Disclosed is method of measuring the displacement between a reference region of a reference image and a sample region of a sample image. The method spatially varies the reference region using a one-dimensional filter having complex kernel values, wherein a length (radius) and direction (angle or tangent segment) of the filter is a function of position in the reference region. The method then measures a displacement between the reference region and the sample region by comparing the spatially varied reference region and the sample region.

Many applications require the measurement of relative spatial distortions between a pair of similar two-dimensional images. Each pair will often consist of a faithful representation of an original, which may be called a "reference" image, and a degraded representation of this original, which may be called the "target" image.
The degradation of the target image with respect to the reference image can take many forms. As examples, the target image may be a printed and scanned version of the reference image; it may be a feature which has moved in a portion of a video sequence; or it may be obtained from a digital photograph captured under different conditions from the reference image.
The terms "reference" and "target" can be interchanged for some applications, and there may not be differences in quality between the two images. Sometimes they may be taken from a single image, or from a series of images.
Degradation in quality can arise due to spatial distortion between the two images. Estimating the distortion can provide for accommodation or correction of the distortion. The basis of many spatial distortion estimation methods is shift estimation, in which an estimate is made of the translation required of one image to best align it with the other.
Where spatial distortion is not just a simple translation, shift estimation can be used to determine translation between pairs of reference and target tiles (also referred to as patches) extracted from the reference and target images respectively. A collection of shift estimates from multiple locations in the images can be used to determine more complicated spatial distortions such as rotation, scaling, arbitrary affine distortion, perspective distortion, and non-linear distortion, such as barrel distortion.
The measurement of spatial distortion between tiles supports many applications. Such a measurement can be used for the direct measurement of alignment quality in printing and/or scanning devices; for assisting in the adjustment of the printing or scanning devices; or as a pre-processing step to allow accurate alignment of two images, one directly over the other, to allow direct comparison of a printed copy with its original. This comparison can allow evaluation of the quality of printing, and also verification that the printed output is free from defects. Such measurement can also provide information about the physical state of an imaging system, where a rotation angle, or a scale factor, represent a proxy for another physical variables in the system.
Several techniques have been used for such shift estimation, including correlation, phase correlation, least-squares fitting, and gradient-based shift estimation (GBSE).
The correlation operation, denoted by , is a method of comparing two tiles and which calculates the summed products of corresponding pixels in two tiles at multiple shift positions:
  h  =                    f        ⊗        g            ⇔              h                          (                      x            ,            y                    )                      =                  ∑                  i          ,          j                                                                      f                                (                          i              ,              j                        )                          ·                  g                                (                                          x                +                i                            ,                              y                +                j                                      )
If there exists a position of maximum matching overlap between the two tiles, the value of the correlation will be a maximum at this position.
Correlation can be performed efficiently using the Fourier Transform, where (f) is the Fourier transform of f, −1(f) is the inverse Fourier transform, and, (g)* is the conjugate of the Fourier transform of g:fg=−1(((f)·(g)*)
To achieve a sharp, easily-detectible correlation peak, phase correlation, in which each term in the correlation product is replaced by a complex value with unit modulus, can be used, and is denoted by :
      (          f                    ⊗        ^                  g        )    =            ℱ              -        1              (                            (                                    ℱ                                            (                f                )                                      ·                                          ℱ                                                  (                  g                  )                                            *                                )                                  (                      u            ,            v                    )                                                          (                                          ℱ                                                  (                  f                  )                                            ·                                                ℱ                                                        (                    g                    )                                                  *                                      )                                          (                          u              ,              v                        )                                        )
A pre-processing step for the reference and target tile is necessary to assist with phase correlation as a shift-estimation method. In a phase correlation operation, the edges of a tile can form a very strong feature, as they can appear very similar to a strong line segment. This may result in a "false" correlation peak being formed at the origin by a match of the edges of one tile with the edges of the other, or anywhere else by a match of the edges of one tile with a line feature in the other. To mitigate this effect, the two tiles can be pre-processed using a combination of padding, high-pass filtering, and a half-Hann window, or similar, on the edge pixels. Such techniques are known in the art. Applying a window, such as a half Hann window, to pixels near the tile edges is sometimes referred to in this disclosure as hedging.
It is also necessary to choose a tile containing appropriate detail for shift estimation purposes. The tile must contain sufficient high-frequency or mid-frequency information with orientation of at least two substantially different angles. If no high-frequency information is present in the tile, the correlation peak will be broad and subject to distortion by any lighting gradient in the input tiles, and is likely to lead to inaccurate shift estimation. If the frequency content exists substantially in a single direction, then shift estimation will be inaccurate in a direction orthogonal to the tile features. If a tile contains periodic features, such as a grid of lines or a dotted line, then there may be ambiguity in a matching shift, possibly resulting in incorrect shift estimation also.
If the two tiles are shifted relative to each other, and have been chosen to have appropriate detail for shift estimation, then a correlation peak will appear at a displacement from the origin directly corresponding to the shift between the two tiles.
By measuring tiles of corresponding portions of the reference and the target image in several places, a more complicated global transform than just shift can be measured.
For example, by measuring relative shift at three non-collinear positions, an affine transform can be derived relating the two tiles. By measuring relative shift at many points, a least-squares fit to some global transformation may be derived, or a complete "warp map" estimated for one or both images which can relate every pixel in one image to a pixel position in the other.
In many applications, it is common for there to be a small relative rotation between the two tiles being measured. For example, the rotation may be caused by a rotation of a page on a scanner platen, or the rotation of paper inside the feed path during printing, or by a small misalignment of a camera.
The introduction of a small relative rotation between two tiles can have a marked and deleterious effect on shift estimation. For example, for a 128×128 tile, a measured accuracy of phase correlation is reduced from an error of below 0.02 pixels at 0°, to an error of 0.15 pixels at 1° and almost a whole pixel at 2°.
Aside from the effect of a small rotation on individual tiles, a small rotation can cause the local shift between two images to change markedly across the whole image. For example, a 600 dpi scan of a piece of Letter-sized paper of 8.5×11 inches has dimensions of approximately 5,100×6,600 pixels. A 1° relative rotation between the reference and the scanned target image will result in a local shift of more than 100 pixels difference between the top and the bottom of the page. Such a shift will substantially reduce the common overlap between two tiles of size 128×128 and hence greatly reduce shift estimation accuracy for these tiles.
The two negative effects of rotation on shift estimation, namely decreasing accuracy and larger shift, both combine to greatly reduce shift estimation accuracy, to the point where shift estimation is likely to fail completely.
Such effects require that several, potentially inaccurate, measurements must be taken at corresponding positions of the reference and target images before a global transform can be derived. Because of the potential unknown shift between the reference and target tiles, it is also necessary to extract tiles of size much larger than is necessary to estimate shift in exactly corresponding tiles in order to ensure that there will be sufficient overlapping in relatively shifted tiles.
A spatially varying blur has been proposed to reduce the effect of rotation and scaling on correlation. However, such a blur will remove almost all high frequencies in a reference tile except at the very centre of the tile. As it is the high frequencies in a tile which provide the sharpness of a correlation peak, this operation can also greatly reduce shift estimation accuracy.
Correction measures have been proposed for the GBSE method which afford some robustness against rotation and scaling. However, such measures are only effective where the largest shift in tiles being measured is less than a single pixel. Under a rotation of 2°, the difference in shift from the top to the bottom of a tile is 2 pixels for a 64×64 tile, and 4.5 pixels for a 128×128 tile.
Two simple techniques can reduce the effect of rotation on shift estimation methods. Using a smaller tile can reduce the effect of rotation on shift estimation, but will also reduce the maximum shift that can be estimated. Down-sampling both tiles before measurement can also reduce the effect of rotation on shift estimation, but will also reduce accuracy, as measured shifts will be only a fraction of the true shift.
Note that relative image scaling has a similar effect to that of rotation on shift estimation. However, a relative scaling can usually be discounted in many applications, because the scaling factor of optical and print devices is known prior to the commencement of processing and so can be corrected automatically, if it is necessary to do so.
A least-squares fit can model and measure rotation, scaling and/or shift for pairs of tiles, but such methods usually involve an iterative search, and can be very slow.
Fourier techniques involving log-polar transforms and multiple correlations can also be used to estimate rotation, scaling and translation over a very wide range, but they are also very slow.
While it is possible to achieve some robustness to rotation with the above methods, this robustness is generally at the expense of measurement accuracy, and these methods do not provide a way to directly estimate rotation angle or scaling using only a single measurement.

Estimation of shift and small image distortion


An actuator assembly is provided having a ramp for unloading a transducing head from a storage medium. The actuator assembly includes an actuator arm rotatable about a pivot point and configured to access data on a storage medium. The actuator arm has a base end coupled to a lift tab and a distal end coupled to a transducing head. The actuator assembly also includes an inclined surface located adjacent the base end. The inclined surface is configured to engage with the lift tab to guide the transducing head away from the storage medium.

