A film quality inspecting method comprising applying a measuring beam having a specific wavelength to an annealed silicon film formed on a substrate in a direction inclined with respect to the silicon film, measuring a reflection intensity or reflectivity of a reflection beam reflected by the silicon film as a result of the application, and inspecting a film quality of the silicon film based on a measurement value obtained by the measurement.

1. Field of the Invention
The present invention relates to a method and apparatus for inspecting a film quality of a polysilicon film formed on a substrate of, for example, an LCD (Liquid Crystal Display).
2. Description of the Related Art
In the manufacturing of an LCD, a laser beam is often applied to an amorphous silicon film (hereinafter referred to as a-Si) film formed on a substrate of the LCD to thereby transform it into a poly-silicon (hereinafter referred to as p-Si) film, thus forming a semiconductor film having a high electron mobility. In this case, an excimer laser beam is applied to the a-Si film by the use of an ELA (Excimer Laser Anneal) method.
According to a process using this ELA method, the a-Si film is melted and crystallized instantaneously to give less thermal damages to the substrate, thus making it possible to form a p-Si film by a low temperature process at about 450° C. or less. This gives an advantage of being able to form the p-Si film using an inexpensive glass substrate with a large area.
The electron mobility is here indicated as μ=|vd/E|(cm2/SV), which gives a value/unit field of an average moving speed (drift speed: vd (cm/s)) of the electrons in crystal when an electric field E (V/cm) is applied to the crystal.
By using such a p-Si film, a TFT (Thin Film Transistor) with a high electron mobility can be formed on a glass substrate by a low temperature process. By using a p-Si film and a TFT, the problem can be solved to thereby obtain a thin and high-definition LCD of a so-called driver monolithic type in which a driver-section TFT and a picture-element section TFT are formed on a glass substrate.
When an a-Si film is transformed into a p-Si film through annealing by use of the laser beam, however, it is necessary to monitor whether it is formed into an appropriate crystal state (particulate diameter: 0.2–1.0 μm or more).
In monitoring of the crystal state, to check the crystal state the securest technology is to monitor the entire glass substrate directly through an optical microscope, which method however cannot possibly be applied to a field production line. To automate this method so that it may match the actual production line, there is available a technology disclosed in Jpn. Pat. Appln. KOKAI Publication No. 8-51078, which utilizes correlation between a crystallization ratio and a refractive index of a film to determine the refractive index using a semiconductor laser ellipsoid with a wavelength of 1294 nm, thus deciding whether a relevant product is to be accepted or rejected.
Furthermore, for example, Jpn. Pat. Appln. KOKAI Publication No. 3-97219 discloses a technology for, while applying an inspecting beam, optimizing the crystal state of the substrate to be processed, on the basis of a resultantly detected beam intensity.
Furthermore, Jpn. Pat. Appln. KOKAI Publication No. 6-244276 discloses a technology for, when detecting/evaluating a change in phase such as a crystal or amorphous state of a semiconductor film by applying energy beam, applying an annealing laser beam vertically to the semiconductor film to receive a resultant reflection beam spectrally so that a spectral reflectivity distribution thereof may be compared to data stored in a database, thus evaluating the crystallization state of the semiconductor film.
Furthermore, Jpn. Pat. Appln. KOKAI Publication No. 6-244255 discloses a technology for using a spectral profile of the reflection beam of a silicon film to thereby calculate its poly-crystallinity ratio and amorphous-ness ratio.
Furthermore, Jpn. Pat. Appln. KOKAI Publication No. 11-274093 discloses a technology for applying a processing laser beam and a measuring laser beam simultaneously to a silicon film to monitor their reflectivity, thus determining the layer state of the silicon film.
Furthermore, Jpn. Pat. Appln. KOKAI Publication No. 2000-133614 discloses a technology for applying the laser beam in pulse to a silicon layer to determine a state of the silicon layer based on a time-wise attenuating waveform.
Furthermore, Jpn. Pat. Appln. KOKAI Publication No. 11-121378 discloses a technology for measuring a reflectivity of a glass substrate on its back side on which a silicon layer is formed, to determine a state of the silicon layer based on the measurement of the reflectivity.
By the technology disclosed in Jpn. Pat. Appln. KOKAI Publication No. 8-51067 for optimizing the crystal state of the substrate to be processed only based on the intensity of the inspecting beam, however, the substrate cannot be heated sufficiently, so that a part thereof where the a-Si film is not melted can be known for sure but a part thereof where the a-Si film is melted but fine crystal particulate (particulate diameter: 0.01–0.02 μm approximately) transformed into a granular state owing to excessive heating, that is, a part where micro-crystal silicon (μ-cSi) is formed cannot be detected.
This part where the granular-state fine crystal particulate is formed has an extremely low average electron mobility, not higher than a value of 100 (cm2/S·V) supposed to be appropriate in formation of a driver section TFT. By this method, therefore, it is impossible to know whether a p-Si film is formed uniformly, thus possibly deteriorating the yield of manufacturing the TFT.
Furthermore, by the technology disclosed in Jpn. Pat. Appln. KOKAI Publication No. 3-97219 for applying a visible reference laser beam to a site where the excimer laser beam is being applied to evaluate a crystallization level of the site based on a change in intensity of the resultant transmission or reflection beam, there is a problem that it is impossible to obtain information of re-crystallization after actual poly-crystallization.
Furthermore, by this method, the excimer laser beam is applied in pulse by a few shots, so that when the visible reference laser beam is applied, its transmission or reflection beam changes in intensity, thus giving rise to a problem of difficulty to decide crystallinity. Besides, there is a problem of complexity of an apparatus for electrically processing and detecting the time-wise changing intensity of the transmission or reflection beam.
Furthermore, by the technology disclosed in Jpn. Pat. Appln. KOKAI Publication No. 8-51078 for measurement by use of a semiconductor laser ellipsoid, it is necessary to know an accurate film thickness beforehand for calculating the refractive index. Besides, calculation thereof takes much time, thus deteriorating the throughput. Moreover, an optical system for the measurement apparatus becomes large and complicated.
Furthermore, by the technology disclosed in Jpn. Pat. Appln. KOKAI Publication No. 6-224276, the annealing laser beam is applied vertically to a semiconductor film to receive its reflection beam spectrally in order to then compare its spectral reflectivity distribution to the data stored in a database and evaluate a crystallization state of the semiconductor film, so that it is necessary to measure the spectral reflectivity of the semiconductor film for each waveform and also create the data of its consecutive profiles, thus suffering from complex data processing. This problem holds true also with the technology disclosed in Jpn. Pat. Appln. KOKAI Publication No. 6-244255.
Furthermore, by the technology disclosed in Jpn. Pat. Appln. KOKAI Publication No. 11-274093, the processing laser beam and the measuring laser beam are applied simultaneously to a silicon film to monitor the reflectivity thereof in order to detect a layer state of the silicon film, so that the reflectivity of the processing laser beam and that of the measuring laser beam are added to each other to give rise to mutual interference of the beam, thus disqualifying the method for use in accurate measurement.
Furthermore, by the technology disclosed in Jpn. Pat. Appln. KOKAI Publication No. 2000-133614, the laser beam is applied in pulse to a silicon layer to determine a state of the silicon layer based on the shape of the time-wise attenuating waveform, thus complicating the processing of data such as waveform data.
Furthermore, by the technology disclosed in Jpn. Pat. Appln. KOKAI Publication No. 11-121378, reflectivity of a glass substrate is measured on its back side on which a silicon layer is formed, to determine a state of the silicon based on the measurement, thus making it impossible to directly determine the surface state of the silicon layer itself.
In view of the above, it is an object of the present invention to provide a film quality inspecting method and apparatus which can inspect a crystal state of a silicon substrate speedily and simply.

Film quality inspecting method and film quality inspecting apparatus


A design and evaluation method for interconnect wires of integrated circuits is provided to detect, analyze and predict response of interconnect layout to integrated-circuit manufacture processes.

