A process for color graphics image processing, related to detection and segmentation of sweeps, is provided. An input graphics image is transformed into a three-dimensional histogram in an appropriate color space 104 (e.g., CIELUV). Two-dimensional histograms are estimated from the three-dimensional histogram 106. The two-dimensional histograms are processed to detect and segment sweeps 108. Sweep segment information from the processing of the two-dimensional histograms is combined 110. The combined sweep segment information is used to process the input graphics image to identify and segment sweeps 112. Post-processing may be optionally and selectively used to reject false alarms (i.e., areas falsely identified as sweeps) 114.

The present invention relates to color graphics image processing. It finds particular application in conjunction with detection and segmentation of sweeps in color graphics images, and will be described with particular reference thereto. However, it is to be appreciated that the present invention is also amenable to other like applications.
Content-based image classification has emerged as an important area in multimedia computing due to the rapid development of digital imaging, storage, and networking technologies. A reproduction system, such as a copier or a printer, strives for a pleasing rendering of color documents. Picture/graphics classifiers have been developed to differentiate between a picture image and a graphics image with high accuracy by analyzing low-level image statistics.
For example, U.S. Pat. No. 5,767,978 to Revankar et al. discloses an adaptable image segmentation system for differentially rendering black and white and/or color images using a plurality of imaging techniques. An image is segmented according to classes of regions that may be rendered according to the same imaging techniques. Image regions may be rendered according to a three-class system (such as traditional text, graphic, and picture systems), or according to more than three image classes. In addition, only two image classes may be required to render high quality draft or final output images. The image characteristics that may be rendered differently from class to class may include half toning, colorization and other image attributes.
A color output device such as a CRT computer monitor, liquid crystal display, inkjet printer, xerographic printer, etc can display a limited range of colors (the gamut of the output device). If the colors in an image do not reside wholly with in an output device gamut, a gamut-mapping algorithm is often applied to map the image colors to colors that the output device can produce. A simple approach is to preserve in-gamut colors without alteration and clip out-of-gamut colors to the closest in-gamut color. More sophisticated techniques can be used. Ideally, the gamut-mapping algorithm used should be tailored to the image type. For example, a region of smoothly varying colors should appear smoothly varying on the output device. Were the colors of a sweep to exceed the gamut of an output device, the aforementioned clipping approach will show disagreeable artifacts. In fact, it may be desirable to sacrifice color fidelity within the gamut to achieve a smooth color transition. Thus knowing that a region is, or contains, a sweep aids in color reproduction. In general, coloring schemes (gamut-mapping algorithms) are tailored for specific types of images to obtain quality reproduction. Once an image has been identified as a graphics image, further identification of image characteristics can be used to fine-tune the coloring schemes for more appealing reproductions. The most prominent characteristics of a graphics image include patches or areas of the image with uniform color and areas with uniformly changing colors. This invention focuses on the identification of the second characteristic.
One example where areas with uniformly changing color can usually be observed is in the gradient backgrounds of color business presentation slides. These areas of uniformly changing color are called sweeps and are constructed in the three-dimensional color space as a line during the construction of the synthetic graphics. A sweep is constructed by a mathematical formula to cause adjacent pixels to change color in a smooth, predictable way. For example, one can use linear interpolation of two colors specified for the sweep and render the original image by plotting pixels of interpolated colors such that neighboring spatial regions are rendered with colors from neighboring color regions. One can contemplate other mathematical descriptions of curves that achieve like effects. If such a document is printed or scanned, the sweeps do not exactly contain the colors on the line due to halftone noise introduced. If a reproduction system can correctly identify and segment the sweep areas in an image, the original sweeps can be reconstructed in the color space and rendered. The sweeps thus rendered will be very smooth and the noise introduced by the halftone will not be reproduced. Secondly, if the extreme colors of the sweep can be automatically identified, the coloring schemes can be tailored to maximize the smoothness as well as contrast and differentiation among colors to render business graphics documents.
Further identification of the properties of the graphics image can be used to fine-tune the coloring scheme to obtain a more appealing reproduction. The detection of sweeps in a graphics image can be used to reconstruct synthetic sweeps that may otherwise be perturbed due to half toning, scanning artifacts, or aging of a document or for other reasons. The extent of the sweeps (i.e., the change from color 1 to color 2) may also be used to tailor the coloring scheme to achieve best smoothness, contrast and differentiation among colors in the reconstructed sweeps.
The present invention proposes a new and improved method for detecting and segmenting sweeps in a color graphics image that overcomes the above-referenced problems and others.

Detection and segmentation of sweeps in color graphics images


Bubble plasma ionisation probe for analysing liquids by mass spectrometry. A means of a detecting analytes dissolved in a liquid by mass spectrometry is described. Gas flows from a source through a first conduit 105 and thereafter through a coaxial second conduit 103 that also serves as the inlet to the mass spectrometer 102. The coaxial arrangement of conduits is submerged in the liquid to be analysed 301. Using a feedback loop, the gas pressure is adjusted and controlled such that an attached bubble 302 forms at the open end of the first conduit 105. A plasma 305 is provided in the bubble. The plasma is preferably generated by a dielectric barrier discharge between a collar electrode 107 and mass spectrometer inlet 103. Analytes dissolved in the liquid are both desorbed form the gas-liquid interface and ionised by the action of the plasma. Ions formed in this way become entrained in the gas flow and are consequently transferred to the mass spectrometer, where they are analysed.

Mass spectrometry (MS) is a sensitive technique used in the field of chemical analysis to detect, identify, and characterise molecules. Typically, the molecule of interest (the analyte) is mixed with a matrix such as a solvent or deposited on a substrate. A means of releasing or desorbing the analyte from the matrix or substrate, and a method of ionising the analyte are required. The resulting positively or negatively charged ions may then be separated according to their mass (specifically, their mass-to-charge ratio, m/z) by a mass analyser employing electric fields, magnetic fields, or combinations thereof, and subsequently detected by an ion detector. Mass analysers operate at very low pressures (vacuum conditions) to ensure that the trajectories of the ions are dominated by the applied fields rather than by collisions with neutral gas molecules. However, it is often convenient to perform ionisation at atmospheric pressure. When this is the case, a flow of ambient gas and entrained ions from the ion source is drawn into the vacuum system through a small aperture or capillary tube.
Electrospray ionisation (ESI) is the most common method of analysing liquid solutions. This technique requires that a sample of the liquid is delivered via capillary tubing to a sharp tip. In response to an applied electric field, a fine jet of liquid is ejected from the tip, which subsequently breaks up into a plume of charged droplets. Wholly aqueous solutions do not spray well, as the surface tension of water is high. Typically, an organic solvent that is miscible with water, such as acetonitrile or methanol, is added to reduce the surface tension.
Analyte ions are released into the gas phase following a process of solvent evaporation and droplet fissioning. These ions are then drawn into the mass spectrometer inlet and subsequently analysed.
Despite its widespread use, ESI-MS is often inconvenient and problematic. At the very least, a means of withdrawing a sample from a vessel or diverting a sample from a continuous flow must be devised. An extraction or dilution step may be required as even moderate concentrations of dissolved salts and other involatile solutes are known to deposit on mass spectrometer inlets and ion optics, resulting in loss of sensitivity. Preparation of the sample in a solvent system compatible with ESI, desirably comprising an organic component and an acidic or basic chemical modifier, adds further laborious chemical handling. Filtering of the solution may be necessary as particulates tend to block the ESI capillary. If multiple solutes are present, it is common practice to first separate the components by liquid chromatography (LC) in order to negate the effects of ion suppression. Hence, a person of skill in the art will understand that analysis by ESI-MS involves delays, multiple manual or automated processing steps, use of chemical consumables, and additional equipment. It will also be appreciated that ESI-MS is a destructive technique; the liquid sample is consumed and cannot be recovered. While this is of little consequence when a plentiful supply of liquid is available, in some applications, for example, microfluidic processing, the loss may be unacceptable.
It is clear from the foregoing discussion that applications demanding prompt and convenient detection of analytes in solution are not well-served by conventional ESI-MS. There is, therefore, a need for a more rapid and direct means of analysing liquid solutions.
A suite of techniques known as ambient ionisation mass spectrometry have the desired attributes. Ambient ionisation refers to ionisation performed at atmospheric pressure without any sample preparation, and typically also without chromatographic separation. There are now very many examples of ambient ionisation techniques, offering different means of firstly releasing the analyte from the substrate and secondly, ionising the analyte. Analytes are generally desorbed from solid surfaces using lasers, plasmas, or liquid extraction. Clearly, the analyte of interest must be present near or on the surface, which is frequently the case. Although relatively uncommon, liquid surfaces can also be probed using these desorption techniques. However, the analysis is then not necessarily representative of analytes dissolved in the bulk liquid. Atmospheric oxidation, thermal and concentration gradients, frothing, floating precipitates, and phase separation are all commonplace and likely to compromise the analytical value of the mass spectra recorded. More importantly, the task of presenting a surface for analysis when the liquid of interest is flowing in pipes or stored in vats is not trivial. Liquids can also be presented for ambient ionisation as a jet or a mist of nebulised droplets. However, as with ESI, this requires a means of withdrawing or diverting a sample, which is then permanently lost.
Hence, there is a need for a new ionisation probe for bulk liquids that overcomes the drawbacks and limitations of traditional ESI and existing ambient ionisation techniques.

System and method for detecting analytes dissolved in liquids by plasma ionisation mass spectrometry


Plural main cores and plural sub-cores are arranged spaced apart from each other along a direction orthogonal to a rotating direction of a heat belt. The plural main cores are opposed to a first area where a sheet having first width in the heat belt passes. The plural sub-cores are opposed to second areas that are areas excluding the first area in an area where the sheet having second width larger than the first width in the heat belt passes. The plural sub-cores have thickness in the direction orthogonal to the rotating direction of the heat belt smaller than the thickness of the plural main cores.