A typical data storage system includes a housing that encloses a variety of components. For example, in a disc drive, the components include at least one rotating disc having data on one or more surfaces that are coated with a medium for storage of digital information. The disc(s) are mounted on a spindle motor that causes the disc(s) to spin. Each surface of the disc(s), which are coated with a medium, pass under a respective bearing slider surface. Each slider carries transducers, which write information to and read information from the data surfaces of the disc(s). The slider and transducers are often together referred to as the "head."
An actuator assembly moves the head or heads from an inner diameter to an outer diameter of a storage medium and across data tracks under control of electronic circuitry. The actuator assembly includes a track accessing arm, a suspension for each head and a voice coil motor. In general, each head is supported by a suspension that is in turn attached to the track accessing arm. The voice coil motor rotates the track accessing arm about a pivot shaft to position a head over a desired data track.
When the data storage system is de-energized, the actuator assembly can move the head or heads attached to the track accessing arm to a location on the storage medium designated as the "park" location. The park location is usually located about an outer diameter or an inner diameter of the storage medium and is typically called the landing or parking zone of the medium. The landing zone of the storage medium generally does not include any useable data because of the physical contact between the head and the storage medium in the landing zone. In addition, the landing zone can be roughened to minimize stiction of the head against the storage medium.
Alternatively, the actuator assembly can move the head(s) to a load/unload ramp, which serves as a park location that is adjacent the storage medium. Generally, the load/unload ramp is a stationary component that guides the head(s) and lifts them off the surface of the storage medium during unload and guides the head(s) to move down the ramp during loading onto the storage medium. Unlike utilizing a landing zone on the storage medium to park the heads, a load/unload ramp provides a place for the head(s) to be positioned away from the storage medium such that more space of the storage medium can be used for useable data.
A load/unload ramp positioned adjacent the storage medium, however, requires space in the data storage system, thereby limiting how small the data storage system can be. This especially becomes problematic in smaller form factors. In addition, the load/unload ramp positioned adjacent the storage medium can be difficult to assemble. High precision is needed in assembling the load/unload ramp such that the delicate suspension and head are able to properly merge onto the ramp. Therefore, there is a need to load and unload a head of a disc drive that does not limit data storage space, is easy to assemble and is cost effective.

Load/unload ramp for an actuator assembly in a data storage device


Past systems have attempted to cool the combustor end or tip of fuel injection nozzles, however, such methods have failed to attain adequate cooling and life. The present system or structure for cooling a tip or combustion end of a fuel injection nozzle is accomplished with a twofold structure. First, a plurality of openings being acutely positioned in the combustor end about a plurality of base circles provide effective air-sweep cooling. Secondly, the convection cooling of a back face and a combustion face provides effective convection cooling. The two structures are combined to provide an effective, efficient cooling of the combustor end or tip. The combustor end of the fuel injection nozzle is maintained at a temperature low enough to prevent failure of the combustor end through oxidation, cracking and buckling and the air-sweep avoids carbon deposits on the combustor face.

The front face of a fuel injection nozzle is exposed to high temperature combustion gases that can reach temperatures as high as 2200 degrees C. Due to the extremely high levels of turbulence generated by swirl and primary zone jets, the heat transfer rates to the fuel injection nozzle tip are increased, it is important that the front face of the fuel injection nozzle tip be adequately cooled. Typical cooling techniques include convection and air-sweep cooling.
If a convection cooled fuel injection nozzle tip is cooled excessively, it tends to accumulate deposits of combustion generated carbon that can interfere with fuel atomization and dispersion, resulting in poor combustion efficiency and hot spots. If the injector is allowed to run at temperatures higher than 800 degrees C., failure of the front face can cause secondary damage to the combustor walls through oxidation, cracking, and buckling. The combustor exit temperature profile and pattern factor can deteriorate, resulting in damage to the downstream gas turbine components.
An example of past injection nozzles in which an attempt has been made to cool the front face is disclosed in U.S. Pat. No. 4,977,740 issued on Dec. 18, 1990 to Thomas J. Madden et al. The injection nozzle disclosed includes an air passage through which cooling air is directed into contact with the inside surface of a conical deflector portion of a conical deflector section. Thus, an attempt to cool the tip by convection at the inner surface is disclosed.
Another example of an injection nozzle attempting to cool a front face is disclosed in U.S. Pat. No. 4,798,330 issued on Jan. 17, 1989 to Alfred A. Mancini et al. Cooling air passes through an air swirl chamber and terminates in an outer air discharge orifice. A portion of the air exits an aperture in the front face and is used to attempt to cool the front face.
Another example of an injection nozzle attempting to cool a front face is disclosed in U.S. Pat. No. 4,600,151 issued on Jul. 15, 1986 to Jerome R. Bradley. The injection nozzle disclosed includes an air passage through which cooling air is directed into contact with the inside surface of a frusto-conical portion of a shroud member.
Another example of an injection nozzle attempting to cool a front face is disclosed in U.S. Pat. No. 3,866,413 issued Feb. 18, 1975 to Geoffrey J. Sturgess. Cooling air enters through a plurality of ports and cools the dome.
Another example of an injection nozzle attempting to cool a front face is disclosed in U.S. Pat. No. 3,684,186 issued Aug. 15, 1972 to William F. Helmrich. This patent discloses a secondary air swirl chamber formed by a portion of a shroud. The air exiting the chamber partially cools the front face prior to being mixed with fuel.
Another example of an injection nozzle is disclosed in U.S. Pat. No. 3,483,700 issued Dec. 16, 1969 to John G. Ryberg et al. The patent discloses a front face having a plurality of scoops formed therein. A mixture of fuel and air pass through the scoops into a combustion chamber. The mixture of fuel and air attempts to cool the front face.
Many attempts have been made to improve front face cooling and to extend the life of fuel injection nozzles. Experimentation has shown that it is difficult to achieve optimum front face temperature with both gaseous and liquid fuels over the complete range of loads and ambient conditions in a gas turbine engine. Thus, using convective cooling or air-sweep alone does not appear to solve the front face cooling problem. It appears that a combination of convective cooling and air-sweep cooling usually has better durability. This is due to the lower front face temperature and avoidance of carbon deposits by air-sweeping action.


An electronic social networking environment enables the transfer of stored value between users of the environment. A transfer may be in the form of a gift from one user to another. The stored value may represent actual currency or virtual currency. The stored value may be redeemed within or outside the electronic social networking environment, and may be redeemed with one or more merchants. The stored value may be redeemed for a physical item or service or for a virtual item or service.

Gift cards and certificates are a popular way of giving gifts. In a typical gift card scenario, the gift giver travels to a merchant and purchases a card that is associated with a certain amount of stored value, often the purchase price. The giver then mails or delivers the card to the recipient, who redeems the value by traveling to the merchant, picking out an item to purchase, and presenting the gift card as a form of payment. This scenario is inconvenient for both the giver and the recipient, especially if the giver and recipient live in widely separated locations, or if the recipient does not live near a retail location of the merchant at which a received card is redeemable.

Systems and methods for stored-value exchange within social networking environments


A vacuum switch with an elongated cartridge comprising a cylindrical housing sealed by two end plates. Inside the cylindrical housing there are two arcing contacts, one stationary and one movable. The stationary contact is securedly affixed to one of the end plates, whereas the other movable contact is mounted to axially slide inside the cartridge. At least two portions of turn are mounted in parallel. Each portion has a first end electrically connected to one of the arcing contacts and a second end electrically connected to the current input strip of the contact. The first and second ends of each portion of turn are electrically connected by a branch-off designed to disperse a part of the main current trough the potions of turn during breaking.

The present invention relates to a vacuum electrical switch designed to perform breaking in an electrical circuit notably a low or medium voltage circuit.
A circuit breaker of this kind is known as described in the Patent Application FR-2,682,808 filed by the applicant comprising a vacuum cartridge in which there are housed two arcing contacts, one stationary one of these contacts being securedly affixed to one of the end plates whereas the other, movable, contact is mounted with axial sliding inside the cartridge between a closed position and a position in which the contacts are separated resulting in formation of an arcing current. This circuit breaker comprises in addition a coil arranged coaxially outside the cartridge facing the separation gap of the arcing contacts, this coil being designed to produce an axial magnetic field in the arc formation zone. One of the shortcomings of this type of circuit breaker stems from the fact that the coil being connected in series with the arcing contacts, the whole of the main current flows through the coil. This results in it being necessary to provide a coil of large cross-section which therefore presents large overall dimensions and gives rise to considerable losses.
One of the solutions to this problem consists, as described in patent application Ser. No. 9,413,408 filed by the applicant, in fitting a branch-off means between the two ends of the coil, said means being designed to branch a part of the main current off through the coil during breaking in order to create a reduced axial magnetic field and thereby a reduced loss. However, in this embodiment, the thermal losses remain high.

Vacuum electrical switch or circuit breaker


In one embodiment, the fixing apparatus of the present invention is a fixing apparatus in which while recording paper is transported sandwiched between a heating roller and a pressure roller that are pressed against each other, the recording paper is guided by a guide member, and heat and pressure are applied to the recording paper to fix toner on the recording paper, the fixing apparatus configured with the guide member rotatably provided such that the guide member can be removed from the transport path of the recording paper, and the center of rotational movement of the guide member matched with a shaft of the heating roller or a shaft of the pressure roller.

