells grow in size and complexity. Improved control over sort operations are possible by taking into account the structure and the position of the structured ranges of cells. The U.S. Pat. No. 5,033,009 is an interesting piece of prior art, that develops the concepts of pattern data and variable data that may be integrated to generate a worksheet file through a worksheet file generator. This invention however shows many limitations preventing it from solving the set of issues presented here above and, in particular: It aims at producing a new output spreadsheet from a set of two input files, while there is a need, within a user application environment, to create and manipulate new entities within an existing electronic spreadsheet file, that the user is familiar with. It contains no mechanism allowing the direct update of the output spreadsheet, other than the regular spreadsheet tool. It contains no capability to manipulate within the same spreadsheet file, a variable number of different structures and a variable number of instances of each of those structure. The granularity is limited to the spreadsheet file, while the required granularity is that of a structured range of cells. The so called “file format specification” really mixes structure information (such as number and relative position of columns and rows), presentation information (such as font, color, background, etc.), contents information (such as formulas, etc.). |
<SOH> SUMMARY OF THE INVENTION <EOH>As defined in independent claims, the present invention is directed to a method, system and program for exporting-importing the content of input cells from a source scalable template instance in a source multi-dimensional spreadsheet to a destination scalable template instance in a destination multi-dimensional spreadsheet; a multi-dimensional spreadsheet comprising a plurality of cells identified by a cell address along each dimension; a scalable template instance comprising a variable number of contiguous elements of same size ordered and aligned along a given spreadsheet dimension and structured according to information defined in an associated scalable template; an element being defined as a range of cells; a range of cells comprising one or a plurality of cells; said scalable template comprising an element profile; an element profile defining a cell content and a cell destination for each cell within each element; said cell destination specifying whether the cell is an input cell for receiving an entry or an output cell for producing a result. The method comprises the steps of: Detecting a command for exporting-importing input cells from a source scalable template instance in a source spreadsheet to a destination scalable template instance in a destination spreadsheet; Identifying the source scalable template associated with the source scalable template instance; Identifying cells, if there are any, defined as input cells in the element profile of the source scalable template; Identifying the destination scalable template associated with the destination scalable template instance; Identifying cells, if there are any, defined as input cells in the element profile of the destination scalable template; Copying cell per cell, the content of each input cell of the source scalable template instance in each input cell of the destination scalable template instance. Further embodiments of the invention are provided in the appended dependent claims. The foregoing, together with other objects, features, and advantages of this invention can be better appreciated with reference to the following specification, claims and drawings. |
Device and method for exercising a body part of a person |
The present invention relates to a device for exercising a body part of a person, comprising a substantially annular member, means for gripping the member, the gripping means being arranged substantially in the centre of the annulus, a weight and means for guiding the weight along the member for generating a centrifugal force caused by rotation of the weight along the annular member. The present invention also relates to a method of exercising a body part of a person. |
1-16. (canceled) 17. A device for exercising a body part of a person, comprising: a) a substantially annular member; b) means for gripping the member, the gripping means being arranged substantially in the centre of the annulus; c) a weight; and d) means for guiding the weight along the member for generating a centrifugal force caused by rotation of the weight along the annular member. 18. The device according to claim 17, wherein the guiding means comprise a passage through the annular member, the weight rotatable along said passage. 19. The device according to claim 18, wherein the annular member is a hollow member and the weight comprises one or more balls, the balls being dimensioned so as to be freely movable inside the hollow member. 20. The device according to claim 18, wherein the annular member is a hollow member and the weight comprises a liquid, the liquid being rotatable inside the reservoir formed by the hollow member. 21. The device according to claim 17, wherein the guiding means comprise a bracket to which the weight is mounted, the bracket being provided with a slide for sliding the weight in a track provided in the periphery of the annular member. 