Trends in the design and manufacture of microelectronic dies, or integrated circuits (ICs) are toward increasing miniaturization, circuit density, robustness, operating speeds and switching rates, while reducing power consumption and defects in the ICs. ICs are made up of a tremendous number (e.g., millions to hundreds of millions) of devices (e.g., transistors, diodes, capacitors, etc.), with each component being made up of a number of delicate structures, manufactured through a number of process steps. As IC manufacture technology continues to evolve and manufacturing of smaller sized components and more compact ICs become reality, the delicate structures likewise become smaller, more compact, and correspondingly, more delicate.
At 90- and 65-nanometer technology nodes and beyond, many (e.g., 10 or more) layers of conductor wires are required to interconnect the many smaller, more compact and more delicate structures in the ICs in accordance with the design specifications. (Note that these many layers of interconnect conductor wires are insulated by a dielectric layer in between them. Such a dielectric layer is called an interconnect dielectric layer, an inter-wire dielectric layer, or an inter-wire-layer dielectric layer, hereafter.) Consequently, increasingly smaller, more compact and more delicate features of the interconnect conductor wires are becoming essential to handle such formidable task in the design and manufacture of the ICs. However, the smaller, more compact and more delicate interconnect conductor wire features are beginning to interact with the IC manufacturing processes, causing product yield loss. Such phenomena include, but not limited to, the interaction between the interconnect conductor wire features and the planarization process of the interconnect conductor and dielectric layers, the interaction between the interconnect conductor wire features and the lithography process that defines the interconnect conductor wire features, and the interaction between the interconnect conductor wire features and the plasma involved interconnect dielectric deposition and etch process or the plasma-involved interconnect conductor etch process.
The interaction between the interconnect conductor wire features and the planarization process of the interconnect conductor and dielectric layers such as, but not limited to, the chemical-mechanical polish (CMP) process, can cause non-uniformity of the conductor wire and dielectric thickness due to the dishing on the conductor wire surface and the erosion on the dielectric surface. Such effect reduces thickness of the interconnect conductor and dielectric layers, thus increasing the conductor wire resistance and the dielectric capacitance which can cause significant timing delays in circuits. Since there can be up to ten or more interconnect conductor and dielectric layers in the 65-nanometer technologies and beyond, the accumulated effect of the non-uniformity of the interconnect conductor wire and dielectric thickness can be formidable after all interconnect conductor and dielectric layers receive the planarization process.
The interaction between the interconnect conductor wire features and the lithography process can cause the conductor wires either short or open. Such interaction may increase or decrease the width and also change the shape of the conductor wires which run through the circuits. The lithography process defines and forms the physical features of the transistor gates in circuits in the case of polysilicon interconnect wires. The change of the transistor gate length, width or shape can either reduce the on-state drive current or increase the off-state leakage of the transistors, thus degrading transistor performance and therefore the circuit or product performance and yield.
The interaction between the interconnect conductor wire features and the plasma-involved interconnect dielectric deposition and etch process or the plasma-involved interconnect conductor etch process can cause damage to transistor gate oxides via the plasma induced charging current. Degradation of the transistor gate oxides by such effect has become one of the serious transistor reliability concerns in the industry.
To improve manufacturing yield loss, manufacture-friendly layout design of the products (circuits that make products) has become increasingly important. To achieve a good layout design as such, understanding how the interconnect conductor wire features, such as the width, length, shape, spacing, density, pattern, etc. of the conductor wires, interact with the IC manufacturing tools and processes associated with the interconnect conductor and dielectric planarization process, the interconnect conductor lithography process, and the plasma-involved interconnect dielectric deposition and etch and the interconnect conductor etch process is the key.
To date, a thorough and complete understanding of such interaction has not been rendered yet, partly because a thorough and complete design covering the best possible scenarios of the interconnect conductor wire features in product circuits has not been realized.

Evaluation method for interconnects interacted with integrated-circuit manufacture


An ink cartridge for an ink-jet recording apparatus, comprises: a tank housing containing ink, the ink being visible from an outside; and indications, marked along a depth direction of the tank housing, for displaying the number and size of record sheets which can be subjected to printing, corresponding to a quantity of remaining ink. Alternately, at least an ink consumption state and enablement or disablement of printing are displayed on a cathode ray tube (CRT) screen.

The invention relates to an ink-jet recording apparatus such as an ink-jet printer, an ink jet facsimile printer or an ink-jet plotter, and particularly to an ink cartridge for an ink-jet recording apparatus which can accurately detect and display the consumption state of ink in the recording apparatus, thereby preventing an accidental event such as a sudden ink end from occurring, and also to an apparatus for detecting and displaying an ink consumption state of an ink cartridge.
One method of detecting the quantity of remaining ink of an ink cartridge in an ink-jet recording apparatus is disclosed in FIG. 3 of Japanese patent Application Laid-open No. Hei. 7-125236. In the method, a scale for visual checking is formed on an ink chamber of an ink tank so that the number of sheets which can be further subjected to printing is displayed.
The above method technique has a convenience that the user can know the quantity of remaining ink as required by means of a relatively simple method. However, the user cannot know which size corresponds to the displayed number of sheets which can be further subjected to printing. Therefore, the conventional method technique has room for improvement.
Moreover, the above method has a drawback that an ink chamber in which a porous member is not housed is required and the ink chamber is required to be composed of a transparent material so that the quantity of remaining ink can be seen from the outside, thereby restricting the shape of an ink cartridge.
The conventional method technique has a further drawback that, in order to visually check the ink cartridge, it is necessary that the cover of a printer is opened or the ink cartridge is detached from the printer.
The detachment of an ink cartridge may cause the following problems. When an ink cartridge in use is detached, air is allowed to enter the ink supply path, thereby producing a problem that an ejection failure may occur. During the process of detaching an ink cartridge in use, there arise problems in that the user's hands or the like may be soiled with ink, and that the user may be anxious about damage to the printer or the ink cartridge.

Ink cartridge for an ink-jet recording apparatus, and a system for detecting and displaying an ink consumption state of an ink cartridge


A method for fabricating a memory device of this invention includes at least the following steps. A tunnel dielectric layer is formed over a substrate. A gate is fowled over the tunnel dielectric layer. At least one charge storage layer is formed between the gate and the tunnel dielectric layer. Two doped regions are formed in the substrate beside the gate. A word line is formed on and electrically connected to the gate, wherein the word line having a thickness greater than a thickness of the gate.

1. Field of the Invention
This invention relates to an integrated circuit (IC) device and fabrication thereof, and more particularly relates to a memory device and a method for fabricating the same.
2. Description of Related Art
A memory is a semiconductor device for storing information or data. As the computer microprocessors become more and more powerful, programs and operations executed by the software are increased correspondingly. Consequentially, the demand for high storage capacity memories is getting more.
Among various types of memory products, a non-volatile memory allows multi-time data programming, reading and erasing operations, and the data stored therein can be retained even after the power to the memory is terminated. With these advantages, the non-volatile memory has become one of the most widely adopted memories for personal computers and electronic equipment.
Electrically programmable and erasable non-volatile memory technologies based on charge storage structures and known as Electrically Erasable Programmable Read-Only Memory (EEPROM) and flash memory are used in various modern applications. A flash memory is designed with an array of memory cells that can be independently programmed and read. Traditional flash memory cells store charges in a floating gate, but another type of flash memory uses a charge-trapping structure, such as a layer of non-conductive SiN material, instead of a floating gate including a conductive material. When a charge-trapping cell is programmed, charges are trapped and do not move through the non-conductive layer. The charges are retained by the charge trapping layer until the cell is erased, retaining the data state without continuously applied electrical power. Charge-trapping cells can be operated as two-sided cells. That is, because the charges do not move through the non-conductive charge trapping layer, the charges can be localized on different charge-trapping sites. On the other words, in the flash memory devices with the use of the charge-trapping structure, more than one bit of information is stored in each memory cell.
A single memory cell can be programmed to store two physically separated bits in the trapping structure, in the form of a concentration of charges near the source and another concentration of charges near the drain. Programming of the memory cell can be performed by Channel Hot Electron (CHE) injection, which generates hot electrons in the channel region. Some of the hot electrons gain enough energy to be trapped in the charge-trapping structure. By interchanging the biases applied to the source and drain terminals, charges are trapped either in a portion of the charge-trapping structure near the source region, near the drain region, or both.
Usually, one of four distinct combinations of bits 00, 01, 10 and 11 can be stored in a memory cell having a charge-trapping structure, wherein each combination has a corresponding threshold voltage (Vt). In a read operation, the current flowing through the memory cell varies depending upon the Vt of the cell. Typically, such current has one of four different values each corresponding to a different Vt. Accordingly, by sensing such current, the particular bit combination stored in the cell is determined.
The total available charge range or Vt range may be referred to as the memory operation window. In other words, the memory operation window is defined by the difference between the program level and the erase level. A large memory operation window is desired as good level separation between states is needed for cell operation. The performance of two-bit memory cells, however, is often degraded by the so-called "second bit effect" in which localized charges in the charge-trapping structure interact with each other. For example, during a reverse read operation, a read bias is applied to the drain terminal and the charge stored near the source region (i.e., a "first bit") is sensed, then the bit near the drain region (i.e., the "second bit"), however, creates a potential barrier for reading the first bit near the source region. This barrier may be overcome by applying a bias with a suitable magnitude, using the drain-induced barrier lowering (DIBL) effect to suppress the effect of the second bit near the drain region and allow the sensing of the storage status of the first bit. However, when the second bit near the drain region is programmed to a high Vt state and the first bit near the source region is at un-programmed state, the second bit raises this barrier substantially. Thus, as the Vt associated with the second bit increases, the read bias for the first bit becomes insufficient to overcome the potential barrier created thereby, and the Vt associated with the first bit is raised as a result of the higher Vt of the second bit reducing the memory operation window. The second bit effect decreases the memory operation window for 2-bit/cell operation, so there is a need for methods and devices capable of suppressing the second bit effect in memory devices.
On the other hand, a known non-volatile memory process includes the following steps. A blanket conductive layer is formed and then patterned into parallel linear conductive layers through a lithography process and a first etching process, bit lines are formed in the substrate between the linear conductive layers, and a dielectric layer is filled between the linear conductive layers. After word lines are formed, the linear conductive layers not covered by the word lines are removed by a second etching process so that the conductive layers remaining under the word lines serve as gates.
However, as shown in FIG. 12 and FIG. 13 as the I-I cross-sectional view of the structure in FIG. 12, because the linear conductive layers usually have inclined sidewalls to facilitate the dielectric filling, the conductive material on the sidewalls of the dielectric layer 150 above the bit lines 100 is not easy to remove in the etching process of the linear conductive layer and forms stringers 200 thereat. Thus, the gates under neighboring word lines 300 are shorted with each other through the stringers 200. Hence, the stringer problem also has to be solved.

Method of fabricating memory device with charge storage layer at gap located side of gate dielectric underneath the gate


A compact and inexpensive air-cooled laser device, having heat radiating fins configured to sufficiently cool a heat-receiving member thermally connected to a laser diode module positioned within a housing of the laser device having a substantially sealing structure. A flow direction of air flowing between heat radiating fins of a first fin set and a flow direction of air flowing between heat radiating fins of a second fin set are generally opposed to each other. Further, the first and second fin sets are positioned adjacent to each other, and thus an inflow area of the first fin set and an outflow area of the second fin set are also adjacent to each other. Therefore, most of the air after flowing between the fins of the first fin set is deflected by colliding with an inner wall of a housing, and then enters between the fins of the second fin set.

