Polymeric compositions and methods of making same having improved coefficient of friction and blocking properties. The polymeric compositions include a linear low density polyethylene with additives such as a fluoroelastomer and an acid scavenger. The polymeric compositions may further comprise other additives such as antiblock agents, slip agents, stabilization additives, or combinations thereof. The methods include adding additives such as a fluoroelastomer and an acid scavenger to a polymer resin and forming end use articles such as film from the polymeric compositions.

Various properties of polymers, such as the slickness of the polymer or the blocking tendency, may be modified through use of additives. End-use articles may have various combinations of slickness and blocking depending upon their intended use. For example, it may be desirable for polymeric liners that protect the beds of trucks to have a low slickness or high coefficient of friction (COF) to prevent slipping and injury. As another example, it may be advantageous for a polymer such as those used to construct food coverings to be highly blocking. Alternatively, polymers used to construct commercial food packaging containers may be required to have a low blocking tendency in order to facilitate their opening under high-throughput manufacturing conditions. Thus, additives may be used to achieve desirable blocking and COF properties. However, as the levels of additives increase, other properties of the polymer may undesirably change. For example, as additive levels increase, polymer films may become hazy. Thus, a need exists for additives, alone or in combination, that modify the coefficient of friction and/or the blocking properties of polymers to achieve the desired characteristic for a particular application while maintaining other beneficial mechanical or optical properties.


A power generator park provided, which includes at least two power generator devices. Each power generator device has a switching converter for providing an electrical output power. A central controller is provided for providing switching parameter settings to the switching converters. Each of the at least two power generator devices further includes a timing unit for receiving a common time signal. The switching converter of each of the at least two power generator devices is configured for controlling at least one switching parameter in response to the respective switching parameter setting with a temporal coordination based on the common time signal.

Harmonic disturbance is one of the disadvantages of using a frequency converter in power generation. The switching circuit of the frequency converter is one of the main sources of generating harmonic oscillations. Several measures for reducing said harmonic impact are known, e.g. grid filters, increasing the switching frequency, or paring of a number of turbines by optic fibre in order to desynchronize switching phases between the turbines. However, the known measures have at least one of the disadvantages of being expensive, increasing electrical losses or being limited in physical range in the case of paring turbines.
In view of the above-described situation, there exists a need for an improved technique that enables to provide a power generator park with at least two power generator devices, while substantially avoiding or at least reducing one or more of the above-identified problems.

Active desynchronization of switching converters


A recording tape cartridge which includes a case, a reel including a hub accommodated in the case, a locking member supported to be non-rotatable relative to the case and disposed within the hub, and a switching member disposed in the case. The hub is provided with an engaging portion therein. The locking member can attain a rotation-locking position, at which the locking member engages with the engaging portion and fills a gap between the reel and the case in an axial direction of the reel, and a rotation-enabling position, at which the state of engagement with the engaging portion is released and the locking member being withdrawn from the gap. The switching member retains the locking member at the rotation-locking position at times of non-use of the recording tape, and moves the locking member to the rotation-enabling position when operated in a predetermined direction by a drive device.

1. Field of the Invention
The present invention relates to a recording tape cartridge which rotatably accommodates a reel onto which recording tape, such as a magnetic tape or the like, is wound.
2. Description of the Related Art
Recording tapes such as magnetic tapes and the like are used as external recording media for computers and the like. "One-reel" recording tape cartridges, which rotatably accommodate a single reel around which a recording tape is wound, require little space when stored and can record large amounts of information, and are employed as such recording tapes.
Such a recording tape cartridge is equipped with a brake mechanism such that the reel does not rotate in the case at times of non-use of the recording tape cartridge (see, for example, Japanese Patent Application Laid-Open (JP-A) No. 63-251983). JP-A No. 63-251983 discloses a structure in which a reel hub, which is formed in a cylindrical tube shape with a base, and which structures an axially central portion of a reel is provided with an engaging gear formed in an annular form at a bottom face of the reel hub, and a disk-shaped locking which member is provided with a braking gear which is meshable with the engaging gear being inserted in the reel hub. The locking member is supported to be non-rotatable with respect to the case but slidable in an axial direction of the reel. The braking gear of the locking member can mesh with the engaging gear of the reel by urging force of a compression coil spring which is provided between the locking member and the case. In this state, the reel is pressed against a bottom plate of the case by the urging force of the compression coil spring, and the braking gear is meshed with the engaging gear by the urging force. Thus, rotation of the reel relative to the case is locked.
In this structure, a through-hole is formed in a base portion of the reel hub. A release portion of a drive device advances in through this through-hole and pushes up the locking member against the urging force of the compression coil spring. Accordingly, the state of meshing of the braking gear with the engaging gear is released. As a result, rotation of the reel relative to the case is enabled (permitted). The release portion of the drive device is provided at a rotating shaft, together with a driving gear which meshes with a reel gear formed at an end face of the reel hub. The release portion pushes up the locking member in accordance with an operation of meshing the driving gear with the reel gear. As a result, when the rotating shaft drives to rotate the reel, the locking member, which is non-rotatable with respect to the case, and the release portion, which rotates integrally with the rotating shaft, slidingly contact one another while being pushed against each other by the urging force of the compression coil spring. Thus, in order to reduce rotational resistance which is generated in accordance with this sliding contact, the locking member and the release portion are both formed by resin materials.
Further, structures have been devised in which a release member, between a locking member and a base portion of a reel hub, rotates integrally with the reel (see, for example, the specification of Japanese Patent No. 3,187,022). Specifically, the release member is pushed by a release portion of a drive device and, together with the locking member, is pushed up against urging force of a compression coil spring. Thus, the locking member is pushed up to the release portion via the release member, and releases a locked state of the reel. Hence, with this structure, when the reel is driven to rotate, the release member rotates integrally with the reel. Therefore, rather than the release portion slidingly contacting the release member, the release member and the locking member slidingly contact one another.
However, structures are known in which locking members do not slide-contact other components at times of driving for rotation of a reel (see, for example, JP-A No. 11-25648). In such a structure, an engaging gear is formed at an outer peripheral portion of a flange of the reel. Two locking members, which are supported to be rotatable in the case and are urged in a direction of meshing with an engaging gear, mesh with the engaging gear and hence lock rotation of the reel. When such a recording tape cartridge is loaded at a drive device, the locking members are pushed by respective engaging portions of the drive device and are rotated against the urging force. Thus, the meshing of the locking members with the engaging gear is released and rotation of the reel is enabled. These release portions are provided respectively separately from a rotating shaft, and push the locking members in accordance with loading of the recording tape cartridge (the case) into the drive device or an operation of lowering the cartridge. Further, at this structure, a compression coil spring for pushing the reel against the case and/or the rotating shaft is coupled with the reel via a bearing, such that relative rotation of the compression coil spring with respect to the reel is absorbed by the bearing.
However, with the structures described in JP-A No. 63-251983 and the specification of Japanese Patent No. 3,187,022, the urging force of the compression coil spring acts as a drag at a region of sliding contact between the locking member and the release member or the release portion of the drive device. Therefore, if, in correspondence with an increase in recording capacity, the recording tape is lengthened and a rotation speed of the reel is increased and/or a duration of continuous driving is lengthened, the occurrence of abrasion at the sliding contact region will be a matter of concern. Further, in the structure described in JP-A No. 11-25648, an urging mechanism which urges the locking member in the direction of meshing with the engaging gear is a separate component from a compression coil spring which urges the reel toward a bottom plate of the case. Therefore, relative rotation of the reel and the compression coil spring cannot be absorbed by the locking member rotating relative to the reel. Accordingly, it is necessary to absorb such relative rotation with a costly bearing.
Further, the recording tape cartridges relating to the structures described above are structures in which, at times of non-use of the recording tape, the reel is pressed against the bottom plate of the case by the urging force of the compression coil spring. Therefore, it is not possible to obstruct (lock) vertical movement of the reel within the case when a force opposing the urging force of the compression coil spring acts thereon. Consequently, if, for example, a portion of the reel at which the reel gear is formed and which is exposed from the case (an outer face of the base portion of the reel hub) is pushed against or is subjected to an impact due to falling, the reel moves very loosely in the case, which leads to damaging the recording tape, whose one end portion is retained in the case by means of a leader member.
Thus, consequent to the provision in conventional recording tape cartridges of compression coil springs which urge reels relative to cases directly or via locking members, various problems have occurred.


The present invention provides a protease obtained from Bacillus, which is enzymatically active at alkaline pH and high temperature in the presence of surfactants. In a preferred embodiment, the protease is isolated from Bacillus sp. SD 114 and has a molecular weight of about 29,000 and a pI of about 10.

In recent years, environmental pollution has become a social issue. With regulation of the use of phosphate as an ingredient in detergents, an enzyme has been mixed with a detergent to improve detergency. Detergents with an enzyme such as protease, amylase, cellulase and lipase are currently marketed. Particularly, protease can degrade organic stains of clothes, 10 to 40% of which are caused by proteins and which cannot be cleaned with conventional detergents. Protease has become an essential ingredient improving detergency.
As protease for detergents, there are many enzymes originated from microorganisms which are active in the alkaline pH range, and proteases such as Kazusase (Showa Denko K. K.), Savinase (Novo), Maxacal (Gist), Alcalase (Novo) and Biosam (Showa Denko K. K.) have been used. With spreading of automatic dish washers, an enzyme usable for automatic dish washers is being required. Protease is effective on protein stains on dishes from egg yolk, dairy products, etc. However, generally inactivation of enzymes is accelerated in an aqueous solution at high temperature. Thus, an enzyme having an advantage in stability is required. Although Esperase (Novo), etc. have been currently used for this purpose, these enzymes do not have entirely satisfactory activity and stability. The protease which is known to be the most stable in surfactants at present is a protease produced by Bacillus strain SD 521 (patent application number 191781 of 1991). However, an even more stable protease is desired.
Therefore, the object of the present invention is to provide an alkaline protease more stable in the presence of a surfactant, manufacturing method of the alkaline protease, use of the protease for detergent, etc., and a microorganism producing the protease.

