The methods and apparatuses herein relate to inkjet printing a substrate at a desired print resolution. A substrate advances at a first speed under the first printhead and the second printhead such that a desired print resolution exceeds the maximum print resolutions of a first printhead and a second printhead. When the substrate is advancing at the first speed, the first printhead ejects ink onto the advancing substrate at a first firing frequency to create a first printed zone, and the second printhead ejects ink onto the advancing substrate at a second firing frequency to create a second printed zone. In turn, the first printed zone and the second zone together define a printed region having the desired print resolution.

Along an assembly line, diapers and various types of other disposable absorbent articles may be assembled by adding components to and otherwise modifying advancing, continuous webs of material. Webs of material and component parts used to manufacture diapers may include: backsheets, topsheets, absorbent cores, front and/or back ears, fastener components, and various types of elastic webs and components such as leg elastics, barrier leg cuff elastics, and waist elastics. In some configurations, graphics are printed on individual components and/or continuous webs of material used to assemble the absorbent articles. The graphics may be provided by printing ink on substrate materials by various printing methods, such as flexographic printing, rotogravure printing, screen-printing, inkjet printing, and the like.
In some configurations, the printing operations are performed separate to the assembly process, such as for example, printing the substrates offline wherein the printed substrates may be stored until needed for production. For example, printing operations may be accomplished on discrete printing lines, separately from converting lines that are dedicated to manufacturing disposable absorbent articles. After printing on the printing lines, the printed substrates are delivered to the converting lines, such as in a form of continuous webs comprising printed images thereon. However, the above practice of separately printing the substrates offline from the converting lines typically requires additional cost associated with handling, winding and unwinding, storing and shipping of the substrates. In addition, the above steps can negatively affect the quality of the printed substrate, resulting in uneven and often excessive deformations of the wound layers of the substrate inside the roll due to uneven distribution of the compression forces inside the roll. Furthermore, the separately printed substrates often require special registration control methods to ensure proper phasing of the printed images with the converting operations to effect a desired and consistent positioning of the printed image in the produced article.
In an attempt to overcome the aforementioned drawbacks to offline printing, the graphic printing may be done online during the article assembly process. However, combining printing operations with converting operations may create other challenges in performing such printing processes when attempting to maintain aesthetically pleasing final assemblies. For example, contact printing processes, such as flexographic and rotogravure printing processes, may be capable of operating effectively on certain substrates at relatively high production rates. However, such contact printing processes have relatively low degrees of flexibility with regard to the ability to change the design of a printed graphic. When utilizing such contact printing methods, changes in graphic designs would often necessitate the shutdown and restart of the entire converting operation. In contrast, some types of printing processes, such as non-contact inkjet printing processes, may provide relatively high degrees of flexibility and ease with regard to the ability to change the design of a printed graphic. In some configurations, a change in graphic design can be implemented by simply inputting commands to a programmed printhead controller to select a desired image to be printed. However, such non-contact printing processes may have limited ability to print graphics at desired print resolutions at relatively high speed production rates.
For example, drop-on-demand inkjet printheads may be configured to discharge ink from orifices in the printhead onto an area of a substrate advancing in a machine direction MD beneath the printhead. Each time the printhead "fires," a drop of ink is discharged from an orifice. The frequency at which the printhead fires affects the print resolution in the machine direction of the printed area on the substrate in dots per inch (dpi). For a given machine direction substrate advancement speed, a higher firing frequency will yield a higher MD print resolution (dpi), and conversely, a lower firing frequency will yield a lower MD print resolution (dpi). Thus, depending on the MD advancement speed of a substrate, a printhead may be programmed to fire at a frequency high enough to achieve a desired MD print resolution. However, when utilizing such printheads in converting lines operating at high production rates, substrates may be required to advance at speeds past the printhead such that printhead would have to fire at frequency that would exceed the maximum frequency of the printhead in order to achieve the desired MD print resolution. As such, in some scenarios, the converting line would either have to operate at relatively lower production speeds to achieve the desired MD print resolutions, or operate at relatively higher production rates while printing graphics with less than desired MD print resolutions.
Consequently, there remains a need to configure converting lines with online non-contact printheads to print areas of substrates at desired MD print resolutions, wherein the converting lines are operable at relatively high productions speeds while printing desired MD print resolutions achievable above the maximum firing frequencies of the printheads.

Method and apparatus for inkjet printing absorbent article components at desired print resolutions


A system, a method, and a computer program product for monitoring of events and key figures are disclosed. An event in a plurality of events associated with a business process is identified. The identified event is monitored. A business value of the identified event is determined in real time. Based on the determined real-time business value, at least one key figure associated with the monitored event is retrieved and displayed in a user interface.

In today's world, data is vital to operations of many businesses, whether large or small. On regular basis, businesses rely, use, process and/or store vast amounts of data that can be related to businesses' finances, operations, logistics, customers, and many other aspects of their operations. Proper storage of data and fast access to such data are important to smooth operations of the businesses.
Occurrences and issues in a business process and system state often need to be made visible in a unified tool and, in addition, may need to be ranked based on importance of the business process to a particular business. The state of the business objects/data/systems may need to be evaluated at a point of time, such as, at the beginning and/or during investigation of various issues that may be associated with a business process. However, the conventional system do not provide for such evaluation and/or monitoring of issues that allow businesses real time determination of which issue to resolve first and how it would affect their operations.


A miniature motor including a electrically-conductive motor case is provided with a magnet fixedly fitted thereto. A non-electrically conductive case cover is provided holding a brushgear piece as a brush terminal piece. A ground terminal is provided in the form of an electrically conductive contacting piece in contact with case contacting piece. The electrically conductive contacting piece is formed into an essentially U shape. A case cover is provided with a groove for causing the tip of the case contacting piece to be plastically deformed providing electrical contact such that one of the brushes is electrically connected to the motor case via the ground terminal.

1 . Field of the Invention
This invention relates to a miniature motor, and more particularly to a miniature motor having such a construction that any one of the brushes of the brushgear is adapted to be electrically connected to the motor case.
2 . Description of the Pertinent Prior Art
A miniature motor to which this invention is applied has such a construction that a permanent magnet formed into an arc-segment shape is fixedly fitted in a case made of a metallic material, such as mild steel and formed into a bottomed hollow cylindrical shape; a rotor consisting of an armature and a commutator is rotatably fitted to the case; the open end of the case is engaged with a case cover made of an insulating material; and brushes made of an electrically conductive material are provided on the case cover; power being fed to the armature from brush terminals connected to a power source via the brushes and the commutator.
In d-c miniature motors having the aforementioned construction, for example, miniature motors used for automotive electrical components, it is often required that any one of the brush terminals be grounded after having been connected to an electrically conductive motor case.
The conventional method of grounding the miniature-motor body is as follows. A through-hole 8 through which a brush terminal piece 5 is protruded from the inside to the outside is provided on a case cover 7, as shown in FIG. 1 and the brush terminal piece 5 is passed through the through-hole 8 and fixedly fitted by inserting a leg of a split pin 13, made of an electrically conductive material and formed into an essentially U shape, into the through hole 8 from the inside of the case cover 7. After that, when the engaging surface of the case cover 7 is engaged with the motor case 1, another leg of the split pin 13 is forced onto the inside wall of the motor case 1, causing the brush having brush terminal piece 5 and the motor case 1 to be electrically connected.
Another conventional method is as Follows. A leg of the split pin 13 is spot-welded in advance to the motor case 1, and another leg of the split pin 13 is inserted into the through-hole 8 to fixedly fit and electrically connect the brush having the brush terminal piece 5 In FIG. 1, numeral 14 indicates a shouldered part with which the motor case 1 is engaged, and 15 a groove.
However, the construction in the former example, in which a leg of the split pin 13 is held by the motor case 1 and the case cover 7, is unstable in terms of electrical contact. The construction in the latter example, in which a leg of the split pin 13 is spot-welded to the motor case 1 can ensure stable electrical contact, but results in increased cost due to the spot-welding process involved. In addition, the spot welder has to be maintained at all times.


A flexible coupling for effecting a precisely aligned and repeatable blind mounting of the driver and driven halves thereof at a single time and in a single stage. The drive half can toggle and includes a plurality of multi-length teeth, and the driven half includes a rotatable disc member having a plurality of overlapping sloped slots for fully receiving and engaging the multi-length teeth of the driver half at the time and stage when the driven half is axially moved into the driver half by only a small axial force.