1. Field of the Invention
The present invention relates to an air-cooled type laser device having a laser diode as a light emitting source or an excitation light source, and having a structure for radiating heat generated from the laser diode.
2. Description of the Related Art
Generally, in a laser device, having a laser diodes (or semiconductor lasers) as a light emitting source or an excitation light source, there are two types, i.e., an air-cooled type in which heat generated by a laser diode module including a laser diode is radiated by air; and a water-cooled type which is connected to a circulation type cooling water supply device (or a chiller).
The air-cooled type laser device is more advantageous than the water-cooled type, in that the air-cooled type is easily moved, an occupied area thereof is small, restrictions of an installation location thereof are few, and an installation cost thereof is low, etc. However, in the air-cooled type, it is difficult to decrease the temperature of the laser diode module to the same degree of the water-cooled type. In particular, since a high-power laser device must have many laser diode modules having a large amount of heat generation, it is necessary to provide an effective heat radiating structure to the laser device in order to prevent the laser device from having to be increased in size.
As a relevant prior art document, JP 2008-021899 A discloses a laser oscillator having a semiconductor laser heat radiating member to radiate heat generated by a semiconductor laser array, a fiber laser heat radiating member to radiate heat generated by an optical fiber for a fiber laser, a cooling fan for sending cooling air, and a guide member for guiding the cooling air from the cooling fan.
JP 2012-059952 A discloses a structure for cooling an electronic device, including a heat radiator having an L-shaped heat pipe, a plurality of heat radiating fins attached to a substantially horizontal part of the heat pipe, and a heat receiving plate to which substantially vertical portions of the heat radiating fins are attached; a plurality of electronic devices attached to the heat receiving plate; and a container for containing the plurality of electronic devices.
JP 2009-239166 A discloses a flat heat sink including: a plurality of thin plates layered having an air guiding portion and a hollow portion for containing a centrifugal fan, the thin plated being layered with a certain gap therebetween; at least one heat radiating fin part connected to ends of the thin plates, in which air guided by the air guiding portion of the thin plates flows through the heat radiating fin part; and at least one heat pipe, having one end which is thermally connected to the portion of the thin plate thermally connected to a heating component and the other end which is thermally connected to the heat radiating fin part, in which at least a part of the heat pipe is positioned so as to form a space between the thin plates and the heat pipe.
Further, WO 2014/092057 A1 discloses a cooling unit having a heat receiving block thermally connected to an electronic component constituting a heating element, a heat pipe vertically positioned on the heat-receiving block and configured to receive and transfer heat of the heat-receiving block, and a plurality of heat radiating fins arranged on the heat pipe. The heat radiating fins are constituted by a first fin set arranged on a linear portion of the heat pipe and a second fin set arranged on a bent portion of the heat pipe.
In an open-type air-cooled laser device, in which external air is sucked as cooling air into the laser device, and the air heated by a laser diode in the laser device is discharged from the laser device, when the outside air temperature (or the ambient temperature) of the laser device is increased, the temperature of the air sucked into the laser device is also increased, whereby it is difficult to effectively cool the laser diode. Therefore, in order to extend a life of the laser diode module and improve reliability thereof, a panel cooler may be used so as to cool the air within a housing (or the laser device) having a substantially sealing structure, and a heat radiating fin set may be cooled by the cooled air, in which the fin set is thermally connected to a heat-receiving member which receives heat from the laser diode.
However, in a laser device having a high optical output (i.e., having a laser diode module with a large amount of heat generation), it is necessary to arrange a large fin set (in particular, having a large inflow area) in the laser device in order to sufficiently lower the temperature of the heat-receiving member, whereby the housing (or the laser device) may be increased in size.
The above related art documents do not provide a sufficient solution for solving the above problems. For example, although an open-type air-cooled laser oscillator is disclosed in FIG. 5 of JP 2008-021899 A, it is necessary to reflux the air discharged from an outlet port into an inlet port again and arrange a flow path therefor, when the laser oscillator is positioned in a housing having a substantially sealing structure. Further, in order to obtain high cooling characteristics, it is necessary to circulate a large amount of air at a high velocity. Accordingly, it is necessary to increase a cross sectional area of the flow path, whereby the device is increased in size. When the device is increased in size, an installation area and a weight thereof are also increased. Further, due to increase in a surface area of the device, a heat input from the outside to the device is also increased, whereby it is necessary to use a panel cooler having high cooling capability, by which a device cost and an operation cost thereof are increased.

Air-cooled laser device having heat-transfer member with heat radiating fins


Some embodiments of the present disclosure relate to a displacer for reducing the consumption of a cryogen used in a superconductive magnet device. The displacer may occupy some space within the cryogen storage cavity or limit the cryogen into a relatively small space surrounding a superconductive coil in the cryogen storage cavity. The displacer may also include a displacer cavity that may be vacuum or contain a cryogen or another substance.

Conventionally, in a magnetic resonance imaging (MRI) system superconducting magnets are used to generate one or more magnetic fields, e.g., a main magnetic field, a gradient magnetic field, or a shielding magnetic field. Because of the characteristics of the superconducting material, most superconducting magnets need to work at an extremely low temperature for providing a stable magnetic field. For example, the operation temperature of superconducting magnet made by NbTi is approximately 4.2K, and the operation temperature of superconducting magnet made by MgB2 is approximately 20-30K. Usually a liquid cryogen, such as liquid nitrogen, liquid helium, liquid hydrogen and liquid neon, may be used to provide such a low temperature environment. Such a liquid cryogen may be continuously consumed during the transportation of an MRI system from a manufacturer to a hospital or during the operation of the MRI system, and thus the cryogen may need to be re-filled regularly or from time to time.
The volume of a liquid cryogen needed in an MRI system may at least partially depend on the size of system cavities housing the liquid cryogen. Since the liquid cryogen, e.g., liquid helium, may be expensive, there is a need for a more efficient and cost-efficient way to control or adjust the size of such system cavities and improve the cooling efficiency, in order to reduce the consumption of such an expensive cryogen.

Displacer in magnetic resonance imaging system

SHANGHAI UNITED IMAGING HEALTHCARE CO., LTD.


A membrane-based assay device for detecting the presence or quantity of an analyte residing in a test sample is provided. The device utilizes time-resolved fluorescence to detect the signals generated by excited fluorescent labels. Because the labels can have relatively long emission lifetime, short-lived background interference can be practically eliminated through delayed fluorescence detection. In addition, the resulting fluorescent reader can have a simple and inexpensive design. For instance, in one embodiment, the reader can utilize a silicon photodiode and a pulsed light-emitting diode (LED) to accurately excite labels and detect fluorescence on a membrane-based assay device without requiring the use of expensive components, such as monochromators or narrow emission band width optical filters.

Assays have been developed that employ fluorescent labels to facilitate detection of the analyte. Fluorescence is generally the result of a three-stage process. In the first stage, energy is supplied by an external source, such as an incandescent lamp or a laser, and absorbed by the fluorescent compound, creating an excited electronic singlet state. In the second stage, the excited state exists for a finite time during which the fluorescent compound undergoes conformational changes and is also subject to a multitude of possible interactions with its molecular environment. During this time, the energy of the excited state is partially dissipated, yielding a relaxed state from which fluorescence emission originates. The third stage is the fluorescence emission stage wherein energy is emitted, returning the fluorescent compound to its ground state. The emitted energy is lower than its excitation energy (light or laser) and thus of a longer wavelength. This shift or difference in energy or wavelength allows the emission energy to be detected and isolated from the excitation energy.
Conventional fluorescence detection typically utilizes wavelength filtering to isolate the emission photons from the excitation photons, and a detector that registers emission photons and produces a recordable output, usually as an electrical signal or a photographic image. However, several problems exist with conventional fluorescent detection techniques. For instance, most biological fluids possess autofluorescence that can decrease detection accuracy. The assay device may also possess some autofluorescence. These interferences are enhanced by the small Stokes shifts of many conventional fluorescent labels, e.g., between 20 to 50 nanometers.
In response to some of the problems with conventional fluorescence detection techniques, a technique known as "time-resolved" fluorescence was developed. Time-resolved fluorescence involves exciting the fluorescent label with a short pulse of light, then waiting a certain time (e.g., between approximately 100 to 200 microseconds) after excitation before measuring the remaining long-lived fluorescent signal. In this manner, any short-lived fluorescent background signals and scattered excitation radiation are eliminated. Although "time-resolved" techniques have been successfully employed in some types of assay devices, such as cuvette-based instruments, problems nevertheless remain in incorporating time-resolved techniques in other types of assay devices, such as membrane-based devices.
In particular, conventional time-resolved systems, such as those based on monochromators, involve very complex and expensive instruments. For example, a typical research-grade laboratory fluorimeter is a dual monochromator system, with one monochromator used to select the excitation wavelength and another monochromator used to select the detection wavelength. This level of complexity drastically increases the costs of the system and also requires a bulky, non-portable, and heavy instrument. In addition, conventional time-resolved systems are also problematic when used in conjunction with membrane-based assay devices. Specifically, in a membrane-based device, the concentration of the analyte is reduced because it is diluted by a liquid that can flow through the porous membrane. Unfortunately, background interference becomes increasingly problematic at such low analyte concentrations because the fluorescent intensity to be detected is relatively low. Because the structure of the membrane also tends to reflect the emitted light, the ability of the detector to accurately measure the fluorescent intensity of the labeled analyte is substantially reduced. In fact, the intensity of the emitted fluorescence signal is typically three to four orders of magnitude smaller than the excitation light reflected by the porous membrane.
As such, a need currently exists for a simple, inexpensive, and effective system for measuring the fluorescence in a membrane-based assay device.