1. Field of the Invention
The present invention relates to a fixing apparatus used in an electrophotographic image forming apparatus.
2. Description of the Related Art
This type of image forming apparatus is provided as a copy machine, a printer, a facsimile apparatus, or the like. In this apparatus, an electrostatic latent image is formed on a photosensitive body, the electrostatic latent image on the photosensitive body is developed using toner to form a toner image on the photosensitive body, the toner image is transferred from the photosensitive body to recording paper, and heat and pressure are applied to the recording paper to fix the toner image on the recording paper.
Recently, reduction in the size of those various image forming apparatuses has been advancing, reducing excess space inside the apparatus, so that many components are arranged close to each other. Thus, when a jam occurs, in which recording paper in the midst of transport becomes blocked, it is difficult to remove the recording paper. Several opening-closing locations are provided along the transport path so that the transport path is opened by opening these opening-closing locations, but because many components are also disposed around the transport path, even if the transport path is opened, those components may be a hindrance to removing the recording paper. Also, there is a risk that when removing the recording paper, the recording paper will be rubbed against a peripheral component, leading to a reduction in component precision or damaging a component.
In a fixing apparatus, while transporting recording paper sandwiched between a heating roller and a pressure roller, heat and pressure are applied to the recording paper to fix toner on the recording paper by melting the toner with heat, so a jam may occur due to the recording paper rolling around the heating roller or the pressure roller, and thus an opening-closing location is also provided in the vicinity of the fixing apparatus so that it is possible to remove the recording paper.
Also, in the fixing apparatus, a guide member is provided in order to guide the recording paper, but because this guide member hinders the removal of recording paper, a configuration is adopted in which it is possible to move the guide member when removing the recording paper.
For example, in a fixing apparatus according to the related art as shown in FIG. 9, the recording paper is transported sandwiched between a heating roller 101 and a pressure roller 102, the recording paper is guided between a paper separation plate 104 and a guide member 103, and the recording paper is further transported by a transport roller 105. The guide member 103 is rotationally supported axially by a shaft 103a. When a recording paper jam has occurred, the guide member 103 is rotated around the shaft 103a in the direction of arrow C, removing the guide member 103 from the recording paper transport path as indicated by the double-dotted line, and thus the area around the transport path is widely vacated so that the recording paper can easily be removed.
Also, in JP H02-81855A, on the downstream side of the fixing apparatus in the transport direction of the recording paper, a transport mechanism including the transport roller or the like is removed from the fixing apparatus, thus opening the downstream side of the fixing apparatus, so that it is possible to remove recording paper jammed in the fixing apparatus.
However, in order to rotate the guide member 103 around the shaft 103a along the trajectory tr of the double-dotted line as shown in FIG. 9, a large space for evacuating the guide member 103 is necessary, and this space prevents a reduction in the size of the image forming apparatus. Also, the space therefore cannot be made sufficiently large, and even if the guide member 103 is rotated, it is not possible to widely vacate the area around the transport path, and thus the recording paper cannot be easily removed. In addition, when the user makes an excessive attempt to remove the recording paper, there is a risk that the user's hand will touch the heating roller, or that the heating roller 101, the pressure roller 102, the paper separation plate 104, a temperature sensor (not shown), or the like will be damaged.
Also, even in a state with the guide member 103 positioned at a prescribed position when guiding the recording paper, the guide member 103 occupies a large amount of space, and this also prevents a reduction in the size of the image forming apparatus.
Also, as disclosed in JP H02-81855A, in a case in which a transport mechanism including the transport roller or the like is removed from the fixing apparatus, a large space for evacuating the guide member is necessary, thus preventing a reduction in the size of the image forming apparatus.


A protective device for the upturned tip of snow skis which is in the form of a cap made from a resiliently flexible, weatherproof material and which provides a cushioning surface to the tip of the ski as protection against injury to skiers who may be hit by runaway skis. The cap is preferably mounted to the ski tip by a weather resistant adhesive so as to be in place at all times. In an alternative embodiment, the cap may be provided with friction producing elements to resist inadvertent removal while allowing its interchangability between multiple skis.

Modern skis have sharp tips at their forward ends which can inflict injuries on skiers when fallen upon or when skiers are hit by runaway skis.
Prior devices have been proposed to provide protective means for skis to prevent marring of their surfaces as well as to reduce injuries resulting from collisions. For example, U.S. Pat. No. 3,424,469 to Hooker provides a protective strip of strong, resilient material bonded to the top edge corners of skis to prevent chipping and burring of those edges. This strip provides little or no protection against injury inflicted by the ski tip.
U.S. Pat. No. 3,876,216 to Wehr discloses a safety head to be fastened to the front end of a ski and thereby enclose the ski tip. However, the device includes a metal cap which reduces its effectiveness. Furthermore, the bulbous shape of the Wehr device hinders the flow of the ski through snow, particularly deep powder.
U.S. Pat. No. 4,083,572 to May, Jr., provides a ski tip attachment in the form of a sleeve which fits over a ski tip and has a means for mounting a light source so as to extend beyond the ski tip. The purpose of this device is to provide illumination in front of a skier, not cushioning for the ski tip. The light fixture itself presents a hazard to skiers in the event they are struck by the ski.
None of the devices of the prior art provide a simple protective means for the forward tip of the ski which provides adequate protection against injury while not interfering with the operation of the ski.


According to one embodiment, a method of manufacturing a display device, includes preparing a first substrate formed such that a first resin layer is formed on a first support substrate, preparing a second substrate formed such that a second resin layer is formed on a second support substrate, attaching the first substrate and the second substrate, peeling the second support substrate from the second resin layer by radiating a first laser beam toward the second substrate, mounting a signal supply source on a first mounting portion in a state in which the second resin layer, which is opposed to the first mounting portion, is warped in a direction away from the first mounting portion, and adhering the first resin layer and the second resin layer.

Flat-panel display devices, such as an organic electroluminescence (EL) display device and a liquid crystal display device, have been used in various fields. In recent years, as regards mobile information terminal devices such as mobile phones and PDAs (personal digital assistants), there has been an increasing demand for a display device having a less thickness and a less weight.
For example, such a technique has been proposed that peeling of a connection part is suppressed by providing a wiring board between a flexible first substrate and a flexible second substrate on the outside of a display portion. In addition, as another example, such a technique has been proposed that a flexible display panel module is sandwiched between two resin sheets, these two resin sheets are thermocompression-bonded, and a flexible printed circuit board, which is connected to an end portion of the display panel module, is also sandwiched between the two resin sheets, thereby enhancing sealing properties and ensuring protection against the external environment.
On the other hand, there has been a demand for simplifying a manufacturing process and improving productivity in achieving mass-production of display devices, while enhancing reliability.

Display device and method of manufacturing the same


A method of measuring a parameter of a structure (212) on a medical image (200) comprises a measurement tool (220) displayed on a slice of the image. An automated point detection function identifies a point within at least one region (250) of the image that optimizes the placement of the respective end of the measurement tool (220). The region may be 2-d or 3-d. The identified point(s) are then used to calculate the parameter, which may be distance, angle, area or volume. The measurement tool (320) may move to the identified points (330, 340). A system (2000), computer program and computer-readable medium are also provided. The invention may make the measurement of tumors, and measurements of the spacing within or between various structures on a medical image, more accurate and/or more consistent.