This invention relates to electrostatography, and more particularly to a flexible coupling for transmitting drive torque to a removably component, of an electrostatographic copier or printer, that may b be installed at one time, but not started up for operation unit a later time.
As disclosed for example in U.S. Pat. No. 2,295,003, it is well known to use flexible drive couplings for transmitting drive torque to a driven machine component. Such a coupling could be used for drive coupling a removable component such as copy sheet handling apparatus or development apparatus in an electrostatographic copier or printer, for example, to the main drive of such copier or printer.
Normally such a machine component is installed at one time, but not started up for operation until a later time, and such installation usually is accomplished in the blind. During such installations, the driver and driven halves of the coupling are also more likely, than not, to be misaligned, for example, rotationally. As a consequence, full engagement of the coupling halves is usually achieved in two different stages, at two different times.
Specifically, when the machine component such as the development apparatus above is being installed, a first stage of such two stage engagement will be to move the driven or load half of the coupling axially into the driver half of the coupling unit such axial motion is stopped. Unfortunately however, because of rotational misalignment, such axial motion-stopping contact may not represent full axial engagement between the coupling halves. As a consequence, a second stage involving some rotation of one of the halves at the later startup time, will be necessary in order to allow the driven half to move axially further into the driver half, thereby achieving full engagement.
Such two-stage, two-time engagement of a coupling have been found to result in undesirable shock loads or torque spikes, as well as, in self-defeating coupling wear of the mounting surfaces of the coupling halves. Torque spikes occur during the second stage because at the alter startup time the driver shaft must rotate, under a torque load, through some angle, before the two halves fully engage or close axially. During such rotation at such startup time, the driver half achieves an angular velocity, before the full load of the driven half is added thereto. As a consequence, the load of the driven component is added as a step function to the torque of the already moving driver shaft. The result is a shock load, that is, a torque transient or torque spike, on the driver shaft.
Such torque spikes usually are also transmitted backwards through the driver half, all the way back to the drive means, where they could undesirably interfere with the performance of other driven components int he machine. In the case of the development apparatus of an electrostatographic copier or printer, for example, such torque spikes can result in mechanical perturbations of the image development components of such copier or printer, and hence in defective or poor quality images.
In addition, self-defeating coupling wear of coupling surfaces occurs because final axial engagement motion between the driver and driven halves of the coupling occurs while torque is being transmitted by the moving driver shaft. Since the normal force on the engaging surfaces of the coupling halves is directly proportional to the torque being transmitted, the higher the torque load, the higher the coupling force must be in order to insure complete engagement. Such a high coupling force occurring before full or complete engagement of the force-transmitting surfaces of the coupling halves will undesirably result in a very high initial pressure on the initial and partial points of contacts of such forces.
As further axial penetration or movement occurs during this second stage of engagement, this torque-inflicted high force will be distributed over more and more of the force-transmitting surfaces until full penetration is achieved. Such high initial pressure results in self-defeating coupling wear of the initial points of contacts on such surfaces by gradually radiusing such points of initial contact, and thereby gradually sloping the surfaces. As such slopes increase, an axial force component that tends to defeat coupling by forcing the coupling halves open, begins to develop, and is experienced each time coupling or closing of the coupling halves is attempted.


The present invention provides a storage container containing one or more packets of toilet paper. The container is adapted to have at least part of a wall thereof removed to permit access to the contents of the container for removal thereof from the container and is provided with a device located on or adjacent an outer face of the container wall for preferentially releasing a scent or other volatile material externally of the container into the environment of the container and substantially not into the interior of the container. Preferably, the volatile material releasing device is adapted to be actuated to release the material prior to removal of the container wall to permit access to the contents of the container. The invention also provides a disc or the like carrying the volatile material enclosed thereon by a removable cover foil.

Rolls of toilet paper are typically sold in packs containing two, four or more rolls so that the purchaser has to store the rolls which are not immediately required, usually in an unwrapped condition once the outer wrapping for the packs has been removed to gain access to the first roll. However, in the interests of economy, the packaging for such packs of toilet rolls is flimsy and often has no aesthetic appeal. The spare rolls are therefore stored out of sight and often not within immediate reach of the toilet where they are required. For example, they may be stored under a kitchen sink or in an airing cupboard. However, such locations are often under conditions which adversely affect the quality of the tissue paper from which the toilet paper is made.
The manufacturers of such paper impose strict quality controls on moisture and on chemicals in the paper so that it is acceptable to touch and does not bring potentially hazardous chemicals into contact with sensitive skin. However, when stored by the user much of the quality control is negated, for example when unwrapped toilet rolls are stored in the immediate vicinity of bleach or other strong chemical or abrasive cleaners. Where an unwrapped roll is stored adjacent a hot water cylinder, the paper loses up to 5% of its weight in 12 hours as the moisture required to retain its soft texture evaporates.
It has been proposed to impregnate toilet paper with a scent composition, but this requires a change to the conventional toilet paper manufacturing techniques. It has also been proposed to incorporate a scent sachet or block into a toilet paper pack to impart a scent to the paper, see for example U.S. Pat. Nos. 3,711,024 and 4,513,862. However, the scent composition was either in direct contact with the toilet paper or was located so that it would permeate preferentially into the interior of the paper container rather than into the environment, so as to impart scent to the paper as it was being used.
Scent compositions typically contain aromatic oils and anti-oxidants and these can be strongly absorbed by toilet paper if they are allowed to come into contact with the paper. As a result, such impregnated papers could give rise to allergic reactions and discomfort for a user of the paper.
Furthermore, by impregnating the toilet paper itself or by locating the scent carrier inside the packing for the paper, the scent is only available after the package has been opened. As a result, such packages can not be used both to retain the characteristics of the paper, such as moisture content, and the integrity of the package against intrusion from chemicals in the environment (which require that the package remain closed); and to permit escape of a scent into the environment during storage prior to use (which requires that the package be opened). As a result, there is no incentive for a user to store a spare roll in the toilet since it could not release its scent until actually in use.
In British Patent No. 430,577 there is described a toilet paper holder which incorporates a perforated holder for a scent block which allows scent to permeate both onto the paper during use and into the environment around the holder. However, such a holder does not form part of the packaging for the toilet paper and requires that the packaging around the paper be at least partially removed prior to insertion of the paper into the holder. As a result, not only is the paper exposed during use to the scent composition, with the attendant risk of contamination of the paper, but the scent holder does not form part of the packaging within which the toilet paper is sold and stored prior to use, thus requiring that the holder be purchased as a separate item. Again, there is no incentive for a user to store a spare packet of toilet paper in the toilet.
I have devised a form of package for a toilet roll which reduces the above conflicting problems with existing designs and enables a toilet roll to be stored prior to use under controlled conditions (thus preserving its quality and protecting it against contamination), which can be made visually attractive and releases a scent into its environment prior to use (thus providing an incentive to a user to store a spare toilet roll in the toilet) without the need for the user to purchase anything other than the toilet roll and it packaging.


The present disclosure provides a gaming system, device, and method providing wild reel wager options for a spinning reel type wagering game. The wagering game includes: a plurality of reels; a plurality of symbols; and one or more wild reel wager options, each of which is associated with one of a plurality of wild reel wager amounts. If a player wagers one of the wild reel wager amounts on a play of the wagering game, the gaming system determines, based on the wild reel wager option associated with that wild reel wager amount, a set of one or more of the reels to be wild reels, and causes each of the determined set of the reels to be wild reels for that play. The gaming system causes each of the reels to spin and display one or more of the symbols, and provides any awards based on the displayed symbols.

Gaming machines that provide players awards in primary or base games are well known. These gaming machines generally require a player to place a wager to activate a play of the primary game. For many of these gaming machines, any award provided to a player for a wagered-on play of a primary game is based on the player obtaining a winning symbol or a winning symbol combination and on the amount of the wager (e.g., the higher the wager, the higher the award). Winning symbols or winning symbol combinations that are less likely to occur usually provide higher awards.
For such known gaming machines, the amount of the wager placed on the primary game by the player may vary. For instance, the gaming machine may enable the player to wager a minimum number of credits, such as one credit (e.g., one cent, nickel, dime, quarter, or dollar) up to a maximum quantity of credits, such as five credits. This wager may be placed by the player a single time or multiple times in a single play of the primary game. For instance, gaming machine configured to operate a slot game may have one or more paylines, and the gaming machine may enable a player to place a wager on each payline for a single play of the slot game. Thus, it is known that a gaming machine, such as one configured to operate a slot game, may enable players to place wagers of substantially different amounts on each play of the primary game ranging, for example, from one credit up to 125 credits (e.g., 5 credits on each of twenty-five separate paylines). This is also true for other wagering games, such as video draw poker, where players can place wagers of one or more credits on each hand, and where multiple hands can be played simultaneously. Accordingly, it should be appreciated that different players play at substantially different wagering amounts or levels and at substantially different rates of play.
Various slot games include a plurality of reels, at least one of which includes a plurality of wild symbols positioned adjacent to one another on the reel to form a stack or stacks of wild symbols on the reel. During play, the reels are spun and one or more of the wild symbols of the stack or stacks of wild symbols may be generated and displayed as a result of the spin of the reels. That is, for a spin of the reels, one or more wild symbols may or may not be generated and displayed. The fact that the wild symbols are not guaranteed to be generated for each spin of the reels may frustrate players, especially those who enjoy large amounts of action and a high hit frequency while playing slot games. Accordingly, there is a continuing need to provide new wagering games that enable players to guarantee that one or more wild symbols will be generated during game play.

This patent is subject to a terminal disclaimer.

Gaming system, gaming device, and method providing one or more wild reel wager options


Film forming areas for recording main information are formed on surfaces on which two substrates (11a, 11b) are adhered to an adhesive layer (3). An inner-circumference portion (18) adjacent to the film forming area as a main-information area (12a, 12b) of the substrate has an individual recognizing area (4a) for read only on an optical disk (10), to which identification information for uniquely recognizing the optical disk is recorded. The identification information is formed by recording a pattern having a predetermined difference in tint to the individual recognizing area on the optical disk by printing, before adhering the two substrates to the adhesive layer. The individual recognizing area on the optical disk may be provided at an outer-circumference portion adjacent to the film forming area as the main-information area on the substrate.