Alkaline protease, process for the production thereof, use thereof, and microorganism producing the same


A method and associated system for determining a maintenance status for a pantograph arranged on a vehicle and/or a contact wire intended to be in electrical contact with the pantograph. Monitoring at least longitudinal, vertical or lateral accelerations of the pantograph. Detecting an acceleration pattern based on the monitored accelerations of the pantograph. Determining accelerations in a direction above a predetermined value in the detected acceleration pattern. Determining a maintenance status for the pantograph and/or the contact wire based on the detected acceleration pattern, and wherein the maintenance status indicates a level of wear on the pantograph and/or the contact wire.

A pantograph is commonly used for collecting power through contact with an overhead contact wire. Pantographs may be mounted on, for example, trains, trams and electric buses. The pantograph is in contact with an overhead contact wire through a carbon rail. Graphite conducts electricity while working as a lubricant. As graphite is relatively brittle, pieces may break off during operation. Worn-down pantographs can seize the overhead wire and tear it down, causing long disruptions in, for example, train services.
The contact wire being in electrical contact with the pantograph is also worn down with time. This might result in parts of the overhead power line, besides the contact wire to unwantedly come in contact with a passing pantograph, such as the clamps holding the contact wire from above. This might result in the pantograph to cling on to, or be damaged by, the parts of the overhead power line that is not meant to be in contact with the pantograph.
One solution for avoiding this problem is monitoring pantographs passing certain points of a railway system. These are normally based on a vision system which takes pictures of the pantographs and performs an analysis based on computer vision algorithms. However, it would be very expensive to mount cameras over a whole railway system.
Another solution, also referred to as auto drop, is to have an automatic lowering function in the pantograph, where the pantograph is lowered when the rail in contact with the contact wire is damaged. Automatic lowering is commonly implemented via air tubes in the carbon rail in contact with the lifter, lifting the pantograph via air pressure. If the rail is damaged or run down, the air tubes may leak, and in response the pantograph is lowered. However, this solution does not provide any way of monitoring the need for maintenance before the pantograph breaks.
Therefore, a challenge in the present field is how to provide better maintenance monitoring for pantographs and the wire intended to be in electrical contact with the carbon rail.

Detection of maintenance status for a pantograph and/or a contact wire


Thrombin-based assays are disclosed for determining antithrombin III (ATIII) present in a plasma sample. The assays involve a heparin derivative which, like heparin, effectively enhances the antithrombin activity of ATIII, but which, unlike heparin, does not substantially enhance the antithrombin activity of Heparin cofactor II (HCII). In the present assay, HCII contributes about 15% or less to the determined antithrombin activity. A lyophilized reagent composition, useful in the ATIII assay and comprising thrombin and a heparin derivative, or alternatively comprising thrombin and heparin, is also disclosed. A high-calibrator plasma reference useful in the ATIII assays and in assays for other plasma constituents is also disclosed. Kits employing the several aspects of the invention are disclosed as well.

The present invention generally relates to protocols for evaluating the hemostasis of a patient at risk of developing thrombosis, and specifically, to diagnostic assays for determining the level of antithrombin III present in a plasma sample withdrawn from a patient. The invention particularly relates, in a preferred embodiment, to a chromogenic thrombin-based (ie, type IIa) assay for determining antithrombin III. The invention also relates to a heparin derivative, to a reagent composition and to a high-calibrator plasma reference useful in such assays and to kits employing the same.
The advantageous formation of blood clots during wound healing and the undesirable development of thrombi in connection with thrombosis both involve the proteolytic action of the serine protease thrombin on fibrinogen. The level of thrombin present in vivo is primarily regulated by the heparin-catalyzed thrombin inhibitor, antithrombin III (ATIII). Hence, the level of ATIII present in vivo is of significant clinical importance for diagnosing and monitoring patients at risk for excessive bleeding, due to abnormally high levels of ATIII, or at risk for developing thrombi, due to abnormally low levels of ATIII.
One type of assay for antithrombin III is based on the capability of ATIII present in a plasma sample to inhibit the proteolytic activity of exogenously added thrombin in the presence of heparin. The residual, uninhibited thrombin is then determined by methods typically involving, for example, thrombin-specific chromogenic substrates and spectrophotometric analyses, or alternatively, fibrinogen and clot-forming analyses.
However, such thrombin-based ATIII assays--also referred to as factor IIa ATIII assays--are inaccurate due to the activity of a second heparin-catalyzed thrombin-inhibitor, heparin cofactor II (HCII). See Tollefson et al., Heparin Cofactor II, Jrnl. Biol. Chem. 257:5, pp. 2162-2169 (1982). That is, thrombin-based assays known in the art measure the levels of exogenous thrombin remaining after the thrombin has reacted with both ATIII and HCII--not just with ATIII. The inaccuracy of such assays are of particular clinical concern for ATIII-deficient patients. In cases where HCII is in the high normal range and ATIII is determined using thrombin-based assays known in the art, an ATIII deficiency can be masked by the HCII antithrombin activity.
Several approaches have been developed for avoiding the masking effect of HCII. One proposed approach for a factor IIa assay involved the use of bovine thrombin in the presence of relatively low concentrations of heparin. See Friberger et al., Antithrombin Assay--The Use of Human or Bovine Thrombin and the Observation of a "Second" Heparin Cofactor, Thrombosis Research 25, pp. 433-436 (1982). This approach, however, did not provide a commercially recognized solution to the problem.
Another approach is described in U.S. Pat. No. 5,646,007 to Enomoto et al., wherein a chromogenic thrombin-based ATIII assay is conducted in the presence of salt at a concentration ranging from about 0.2 M to about 0.9 M, and preferably at a concentration greater than about 0.3. While this approach offers some benefits with respect to limiting the effect of HCII activity against thrombin, the sensitivity of chromogenic assays for thrombin decreases as the concentration of salt increases, due to an allosteric effect on thrombin in the presence of such higher salt concentrations. Reduced sensitivity is of particular commercial significance for ATIII assays performed using automated analyzers.
According to yet another approach, the ATIII assay is performed using exogenously added factor Xa as an indicator instead of thrombin. See Demers et al., An Antithrombin III Assay Based on Factor Xa Inhibition Provides A More Reliable Test to Identify Congential Antithrombin III Deficiency Than an Assay Based on Thrombin Inhibition, Thrombosis and Hemostasis 69:3 pp. 231-235 (1993). Unlike thrombin, factor Xa is not inhibited by HCII. However, factor Xa-type ATIII assays are more expensive than factor IIa-type assays. Moreover, factor Xa can be less stable than thrombin under certain conditions, and the factor Xa-based assays can require a greater degree of dilution. As such, factor Xa ATIII assays are less suitable for use with automated analyzers.
Assays for determining ATIII, and in fact, assays for determining other plasma constituents, have other common problems when the assay protocol involves correlation of a determined amount using a standard curve developed from reference plasma samples of known constituent concentration. Because reference plasmas known in the art typically have high-end constituent concentrations of less than about 105% of normal, it is not possible to directly determine a plasma constituent which is substantially above the normal concentration range of that constituent (e.g. about 110% or more). Instead of making such determination directly, it is presently necessary to dilute the patient plasma sample (e.g. 1:1 in saline), reperform the determination, and then multiply the determined amount by the dilution factor (e.g. 2 for a 1:1 dilution).

Thrombin-based assay for antithrombin III


The present invention is a method and apparatus for the efficient processing of binary images represented as a run length encoded data stream. The system employs a CPU and cache or other memory for efficiently scaling or scaling and rotating parsed RLE date. Subsequently, the scaled RLE data can be decoded to produce a scaled image bitmap.