A variety of technologies can be used to provide medical images. Typical modern sources of medical images are ultrasound scans, CT scans and MRI scans.
Most medical imaging involves images of humans. However, images may also be obtained of non-human animals, particularly as part of medical research projects. Medical images need to be read, analysed and reviewed by specialists.
Medical images may include information about a wide variety of anatomical features, structures, spaces and distances. For example, an image may show various types of healthy tissue, such as bone and/or organs, within the body. An image may also show abnormal tissues, such as tumours, cysts, swollen glands or other lesions. The word 'tumour' should henceforth be construed to include other types of abnormal tissues.
It is often necessary to estimate the size and volume of anatomical structures that are shown in medical images. The size of healthy tissue may be determined in order, for example, to measure growth in children.
These estimates may also serve, for example, to monitor the growth of abnormal tissue. Both the size of abnormal tissue, and the spacing between abnormal tissue and healthier tissue, may be of interest.
Here a 'structure' should be interpreted very broadly, and might include:
(i) A single entity, such as an organ, bone or tumour.
(ii) A group of essentially separate objects, such as ribs in a rib cage, or two separate tumours visible on one image.
(iii) A gap bordered by two or more objects or edges, such as the spacing between a tumour and the surface of a body, or between a tumour and a nearby organ.
Henceforth, a 'structure' that may be measured on an image may in fact be a single entity, or even a spacing between two different entities.
One prior art example where measurements are necessary is in the reading of images from cancer patients. Measurements of the principal dimensions of any suspected tumours are typically required for diagnosis and staging of disease. These measurements are also required for assessing the efficacy of any administered treatment.
In other fields of medicine, it may be necessary to obtain estimates of:
(i) The size or volume of normal anatomy, e.g. organs; or
(ii) Distances or angles between anatomical structures.
Much existing medical practice was developed for non-digital 2-d images, such as X-Ray films. Radiologists may obtain measurements directly from the hard copy of the image, using callipers or a ruler.
However, medical images are increasingly obtained and manipulated in digital format. In digital Radiology, either 2-d ('2-d') or 3-d ('3-d') images may be available. If the original image was only 2-d, then a user views a 2-d representation of that image.
A 3-d image from a scan typically includes a large volume of data points. Henceforth, the word 'image' describes the collection of all these data points. Normally therefore an 'image' will mean a 3-d image, but some embodiments of the present invention are applicable to 2-d images, such as those often obtained from ultrasound scans.
A user will normally view only one individual 2 dimensional 'slice' through the 3-d image. An image slice from a 3-d image is simply a 2-d representation, consisting of those data points that lie on a particular 2-d plane through the 3-d image. A typical 3-d image, such as one from an MRI scan, will have a matrix of regularly spaced data points. As a non-limiting example, the MRI-scan may have data points whose centres are spaced by 1 millimeter in the x- and y-directions across any plane of the scan. Consecutive planes may, for example, be parallel and separated by 7 millimeters.
Although it is usual for data points to be in the plane of a viewed image slice, it is possible that the points only lie near to the plane of the slice, for example when an 'off-axis' viewing angle has been selected.
Medical imaging workstations commonly provide tools for obtaining the required measurements directly from the displayed image slices.
Examples of the tools available on medical imaging workstations are digital callipers or a digital ruler. When working with such tools, the user is typically required to select and then click onto two reference points on the image slice. The workstation then calculates the real-world distance between the two reference points, and reports the result in cm or mm. Here 'real-world' means the distance on the object that was scanned, rather than the distance across the screen.
FIG. 1 generally illustrates a conventional ruler, available on current medical imaging workstations.
In FIG. 1, reference 100 indicates a medical image slice. Image slice 100 is displayed on a screen 105, which may be part of a medical imaging workstation.
Reference 110 indicates schematically the outer edge of a portion of medical image slice 100, i.e. of the object that was scanned. Reference 110 may, for example, indicate the outer edge of a torso.
Reference 112 shows a structure, also in cross-sectional view, that is located on medical image slice 100. Structure 112 might be a tumour, but might instead be an organ. Only portions of the tumour or organ that lie in the plane of the image slice 100 will be visible. Other portions that lie in neighbouring image slices, will not be visible on slice 100.
Reference 120 shows a linear ruler, which is unidirectional. A user has aligned linear ruler 120 between points 130 and 140 on structure 112, having selected these points as being of significance. The user has identified points 130 and 140 as being the end points of the longest axis or diameter of structure 112.
The linear ruler 120 then provides a readout of the distance between points 130 and 140. The readout is shown as 28 mm on FIG. 1. The numerical value of the measurement may be superimposed on the displayed slice 100, adjacent to the linear ruler 120, as shown in FIG. 1. Alternatively or in addition, the measurement may be displayed elsewhere on the screen, or recorded elsewhere, such as in a table accessible by viewing another screen.
Two examples of alternative workstation tools are:
(i) A virtual ruler. This tool requires the user to click, and sometimes also drag, either end of the ruler to the appropriate locations on the medical image.
(ii) A virtual protractor. This tool requires the user to click and drag either end of a pair of 'hinged' lines to the appropriate locations on the medical image. The workstation then reports the angular measurement.
Such tools as the virtual ruler and virtual protractor almost exclusively operate in 2D images, or in 2D slices extracted from 3D images.
The types of measurement of interest on a medical image may include:
(i) The largest diameter or length, in the plane of acquisition of the image. This diameter is known as the 'long axis'.
(ii) The largest diameter or length, perpendicular to the long axis. This diameter is known as the 'short axis'.
(iii) The volume.
(iv) One or more other distances.
(v) One or more angles.
Within the field of oncology, it is common clinical practice to measure the size of suspected tumours. This size measurement is made using the long and short axes, in a particular plane. Here 'plane' is important. It means a particular direction, in which the slice must be taken.
Two standard methods are in widespread use for the evaluation of treatment response in oncology. One, referred to as the 'WHO' standard, requires that both the long and short axes of each tumour be measured. The other method is the 'RECIST' standard. The 'RECIST' standard requires only measurement of the long axis of each tumour. In a recent version, RECIST 1.1, the measurement of the short axis is used for assessing lymph-nodes, instead of the measurement of the long axis.
The digital ruler and calliper tools provided on medical imaging workstations require the user to carry out either two or three manual steps. These steps are the following sequence, with at least step 1 and one of steps 2 or 3 being necessary:
Step 1: Manually select the slice, i.e. the particular 2-d image from amongst all the image data or images that were taken of the structure. Normally, the 2-d image slice that is selected will be the one that appears to have the longest tumour dimension.
Step 2: On screen, define the start and finish of the long axis measurement, and use a ruler or digital callipers to make the measurement.
Step 3: On screen, define the start and finish of the short axis measurement, and use a ruler or digital callipers to make the measurement.
The known prior art has a number of disadvantages regarding the accuracy, reproducibility and optimality of measurement tool control and placement. Some of these disadvantages are as follows:
(i) The user must judge the appropriate locations in the slice at which to specify the control points of the measurement tool, in order to obtain the required measurement. For some features, this is relatively straightforward. However, for other features, the true boundary may be unclear. The result is variability in the measurements obtained, for example by different users, even when those users are experienced.(ii) The interface for the interaction required, typically a computer mouse, may be hard to control precisely, leading to inaccurate placement or variability even between the same user making a measurement twice.(iii) The screen resolution at which the slice and interactive tool location are displayed may affect the accuracy to which the control point can be placed.(iv) For some types of measurement, such as the long axis and short axis, the approximate axis placement and direction may be easily discernable to the user. However, the selection of optimal image slice, axis direction and control point position placement may be significantly harder. This may lead to errors from arbitrary choice of placement. It may also lead to laborious measurements, when repeat measurements are undertaken for optimisation.(v) For measurements of the same object across a series of images, the measurements usually require consistency. This requirement may relate, for example, to slice orientation, slice choice, the definition of the object boundary, or axis direction. Although clinical users will attempt to be consistent, accurate and reproducible placement of control points to enforce such consistency across images in a series is difficult and error prone.
Increasingly, volumetric measurements are becoming of interest in medical imaging. Here it is necessary either to manually delineate the tumour or other structure, or to use automated or semi-automated algorithms. Examples of such algorithms are known from the following prior art publications:    (i) Marie-Pierre Jolly and Leo Grady, "3D General Lesion Segmentation in CT", Proc. of ISBI 2008, Paris, France, May 14-17 2008. pp. 796-799.    (ii) Radiology reference: Zhao B, Reeves A P, Yankelevitz D, Henschke C I. Three-dimensional multi-criterion automatic segmentation of pulmonary nodules of helical CT images. Opt Eng 1999; 38:1340-1347.
Automated and semi-automated volumetric approaches attempt to overcome the limitations of ruler based approaches. They achieve this by enabling the user to define a 2-d or 3-d segmentation of the object requiring measurement, for example a tumour. The volume and maximum dimensions can then be derived from such segmentations.
Where a tumour has clear well-defined boundaries, such automated and semi-automated volumetric techniques can be useful. However, in many cases, medical images exhibit poorly defined boundaries. In addition, tumours are often within or adjacent to tissue of a similar radiological appearance. It is therefore difficult to distinguish tumour tissue from other tissues present in the same region of the image.
In such cases, existing tools for automated or semi-automated volumetric techniques either completely fail, or require a significant degree of user intervention to produce a successful result. This can be unsatisfactory, because in many cases the user is compelled to produce an accurate 2-d or 3-d segmentation, when all that was required was a simple 2-d linear measurement.
There is a need for a simple, fast, accurate and reproducible method for the placement of control points of measurement tools. This need arises when determining measurements of an object, such as healthy tissue, or a tumour or other structure, from a medical image.
Consistency of control point placement for measurements over a series of images is also important. This need applies to a series of images that are obtained by one technique at the same time, and to such a series obtained at different times. It also applies to multiple images obtained by different techniques, such as MRI and CT scans, whether during an investigation at one point in time or on different occasions.


An easy open can end having shallow panel integrally formed in the tear away panel and a tab nose bead formed on the panel proximate the rivet, a method of further forming a can end to incorporate the aforedescribed features, and tooling for the further forming of the easy opening end.