1. Field of the Invention
The present invention relates to an optical disk which is formed by adhering two surfaces for forming information to an adhesive layer. More particularly, the present invention relates to an optical disk having an individual recognizing function, which can be managed as a product easily and effectively and in which the falsification can be prevented.
2. Description of the Related Art
Distribution media such as an optical disk are widely used due to the large capacity and the low cost for forming pits. In particular, various applications are proposed with a CD (Compact Disk) and a DVD (Digital Video Disk) by using the large capacity thereof.
In accordance with the large capacity for storing data in the optical disk, a variety of copy managements are proposed so as to prevent an easy copy. However, hacking causes heavy damage to copy managements all over the world.
Under such a situation, data is recognized every disk and an illegal copy is prevented. Further, the management for each optical disk is regarded as important for improving the protection of contents, the higher copy management, and the security.
Referring to FIG. 1, an optical disk 110 is used as an optical disk having the above-mentioned individual recognizing function according to the related art. The optical disk 110 is formed by adhering to an adhesive layer 3, surfaces having aluminum film forming areas 112a and 112b made of thin aluminum films on two ring disk-shaped polycarbonate substrates 111a and 111b. Main information is recorded to the aluminum film forming areas 112a and 112b by using laser beams or the like. The main information is read by radiating reading beams which are condensed by a condenser lens 115.
As shown in FIG. 1, a management identifier area 117 of an optical disk lot is provided at a center-side peripheral of the aluminum film forming area 112b to which the main information is recorded, on an inner-circumference portion 118 of the ring disk-shaped polycarbonate substrate 111b. Management information such as title, order name, and lot number is recorded to the management identifier area 117 by printing. In the case of the above recording, linear information upon exposure is recorded to the corresponding area such as a number, a character, and a barcode upon exposing an optical disk stamper, as surface information which can visually be recognized in general. In the manufacturing after exposing the optical disk stamper, a CCD camera or the like identifies and manages the management information. Consequently, it is advantageous to prevent trouble such as the mixing of foreign materials by identifying the above management information.
Further, as disclosed in Japanese Unexamined Patent Application Publication No. 2000-163883, main information is recorded to an optical disk. Additional-information area data is also recorded to the optical disk. In the above-described optical disk, effectively, the copyright of contents is protected and illegal software operation is prevented.
Referring to FIG. 2, an optical disk disclosed in the above Publication will be described in followings. The optical disk 200 has a main-information area 212 and an additional-information area 213 in a substrate 211 thereof. The additional-information area 213 has an area for inhibiting the reading of the recorded data and a control area indicating whether information on the prohibition of reading is present or absent. A reading device of the optical disk 200 does not externally output the information on the prohibition of reading and, therefore, the information on the prohibition of reading is not downloaded when information except therefor is downloaded. As a consequence, the information on the prohibition of reading includes a cipher key for the main information, thereby preventing the normal reading of cipher data which is downloaded. If the information on the prohibition of reading might be read, a manufacturer can find an illegal source by including management information such as an order side in the information on the prohibition of reading.
The optical disk having the conventional individual recognizing function has a problem to erroneously operate the optical disk to which data to be downloaded excluding the main information is recorded.
The management information on each optical disk is not subjected to a specific countermeasure.
In the related art shown in FIG. 1, the optical disk records the management information such as the title, the order-side name, and the lot identification information. In the case that high-priced data contents are installed in a CD-ROM, a management number for each customer is additionally input to the above-described management information. However, actually, each optical disk is not subjected to detailed management. Therefore, an optical disk having another management information might erroneously be operated by inputting the management number of any customer.
In the related art shown in FIG. 2, although the illegal copy and the falsification of the recorded contents are prevented, the management measurement against the downloading of information to an erroneous area is not adopted.
To solve the above-described problems, it is an object of the present invention to provide an optical disk having an individual recognizing function for effectively managing each optical disk, which is suitable to product management for easily inhibiting the illegal use of manufactured and sold optical disks.
In the present invention, there is provided an optical disk having an individual recognizing function and a ring disk-shaped body, comprising a first substrate having a first principal surface, a second substrate having a second principal surface, an adhesive layer, principally. The adhesive layer is sandwiched between the first principal surface of the first substrate and the second principle surface of the second substrate and to which the first substrate and the second substrate are adhered. And a ring disk-shaped main-information area to which main information is recorded or is read by laser beams, provided on at least one of the first principal surface and the second principal surface. In the above-described optical disk having the individual recognizing function, at least one of the first principal surface and the second principal surface has an individual recognizing area. On the individual recognizing area, identification information for uniquely recognizing the optical disk is recorded before adhering the first substrate and the second substrate. The individual recognizing area is placed to at least one of an inner-circumference portion and an outer-circumference portion adjacent to the main-information area on the substrate. This position exists when the optical disk is perspectively viewed in the vertical direction of the first principal surface and the second principal surface. In the individual recognizing area, after adhering the first substrate and the second substrate to the adhesive layer, the identification information can be read but cannot be recorded and changed by using the laser beams used for recording or reading the main information to the main-information area.
That is, the optical disk in the present invention is formed by adhesion of at least two surfaces used for forming information to the adhesive layer. The optical disk has the individual recognizing area for read only. The individual recognizing area is placed to at least one of an inner-circumference portion and an outer-circumference portion adjacent to the main-information area on the substrate for recording the main information to one of the adhering surfaces. At the individual recognizing area, the identification information for uniquely recognizing the optical disk is recorded.
With the above-described structure, when the optical disk is loaded, the identification information for each optical disk can be uniquely read from the individual recognizing area on the optical disk by using, e.g., the reading beams. Therefore, the downloading destination can certainly be confirmed. It is possible to read the recorded main information by only the reading device having identification information which completely matches the above-described identification information for each optical disk.
That is, the security can be highly ensured by using the management and the identification of each optical disk. Not only by inputting a password but also by combining the identification of the optical disk and the password, a user is determined or authenticated. Simultaneously, the optical disk can safely be used while highly maintaining the confidentiality of data.
Preferably, the above-described identification information may be recorded and formed by printing a pattern having a predetermined difference in tint at the individual recognizing area. With the structure, the printed identification information can be read by the reading beams and, further, can visually be recognized by the difference in tint. Therefore, upon loading, the optical disk can be identified and can be checked in advance.
Preferably, the pattern having the predetermined difference in tint may be at least one of a character, a number, a barcode, and a drawing. Further, preferably, the printing may be any of screen printing, ink-jet printing, offset printing, and ink stamp.
Moreover, with the above-described structure, the identification information for each optical disk is recorded to the individual recognizing area on the substrate surface which is adhered to the adhesive layer by the printing so as to prevent the easy falsification of the optical disk. Thus, the optical disk must be broken to change the data of the optical disk on purpose. Therefore, the above-described structure becomes safe against the falsification.
Preferably, the above-described individual recognizing area may be adjacent to a management area which is provided at a circumference portion of the main-information area. Further, the individual recognizing area can function as a part of the management area.
When two surfaces for forming information are adhered to an adhesive layer, the optical disk may comprise an individual recognizing area for read only on one of the adhering surfaces and a film forming area on the other of the adhering surfaces. At the individual recognizing area, identification information for uniquely recognizing the optical disk is recorded to at least one of an inner-circumference portion and an outer-circumference portion adjacent to a main-information area for recording main information on the surfaces. The film forming area is used for covering the individual recognizing area. Preferably, the film forming area for covering the individual recognizing area may be formed as a part of the main-information area.
With the above-described structure, the film forming area is total reflection or half-transparent, and reaches the back of a reading-beam irradiated surface of the individual recognizing area. Therefore, it is possible to identify with a higher recognizing ratio and with high contrast, the recorded contents having the difference in tint. In particular, advantageously, information such as a printed mark is visually checked.
As mentioned above, advantages of the present invention are as follows.
According to a first advantage, the product management of the optical disk can easily be performed.
Because, in the processing for manufacturing the optical disk, the printing enables the area whose tint can visually be identified, including the character, the number, the barcode, the drawing, etc. to be formed at an area other than the main-information area. Further, the security can effectively be assured by recognizing and collating the formed area with the reading beams or combining the formed area and a specific password after the recognition and collation.
According to a second advantage, the optical disk cannot be falsified.
Because, in the processing for manufacturing the optical disk, the area capable of identifying each optical disk can be formed by the printing before adhesion of substrates. Thus, the data at the formed area of the completed optical disk cannot be falsified. If performing such a falsification that the adhesion of the substrates in the optical disk is peered and new data is recorded, the polycarbonate (PC) substrate is broken or mechanical characteristics are extremely deteriorated because the strength of adhesion is high. The reading of the optical disk becomes impossible. Actually, the optical disk becomes unavailable.

Optical disk having individual recognizing function


Electrical interconnects for integrated circuits and methods of fabrication of interconnects are provided. Devices are provided comprising copper interconnects having metallic liner layers comprising silver and a second component, such as, lanthanum, titanium, tungsten, zirconium, antimony, or calcium. Methods include providing a substrate having a trench or via formed therein, forming a silver alloy layer, comprising silver and a second component selected from the group consisting of lanthanum, titanium, tungsten, zirconium, antimony, and calcium, onto surfaces of the feature, depositing a copper seed layer, and depositing copper into the feature.