22. The device according to claim 17, wherein the weight comprises a second annular member of a larger diameter than the first annular member and wherein the guiding means comprise a plurality of bearings arranged between the first and second annular members. 23. The device according to claim 17, wherein the annular member is hand-held. 24. The device according to claim 17, wherein the gripping means comprise a transverse handle attached to the annular member for gripping by the person. 25. The device according to claim 24, wherein the handle is detachably attached to the annular member. 26. The device according to claim 17, wherein the gripping means comprise a sleeve for gripping said body part of the person. 27. The device according to claim 26, wherein the sleeve is provided with straps for attaching the sleeve to said body part. 28. The device according to claim 17, wherein the gripping means comprise an elastic fabric provided with a central opening into which the body part can be inserted for gripping the body part. 29. The device according to claim 17, wherein the annular member is manufactured of a plurality of injection-molded material. 30. The device according to claim 17, wherein the annular member is manufactured of plastic. 31. The device according to claim 17, wherein the total weight of the device ranges from 0.2 kg to 3 kg, preferably from 0.3 kg to 0.9 kg. 32. A method of exercising a body part of a person with the device of claim 17, the method comprising the steps of: a) arranging the body part to be exercised in the centre of the annular member; b) attaching the body part to the annular member; and c) moving the body part causing the weight to rotate along the annular member for exerting a centrifugal exercising force on at least said body part. |
Protein associated with cell growth, differentiation, and death |
Various embodiments of the invention provide human proteins associated with cell growth, differentiation, and death (CGDD) and polynucleotides which identify and encode CGDD. Embodiments of the invention also provide expression vectors, host cells, antibodies, agonists, and antagonists. Other embodiments provide methods for diagnosing, treating, or preventing disorders associated with aberrant expression of CGDD. |
1. An isolated polypeptide selected from the group consisting of: a) a polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO:1-27, b) a polypeptide comprising a naturally occurring amino acid sequence at least 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:2-5, SEQ ID NO:7, SEQ ID NO:9-10, SEQ ID NO:12, SEQ ID NO:14-15, SEQ ID NO:18-19, SEQ ID NO:22-23, and SEQ ID NO:27, c) a polypeptide comprising a naturally occurring amino acid sequence at least 98% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:1 and SEQ ID NO:17, d) a polypeptide comprising a naturally occurring amino acid sequence at least 96% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:6 and SEQ ID NO:8, e) a polypeptide comprising a naturally occurring amino acid sequence at least 99% identical to the amino acid sequence of SEQ ID NO:11, f) a polypeptide comprising a naturally occurring amino acid sequence at least 95% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:13 and SEQ ID NO:16, g) A polypeptide comprising a naturally occurring amino acid sequenc at least 94% identical to an amino acid squence selected from the group consisting of SEQ ID NO:20, SEQ ID NO:24, and SEQ ID NO:26, h) a biologically active fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-27, and i) an immunogenic fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-27. 2. An isolated polypeptide of claim 1 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:1-27. 3. An isolated polynucleotide encoding a polypeptide of claim 1. 4. An isolated polynucleotide encoding a polypeptide of claim 2. 5. An isolated polynucleotide of claim 4 comprising a polynucleotide sequence selected from the group consisting of SEQ ID NO:28-54. 6. A recombinant polynucleotide comprising a promoter sequence operably linked to a polynucleotide of claim 3. 7. A cell transformed with a recombinant polynucleotide of claim 6. 8. (canceled) 9. A method of producing a polypeptide of claim 1, the method comprising: a) culturing a cell under conditions suitable for expression of the polypeptide, wherein said cell is transformed with a recombinant polynucleotide, and said recombinant polynucleotide comprises a promoter sequence operably linked to a polynucleotide encoding the polypeptide of claim 1, and b) recovering the polypeptide so expressed. 10. A method of claim 9, wherein the polypeptide comprises an amino acid sequence selected from the group consisting of SEQ ID NO:1-27. 11. An isolated antibody which specifically binds to a polypeptide of claim 1. 12. An isolated polynucleotide selected from the group consisting of: a) a polynucleotide comprising a polynucleotide sequence selected from the group consisting of SEQ ID NO:28-54, b) a polynucleotide comprising a naturally occurring polynucleotide sequence at least 90% identical to a polynucleotide sequence selected from the group consisting of SEQ ID NO:28-37, SEQ ID NO:39-51, and SEQ ID NO:54, c) a polynucleotide comprising a naturally occurring polynucleotide sequence at least 99% identical to a polynucleotide sequence of SEQ ID NO:52, d) a polynucleotide comprising a naturally occurring polynucleotide sequence at least 94% identical to a polynucleotide sequence of SEQ ID NO:54, e) a polynucleotide complementary to a polynucleotide of a), f) a polynucleotide complementary to a polynucleotide of b), g) a polynucleotide complementary to a polynucleotide of c), h) a polynucleotide complementary to a polynucleotide of d), and i) an RNA equivalent of a)-h). 