An image forming apparatus reads an image from an original document, forms a toner image corresponding to the read image on a sheet, and fixes the toner image on the sheet using a fixing device.
The fixing device holds the sheet between a rotating member, for example, a fixing roller or a heat belt and a pressing member, for example, a press roller and applies heat and pressure to the sheet to thereby fix the toner image on the sheet.
An excitation coil for induction heating is provided near the rotating member. High-frequency current flows to the excitation coil, whereby a high-frequency magnetic field is generated from the excitation coil. Eddy-current is generated in the rotating member by the high-frequency magnetic field. The rotating member generates heat with Joule heat based on the eddy-current.
When a small-size sheet passes between the rotating member and the pressing member, the temperature on both the sides of the rotating member not in contact with the sheet is higher than the temperature in the center of the rotating member in contact with the sheet. When the temperature on both the sides of the rotating member rises to be higher than the temperature in the center thereof, the hardness of an elastic member such as rubber forming both the sides of the rotating member falls earlier than the hardness of an elastic member such as rubber forming the center. Therefore, the life of the rotating member is reduced.
Immediately after the small-size sheet passes between the rotating member and the pressing member, when a full-size sheet passes between the rotating member and the pressing member, a toner on the full-size sheet offsets to both the sides of the rotating member in a high-temperature state and causes a fixing failure.
Therefore, in JP-A-2001-318545, first cores are arranged in a position corresponding to an area where sheets of all usable sizes pass and second cores having a Curie point lower than that of the first cores are arranged in positions corresponding to areas excluding the passing area. When temperature rises to exceed the Curie point, the magnetic permeability of the second cores falls and the second cores prevent magnetic fluxes from passing. Consequently, a temperature rise of the rotating member in the sheet non-passing area is suppressed.
However, in this case, since two kinds of cores having different Curie points have to be prepared, cost increases.

Fixing device and image forming apparatus


A tool is used for end-to-end jointing a fiber to another fiber or to an optical connector end-piece by means of a module including a receiving housing enabling a fiber to be inserted at one end at least and wedging action arrangements for fixing the fibers at the bottom of the housing that are operated by pressing them in. The tool carries out the following operations successively and possibly simultaneously for two fibers: partial stripping of each fiber, end cleavage for end-to-end jointing, positioning of each cleaved fiber in the module where it is jointed and crimping of each fiber in a jointing position in the module. These operations are carried out in a cycle commanded by continuous rotation in a particular direction of a rotary drive shaft of the tool after manual fitting of each fiber and the module at particular positions on the tool.

1. Field of the Invention
The invention concerns a tool for carrying out all of the operations for end-to-end jointing a fiber either to another fiber or to an optical connector member by means of a connection module including a receiving housing enabling a fiber to be inserted at one end at least and wedging action means for fixing the fibers at the bottom of the housing which are operated by pressing them in.
2. Description of the Prior Art
Butt jointing one or two optical fibers entails delicate operations including in particular shaping the end of each fiber to be end-to-end jointed, accurately positioning the end(s) to assure high quality optical continuity and fastening each fiber after appropriate positioning.
The use of jointing modules and in particular splicing modules for accurately positioning fibers to be butt jointed and fastening of the fibers after positioning is known in itself.
However, connecting fibers by means of such modules does not eliminate the preliminary operations referred to above, although these modules can facilitate some of them.

Tool for connecting a fiber to another fiber or to an optical connector member by means of a connection module


In a sticky note printer, a sticky note is peeled off and fed one by one from a bundle of notes set in position. In empty-feed motion, the sticky note is fed in a normal direction from a peel-off position through a sticky note ejecting slot to a pull-out position in which the sticky note protrudes outside the sticky note printer. In feed-back motion, the sticky note is fed in a reverse direction from the pull-out position to a retracted position in which printing can be performed. In feed-again motion, the sticky note is fed in the normal direction from the retracted position to the pull-out position. The empty-feed motion is made when the sticky note has been pulled away from the pull-out position. The feed-back motion or the feed-again motion is made, when an instruction for printing is given, in a manner synchronized with the printing operation.

1. Technical Field
The present invention relates to a sticky note printer for printing on a sticky note to be peeled off one by one from a bundle of sticky notes. It also relates to a method of controlling the sticky note printer.
2. Related Art
Conventionally, as this kind of sticky note printer, there is known the following one. Namely, a sticky note is peeled off one by one from the upper surface of a bundle of sticky notes contained inside the sticky note printer. Printing is performed on a printing surface of the sticky note while feeding it, and the printed sticky note is ejected out of an ejecting slot provided ahead as seen in the feeding direction thereof. In this kind of sticky note printer, when a user wishes to use the sticky note for manual writing thereon instead of printing with the sticky note printer, print execution key is depressed without data input so that the sticky note can be ejected without printing thereon. JP-A-2003-11437 is an example of related art.
However, in this sticky note printer, the user must operate the key also in case he or she wishes to use the sticky note in a print-free state (i.e., a state in which printing is not made on the sticky note), in the same manner as in the case of using it by performing printing thereon. Particularly, in case a plurality of print-free sticky notes are needed, the key operation must be made for the same number of times as the number of sheets of the sticky notes. This kind of repeated operation of the key is troublesome because the sticky notes cannot be made readily available for use when it is needed.

Sticky note printer and method of controlling the same


A semiconductor device includes a substrate having an active region, a gate structure intersecting the active region and extending in a first direction parallel to a top surface of the substrate, a first source/drain region and a second source/drain region disposed in the active region at both sides of the gate structure, respectively, and a first modified contact and a second modified contact in contact with the first source/drain region and the second source/drain region, respectively. The distance between the gate structure and the first modified contact is smaller than the distance between the gate structure and the second modified contact.

The inventive concepts relate to a semiconductor device and to a method of manufacturing the same. More particularly, the inventive concepts relate to a semiconductor device including a field effect transistor and to a method of manufacturing the same.
Semiconductor devices are widely used in the electronics industry because of their small sizes, multi-functional characteristics, and/or low manufacturing costs. Semiconductor devices may be categorized as any one of semiconductor memory devices storing logical data, semiconductor logic devices processing logical data, and hybrid semiconductor devices having both the function of semiconductor memory devices and the function of semiconductor logic devices. As the electronics industry has developed the demand for semiconductor devices with improved characteristics have increased. For example, semiconductor devices which are more reliable, operate at higher speeds, and/or provide greater numbers of functions are ever in demand. As a result of satisfying these demands, the architecture and structure of elements of semiconductor devices have become more and more complicated and semiconductor devices have become more highly integrated.

Semiconductor device and method for manufacturing the same


To ensure that the leading edge of the sheet ejected onto a tray 12 does not push and move loaded sheets in advance, loaded sheets are retained at position (II) by a retaining roller. A roller (returning roller in this case) 121 for applying external force to a sheet S ejected onto the tray 12 and moving the sheet toward a end face 131 for alignment is displaced to a different position in the direction of ejection “a”, thereby firmly gripping the trailing edge of the sheet S ejected on the tray 12.