1. Field of the Invention
The embodiments of the present invention relate generally to semiconductor processing, integrated circuits, metal electrical interconnects, and liner layers for metal interconnects.
2. Background Information
The desire for ever-smaller integrated circuits (IC) places enormous performance demands on the materials used to construct IC devices. In general, an integrated circuit chip is also known as a microchip, a silicon chip, or a chip. IC chips are found in a variety of common devices, such as the microprocessors in computers, cars, televisions, CD players, and cellular phones. A plurality of IC chips are typically built on a silicon wafer (a thin silicon disk, having a diameter, for example of 300 mm) and after processing the wafer is diced apart to create individual chips. A 1 cm2 IC chip having feature sizes around of about 90 nm can comprise hundreds of millions of components. Current technologies are pushing feature sizes even smaller than 45 nm.


A cover for a substrate including: a body defining a cavity, for positioning over the substrate to form a reaction chamber; and a projection extending from the body to define a fluid reservoir, when the cover is fitted to the substrate, the fluid reservoir being in fluid communication with the cavity.

Microscope slides are commonly used to view samples of material under a microscope. The samples may contain human tissue, and may require treatment such as staining, so that properties of the sample can be identified. Other materials such as DNA, RNA, or proteins may be included on the slide.
It is common for several reactions to be undertaken on a sample on a slide. Once the reactions have taken place the slide may be viewed under a microscope. Performing the reactions on the slide can be difficult to automate, as the tissue samples require careful preparation and certain reactions require carefully controlled environments.

Microscope slide cover with integrated reservoir


A trailer adaped for a boat that includes a U-shaped chassis having wheels and a number of struts supported by the chassis and slings or the like oriented between struts coordinated in pairs is described. The slings support the boat by abutting against an outer surface of a boat hull. Also, the chassis may be formed by two flexurally rigid branches, each one turnably related and connected with a connecting part of a first end portion of each branch. Further selected struts may consist of one hydraulic piston-cylinder arrangement each. The piston-cylinder arrangements are hydraulically interconnected such that hydraulic oil may be distributed under an overpressure between the arrangements, in correlation with the rocking and/or rolling motion of the hull, including the twisting motion of the branches in relation to the ground and the twisting motion thereof in relation to the connecting part.

Methods and arrangements to construct trailers for boats are previously known in a number of different embodiments.
As an example of the background of the invention and the technical field to which the invention relates, it may be mentioned that, at least by public practice, previously a trailer adapted for a boat is known, having a chassis shaped like a "U", provided with wheels and having a number of vertically adjustable struts supported by the chassis and one or more carrying slings or the like oriented between struts coordinated in pairs, which slings are intended to let said boat be supported hanging in the same carrying slings by directly or indirectly abutting against an outer surface of a hull belonging to the boat.
Said chassis is formed by two flexurally rigid branches, each one being turnably related and connected with a connecting part of a first end portion of the respective branch and where at least one strut, out of a selected number of struts, consists of a hydraulically operating piston-cylinder arrangement, having the cylinder part facing towards and attached to the chassis and the piston part arranged movable up and down by means of a hydraulic oil supplied or drawn off via valve arrangements designed for this.
A trailer, of this category, has piston-cylinder arrangements coordinated in pairs, one pair for the stem of the boat, one or two pairs for the stern of the boat, and which are vertically adjustable in synchronism, in order to keep the hull of the boat hanging in carrying slings.
One or both of the astern carrying slings will come to carry the main part of the weight of the boat, with a larger friction effect activable between the carrying slings and the astern portion of the hull of the boat, while the forward carrying sling will come to carry a considerably lesser part of the weight of the boat, with a considerably lesser friction effect activable between the carrying sling and the forward portion of the hull of the boat.
This implies that a rocking or rolling of the hull of the boat, about a longitudinal axis assigned to the hull of the boat, caused primarily by a twisting of one branch relative the other branch in relation to the connecting part, will, by virtue of the lesser friction effect, create a relative motion between the forward carrying sling and the forward portion of the hull of the boat, a relative motion that normally may inflict larger or smaller damages to the forward portion of the hull of the boat as well as normally may inflict wear of the carrying sling.


This invention provides an isolated nucleic acid encoding a human MCH1 receptor, a purified human MCH1 receptor, vectors comprising isolated nucleic acid encoding a human MCH1 receptor, cells comprising such vectors, antibodies directed to a human MCH1 receptor, nucleic acid probes useful for detecting nucleic acid encoding human MCH1 receptors, antisense oligonucleotides complementary to unique sequences of nucleic acid encoding human MCH1 receptors, transgenic, nonhuman animals which express DNA encoding a normal or mutant human MCH1 receptor, methods of isolating a human MCH1 receptor, methods of treating an abnormality that is linked to the activity of a human MCH1 receptor, as well as methods of determining binding of compounds to mammalian MCH1 receptors.