This patent is subject to a terminal disclaimer.

Membrane-based assay devices that utilize time-resolved fluorescence


An auto-focusing method for determining an in-focus position of a plurality of wells in at least a portion of a multi-well plate, the method including using a first objective lens having a first magnification to identify, in each of at least three wells of a selected subset of the plurality of wells, an in-focus position of each well with respect to the first objective lens, on the basis of at least three the in-focus positions, computing a plane along which the at least three wells will be in focus with respect to at least one objective lens having a second magnification that is not greater than the first magnification, and using the at least one objective lens to scan, along the plane, at least some of the plurality of wells in the portion of the plate.

The present invention generally relates to the field of optical measurement and/or inspection techniques and more specifically relates to an auto-focus method and device, particularly useful when viewing non planar surfaces.
Auto focusing is an essential feature in many automated inspection fields such as the computer chip industry, biomedical research, data reading/recording in optical information carriers, etc. Specifically, when analyzing samples in multiwell plates including a plurality of wells on a single plate, auto focusing of a microscope viewing the contents of the wells can enable more efficient work procedures as the operator need not focus the objective on each well in the plate separately.
Various auto focusing methods for inspection of a multiwell plate have been disclosed in the past, such as in U.S. Pat. No. 7,109,459. However, when using wells having a non-planar bottom, such as a multiwell plate having wells with a U-shaped bottom, such as are used, for example, for growing living cells into spheroids, existing autofocus methods may require image analysis which is time-consuming.
In some cases, a multiwell plate is analyzed or is visualized using an oil immersion lens having a high numerical aperture. In such cases, focusing the objective using laser based autofocusing methods as described in U.S. Pat. No. 7,109,459 is difficult or impossible, as the similar refraction index of the lens and solution in the wells cancels one of the refraction points and a corresponding scanning peak, causing difficulty in focusing the objective lens.
Thus there are needs: (a) for auto focusing a microscope on a multiwell plate, which is suitable for multi-well plates having wells with a non-planar bottom surface; (b) to separate focusing process from scanning process to allow higher scanning and imaging speed; and (c) for a method for auto focusing a microscope using an oil immersion lens on a multiwell plate.

Method and device for scanning wells in a multi-well plate


An over-sampling type clock recovery circuit includes a phase difference determining section and a phase adjusting section. The phase difference determining section determines a phase difference between a data signal and a plurality of clock signals using majority determination, to produce a phase adjustment signal. The phase adjusting section adjusts phases of the plurality of clock signals based on the phase adjustment signal.

1. Field of the Invention
The present invention relates to a clock recovery circuit in which clock signals are extracted from an inputted data signal, and more particularly, to an over-sampling type clock recovery circuit which performs sampling with a plurality of clock signals having different phases.
2. Description of the Related Art
In recent years, a high-speed protocol is proposed, such as Gbit Ethernet and Fiber Channel for data transmission. For this purpose, high speed processing is requested to a clock recovery circuit which extracts a clock signal from a data signal in a high speed transmission and a PLL circuit which establishes frequency synchronization between an internal clock signal and the transmitted clock signal. In order to respond to such a request, as disclosed in 1996 IEEE International Solid-State Circuits Conference, an over-sampling-type clock recovery circuit is proposed in which a transmitted data signal is sampled with a plurality of clock signals with different phases generated by an internal circuit.
FIG. 1 shows a block diagram of a clock recovery circuit which is disclosed in the conventional example. A data signal is supplied to eight phase comparators TIPD0 to TIPD7. Each phase comparator TIPD is supplied with every three clock signals of 24 clock signals having fixed delays outputted from a fixed delay circuit FD and detects a phase state between the data signal supplied and three clock signals.
When the data signal is delayed more in relation to the clock signals, the phase comparator TIPD detects the leading of the clock signal in phase to set a dn signal as an output of the circuit to an enable state and an up signal as another output of the circuit to a disable state. Similarly, when detecting the delay of the clock signals in phase, the phase comparator TIPD sets the up signal to the enable state and the dn signal to the disable state. FIGS. 2A to 2F show a locking state. In this case, there is no delay or leading the clock signals in phase as shown in FIGS. 2A to 2D. Therefore, both of the up signal and the dn signal are set to the disable state, as shown in FIGS. 2E and 2F. On the other hand, FIGS. 3A to 3D shows the delay state of the clock signals. At this time, the up signal is set to the enable state, as shown in FIG. 3E and the dn signal is set to the disable state, as shown in FIG. 3F. In case of the leading state of the clock signals, the up signal is set to the disable state, and the dn signal is set to the enable state.
Each of charge pumps CP0 to CP7 increases the output voltages when the up signal is set to the enable state and decreases the output voltage when the dn signal is set to the enable state. A low pass filter LPF inputs the output voltages from the charge pumps CP0 to CP7 and integrates the change of these voltages. A variable delay circuit VD is supplied with the output voltage of the low pass filter LPF and a reference clock signal which is the output of a voltage controlled oscillator VCO. The variable delay circuit VD delays the reference clock signal in accordance with the output voltage from the low pass filter LPF. The fixed delay circuit FD is supplied with the output of the variable delay circuit FD and generates the 24 clock signals having fixed delays from the supplied clock signal.
In this way, in the conventional clock recovery circuit, each of the eight phase comparators TIPD0 to TIPD7 detects the leading or delay state of the clock signals in phase to set the up signal or dn signal is set to the enable state. As a result, the voltage outputted from the corresponding charge pump CP increases or decreases. Therefore, the variable delay circuit VD delays the reference clock signal based on the output voltage from the low pass filter LPF. The fixed delay circuit FD generates the 24 clock signals from the delayed reference signal. As a result, the phase leading or delay state of the clock signals in each of the phase comparators TIPD0 to TIPD7 is set to an adequate state so that the appropriate sampling of the data signal can be realized.
However, in the conventional clock recovery circuit, there is a problem. That is, the data sampling cannot be correctly performed when the phase differences are generated between the 24 clock signals due to the influence of a layout of wiring patterns in the clock recovery circuit. Especially, the data sampling cannot be correctly performed when the phase differences are generated between three clock signals supplied to the phase comparator TIPD. For example, when the a phase shift (delay) of the clock signal is generated in one of the three clock signals as shown in FIG. 3D, the phase comparator TIPD detects a clock delay state so that the up signal is set to the enable state. For this reason, the charge pump CP receives the up signal of the enable state and the fixed delay circuit FD delays the 24 clock signals. As a result, a correct data sampling cannot be performed in the whole clock recovery circuit including other phase comparators TIPD.
In addition to the above conventional example, a digital signal receiving apparatus is disclosed in Japanese Laid Open Patent application (JP-A-Showa 61-145945). In this reference, the digital signal receiving apparatus is composed of a reproducing section and a majority determining section and a conversion section. The reproducing section reproduces clock signals having a basic clock signal frequency fr and a frequency n (n is a positive integer equal to or larger then 3) times of the basic clock signal frequency fr locked to a digital reproduction signal in phase. The majority determining section extracts n samples values during one bit of the digital reproduction signal based on nfr clock signals, and determines binary values of the n sample values on the majority side as a value during the bit. The converting section converts the determined value to have 1/fr width. Thus, the digital reproduction signal is shaped in units of basic clocks fr of the digital reproduction signal.
Also, a data sampling converting circuit is disclosed in Japanese Laid Open Patent application (JP-A-Showa 61-214842). In this reference, the data sampling converting circuit is composed of a clock reproducing circuit, a frequency dividing circuit and a determining circuit. The clock reproducing circuit reproduces a clock pulse from a character multiplexed signal. The frequency dividing circuit divides the reproduced clock signal in frequency to 1 to n-th, and generates n sampling pulses with different phases. The determining circuit performs sampling of the character multiplexed signal with the n sampling pulses and determines based on majority determination of m continuous sampling results whether a digital data is in a high level or a low level.
Also, a demodulation data identifying and determining apparatus is disclosed in Japanese Laid Open Patent application (JP-A-Heisei 3-69238). In this reference, the demodulation data identifying and determining apparatus is composed of a detecting and demodulating circuit, a comparator, a clock reproducing circuit, a timing determining section, a latch circuit. The detecting and demodulating circuit demodulate an input signal to output a base band signal. The comparator converts the base band signal into a binary signal. The clock reproducing circuit reproduces a reproduction clock signal having the same frequency as a bit rate of a transmission data, and generates a clock signal faster than the reproduction clock signal. The timing determining section performs sampling of the binary signal using the clock signal and performs majority determination to a plurality of values corresponding to a plurality of sampling points to output the result of the majority determination. The latch circuit latches the output from the timing determining section in accordance with the reproduction clock signal to output as a reproduced digital data.
Also, a digital signal reproducing circuit is disclosed in Japanese Laid Open Patent application (JP-A-Heisei 4-11431). In this reference, the digital signal reproducing circuit is composed of a demodulating section, a sampling section and a majority determining section. The demodulating section demodulates a digital modulated signal. The sampling section performs sampling of the demodulated digital signal in accordance with clock signals from a clock source. The majority determining section performs majority determination to a plurality of sampling values supplied from the sampling section.

Over-sampling type clock recovery circuit using majority determination


The invention provides an effective method for subjecting the inner surface of a tubular body made of a plastic resin to a treatment with low temperature plasma according to which the tubular body is dipped in an insulating oil bath while the inside of the tubular body is filled with a plasma gas under a reduced pressure and electric power for the generation of a low temperature plasma is supplied to electrodes surrounding the tubular body in the insulating oil. Several of the problems in the prior art methods can be solved by the present invention such as undesirable thermal degradation of the tube surface by the evolved by the electric discharge, and power loss due to the generation of plasma outside the tubular body. When the method of the invention is applied to the treatment of a continuous length tubular body, the tubular body is continuously moved in the insulating oil through the electrodes surrounding it, with the optional provision of a sleeve made of an insulating material placed between the electrodes and the tubular body, so as that the tubular body is free from adverse effects caused by direct contact with the electrodes.