13. (canceled) 14. A method of detecting a target polynucleotide in a sample, said target polynucleotide having a sequence of a polynucleotide of claim 12, the method comprising: a) hybridizing the sample with a probe comprising at least 20 contiguous nucleotides comprising a sequence complementary to said target polynucleotide in the sample, and which probe specifically hybridizes to said target polynucleotide, under conditions whereby a hybridization complex is formed between said probe and said target polynucleotide or fragments thereof, and b) detecting the presence or absence of said hybridization complex, and, optionally, if present, the amount thereof. 15. (canceled) 16. A method of detecting a target polynucleotide in a sample, said target polynucleotide having a sequence of a polynucleotide of claim 12, the method comprising: a) amplifying said target polynucleotide or fragment thereof using polymerase chain reaction amplification, and b) detecting the presence or absence of said amplified target polynucleotide or fragment thereof, and, optionally, if present, the amount thereof. 17. A composition comprising a polypeptide of claim 1 and a pharmaceutically acceptable excipient. 18. A composition of claim 17, wherein the polypeptide comprises an amino acid sequence selected from the group consisting of SEQ ID NO:1-27. 19. (canceled) 20. A method of screening a compound for effectiveness as an agonist of a polypeptide of claim 1, the method comprising: a) exposing a sample comprising a polypeptide of claim 1 to a compound, and b) detecting agonist activity in the sample. 21. (canceled) 22. (canceled) 23. A method of screening a compound for effectiveness as an antagonist of a polypeptide of claim 1, the method comprising: a) exposing a sample comprising a polypeptide of claim 1 to a compound, and b) detecting antagonist activity in the sample. 24. (canceled) 25. (canceled) 26. A method of screening for a compound that specifically binds to the polypeptide of claim 1, the method comprising: a) combining the polypeptide of claim 1 with at least one test compound under suitable conditions, and b) detecting binding of the polypeptide of claim 1 to the test compound, thereby identifying a compound that specifically binds to the polypeptide of claim 1. 27. (canceled) 28. A method of screening a compound for effectiveness in altering expression of a target polynucleotide, wherein said target polynucleotide comprises a sequence of claim 5, the method comprising: a) exposing a sample comprising the target polynucleotide to a compound, under conditions suitable for the expression of the target polynucleotide, b) detecting altered expression of the target polynucleotide, and c) comparing the expression of the target polynucleotide in the presence of varying amounts of the compound and in the absence of the compound. 29. A method of assessing toxicity of a test compound, the method comprising: a) treating a biological sample containing nucleic acids with the test compound, b) hybridizing the nucleic acids of the treated biological sample with a probe comprising at least 20 contiguous nucleotides of a polynucleotide of claim 12 under conditions whereby a specific hybridization complex is formed between said probe and a target polynucleotide in the biological sample, said target polynucleotide comprising a polynucleotide sequence of a polynucleotide of claim 12 or fragment thereof, c) quantifying the amount of hybridization complex, and d) comparing the amount of hybridization complex in the treated biological sample with the amount of hybridization complex in an untreated biological sample. wherein a difference in the amount of hybridization complex in the treated biological sample is indicative of toxicity of the test compound. 30-109. (canceled) |
<SOH> BACKGROUND OF THE INVENTION <EOH>Human growth and development requires the spatial and temporal regulation of cell differentiation, cell proliferation, and apoptosis. These processes coordinately control reproduction, aging, embryogenesis, morphogenesis, organogenesis, and tissue repair and maintenance. At the cellular level, growth and development is governed by the cell's decision to enter into or exit from the cell division cycle and by the cell's commitment to a terminally differentiated state. These decisions are made by the cell in response to extracellular signals and other environmental cues it receives. The following discussion focuses on the molecular mechanisms of cell division, embryogenesis, cell differentiation and proliferation, and apoptosis, as well as disease states such as cancer which can result from disruption of these mechanisms. |