1. Field of the Invention
The present invention relates to a sheet-like medium alignment apparatus, sheet-like medium post-treatment apparatus and image forming apparatus.
2. Description of the Prior Art
A sheet-formed medium alignment apparatus provided with a returning means consisting of a rotating body is known in the prior art, wherein a sheet-formed medium is ejected onto a loading means by an ejecting means and the end of the aforementioned sheet-formed medium on the upstream side in the direction of ejection is pressed against the vertical wall (end fence) provided at the alignment position, whereby the sheet-formed medium is aligned and loaded. External force is applied to the sheet-formed medium ejected onto the aforementioned loading means (tray), and the medium is fed to the aforementioned vertical wall so as to be aligned.
The sheet-like medium handled in the present specification includes duplicating paper, transfer paper, recording paper, cover sheet, offset paper (divider), computer sheets, special paper, OHP sheet and others. In the following description, they will be genetically called sheets.
In an image forming apparatus, a punching unit for punching filing holes on the imaged sheets ejected from the image forming apparatus, staple means, and a sheet-like medium post-treatment apparatus for post-treatment such as stamping, the sheets ejected from the ejecting means are loaded on a tray as a loading means called an ejection tray or loading tray. The sheets loaded on the loading means are automatically aligned for subsequent use. In this case, the major point is the degree of sheet alignment, namely, accuracy of alignment.
In FIG. 77 illustrating an example of the prior art sheet treatment apparatus, for example, sheets S1 with an image created thereon by an image forming apparatus (not illustrated) are fed to the sheet processing apparatus, and are led to a pair of ejection rollers 3 as an ejecting means comprising a lower roller 3a and a upper roller 3b through the ejection sensor for detecting the passage of this sheet. Then sheets are ejected in the direction of ejection "a" (orthogonal to the axial direction of the lower roller 3a within the common tangential plane between a lower roller 3a and a upper roller 3b) on a direct extension of the aforementioned feed direction.
A vertical wall (end fence) 131 is provided below the ejection roller 3, and a tray 12 is located in such a way that it crosses this end fence 131. A tray 12 has a slope which is higher on the downstream side of ejection direction than the fence 131, and sheets are loaded on this slope. Further, tray 12 is movable in the vertical direction, and a sheet surface feeler (not illustrated) detects the top surface of the tray 12 (the top surfaces of the sheets when the sheets are loaded). As sheets are stacked on the tray 12, the tray 12 is lowered, and control is made to ensure that the distance from the nip of an ejection roller to the top surface of the sheet on the tray 12 will be kept constant.
Depending on the ejection speed, the intermediate position of the sheets S1 ejected from the ejection roller 3 to the tray 3 may be bent in the process of ejection while the rear ends of the sheets S1 are still gripped by the ejection roller 3 as shown in FIG. 77, and the sheets S1 may be fed out with the leading edge thereof kept in contact with the loaded sheets S″ which are already loaded on the tray 12.
Under this condition, the leading edges of sheets S1 moves the sheets S2 located on the top surfaces of the loaded sheets S″ toward the downstream side in direction of ejection a; therefore, the trailing edges of the sheets S2 aligned after having been pressed against the end fence 131 by the inclination of the tray 12 are separated from the end fence 131 and is misaligned toward the downstream side in the direction of ejection, with the result that the trailing edge is misaligned.
In the paper copying industry, a bundle of loaded sheets may be fed to the next process to be processed by a punching machine, for example, and this requires excellent alignment accuracy. If a bundle of sheets has a poor alignment accuracy, the bundle taken out of the tray has to be aligned again by human hand before it is fed to the punching machine, with the result that work efficiency is reduced. To solve this problem, the upstream segment, e.g., copying industry requires very severe alignment accuracy of the loaded sheets. Improvement of alignment accuracy is urgently required at present.
To solve this problem of misalignment resulting from the loaded sheet being moved by the leading edge of the ejected paper according to the prior art, a retaining roller 121′ as a retaining means is provided at a central position along the width of the sheet between the ejection roller 3 and the upper surface of the tray 12 in such a way that it can be rotated and driven, as shown in FIG. 78.
The retaining roller 121′ is fixed at a specified position on the immovable member, and is kept in a light contact with the upper surface of the tray 12 (the top surface of the sheet when the sheet is loaded). When paper is loaded on the tray 12, even if the leading edge of the paper ejected on the tray 12 attempts to move the loaded paper, the loaded paper is exposed to the force opposite to the direction of ejection "a" while being pressed by the retaining roller 121′, and is kept pressed against the end fence 131.
The sheet S1 ejected from the ejection roller 3 onto the tray 12 in the manner mentioned above is held by the retaining roller 121′, and is pressed against the end fence 131. This eliminates the so-called vertical misalignment on the trailing edge in the direction of ejection a.
When the retaining roller 121′ is rotating in the arrow-marked direction as shown in FIG. 78, the retaining roller 121′ has also a function of returning the sheet to the side of the end fence 131. The roller in this case is referred to as a returning roller. As shown in FIG. 79, the returning roller 121′ is kept in a light contact with the top surface on the tray 12 and is driven in such a way as to move the contact surface toward the upstream side in the direction of ejection a, so the sheets fed onto the tray 12 whose trailing edges are gripped by the returning roller 121′ are returned opposite to the direction of ejection "a" and are pressed against the end fence 131.
The sheets S1 ejected by the ejection roller 3 and loaded on the tray 12 in the manner mentioned above are gripped by the returning roller 121′. Or those sheets which have been ejected slightly farther in the direction of ejection "a" than the returning roller 121′ are slid under its own weight along the inclination of the tray 12, and their trailing edges are gripped by the returning roller 121′ to be pressed against the end fence 131, whereby the trailing edge is aligned.
These sheets fall under free conditions without any restriction on the distance from the ejection roller 3 to the tray 12, namely, on the distance of free fall of the sheet until they are loaded on the tray 12 by free falling after their trailing edges are released from the ejection roller 3. So a slight displacement will be formed between sheets under the influence of air, and alignment accuracy will be adversely affected. However, these sheets are correctly pressed against the end fence 131 due to the inclination of the tray 12 and the action of the returning roller 121, with the result that basically excellent alignment accuracy is ensured.
Another known art is a sheet-like medium alignment apparatus provided with a sorting means for sorting the sheet-like media fed upward one after another from the image forming apparatus. Such a sheet-like medium alignment apparatus is characterized by operation by an aligning means for aligning the sheet trailing edge, operation by a returning means for returning the sheet to the end fence and sorting operation by the aforementioned sorting means. These operations are performed by using the aforementioned time intervals of sheet-like media being fed one after another.
For example, when the sheet-like medium has been ejected and loaded onto the tray, the following operations are required before the next sheet is ejected; (1) a returning operation for ensuring alignment in the direction of ejection by returning the sheet-like medium with the returning roller until it is pressed against the end fence in order to ensure alignment between the sheet-like medium immediately after ejection and the edge of the already ejected sheet-like medium in the direction of ejection; (2) an alignment operation of gripping the end face in the direction of shift by the aligning means together with the sheet-like medium of the same portion already ejected in order to improve the alignment of the edge of the sheet-like medium in the direction of shift; and (3) a sorting operation by shifting the tray (or an aligning member) by a specified distance only during the time between ejection of the sheet-like medium at the end of this portion and ejection of the first sheet-like medium of the next portion.


An active array radar system is controlled by photonic signals. The array of N antenna elements is divided into M subarrays, each having N/M antenna elements. Tunable lasers provide M optical wavelengths within non-overlapping bands. For reception, the microwave signals are optically modulated onto a single fiber for each subarray. Time delays are introduced for an offset between elements in a subarray and for an offset between subarrays. By using wavelength division multiplexing, a true time delay is attributed to each antenna element on the array. A non-coherent optical combiner having an array of N photodetectors demodulates the receive signals and recovers the coherent sum of the RF signals.

Wideband multifunction radars are capable of concurrently performing hemispheric surveillance, tracking and simultaneously illuminating multiple targets in diverse environments. It is widely recognized that only active phased array antenna and radar systems with their inherent waveform flexibility, high stability and beam switching speed can successfully cope with this broad mission.
For the control of phased array radars, photonic architectures can be broadly characterized as either optically coherent or non-coherent. Although optically coherent architectures have been laboratory demonstrated on a limited scale, their application to a tactical system, where thousands of optical signals must be phase locked is not practical.
The performance issues facing active phased array radars are radio frequency (RF) bandwidth (shared multifunction apertures, imaging, adaptive nulling), true time delay steering (wide instantaneous bandwidth), electromagnetic interference (EMI) and beam steering control. Realizable active arrays providing this performance are limited in weight and size and are generally costly. In particular, transmit/receive T/R modules and array substructures are key cost drivers.

Reactive combiner for active array radar system


A multi-signal radio frequency (RF) source includes an RF source; and a switch including an input in communication with an output of the RF source, a first output and a second output. The switch is configured to selectively connect the input to one of the first output and the second output. An RF generator in communication with the first output of the multi-signal RF source is configured to generate plasma in a processing chamber. A remote plasma generator in communication with the second output of the multi-signal RF source is configured to supply remote plasma to the processing chamber.

The background description provided here is for the purpose of generally presenting the context of the disclosure. Work of the presently named inventors, to the extent it is described in this background section, as well as aspects of the description that may not otherwise qualify as prior art at the time of filing, are neither expressly nor impliedly admitted as prior art against the present disclosure.
Substrate processing systems may be used to perform etching, deposition, and/or other treatment of substrates such as semiconductor wafers. Example processes that may be performed on a substrate include, but are not limited to, chemical vapor deposition (CVD), plasma enhanced chemical vapor deposition (PECVD), atomic layer deposition (ALD), atomic layer etch (ALE), plasma enhanced atomic layer deposition (PEALD) and/or other etch, deposition, and cleaning processes.
During processing, a substrate is arranged on a substrate support, such as a pedestal, an electrostatic chuck (ESC), etc. in a processing chamber of the substrate processing system. A process gas mixture is introduced into the processing chamber to treat the substrate. In some examples, plasma may be struck to enhance chemical reactions within the processing chamber.
After a predetermined interval or processing of a predetermined number of substrates, the processing chamber may be cleaned. Some processing chambers include a remote plasma generator that generates plasma externally and supplies the plasma to the processing chamber to remove buildup of film or other substances on interior surfaces of the processing chamber.

Radio frequency (RF) signal source supplying RF plasma generator and remote plasma generator


An apparatus is provided to calculate a quantity indicating a charged state of an on-vehicle battery. The battery powers a starter starting up an on-vehicle engine. In the apparatus, a plurality of pairs of data consisting of current and voltage of the battery are acquired at predetermined sampling intervals during a cranking period of the engine in response to starting up the starter. At intervals, a value of an internal resistance of the battery is calculated based on the plurality of pairs of data of current and voltage. The internal resistance is one kind of the charged-state indicating quantity. An open voltage difference is calculated, which is a difference between a pseudo circuit-open voltage of the battery given before starting up the starter and a pseudo circuit-open voltage of the battery given after the cranking period. The value of the internal resistance is corrected using the open voltage difference.