The present invention relates to a method for the treatment of inner surfaces of a tubular body made of a plastic with low temperature plasma with an object to improve or modify the properties of the surface.
It has been established that the surface properties of shaped articles made of a synthetic plastic resin can be improved or modified when the surface of the article is treated with or exposed to an atmosphere of low temperature plasma with or without deposition of a polymeric substance formed by the plasma. The surface properties improved or modified by the plasma treatment include, for example, affinity with water, printability, adhesivity, anti-electrostatic property and the like as well as the resistance against bleeding or blooming of the plasticizer and other additives contained in the plastic resin on the surface of the shaped article.
The above described effects obtained by the plasma treatment are considerably or sufficiently remarkable but the applicability of the technique of plasma treatment is limited to the outwardly exposed surfaces of shaped articles such as the outer surfaces of sheets, films, rods, tubes, bottles and other irregular forms. For example, the prior art technique of the plasma treatment can hardly be applied to the inner surfaces of hollow bodies such as tubes. This is because no convenient and reliable method was known hitherto for generating stable low temperature plasma in such a confined space surrounded by the plastic walls.
On the other hand, there is a growing demand for the technique of treating inner surfaces of hollow bodies, e.g. tubes, with low temperature plasma. For instance, the tubes and hoses used in the fields of medical technologies and food industries such as the tubes for transfusion of blood and other therapeutic fluids or hoses for transportation of beverages and edible fats or oils as well as many other tubes or hoses for industrial uses must be absolutely free from migration or bleeding of the plasticizer and other additives toward the inner surface thereof. In addition, many tubular bodies used with a medical purpose as embedded in or in contact with the living tissues of human body such as catheters, artificial vascular tracts, artificial esophagi and the like are desired to have improved adaptability to living body, e.g. antithrombosis and adaptability to tissues.
Therefore, development of a convenient and reliable technique for the continuous treatment of inner surfaces of tubular bodies with low temperature plasma is a very urgent problem in the field of plastics processing.

Method for the treatment of inner surfaces of a tubular body of a plastic with low temperature plasma

Agency of Industrial Science & Technology


A method of making an iron base magnetic material alloy powder includes the steps of: preparing an iron base magnetic material alloy containing at least 50% by mass of iron; and pulverizing the magnetic material alloy using a pin mill. A portion of the mill, which comes into contact with the magnetic material alloy, is made of a cemented carbide material at least partially.

The present invention relates to a method of making an iron base magnetic material alloy powder containing at least 50% by mass of iron and also relates to a method of making a magnetic material product out of the powder.
The present invention is applicable to various iron base magnetic material alloys that include not only hard magnetic material alloys, but also soft magnetic material alloys and nanocomposite magnets including hard and soft magnetic phases in combination. The magnetic material products made by the method of the present invention cover a wide range including not just permanent magnets like sintered or bonded magnets, but magnetic shield materials as well.
In the known processes, various types of milling machines such as jet mills, power mills and ball mills have been used widely to pulverize magnetic material alloys. However, it is impossible to obtain a powder of a particle size as large as about 100 xcexcm using a jet mill. Using a power mill or ball mill on the other hand, the resultant particle size distribution cannot be a single normal distribution. For these reasons, a pin disk mill has been used most often to prepare a powder of a mean particle size of 10 xcexcm through 100 xcexcm by pulverizing a magnetic material alloy. Various techniques of pulverizing an iron base magnetic material alloy with a pin disk mill are disclosed in Japanese Laid-Open Publication Nos. 3-14203, 3-46202 and 10-321427, for example.
A pin disk mill is a kind of impact crusher. Normally, a pin disk mill includes two disks that are disposed to face each other. On one side of each of these two disks, multiple milling pins (which will be herein referred to as xe2x80x9cpinsxe2x80x9d simply) are arranged so as not to collide against each other. At least one of the two disks rotates at a high velocity. A workpiece to be pulverized by the pin disk mill is loaded into the space between the two disks. The workpiece collides against the pins on the rotating and/or non-moving disks and is pulverized due to the impact generated. The disks and pins of a pin disk mill are made of austenitic stainless steel (JIS SUS304), for example.
However, we found that if an iron base magnetic material alloy, containing at least 50% by mass of iron, is pulverized with a pin disk mill, the pins will be soon worn out during the pulverization process so that the particle size distribution of the resultant powder changes with time. An intermetallic compound contained in a nanocomposite magnet and a boride phase such as Fe23B6, in particular, have high hardness. Accordingly, these materials considerably wear the pins and blades of a milling machine, and the particle size distribution changes noticeably with time. When a milling machine like this is applied to manufacturing of magnetic material products including magnets, such a change in particle size distribution deteriorates the magnetic properties of the final products. For example, if the mean particle size increases as a result of the size distribution changing, then the percentage of magnetic powder particles successfully filled in might decrease in an injection or compaction molding process. In the current state of the art, that unwanted size distribution changing is unavoidable unless pins or other parts of the machine are replaced frequently. In that case, however, the throughput will decrease considerably. Additionally, the manufacturing costs will also rise because additional personnel costs are required for the exchange.
It is therefore an object of this invention to provide a method of making an iron base magnetic material alloy powder while avoiding both the short-term wear of pins and other parts and particle size distribution changing even when the material alloy is pulverized with a pin mill.
Another object of the present invention is to provide magnetic material products like bonded magnets by utilizing the inventive method of making an iron base magnetic material alloy powder.
An inventive method of making an iron base magnetic material alloy powder includes the steps of: a) preparing an iron base magnetic material alloy containing at least 50% by mass of iron; and b) pulverizing the magnetic material alloy using a pin mill. A portion of the mill, which comes into contact with the magnetic material alloy, is made of a cemented carbide material at least partially.
In one embodiment of the present invention, the cemented carbide material is preferably tungsten carbide.
In another embodiment, an iron base magnetic material alloy powder of a mean particle size of 10 xcexcm through 100 xcexcm may be obtained by pulverizing the magnetic material alloy using a pin mill.
In this particular embodiment, the step a) preferably includes: forming a melt of a material alloy; and quenching the material alloy to form a solidified alloy.
Specifically, the magnetic material alloy is preferably an Fexe2x80x94Rxe2x80x94B alloy, where Fe is iron, B is boron and R is a rare earth element. Part of boron atoms in the above alloy may be replaced with carbon atoms. R is preferably selected from the group consisting of Pr, Nd, Dy and Tb.
More specifically, the magnetic material alloy is preferably a nanocrystalline magnetic material for a nanocomposite magnet, for example. Alternatively, the magnetic material alloy may also be a soft magnetic material or a magnetostrictive material.
In still another embodiment, the pin mill preferably includes a rotating disk and multiple pins arranged on the disk, and at least part of the pins are preferably made of the cemented carbide material.
According to an inventive method of making a magnetic material product, a magnetic material product is formed out of an iron base magnetic material alloy powder that has been prepared by any of the embodiments of the inventive method of making an iron base magnetic material alloy powder.
In one embodiment of the present invention, the magnetic material product may be a permanent magnet such as a bonded magnet.
An inventive method of preparing an iron base alloy powder for a permanent magnet includes the steps of: a) cooling a melt of an Fexe2x80x94Bxe2x80x94R alloy by a quenching process to obtain a solidified alloy with a thickness of 80 xcexcm through 300 xcexcm; b) heat-treating and crystallizing the solidified alloy to impart permanent magnet properties to the alloy; and c) pulverizing the alloy using a pin mill to obtain a powder of a mean particle size of 10 xcexcm through 100 xcexcm. A portion of the pin mill, which comes into contact with the alloy, is made of a cemented carbide material at least partially.
In one embodiment of the present invention, the method may further include the step of coarsely pulverizing the solidified alloy before the step b) is performed.
In another embodiment of the present invention, before the step b) is performed, the solidified alloy may have a structure in which an amorphous phase; at least one metastable phase selected from the group consisting of Fe23B6, Fe3B and R2Fe23B3 phases; and an R2Fe14B phase co-exist. Alternatively, the solidified alloy may also have an amorphous structure before the step b) is performed.
In still another embodiment, the alloy imparted with the permanent magnet properties may be expressed by a formula Fe100-x-yRxBy where R is at least one rare earth element. R is preferably selected from the group consisting of Pr, Nd, Dy and Tb. In this formula, x is equal to or greater than 2 atomic percent and equal to or less than 6 atomic percent, and y is equal to or greater than 15 atomic percent and equal to or less than 20 atomic percent. The alloy preferably includes, as constituent phases, Fe, an Fexe2x80x94B alloy, and a compound with an R2Fe14B crystal structure. A mean crystal grain size of the constituent phases is preferably 100 nm or less.
An inventive method of producing a bonded magnet includes the steps of: preparing an iron base alloy powder for a permanent magnet by any of the embodiments of the method of preparing an iron base alloy powder; and molding the iron base alloy powder.

Method of making iron base magnetic material alloy powder


An active matrix substrate including: gate lines; source lines arranged in a direction orthogonal to each of the gate lines; a gate short-circuit line to short-circuit the gate lines; a source short-circuit line to short-circuit the source lines; gate line thin film transistors each having a drain electrode being connected to the corresponding one of the gate lines, and a source electrode being connected to the gate short-circuit line; and source line thin film transistors each having a drain electrode being connected to the corresponding one of the source lines, and a source electrode being connected to the source short-circuit line, in which the gate line thin film transistors and the source line thin film transistors are of depletion-mode, and the gate electrode of each of the source line thin film transistors is connected to the gate short-circuit line.