Throughout this application, various publications are referenced in parentheses by author and year. Full citations for these references may be found at the end of the specification immediately preceding the sequence listings and the claims. The disclosure of these publications in their entireties are hereby incorporated by reference into this application to describe more fully the state of the art to which this invention pertains.
Neuroregulators comprise a diverse group of natural products that subserve or modulate communication in the nervous system. They include, but are not limited to, neuropeptides, amino acids, biogenic amines, lipids and lipid metabolites, and other metabolic byproducts. Many of these neuroregulator substances interact with specific cell surface receptors which transduce signals from the outside to the inside of the cell. G-protein coupled receptors (GPCRs) represent a major class of cell surface receptors with which many neurotransmitters interact to mediate their effects. GPCRs are predicted to have seven membrane-spanning domains and are coupled to their effectors via G-proteins linking receptor activation with intracellular biochemical sequelae such as stimulation of adenylyl cyclase.
Melanin-concentrating hormone (MCH) is a cyclic peptide originally isolated from salmonid (teleost fish) pituitaries (Kawauchi et al., 1983). In fish the 17 amino acid peptide causes aggregation of melanin within the melanophores and inhibits the release of ACTH, acting as a functional antagonist of xcex1-MSH. Mammalian MCH (19 amino acids) is highly conserved between rat, mouse, and human, exhibiting 100% amino acid identity, but its physiological roles are less clear. MCH has been reported to participate in a variety of processes including feeding, water balance, energy metabolism, general arousal/attention state, memory and cognitive functions, and psychiatric disorders (for reviews, see Baker, 1991; Baker, 1994; Nahon, 1994; Knigge et al., 1996). Its role in feeding or body weight regulation is supported by a recent Nature publication (Qu et al., 1996) demonstrating that MCH is overexpressed in the hypothalamus of ob/ob mice compared with ob/+mice, and that fasting further increased MCH mRNA in both obese and normal mice during fasting. MCH also stimulated feeding in normal rats when injected into the lateral ventricles (Rossi et al., 1997). MCH also has been reported to functionally antagonize the behavioral effects of xcex1-MSH (Miller et al., 1993; Gonzalez et al, 1996; Sanchez et al., 1997); in addition, stress has been shown to increase POMC mRNA levels while decreasing the MCH precursor preproMCH (ppMCH) mRNA levels (Presse et al., 1992). Thus MCH may serve as an integrative neuropeptide involved in the reaction to stress, as well as in the regulation of 1feeding and sexual activity (Baker, 1991; Knigge et al., 1996).
The gene encoding the MCH precursor (ppMCH) has been cloned and encodes two additional peptidies, neuropeptide EI (13 AA) and neuropeptide GE (19AA) (Nahon et al., 1989), which may also have biological activity. MCH peptide is synthesized primarily in hypothalamic neurons (the zona incerta and lateral hypothalamus) which project diffusely to many brain areas and to the pituitary (Bittencourt et al., 1992); NEI has also been identified in medium from explanted hypothalamic neurons (Parkes and Vale, 1993). Localization studies of the MRNA indicate that MCH is also present in the periphery (testes and GI tract; Hervieu and Nahon, 1995) but the highest concentrations are in the hypothalamus. There is also evidence for differential tissue-dependent processing of proMCH in mammals. A shorter MCH gene transcript that may result from alternate splicing was found in several brain areas and peripheral tissues, and a different peptide form was also found in the periphery (Viale et al., 1997). In humans, the gene encoding authentic MCH has been localized to chromosome 12, but two copies of a variant (truncated) gene are present on chromosome 5 (Breton et al., 1993); the functional significance, if any, of the variant is not yet known. Finally, the rat MCH gene may encode an additional putative peptide in a different reading frame (Toumaniantz et al., 1996).
Although the biological effects of MCH are believed to be mediated by specific receptors, binding sites for MCH have not been well described. A tritiated ligand ([3H]-MCH) was reported to exhibit specific binding to brain membranes but was unusable for saturation analyses, so neither affinity nor Bmax were determined (Drozdz and Eberle, 1995). Radioiodination of the tyrosine at position thirteen resulted in a ligand with dramatically reduced biological activity (see Drozdz and Eberle, 1995). In contrast, the radioiodination of the MCH analogue [Phe13,Tyr19]-MCH was successful (Drozdz et al., 1995); the ligand retained biological activity and exhibited specific binding to a variety of cell lines including mouse melanoma (B16-F1, G4F, and G4F-7), PC12, and COS cells. In G4F-7 cells, the KD=0.118 nM and the Bmax xcx9c1100 sites/cell. Importantly, the binding was not inhibited by xcex1-MSH but was weakly inhibited by rat ANF (Ki=116 nM vs. 12 nM for native MCH) (Drozdz et al., 1995). More recently specific MCH binding was reported in transformed keratinocytes (Burgaud et al., 1997) and melanoma cells (Drozdz et al., 1998), where photo-crosslinking studies suggest that the receptor is a membrane protein with an apparent molecular weight of 45-50 kDaltons, compatible with the molecular weight range of the GPCR superfamily of receptors. No radioautoradiographic studies of MCH receptor localization using this ligand have been reported as yet.
Signal transduction mechanisms for MCH receptors remain obscure. No direct evidence supporting G-protein coupling exists in mammals, but two lines of weak evidence exist in teleost fish for Gxcex1q- and/or Gxcex1i-type coupling: 1) indirect evidence exists for MCH acting via phospholipase C in teleost fish melanophores (phospholipase C inhibitors and protein kinase C inhibitors shift the MCH dose-response curve to the right, and TPA mimics MCH at low doses (Abrao et al., 1991)); and 2) MCH-elicited pigment aggregation in fish melanophores is associated with a reduction in basal cAMP levels, similar to that observed with norepinephrine (Svensson et al., 1991; Morishita et al., 1993). Arguing against G-protein coupling is the general structural homology of MCH with ANF, whose receptors are not in the GPCR superfamily. Recently the actions of MCH were reported to be mediated via activation of a phosphatidylinositol-3-kinase pathway which is typical of tyrosine kinase and cytokine receptors (Qu et al., 1998); however, since multiple signaling pathways (receptor cross talk) may produce this mediator no conclusions can be reached regarding MCH signal transduction pathways in mammalian systems.
The localization and biological activities of MCH peptide suggest that the modulation of MCH receptor activity may be useful in a number of therapeutic applications. The role of MCH in feeding is the best characterized of its potential clinical uses. MCH is expressed in the lateral hypothalamus, a brain area implicated in the regulation of thirst and hunger (Grillon et al., 1997); recently orexins A and B, which are potent orexigenic agents, have been shown to have very similar localization to MCH in the lateral hypothalamus (Sakurai et al., 1998). MCH mRNA levels in this brain region are increased in rats after 24 hours of food-deprivation (Hervxc3xa9 and Fellman, 1997); after insulin injection, a significant increase in the abundance and staining intensity of MCH immunoreactive perikarya and fibres was observed concurrent with a significant increase in the level of MCH MRNA (Bahjaoui-Bouhaddi et al., 1994). Consistent with the ability of MCH to stimulate feeding in rats (Rossi et al., 1997) is the observation that MCH MRNA levels are upregulated in the hypothalami of obese ob/ob mice (Qu et al., 1996), and decreased in the hypothalami of rats treated with leptin, whose food intake and body weight gains are also decreased (Sahu, 1998). MCH appears to act as a functional antagonist of the melanocortin system in its effects on food intake and on hormone secretion within the HPA (hypothalamopituitary/adrenal axis) (Ludwig et al., 1998). Together these data suggest a role for endogenous MCH in the regulation of energy balance and response to stress, and provide a rationale for the development of specific compounds acting at MCH receptors for use in the treatment of obesity and stress-related disorders.
In all species studied to date, a major portion of the neurons of the MCH cell group occupies a rather constant location in those areas of the lateral hypothalamus and subthalamus where they lie and may be a part of some of the so-called xe2x80x9cextrapyramidalxe2x80x9d motor circuits. These involve substantial striato- and pallidofugal pathways involving the thalamus and cerebral cortex, hypothalamic areas, and reciprocal connections to subthalamic nucleus, substantia nigra, and mid-brain centers (Bittencourt et al., 1992). In their location, the MCH cell group may offer a bridge or mechanism for expressing hypothalamic visceral activity with appropriate and coordinated motor activity. Clinically it may be of some value to consider the involvement of this MCH system in movement disorders, such as Parkinson""s disease and Huntingdon""s Chorea in which extrapyramidal circuits are known to be involved.
Human genetic linkage studies have located authentic hMCH loci on chromosome 12 (12q23-24) and the variant hMCH loci on chromosome 5 (5q12-13) (Pedeutour et al., 1994). Locus 12q23-24 coincides with a locus to which autosomal dominant cerebellar ataxia type II (SCA2) has been mapped (Auburger et al., 1992; Twells et al., 1992). This disease comprises neurodegenerative disorders, including an olivopontocerebellar atrophy. Furthermore, the gene for Darier""s disease, has been mapped to locus 12q23-24 (Craddock et al., 1993). Dariers"" disease is characterized by abnormalities I keratinocyrte adhesion and mental illnesses in some families. In view of the functional and neuroanatomical patterns of the MCH neural system in the rat and human brains, the MCH gene may represent a good candidate for SCA2 or Darier""s disease. Interestingly, diseases with high social impact have been mapped to this locus. Indeed, the gene responsible for chronic or acute forms of spinal muscular atrophies has been assigned to chromosome 5q12-13 using genetic linkage analysis (Melki et al., 1990; Westbrook et al., 1992). Furthermore, independent lines of evidence support the assignment of a major schizophrenia locus to chromosome 5q11.2-13.3 (Sherrington et al., 1988; Bassett et al., 1988; Gilliam et al., 1989). The above studies suggest that MCH may play a role in neurodegenerative diseases and disorders of emotion.
Additional therapeutic applications for MCH-related compounds are suggested by the observed effects of MCH in other biological systems. For example, MCH may regulate reproductive functions in male and female rats. MCH transcripts and MCH peptide were found within germ cells in testes of adult rats, suggesting that MCH may participate in stem cell renewal and/or differentiation of early spermatocytes (Hervieu et al., 1996). MCH injected directly into the medial preoptic area (MPOA) or ventromedial nucleus (VMN) stimulated sexual activity in female rats (Gonzalez et al., 1996). In ovariectomized rats primed with estradiol, MCH stimulated luteinizing hormone (LH) release while anti-MCH antiserum inhibited LH release (Gonzalez et al., 1997). The zona incerta, which contains a large population of MCH cell bodies, has previously been identified as a regulatory site for the pre-ovulatory LH surge (MacKenzie et al., 1984). MCH has been reported to influence release of pituitary hormones including ACTH and oxytocin. MCH analogues may also be useful in treating epilepsy. In the PTZ seizure model, injection of MCH prior to seizure induction prevented seizure activity in both rats and guinea pigs, suggesting that MCH-containing neurons may participate in the neural circuitry underlying PTZ-induced seizure (Knigge and Wagner, 1997). MCH has also been observed to affect behavioral correlates of cognitive functions. MCH treatment hastened extinction of the passive avoidance response in rats (McBride et al., 1994), raising the possibility that MCH receptor antagonists may be beneficial for memory storage and/or retention. A possible role for MCH in the modulation or perception of pain is supported by the dense innervation of the periaqueductal grey (PAG) by MCH-positive fibers. Finally, MCH may participate in the regulation of fluid intake. ICV infusion of MCH in conscious sheep produced diuretic, natriuretic, and kaliuretic changes in response to increased plasma volume (Parkes, 1996). Together with anatomical data reporting the presence of MCH in fluid regulatory areas of the brain, the results indicate that MCH may be an important peptide involved in the central control of fluid homeostasis in mammals.