1. Field of the Invention
The present invention relates to an apparatus for calculating a quantity indicating the charged state (also called "internal charged state" or "internal state") of a secondary (rechargeable) battery mounted on a vehicle, and in particular, to the apparatus that calculates the charged state using at least a plurality of pairs of voltage and current acquired from the on-vehicle battery.
2. Description of the Related Art
In general, it is required that the capacity and safety of on-vehicle battery systems be strictly managed. To perform such a management, the charged state of an on-vehicle battery system should be estimated with precision.
Several apparatuses to provide some techniques for the estimation have now been proposed. Such techniques use, for example, pseudo circuit-open voltage, internal resistance, charged rate, and/or remaining capacity. For example, as to detecting the internal resistance, there have been known Japanese Patent Laid-open Publication Nos. 2002-343444 and 2005-146939, in which a regression line is obtained on a current/voltage characteristic of a battery system to compute the amount of its slope as an internal resistance of the battery system. Another technique is provided by Japanese Patent Laid-open Publication No. 2002-168929. According to this publication, pairs of voltage/current of an on-vehicle battery are sampled during a period of time during which current consumed by a starter increases from zero to a peak value as high as some 1000 A in response to the start up of the starter, and then the acquired pairs of voltage/current are used to calculate the internal resistance of the battery in controlling the battery state.
In the period of time during which the starter-consuming current increases in response to the startup (hereinafter, this period is referred to as a "starter-current increasing period," refer to FIG. 13), large changes in the current necessary for calculating the internal resistance with precision can be acquired in a short period of time. Thus, in this period of time, the influence of changes in the polarization of the battery in the calculation can be neglected, so that it may be expected that the internal resistance is detected with precision, with very small error due to polarization changes.
However, the foregoing starter-current increasing period is very short (for example, 2-5 msec). This means that a signal processing circuit to acquire a large number of pairs of voltage/current in such a short time should have a high signal processing performance. Specifically, this signal processing circuit includes a current sensor and an A/D converter for digitizing the current and voltage acquired, so that these circuit components need a higher sampling rate. To have such a high signal processing performance results in a rise in parts costs of the signal processing circuit.
In addition, a high-amplitude current which instantaneously reaches a value as high as 1000 A flows through the starter in the starter-current increasing period. The current sensor should therefore have a very large dynamic range, which also becomes. a factor in raising the parts costs.
On the other hand, it is inevitable that the fast-operating current sensor and the analog/digital signal processor are influenced largely by high-frequency components of radio noise and thermal noise, thereby lowering the S/N (signal to noise) ratio.
In this way, to produce voltage/current paired data in the starter-current increasing period involves a high S/N, a fast sampling performance and a wide dynamic range at the sensor and signal processing circuit. This is not practical as it burdens the circuit with a high operational performance. In other words, sampling voltage and current data during the starter-current increasing period is not practical.
To remove this difficulty, it may be possible to sample voltage and current data during a cranking period (or cranking time; refer to FIG. 13) following the starter-current increasing period in an engine startup period (refer to FIG. 13). In the cranking period, the engine starts to generate torque while the starter current decreases gradually. Hence using this cranking period, the burden of the sensor and circuit may be less.
However, since the cranking period is longer than the starter-current increasing period, the fact that changes in the polarized state of the battery during calculation of a charged state thereof cannot be negligible.

Apparatus for calculating quantity indicating charged state of on-vehicle battery


A triggering device for a safety apparatus includes first and second deceleration detecting sensors located within first and second doors of a vehicle respectively or located at positions near the first and second doors respectively. Each of the first and second deceleration detecting sensors is operative for detecting a deceleration. A first signal processing section includes first and second signal processors for processing a detection signal of the first deceleration detecting sensor, and for implementing signal processing with two different processing levels respectively. A second signal processing section includes third and fourth signal processors for processing a detection signal of the second deceleration detecting sensor, and for implementing signal processing with two different processing levels respectively. A first safety device located at the first door is operative for protecting an occupant in the vehicle. A second safety device located at the second door is operative for protecting an occupant in the vehicle. First and second trigger components are operative for triggering the first and second safety devices respectively. One of the first and second trigger components is controlled to trigger one of the first and second safety devices on the basis of results of the signal processing by the first signal processor and the fourth signal processor. The other of the first and second trigger components is controlled to trigger the other of the first and second safety devices on the basis of results of the signal processing by the second signal processor and the third signal processor.

1. Field of the Invention
This invention relates to a triggering device for a vehicle occupant safety apparatus such as an air-bag apparatus or a vehicle safety-belt pretensioner (tightener).
2. Description of the Prior Art
U.S. Pat. No. 5,107,245 discloses a control arrangement for the occupant restraint system of an automotive vehicle which includes an acceleration pickup for sensing deceleration of the vehicle and providing an acceleration signal. A trip device is in the occupant restraint system. A microcomputer processes the acceleration signal. The microcomputer supplies one or more trip signals to the trip device when the result of processing of the acceleration signal fulfills a criterion for activation of the occupant restraint system. A monitoring circuit external to the microcomputer includes an associated stable oscillator providing a reference signal. The monitoring circuit serves to monitor, as to correct frequency by comparison with the reference signal, a check signal derived from a clock signal of the microcomputer. The monitoring circuit produces an enable signal when the check signal has the correct frequency. The monitoring circuit activates an indicating means when the check signal is found to be incorrect. The monitoring circuit prevents the supply of the trip signal to the trip device in response to the disappearance of the enable signal.
U.S. Pat. No. 5,359,515 corresponding to Japanese published PCT application 4-506495 discloses a vehicle occupant safety system which includes a sensor device having at least two sensors, and a processing device having at least two processing circuits for the respective sensor signals. The vehicle occupant safety system in U.S. Pat. No. 5,359,515 further includes a computing system and a trigger circuit each having at least two stages for a safety device. For providing a high degree of safety with relatively low costs, the computing system is constructed as a single-computer system in such a way that it processes the data of the two processing circuits in two programs with staggered timing with respect to one another.
Japanese published unexamined patent application 5-69791 discloses a side-crash sensing system for automotive side air-bag devices in which an air-bag trigger component is controlled in response to the output signals of plural acceleration sensors.


A ceramic member-electric power supply connector coupling structure includes a ceramic member with a hole and is provided with a metallic member therein so as to be partially exposed to the hole. An electric power supply connector and a tubular atmosphere-shielding member are provided in the hole. Further, a stress-mitigating, low heat expansion conductor is provided inside the atmosphere-shielding member and the power supply connector is partially positioned therein. The atmosphere-shielding member is gas-tightly joined to the power supply connector, and the expansion conductor and the tubular atmosphere-shielding member are joined to the metallic member. The coupling structure has high heat and corrosion resistance, high joining strength, and remains highly conductive even at high temperature conditions in an oxidative or corrosive environment.

(1) Field of the Invention
The present invention relates to ceramic member-electric power supply connector coupling structure.
(2) Description of Related Art
Nowadays, electrostatic chucks are being used to adsorb and hold semiconductor wafers in transferring, light-exposing, film-forming such as CVD and sputtering, fine processing, washing, etching, dicing, etc. for semiconductor wafers. Dense ceramics are noted for substrates of such electrostatic chucks. Particularly in the semiconductor producing apparatus, a halogen based corrosive gas such as ClF.sub.3 is often used as an etching gas or a cleaning gas. In order to rapidly heat and cool the semiconductor wafer while being held by such a substrate, the substrate of the electrostatic chuck is desired to have high heat conductivity. Further, it is desired that the substrate have such heat shock resistance so as not to be destroyed by rapid temperature changes. Dense alumina nitride and alumina have high corrosion resistance against the halogen based corrosion gas mentioned above.
In the field of the semiconductor producing apparatuses, susceptors in with built-in high frequency electrodes for generating plasma have been practically used. In the field of such high frequency electric power generating apparatuses, a metal electrode is buried in a substrate of aluminum nitride or dense alumina. Further, in the field of the semiconductor producing apparatuses, ceramic heaters in which a metallic resistor is buried in a substrate of aluminum nitride or alumina for controlling the temperature of a wafer in each process.
In these apparatuses, it is necessary that the metal electrode be buried in the ceramic substrate made of aluminum nitride or the like, and that the metal electrode be electrically coupled to an external electric power supply connector. However, a coupling portion for this purpose is exposed to a heat cycle between extreme high temperatures and low temperatures in an oxidative atmosphere and further in a corrosive gas atmosphere. Such a joining portion is desired to maintain high joining strength and excellent electric coupling performance for a long time period even under such a bad condition.
The present inventors have continuously studied the coupling structures as mentioned above. For example, a Japanese patent application No. 8-24,835 disclosed that the tip of an electric power supply connector was coupled to a metal electrode in a susceptor with an Al alloy brazing material, a Cu alloy brazing material or a Ni alloy brazing material having high corrosion resistance. Further, JP8-24,836 proposed that a mesh or net metal electrode be buried in an AlN ceramic, while a part of the mesh or net metal electrode be exposed, and the exposed mesh or net portion and the AlN ceramic be both brazed to a tip face of the electric power supply connector.
Although these Japanese patent applications proposed the brazing methods which would ensure high corrosion resistance against the halogen based corrosive gas and the plasma, a specific coupling structure which would maintain high joining strength and excellent conductivity even under exposure to high temperatures and heat cycle in the oxidative atmosphere has not been investigated in detail with respect to the coupling structure for the connector and the metallic electrode.

Ceramic member-electric power supply connector coupling structure


Disclosed are a heat transfer medium and a heat transfer method that uses the heat transfer medium. The heat transfer medium comprises a light-transparent substrate coated with a plurality of nano particles. The nano particles absorb light incident thereon to thereby produce heat, which is transferred to a target object to be heated. Nano particles can be applied onto a target object. After heating, the particles are removed by etching. Nano particles can be selectively applied to the light-transparent substrate or directly to a target object to be heat so as to localize heat-production and thus heat selective portions of the target object.

This disclosure relates to a heat transfer medium and a heat transfer method that uses the same.
A film formed on a glass or plastic substrate is crosslinked, ordered, plasticized, or crystallized by the application of heat. However, because of differential expansion between the film and the glass or the plastic substrate, fracture of the glass substrate or deformation of the plastic substrate often occurs. In particular, a sintering process that uses high temperature cannot be easily applied to a plastic substrate because inhomogeneous contraction of the substrate occurs.
Further, for example, titanium oxide (TiO2), i.e., a transparent porous electrode material used in a photovoltaic (PV) cell should be sintered at 470° C. Thus, plastic materials cannot be readily used as a substrate for the photovoltaic cell.