(1) Field of the Invention
The present invention relates to an active matrix substrate, a display panel using the substrate, and a testing method for the active matrix substrate and the display panel, and particularly relates to a protection circuit for the active matrix substrate and the display panel using the active matrix substrate.
(2) Description of the Related Art
Along with the increased demand for better display apparatus in recent years, Liquid Crystal Display (LCD) panels and organic electroluminescence (EL) display panels have been attracting attention as thin display panels with low power consumption. The display panels have two-dimensionally arranged pixels.
For example, in an active matrix organic EL display panel, thin film transistors (TFT) are provided at intersections of scanning lines and data lines. Storage capacitors, gates of driving transistors, and compensating circuits are connected to the TFTs. The TFTs are turned ON through selected scanning lines, input data signals and others are provided from the data lines to the driving transistors, the storage capacitors, and the compensating circuits. The driving transistors, storage capacitors, and the compensating circuits control brightness and timing of light emitted from the organic EL element. This configuration of the pixel driving circuit allows an active matrix organic EL display panel to have the organic EL element emit light until next scanning (selection). Consequently, even when a duty cycle increases, it does not result in decrease in display brightness.
However, the active matrix organic EL display panel has a complex pixel driving circuit configuration. Because of this, electric malfunctions such as uneven characteristics of the pixel driving circuit devices, short-circuited lines, and opened lines. In order to compensate the uneven characteristics and to improve yield at the time of manufacturing, it is necessary to perform sufficient testing on arrays of active matrix substrate during the manufacturing process, and testing on display operations of display panels after completion before mounting components to be mounted. At the time of testing, when an external measuring device and a measuring subject, that is, an active matrix substrate or a display panel are connected, or when no external measuring device is connected during the manufacturing process, there is a possibility that static electricity flows into an active matrix substrates, causing electrostatic breakdown of the pixel circuits. Patent Literature 1 (Japanese Unexamined Patent Application Publication No. H11-142888 discloses a configuration for protecting the display panel from the electrostatic breakdown at the time of manufacturing and testing an LCD.
FIG. 7 is a planar view schematically illustrating signal input terminals of the LCD apparatus according to Patent Literature 1. FIG. 7 shows an array substrate 501 on which display switching element such as a TFT (not illustrated) is bonded with a facing substrate 502. The facing substrate 502 includes a display region 503. In the array substrate 501, source lines 504 and gate lines 505 are provided as many as necessary for displaying images. Each of the source lines 504 has a testing signal voltage input terminal 506, and each of the gate lines 505 has a testing signal voltage input terminal 507. A short-circuit ring 508 made of low-resistance material such as metal is provided at the outer periphery of the array substrate 501. The short-circuit ring 508, the source lines 504, and the gate lines 505 are electrically connected via depletion-mode TFTs 509. The gate electrodes of the depletion-mode TFTs 509 are connected to the lines 510 on an arbitrary unit bases, and controlled by a gate voltage input terminal 511 on the unit basis.
With the configuration described above, during the manufacturing process of the LCD apparatus, no voltage is applied to the gate electrode of the depletion-mode TFTs 509, and all of the source lines 504, all of the gate lines 505, and the short-circuit ring 508 conduct via the depletion-mode TFT 509 which is in ON state. With this, it is possible to take measures for preventing electrostatic breakdown. When testing the LCD apparatus, for example, in the case of array testing probing array substrate for array defect, or in the case of panel lighting-up display testing probing the LCD panel before mounting components, it is necessary that probes and others contact the testing signal voltage input terminals 506 and 507 to apply individual testing signals and lighting-up signal voltages. In this case, it is necessary for all of the source lines 504 and the gate lines 505 to be electrically open to each other and with the short-circuit ring 508. Thus, negative OFF voltage is applied to the gate electrode of the depletion-mode TFT 509 from the gate voltage input terminal 511. With this, the lines are completely open, allowing highly precise testing and lighting-up display without being affected by signals from neighboring lines. When the depletion-mode TFTs 509 as ESD protecting elements are not necessary after the testing, the connection may be cut off at a cutting line 512. Alternatively, when leaving the depletion-mode TFTs 509 which is a ESD protecting element as a measure for preventing electrostatic breakdown during mounting process or after the manufacturing is complete, applying a negative OFF voltage to the gate voltage input terminal 511 at all times allows the lines to be open.

Active matrix substrate, display panel, and testing method for active matrix substrate and display panel


Peptide motifs which define specificity of tumor-derived endothelial cells. These peptides possess a charge motif of positive-positive-hydrophobic which is important in determining the specificity of binding to tumor-derived endothelium. The specific molecular peptide motifs will facilitate diverse therapeutic and diagnostic applications including: anti-angiogenic therapies to be used in alone or in conjunction with standard therapies; imaging tools for both detection of very small metastasis that are undetectable by current techniques; for monitoring tumor response; for targeting and directing chemotherapy drugs to the tumor; for treatment of chronic inflammatory diseases such as rheumatoid arthritis and psoriasis, for treating some forms of blindness; as well as other diagnostic and therapeutic applications.

Vascular endothelial cells cover the entire inner surface of blood vessels in the body. They play an important role in tissue homeostasis, fibrinolysis and coagulation, blood-tissue exchange, vascularization of normal and neoplastic tissues, and blood cell activation and migration during physiological and pathological processes. A unique aspect of endothelial cells is that although they present many common functional and morphological features, they also display remarkable heterogeneity in different organs. It has been shown that bovine aortic endothelial cells, when co-cultured with cells or matrix proteins from various organs, will change their phenotype to reflect their interaction with that particular tissue type. These phenotypes are, in part, mediated by molecular markers, which are expressed by these endothelial cells specific for the unique interaction. Based on the unique histologic appearance of tumor vasculature, it is postulated that expression of specific molecular endothelial markers probably also exist for the tumor-endothelial interaction. The ability to target these molecules would, in effect, specifically target the tumor endothelium, and hence, the tumor. Previous attempts to identify and target these specific molecular endothelial molecules have failed.
The importance of pathologic angiogenesis is well established in the clinical setting of cancer. Solid tumors are unable to grow much larger than 2 mm in diameter without a blood supply, and in order to express a malignant phenotype, tumors must induce new vessel growth. Tumors recruit endothelial cells during the process of angiogenesis. The recruited endothelial cells differentiate and express unique molecular markers specific for their association with tumor cells. The ability to identify and target these molecular markers would allow for specific targeting of the tumor vasculature as well as the tumor itself. Currently, there are no viable directed therapies targeting the endothelial cells and therapies are needed to provide novel and specific treatment alternatives.
Until recently, identification of tissue-specific endothelial markers has progressed slowly, partly because of difficulties in isolating pure populations of endothelial cells from tissues. A powerful technique utilizing phage display peptide libraries has been developed that allows for the selection of peptide sequences with desired binding specificities. In this system, peptides with as many as 109 permutations are expressed on the phage surface by fusion with a phage surface protein. The desired peptides are selected on the basis of binding to the target molecule. The strength of this technology is its ability to identify interactive proteins and other molecules without pre-existing notions about the nature of the interaction.
Using this methodology, various peptides with binding specificity to angiogenic endothelium and endothelial cells from various organs have been identified. These peptide sequences are typically three amino acids in length and the best characterized of these sequences is represented by the RGD (Arg-Gly-Asp) motif. This sequence was originally discovered in fibronectin, and later re-identified using in vivo phage peptide display library animal experiments. RGD is the cell attachment site for many other adhesive proteins.
The finding that only 3 amino acids would form an essential recognition site for cells in a very large protein was initially received with some skepticism. However, the observation was soon confirmed with regard to fibronectin and then extended to other proteins. Since then, other peptide motifs that identify and bind to specific targets on the endothelial cells of angiogenic vessels, brain, lungs, retina, and kidneys have been reported (Table 1). Also, the functional specificity of the 3-amino acid motif, NGR (Arg-Gly-Asp), has recently been described for angiogenic endothelium. It is important to point out that the reported motifs with binding to tumor endothelium are, in fact, specific for angiogenic endothelial cells and not specific for tumor-derived endothelium.
TABLE 1Reported Peptide Motifs and Targeted TissuePeptide MotifsTissue TargetRDGAngiogenicNGR  EndotheliumGSLGFELungRDVRetinaSRLBrain


In an electrophotographic device, a heat roller is heated by a heater, and upon instruction of start of a print operation, the temperature Tf of the heat roller is detected by a temperature sensor. When the temperature Tf is above a predetermined temperature Tv at which high voltage is applied, the high voltage is applied. Thereafter, the temperature Tf of the heat roller is detected again, and if the temperature Tf is above a predetermined temperature Ts at which the sheet is fed, the solenoid clutch is switched on to feed the sheet. If the print operation is not terminated, the temperature of the heat roller is detected again, and it is checked whether the temperature of the heat roller is above a predetermined fixing temperature Tp.