<SOH> SUMMARY OF THE INVENTION <EOH>Various embodiments of the invention provide purified polypeptides, proteins associated with cell growth, differentiation, and death, referred to collectively as ‘CGDD’ and individually as ‘CGDD-1,’ ‘CGDD-2,’ ‘CGDD-3,’ ‘CGDD-4,’ ‘CGDD-5,’ ‘CGDD-6,’ ‘CGDD-7,’ ‘CGDD-8,’ ‘CGDD-9,’ ‘CGDD-10,’ ‘CGDD-11,’ ‘CGDD-12,’ ‘CGDD-13,’ ‘CGDD-14,’ ‘CGDD-15,’ ‘CGDD-16,’ ‘CGDD-17,’ ‘CGDD-18,’ ‘CGDD-19,’ ‘CGDD-20,’ ‘CGDD-21,’ ‘CGDD-22, ’ ‘CGDD-23,’ ‘CGDD-24,’ ‘CGDD-25,’ ‘CGDD-26,’ and ‘CGDD-27’ and methods for using these proteins and their encoding polynucleotides for the detection, diagnosis, and treatment of diseases and medical conditions. Embodiments also provide methods for utilizing the purified proteins associated with cell growth, differentiation, and death and/or their encoding polynucleotides for facilitating the drug discovery process, including determination of efficacy, dosage, toxicity, and pharmacology. Related embodiments provide methods for utilizing the purified proteins associated with cell growth, differentiation, and death and/or their encoding polynucleotides for investigating the pathogenesis of diseases and medical conditions. An embodiment provides an isolated polypeptide selected from the group consisting of a) a polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO:1-27, b) a polypeptide comprising a naturally occurring amino acid sequence at least 90% identical or at least about 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:1-27, c) a biologically active fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-27, and d) an immunogenic fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-27. Another embodiment provides an isolated polypeptide comprising an amino acid sequence of SEQ ID NO:1-27. Still another embodiment provides an isolated polynucleotide encoding a polypeptide selected from the group consisting of a) a polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO:1-27, b) a polypeptide comprising a naturally occurring amino acid sequence at least 90% identical or at least about 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:1-27, c) a biologically active fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-27, and d) an immunogenic fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-27. In another embodiment, the polynucleotide encodes a polypeptide selected from the group consisting of SEQ ID NO:1-27. In an alternative embodiment, the polynucleotide is selected from the group consisting of SEQ ID NO:28-54. Still another embodiment provides a recombinant polynucleotide comprising a promoter sequence operably linked to a polynucleotide encoding a polypeptide selected from the group consisting of a) a polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO:1-27, b) a polypeptide comprising a naturally occurring amino acid sequence at least 90% identical or at least about 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:1-27, c) a biologically active fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-27, and d) an immunogenic fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-27. Another embodiment provides a cell transformed with the recombinant polynucleotide. Yet another embodiment provides a transgenic organism comprising the recombinant polynucleotide. Another embodiment provides a method for producing a polypeptide selected from the group consisting of a) a polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO:1-27, b) a polypeptide comprising a naturally occurring amino acid sequence at least 90% identical or at least about 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:1-27, c) a biologically active fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-27, and d) an immunogenic fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-27. The method comprises a) culturing a cell under conditions suitable for expression of the polypeptide, wherein said cell is transformed with a recombinant polynucleotide comprising a promoter sequence operably linked to a polynucleotide encoding the polypeptide, and b) recovering the polypeptide so expressed. Yet another embodiment provides an isolated antibody which specifically binds to a polypeptide selected from the group consisting of a) a polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO:1-27, b) a polypeptide comprising a naturally occurring amino acid sequence at least 90% identical or at least about 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:1-27, c) a biologically active fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-27, and d) an immunogenic fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-27. Still yet another embodiment provides an isolated polynucleotide selected from the group consisting of a) a polynucleotide comprising a polynucleotide sequence selected from the group consisting of SEQ ID NO:28-54, b) a polynucleotide comprising a naturally occurring polynucleotide sequence at least 90% identical or at least about 90% identical to a polynucleotide sequence selected from the group consisting of SEQ ID NO:28-54, c) a polynucleotide complementary to the polynucleotide of a), d) a polynucleotide complementary to the polynucleotide of b), and e) an RNA equivalent of a)-d). In other embodiments, the polynucleotide can comprise at least about 20, 30, 40, 60, 80, or 100 contiguous nucleotides. Yet another embodiment provides a method for detecting a target polynucleotide in a sample, said target polynucleotide being selected from the group consisting of a) a polynucleotide comprising a polynucleotide sequence selected from the group consisting of SEQ ID NO:28-54, b) a polynucleotide comprising a naturally occurring polynucleotide sequence at