Heat transfer medium and heat transfer method using the same


A cable tie with an elongated tongue with two ends and two broad sides, a tip at one end of the tongue, a set of ratchet teeth extending along one broad side of the tongue, and a locking head at the other end of the tongue, the locking head having sides defining an opening for receiving the tip of the tongue, and a movable pawl that is hinged at one side of the opening, with another side of the opening defining an abutment wall that is across the opening from the pawl. The pawl engages with one or more of the ratchet teeth when the tongue has been inserted through the opening with the set of ratchet teeth facing the pawl. The abutment wall defines at least one protruding cross member, to strengthen the abutment wall.

Cable ties are useful for quickly and securely retaining together two or more items, for example the conductors in a wiring harness. Several examples of cable ties are shown in U.S. Pat. Nos. 5,263,231; 5,440,786; and 5,615,455. In a general sense, a cable tie is an elongated tongue with a tip at one end and a locking head at the other end. A set of ratchet teeth are located on the underside of the tongue. The locking head has an integral movable pawl that is hinged at one side of an opening in the locking head. When the tip is inserted in the opening and pulled through the head, the pawl engages with the ratchet teeth to prevent the tip from being pulled back out of the opening.
When force is applied to an engaged cable tie, the tongue is pulled in a direction opposite to that in which it was inserted in the head. This causes the pawl to be pulled farther away from its attachment point, which pushes the tongue against the side of the opening opposite the pawl, termed the "abutment wall". If sufficient force is applied, the abutment wall can bow outward, which can cause the ratchet teeth to release from the pawl.
One manner to alleviate this bowing is to increase the thickness of the abutment wall. However, the increased thickness requires an increase in the residence time of the product in the injection mold, so that the plastic cools sufficiently before the mold is opened to prevent shrinkage of the abutment wall. One proposed solution to this problem is disclosed in U.S. Pat. No. 5,615,455. The abutment wall includes a plurality of apertures extending within the abutment wall parallel to the direction of insertion of the tip in the head. The apertures are not exposed to the abutment surface. The apertures are elongated, and pairs of apertures extend along a common axis from opposite ends of the abutment wall, but do not join each other. This design is described as not requiring as much material as a similar thickness solid wall and so not being significantly subject to deformation when the injected plastic material cools.
However, this product would be extremely difficult to manufacture. In order to create the apertures in the abutment wall, the mold would have to have a series of very small pins that would be subject to deformation and breakage. In addition, much of the abutment wall is substantially thicker than the rest of the walls of the head. Accordingly, this design likely would not significantly decrease the amount of time that the product would need to be maintained in the mold to cool sufficiently before it is ejected from the mold so as not to cause bowing of the abutment wall.


The present invention involves a method and apparatus for making an intermetallic casting (e.g. a titanium, nickel, iron, etc. aluminide casting) wherein a charge of a solid first metal protected from air as required is disposed in a vessel, and a charge of a second metal that reacts exothermically with the first metal is melted in another vessel. The molten second metal is introduced to the vessel containing the charge of the first metal so as to contact the first metal. The first and second metals are heated in the vessel to exothermically react them and form a melt for gravity or countergravity casting into a mold. The exothermic reaction between the first and second metals releases substantial heat that reduces the time needed to obtain a melt ready for casting into a mold. In particular, the exothermic reaction between the first and second metals, in effect, reduces the residence time of the intermetallic melt in the vessel. This reduced residence time, in turn, reduces potential contamination of the melt by reaction with the vessel material. Moreover, the energy requirements needed to heat and melt the metals in the vessel are considerably reduced. Low cost forms of the first and second metals can be used in practicing the invention. As a result, overall casting costs are reduced. The method and apparatus of the invention can be used to produce large numbers of low cost, low contamination intermetallic castings as needed by the automobile, aerospace, and other industries.

Many alloys with high weight percentages of a reactive metal, such as titanium, react with air and most common crucible refractories to the degree that the alloy is contaminated to an unacceptable extent. As a result, it is common to melt such alloys in water cooled, metal (e.g. copper) crucibles using electric arc or induction to generate heat in the alloy charge.
U.S. Pat. No. 4 738 713 is representative of one such melting technique. The patented melting method is very inefficient in the use of electrical power. Moreover, experience with such a method indicates that the amount of melt superheat achievable is limited and sensitive to crucible life. However, the method is in use since the method can use lower cost melt stock than consumable arc melting techniques which require specially prepared melting electrodes of the alloy desired.
Arc melting techniques using water cooled copper crucibles (e.g. see U.S. Pat. No. 2 564 337) can provide higher superheats in melting the reactive alloys. However, arc melting techniques, as well as induction melting techniques, are dangerous due to the potential for explosion in the event of crucible failure wherein cooling water comes into contact with the molten reactive alloy to form hydrogen gas. Both arc melting and induction melting techniques are practiced in remote manner, such as from behind explosion proof walls in specially constructed buildings with blow-out walls. As a result, operation of such cold-wall metal crucibles or furnaces has been costly with good process control difficult to achieve.
Some prior art workers have melted and cast reactive alloys, such as titanium alloys, using calcium oxide crucibles. However, contamination of the alloy melt with oxygen is rapid and, with some alloys containing aluminum, extensive aluminum oxide vapor is evolved in such amounts as to preclude practical operation of traditional casting units by contaminating vacuum systems and chambers associated with the casting unit.
Other prior art workers, see U.S. Pat. No. 3 484 840, have rapidly melted titanium alloys in graphite lined crucibles in order to avoid harmful contamination of the melt. The patented process does not permit accurate control of the melt temperature and excessive melt contamination can occur if the heating cycle is too long. In addition, control of the melt flow out of the bottom of the crucible is difficult since melting of the center portion of a metal disc at the crucible bottom is employed to this end. With this arrangement, the melt flow orifice will vary with the melting rate, charge diameter, and disc size, making control of melt flow difficult.
Intermetallic alloys, such as especially TiAl, have received considerable attention in recent years for use in the aerospace and automobile industries in service applications where their high strength at elevated temperature and relatively light weight are highly desirable. However, these intermetallic alloys contain a majority of titanium (e.g. so-called gamma TiAl includes 66 weight % Ti with the balance essentially Al) which makes melting and casting without contamination difficult and very costly. In order to be adapted for use in such components as automobile exhaust valves, the intermetallic alloys must be melted and cast without harmful contamination in a high production, low cost manner.
It is an object of the present invention to provide a method and apparatus useful for, although not limited to, making intermetallic castings without harmful contamination in a high production, low cost manner especially suited to the requirements of the automobile, aerospace and other industries.
It is another object of the present invention to provide a method and apparatus for making intermetallic castings using a refractory melting vessel and a combination of molten and solid melting stock in a manner to avoid harmful contamination of the melt by reaction with the vessel.
It is another object of the invention to provide a method and apparatus for making intermetallic castings in a low cost manner by virtue of using relatively low cost melting stock which requires reduced energy requirement in order to yield a melt ready for casting into a mold.

Method and apparatus for making intermetallic castings


Provided a touch display panel includes a signal transmission layer, an insulation layer, and a touch layer disposed in stack. A surface of the signal transmission layer is provided with first concave-convex structure. The insulation layer covers the first concave-convex structure, and a surface thereof is provided with a second concave-convex structure at least partially overlapping the first concave-convex structure in a light exit direction. The second concave-convex structure includes a second convex portion, a second concave portion, and a second connecting portion, thickness of the second connecting portion smaller than either thickness of the second convex portion or thickness of the second concave portion. A connection via hole is further provided, penetrates at least the second connecting portion, exposes part of the signal transmission layer, and the touch layer electrically connected to the signal transmission layer through the connection via hole.

With the rapid development of the display technologies, touch display panels are widely used. A touch display panel combines a touch panel and a display panel, to enable the display panel to have functions of both displaying and perceiving a touch input. In order to realize the touch control function, it is generally necessary to bridge between different film layers, and it is prone to presenting a problem of poor contact.

Touch display panel and touch display device

Hubei Yangtze Industrial Innovation Center Of Advanced Display Co., Ltd.


A method is described for generating a novel cancer stem cell line that possesses characteristics associated with stem cells, by co-culturing a human immortalized cell line and bone marrow-derived mesenchymal stem cells, and the novel cancer stem cell line established thereby. This method is able to readily generate cancer stem cells that are low in the level of structural chromosomal aberrations and are excellent in oncogenicity, and is effectively applicable to the development of anti-cancer drugs and personalized drugs.