1. Field of the Invention
This invention relates to an electrophotographic device and method in which a print time required for printing a first print sheet is shortened.
2. Description of the Related Art
The construction and operation of the laser printer will be described with reference to FIG. 4.
When a sheet 11 is fed from an automatic sheet supply device 10, which is provided at a lower side in a laser printer body 1, the sheet 11 is fed to an image forming portion 15 while being guided by a sheet guide 12. If at this time a sheet detection sensor 13, provided adjacent the sheet guide 12, detects that the sheet 11 passes therethrough, in response to a sheet detection signal, a pair of resist rollers, which are provided downstream of the sheet guide 12 with respect to the sheet detection sensor 13, starts their rotational motion after a predetermined time elapses. The sheet 11 is subjected to a distortion correcting treatment in contact with the resist rollers 14 and is fed to the downstream side of the sheet guide 12 through the rotational motion of the resist rollers 14 while being sandwiched by the resist rollers 14. The sheet 11 is guided by a sheet guide 16 provided at the downstream side of the resist rollers 14 and fed to the image forming portion 15 while being guided by a carry roller 17 provided at the downstream side of the sheet guide 16 so as to be in close contact with a photosensitive drum 20.
In the vicinity of the image forming portion 15 are provided a scanner unit 21 for performing an exposure process to form an electrostatic latent image on the photosensitive drum 20, a developing device 22 for developing the electrostatic latent image formed by the exposure process, an image transfer portion 18 for transferring the developed electrostatic latent image onto the sheet 11, and a discharger 19 for discharging the sheet 11 to exfoliate the sheet from the photosensitive drum 20 after the image transferring process. In the image forming portion 15, the electrostatic latent image is formed on the photosensitive drum 20 by the exposure process of the scanner unit 21, and developed by charged toner that is supplied from the developing device 22. A toner image that has been developed through the developing process in the image transfer portion 18 is transferred onto the sheet 11. The charged sheet 11 is discharged in the discharger 19 after the image transfer process. The charged sheet 11 is brought to a state where no electrical affection is given to the sheet 11 and exfoliated from the photosensitive drum 20.
The sheet 11, which has been discharged in the discharger 19, is guided to a carry guide portion 23 disposed at the downstream side of the image forming portion 15 and fed to a fixing device 24 disposed at a further downstream side. After the toner image on the sheet 11 is fully fixed, the sheet 11 is guided to a sheet discharge portion 27 and fed onto a sheet discharge tray 29 through rotation of a pair of discharge rollers 28.
A heat roller 25 for fixing the toner image on the sheet 11 is provided in the fixing device 24. The heat roller 25 is provided with a heater 26 to supply heat to the heat roller 25. A temperature sensor 31 for detecting temperature of the heat roller 25 is secured to a frame of the fixing device 24 so as to be contacted with the heat roller under pressure. Further, a support roller 32 is provided so as to be paired with the heat roller 25. The sheet 11 fed from the carry guide portion 23 is pinched by the heat roller 25 and the support roller 32 and fed from the fixing device 24 to the sheet discharge portion 27 by feed-out rollers 33. A fan motor 30 is provided in the vicinity of the fixing device 24.
In the laser printer thus constructed, simultaneously with the start of a print operation, the heater 26 in the fixing device 24 is turned on to heat the heat roller 25. Upon the turn-on of the heater 26, the inside of the printer body 1 is warmed by the heat. In order to prevent the output power of a laser beam from being fluctuated due to the warming of the scanner unit 21, etc., the fan motor 30 is rotated to discharge warmed air in the printer body 1 to the outside of the printer body 1, so that the inside of the printer body 1 is cooled. The temperature of the heat roller 25 is detected by the temperature sensor 31, which is contacted with the heat roller 25 under pressure. If the detected temperature is below a predetermined temperature, the heater 26 is turned on, while if the detected temperature is above the predetermined temperature, the heater 26 is turned out. Through this operation, the heat roller 25 is controlled so that its temperature becomes constant.
Conventionally, in the laser printer thus constructed, the temperature of the heat roller 25 is detected by the temperature sensor 31 upon start of the print operation.
After the detected temperature reaches a temperature above a predetermined fixing temperature at which the toner image transferred onto the sheet 11 is fully fixed on the sheet 11, a high voltage is applied to the developing device 22 to drive the developing device 22 containing the photosensitive drum 20, the image transfer portion 18, the discharger 19, etc., and the feeding operation of the sheet 11 is started after a predetermined time elapses. Subsequently, the toner image is formed on the sheet 11 in the image forming portion 15, and the sheet 11 is fed to the fixing device.
As described above, in the conventional electrophotographic device, after the temperature of the heat roller 25 reaches the predetermined temperature, the high voltage is applied, and the sheet feeding operation of the sheet 11 is started. Therefore, a print time required for completely printing a first sheet (first print time) is extremely long. That is, it takes several seconds for the temperature of the heat roller 25 to reach the predetermined value, and further it takes several seconds for the developing device 22 to be supplied with high voltage and kept in a development-permissible state. In addition, it takes several seconds for the sheet 11 to be fed to a predetermined position where the toner image is transferred onto the sheet 11. Therefore, several seconds, for example 13 to 14, are required to prepare the print operation for the first sheet, and about 23 to 24 seconds are required from the termination of the print operation for the first sheet until the discharging operation of the first sheet.

Electrophotographic device and method for shortening a print time


A fiber-pigtailed assembly for an optical detector with low back reflection and minimal polarization-dependent responsivity has a detector surface mounted adjacent a beveled end of a fiber pigtail such that the detector surface is tilted and rotated with respect to the beveled end of the fiber pigtail. Also an external optical fiber may be coupled to the fiber pigtail with low back reflection and minimal polarization-dependent responsivity by having an input ferrule at the end of the external optical fiber, the end being beveled; by having an intermediate ferrule at a coupling end of the fiber pigtail, the coupling end being beveled while the other end of the ferrule is beveled by the same amount but approximately orthogonal to the coupling end; and by having an output ferrule on the fiber pigtail adjacent to the intermediate ferrule, the end of the output ferrule adjacent to the intermediate ferrule being beveled. The ferrules are maintained in position so that the beveled ends of the intermediate ferrule are parallel to the corresponding beveled ends of the input and output ferrules and there is a gap between the input and intermediate ferrules. The beveled ends of the ferrules at both the coupler and detector ends of the fiber pigtail introduce fixed amounts of polarization-dependent responsivity while reducing back reflection, while the tilt of the detector surface at the detector end and the opposite approximately orthogonal bevel of the intermediate ferrule at the coupler end compensate and essentially eliminate such polarization-dependent responsivity.

The present invention relates to coupling light onto an optical detector, and more particularly to a fiber-pigtailed assembly that couples light from an optical fiber onto an optical detector having a relatively large area such that the polarization-dependent responsivity and back reflection are very low.
Polarization-dependent responsivity (PDR) is the ratio of the maximum photo-current divided by the minimum photo-current generated in an optical detector for a given flux of photons over all possible states of polarization and correlates to polarization-dependent loss (PDL). Ideally PDR is zero dB. Reflectivity is the flux of photons that travel backward to the optical source divided by the flux of photons impinging upon the optical detector, usually expressed in dB. Ideally the reflectivity is minus infinite dB.
Low back reflection and low PDR tend to be difficult to achieve simultaneously. Usually methods that improve one make the other worse. For some types of test equipment that measure the characteristics of fiber-optic components it is important to have an optical detector with both low reflectivity and low PDR. Typical requirements for back reflection and PDR are −45 dB and 0.03 dB, respectively. Extraordinary requirements are −65 dB and 0.003 dB, respectively.
While these requirements are important for test-and-measurement (T&M) applications, they are not typically necessary for the majority of people who use fiber-pigtailed detectors. Since T&M applications are a small percentage of the overall market for such devices, it is often difficult or impossible to find a company that can or will build such a device for the limited T&M market.
A common method of reducing back reflection is to use various optical coatings that are designed for low reflectance. These coatings are based on interference, however, and so exhibit wavelength dependence. Even at the optimized wavelength, coatings have difficulty achieving the best-desired specifications. For applications involving wide-band detection, i.e., over many hundreds of nanometers of wavelength, the performance of such coatings is a serious limitation.
Another common method of achieving low back reflection is to tilt the surface of the optical detector relative to the input fiber. The resulting reflected light is thus angled such that it fails to couple to guided fiber modes and is quickly lost. Unlike coatings, tilted surfaces are inherently broadband, resulting in very low reflectivity. Tilting the optical surface, however, introduces PDR. This is largely the result of the fact that the power in the reflected light from a tilted surface is a function of the state of polarization. This is often the source of the low PDR/low back reflection trade off.
In T&M applications using photodetectors to measure optical power requirements typically calls for low back reflection to help avoid instabilities that result from feedback into the laser source, while also calling for low PDR. The problem is that the optimum way of achieving low back reflection, as indicated above, is to use tilted surfaces, yet tilted surfaces introduce polarization dependencies. This problem is amplified in pigtailed optical detectors because the optical pigtail acts like a weak Fabry-Perot resonator, with a birefringent medium (the fiber itself) between mirrors (the reflective ends of the fiber pigtail).
In a Fabry-Perot resonator without birefringence between the mirrors the transmitted and reflected fields add coherently to produce the characteristic wavelength-dependent transmission of these resonators. The introduction of a birefringent material between the mirrors causes relative rotation between reflection/transmission terms that ordinarily would add. However rotation of these terms interferes with their ability to coherently mix, resulting in modulation of the transmitted optical power, i.e., the modulation is a function of the birefringence and wavelength. Thus a simple component made of parts that individually have no polarization-dependent loss (PDL) may exhibit significant PDL. When pigtailed to the optical detector, the fiber assembly and detector together constitute a device that may show considerable PDR. Assemblies with normal incidence, where PDL might be expected to be least, actually show more polarization dependence than those with tilted surfaces. This is because the PDL of the weak Fabry-Perot resonator inherent in the fiber pigtail is amplified by the relatively strong reflection at normal incidence.
What is desired is a fiber-pigtail assembly for an optical detector that provides both low PDR and low back reflection sufficient to meet or exceed even extraordinary specifications.


A cover mechanism in a cartridge for an electric stapler comprises a movable wall, a cover body, and securing mechanism. The cartridge includes a storage portion for storing piled-up sheet-like staples each having linear-shaped staples connected together in a sheet shape. The movable wall is formed on a side wall of the storage portion and capable of swinging inwardly and outwardly. The cover body is disposed over an opening of the storage portion for insertion of the sheet-like staples and includes a covering portion. The covering portion of the cover body covers an outside portion of the movable wall and is respectively formed on two sides of the cover body. The securing mechanism secures together the covering portion of the cover body and the movable wall. Secured state between the covering portion of the cover body and the movable wall is removed when any sheet-like staples do not remain within the storage portion.