1. Field of the Invention
The present invention relates to easy-open ends for product containers, particularly, beverage and beer cans. In particular, the present invention provides an improved method for forming easy-open ends, improved tooling, and an improved can end that demonstrates superior functionality, particularly in its opening characteristics.
2. Prior Art
Many metallic cans for holding beverages or other products are provided with easy-open can ends, wherein a pull tab attached to a tear strip that is defined by a score in the can end. The pull tab may be lifted and then pulled to provide an opening in the can end for dispensing the can's contents. For ecological and safety reasons, many regions require that the tear strip and attached pull tab be retained to the can end after opening. In order to meet these requirements, various designs have been suggested by the prior art for ensuring that the tear strip and pull tab do not become separated from the can end. Generally, the pull tab is retained on the can end by means of a rivet. Methods of forming a can end can be found in U.S. Pat. Nos. 4,465,204 and 4,530,631 both to Kaminski et al., and assigned to the assignee of the instant invention. These patents are incorporated by reference as if fully set forth herein.
In the manufacture of an easy-open can end, a can end shell is first formed from a metal sheet product, preferably an aluminum sheet product. The can end shell is then transferred to a conversion press. In the typical operation of a conversion press, a can end shell is introduced between an upper tool member and a lower tool member which are in the open, spaced apart position. A press ram advances the upper tool member toward the lower tool member in order to perform any of a variety of metal forming operations such as rivet forming, paneling, scoring, embossing, tab securing, and final staking. After performing an operation, the press ram retracts until the upper tool member and lower tool member are once again in the open, spaced apart position. The partially converted shell is transported to the next successive tooling operation until an easy-open can end is completely formed and discharged from the press. As one shell leaves a given tooling operation, another shell is introduced to the vacated operation, thus continuously repeating the entire easy-open can end manufacturing process.
In certain canned products, such as carbonated beverages, there is substantial internal pressure that can be in the order of 90 to 100 psi or even greater, and must be quickly and safely vented during the initial opening of the can end by the consumer. According, can ends are constructed for venting or releasing the internal pressure of the container during the initial operation of the easy open mechanism of the end. The mechanism of venting is described in prior art patents such as U.S. Pat. Nos. 4,015,744 and 4,030,631, the contents of which are incorporated by reference herein as if fully set forth. As briefly mentioned above, the easy open mechanism includes an end panel which is attached to the can body or container. A tear panel is defined in the end panel by a scoreline. An operating tab including a nose which extends partially over the tear panel is connected by a rivet to the end panel. The rivet defines a pivot point for tab operation. My co-pending patent application U.S. Ser. No. 08/476,406, filed Jun. 7, 1996, entitled, "Improved Easy Open Container End, Method of Manufacture, and Tooling" discloses new features that cooperates with the scoreline.
Basically, initial lifting of the tab produces an upward force on the rivet and a downward force on the edge of the tear panel adjacent a beginning point of the tear panel scoreline. This in turn causes an initial opening of the tear panel beneath the nose of the tab in an area referred to as the vent region of the can end. Further lifting motion of the tab causes the tear panel to separate progressively along its scoreline, leaving a small integral connection or hinge between the end panel and the tear panel, about which the tear panel is rotated. The separation of the tear panel defines an opening through which container's contents can be poured.
As mentioned above, there can be substantial internal gas pressure in the container. During the initial opening motion, this gas pressure must vent safely. It is the typical practice to define a small vent opening with a hook formation at the radially inward end of the scoreline. The vent opening or region extends to a score stop located in the region where the tear panel scoreline proceeds outward at the end. Typically, the score stop is in the form of a shallower segment of the scoreline of relatively short length as described in U.S. Pat. No. 4,503,989. The contents of this patent are incorporated herein by reference as if fully set forth. This score stop provides an increase in tear resistance along the scoreline. This opening process can be identified by the initial "pop" that is heard when the tab is lifted, followed by the "metal tearing" sound that accompanies the separation of the tear panel from the can end as the nose of the tab is "pushed" against the tear panel.
The continuing evolution toward larger tear away panel opening areas relative to the overall surface area of the can end has created several challenges in the can making industry. This relative size of the tear away panel is at least in part the result of the continuous down-sizing of can end diameters.
It is useful to understand what is meant by reference to a "large" opening end or to "larger" tear away panels. For example, a conventional 202 easy open end has a tear away panel that defines an area of approximately 0.450 square inches. The same 202 easy open end that is equipped with a larger tear away panel has a panel that defines an area of approximately 0.596 square inches. Accordingly, a large opening end may be characterized as being between about 20% and 40% larger than a conventional tear panel. Among the challenges associated with larger tear away panels are: the prevention of missiling or tear panel blow off, i.e., the catastrophic failure of the tear panel; the efficient mechanical operation of the larger tear panel with the use of the existing tab; the avoidance of the partial opening or incomplete opening of the tear panel; and maintaining "pop" and "push" values at a level that is satisfactory and convenient to the end user. Examples of large opening ends are available in my co pending patent applications, including application Ser. No. 29/048,638.
The instant invention also addresses a technique for providing heightened control of the panel opening process through the use of a tab nose bead formed into the tear away panel.
It is an object of this invention to provide a can end having a large opening tear panel that demonstrates improved and consistently-acceptable operational capabilities.
It is yet another object of this invention to provide a can end tear away panel configuration suitable for use with both conventional and large opening ends.
It is still another object of this invention to provide an improved set of tooling for the manufacture of converted can ends.
It is another object of this invention to provide a converted can end and a method for manufacturing the same.

Easy open container end with method of manufacture, and tooling


A method of making a red pigmented composition is disclosed which includes (a) preparing an aqueous extract of Garcinia indica fruit comprising at least one red colorant; (b) treating the extract with a cation exchange resin so that one or more red colorant associates with the resin; (c) eluting the red colorant from the resin with an eluting solution containing one or more alcohol such as methanol, ethanol and isopropanol and one or more acid such as hydrochloric acid, citric acid, acetic acid, tartaric acid and hydroxy citric acid to yield a red-colored eluate; (d) collecting and concentrating the eluate to provide a concentrate; and (e) adding an antioxidant agent and/or placing the concentrate in an aseptic container in a non-oxidizing atmosphere. A combination comprising the resulting stabilized Garcinia extract in aseptic packaging in a non-oxidizing atmosphere is also disclosed, along with methods of use.

1. Technical Field of the Invention
The present invention generally relates to plant-derived natural red pigment, and more particularly to anthocyanins from the fruit of Garcinia indica. Still more particularly, the present invention relates to methods of extracting and stabilizing this pigment, and its use as a colorant.
2. Description of Related Art
Natural red color or hues of red color are frequently employed for adjusting the color of various foodstuffs, beverages, pharmaceuticals and the like. Some of the conventional red colorants in use today are derived from insects, for example, cochineal. Other red colorants are synthetic in origin. As a result, many of the existing red colorants have distinct disadvantages with respect to suitability for use in foodstuffs and beverages meant for human consumption.
In recent times, a variety of natural sources of red colorants have been identified and methods for extraction of natural red pigments have been described. For example, a natural red color has been extracted from grape skin and is has been standardized with respect to specific color value and percentage of anthocyanin content. This grape-derived pigment has been stabilized for use in dairy, beverages, and confectionary. While this natural pigment is satisfactory for some purposes, the problem remains that it does not give the precise hues that are desired in some food and beverage products.
U.S. Pat. No. 4,172,902 (Asen et al.) describes a method for extracting an anthocyanin red color from the 'Heavenly Blue' morning glory flower. Although morning glories provide an excellent red pigment, the availability of this natural source is too limited for widespread or commercial use. Therefore, there are problems associated with making use of this anthocyanin pigment for coloring foodstuffs and beverages.
U.S. Pat. No. 5,908,650 (Lenoble et al.) describes certain anthocyanin-based colors that are stabilized with respect to loss of color due to pH, heat or light by water-soluble pigment-improving extracts of plant material such as rosemary, sage and peppermint. The active pigment-improving agent is said to be a flavonoid glycuronide or a flavonoid glucuronide.
U.S. Pat. No. 6,132,791 (Fox) describes the extraction of a natural red sunflower anthocyanin colorant that is said to have naturally stabilized color qualities. According to the procedure described in that patent, sunflower hulls are heated in an aqueous solution at pH 2-6. to produce a red juice that is heat and light stable over a pH range of about 1-6.
U.S. Pat. No. 6,180,154 (Wrolstad et al.) describes a natural colorant preparation from potato extract. However, the presence of steroidal glyco-alkaloids in potato introduces the potential for toxicity in red color extracts obtained from red potato. One way to address this problem is to develop a variety of red potato that is lower in the toxic glyco-alkaloid, and to use it for extraction of the red potato pigment.
Japanese Patent Nos. 223756 and 25460 describe studies in which red pigments were extracted from red cabbage and the extracts were evaluated for anthocyanin color values. Although accepted and proven methods for extraction of red color from red cabbage exist, even those methods have practical shortcomings, which preclude the cost effective application of such methods, especially for commercial applications. One such drawback is that methods, which employ alcohol extraction of the red pigment, can leave traces of the alcohol in the product. If alcohol remains in the extract, even in small amounts, it can adversely affect the filtration membrane used for concentration of the pigment extract. Another drawback is that when alkali is used for extraction of color pigments, stability of the pigment solution is badly affected, leading to degradation of the pigment by the alkali. Methods that use sulfuric acid or sulfate liquor for extraction of red coloring from red cabbage have as a shortcoming the generation of sulfur dioxide during heating. Sulfur dioxide production is highly undesirable for environmental safety reasons as well as because of its tendency to form foul smelling sulfur-containing compounds in the final product.
WO 02/14477 describes certain anthocyanin pigments isolated from the fruits of Garcinia indica.
While the demand for natural red pigment remains high, the existing colorants and their methods of preparation are not able to meet the existing demand. Even though some of the known sources are renewable, or can be grown in great quantity, the supply of satisfactory red colorants is not adequate for current demand. There is still an unmet need for practical red colorant compositions that are safe for human consumption, avoid discoloring or fading, and impart to foods and other products the desired hues.


A controlled failure rope and method of making the same. The controlled failure rope comprises first and second portions. The first portion is formed of a first material having a first set of tension failure characteristics. The second portion is formed of a second material having a second set of tension failure characteristics. The first and second sets of tension failure characteristics differ such that, when the rope is subjected to tension loads above a tension threshold, the first portion of the rope begins to fail before the second portion of the rope, therefore providing a prior indication of possible rope failure before the rope becomes completed separated.