Field of the Invention
The present invention relates to a method for generating a cancer stem cell line from an immortalized cell line. More particularly, the present invention relates to a method for generating a novel cancer stem cell line that possesses characteristics associated with stem cells, by co-culturing a human immortalized cell line and bone marrow-derived mesenchymal stem cells, and the novel cancer stem cell line established thereby.
Description of the Related Art
Cancer stem cells (hereinafter referred to as "CSCs", interchangeably used for tumor stem cells) are primary tumor cells that exhibit self-renewal, proliferative capacity and multi-differentiation, forming a microenvironment where blood vessels, mesenchymal stem cells and a variety of cancer cells are found. Now, there are four methods of isolating cancer stem cells from tumor tissue using characteristics of cancer stem cells:
first, MACS (Magnetic-Activated Cell Sorting) and FACS (Fluorescence-Activated Cell Sorting), using antibodies against specific markers expressed by tumor stem cells;
second, side population discrimination by a dye exclusion assay that takes advantage of the high activity of an ABC reporter predominantly in leukemia and multiple myeloma;
third, isolation using the activity of such enzymes that are overexpressed in tumor stem cells as aldehyde dehydrogenase (ALDH); and
fourth, segregation of tumor stem cells from differentiated cancer cells by forming a tumorsphere in the presence of growth factors (EGF and bFGF) in a serum-free medium.
These methods, although readily isolating CSCs from cancer cells, are not effective in securing a multitude of CSCs since the CSCs are different in ratio from each other. Also, the CSCs isolated by each isolation method differ in oncogenesis from one to another. In addition, since characteristics of CSCs are changed during cultivation, isolation and culture methods are further studied. Moreover, it takes a significant time to obtain tumor tissues from cancer patients according to legal and administrative matters.
Hence, there is a need for a method for generating cancer stem cells that overcomes the conventional problem of isolating a small population of cancer stem cells and that can secure a multitude of homogenous cancer stem cells, with few legal or administrative limitations.
As a background of the present invention, Korean Patent No. 10-1242726 (issued Mar. 13, 2013) discloses a method of diagnosing cancer with a cancer stem cell property by measuring the expression level of aldehyde dehydrogenase (ALDH). Korean Patent Publication No. 10-2012-0099904 (issued Sep. 12, 2012) describes a tumor stem cell-targeting peptide GICT that can selectively recognize and bind malignant, undifferentiated glioma cells, and a method for diagnosing encephaloma. Korean Patent No. 10-0783199 (issued Dec. 6, 2007) describes a cancer stem cell line GBM 2, established from human glioblastoma multiforme tissue, having resistance to drugs.
However, nowhere is a method of easily, quickly and efficiently generating cancer stem cells from an immortalized cell line and maintaining the cancer stem cells found in previous literature.
Leading to the present invention, intensive and thorough research into the mass production of cancer stem cells having high oncogenic potential resulted in the finding that cancer stem cells can be derived from an immortalized cell line which is co-cultured with mesenchymal stem cells.
References relevant to the subject matter of the present disclosure include the following:
In vitro generation of human cells with cancer stem cell properties. Scaffidi P, Misteli T. Nat Cell Biol. 2011 Aug. 21; 13(9):1051-61.
SSEA-1 is an enrichment marker for tumor-initiating cells in human glioblastoma. Son M J, Woolard K, Nam D H, Lee J, Fine H A. Cell Stem Cell. 2009 may 8; 4(5):440-52
CD133, CD15/SSEA-1, CD34 or side populations do not resume tumor-initiating properties of long-term cultured cancer stem cells from human malignant glio-neuronal tumors. Patru C, Romao L, Varlet P, Coulombel L, Raponi E, et al., BMC Cancer. 2010 Feb. 24; 10:66.
The micro-RNA 199b-5p regulatory circuit involves Hest, CD15, and epigenetic modifications in medulloblastoma. Andolfo I, Liguori L, De Antonellis P, Cusanelli E, Marinaro F, Pistollato F, Garzia L, et al., Neuro-Oncology. 2012 Jan. 22; 14(5):596-612.

Method for generating cancer stem cells from immortalized cell lines

KOREA UNIVERSITY RESEARCH AND BUSINESS FOUNDATION


A boat trailer ladder assembly for entering or exiting the bow of a boat on a boat trailer includes:

1. Technical Field
The present invention relates to a ladder assembly on a boat trailer for facilitating entry to and exit from the bow of a boat on the trailer, more particularly an adjustable boat trailer bow entry ladder assembly having a base platform, a brace device, and a boarding rail on one side.
2. Background Information
Boating is a very popular pastime in geographic areas that are close to large bodies of water. With this popularity, boats have increased in number and grandeur. Since most boat owners use boat trailers to haul their boats to the bodies of water, larger and larger sized boats are being towed by large trailers with two and three axels to accommodate these big boats. Occasionally, one even sees a four axel trailer at the boat ramp. These large boats have a high freeboard and require ladders to climb into the boat when the boat is parked on the trailer. Also, boaters often go boating by themselves and do not have qualified assistants to help launch or retrieve the boat. The boat trailer ladder assembly of the present invention facilitates the off-loading (launching) and on-loading of a boat onto a boat trailer as the trailer sits with its hubs in the water on a sloping boat ramp connected to a tow vehicle.
Currently available boat ladders include ladders that are mounted on a boat stem for entering the boat from the water, or exiting the boat into the water (e.g., for swimming or water skiing). They also include folding ladders mounted on a boat. Ladders mounted on a ship for traveling to and from an upper deck of the ship are also known.
During the launching (off-loading) phase, the boater can disconnect the trailer's attaching cable or strap, and use the bow ladder assembly of the present invention to step up from the boat trailer into the boat. The boater can then power up the boat, back the boat off the trailer, and then dock and secure the boat. The boater can then leave the boat and retrieve the unloaded trailer from the loading ramp.
After the outing, loading the boat back onto the boat trailer requires boating skills. For example, the boater must move the trailer to the boat ramp, and line up and propel the boat to where the retrieving cable or strap of the trailer can be attached to the boat. The boat can then be winched onto the trailer. This loading phase is especially difficult after a tiring day in the sun water skiing or the like. Often the boat is propelled up to the attaching post, but the boat must still be secured to the boat before the boat trailer can be pulled out of the water. The present invention allows the boat operator to safely descend to the trailer platform from the bow of the boat, secure the boat, and step out onto the dry portion of the ramp. Where the tow vehicle is a pickup truck, the boater can step directly onto the tow vehicle from the ladder assembly. The tow vehicle and loaded trailer can be driven up the ramp and onto a level area to allow other boaters to either retrieve or launch their boats.
Another advantage of the present invention is that it provides a permanent, secure bow entry ladder, so the user can work on the boat at home or in dry storage, for example. A stable step ladder entry for accomplishing boat repairs is highly desirable for safety and efficiency.

Abstract: (a) a generally trapezoidal-shaped platform portion attachable to the boat trailer between a winch assembly of the trailer and a trailer hitch assembly of the trailer; and

Abstract: (b) a ladder portion including a boarding ladder and a brace device, the boarding ladder including two substantially parallel, spaced apart side rails and a plurality of ladder steps extending between the ladder side rails, the ladder steps having a spaced horizontal relationship with one another, the lower ends of the boarding ladder being attached to the platform portion, the brace device having an upper end movably affixed to at least one of the ladder steps or one of the side rails of the boarding ladder; wherein a lower end of the brace device is attachable to a post of the winch assembly of the boat trailer.


A vibration isolator is composed of a cylindrical elastomer body and a cylindrical inner fixing member and an outer fixing member both made of a metallic material. The inner fixing member and the outer fixing member have flange parts formed along the edges thereof. The inner fixing member which has a smaller diameter than the outer fixing member is fixed to the inside diameter side of the elastomer body and the outer fixing member is fixed to the outside diameter side of the elastomer body. The elastomer body is formed of either an elastomer having a thermal conductivity in the range of from 1.3.times.10.sup.-3 to 7.1.times.10.sup.-3 cal/cm.cndot.sec.cndot..degree. C. or a elastomer composition containing 50 to 200 parts by weight per 100 parts by weight of rubber. The vibration isolator constructed as described above enables the spring constant in the direction perpendicular to the axis to be increased without reducing the effect of isolating vibration so as to decrease the displacement of the motor and improve the accuracy of positioning thereof. It also provides effective radiation of the heat generated by the motor and prevents the motor from temperature elevation.

1. Field of the Invention
This invention relates to a vibration isolator for a motor which is used for the purpose of preventing such stepping motors as are serving to feed papers in a facsimile or a copying machine or operate a printing head in a printer from generating vibration or emitting noise.
2. Description of the Related Art
In recent years, vibrations and noises emanating from various office automation (OA) machines copiously adopted for clerical works in consequence of the automation of business offices have come to pose a problem. One of the causes for the problem resides in the fact that when the motors built in the OA machines are in operation, the vibrations of these motors are transmitted to the frames of the machines. The practice of interposing a vibration isolator between the motors and the frames of the machines has been heretofore resorted to for precluding transmission of vibration and abating noise. FIG. 1A and FIG. 1B illustrate a conventional vibration isolator 1 to be used in the installation of a stepping motor. This vibration isolator 1 has a rubber body 4 (made of chloroprene or butyl rubber, for example) attached by means of vulcanization between two metal pieces containing fixing holes 2, . . . and is provided at the center thereof with a through hole 5 for allowing insertion therethrough of the drive shaft of a stepping motor (JP-U-1-71,964). This vibration isolator 1 is used as in a platen drive mechanism for a printer illustrated in FIG. 2 or in a paper feeding mechanism illustrated in FIG. 3, for example. It is inserted between a stepping motor 6 and a frame 7 and fastened thereto with bolts which are fitted into the fixing holes 2, . . . .
In the conventional vibration isolator 1, however, the spring constant thereof in the axial direction (namely in the direction of compression) is 1, whereas the spring constant thereof in the direction perpendicular to the axis (namely in the direction of shearing) is 0.2. Because of the small spring constant in the shearing direction as compared with that in the axial direction, this vibration isolator 1 is at a disadvantage in tending to be affected by a displacement in the shearing direction and being deficient in accuracy of positioning. In the case of such a gear drive device as the platen drive mechanism of the printer of FIG. 2, when a pinion 9 disposed around a drive shaft 8 of the stepping motor 6 rotates a gear 12 disposed round a platen shaft 11 of a platen 10, the drive shaft 8 and the pinion 9 are inevitably displaced in the shearing direction in response to the vibration of the stepping motor 6 because the spring constant of the vibration isolator 1 in the shearing direction (in the direction perpendicular to the drive shaft 8) is small. As a result, the backlash between the pinion 9 and the gear 12 is fluctuated to degrade the accuracy of positioning. In the case of such a belt drive device as the paper feeding mechanism of FIG. 3, since a pulley 13 disposed round the drive shaft 8 of the stepping motor 6 is connected to another pulley 14 through the medium of a belt 15, the tension of the belt 15 acts on the pulley 13 and the drive shaft 8 and consequently displaces the drive shaft 8, for example, in the shearing direction (in the direction perpendicular to the drive shaft 8).
For the elimination of these drawbacks, measures such as increasing the hardness of the rubber body 4 and decreasing the thickness thereof which are intended to increase the spring constant of the vibration isolator 1 in the direction perpendicular to the shaft thereof have been adopted. The effect of isolating vibration, however, is rather degraded when the spring constant in the direction perpendicular to the shaft is increased by these measures.
Incidentally, rubber has a thermal insulation. When the stepping motor 6 is set to driving as fixed on the frame 7 through the medium of the vibration isolator 1, therefore, the heat generated in the stepping motor 6 is insulated by the vibration isolator 1 and accumulated in the stepping motor 6 itself. The stepping motor 6, therefore, is at a disadvantage in acquiring satisfactory properties only with difficulty and suffering a decrease in service life.