1. Field of the Invention
The present invention relates to a cover and a cover mechanism for use in a cartridge for an electric stapler, in which a cover body is mounted over the cartridge to be removably mounted into the electric stapler and the cover body cannot be opened before sheet-like staples stored in the cartridge are all consumed up.
2. Description of the Related Art
Generally, in a cartridge for an electric stapler, there is formed a storage portion capable of receiving and storing therein a refill (a component formed in such a shape as shown in FIG. 1 of JP-A-7-148674, which is also referred to as an inner cartridge) in which sheet-like staples each composed of a plurality of linear-shaped staples connected together in a sheet manner are piled up on top of another and are packed simply. In the upper portion (or lower portion) of the storage portion, there is formed an opening and thus the refill can be inserted into the storage portion of the cartridge through this opening. When the cartridge is mounted into the main body of the electric stapler with the present opening facing upwardly (or downwardly), the sheet-like staples are supplied sequentially in order starting at the nearest one to the opening from the storage portion to a drive portion of the cartridge, where the staples can be driven into a member to be stitched.
As shown in FIG. 5, in case where an operator removes a cartridge when one or more sheet-like staples 21 still remain within a storage portion 20 and, under an illusion that no sheet-like staple 21 remains within a refill 22, the operator opens a cover 23 to try to pull out the refill 22 from an opening formed in the cartridge in order to replace the refill 22 with a new one, since the refill 22 is structured such that it can be removed from the cartridge only after the sheet-like staples 21 are all consumed up, if the operator tries to pull out the refill 22 forcibly, then the refill 22 itself can be damaged or the sheet-like staples 21 may be broken. In this state, even if the operator gives up removing the refill 22, inserts it again into the main body of an electric stapler, and tries to drive the staples, because the refill or sheet-like staples are damaged and deformed, there is a fear that a feedmechanism fails to operate properly, which results in the poor feeding of the sheet-like staples.

Cover mechanism in cartridge for electric stapler


In a method of and apparatus for producing sub-micron bubbles in liquids, slurries, and sludges, gas is maintained on the interior of the gas permeable partition at predetermined pressure. Relative movement between the gas permeable partition and the surrounding material forms sub-micron sized bubbles in the liquid, slurry, or sludge.

Gas-liquid, gas-slurry, and gas-sludge reactions (hereinafter referred to collectively as gas-liquid reactions) present unique problems not found in single phase reactions. The rate and efficiency of gas-liquid reactions is dependent on the amount of contact between the gas and the liquid. The contact occurs at the interface of the liquid and the gas and is, therefore, dependent upon the surface area of the gas bubbles in the liquid. For a given amount of gas, the smaller the bubbles, the greater the surface area. It is therefore advantageous to produce smaller bubbles in order to achieve the best reaction efficiency.
The efficiency of gas-liquid reactions is particularly important in wastewater treatment systems. For example, one of the primary processes in treating municipal and some industrial wastewater streams is known as an activated sludge system. In an activated sludge system, incoming wastewater, typically under gravity flow conditions, enters a large, typically rectangular aeration basin. Within the basin a manifold system of aerators served by one or more large air compressors puts air into the wastewater. The oxygen in the air allows naturally occurring bacteria (the activated sludge) to oxidize contaminants in the wastewater.
The aerators used in conventional wastewater treatment plants are typically disks with small pores which are referred to as diffusers. Conventional diffusers are able to produce bubbles in the 100-500 micron range. These relatively large bubbles tend to rise quickly in the aeration basin, limiting the amount of oxygen that can transfer from the gas bubble to the water. As a result, extremely large quantities of air must be passed through the diffuser in order to ensure that an appropriate amount of oxygen enter the water.
Conventional diffusers tend to plug over time. When a diffuser is plugged, the air pressure behind the diffuser can blow the diffuser head completely off of the riser pipe to which it was attached. If a diffuser head blows off of the riser pipe, the pressure drop across the diffuser is eliminated. As the diffusers and riser pipes are manifolded together, any reduction in pressure drop reduces efficiency across the entire system.
Replacing a conventional diffuser requires that the activated sludge system or a portion of the system be taken off line and drained so that the diffuser may be replaced. Thus, a need exists for improvements in the art of diffuser design which facilitate the generation of sub-micron sized bubbles in the wastewater treatment systems.
Diffuser manufacturers have heretofore attempted to generate sub-micron sized bubbles in activated sludge systems by fabricating diffusers with very small outlet holes. All such attempts have been unsuccessful because the problem of diffuser plugging is exacerbated when diffuser outlet hole size is reduced.

Method of and apparatus for producing sub-micron bubbles in liquids, slurries, and sludges


A parallel resonant circuit for powering a gas discharge lamp achieves power factor correction by using a floating power supply having adjustable voltage and impedance level. The floating power supply is powered by a transformer and placed in series with the rectified AC power line.

Gas discharge lamps can be operated most efficiently by AC (alternating current) power at a relatively high frequency (on the order of 35 KHz (kilohertz). However, line AC power is supplied by utility companies at low frequencies of around 50 or 60 Hz (hertz). To obtain high efficiency operation of the lamps, the AC power at the first low frequency is converted to AC power at a second high frequency.
The conversion of the AC power from one frequency to another is accomplished by a ballast circuit. The AC power at the first low frequency is rectified into DC (direct current) power, and then stored as energy in a relatively large electrolytic capacitor. The energy stored in the electrolytic capacitor is then chopped by an inverter into AC power at a second high frequency.
In this kind of circuit, whenever the voltage of the line AC power is greater than the voltage stored in the electrolytic capacitor, a relatively large surge of current passes into the electrolytic capacitor, causing the line current drawn to be "peaky". This circuit thus has a poor power factor.
One solution is to place a floating voltage supply in series with the incoming line to the capacitor. Such a supply presents several problems. First, the voltage on the supply must be controlled so as to match the voltage on the electrolytic capacitor, otherwise the waveform of the power drawn from the line will be distorted. Second, the impedance of the supply must be adjustable so as to control the amount of power drawn from the power line. If not, the inverter will either produce too much power or there will be little correction of the power factor. Finally, the source of the power for the floating voltage supply must be stable and have low impedance.
A circuit which provides a floating voltage supply in series with the incoming line and has an adjustable impedance and an adjustable voltage level is thus desirable.

Circuit for powering a gas discharge lamp


The present invention relates to compounds of formula 1 ##STR1##. and to pharmaceutically acceptable salts and solvates thereof, wherein Z, R, R.sup.3 and R.sup.4 are as defined herein. The invention also relates to pharmaceutical compositions containing the compounds of formula 1 and to methods of inhibiting abnormal cell growth, including cancer, in a mammal by administering the compounds of formula 1 to said mammal.

This invention relates to a series of novel imidazolidin-4-one derivatives that are useful in the treatment of hyperproliferative diseases, such as cancers, in mammals. This invention also relates to a method of using such compounds in the treatment of hyperproliferative diseases in mammals, especially humans, and to pharmaceutical compositions containing such compounds.
Compounds that are useful in the treatment of hyperproliferative diseases are also disclosed in the following co-pending patent applications: PCT international patent application number PCT/IB97/00675, which designates the United States and was filed on Jun. 11, 1997; U.S. provisional patent application Ser. No. 60/041846 (filed Apr. 9, 1997); U.S. provisional patent application Ser. No. 60/031862 (filed Nov. 27, 1996); U.S. provisional patent application Ser. No. 60/028881 (filed Oct. 17, 1996); PCT international patent application number PCT/IB97/00584, which designates the United States and was filed on May 22, 1997; U.S. patent application Ser. No. 08/653,786 (filed May 28, 1996); PCT international patent application publication number WO 96/40142, which designates the United States and was published on Dec. 19, 1996; PCT international patent application publication number WO 97/13771, which designates the United States and was published on Apr. 17, 1997; PCT international patent application publication number WO 95/23141, which designates the United States and was published on Aug. 31, 1995; U.S. provisional patent application number 60/020696 (filed Jun. 27, 1996); International Patent Application PCT/US92/11292, which designates the United States and was published on Jul. 22, 1993 as WO 93/14085; U.S. Patent 4,876,259, which issued on Oct. 24, 1989; International Patent Application PCT/IB95/00189, which designates the United States and was filed on Mar. 20, 1995; U.S. patent application Ser. No. 08/236,743, which was filed on Apr. 29, 1994.
Oncogenes frequently encode protein components of signal transduction pathways which lead to stimulation of cell growth and mitogenesis. Oncogene expression in cultured cells leads to cellular transformation, characterized by the ability of cells to grow in soft agar and the growth of cells as dense foci lacking the contact inhibition exhibited by non-transformed cells. Mutation and/or overexpression of certain oncogenes is frequently associated with human cancer.
To acquire transforming potential, the precursor of the Ras oncoprotein must undergo farnesylation of the cysteine residue located in a carboxyl-terminal tetrapeptide. Inhibitors of the enzyme that catalyzes this modification, farnesyl protein transferase, have therefore been suggested as agents to combat tumors in which Ras contributes to transformation. Mutated, oncogenic forms of Ras are frequently found in many human cancers, most notably in more than 50% of colon and pancreatic carcinomas (Kohl et al., Science, Vol. 260, 1834 to 1837, 1993). The compounds of the present invention exhibit activity as inhibitors of the enzyme farnesyl protein transferase and are therefore believed to be useful as anti-cancer and anti-tumor agents.

Imidazolidin-4-one derivatives useful as anticancer agents