The present invention is directed to image processing and in particular to image scaling. As will be appreciated, scaling of an image is a fundamental element of an image processing system, be it a dedicated image processing system or one that is part of a digital printer, facsimile machine, or multifunctional device. The present invention is directed to a high speed method and apparatus for accomplishing one or two dimensional scaling of digitized images that are represented in a run length encoded manner.
Heretofore, a number of patents and publications have disclosed methods for image scaling, the relevant portions of which may be briefly summarized as follows:
R. Tuhro described in the Xerox Disclosure Journal, Vol. 5, No. 6, November/December 1980 (p. 639) Image Scaling Using Bit Throw-away Memory. In the disclosure, a logic circuit for accomplishing the scaling at a high data rate is taught.
U.S. Pat. No. 5,303,334 to Snyder et al., issued Apr. 12, 1994, teaches a system for rendering a graphic image. In particular, the system employs opcodes, wherein the opcodes are described as representing instructions to scale a source image and rotate a source image.
U.S. Pat. No. 5,245,441 to Ruben, issued Sep. 14, 1993, and incorporated by reference for its teachings related to CCITT compression, discloses an image processing method and apparatus, where an image stream is represented logically as a series of run length codes. During a decompression operation, CCITT encoded data is received, decoded into a full raster image, and clipping, windowing and scaling operations are then applied. At col. 8, lines 43-54, Ruben teaches the use of codes representing pixels of the same color and the performance of mathematical operations on such codes without converting them back into run lengths.
U.S. Pat. No. 5,113,494 to Menendez et al., issued May 12, 1992, appears to disclose a pipelined raster image processor. In the preferred embodiment, Menendez et al. describes a raster image processor (RIP) capable of performing several different image processing operations. The RIP contains a scaler, which receives output from a decompressor, for scaling the decompressed image from one resolution to another. The scaler is connected to a bus by which the image data is transferred on a block-by-block basis.
U.S. Pat. No. 5,239,625 to Bogart et al., issued Aug. 24, 1993, teaches the merging of images, particularly images represented in compressed format using run length encoding techniques. To accomplish scaling, the low resolution rasterization is multiplied by repeat pixel counts reflected in the run length data for a single raster line and identical lines are represented with repeat line counts.
In accordance with the present invention, there is provided a method, operating on a programmable data processing system, for scaling an image represented as a run length encoded data stream to produce a scaled run length encoded data stream representing a scaled version of the image, comprising the steps of: parsing the run length encoded data stream to determine the lengths of continuous runs of a color; multiplying each of the lengths by a scaling factor to produce a stream of scaled run lengths; applying at least one scaling rule to the stream of scaled run lengths to alter a run length therein; and outputting the scaled run lengths as a scaled run length encoded data stream.
In accordance with another aspect of the present invention, there is provided a method, operating on a programmable data processing system, for processing an image represented as a run length encoded data stream to produce a second run length encoded data stream representing a processed version of the image, comprising the steps of: parsing the run length encoded data stream to determine the lengths of continuous runs of a color; multiplying each of the lengths by a scaling factor to produce a stream of scaled run lengths; applying at least one scaling rule to the stream of scaled run lengths to alter a run length therein; and rotating the scaled run length encoded data stream while decoding the run length encoded data stream to produce a binary array of image signals, said binary array of image signals representing the image at a different resolution and orientation.
In accordance with yet another aspect of the present invention, there is provided an apparatus for scaling a run length encoded data stream, comprising: an input buffer for storing at least a portion of the run length encoded data stream; means for parsing the run length encoded data stream to determine the lengths of continuous runs of a color; arithmetic circuitry for multiplying each of the lengths by a scaling factor to produce a stream of scaled run lengths; and memory for storing the scaled run lengths as a scaled run length encoded data stream.
One aspect of the present invention deals with a basic problem in image processing, the fast scaling of image bitmaps. Resolution of this problem finds practical application in various image output devices where an image generated at a first resolution is constrained to be printed at a second resolution. For example, an image may be generated or scanned in at 300 dots per inch (dpi) but printed using an a print engine capable of rending marks on a substrate at 600 dpi. Alternatively, one may wish to print an image in a magnified or reduced fashion.
This aspect is further based on the discovery of a technique that alleviates this problem of different resolutions. The technique employs the compressed form of an image, when it has been represented as a run length encoded bit stream, to accomplish the scaling or resolution conversion in a computationally efficient manner. In particular, the preferred embodiment of the invention relies upon a fast scaling technique operating on run length encoded data to facilitate the rapid scaling during decoding of the run length data.
This technique can be implemented, for example, by any image processing system, be it hardware or software based. Machines implementing the invention may include printers, scanners, facsimile machines as well as multifunction machines. The hardware required preferably includes a microprocessor or similar control circuitry to control memory access (e.g., read/write) and to perform simple arithmetic operations on the stored data.
The technique described above is advantageous because it is not only simple but efficient. Furthermore, it can be adapted to any image processing system in which run length encoded data is generated or employed, making it available for use in any of a number of digital image processing systems, particularly those using run length encoding for data compression. The techniques of the invention are advantageous because they permit the highly efficient scaling of image bitmaps. The present invention is one of a plurality of image processing operations that can be applied to compressed image formats to enable faster processing of image data in an image processing system. Some of the related techniques can be used to perform image processing while decoding a run length encoded image. Other techniques include the scaling of an image while decoding.

Method and apparatus for the fast scaling of an image


Compact or convenient transaction cards comprising protective sleeves for full-sized and smaller-sized cards, cut lines and rotatable means for forming “fanned” cards, rollable cards, collapsible cards, cards having hinges or axes for rotating parts to form full-sized cards from smaller-sized cards, housings for having lights and sounds emanating therefrom, and the like are provided.

It is, of course, generally known to provide transaction cards for providing means for purchasing goods or services without the use of paper money or coinage. Specifically, transaction cards may represent credit, whereby a user of the transaction card may present the card in lieu of the paper money or coinage. Alternatively, transaction cards may be debit cards, whereby electronic money, such as money stored in an account, is removed from the account each time that the transaction card is used. In addition, transaction cards may have a certain amount of money, or other valuable commodity, recorded thereon, whereby a user of the transaction card may remove the money directly from the transaction card. For example, retail stores now offer cards that can be purchased for a certain amount of money. That amount, or any other amount, may be represented on the transaction card. When the transaction card is utilized, the amount represented on the card may be reduced until the transaction card represents that it cannot be utilized anymore, or that the card represents that it is not worth any more money. Of course, other value besides currency may be represented on the transaction card, such as equivalent goods or services.
Transaction cards typically have a magnetic stripe provided, or some other means, for storing information relating to the transaction card, such as a security code, and information relating to an account or an amount of money that the transaction card may represent. For example, if the transaction card is a credit card, the information contained on the magnetic stripe may relate to an account whereby use of the credit card may alert the account to release funds for the purchase of goods or services. Of course, the magnetic stripe or other means may further contain any other information to allow the transaction card to be utilized. The transaction card is typically fed into or through a reader that reads the information contained on the magnetic stripe to extract the information as needed when the transaction card is being used.
The transaction card may further contain other features that allow for the secure and efficient use of the transaction card, such as holographic security devices, signature panels, pictures of the owner of the transaction card, embedded microchips, or any other item or element that may be useful for the transaction card.
Transaction cards are typically sized according to standards set by the International Organization for Standardization (ISO). This means that most transaction cards being utilized are of the same size and dimensions, typically about 2.5 inches by about 3 inches in a generally rectangular configuration. However, a transaction card having dimensions according to this standard is relatively large and difficult to store in a convenient way except loose in a pocket, wallet or purse, or contained within a slot in a wallet or purse allowing for the snug fit of the transaction card. Transaction cards are, therefore, highly susceptible to being lost or stolen. Other shapes and sizes would allow the transaction cards to be attached to, secured with, or otherwise stored with other items, such as keychains, for example.
A need exists, therefore, for a transaction card having the capability to be stored with items or in smaller areas than are currently allowed. For example, a need exists for a transaction card that may be clipped or otherwise attached to a keychain, or some other means for securing the transaction card to another item, yet is small enough to remain inconspicuous and compact, but handy. Further, a need exists for a transaction card having the above-noted advantages and further that maintains the information or other features typically disposed on or within a transaction card.

American Express Travel Related Services Company, Inc.


In accordance with the present invention there is provided a pharmaceutical composition useful for the treatment or prophylaxis of viral infections comprising tipranavir and at least one antiviral active compound of formula (I)

Human immunodeficiency virus (HIV) is recognized as the causative agent in AIDS.
Current therapies for HIV infection focus on inhibiting the activity of viral enzymes which are essential to the life cycle of the virus. The agents that are presently in use fall mainly into three classes, designated Nucleoside Reverse Transcriptase Inhibitors (NRTIs), Non-nucleoside Reverse Transcriptase Inhibitors (NNRTIs), and Protease Inhibitors (PIs). Presently, combination therapies, i.e. the selection of two or more antiretroviral agents taken together to make up a "drug cocktail," are the preferred treatment for HIV infection. Combination therapies have been shown to reduce the incidence of opportunistic infections and to increase survival time. Typically, the drug cocktail combines drugs from different classes, so as to attack the virus at several stages in the replication process. This approach has been shown to reduce the likelihood of the development of virus forms that are resistant to a given drug or class of drugs.
Treatment failure with rebound of the amount of HIV which can be measured in the blood is common for patients treated with combination antiretroviral regimens. Resistance to the drugs in the drug regimen develops as the virus replicates in the presence of these drugs. Because of structural similarities of the drugs within an antiretroviral class, cross resistance is commonly seen to the other members of that class (for example virologic failure on a regimen containing an NNRTI will lead to cross resistance to the other first generation NNRTI agents). As patients experience repeated virologic failure on antiretroviral combination therapy, their viruses develop broad multi-class antiretroviral drug resistance which limits the effectiveness of the next round of antiretroviral therapy. Many highly treatment experienced patients have been exposed to all three classes of antiretroviral drugs and cannot obtain two active drugs to form the core of a new, effective antiretroviral drug regimen.
Tipranavir is a known agent for the treatment of HIV infection.
Tipranavir, also known as U-140690 and PNU-140690, is an HIV protease inhibitor. Chemically, tipranavir is (6R)-3-((1R)-1-[3-({[5-trifluoromethyl)(2-pyridyl)]sulfonyl}amino)phenyl]propyl}-4-hydroxy-6-(2-phenylethyl)-6-propyl-5,6-dihydro-2H-pyran-2-one or ([R-(R*,R*)]-N-[3-[1-[5,6-dihydro-4-hydroxy-2-oxo-6-(2-phenylethyl)-6-prop yl-2H-pyran-3-yl]propyl]phenyl]-5-(trifluoromethyl)-2-pyridinesulfonamide) and has the following structural formula:

Tipranavir and methods for its synthesis and use in the treatment of HIV are described in WO 95/30670 and corresponding U.S. Pat. No. 5,852,195. Pharmaceutical formulations suitable for the oral administration of tipranavir are described in WO 99/06043 and WO 99/06044, and the corresponding U.S. Pat. Nos. 6,121,313 and 6,231,887.
As tipranavir is metabolized relatively rapidly by the cytochromes P450, especially the Cyp3A4 isoform, it is preferred to co-administer an inhibitor of Cyp3A4 in order to obtain therapeutically effective blood levels of tipranavir. The use of ritonavir for this purpose is described in U.S. Pat. No. 6,147,095. The use for this purpose of other inhibitors of Cyp3A4 is also possible.
Furthermore Compounds of the Formula (I)
wherein Base is selected from the group consisting of thymine, cytosine, adenine, guanine, inosine, uracil, 5-ethyluracil and 2,6-diaminopurine, or a pharmaceutically acceptable salt or prodrug thereof, are described in the WO 88/00050 and WO 91/01137 for the therapeutic and prophylactic control and treatment of AIDS, HIV infections, hepatitis B virus (HBV) infections and retrovirus infections in animals and man. These nucleoside compounds are transformed by cells or enzymes to triphosphates which inhibit the reverse transcriptase of retrovirus as well as the activity of DNA dependent polymerase of hepatitis B virus.
Combinations of tipranavir with at least one compound of the formula (I) which exhibit potent therapeutic activity against HIV and HBV would greatly aid in the development of new combination therapy against human retroviral (HRV) infections and HBV.