least 90% identical or at least about 90% identical to a polynucleotide sequence selected from the group consisting of SEQ ID NO:28-54, c) a polynucleotide complementary to the polynucleotide of a), d) a polynucleotide complementary to the polynucleotide of b), and e) an RNA equivalent of a)-d). The method comprises a) hybridizing the sample with a probe comprising at least 20 contiguous nucleotides comprising a sequence complementary to said target polynucleotide in the sample, and which probe specifically hybridizes to said target polynucleotide, under conditions whereby a hybridization complex is formed between said probe and said target polynucleotide or fragments thereof, and b) detecting the presence or absence of said hybridization complex. In a related embodiment, the method can include detecting the amount of the hybridization complex. In still other embodiments, the probe can comprise at least about 20, 30, 40, 60, 80, or 100 contiguous nucleotides. Still yet another embodiment provides a method for detecting a target polynucleotide in a sample, said target polynucleotide being selected from the group consisting of a) a polynucleotide comprising a polynucleotide sequence selected.from the group consisting of SEQ ID NO:28-54, b) a polynucleotide comprising a naturally occurring polynucleotide sequence at least 90% identical or at least about 90% identical to a polynucleotide sequence selected from the group consisting of SEQ ID NO:28-54, c) a polynucleotide complementary to the polynucleotide of a), d) a polynucleotide complementary to the polynucleotide of b), and e) an RNA equivalent of a)-d). The method comprises a) amplifying said target polynucleotide or fragment thereof using polymerase chain reaction amplification, and b) detecting the presence or absence of said amplified target polynucleotide or fragment thereof. In a related embodiment, the method can include detecting the amount of the amplified target polynucleotide or fragment thereof. Another embodiment provides a composition comprising an effective amount of a polypeptide selected from the group consisting of a) a polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO:1-27, b) a polypeptide comprising a naturally occurring amino acid sequence at least 90% identical or at least about 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:1-27, c) a biologically active fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-27, and d) an immunogenic fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-27, and a pharmaceutically acceptable excipient. In one embodiment, the composition can comprise an amino acid sequence selected from the group consisting of SEQ ID NO:1-27. Other embodiments provide a method of treating a disease or condition associated with decreased or abnormal expression of functional CGDD, comprising administering to a patient in need of such treatment the composition. Yet another embodiment provides a method for screening a compound for effectiveness as an agonist of a polypeptide selected from the group consisting of a) a polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO:1-27, b) a polypeptide comprising a naturally occurring amino acid sequence at least 90% identical or at least about 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:1-27, c) a biologically active fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-27, and d) an immunogenic fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-27. The method comprises a) exposing a sample comprising the polypeptide to a compound, and b) detecting agonist activity in the sample. Another embodiment provides a composition comprising an agonist compound identified by the method and a pharmaceutically acceptable excipient. Yet another embodiment provides a method of treating a disease or condition associated with decreased expression of functional CGDD, comprising administering to a patient in need of such treatment the composition. Still yet another embodiment provides a method for screening a compound for effectiveness as an antagonist of a polypeptide selected from the group consisting of a) a polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO:1-27, b) a polypeptide comprising a naturally occurring amino acid sequence at least 90% identical or at least about 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:1-27, c) a biologically active fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-27, and d) an immunogenic fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-27. The method comprises a) exposing a sample comprising the polypeptide to a compound, and b) detecting antagonist activity in the sample. Another embodiment provides a composition comprising an antagonist compound identified by the method and a pharmaceutically acceptable excipient. Yet another embodiment provides a method of treating a disease or condition associated with overexpression of functional CGDD, comprising administering to a patient in need of such treatment the composition. Another embodiment provides a method of screening for a compound that specifically binds to a polypeptide selected from the group consisting of a) a polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO:1-27, b) a polypeptide comprising a naturally occurring amino acid sequence at least 90% identical or at least about 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:1-27, c) a