A new and distinct cultivar of Geranium plant named ‘Sil Quirin’, characterized by its semi-double to double type purple-colored flowers, medium green-colored foliage with faint zonation, and vigorous, semi-upright to trailing growth habit.

The present invention relates to a new and distinct cultivar of Geranium plant botanically known as Pelargonium peltatum and hereinafter referred to by the cultivar name 'Sil Quirin'.
The new cultivar originated in a controlled breeding program in Weener, Germany during Summer 2000. The objective of the breeding program was the development of Pelargonium peltatum cultivars that are moderately vigorous with unique flower coloration, medium to dark green-colored foliage, trailing growth habit, and low oedema susceptibility.
The new Geranium cultivar is the result of cross-pollination. The female (seed) parent of the new cultivar is 'Hillscheider Amethyst', not patented, characterized by its semi-double type violet-colored flowers, medium green-colored foliage with very weak zonation, and moderately, vigorous to vigorous, semi-upright growth habit. The male (pollen) parent of the new cultivar is 'Royal Blue', not patented, characterized by its double type medium to dark purple-colored flowers, medium green-colored foliage without zonation, and vigorous, semi-upright growth habit. The new cultivar was discovered and selected as a single flowering plant within the progeny of the above stated cross-pollination during June 2001 in a controlled environment at Weener, Germany.
Asexual reproduction of the new cultivar by terminal stem cuttings since June 2001 at Weener, Germany and West Chicago, Ill. has demonstrated that the new cultivar reproduces true to type with all of the characteristics, as herein described, firmly fixed and retained through successive generations of such asexual propagation.


Methods, devices, and systems (for outputting a case summary) receive an electronic medical record (EMR) (and generally electronic records) for the medical patient, extract medical data from the EMR, provide a list of medical problems relevant to the EMR, identifying relations between the medical problems and the medical data using a question-answering (QA) system, and output the clinical summary for the EMR. The clinical summary comprises the list of medical problems, the medical data, and the relations.

The present disclosure relates to question-answering technology, and more specifically, to systems and methods for creating patient case summaries from electronic medical records (EMRs) using question-answering technology.
In the medical domain, a patient's medical conditions and treatment history are often stored in collection referred to as an electronic medical record (EMR). An EMR may include large volumes of plain text clinician notes, procedures performed along with results, structured data such as medications, and images such as CT scan images. An EMR may contain both structured and unstructured data resulting from a variety of medical care encounters of a patient with medical care providers. Examples of information that may be contained in an EMR include demographic information, family and social history, reports from care providers, procedures undergone, medications prescribed, diagnostic test results, vital signs, and administrative reports. Therefore, EMRs tend to be large; for example, an EMR of a single patient may contain hundreds of megabytes of structured and unstructured content. An aggregated clinical summary of patient information in the EMR is of high value in patient care if it shows the most important points relevant to patient care.

This patent is subject to a terminal disclaimer.

Electronic medical record summary and presentation

International Business Machines Corporation


The present invention provides an electric incinerating toilet bowl and an incineration control method for the electric incinerating toilet bowl which can remove not only odor components but also smoke and soot generated when paper liners burn to thereby prevent the odor components and the smoke and soot from being exhausted. The incineration control method heats a smoke and soot removing filler layer to a smoke and soot removing temperature not lower than 350° C. by actuating a filler heating heater in response to input of a treatment start signal, carries out an incineration treatment by actuating an incinerating heater and an exhaust blower when a temperature of the smoke and soot removing filler layer has risen to a smoke and soot removing temperature, stops the incinerating heater and the filler heating heater when a temperature of an incineration chamber rises to a preset incineration treatment end temperature, and stops the exhaust blower when a temperature in the electric incinerating toilet bowl has dropped to a preset exhaust end temperature after the stop of the incinerating heater.

As a toilet bowl installed in a place without water supply and sewerage systems, there is a known electric incinerating toilet bowl in which excrement dropped with paper liners into an incineration chamber of an incinerator disposed below a toilet seat is incinerated by heating by an incinerating heater, the excrement and the paper liners are turned into odorless and sterile mineral incinerated ash, and odor components in burning exhaust gas generated in the incineration, e.g., nitrogen compounds such as ammonia are removed by a deodorizing catalyst. Although this electric incinerating toilet bowl is more expensive than a storage toilet bowl which is often used in a general temporary toilet, the stored excrement need not be transported to a treatment facility and treated and therefore the electric incinerating toilet bowl is sanitary, suitable for toilets installed in construction sites in urbanization areas, camp sites, training yards, outdoor sports facilities, and underground construction spaces, and best suitable for toilets installed in overcrowded spaces such as basements and shield tunnel construction sites where people are living or working (see Patent Document 1, for example).

Electric incinerating toilet bowl and incineration control method for electric incinerating toilet bowl


A work apparatus is comprised of a blower unit including a drive motor, a volute casing, a fan rotatably supported within the volute casing and driven by the drive motor, and an airflow duct connected to the volute casing, thereby blowing out or sucking in air through the airflow duct; and of an airflow tube coupled to the airflow duct of the blower unit and having an open distal end for blowing out or sucking in air through the airflow tube. The airflow tube is provided with a grip handle adapted for being held and operated by the operator. Within the airflow tube is arranged an electrically conductive wire at least between the grip handle and the open distal end, beyond which is provided an electrically grounding wire connected to the electrically conductive wire and drooping therefrom to be touchable to earth.

Blower apparatuses have been conventionally known and used in the art as a kind of work apparatuses used for blowing off fallen leaves on the ground or the like. A blower apparatus comprises a power-operated blower unit and an airflow tube (blowoff tube). The blower unit includes a drive motor, a volute casing, a fan rotatably supported within the volute casing and driven by the drive motor, and an airflow duct (a blow-out duct) connected to the volute casing for blowing out air impelled by the fan. The airflow tube is coupled to the airflow duct of the blower unit to blow out air from the open distal end of the airflow tube. In this type of blower apparatus, the air flowing out from the airflow duct passes through the airflow tube before it blows out from the open distal end, which is apt to cause generation of electrostatic charge on the volute casing and the airflow tube by the friction between air (including dust) and the inner circumferential walls of the volute casing and the airflow tube. Under these circumstances, when the user or operator of the blower apparatus holds the grip handle provided on the airflow tube, the electrostatic charge accumulated on the airflow tube would burst through to the hand of the operator, giving a harsh attack to the operator.
Various configurations have been conventionally proposed in the art to avoid unwanted attack of electrostatic discharge. An example of blower apparatuses with an arrangement provided within the blower tube for avoiding electrostatic discharge attack is disclosed in JP 2008-106660 A. The arrangement comprises a charge removing conductive wire provided within the airflow tube and having a free end positioned at the logitudinally intermediate point of the airflow tube and another end led outside the airflow tube through between the straight tube component and the elbow tube component of the airflow tube and electrically connected to the engine via an electrically conductive wire. The other end of the charge removing conductive wire which is connected to the electrically conductive wire is folded back toward the air to constitute a discharging wire. When this blower apparatus is in operation to blow out air from the airflow tube, the electrostatic charge generated on the inner wall of the airflow tube is gathered by the charge removing conductive wire violently streaming within the airflow tube and is discharged mostly to the engine and partly to the air.
Another example of blower apparatuses with an arrangement provided within the blower tube for avoiding electrostatic discharge attack is disclosed in U.S. Pat. No. 7,979,958 B2. The arrangement comprises a potential compensating conductor having a free end positioned centrally in the blower tube and another end connected to the drive motor, and an electrically conductive configuration from the potential compensating conductor and the drive motor to the ground device through the body of the operator, so that the charges on the potential compensating conductor and on the drive motor can be conducted away into the ground.
With the first example as mentioned above in which the electrostatic charge generated in the airflow tube is conducted away to the engine via the charge removing conductive wire, a potential difference may be established between the engine and the operator, and the electrostatic charge accumulated on the engine may flow through the throttle wire which is for controlling the throttle valve of the engine or through the lead wire which is for stopping the engine, and may attack the operator's hand holding the grip handle to which both the wires are extended from the engine. The operator should feel very uncomfortable.
With the second example as mentioned above in which the electrostatic charge on the potential compensating conductor and the engine is expected to be conducted away to the ground through the operator, it would be hard to thoroughly discharge the accumulated charge. Both of the above mentioned inconveniences would be obviated by hanging a conductive chain from the engine to reach the ground, but such an arrangement would cause another inconvenience for the operator to erroneously step on the chain during the operation.


An adenoviral supervector system is disclosed that is capable of expressing more than 7.5 kilobases of heterologous DNA in a replication defective adenoviral vector. The supervector system comprises an adenoviral vector construct and a helper cell. The vector construct is capable of being replicated and packaged into a virion particle in the helper cell. In particular, the helper cell expresses DNA from the E2 region of the adenovirus 5 genome and complements deletions in that region in the vector construct.