This invention provides an isolated nucleic acid encoding a human MCH1 receptor or a mutant of such human MCH1 receptor which is activated by MCH or an analog or homolog thereof.
This invention provides a nucleic acid encoding a human MCH1 receptor, wherein the nucleic acid (a) hybridizes to a nucleic acid having the defined sequence shown in FIG. 1 (SEQ ID NO: 1) under low stringency conditions or a sequence complementary thereto and (b) is; further characterized by its ability to cause a change in the pH of a culture of CHO cells when an MCH1 ligand is added to the culture and the CHO cells contain the nucleic acid which hybridized to the nucleic acid having the defined sequence or its complement.
This invention provides a purified human MCH1 receptor protein.
This invention provides a vector comprising a nucleic acid encoding a human MCH1 receptor, particularly a vector adapted for expression of the human MCH1 receptor in mammalian or non-mammalian cells. One such vector is a plasmid designated pEXJ.HR-TL231 (ATCC Accession No. 203197) which comprises a nucleotide sequence encoding a human MCH1 receptor.
This invention also provides a cell comprising a vector which comprises a nucleic acid encoding a human MCH1 receptor as well as a membrane preparation isolated from such cells.
This invention further provides a nucleic acid probe comprising at least 15 nucleotides which specifically hybridizes with a nucleic acid encoding a mammalian MCH1 receptor, wherein the probe has a unique sequence corresponding to a sequence present within the nucleic acid which encodes the human MCH1 receptor or its complement, both of which are present in plasmid pEXJ.HR-TL231 (ATCC Accession No. 203197).
This invention further provides a nucleic acid probe comprising at least 15 nucleotides which specifically hybridizes with a nucleic acid encoding a mammalian MCH1 receptor, wherein the probe has a unique sequence corresponding to a sequence present within (a) the nucleic acid sequence shown in FIG. 1 (SEQ ID NO: 1) or (b) the reverse complement thereof.
This invention also provides an antisense oligonucleotide having a sequence capable of specifically hybridizing an RNA encoding a human MCH1 receptor, so as to prevent translation of the RNA and an antisense oligonucleotide having a sequence capable of specifically hybridizing to the genomic DNA encoding a human MCH1 receptor.
This invention further provides an antibody capable of binding to a human MCH1 receptor as well as an agent capable of competitively inhibiting the binding of the antibody to a human MCH1 receptor.
This invention provides a pharmaceutical composition comprising (a) an amount of the oligonucleotide described above capable of passing through a cell membrane and effective to reduce expression of a human MCH1 receptor and (b) a pharmaceutically acceptable carrier capable of passing through the cell membrane.
Moreover, this invention provides a transgenic, nonhuman mammal expressing DNA encoding a human MCH1 receptor. This invention also provides a transgenic, nonhuman mammal comprising a homologous recombination knockout of the native human MCH1 receptor. This invention further provides a transgenic, nonhuman mammal whose genome comprises antisense DNA complementary to the DNA encoding a human MCH1 receptor so placed within the genome as to be transcribed into antisense mRNA which is complementary to MRNA encoding the human MCH1 receptor and which hybridizes to mRNA encoding the human MCH1 receptor, thereby reducing its translation.
In one embodiment this invention provides a process for identifying a chemical compound which specifically binds to a mammalian MCH1 receptor which comprises contacting cells containing DNA encoding and expressing on their cell surface a mammalian MCH1 receptor, wherein such cells do not normally express the mammalian MCH1 receptor, with the compound under conditions suitable for binding, and detecting specific binding of the chemical compound to the mammalian MCH1 receptor.
This invention provides a process for identifying a chemical compound which specifically binds to a mammalian MCH1 receptor which comprises contacting a membrane preparation from cells transfected with DNA encoding and expressing on their cell surface the mammalian MCH1 receptor, wherein such cells do not normally express the mammalian MCH1 receptor, with the compound under conditions suitable for binding, and detecting specific binding of the chemical compound to the mammalian MCH1 receptor.
This invention provides a process involving competitive binding for identifying a chemical compound which specifically binds to a mammalian MCH1 receptor which comprises separately contacting cells expressing on their cell surface the mammalian MCH1 receptor, wherein such cells do not normally express the mammalian MCH1 receptor, with both the chemical compound and a second chemical compound known to bind to the receptor, and with only the second chemical compound, under conditions suitable for binding of both compounds, and detecting specific binding of the chemical compound to the mammalian MCH1 receptor, a decrease in the binding of the second chemical compound to the mammalian MCH1 receptor in the presence of the chemical compound indicating that the chemical compound binds to the mammalian MCH1 receptor.
This invention provides a process involving competitive binding for identifying a chemical compound which specifically binds to a mammalian MCH1 receptor which comprises separately contacting a membrane fraction from a cell extract of cells expressing on their cell surface the mammalian MCH1 receptor, wherein such cells do not normally express the mammalian MCH1 receptor, with both the chemical compound and a second chemical compound known to bind to the receptor, and with only the second chemical compound, under conditions suitable for binding of both compounds, and detecting specific binding of the chemical compound to the mammalian MCH1 receptor, a decrease in the binding of the second chemical compound to the mammalian MCH1 receptor in the presence of the chemical compound indicating that the chemical compound binds to the mammalian MCH1 receptor.
This invention provides a method of screening a plurality of chemical compounds not known to bind to a mammalian MCH1 receptor to identify a compound which specifically binds to the mammalian MCH1 receptor, which comprises (a) contacting cells transfected with and expressing DNA encoding the mammalian MCH1 receptor with a compound known to bind specifically to the mammalian MCH1 receptor; (b) contacting the preparation of step (a) with the plurality of compounds not known to bind specifically to the mammalian MCH1 receptor, under conditions permitting binding of compounds known to bind the mammalian MCH1 receptor; (c) determining whether the binding of the compound known to bind to the mammalian MCH1 receptor is reduced in the presence of the compounds within the plurality of compounds, relative to the binding of the compound in the absence of the plurality of compounds; and if so (d) separately determining the binding to the mammalian MCH1 receptor of compounds included in the plurality of compounds, so as to thereby identify the compound which specifically binds to the mammalian MCH1 receptor.
This invention provides a method of screening a plurality of chemical compounds not known to bind to a mammalian MCH1 receptor to identify a compound which specifically binds to the mammalian MCH1 receptor, which comprises (a) contacting a membrane preparation from cells transfected with and expressing DNA encoding a mammalian MCH1 receptor with a compound known to bind specifically to the mammalian MCH1 receptor; (b) contacting the preparation of step (a) with the plurality of compounds not known to bind specifically to the mammalian MCH1 receptor, under conditions permitting binding of compounds known to bind the mammalian MCH1 receptor; (c) determining whether the binding of the compound known to bind to the mammalian MCH1 receptor is reduced in the presence of the compounds within the plurality of compounds, relative to the binding of the compound in the absence of the plurality of compounds; and if so (d) separately determining the binding to the mammalian MCH1 receptor of compounds included in the plurality of compounds, so as to thereby identify the compound which specifically binds to the mammalian MCH1 receptor.
This invention provides a method of detecting expression of a mammalian MCH1 receptor by detecting the presence of MRNA coding for the mammalian MCH1 receptor which comprises obtaining total mRNA from the cell and contacting the MRNA so obtained with a nucleic acid probe under hybridizing conditions, detecting the presence of MRNA hybridizing to the probe, and thereby detecting the expression of the mammalian MCH1 receptor by the cell.
This invention provides a method of detecting the presence of a mammalian MCH1 receptor on the surface of a cell which comprises contacting the cell with an antibody under conditions permitting binding of the antibody to the receptor, detecting the presence of the antibody bound to the cell, and thereby detecting the presence of the mammalian MCH1 receptor on the surface of the cell.
This invention provides a method of determining the physiological effects of varying levels of activity of human MCH1 receptors which comprises producing a transgenic, nonhuman mammal whose levels of human MCH1 receptor activity are varied by use of an inducible promoter which regulates human MCH1 receptor expression.
This invention provides a method of determining the physiological effects of varying levels of activity of human MCH1 receptors which comprises producing a panel of transgenic, nonhuman mammals each expressing a different amount of human MCH1 receptor.
This invention provides a method for identifying an antagonist capable of alleviating an abnormality wherein the abnormality is alleviated by decreasing the activity of a human MCH1 receptor comprising administering a compound to the transgenic, nonhuman mammal and determining whether the compound alleviates the physical and behavioral abnormalities displayed by the transgenic, nonhuman mammal as a result of overactivity of a human MCH1 receptor, the alleviation of the abnormality identifying the compound as an antagonist. This invention also provides an antagonist identified by this method. This invention further provides a pharmaceutical composition comprising an antagonist identified by this method and a pharmaceutically acceptable carrier.
This invention provides a method of treating an abnormality in a subject wherein the abnormality is alleviated by decreasing the activity of a human MCH1 receptor which comprises administering to the subject an effective amount of this pharmaceutical composition, thereby treating the abnormality.
This invention provides a method for identifying an agonist capable of alleviating an abnormality in a subject wherein the abnormality is alleviated by increasing the activity of a human MCH1 receptor comprising administering a compound to a transgenic, nonhuman mammal, and determining whether the compound alleviates the physical and behavioral abnormalities displayed by the transgenic, nonhuman mammal, the alleviation of the abnormality identifying the compound as an agonist. This invention also provides an agonist identified by this method. This invention further provides a pharmaceutical composition comprising an agonist identified by this method and a pharmaceutically acceptable carrier. This invention provides a method of treating an abnormality in a subject wherein- the abnormality is alleviated by increasing the activity of a human MCH1 receptor which comprises administering to the subject an effective amount of this pharmaceutical composition, thereby treating the abnormality.