Pharmaceutical composition of antiviral agents

Abstract: wherein Base is selected from the group consisting of thymine, cytosine, adenine, guanine, inosine, uracil, 5-ethyluracil and 2,6-diaminopurine, or a pharmaceutically acceptable salt or prodrug thereof.


A communication apparatus is provided. The communication apparatus includes a transmission unit adapted to transmit data via a network, a receiving unit adapted to receive data supplied via the network, an interface unit adapted to supply to-be-transmitted data to the transmission unit and extract particular information from data received by the receiving unit, and a control unit configured to control an operation state of the interface unit.

The present disclosure relates to an apparatus, method and program for communication, and more particularly, to an apparatus, method and program for communication, which allow a reduction in power consumption.
In an Ethernet® network system, it is known to perform auto-negotiation to optimize communication (see for example, IEEE Std 802.3-2002 Section Two, "28. Physical Layer link signaling for 10 Mb/s, 100 Mb/s and 1000 Mb/s Auto-Negotiation on twisted pair", 8 Mar. 2002, Pages 213-260, IEEE). In the auto-negotiation, a network device sends a pulse signal (a link pulse signal) to another network device with which to communicate to notify it of the allowable communication speed or the communication mode.
However, the auto-negotiation is for optimization of communication, but reduction in power consumption of network devices connected to each other is not taken into account.
In recent years, a great increase in the communication speed has been achieved, and a corresponding increase in the operating frequency and operating speed of network devices have been achieved. However, this results in an increase in power consumption, and thus there is now a need to reduce the power consumption.
In the case of a 10 Gigabit Ethernet® system according to the standard IEEE802.2ae established by IEEE (Institute of Electrical and Electronic Engineers), it is required to use an optical cable as a transmission medium to achieve a high transmission speed. However, a network device adapted to transmit/receive an optical signal needs high power consumption, and thus it is very desirable to reduce the power consumption.

Apparatus, method, and program for communication


A double-balanced golf club head including a club head body and a neck tube for securing a golf club shaft to the club head body, wherein the neck tube is peripherally attached to two opposite engagement grooves at two opposite sides of the club head body, having one end fastened to a blind hole at one end of the face panel of the club head body and an opposite end inserted through a through hole on an opposite end of the face panel of the club head body and then turned upwardly inwards and then upwardly backwards and terminating in a coupling end for connection to a golf club shaft.

The present invention relates to a golf club head, and more particularly to a double-balanced golf club head whose center of gravity can be conveniently positively adjusted after its fabrication.
It is well known that the location of the center of gravity of a golf club head greatly affects its performance. Therefore, a golf club head is generally equipped with a counterweight, that adjusts the center of gravity of the golf club head. However, after the counterweight has been installed and the fabrication of the golf club head has been done, the center of gravity of the golf club head cannot be further adjusted.

10F-2, No. 45, Cheng Ta Rd., Ling Ya Dist.

14F., Bldg. C, No. 536, Feng Tung Rd., Feng Shan


Systems and methods for providing a plurality of advanced telephony services using a metaservice are described. In an embodiment of the present invention, a service provider installs a metaservice on the processor and associates the metaservice with a directory number on the switch. The metaservice acts as a pseudo service. When the service provider receives a subsequent request for an advanced telephony service, the service associates the requested service with the directory number through the metaservice, thereby avoiding many of the provisioning steps that are conventionally required to set up each service.

Local telephone service providers have historically set a high standard for quality and reliability. For example, the traditional measure of reliability has been five nines or 99.999% reliability, which translates to just five minutes and fifteen seconds of downtime per year. The service providers have achieved these high standards by rigorously controlling the methods for development and deployment of new services and features in their legacy telecommunications infrastructures. However, as telecommunications technology evolves, and as the competitive environment changes, these conventional methods have become impediments to the service provider's ability to successfully compete against providers using new and faster, but not necessarily better, methods.
In a legacy system, the service provider must perform a multitude of steps to develop, test, and deploy a single service. These steps include changes to provisioning systems, billing systems, and customer support methods as well as changes to marketing and sales plans. The costs involved in these changes can amount to millions of dollars for each new service. The high cost of a new service deters the service provider from offering a service for which the service provider has difficulty estimating the size of the target market or for which the service provider knows only a small market exists. To remain competitive, service providers have a need to minimize these costs for new services.
One way in which service providers are attempting to minimize the costs of service development and deployment is to begin to transition their legacy systems to newer, faster, and more flexible systems, such as those based on the Internet protocols. These new systems hold great promise for service provisioning, support, and billing. These newer systems provide efficiency and cost benefits to service providers and provide benefits to subscribers as well, including graphical user interfaces that allow the subscriber to control complicated services through simple commands and that provide great flexibility to subscribers with more advanced skills. Furthermore, the majority of conventional programming and network advances focus on Internet service development and support, such as Java and similar languages, encryption and authentication procedures, multimedia compression and congestion access control, and network management.
One challenge facing the service provider is successfully managing the transition. Service providers have begun some measures to integrate the legacy and newer systems, such as adding softswitches and application servers, but one key challenge remains—maintaining quality and reliability while increasing the speed of development and deployment of new services. Service providers have a need for systems and methods that allow the rapid development and deployment of advanced telephony services, including Internet protocol based services, in conventional, legacy telecommunications infrastructures.

Systems and methods for providing advanced telephony services

AT&T Delaware Intellectual Property, Inc.


The present invention relates to an automatic injection training device comprising an elongated housing having a distal end and an opposite proximal end and extending along a longitudinally axis (L); a tubular demo container axially and rotationally fixed relative to the elongated housing and having a tubular wall extending along the longitudinally axis (L); a reloadable plunger assembly comprising a plunger rod which is movable in the demo container between a first and a second position and a first energy accumulating element configured to move the plunger rod from the first to the second position; an actuation assembly configured to hold the plunger rod in the first position and to release the plunger rod from the first position. The invention is characterized in that the device further comprises a first signal generating element releasably connected to the plunger rod and a second signal generating element fixedly connected to the plunger rod, and wherein each signal generating element is configured to interact independently from each other for generating audible feedback signals.

Automatic injection devices for delivering active substances are well known in the art. In many cases, training versions of such devices are required for showing potential users (e.g., patients or healthcare providers) how a device should be employed and for illustrating the advantages of the device. Such devices are frequently called "promotion" or "training" devices. The devices should mimic the function of different steps corresponding to a real injection device, but should not be capable of injecting an active substance.
Document U.S. Pat. No. 5,071,353 describes a training device for an automatic injector. The device comprises a cylindrical outer sleeve in the rear position of which a discharge mechanism is connected. The discharge mechanism comprises a plunger, a coil spring which acts on the plunger, a locking device, and a safety element. However, this device does not provide means allowing an accurate simulation of the resistance acting on the discharge mechanism of a regular injection device when an active substance is ejected.
WO 2011/151315 discloses a training cartridge for a drug delivery device as well as a method for resetting the cartridge. The cartridge comprises a body of substantially cylindrical shape, a piston that is slidably disposed in the body in an axial direction, and a closure means disposed at an axial end portion of the body. The piston and the closure means confine an interior volume coupled to the exterior via at least one fluid escape channel. According to the method disclosed, several steps are required for resetting the cartridge.