biologically active fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-27, and d) an immunogenic fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-27. The method comprises a) combining the polypeptide with at least one test compound under suitable conditions, and b) detecting binding of the polypeptide to the test compound, thereby identifying a compound that specifically binds to the polypeptide. Yet another embodiment provides a method of screening for a compound that modulates the activity of a polypeptide selected from the group consisting of a) a polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO:1-27, b) a polypeptide comprising a naturally occurring amino acid sequence at least 90% identical or at least about 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:1-27, c) a biologically active fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-27, and d) an immunogenic fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-27. The method comprises a) combining the polypeptide with at least one test compound under conditions permissive for the activity of the polypeptide, b) assessing the activity of the polypeptide in the presence of the test compound, and c) comparing the activity of the polypeptide in the presence of the test compound with the activity of the polypeptide in the absence of the test compound, wherein a change in the activity of the polypeptide in the presence of the test compound is indicative of a compound that modulates the activity of the polypeptide. Still yet another embodiment provides a method for screening a compound for effectiveness in altering expression of a target polynucleotide, wherein said target polynucleotide comprises a polynucleotide sequence selected from the group consisting of SEQ ID NO:28-54, the method comprising a) exposing a sample comprising the target polynucleotide to a compound, b) detecting altered expression of the target polynucleotide, and c) comparing the expression of the target polynucleotide in the presence of varying amounts of the compound and in the absence of the compound. Another embodiment provides a method for assessing toxicity of a test compound, said method comprising a) treating a biological sample containing nucleic acids with the test compound; b) hybridizing the nucleic acids of the treated biological sample with a probe comprising at least 20 contiguous nucleotides of a polynucleotide selected from the group consisting of i) a polynucleotide comprising a polynucleotide sequence selected from the group consisting of SEQ ID NO:28-54, ii) a polynucleotide comprising a naturally occurring polynucleotide sequence at least 90% identical or at least about 90% identical to a polynucleotide sequence selected from the group consisting of SEQ ID NO:28-54, iii) a polynucleotide having a sequence complementary to i), iv) a polynucleotide complementary to the polynucleotide of ii), and v) an RNA equivalent of i)-iv). Hybridization occurs under conditions whereby a specific hybridization complex is formed between said probe and a target polynucleotide in the biological sample, said target polynucleotide selected from the group consisting of i) a polynucleotide comprising a polynucleotide sequence selected from the group consisting of SEQ ID NO:28-54, ii) a polynucleotide comprising a naturally occurring polynucleotide sequence at least 90% identical or at least about 90% identical to a polynucleotide sequence selected from the group consisting of SEQ ID NO:28-54, iii) a polynucleotide complementary to the polynucleotide of i), iv) a polynucleotide complementary to the polynucleotide of ii), and v) an RNA equivalent of i)-iv). Alternatively, the target polynucleotide can comprise a fragment of a polynucleotide selected from the group consisting of i)-v) above; c) quantifying the amount of hybridization complex; and d) comparing the amount of hybridization complex in the treated biological sample with the amount of hybridization complex in an untreated biological sample, wherein a difference in the amount of hybridization complex in the treated biological sample is indicative of toxicity of the test compound. detailed-description description="Detailed Description" end="lead"? |
Bioassay unit and substrate for bioassay |
To provide a bioassay system or the like, which can solve the problem of allocating spaces above detecting sections and can also stabilize servo-controlled operation of a disk-shaped plate. Provided is a bioassay system (U) or the like, which is equipped with at least means for immobilizing a nucleotide chain, a peptide, a protein, a lipid, a low molecular-weight compound, a liposome or any other biological substance as a detection substance (D) in a detecting section (3), dropping a target-substance containing solution (S) onto the immobilized detection substance (D), and causing the detection substance (D) and the target substance (T) to interact with each other to prepare a reaction product (R); and means for condensing fluorescence (F), which has been emitted from the fluorescence-labeled substance (D) by irradiating excitation light (P) of a specific wavelength onto the reaction product (R), by a lens (5) arranged on a side of a back surface (102) of the reaction section (3) to determine an intensity of the fluorescence (F). |
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