This invention provides a method for diagnosing a predisposition to a disorder associated with the activity of a specific mammalian allele which comprises: (a) obtaining DNA of subjects suffering from the disorder; (b) performing a restriction digest of the DNA with a panel of restriction enzymes; (c) electrophoretically separating the resulting DNA fragments on a sizing gel; (c,) contacting the resulting gel with a nucleic acid probe capable of specifically hybridizing with a unique sequence included within the sequence of a nucleic acid molecule encoding a human MCH1 receptor and labeled with a detectable marker; (e) detecting labeled bands which have hybridized to the DNA encoding a human MCH1 receptor labeled with a detectable marker to create a unique band pattern specific to the DNA of subjects suffering from the disorder; (f) preparing DNA obtained for diagnosis by steps (a)-( e); and (g) comparing the unique band pattern specific to the DNA of subjects suffering from the disorder from step (e) and the DNA obtained for diagnosis from step (f) to determine whether the patterns are the same or different and to diagnose thereby predisposition to the disorder if the patterns are the same.
This invention provides a method of preparing a purified human MCH1 receptor which comprises: (a) inducing cells to express the human MCH1 receptor; (b) recovering the human MCH1 receptor from the induced cells; and (c) purifying the human MCH1 receptor so recovered.
This invention provides a method of preparing a purified human MCH1 receptor which comprises: (a)inserting nucleic acid encoding the human MCH1 receptor in a suitable vector; (b) introducing the resulting vector in a suitable host cell; (c) placing the resulting cell in suitable condition permitting the production of the isolated human MCH1 receptor; (d) recovering the human MCH1 receptor produced by the resulting cell; and (e) purifying the human MCH1 receptor so recovered.
This invention provides a process for determining whether a chemical compound is a mammalian MCH1 receptor agonist which comprises contacting cells transfected with and expressing DNA encoding the mammalian MCH1 receptor with the compound under conditions permitting the activation of the mammalian MCH1 receptor, and detecting an increase in mammalian MCH1 receptor activity, so as to thereby determine whether the compound is a mammalian MCH1 receptor agonist. This invention also provides a pharmaceutical composition which comprises an amount of a mammalian MCH1 receptor agonist determined by this process effective to increase activity of a mammalian MCH1 receptor and a pharmaceutically acceptable carrier.
This invention provides a process for determining whether a chemical compound is a mammalian MCH1 receptor antagonist which comprises contacting cells transfected with and expressing DNA encoding the mammalian MCH1 receptor with the compound in the presence of a known mammalian MCH1 receptor agonist, under conditions permitting the activation of the mammalian MCH1 receptor, and detecting a decrease in mammalian MCH1 receptor activity, so as to thereby determine whether the compound is a mammalian MCH1 receptor antagonist. This invention also provides a pharmaceutical composition which comprises an amount of a mammalian MCH1 receptor antagonist determined by this process effective to reduce activity of a mammalian MCH1 receptor and a pharmaceutically acceptable carrier.
This invention provides a process for determining whether a chemical compound specifically binds to and activates a mammalian MCH1 receptor, which comprises contacting cells producing a second messenger response and expressing on their cell surface the mammalian MCH1 receptor, wherein such cells do not normally express the mammalian MCH1 receptor, with the chemical compound under conditions suitable for activation of the mammalian MCH1 receptor, and measuring the second messenger response in the presence and in the absence of the chemical compound, a change in the second messenger response in the presence of the chemical compound indicating that the compound activates the mammalian MCH1 receptor. This invention also provides a compound determined by this process. This invention further provides a pharmaceutical composition which comprises an amount of the compound (a MCH1 receptor agonist) determined by this process effective to increase activity of a mammalian MCH1 receptor and a pharmaceutically acceptable carrier.
This invention provides a process for determining whether a chemical compound specifically binds to and inhibits activation of a mammalian MCH1 receptor, which comprises separately contacting cells producing a second messenger response and expressing on their cell surface the mammalian MCH1 receptor, wherein such cells do not normally express the mammalian MCH1 receptor, with both the chemical compound and a second chemical compound known to activate the mammalian MCH1 receptor, and with only the second chemical compound, under conditions suitable for activation of the mammalian MCH1 receptor, and measuring the second messenger response in the presence of only the second chemical compound and in the presence of both the second chemical compound and the chemical compound, a smaller change in the second messenger response in the presence of both the chemical compound and the second chemical compound than in the presence of only the second chemical compound indicating that the chemical compound inhibits activation of the mammalian MCH1 receptor. This invention also provides a compound determined by this process. This invention further provides a pharmaceutical composition which comprises an amount of the compound (a mammalian MCH1 receptor antagonist) determined by this effective to reduce activity of a mammalian MCH1 receptor and a pharmaceutically acceptable carrier.
This invention provides a method of screening a plurality of chemical compounds not known to activate a mammalian MCH1 receptor to identify a compound which activates the mammalian MCH1 receptor which comprises: (a) contacting cells transfected with and expressing the mammalian MCH1 receptor with the plurality of compounds not known to activate the mammalian MCH1 receptor, under conditions permitting activation of the mammalian MCH1 receptor; (b) determining whether the activity of the mammalian MCH1 receptor is increased in the presence of the compounds; and if so (c) separately determining whether the activation of the mammalian MCH1 receptor is increased by each compound included in the plurality of compounds, so as to thereby identify the compound which activates the mammalian MCH1 receptor. This invention also provides a compound identified by this method. This invention further provides a pharmaceutical composition which comprises an amount of the compound (a mammalian MCH1 receptor agonist) identified by this method effective to increase activity of a mammalian MCH1 receptor and a pharmaceutically acceptable carrier.
This invention provides a method of screening a plurality of chemical compounds not known to inhibit the activation of a mammalian MCH1 receptor to identify a compound which inhibits the activation of the mammalian MCH1 receptor, which comprises: (a) contacting cells transfected with and expressing the mammalian MCH1 receptor with the plurality of compounds in the presence of a known mammalian MCH1 receptor agonist, under conditions permitting activation of the mammalian MCH1 receptor; (b) determining whether the activation of the mammalian MCH1 receptor is reduced in the presence of the plurality of compounds, relative to the activation of the mammalian MCH1 receptor in the absence of the plurality of compounds; and if so (c) separately determining the inhibition of activation of the mammalian MCH1 receptor for each compound included in the plurality of compounds, so as to thereby identify the compound which inhibits the activation of the mammalian MCH1 receptor. This invention also provides a compound identified by this method. This invention further provides a pharmaceutical composition which comprises an amount of the compound (a mammalian MCH1 receptor antagonist) identified by this process effective to decrease activity of a mammalian MCH1 receptor and a pharmaceutically acceptable carrier.
This invention provides a method of treating an abnormality in a subject wherein the abnormality is alleviated by increasing the activity of a mammalian MCH1 receptor which comprises administering to the subject an amount of a compound which is a mammalian MCH1 receptor agonist effective to treat the abnormality.
This invention provides a method of treating an abnormality in a subject wherein the abnormality is alleviated by decreasing the activity of a mammalian MCH1 receptor which comprises administering to the subject an amount of a compound which is a mammalian MCH1 receptor antagonist effective to treat the abnormality.
This invention provides a process for making a composition of matter which specifically binds to a mammalian MCH1 receptor which comprises identifying a chemical compound using any of the processes described herein for identifying a compound which binds to and/or activates or inhibits activation of a mammalian MCH1 receptor and then synthesizing the chemical compound or a novel structural and functional analog or homolog thereof. This invention further provides a process for preparing a pharmaceutical composition which comprises administering a pharmaceutically acceptable carrier and a pharmaceutically acceptable amount of a chemical compound identified by any of the processes described herein for identifying a compound which binds to and/or activates or inhibits activation of a mammalian MCH1 receptor or a novel structural and functional analog or homolog thereof.
This invention provides a process for determining whether a chemical compound is a human MCH1 receptor antagonist which comprises contacting cells transfected with and expressing DNA encoding the human MCH1 receptor with the compound in the presence of a known human MCH1 receptor agonist, under conditions permitting the activation of the human MCH1 receptor, and detecting a decrease in human MCH1 receptor activity, so as to thereby determine whether the compound is a human MCH1 receptor antagonist, wherein the DNA encoding the human MCH1 receptor comprises the sequence shown in FIG. 1 (Seq. ID No. 1) or contained in plasmid pEXJ.HR-TL231 (ATCC Accession No. 203197), the known human MCH1 receptor agonist is MCH or a homolog or analog of MCH, and the cells do not express the MCH1 receptor prior to transfecting them.
This invention also provides a process for determining whether a chemical compound specifically binds to and inhibits activation of a human MCH1 receptor, which comprises separately contacting cells expressing on their cell surface the human MCH1 receptor and producing a second messenger response upon activation of the human MCH1 receptor, wherein such cells do not normally express the human MCH1 receptor and the DNA encoding the human MCH1 receptor comprises the sequence shown in FIG. 1 (Seq. ID No. 1) or contained in plasmid pE.XJ.HR-TL231 (ATCC Accession No. 203197), with both the chemical compound and a second chemical compound known to activate the human MCH1 receptor, and with only the second chemical compound, under conditions suitable for activation of the human MCH1 receptor, and measuring the second messenger response in the presence of only the second chemical compound and in the presence of both the second chemical compound and the chemical compound, a smaller change in the second messenger response in the presence of both the chemical compound and the second chemical compound than in the presence of only the second chemical compound indicating that the chemical compound inhibits activation of the human MCH1 receptor, wherein the second chemical compound is MCH or a homolog or analog of MCH.