A method for the diagnosis of brain/neurological disease involving abnormally phosphorylated tau protein using at least one antibody chosen from the group consisting of monoclonal antibody AT180 secreted by the hybridoma deposited at ECACC on Dec. 22, 1992 under No. 92122204, and monoclonal antibody AT270 secreted by the hybridoma deposited at ECACC on Jul. 7, 1993 under 93070774, each of which forms an immunological complex with a phosphorylated epitope of an antigen belonging to abnormally phosphorylated tau protein (PHF-tau) residing in the region spanning positions 143-254 with the following amino acid sequence:

The invention relates to new monoclonal antibodies specific for PHF-tau, to the hybridomas secreting these monoclonal antibodies, and to the antigen recognition pattern of these monoclonal antibodies. The invention also relates to a process for diagnosing brain diseases involving monoclonal antibodies of the invention, more particularly in cerebrospinal fluid (CSF) samples. The invention also relates to a region of the tau molecule modifiable in vivo by the process of phosphorylation, which is found to be associated with Alzheimer""s disease or with other types of dementia and which is specifically recognized by the monoclonal antibodies of the invention.
Alzheimer""s disease (AD) is the most common form of adult-onset dementia. At present, no reliable biochemical test is available for antemortem diagnosis of AD. The disease is therefore diagnosed clinically on the basis of exclusion of other forms of dementia. The diagnosis can be confirmed neuropathologically by the demonstration of large amounts of neuritic (senile) plaques and neurofibrillary tangles (NFT) in particular brain regions (McKhann et al, 1984).
Neurofibrillary tangles consist of paired helical filaments (PHFs). Immunocytochemical evidence suggests that the microtubule-associated protein tau is a major protein component of PHF and NFT (Brion et al., 1985b; Delacourte and Defossez, 1986; Grundke-Iqbal et al., 1986; Kosik et al., 1986; Wood et al., 1986). Definite proof that the tubulin-binding domain of tau is tightly associated with the core of PHFs was obtained via amino acid sequencing (Kondo et al., 1988). Nevertheless it has been suggested that tau peptides may represent only a small portion of the major component of PHF (Wischik et al., 1988).
Tau protein exists in different isoforms, of which 4 to 6 are found in adult brain but only 1 isoform is detected in fetal brain. The diversity of the isoforms is generated from a single gene on human chromosome 17 by alternative mRNA splicing (Andreadis et al., 1992). The most striking feature of tau protein, as deduced from molecular cloning, is a stretch of 31 or 32 amino acids, occurring in the carboxy-terminal part of the molecule, which can be repeated either 3 or 4 times. Additional diversity is generated through 29 or 58 amino acid-long insertions in the NH2-terminal part of tau molecules (Goedert et al., 1989). For simplicity, all numbering in this patent application refers to the tau variant htau40 containing all exons (441 amino acids long) according to Goedert et al (1989).
Under normal circumstances tau promotes microtubule assembly and stability in the axonal compartment of neurons. The microtubule-binding domain in tau is localized in the repeat region of tau (255-381) (Lewis et al, 1990) and is modulated by adjacent regions: the carboxyterminal tail (382-414) and the proline-rich region (143-254) (Drubin and Kirschner, 1991). Stability and bundling of the microtubules is mediated by a short hydrophobic zipper in the carboxyterminal tail of tau (Lewis et al, 1989). Both assembly and stability are regulated by alternative mRNA splicing and phosphorylation.
In normal circumstances adult brain contains 2 to 3 mol phosphate per mole of tau (Selden and Pollard, 1983; Ksiezak-Reding et al, 1992) present amongst others at serine 404 (Poulter et al, 1993), while other results demonstrate that phosphorylation of different sites in normal tau follows different developmental profiles (Lee et al, 1991; Bramblett et al, 1993; Goedert et al, 1993a). Abnormal tau variants of 60, 64 and 68 kDa have been detected exclusively in brain areas showing neurofibrillary changes and senile plaques (Delacourte et al. 1990). The abnormal electrophoretical behavior of tau is due to phosphorylation since alkaline phosphatase treatment of these tau molecules changes their molecular mass to that of normal tau (Goedert et al., 1992; Flament et al., 1990b, Greenberg and Davies, 1990). Currently abnormal phosphorylation sites have been detected in PHF-tau at positions 46, 231, 235, 263 and 396 (Iqbal et al., 1989; Lee et al., 1991; Hasegawa et al., 1992). In four of these sites, the phosphorylated residu is followed by a proline residu, indicating that a proline-directed kinase is involved in some of the abnormal phosphorylations of tau. In addition to these sites ten others are present in htau40, two of which are also abnormally phosphorylated, as indicated by antibody reactivity (Mab tau2: Watanabe et al., 1992; Mab AT8: Biernat et al., 1992, Goedert et al., 1993).
The abnormal phosphorylation of tau in Alzheimer""s disease is due to a shift in the phosphatase/kinase equilibrium. In vitro several kinases can phosphorylate tau: cdc2-kinases (Vulliet et al, 1992; Ledesma et al, 1992), MAP kinases (Drewes et al, 1992, Roder and Ingram, 1991), glycogen synthase kinases (Mandelkow et al, 1992) and TPKI and TPKII (Ishiguro et al, 1992). The phosphatases are less well studied in Alzheimer""s disease and so far only one phosphatase was able in vitro to dephosphorylate the abnormally phosphorylated sites, namely protein phosphatase 2A1 (Goedert et al, 1992).
So far, the detection of PHF-tau in brain extracts, either via antibodies (Mab Alz50: Ghanbari et al., 1990; Mab Ab423: Harrington et al., 1991), or via the change in molecular weight (Flament et al., 1990, Delacourte et al., 1993), or else by functional assay (Bramblett et al. 1992) has been very useful to discriminate dementia with altered cytoskeletal properties from normal aged subjects or from patients with other types of dementia. Nevertheless the detection of PHF-tau in CSF remained impossible, even using antibodies directed at one of the abnormally phosphorylated sites such as serine 202 (Goedert et al., 1993). This can be ascribed to one or more of the following reasons: 1) the low concentration of PHF-tau in CSF, 2) non-even use of phosphorylation sites among all the potential phosphorylation sites, 3) differences in phosphatase sensitivity of these sites, and, 4) too low an affinity constant of the antibodies used.
The aim of the present invention is therefore to provide monoclonal antibodies which allow the reliable and sensitive detection of abnormally phosphorylated tau present in cerebrospinal fluid.
The invention also aims at providing the hybridomas which secrete the above-said monoclonal antibodies.
The invention furthermore aims at providing the epitopes of the abnormally phosphorylated tau protein present in brain homogenates or in body fluids such as cerebrospinal fluid, which are recognized by said monoclonal antibodies.
Finally, the invention aims at providing a process for the detection or diagnosis in vitro of brain diseases involving abnormally phosphorylated tau proteins.
The present invention relates more particularly to a monoclonal antibody which forms an immunological complex with a phosphorylated epitope of an antigen belonging to abnormally phosphorylated tau (PHF-tau) residing in the region spanning positions 143-254 with the following amino acid sequence:
and with said monoclonal antibody being characterized by the the fact that it is capable of specifically detecting abnormally phosphorylated tau protein (PHF-tau) in cerebrospinal fluid (CSF).
The monoclonal antibodies of the invention were selected from a range of monoclonal antibodies obtained by direct immunization with PHF-tau, extracted from human brain tissue derived from Alzheimer patients. More particularly the monoclonal antibodies of the invention are characterized by the fact that they specifically bind to naturally occuring abnormally phosphorylated tau. Further analysis of their epitopes showed that the monoclonal antibodies of the invention are directed at phosphorylated epitopes confined to a particular region of the tau molecule, namely the region between 143 and 254 including several potential phosphorylation sites such as T153 and S235 used by the SP and TP directed kinases. The monoclonal antibodies of the invention are further characterized by the fact that they recognize epitopes which are different from the epitope of the monoclonal antibody AT8 as defined in Goedert et al. (1993) and upon comparison with the AT8 antibodies allow the detection of PHF-tau in CSF. They recognize preferentially PHF-tau either on brain sections, immunoblots or in ELISA and they are surprisingly able to detect PHF-tau in CSF, either alone or in combination with other PHF-tau specific antibodies.
In conclusion, the monoclonal antibodies of the invention are characterized in that they specifically bind to naturally occuring abnormally phosphorylated tau of which the phosphorylation state is confined to a particular region of the tau molecules as specified above, or bind to recombinant non-phosphorylated tau after treatment with proline-directed kinases, which can provoke the phosphorylation of, amongst others, Ser-Pro or Thr-Pro sites in the region as specified. Proline-directed kinases such as MAP kinases (Sturgill et al., 1991). cdc2 kinases (Labbxc3xa9 et al., 1991) and glycogen synthase kinases (Vandenheede et al., 1980) can be purified from various tissues or can be present in brain extracts. The phosphorylation of tau by these kinases is abolished or greatly diminished when one or more of the following serines/threonines are mutated to an amino acid such as Ala: T153, T175, T181, S199, S202, T205, T212, T217, T231, or S235. Consequently, the epitope of these antibodies can be characterized via such mutant tau, or via non-phosphorylated tau such as procaryotically expressed recombinant tau and their phosphorylated homologues, or via synthetic peptides having the same amino acid sequence as parts of the region specified above of the human tau 40 protein and with said peptides being capable of being phosphorylated by said kinases or being incapable of being phosphorylated upon synthesis of the peptides. The epitopes of the present invention are thus defined as the proline rich-region of tau between position 143 and 254 and which can be abnormally phosphorylated at threonine 153 (T153), T175, T181, S199, S202, T205, T212, T217, T231 and S235 or a combination these sites included in the epitope of these antibodies, further referred to as a xe2x80x9cPHF-tau epitopesxe2x80x9d.
The expression xe2x80x9cspecifically detecting abnormally phosphorylated tau proteinxe2x80x9d corresponds to the fact that the monoclonal antibodies of the invention detect abnormally phosphorylated tau in CSF without cross-reacting with normal tau present in CSF.
The expression xe2x80x9cform an immunologically complex withxe2x80x9d means that the monoclonal antibody of the invention binds to the above-said antigen under conditions as mentioned in one of the following techniques:
Light Immunomicroscopy
Brain tissue samples, of e.g. Alzheimer patients obtained at surgery or autopsy, are fixed by immersion in 4% formalin or Bouin""s fixative and embedded in paraffin for sectioning. The monoclonal antibodies of the invention are applied in conjunction with a technique to visualize the formed immune complexes such as the avidin-biotinylated peroxidase complex technique (Hsu et al., 1981) using 3,3xe2x80x2-diaminobenzidine tetrahydrochloride for development of color. Sections are counterstained with Harris haematoxylin stain.
Immunoelectron Microscopy in Tissue Sections