The characteristics of a given type of rope determine whether that type of rope is suitable for a specific intended use. Rope characteristics include breaking strength, elongation, flexibility, weight, abrasion resistance, and coefficient of friction. The intended use of a rope will determine the acceptable range for each characteristic of the rope. The term "failure" as applied to rope will be used herein to refer to a rope being subjected to conditions beyond the acceptable range associated with at least one rope characteristic.
The present invention primarily relates to the performance of rope when the rope fails due to excess tension loads. When a rope is subjected to excess tension loads, the rope fails over time in what will be referred to as a tension failure sequence. For the purposes of the following discussion, it will be assumed that a constant tension load is applied to the rope throughout the tension failure sequence. However, a rope of the present invention may be used in situations in which the tension load varies or is eliminated during the tension failure sequence.
The tension failure sequence varies from rope to rope and from environment to environment. In general, a rope or portion of a rope breaks when all of the fibers of the rope separate or break apart at a given location on the rope. If the fibers are all identical, it is conceivable that all of the fibers will break at the same time. Typically, however, individual fibers differ from each other based on such factors as manufacturing variations and wear on the fibers during use of the rope. Accordingly, when the failure sequence begins, the lower elongating fibers will break first, transferring the load to the remaining fibers. As the entire tension load is transferred to the remaining higher elongating fibers, these also begin to break. When all of the fibers have broken at a given location, the rope is broken.
In a conventional rope, the tension failure sequence typically begins with elongation of the rope. After a certain amount of elongation, the rope breaks, marking the end of the tension failure sequence. At the end of the tension failure sequence, the rope exceeds the acceptable range of elongation and eventually breaks. When the rope breaks, potential energy within the rope is converted into kinetic energy that can cause unpredictable movement of the ends of the rope on either side of the break.
The need thus exists for improved ropes that, when subjected to excess tension loads, fail in a controlled manner; the need also exists for systems and methods for controlling the failure of rope and for producing such improved ropes.

Controlled failure rope systems and methods


The present invention describes the use of radio-labeled antitumor drugs in the treatment of solid tumors by the method of administering a radio-labelled anticancer drug to a patient and imaging at least a part of the patient using Positron Emission Tomography imaging. The method is used to monitor delivery of antitumor drugs to tumors and may be used to predict the effectiveness of therapy with a particular antitumor drug or combination of antitumor drugs, to assess the effectiveness of modulators of cellular accumulation, to individualize therapy and to evaluate the effectiveness of antitumor drugs with respect to particular cancers. Particularly preferred drugs are labeled taxanes, e.g., 11C-paclitaxel and 11C-docetaxel, labeled anthracyclines, e.g., 11C-doxorubicin and 11C-epirubicin, and other radio-labeled drug, e.g. 11C-topotecan and 11C-mitoxantrone. The invention further describes antitumor drugs labeled with the radioactive label 11C and methods of preparing radio-labeled drugs.