This invention further provides a method of screening a plurality of chemical compounds not known to inhibit the activation of a human MCH1 receptor to identify a compound which inhibits the activation of the human MCH1 receptor, which comprises:
(a) contacting cells transfected with and expressing the human MCH1 receptor, wherein such cells do not normally express the human MCH1 receptor and the DNA encoding the human MCH1 receptor comprises the sequence shown in FIG. 1 (Seq. ID No. 1) or contained in plasmid pEXJ.HR-TL231 (ATCC Accession No. 203197), with the plurality of compounds in the presence of a known human MCH1 receptor agonist, under conditions permitting activation of the human MCH1 receptor, wherein the known MCH1 receptor agonist is MCH or a homolog or analog of MCH;
(b) determining whether the activation of the human MCH1 receptor is reduced in the presence of the plurality of compounds, relative to the activation of the human MCH1 receptor in the absence of the plurality of compounds; and if so
(c) separately determining the extent of inhibition of activation of the human MCH1 receptor for each compound included in the plurality of compounds, so as to thereby identify the compound which inhibits the activation of the human MCH1 receptor.
This invention provides a process for making a composition of matter which specifically binds to a human MCH1 receptor which comprises identifying a chemical compound which specifically binds to the human MCH1 receptor and then synthesizing the chemical compound or a structural and functional analog or homolog thereof, wherein the chemical compound is identified as binding to the human MCH1 receptor by a process involving competitive binding which comprises contacting cells expressing on their cell surface the human MCH1 receptor, with both the chemical compound and a second chemical compound known to bind to the receptor, and separately with only the second chemical compound, under conditions suitable for binding of both compounds, and detecting the extent of specific binding of the chemical compound to the human MCH1 receptor, a decrease in the binding of the second chemical compound to the human MCH1 receptor in the presence of the chemical compound indicating that the chemical compound binds to the human MCH1 receptor, wherein the cells do not normally express the human MCH1 receptor, the human MCH1 receptor is encoded by nucleic acid comprising the sequence shown in FIG. 1 (Seq. ID No. 1) or contained in plasmid pEXJ.HR-TL231 (ATCC Accession No. 203197), and the second chemical compound is MCH or a homolog or analog of MCH.
This invention further provides a process for making a composition of matter which specifically binds to a human MCH1 receptor which comprises identifying a chemical compound which specifically binds to the human MCH1 receptor and then synthesizing the chemical compound or a structural and functional analog or homolog thereof, wherein the chemical compound is identified as binding to the human MCH1 receptor by a process involving competitive binding which comprises contacting a membrane preparation from cells expressing on their cell surface the human MCH1 receptor, with both the chemical compound and a second chemical compound known to bind to the receptor, and separately with only the second chemical compound, under conditions suitable for binding of both compounds, and detecting the extent of specific binding of the chemical compound to the human MCH1 receptor, a decrease in the binding of the second chemical compound to the human MCH1 receptor in the presence of the chemical compound indicating that the chemical compound binds to the human MCH1 receptor, wherein the cells do not normally express the human MCH1 receptor, the human MCH1 receptor is encoded by nucleic acid comprising the sequence shown in FIG. 1 (Seq. ID No. 1) or contained in plasmid pEXJ.HR-TL231 (ATCC Accession No. 203197), and the second chemical compound is MCH or a homolog or analog of MCH.
This invention also provides a process for making a composition of matter which is a human MCH1 receptor antagonist which comprises identifying a chemical compound which is a human MCH1 receptor antagonist and then synthesizing the chemical compound or a structural and functional analog or homolog thereof, wherein the chemical compound is identified as a human MCH1 receptor antagonist by a process which comprises contacting cells transfected with and expressing DNA encoding the human MCH1 receptor with the compound in the presence of a known human MCH1 receptor agonist, under conditions permitting the activation of the human MCH1 receptor, and detecting a decrease in human MCH1 receptor activity, so as to thereby determine whether the compound is a human MCH1 receptor antagonist, wherein the cells do not normally express the human MCH1 receptor, the human MCH1 receptor is encoded by nucleic acid comprising the sequence shown in FIG. 1 (Seq. ID No. 1) or contained in plasmid pEXJ.HR-TL231 (ATCC Accession No. 203197), and the known human MCH1 receptor agonist is MCH or a homolog or analog of MCH.
This inventions still further provides a process for making a composition of matter which specifically binds to and inhibits the activation of a human MCH1 receptor which comprises identifying a chemical compound which specifically binds to and inhibits the activation of the human MCH1 receptor and then synthesizing the chemical compound or a structural and functional analog or homolog thereof, wherein the chemical compound is identified as binding to and inhibiting the activation of the human MCH1 receptor by a process which comprises separately contacting cells expressing on their cell surface the human MCH1 receptor and producing a second messenger response upon activation of the human MCH1 receptor, wherein such cells do not normally express the human MCH1 receptor and the human MCH1 receptor is encoded by nucleic acid comprising the sequence shown in FIG. 1 (Seq. ID No. 1) or contained in plasmid pEXJ.HR-TL231 (ATCC Accession No. 203197), with both the chemical compound and a second chemical compound known to activate the human MCH1 receptor, and with only the second chemical compound, under conditions suitable for activation of the human MCH1 receptor, and measuring the second messenger response in the presence of only the second chemical compound and in the presence of both the second chemical compound and the chemical compound, a smaller change in the second messenger response in the presence of both the chemical compound and the second chemical compound than in the presence of only the second chemical compound indicating that the chemical compound inhibits activation of the human MCH1 receptor, wherein the second chemical compound is MCH or a homolog or analog of MCH.
This invention provides a process for preparing a composition which comprises identifying a chemical compound which specifically binds to a human MCH1 receptor, and then admixing a carrier and the chemical compound or a structural and functional analog or homolog thereof, wherein the chemical compound is identified as binding to the human MCH1 receptor by a process involving competitive binding which comprises contacting cells expressing on their cell surface the human MHC1 receptor, with both the chemical compound and a second chemical compound known to bind to the receptor, and separately with only the second chemical compound, under conditions suitable for binding of both compounds, and detecting the extent of specific binding of the chemical compound to the human MCH1 receptor, a decrease in the binding of the second chemical compound to the human MCH1 receptor in the presence of the chemical compound indicating that the chemical compound binds to the human MCH1 receptor, wherein the cells do not normally express the human MCH1 receptor, the human MCH1 receptor is encoded by nucleic acid comprising the sequence shown in FIG. 1 (Seq. ID No. 1) or contained in plasmid pEXJ.HR-TL231 (ATCC Accession No. 203197), and the second chemical compound is MCH or a homolog or analog of MCH.
This invention further provides a process for preparing a composition which comprises identifying a chemical compound which specifically binds to a human MCH1 receptor, and then admixing a carrier and the chemical compound or a structural and functional analog or homolog thereof, wherein the chemical compound is identified as binding to the human MCH1 receptor by a process involving competitive binding which comprises contacting a membrane preparation from cells expressing on their cell surface the human MCH1 receptor, with both the chemical compound and a second chemical compound known to bind to the receptor, and separately with only the second chemical compound, under conditions suitable for binding of both compounds, and detecting the extent of specific binding of the chemical compound to the human MCH1 receptor, a decrease in the binding of the second chemical compound to the human MCH1 receptor in the presence of the chemical compound indicating that the chemical compound binds to the human MCH1 receptor, wherein the cells do not normally express the human MCH1 receptor, the human MCH1 receptor is encoded by nucleic acid comprising the sequence shown in FIG. 1 (Seq. ID No. 1) or contained in plasmid pEXJ.HR-TL231 (ATCC Accession No. 203197), and the second chemical compound is MCH or a homolog or analog of MCH.
This invention also provides a process for preparing a composition which comprises identifying a chemical compound which is a human MCH1 receptor antagonist, and then admixing a carrier and the chemical compound or a structural and functional analog or homolog thereof, wherein the chemical compound is identified as a human MCH1 receptor antagonist by a process which comprises contacting cells transfected with and expressing DNA encoding the human MCH1 receptor with the compound in the presence of a known human MCH1 receptor agonist, under conditions permitting the activation of the human MCH1 receptor, and detecting a decrease in human MCH1 receptor activity, so as to thereby determine whether the compound is a human MCH1 receptor antagonist, wherein the cells do not normally express the human MCH1 receptor, the human MCH1 receptor is encoded by nucleic acid comprising the sequence shown in FIG. 1 (Seq. ID No. 1) or contained in plasmid pEXJ.HR-TL231 (ATCC Accession No. 203197), and the known human MCH1 receptor agonist is MCH or a homolog or analog of MCH.
This invention still further provides a process for preparing a composition which comprises identifying a chemical compound which specifically binds to and inhibits the activation of a human MCH1 receptor, and then admixing a carrier and the chemical compound or a structural and functional analog or homolog thereof, wherein the chemical compound is identified as binding to and inhibiting activation of the human MCH1 receptor by a process which comprises separately contacting cells expressing on their cell surface the human MCH1 receptor and producing a second messenger response upon activation of the human MCH1 receptor, wherein such cells do not normally express the human MCH1 receptor and the human MCH1 receptor is encoded by nucleic acid comprising the sequence shown in FIG. 1 (Seq. ID No. 1) or contained in plasmid pEXJ.HR-TL231 (ATCC Accession No. 203197), with both the chemical compound and a second chemical compound known to activate the human MCH1 receptor, and with only the second chemical compound, under conditions suitable for activation of the human MCH1 receptor, and measuring the second messenger response in the presence of only the second chemical compound and in the presence of both the second chemical compound and the chemical compound, a smaller change in the second messenger response in the presence of both the chemical compound and the second chemical compound than in the presence of only the second chemical compound indicating that the chemical compound inhibits activation of the human MCH1 receptor, wherein the second chemical compound is MCH or a homolog or analog of MCH.

DNA encoding a human melanin concentrating hormone receptor (MCH1) and uses thereof