Brain tissue samples e.g. obtained from Alzheimer patients at surgery or autopsy are fixed in either Bouin""s fixative or 10% buffered formalin before sectioning without embedding (Vibratome). The monoclonal antibody of the invention is used for immunostaining by the indirect immunogold method after which the sections are fixed, embedded and sectioned for electron microscopy, all according to standard protocols known to those skilled in the art (Brion et al., 1985a).
Immunoblotting Procedures
For immunoblotting, fractions enriched in PHF-tau are prepared as described (Greenberg and Davies, 1990). Typically, postmortem tissue, consisting mostly of gray matter from the frontal and temporal cortex, was obtained from histologically confirmed Alzheimer patients. This Alzheimer gray matter brain sample (5-10 g) was homogenized with 10 volumes of cold buffer H (10 mM Tris/1 mM EGTA/0.8 M NaCl/10% sucrose, pH 7.4) in a Teflon/glass Potter S (Braun, Germany) homogenizer. After centrifugation of the homogenate in a 60 Ti MSE rotor at 27,000xc3x97g for 20 min at 4xc2x0 C., the pellet was removed and the supernatant was adjusted to 1% (wt/vol) N-laurosylsarcosine and 1% (vol/vol) 2-mercaptoethanol and incubated while rotating on a mixer (Swelab, Sweden) for 2.5 hours at 37xc2x0 C. The supernatant mixture was centrifuged at 108,000xc3x97g for 35 min at 20xc2x0 C. The PHF-tau containing pellet was gently washed with PBS and finally suspended in 1 ml of the same buffer.
SDS-polyacrylamide electrophoresis is performed under reducing conditions on 12% gels (Laemmli, 1970). After electrophoresis, the proteins are either fixed and stained with Coomassie brilliant blue, or transferred (Towbin et al., 1979) to nitrocellulose sheets (Hybond-C, Amersham) or Immobilon filters (Millipore).
After transfer, the filters are presoaked in PBS containing 0.05% (v/v) Tween 20 (Tween-PBS) and then incubated for 1 h in Tween-PBS containing 5% (w/v) skimmed dried milk and 10% (v/v) newborn calf serum (blocking buffer). Next, the filters are treated overnight at 4xc2x0 C. with a monoclonal antibody according to the invention appropriately diluted in blocking buffer.
The filters are then washed three times in Tween-PBS and treated for 1.5 h at room temperature with horseradish peroxidase-labeled rabbit anti-mouse IgG (Dakopatts, Denmark) diluted 1/3000 in blocking buffer. After three washes in Tween-PBS, streptavidine-biotinylated horseradish peroxidase complex (Amersham), diluted 1/250 in blocking buffer, is applied for 1.5 h at room temperature. Thereafter, the filters are washed three times in Tween-PBS and once in PBS. The filters are then incubated in PBS containing 0.05% (w/v) diaminobenzidine and 0.03% (v/v) hydrogen peroxide until background staining develops.
It should be clear that the formation of an immunological complex between the monoclonal antibodies and the antigen is not limited to the precise conditions described above, but that all techniques that respect the immunochemical properties of the antibody and antigen binding will produce similar formation of an immunological complex.
The present invention relates more particularly to a monoclonal antibody as defined above, characterized by the fact it forms an immunological complex:
either with a phosphorylated epitope located within the sequence defined above (SEQ ID NO 1),
or with any other phosphorylated peptide capable of forming an immunological complex with a monoclonal antibody, which itself is capable of forming a complex with a phosphorylated epitope located in the human tau protein region as shown in SEQ ID NO 1.
Preferred monoclonal antibodies of the invention, AT180 and AT270, are produced by hybridomas deposited at ECACC (European Collection of Animal Cell Cultures, Vaccine Research and Production Laboratory, Public Health and Laboratory Service (PHLS), Centre for Applied Microbiology and Research, Porton Down, GB-Salisbury, Wiltshire SP4 OJG), United Kingdom on Dec. 22, 1992, under No 92122204 or on Jul. 7, 1993 under No 93070774.
The above-mentioned monoclonal antibodies are obtained by a process involving obtention and isolation of hybridomas which secrete these monoclonal antibodies.
The preferred monoclonal antibodies of the invention allow the detection of at least 1, 5, 10 or 20 pg/ml phosphorylated tau as determined in an ELISA using these monoclonal antibodies in the coating phase and incubating them with CSF spiked with different amounts of phosphorylated and non-phosphorylated tau without amplification. Phosphorylated tau is prepared by incubating recombinant non-phosphorylated tau with a rat brain extract capable of phosphorylation of Ser and Thr amino acids at positions corresponding to sites of abnormal phosphorylation of tau (Goedert et al., 1993), as found in tau extracts of brain tissue derived of patients having died of Alzheimer""s disease.
A process for obtaining the hybridomas of the invention involves:
starting from spleen cells of an animal, e.g. mouse or rat, previously immunized in vivo or from spleen cells of such animals previously immunized in vitro with an antigen being preferably abnormally phosphorylated tau (PHF-tau), or a phosphorylated human tau peptide or immunoaffinity purified abnormally phosphorylated tau, as disclosed below, recognized by the monoclonal antibodies of the invention;
fusing said immunized cells with myeloma cells under hybridoma-forming conditions; and
selecting those hybridomas which secrete the monoclonal antibodies which are capable of specifically recognizing a phosphorylated epitope of abnormally phosphorylated tau (PHF-tau) in cerebrospinal fluid (CSF).
The phosphorylated human tau peptide refers to a peptide comprising in its amino acid sequence a phosphorylated sequence comprised in the region spanning amino acids 143 to 254 of human tau and with said peptide being characterized by the fact that it can form an immunological complex with the antibodies of the invention.
The antigen of the invention is advantageously contained in the brain, in the cerebrospinal fluid or the serum of a patient having Alzheimer""s disease, Down""s syndrome, Pick""s disease, subacute sclerosing panencephalitis (SSPE) or other neurological diseases in which the abnormally phosphorylated tau protein is implicated; this antigen provokes an immunological reaction with the monoclonal antibody of the invention.
More particularly, the present invention relates also to monoclonal antibodies as defined above, obtained by a process such as as defined above, characterized in that it involves:
starting from the spleen cells of a mouse previously immunized with abnormally phosphorylated tau (PHF-tau) extracted and purified from a human brain sample of a patient suffering from Alzheimer""s disease (as disclosed in the examples section), or a phosphorylated human tau peptide, or immunoaffinity-purified abnormally phosphorylated tau capable of reacting with the monoclonal antibodies of the invention,
fusing said immunized cells with myeloma cells under hybridoma-forming conditions,
selecting those hybridomas which secrete monoclonal antibodies which specifically recognize PHF-tau and which are capable of specifically detecting PHF-tau in CSF (as illustrated in detail in the examples section).
A process for producing the monoclonal antibodies of the invention involves:
culturing the selected hybridomas as indicated above in an appropriate culture medium; and
recovering the monoclonal antibodies secreted by said selected hybridoma; or alternatively
implanting the selected hybridoma into the peritoneum of a mouse and, when ascites has been produced in the animal;
recovering the monoclonal antibodies then formed from said ascites.
The monoclonal antibodies of the invention can be prepared by conventional in vitro techniques such as the culturing of immobilized cells using e.g. hollow fibers or microcapsules or such as the culturing of cells in homogeneous suspension using e.g. airlift reactors or stirred bioreactors.
The invention also relates to a peptide capable of forming an immunological complex with any of the monoclonal antibodies of the invention, with said peptide being in the phosphorylated form, and,
with the sequence of said peptide comprising, or consisting of phosphorylated parts of the sequence as shown in SEQ ID NO 1, or,
with the sequence of said peptide comprising, or consisting of the sequence of any peptide being capable of forming an immunological complex with anyone of the monoclonal antibodies according to the invention.
Said phosphorylated peptides are preferably from 6 to 100 amino acids long. The peptides according to this embodiment of the invention can be prepared by classical chemical synthesis. The synthesis may be carried out in homogenous solution or in solid phase according to any of the techniques well known in the art.
Phosphorylated peptides are prepared according to any technique known in the art, (f.i. de Bont et al., 1990a; de Bont et al., 1990b; Perich, 1991; Orvos et al., 1989).
According to a preferred embodiment, the present invention relates to a phospohorylated peptide as defined above consisting of or comprising in its amino acid sequence the following sequence:
Val-Arg-Thr-Pro-Pro (amino acid 229-233; human tau 40 numbering, SEQ ID NO 2), with said Thr(231) being phosphorylated and with said peptide being characterized in that it is able to form an immunological complex with the monoclonal antibody AT180 produced by the hybridoma deposited at the ECACC on Dec. 22, 1992 under No. 92122204.
According to another preferred embodiment, the present invention relates also to a phosphorylated peptide as defined above consisting of or comprising in its amino acid sequence the following sequence:
Pro-Lys-Thr-Pro-Pro (amino acid 179-183; human tau 40 numbering; SEQ ID NO 3), with said Thr(181) being phosphorylated and with said peptide being characterized in that it is able to form an immunological complex with the monoclonal antibody AT270 produced by the hybridoma deposited at the ECACC on Jul. 7, 1993 under No. 93070774.
According to yet another embodiment, the present invention relates to a phosphorylated peptide as defined above, which is capable of generating a monoclonal antibody according to any one of claims 1 to 4 upon immunization.
The peptides used for immunization are preferentially in the form in which they are joined to a carrier molecule in order to achieve a good immunogenic response. Such carrier molecules are well known in the art and are coupled to the peptide via linker groups, which are also comprised in the art.
The invention also relates to a process for the post-mortem detection or diagnosis in vitro of a brain/neurological disease involving PHF-tau, such as Alzheimer""s disease, which comprises at least the following steps:
contacting a monoclonal antibody of the invention with a preparation of NFT or a detergent-extracted brain homogenate isolated from a patient having had Alzheimer""s disease or any other disease involving abnormally phosphorylated tau protein (PHF-tau) under conditions suitable for producing an antigen-antibody complex;
detecting the immunological binding of said antibody to said brain homogenate, and possibly separating said complex and recovering the antigen sought in a purified form.
Recovering the antigen sought may be done by first washing the immobilized antibody-antigen complex then formed;
treating this complex with a solution (e.g. 3 M potassium thiocyanate, 2.5 M magnesium chloride, 0.2 M citrate-citric acid, pH 3.5 or 0.1 M acetic acid) capable of producing the dissociation of the antigen-antibody complex; and;
recovering the antigen in a purified form.
The invention relates also to a process for the detection or diagnosis in vitro of brain/neurological disease involving abnormally phosphorylated tau protein, such as in Alzheimer""s disease, which includes:
bringing a sample of CSF, more preferably unconcentrated CSF, or a sample of serum from a patient suspected of suffering from brain disease involving PHF-tau, more particularly Alzheimer""s disease, or proteins or polypeptides as a result of an extraction procedure starting from brain tissues, cerebrospinal fluid or serum known to those skilled in the art (Ibqal et al., 1984; Greenberg and Davies, 1990) into contact under in vitro conditions with a monoclonal antibody of the invention, with said conditions being suitable for producing an antigen-antibody complex; and,