Cancer treatment has made great progress in recent years. Many new therapies are becoming available, and many more patients are treated. Cancer is characterized by unrestricted cell growth; many cancer therapies work by inhibiting cell division. Since normal cells do not divide after maturation, inhibition of cell division primarily affects the cancer cells and this has been a focus of drug development. However, other cells are also affected by antitumor drugs to different degrees and cancer therapies are often extremely toxic to patients. There is also great variability in the efficacy of treatments. Some drugs are more effective than others for certain patients, for certain cancers, or at certain stages of treatment. Often, combinations of drugs with varying dosages are necessary for efficacious treatment, requiring considerable experimentation to optimize drugs and doses.
Among the agents affecting the therapeutic benefits of cancer drugs are the multi-drug resistance transporter (MDR), also called p-glycoprotein (PGP) or ABCB 1. It has recently become clear that MDR is one of a family of such transporters. Klein I, Sarkadi B, Varadi A. An inventory of the human ABC proteins. Biochim. Biophys. Acta 1999; 1461:237–62. The expression of these proteins can be highly variable. MDR is not expressed in all cancer cells, and may be present at variable levels. The expression of MDR affects drug efficacy by altering drug accumulation at the tumor. Because of the variable efficacy of antitumor drugs caused by this and other factors, a critical part of therapeutic monitoring involves determining the drug location in the body, its half-life, and the range of mechanisms that limit its effectiveness.
Accumulation of a drug reflects the net balance over time of influx (delivery to the tumor) and efflux (removal from the tumor). Influx and efflux are equally important, but recent research has focused upon a series of transport proteins that function as efflux pumps for taxanes, anthracyclines, and other drugs. There are many reasons why a tumor may not be sensitive to a particular drug. However, the first parameter to evaluate is accumulation of drug by the tumor. If the drug doesn't accumulate in the tumor, there won't be an effect. Adequate accumulation is always necessary for drug activity. Thus, a method to determine accumulation of a drug in the tumor could be the first step in therapeutic decision-making for the drug.
Traditional approaches to the determination of drug uptake and retention (drug accumulation in the tumor) have been invasive and most frequently require obtaining a biopsy from the patient. In addition to the discomfort and risks associated with biopsy procedures, only a small sample of tissue is typically obtained, which may not be representative of the entire region.
Taxanes
One class of drugs which has proved particularly useful in the treatment of cancer, including solid tumors such as breast cancer, has been the taxanes. Taxanes are diterpenoid compounds with a complex taxane ring as the nucleus. The taxane paclitaxel (I) (Taxol®) was initially isolated from yew bark, although the compound may now be prepared synthetically. A modification of the side chains of paclitaxel has yielded another clinically effective compound, docetaxel (II). Other taxanes have also been developed, and are at various stages of preclinical and early clinical testing. These analogs include differences in functional groups attached to the main baccatin nucleus, as well as different side chains attached at the C-13 position.
                (I) Paclitaxel: R1=R2=acetate, R3=Ph        (II) Docetaxel: R1=OH, R2=acetate, R3=OC(CH3)3
Taxanes, like the vinca alkaloids and colchicine, work by interfering with microtubules, thereby inhibiting mitosis. Taxanes antagonize disassembly of microtubules, by promoting tubulin polymerization, inducing microtubule bundles to form. This leads to arrest of mitosis, and ultimately to cell death. The rate of cell death is proportional to concentration of drug and length of time of administration. Taxanes are highly insoluble and are commonly administered in a solution of surfactants and other vehicles such as ethanol. (Hardman, J. G. and Limbird, L. E., (eds) Goodman and Gilman's The Pharmacological Basis of Therapeutics, Chapter 51, McGraw-Hill, New York, 1996)
The taxane class of anticancer drugs has demonstrated remarkable activity. Docetaxel and paclitaxel, the first two approved drugs in this class, have already altered the standard treatments for breast, lung, and ovarian tumors. Crown J, O'Leary M. The taxanes: an update. Lancet 2000; 355(9210):1176–8. Burris H A 3rd. Docetaxel (Taxotere) in the treatment of cancer. Semin. Oncol. 2000; 27 (2 Suppl 3):1–2. The full scope of antitumor activity for docetaxel and paclitaxel is still under active investigation, with new uses emerging for other tumor types. For example, at present there is considerable interest in the use of docetaxel for treatment of prostate cancer. Oh WK, et al. Docetaxel (Taxotere)-based chemotherapy for hormone-refractory and locally advanced prostate cancer. Semin. Oncol. 1999; 26 (5 Suppl 17):49–54; Petrylak D P. Docetaxel (Taxotere) in hormone-refractory prostate cancer. Semin. Oncol. 2000; 27 (2 Suppl 3):24–9. Other molecules in the taxane class are at much earlier stages of clinical testing.
Anthracyclines
Anthracyclines represent another important class of antitumor drugs. Representative anthracycline drugs include doxorubicin (III) and epirubicin (IV). These anthracyclines are leading agents for the treatment of many tumors, notably breast cancer, lung cancer, and sarcomas. Doroshow J H. Anthracylines and anthracenediones. In: Chabner B A and Longo D L, Cancer Chemotherapy and Biotherapy, 2nd Edition, p. 409, Lippincott-Raven, Philadelphia, 1996. Several mechanisms of action have been proposed, based upon the intercalation of the anthracycline molecules with DNA, and subsequent disruptions of cellular functioning.
                (III) Doxorubicin: A=H; B═OH        (IV) Epirubicin: A=OH; B═H
Other Antitumor Drugs
Because the discovery of anticancer drugs has been well-funded over the last half-century, drugs from a variety of chemical classes are now in routine clinical use. Mitoxantone (V) is an anthracenedione, a chemical class closesly related to anthracyclines. Mitoxantrone was originally developed in an attempt to replace anthracyclines because the anthracenediones have lower cardiac toxicity. However, the antitumor activity of mitoxantrone was generally disappointing and it has a relatively narrow niche in clinical use. Recently, however, mitoxantrone has been demonstrated to substantially reduce the severe pain associated with metastatic prostate cancer, and has changed the management of this large group of cancer patients. Tannock I F, Osoba D, Stockler M R, Ernst D S, Neville A J, Moore M J, Armitage G R, Wilson J J, Venner P M, Coppin C M, Murphy K C. Chemotherapy with mitoxantrone plus prednisone or prednisone alone for symptomatic hormone-resistant prostate cancer: a Canadian randomized trial with palliative end points. J. Clin. Oncol. 1996; 14(6):1756–64.
                (V) Mitoxantrone
Camptothecin is a natural product found in the bark and wood of a Chinese tree. Although it was found to be too difficult for clinical use itself, a number of derivatives have demonstrated clinical activity. Takimoto C H, Arbuck S G. The Camptothecins. In: Chabner B A and Longo D L, Cancer Chemotherapy and Biotherapy, 2nd Edition, p. 463, Lippincott-Raven, Philadelphia, 1996. This class of drugs appears to work by inhibiting the action of topoisomerase I, a key enzyme for the integrity of DNA structure. Irinotecan (CPT-11) was initially approved for treatment of colorectal cancer, and topotecan (VI) initially approved for
                (VI) Topotecanovarian cancer. Both of these two drugs and other camptothecin analogs are acquiring new uses as testing continues. Topotecan has shown activity in lung cancer, and is now also approved for treating these patients. In addition, topotecan is particularly important from the perspective of PET imaging because it is direct-acting (irinotecan is a prodrug that must be activated), and also has limited catabolism, so that the parent molecule is the principal circulating species.
Determination of Sensitivity or Resistance
Although drugs having excellent antitumor activity e.g. taxanes, anthracyclines and others, have been identified, not all tumors respond to a given therapy. Furthermore, all patients are exposed to the risk of severe, life-threatening toxicity with these drugs whether or not their tumors respond. An important tool for individualizing therapy would be a method to rapidly determine whether a specific tumor will be likely to respond to a particular drug without exposing the patient to toxic levels of the drug.
In addition to avoiding needless toxicity, a rapid determination is also important because of the tendency of tumors to become more difficult to treat with time. Thus, if one treatment can be predicted to be unsuitable, alternative treatments can be explored without waiting months to determine that the first treatment did not work.
In some cases, the cause of treatment failure can not be determined. In other cases, a specific biochemical or molecular mechanism can be ascertained. For example, the tumor cells may be intrinsically sensitive to the drug, but inadequate amounts of drug are accumulated in the tumor. There are multiple reasons for drug accumulation failures, but, regardless of the underlying cause, the empirical demonstration that adequate (or inadequate) drug was accumulated has enormous medical value in terms of treatment selection for individual patients. Determining drug accumulation levels in a specific tumor pre-treatment would thus provide a great value in exploring a wide range of treatment options.
In addition to the benefits for individual patients, determination of drug delivery has benefits for the general patient population and for the process of drug development. General patient populations include a mixture of tumors which are chemosensitive and chemoresistant. The demonstration of a substantial effect is made difficult when the responding tumors are diluted in a pool of nonresponding tumors. Thus, any technique which can find tumors likely to respond before treatment has begun will produce an enriched study population, and greatly decrease the numbers of patients required to test the overall potential benefit of the drug.
Position Emission Tomography (PET) imaging or scanning uses positron emitter labeled tracers. Positrons are positively charged electrons which result from the decay of a proton rich and neutron deficient isotope. These emitters are generally short lived. Most positron emitters are produced in medical cyclotrons or accelerators. The half life of 11C is 20 min and of 18F is 110 minutes. PET cameras have a spatial resolution of several millimeters and can be used to image the entire body.
The concept of trying to find radiolabeled probes that would be ideal for the investigation of one or more transport pumps should not be confused with the concept of measuring accumulation of the specific drug to guide therapy. The literature is filled with research that attempts to define drug transport systems. Many groups are attempting to find the "ideal" probe for each transporter. The emerging problem is an explosion in the numbers of transporters that are being discovered. Thus, attempts to guide therapy with a drug based upon ideal probes is fraught with difficulty and confounded by the multiplicity of transport mechanisms, which will vary from tumor-to-tumor.
Clinical attempts to measure drug accumulation with imaging have been reported, including the use of 11C-verapamil, 11C-daunorubicin, or 99mTc-sesta-MIBI. All have been limited because they only target MDR and have additional difficulties.
Verapamil is known to interact with the MDR efflux pump, and Hendrikse et al. have demonstrated that images can be obtained with 11C-verapamil in rats. Hendrikse N H, de Vries E G, Eriks-Fluks L, van der Graaf W T, Hospers G A, Willemsen A T, Vaalburg W, Franssen E J. A new in vivo method to study P-glycoprotein transport in tumors and the blood-brain barrier. Cancer Res. 1999; 59:2411–6. Their work also showed that modulation of MDR in vivo could be demonstrated in rats with 11C-verapamil. Although 11C-verapamil may be an elegant probe for MDR per se, it is neither structurally nor functionally related to the taxanes, anthracyclines, anthracenediones, camptothecin analogs, or any other approved anticancer drugs. It is also important to recognize that, in humans, there is rapid and extensive catabolism of verapamil. Schomerus M, Spiegelhalder B, Stieren B, Eichelbaum M. Physiological disposition of verapamil in man. Cardiovasc. Res. 1976; 10(5):605–12. Verapamil itself constitutes only a small fraction of the circulating radioactivity, so the interpretation of the total radioactivity signal obtained with PET is problematic.
Also, although daunorubicin has been used as a probe in cell culture, where it is a stable molecule, it is not a stable molecule in the body and imaging with this component is not very useful. In humans, daunorubicin is converted rapidly by carbonyl reductase to its alcohol metabolite, daunorubicinol. Thus, the signal observed via external PET imaging of labeled daunorubicin is a mixture of these two chemical entities, which can complicate the interpretation. The plasma ratio of metabolite-to-parent is about 2.5:1 (Galettis P, Boutagy J, M a D D. Daunorubicin pharmacokinetics and the correlation with P-glycoprotein and response in patients with acute leukaemia Br. J. Cancer 1994; 70(2):324–9), so it is possible that the metabolite is the species primarily being imaged. However, it is also possible that tissue uptake is more favorable for the parent, so a different ratio might be found.
99Tc-Sestamibi, which is routinely used for cardiac imaging, has also been explored for tumor imaging. As in the case for verapamil, neither the structural nor functional properties of sestamibi resemble those for anticancer drugs. The clinical imaging results are mixed. This probe seems to have the ability to detect tumors and monitor response in some clinical settings. Mankoff D A, Dunnwald L K, Gralow J R, et al. Monitoring the response of patients with locally advanced breast carcinoma to neoadjuvant chemotherapy using 99mTc-sestamibi scintimammography. Cancer 1999; 85(11):2410–23. It is reported that the efflux rate of 99mTc-sestamibi correlates with antitumor response, at least for one stage of breast cancer. Ciarmiello A, Del Vecchio S, Silvestro P, et al. Tumor clearance of technetium 99m-sestamibi as a predictor of response to neoadjuvant chemotherapy for locally advanced breast cancer. J. Clin. Oncol. 1998; 16:1677–83. However, in lung cancer, no predictive value was found. Sasaki M, Kuabara Y, Yoshida T, et al. Can 99m-Tc-mibi-SPECT predict the treatment response of lung cancer? J. Nucl. Med. 2000; 41:286P.
The invention provides advantages that were not previously available by providing a non-invasive method for determining potential drug efficacy by measuring actual drug accumulation in tumors. This invention allows for the efficient determination of the potentially most efficacious treatment plan for antitumor therapy by allowing for individualized optimization of drugs and dosage.
The invention offers the additional, previously unrealized advantage of developing individualized antitumor therapies specific to a particular patient with a particular type of tumor in a particular stage of development.
The invention also provides a method for determining the effectiveness of particular drugs as treatment for particular cancers over a broad range of the population.

Imaging of drug accumulation as a guide to antitumor therapy

The United States of America as represented by the Department of Health and Human Services


A warning system for making known the presence of an emergency vehicle. A transmitter is mounted in an emergency vehicle that outputs a digital UHF/LMS signal that is detectable within a range. A receiver responds to the digital UHF/LMS signal from the transmitter and is mounted, most preferably to a dashboard of a motor vehicle. The receiver detects from the digital signal the type of emergency vehicle from which the digital signal is originating. In one embodiment the digital signal also includes a unique identifier for the transmitter rather than simply a generic discipline identifier such as police, fire, emergency etc. A visual indicator mounted to the motor vehicle is activated in response to the digital signal from the transmitter to warn a motorist in the motor vehicle of a presence of the emergency vehicle within the range of the transmitter and to warn the transmitting vehicle of the presence of other emergency vehicles within receiving range.

In a modern day motor vehicle, efforts have been made to soundproof the passenger compartment. One result of such soundproofing is that the driver may be unable to hear approaching emergency vehicle having its audio siren turned on. Alternatively, the playing of a radio or stereo at loud volume may make the driver unable to hear an approaching emergency vehicle with the audio siren on. A hearing impaired driver may be unable to hear an approaching emergency vehicle with its siren on. Two or more emergency vehicles of the same or different disciplines, responding to the same or to different dispatchers, approaching the same intersection may not be able to hear the other approaching emergency vehicle due to the audible sound of his or her own siren and hence is unaware of the presence of another emergency vehicle responding to the same or a different emergency call.
If the emergency vehicle is using a silent approach, motorists in the vicinity will not be aware of the presence of the emergency vehicle approaching an intersection if the siren is not turned on. An emergency vehicle (or other patient transport vehicle) transporting a patient and not using an audio siren poses a risk to other motorists who will be unaware of the approaching emergency vehicle.