1. Field of the Invention
The present invention relates generally to the field of viral vectors and the use of such vectors to express foreign DNA in mammalian cells. The invention also relates to the field of gene therapy and particularly gene therapy involving viral vectors to direct genetic material to be expressed in particular tissues. More particularly, it concerns adenovirus and the ability to displace a large amount of the adenoviral genome with heterologous DNA and to replicate the viral construct in a helper cell line and express the foreign DNA in a host cell.
2. Description of the Related Art
Gene therapy is an area that offers an attractive alternative for the treatment of many diseases and disorders. In particular, the ability of viruses to enter a cell and express its genetic material in the host cell raises the possibility of replacing lost or defective gene function in vivo. However, for gene therapy to succeed, there is a need for new vectors with the properties of high therapeutic index, large capacity, targeted gene delivery, and tissue-specific gene expression. High therapeutic index indicates high therapeutic effect with low adverse effect, or in other words, a high rate of cure or improvement of the disorder with low or no side effects. This is a pharmacological concept that applies to all therapeutic agents, including gene therapy vectors. However, currently available gene transfer vectors are not able to meet the requirement of high therapeutic index (Mulligan, 1993), because of the vector-borne cycto- or geno-toxicities that are associated with many of the current gene transfer vectors.
Multiple and targeted gene transfer is particularly relevant to gene therapy for cancer (Friedmann, 1992). Throughout the last decade, studies of oncogenes and tumor suppressor genes have revealed more and more evidence that cancer is a disease developed through a process of multiple cytogenetic disorders (Chiao et al., 1990; Levine, 1990; Weinberg, 1991; Sugimura et al., 1992). Based on this concept of carcinogenesis, new strategies have developed rapidly as alternatives to conventional cancer therapy (Renan, 1990; Lotze et al., 1992; Pardoll, 1992). One of these is gene therapy (Friedmann, 1989), in which tumor suppressor genes, antisense oncogenes, and other related genes are used as therapeutic genes. Some strategies contemplated for gene therapy of cancer are the restoration of tumor-suppressor gene function, the blocking of oncogene expression and the correction of other gene-related disorders in cancer cells. It is believed that to achieve a maximal therapeutic effect, targeted delivery of a combination of these therapeutic genes by a single higher-capacity vector into cancer cells will be essential. Unfortunately, no such vector is currently available.
Another example of a disease for which a large capacity vector might be effective is Duchenne muscular dystrophy (DMD), a lethal, X-linked degenerative disorder of muscle, which affects about 1 in 35,000 newborn males. DMD is caused by a deficiency of dystrophin (Zubrzycka-Gaarn et al., 1988), a 427 kD protein encoded by a 14-kb transcript (Koenig et al., 1987). A possible therapy for this disease would be the restoration of dystrophin function by insertion and expression of the dystrophin gene in the patient's muscles (Blau, 1993; Cox et al., 1993). This therapy would require a vector that could efficiently deliver the 14 kb cDNA into muscle cells and specifically express the DMD protein in the muscle cells. Unfortunately, at the time of this disclosure, there is no vector system available which is capable of delivering more than 7.5 kb of DNA to be expressed in a specific tissue.
Retroviruses were the earliest gene transfer vectors. They were first used to insert gene markers and for transducing the cDNA of adenosine deaminase (ADA) into human lymphocytes (Miller, 1992). Unfortunately, retroviruses have several drawbacks as gene therapy agents, including genotoxicity caused by integration into the host genome, instability, dependence on target cell receptors for infection and proliferation only in actively dividing cells (Miller and Rosman, 1989; Major, 1992). In addition, the maximum gene-carrying capacity of retroviral vectors is under 10 kb (Morgenstern and Land, 1991).
Adeno-associated virus (AAV) has recently been developed as a gene transfer system. Wild-type AAV has high infectivity and specificity in integrating into the host cell genome (Hermonat and Muzyczka, 1984; Lebkowski et al., 1988). However, experimental data has shown that recombinant AAV tend to have low titers and lose their specificity of integration (Samulski et al., 1989). Also, the maximum gene-carrying capacity for AAV is under 5 kb (Walsh et al., 1992).
Herpes simplex virus type-1 (HSV-1) is attractive as a vector for applications directed to the nervous system because of its neurotropic property (Geller and Federoff, 1991; Geller, 1993). The HSV-1 genome has over 70 genes located along a 150-kb DNA molecule (Roizman and Sears, 1990), but the largest foreign DNA insertion in the virus has been 7 kb (Knipe et al., 1978). For example, a helper cell line (E5 cells) available for the propagation of replication-defective HSV-1 has complemented the 5 kb ICP4 gene (Deluca et al., 1985). However, because of its very complex genome, a much greater understanding of the interaction of HSV with host cells is required before a suitable HSV vector system can be engineered. In particular, an appropriate vector backbone has not been developed and issues related to gene expression during latency have not been resolved (Glorioso et al., 1992).
Vaccinia virus, from the poxvirus family, has also been developed as an expression vector (Moss, 1991; Moss, 1992). The vaccinia genome is among the most complex of all animal viruses, comprising approximately 200 discrete protein-coding regions along a nearly 200-kb DNA molecule (Goebel, et al., 1990). It has been shown that approximately 25 kb of foreign DNA could be inserted into the viral genome and packaged into the virion (Smith and Boss, 1983). However, the extreme cytotoxicity of vaccinia virus presents a limitation to its use in gene therapy applications. Until this is overcome, vaccinia virus will not be suitable for in vivo gene therapy. Other potential viral vectors exist (Mulligan, 1993; Kriegler, 1990), but they either are not well characterized or do not have the necessary characteristics for a supervector system.
Adenoviruses have been widely studied and well-characterized as a model system for eukaryotic gene expression. Ad are easy to grow and manipulate, and they exhibit broad host range in vitro and in vivo. This group of viruses can be obtained in high titers, e.g., 109-1011 plaque-forming unit (PFU)/ml, and they are highly infective. The life cycle of Ad does not require integration into the host cell genome. The foreign genes delivered by Ad vectors are expressed episomally, and therefore, have low genotoxicity to host cells. Ad appear to be linked only to relatively mild diseases, since there is no known association of human malignancies with Ad infection. Moreover, no side effects have been reported in studies of vaccination with wild-type Ad (Couch et al., 1963; Top et al., 1971), demonstrating their safety and therapeutic potential as in vivo gene transfer vectors.
Ad vectors have been successfully used in eukaryotic gene expression (Levrero et al., 1991; Gomez-Foix et al., 1992) and vaccine development (Grunhaus and Horwitz, 1992; Graham and Prevec, 1992). Recently, animal studies demonstrated that recombinant Ad could be used for gene therapy (Stratford-Perricaudet and Perricaudet, 1991; Stratford-Perricaudet et al., 1990; Rich et al., 1993). Successful experiments in administering recombinant Ad to different tissues include trachea instillation (Rosenfeld et al., 1991; Rosenfeld et al., 1992), muscle injection (Ragot et al., 1993), peripheral intravenous injection (Herz and Gerard, 1993), and stereotactic inoculation into the brain (Le Gal La Salle et al., 1993).
Generation and propagation of the current Ad vectors depend on a unique helper cell line, 293, which was transformed from human embryonic kidney cells by AD5 DNA fragments and constitutively expresses E1 proteins (Graham, et al., 1977). Since the E3 region is dispensable from the Ad genome (Jones and Shenk, 1978), the current Ad vectors, with the help of 293 cells, carry foreign DNA in either the E1, the E3 or both regions (Graham and Prevec, 1991). In nature, Ad can package approximately 105% of the wild-type genome (Ghosh-Choudhury, et al., 1987), providing capacity for about 2 extra kb of DNA. Combined with the approximately 5.5 kb of DNA that is replaceable in the E1 and E3 regions, the maximum capacity of the current Ad vector is under 7.5 kb, or about 15% of the total length of the vector. More than 80% of the Ad viral genome remains in the vector backbone and is the source of vector-borne cytotoxicity. Also, the replication deficiency of the E1 deleted virus is incomplete. For example, leakage of viral gene expression has been observed with the currently available Ad vectors at high multiplicities of infection (Mulligan, 1993).
Another problem with the currently available vectors is the potential for generation of wild-type virus by recombination. This may occur because the left end of the current Ad vectors has a sequence of about 1.5 kb (9.8-14 mu) overlapping with the E1 fragment in 293 cells (Graham, et al., 1977). Homologous recombinations that generate wild-type virus were detectable when E1 substitution vectors were extensively amplified in 293 cells (personal communication, Dr. Richard Gregory, CANJI, Inc., San Diego, Calif.).
Finally, Ad mutants with deletions at different regions of the viral genome have been rescued by helper viruses that provide the deleted gene products in trans. In cell line W162 (Weinberg and Ketner, 1983), which was stably transfected with the E4 region DNA, the constantly expressed E4 proteins supported propagation of E4 deletion (92-99 mu) mutants (Bridge et al., 1993). However, it has not been believed possible to delete the large E2 region which would provide for the insertion of up to 35 kb of foreign DNA into the adenoviral vector.
Therefore, there still exists an immediate need for an adenoviral supervector system which will have a high therapeutic index, a large carrying capacity of heterologous DNA and the capacity for targeted gene delivery and tissue specific expression. Such a vector system will have utility in a wide variety of in vivo and in vitro applications such a gene therapy protocols, the production of useful protein products in mammalian cell culture, as gene transfer markers or for the diagnosis of genetic deficiencies in particular cell lines.

Abstract: In certain embodiments, the disclosed invention comprises tissue specific expression of up to 30 kb of heterologous DNA directed by an adenoviral vector. Also disclosed are methods of transferring heterologous DNA into mammalian cells.

Board of Regents, The University of Texas System