detecting the immunological binding of said antibody to said sample of brain extract, cerebrospinal fluid or serum, or proteins or polypeptides.
Advantageously, the monoclonal antibodies of the invention are in an immobilized state on a suitable support such as a resin. Alternatively, the present process may be put into practice by using any other immunoassay format known to the person skilled in the art.
The process for the detection of the antigen can then be carried out for instance as follows:
bringing together said antigen-antibody complex formed by the antigen and the antibodies of the invention with:
a second antibody
which can be a monoclonal antibody recognizing an epitope of abnormally phosphorylated tau protein, or an epitope of any phosphorylated tau peptide carrying an epitope, with said epitopes being different from the one of the invention, or
which can be a polyclonal antibody recognizing abnormally phosphorylated tau or a polyclonal antibody recognizing a peptide carrying an epitope of PHF-tau, with said polyclonal antibody being capable of forming an immunological complex with epitopes which are different from the epitope of the invention, with said polyclonal antibody being preferably purified by immunoaffinity chromatography using immobilized tau protein;
a marker either for specific tagging or coupling with said second antibody, with said marker being any possible marker known to the person skilled in the art;
appropriate buffer solutions for carrying out the immunological reaction between the monoclonal antibody of the invention and a test sample on the one hand, and the bound second antibody and the marker on the other hand.
The detection of the immunologically bound monoclonal antibody can be achieved by conventional technology comprised in the art. Advantageously, the second antibody itself carries a marker or a group for direct or indirect coupling with a marker.
The monoclonal antibodies of the invention also enable the diagnosis of Alzheimer""s disease (AD) and of any disease involving the formation of abnormally phosphorylated tau in the region 143 to 254 on the basis of CSF (i.e. to detect modified forms of tau in CSF). The problem associated herewith is that this antigen is present in a very low amount in CSF, so the detection assay must be very sensitive. This sensitivity problem may be further overcome by (i) using a combination of the monoclonal antibodies of the invention, or (ii) a combination of a monoclonal antibody of the invention with any other normal and/or abnormally phosphorylated tau monoclonal antibodies known in the art and/or (iii) by using a monoclonal antibody or a combination of monoclonal antibodies of the invention in combination with an amplification technique such as the catalyzed reporter deposition amplification technique (CARD, Bobrow et al., 1989), allowing a PHF-tau specific ELISA with a higher sensitivity.
The results obtained with the monoclonal antibodies of the invention indicate that elevated PHF-tau levels are found in AD, but may occur also in other neurological diseases where abnormal phosphorylation of tau occurs in the region of tau comprised by amino acids 143 to 254.
According to another embodiment, the present invention relates to a kit for the diagnosis in vitro of one of the following diseases: Alzheimer""s disease, Down""s syndrome, Pick""s disease and other neurological disorders in which abnormally phosphorylated tau protein or paired helical filaments are implicated, characterized in that the kit comprises:
at least one monoclonal antibody of the invention deposited on a microplate;
a preparation containing the sample (CSF, serum or the proteins extracted therefrom) to be diagnosed in vitro,
a second antibody
which can be a monoclonal antibody recognizing an epitope of abnormally phosphorylated tau protein, or an epitope of any phosphorylated tau peptide carrying an epitope, with said epitopes being different from the one of the invention, or
which can be a polyclonal antibody recognizing abnormally phosphorylated tau or a polyclonal antibody recognizing a peptide carrying an epitope of PHF-tau, with said polyclonal antibody being capable of forming an immunological complex with epitopes which are different from the epitope of the invention, with said polyclonal antibody being preferably purified by immunoaffinity chromatography using immobilized tau protein;
a marker either for specific tagging or coupling with said second antibody;
appropriate buffer solutions for carrying out the immunological reaction between the monoclonal antibody of the invention and a test sample on the one hand, and the bound second antibody and the marker on the other hand,
possibly a peptide carrying an epitope of PHF-tau comprised in the region spanning amino acids 143 to 254 for standard purposes, or for competition purposes with respect to the antigen which is sought.
A preferred embodiment of the present invention for the detection or diagnosis in vitro of brain/neurological disease involving abnormally phosphorylated tau protein, such as Alzheimer""s disease relates to a method or a kit as defined above, which comprises a mixture (combination) of monoclonal antibodies of the invention, or a combination of at least one monoclonal antibody of the invention with other antibodies capable of specifically recognizing a region of PHF-tau residing in the region spanning positions 143-254 of human tau 40 (SEQ ID NO 1), with said monoclonal antibodies being preferably chosen from:
(1) the monoclonal antibody AT180 produced by the hybridoma deposited at the ECACC on Dec. 22, 1992 under No. 92122204;
(2) the monoclonal antibody AT270 produced by the hybridoma deposited at the ECACC on Jul. 7, 1993 under No. 93070774;
(3) the monoclonal antibody AT8 produced by the hybridoma deposited at the ECACC on Oct. 8, 1991 under No. 91100806;
and with said mixture being preferably chosen from the following list:
a mixture of monoclonal antibodies comprising the monoclonal antibodies (1) and (2),
a mixture of the monoclonal antibodies comprising the monoclonal antibodies (1) and (3),
a mixture of the monoclonal antibodies comprising the monoclonal antibodies (2) and (3),
a mixture of the monoclonal antibodies comprising the monoclonal antibodies (1), (2) and (3);
with said method or kit being further characterized as containing or using:
a preparation containing the sample to be diagnosed in vitro;
a second antibody
which can be a monoclonal antibody recognizing an epitope of abnormally phosphorylated tau protein, or an epitope of any phosphorylated tau peptide carrying an epitope, with said epitopes being different from the one of the invention, or
which can be a polyclonal antibody recognizing abnormally phosphorylated tau or a polyclonal antibody recognizing a peptide carrying an epitope of PHF-tau, with said polyclonal antibody being capable of forming an immunological complex with epitopes which are different from the epitope of the invention, with said polyclonal antibody being preferably purified by immunoaffinity chromatography using immobilized tau protein;
a marker either for specific tagging or coupling with said second antibody;
appropriate buffer solutions for carrying out the immunological reaction between the monoclonal antibody of the invention and a test sample on the one hand, and the bound second antibody and the marker on the other hand,
possibly a peptide carrying an epitope of PHF-tau for standard purposes, or for competition purposes with respect to the antigen which is sought.
According to yet another preferred embodiment, the present invention relates to a method or kit for detecting or diagnosing in vitro a brain/neurological disease involving abnormally phosphorylated tau protein, such as Alzheimer""s disease, which involves a sandwich ELISA detection format comprising coating and detecting antibodies, with said coating antibodies consisting of at least one monoclonal antibody of the invention, and with said detecting antibodies consisting of at least one monoclonal antibody capable of detecting normal and/or abnormally phosphorylated human tau of which the epitope is different from any of the epitopes of the monoclonal antibodies of the invention. Such a preferred sandwich ELISA format is extensively illustrated in the examples section of the present invention.
Table 1
Detection of PHF-tau and normal tau using PHF-tau specific monoclonal antibodies AT180 and AT270. Microplates coated with saturating amounts of a monoclonal antibody specifically recognizing PHF-tau were incubated with CSF spiked with different amounts of non-phosphorylated or phosphorylated tau, the latter prepared by incubating recombinant non-phosphorylated tau with a rat brain extract capable of phosphorylating Ser and Thr amino acids at positions corresponding to the sites of abnormal phosphorylation of tau (Goedert et al., 1993). Bound antigen was detected as described in the examples section.
Table 2
CSF samples from AD patients, control patients and patients suffering from various non-AD neurological disorders were tested in ELISA using different combinations of capturing antibodies as described (example III). All values are expressed as mOD units except for the determination of total tau which was done using the Innotest htau (Innogenetics, Belgium) and which are expressed in pg/ml CSF.
The different experimental conditions used for each set-up do allow only intra-lane comparison.
Table 3
CSF samples of control patients, AD patients and patients suffering from various non-AD neurological disorders (OND) were assayed using the Innotest htau (Innogenetics, Belgium). From the cohorts of AD patients and OND patients those having high total tau values were selected for further testing using the PHF-tau specific ELISA in which AT8, AT180 and AT270 were used as capturing antibodies and AT120 and HT7 as detecting antibodies as described (Example IV). Results are expressed in pg/ml tau in CSF for total tau (Innotest htau) and as mOD units for the PHF-tau specific ELISA.
Figure 1
Detection of PHF-tau and normal tau using monoclonal antibody AT180. Microplates coated with saturating amounts of monoclonal antibody AT180 specifically recognizing PHF-tau were incubated with CSF spiked with different amounts of non-phosphorylated or phosphorylated tau, the latter prepared by incubating recombinant non-phosphorylated tau with a rat brain extract capable of phosphorylating Ser and Thr amino acids at positions corresponding to the sites of abnormal phosphorylation of tau (Goedert et al., 1993). Bound antigen was detected as described in the examples section.
Figure 2
Detection of PHF-tau and normal tau using monoclonal antibody AT270. Microplates coated with saturating amounts of monoclonal antibody AT270 specifically recognizing PHF-tau were incubated with CSF spiked with different amounts of non-phosphorylated or phosphorylated tau, the latter prepared by incubating recombinant non-phosphorylated tau with a rat brain extract capable of phosphorylating Ser and Thr amino acids at positions corresponding to the sites of abnormal phosphorylation of tau (Goedert et al., 1993). Bound antigen was detected as described in the examples section.
Figure 3
Phosphorylation of wild-type and mutated recombinant tau (expressed from clone human tau 24; Goedert and Jakes, 1990) with the protein kinase activity from rat brain. Immunoblots with anti-tau antiserum 134 and monoclonal antibodies AT8 and AT180. Lanes 1. tau 24; 2, tau 24 plus brain extract; 3, T231 A tau 24; 4, T231 A tau 24 plus brain extract, 5, S235 A tau 24; 6, S235 A tau 24 plus brain extract.
Figure 4
Phosphorylation of wild-type and mutated recombinant tau (expressed from clone human tau 24) with the protein kinase activity from rat brain. Immunoblots with anti-tau antiserum 134 and monoclonal antibodies AT8 and AT270. Lanes 1, tau 24; 2, tau 24 plus brain extract; 3, T175 A tau 24; 4, T175 A tau 24 plus brain extract; 5, T181 A tau 24; 6, T181A tau 24 plus brain extract.