An aircraft cabin apparatus may include a top section, a bottom section, and at least one linkage assembly configured to support the top section in an open position following a rotation of the top section between a closed position and the open position. The top section may include a top surface configured to engage a first edge or surface of a laptop and a support structure proximate to the top surface and configured to engage a second edge or surface of the laptop. The bottom section may include two raised portions along each short edge of the bottom section and a cavity defined by the two raised portions. The top section may be configured to fit within the cavity defined within the bottom section when in the closed position, and may be set at an angle relative to the bottom section when in the open position.

Aircraft cabins typically include a seat back-mounted tray. Depending on a position of an aircraft seat to which the seat back-mounted tray is coupled and/or a size of a seat occupant attempting to support a personal electronic device with the seat tray. In this case, the personal electronic device may not be fully-opened for review by the seat occupant. In addition, the personal electronic device may not be adequately supported by the seat tray.

Aircraft cabin apparatus including personal electronic device holder


A method for manufacturing self-aligned split-gate flash memory cells wherein the split-gate structure is formed by a self-aligned approach, so that the length of a channel can be precisely controlled. Furthermore, sources and drains are formed separately by executing different implantations, so that the dopant parameters of the sources and drains can be changed, based on desired and possibly different characteristics.

1. Field of the Invention
The invention relates to a memory cell process and, in particular, to a method for manufacturing split-gate flash memory cells.
2. Description of the Prior Art
A method for manufacturing electrically erasable programmable read-only memories (EEPROM) is disclosed by Naruke et al. in "A New Flash-Erase EEPROM Cell with a Sidewall Select-Gate on its Source Side" (Technical Digest of IEEE Electron Device Meeting in 1988). Referring to FIGS. 1A and 1B, a first poly-silicon layer and a second poly-silicon layer are formed as a floating gate 10 and a control gate 12, respectively. Next, a third poly-silicon layer is deposited; then, an etch-back technique is utilized to form a selection gate 14 wherein the height of the selection gate 14, defined by the height of the floating gate 10 and control gate 12, is about 0.4 .mu.m. In addition, since etch-back is used in the above process, the selection gate 14 must be parallel to the control gate 12.
The disadvantages of the above-mentioned conventional process are that the selection gate and control gate which are parallel with each other take up too much space and the length of the selection gate is fixed, so that the characteristics of the memory can not be effectively adjusted. Solutions for overcoming these disadvantages are described in "A novel high density contactless flash memory array using split-gate source-side injection cell for 5V-only application" by Y. Ma at a symposium on VLSI Technology in 1994. As shown in FIG. 2, a high-density memory array and high access efficiency can be obtained by forming a parallel selection gate 22. However, due to limitations in the precision of the photolithography used to form the above-mentioned split-gate structure, the length of the selection gate 22 must be increased, thereby consuming a larger amount of space on the substrate and preventing a drain 24 and source 26 from being formed using separate and different implantations selected on the basis of desired and possibly different characteristics.

Method for manufacturing self-aligned split-gate flash memory cells


An integrated system and method for providing a flexible expert system development and runtime environment with an integrated natural language processor and set-oriented knowledge base. The system and process include an input device, a spreading activation module, a reasoning module, a decision module, and a knowledge base. The system and method may also include a natural language processing module. The spreading activation module utilizes the knowledge base, which is set-oriented with named relationships between concepts to traverse the knowledge base efficiently. The reasoning module executes related, nested logic statements which manipulate the complex facts in the knowledge base. The decision module selects the value or values from a list which are most relevant at the moment the module is called. The knowledge base represents all data in a nested, set-oriented manner. The system and method, in turn, produce an output in response to the input or command into the system.

1. Field of the Invention
The present invention relates to the field of expert systems and, more specifically, to the field of expert system analysis through structured knowledge representation in single and parallel processing systems including those used for natural language processing
2. Description of the Related Art
A generalized expert system typically includes a language or system for processing instructions and a representation of the data required for the application domain. A system for understanding natural language input from a user additionally includes specific processing instructions for interpreting natural language input and specific data which describes the user's natural language. All of the above components interact tightly with one another, so that the design or selection of such components significantly affects the resulting system's efficiency, correctness, robustness, and extensibility to advanced hardware platforms.
Natural language systems have processed the disambiguation of user input (e.g. deciding which among many possibly similar and plausible interpretations of the user's input is correct) in numerous methods. An important aspect of each of those methods is to "prune" (e.g. reduce) the total number of candidate interpretations from an initial number which is quite large in a real-world implementation down to a very small number which is practical (e.g. time-efficient) to process. Those methods generally fall into two categories. The first defines criteria which each element of the input sentence must meet, usually by characteristics like number of arguments and in what part of a descriptive hierarchy it must reside (e.g. "x must be some kind of machine"). This method requires continuous and precise, time-consuming maintenance whenever an addition or change is made to the application domain's data. The other method utilizes massive statistical computations on existing text to find other words that are often used with a given word, for example "bank" may be used in one sense with "money" and in another sense with "river". This method is unable to adapt to jargon or highly-specialized application domains while retaining reasonable recognition accuracy. Both of these methods have difficulties such as a decrease in speed of execution when the application domain is large (true for almost every commercial application) and poor success or uncertainty in understanding analogy, metaphor, and user input sentences which do not exactly conform to those expected by the system.
Current implementations for disambiguating natural language input typically are unable to utilize the parallel processing capabilities of multi-processor systems, and therefore create a processing bottleneck on advanced hardware.
The language or system for processing the specific natural language instructions is generally either frame-based, like most expert systems, or a series of sequential statements, often in a specialized language which has special data manipulation facilities like unification and list processing, such as LISP or Prolog.
Current expert systems are typically constructed as a series of "frames" which consist of the equivalent of an "IF" clause, describing the conditions under which this frame is true, and a "THEN" clause that describes the action to take when the "IF" clause is found to be true. Each frame is meant to contain an independent piece of knowledge about the application domain. If a variable, on which any frame depends, changes during execution, the entire frame is automatically placed on the "agenda" (execution list) to fully execute again. This is true whether or not that frame has previously executed. If the frame contains references to external modules written in a procedural language like C, which is usually needed for more complex actions than IF-THEN constructions, those modules are often unable to update the variables which affect the agenda. These expert systems are complex to program, difficult to extend into unique environments, and limited in their ability to combine knowledge from different sources, particularly during runtime.
Specialized languages like CLOS and Prolog do not automatically update any equivalent of an agenda when changing a variable, so that they are unable to have other instructions which depend on that variable updated. Updating is accomplished via such methods as manually-written routines associated with each variable for which this updating is desired. Clearly, this is repetitive and time-consuming.
Certain specialized languages like Prolog have "unification", or pattern-matching capabilities. Although such systems are somewhat flexible they are very slow in execution, so that special commands and programming methodologies need to be utilized to minimize the amount of unification that is actually done. Thus, these languages result in slow response times and are difficult to expand to large applications.
An issue with current implementations of both expert systems and unification-based languages is the need to introduce some level of sequencing of execution for the purposes of efficiency, initialization, grouping of similar procedures, and ease of constructing the data and instructions for the application. Examples of these are knowledge islands and execution priorities in expert systems and Prolog's backtracking. This added-on sequencing defeats or overrides the automatic features described above and creates a requirement for much greater training and expertise for those who build the application knowledge. This requirement for sequencing also makes executing such a language or expert system ineffective on a multiprocessor computer system (utilized for any application, not just natural language), since the frames or unifications are no longer independent time-wise. This sequencing also makes maintenance more difficult and error-prone, since the time dependencies in current implementations are hidden and inconsistent with the model of supposedly independent pieces of knowledge about the application domain.
Many natural language systems use separate storage and processing methods for data describing linguistic properties of words and for data describing the application domain. Frequently, natural language understanding systems utilize completely separate processing steps, where the linguistic analysis produces an output structure describing the sentence which is then used as input by the independent application domain analysis. Both the data separation and the processing separation introduce inefficiencies in processing and reduced accuracy in understanding the natural language command. This separation also makes the creation and updating of the data for an application more complex because information about a single entity in the application domain must be described in two different places with very different methods. This requires a person with significant expertise in linguistics as well as a person with knowledge of the application domain to design and implement the application. Historically, these have been different persons each with specialized training in their area of expertise and this dichotomy continues to be enforced by the development tools provided with current expert systems and natural language systems.
The data required for natural language understanding systems and general expert systems is complex for large commercial projects. This data is typically represented by some combination of lists, structures, and pointers from one data structure to another, with different types of data being represented by different specialized structures. In most systems, data and executable instructions are also represented in very different formats. This proliferation of formats reduces generality and efficiency, limits extensibility, and restricts the access of one type of data while processing another type of data. The proliferation also makes creation of the data more complex, particularly when lists of alternatives and multiple constraints for each alternative are desired.
All of the components of a complex reasoning application such as a natural language understanding system interact so intimately that design decisions in one component have drastic effects on the capabilities, effectiveness, robustness, and extensibility of all of the other components. Therefore, there is a need for a system which is designed in its entirety as a consistent operating whole and there is a need for a system and process that increases overall system efficiency and accuracy in an expert system environment.

System and method for expert system analysis using quiescent and parallel reasoning and set structured knowledge representation