Method for the diagnosis of brain/neurological disease using monoclonal antibodies specific for PHF-tau, hybridomas secreting them, and antigen recognition by these antibodies and their applications

Abstract: with each monoclonal body specifically detecting abnormally phosphorylated tau protein (PHF-tau)in cerebrospinal fluid (CSF).


A transistor includes source/drain electrodes provided on a substrate; a semiconductor oxide layer provided between the source/drain electrodes; a gate electrode facing the semiconductor oxide layer; and a gate insulating layer interposed between the semiconductor oxide layer and the gate electrode, wherein the semiconductor oxide layer has a nano-layered structure including at least one first nano layer comprised of a first material and at least one second nano layer comprised of a second material that are alternatingly stacked one on another to provide at least one interface, and wherein the first material and the second material are different materials that are effective to form an electron transfer channel layer at the interface.

Example embodiments of the inventive concept relate to a transistor, and in particular, to an oxide semiconductor thin film transistor.
A variety of transistors are proposed to meet an increasing demand for small-sized electronic devices. For example, research on thin-film type transistors is actively being conducted.
To meet a demand for a next-generation display technology with large-area, high resolution, and high frame rate, a transistor is needed to have high electron mobility. Oxide semiconductor transistors provide technical advantages, such as high electron mobility and low temperature process compatibility, and thus, there is an increasing interest on the development of the oxide semiconductor transistor.

Oxide transistor with nano-layered structure

ELECTRONICS AND TELECOMMUNICATIONS RESEARCH INSTITUTE


Disclosed is a device useful for preserving tissue samples after extraction from human or animal patients. The device includes a circular blade for taking a tissue sample, the blade being coupled to a sealing cap which mates to one end of a container. A retrieval port is also disclosed for extracting fluids from the container. Methods are also disclosed by which tissue samples may be taken and prepared for storage, processing, culture, or other analysis.

The present invention relates to a device for extraction, collection, transport, processing and preservation of a living tissue sample.
Certain therapies utilize stem cells for the treatment of diseases and conditions in humans and animals. Optimally the stem cells are obtained from the patient, cultured and processed for storage. Many stem cell based therapies require a large number of viable cells. Procedures for culturing and preserving a desired population of stem cells have been well refined over the years. However, one common problem that remains is in collecting the cells and transporting them to another location for culturing.

Vial useable in tissue extraction procedures


A touch screen display apparatus and a method of driving the same in which the touch screen display apparatus includes a first transparent substrate, a gate line and a sensor conductor formed on the first transparent substrate, a data line insulated from and intersecting the gate line and sensor conductor, a second transparent substrate facing the first transparent substrate, and a sensor electrode formed on the second transparent substrate so as to correspond to an intersection of the sensor conductor and the data line, the sensor electrode electrically connecting the sensor conductor with the data line when acted upon by an external pressure.

1. Field of the Invention
The present invention relates to a display apparatus having a touch screen and a method of driving the same.
2. Description of the Related Art
Touch screen displays can be used in place of a conventional keyboard or mouse for data entry. A touch panel, once installed on a liquid crystal panel, allows a user to execute desired operations by touching displayed objects. A touch screen display apparatus can be used in combination with computer-based training and simulated applications, office automation fields, education applications, game applications, and so on.
A conventional touch screen display apparatus is basically constructed of a liquid crystal panel, a touch panel attached to the liquid crystal panel, a controller, a device driver, and application software. The liquid crystal panel includes two plates having a plurality of electrodes and a liquid crystal layer interposed between the two plates. Voltages applied to the electrodes rearrange the liquid crystal molecules to control light transmittance and display images.
A touch panel affixed to an LCD apparatus comprises a pair of substrates facing each other, upper and lower conductive layers formed on the substrates, and a plurality of dot spacers interposed between the pair of substrates. If a user touches a particular position on the touch panel, the upper and lower conductive layers come into contact at the particular position so as to be electrically connected, thereby allowing position information to be identified.
The conventional touch screen display apparatus having a separate touch panel attached to the liquid crystal panel is bulky and not easy to use while in motion. Accordingly, a touch screen display apparatus that is light in weight and small in size would be desirable.

Touch screen display apparatus and method of driving the same


A perpendicular writer of the present invention comprises a main pole connected to two return poles and further includes one or more shorting shields thereby reducing erasure field on double layer perpendicular media. The perpendicular writer may include side shorting shields connecting the first and second return poles thereby modifying the crosstrack field gradient. Additionally, the perpendicular writer may include a top shorting shield modifying the downtrack gradient and may additionally include a bottom shorting shield for further reduction of erasure fields. The distance between the main pole and the shorting shields may be modified to customize the write field gradient.

The present invention relates generally to the storage and retrieval of data within magnetic media. In particular, the present invention relates to the placement of shorting shields around the main pole of a perpendicular writer.
A typical transducing head consists of two portions: a writer portion for storing magnetically encoded information on magnetic media and a reader portion for retrieving the magnetically encoded information from the media. The magnetic media is typically organized into tracks which are further organized into bit fields. The MR sensor travels along a track in close proximity to the media to detect differences in the stored magnetic flux between bit fields. Changes in the magnetic flux from one bit field to another result in a corresponding resistivity change and consequent voltage output from the MR sensor. Since it is the changes from one bit field to another that are detected and result in data output; it is critical that those transitions be sharp, that is, as narrow as possible. Sharp transitions, as well as other characteristics for successful reading, are not controlled by the reader, but instead by the writer and the process used to encode the data within the magnetic media.
A perpendicular writer typically consists of a main pole with at least one adjacent return pole separated from each other at an air bearing surface. Additionally, the magnetic poles are connected by a back via at a region away from the air bearing surface. Positioned between the two poles are one or more layers of conductive coils encapsulated by electrically insulating layers. To write data to the magnetic media, a time varying electrical current, or write current is caused to flow through the conductive coils.
The write current produces a time varying magnetic field in the magnetic poles called the write field. The magnetic poles, back via and the magnetic media are part of a magnetic flux path, which is also referred to as a reluctance circuit. The write field passes from the main pole into the magnetic media, thereby writing to a recording layer within the media. Residual magnetic flux from the main pole closes the reluctance circuit via a soft underlayer of the magnetic media. As magnetic flux passes through recording layer, thereby closing the reluctance circuit through soft underlayer, recorded bits can be destabilized resulting in the information stored in the recording layer being erased.
Recent years have seen a considerable increase in data storage densities. Generally, the storage capacity of a magnetic data storage and retrieval device is increased through use of magnetic media having an increased areal density. Areal density is the number of units of data stored in a unit area of the media. Areal density is determined by two components of the magnetic media: the track density (the number of data tracks per unit width of the magnetic media) and the linear density (the number of units of data stored per unit of length of the data track). To increase the areal density of a magnetic media one must increase the linear density and/or the track density of the magnetic media.
Increases in areal density demand that writers must write to smaller bit fields with increasing flux density. One problem with conventional perpendicular writers is the effect of the write field on adjacent tracks and bit fields. The process of writing one bit field may cause erasure of the magnetic data stored both to the side in adjacent tracks or to the adjacent bit fields in front or behind the write head. That portion of the write field that causes unwanted erasure is referred to as erasure field. There remains a continuing need in the art for improved perpendicular writers with reduced erasure fields.

Head for perpendicular recording with reduced erasure