An L band optical amplifier in disclosed. The optical amplifier includes a signal line which has an input, an output disposed optically downstream of the input, and an amplifying gain medium optically disposed between the input and the output. The optical amplifier further includes a laser optically connected to the first amplifying gain medium and an apparatus for directing C band light into the amplifying gain medium.

The present invention relates to optical amplifiers having operating wavelengths longer than main emission peak wavelengths, and more particularly to erbium doped fiber and waveguide amplifiers operating in the long wavelength regime (1560-1620 nm), especially for wavelength division multiplexing (WDM) applications.
Conventional erbium doped fiber amplifiers (EDFA) have been extensively used in optical telecommunications as means to amplify weak optical signals in the third telecommunication window (near 1550 nm) between telecommunication links. Much work has been done on the design of these amplifiers to provide efficient performance, such as high optical gain and low noise figure. However, with the recent enormous growth of data traffic in telecommunications, owing to the Internet, intranets, and e-commerce, new optical transmission bandwidths are required to provide increased transmission capacity in dense wavelength division multiplexing (DWDM) systems.
There are a few solutions to this demand. One proposed solution is to utilize new materials compositions as a host for the fiber gain medium (instead of silica) such as telluride, which may provide broader amplification bandwidth (up to 80 nm). However, the non-uniform gain shape and poor mechanical properties of telluride glass make these amplifiers difficult to implement in the telecom systems. Also, Raman amplifiers can be considered as an alternative solution to high bandwidth demand, since these amplifiers are capable of providing flexible amplification wavelength with a broad bandwidth. However, these amplifiers place restrictions on optical system architectures because of their required designs for efficient performance, such as long fiber length ( greater than 5 km), high pump power ( greater than 500 mW) and co-pumping configurations. On the other hand, relatively long erbium doped fibers (EDFs) may also provide amplification in the long wavelength range (1565-1625 nm) when they are used with high power pump sources. This range is commonly called xe2x80x9cL bandxe2x80x9d. The conventional range, also known as xe2x80x9cC bandxe2x80x9d is in the wavelength range between 1525-1565 nm.
In principle, L band amplifiers take advantage of the fact that EDFs have higher emission cross-section than absorption cross-section at longer wavelengths. Therefore, for long EDFs, amplified spontaneous emission (ASE) becomes more emphasized at long wavelengths. However, there are still several issues for optimization of L band amplifiers for efficient performance. So far, reported performance of L band EDFAs has been inferior to that of C band EDFAs, with drawbacks as evidenced by higher noise figure (NF) and lower output power and gain. It would be beneficial to provide an L band amplifier with a low noise figure and high output power and gain.
Briefly, the present invention provides an L band optical amplifier. The optical amplifier comprises a signal line including an input, an output disposed optically downstream of the input and an amplifying gain medium optically disposed between the input and the output. The optical amplifier further comprises a laser optically connected to the first amplifying gain medium and means for directing C band light into the amplifying gain medium, wherein the means comprises at least one reflective element optically disposed in the signal.
The present invention also provides an L band optical amplifier. The optical amplifier comprises a signal line including an input, an output disposed optically downstream of the input and an amplifying gain medium optically disposed between the input and the output. The optical amplifier further comprises a laser optically connected to the first amplifying gain medium and means for directing C band light into the amplifying gain medium, wherein the means comprises a C band seed pump optically connected to the signal line between the input and the amplifying gain medium.


A system and method for offloading scalable robotic tasks in a mobile robotics framework. The system comprises a cluster of mobile robots and they are connected with a back-end cluster infrastructure. It receives scalable robotic tasks at a mobile robot of the cluster. The scalable robotics tasks include building a map of an unknown environment by using the mobile robot, navigating the environment using the map and localizing the mobile robot on the map. Therefore, the system estimate the map of an unknown environment and at the same time it localizes the mobile robot on the map. Further, the system analyzes the scalable robotics tasks based on computation, communication load and energy usage of each scalable robotic task. And finally the system priorities the scalable robotic tasks to minimize the execution time of the tasks and partitioning the SLAM with computation offloading in edge network and mobile cloud server setup.

Mobile robots are generally constrained devices in terms of processing power, storage capacity and energy. Cloud robotics and robotic clusters are two prevalent approaches used to augment mobile robot's processing power performing complex robotic tasks including multi-robot simultaneous localization and mapping (SLAM), robotic vision etc. In cloud robotics, mobile robots use remote cloud server over the internet as resources for offloading intensive computation. Though computation offloading in cloud robotics rendered complex tasks such as map merging, cooperative navigation etc.
Cloud robotics in its current form assumes continuous connectivity to the back-end cloud infrastructure. However, in real world situations, especially in disaster scenarios, such assumptions does not hold. To handle the intermittent cloud connectivity and to meet the requirement of latency sensitive applications, there is a need to offload the computationally expensive simultaneous localization and mapping task for mobile robots. Whereas, performing such tasks by sharing computation load among the peer robots, forming a cluster, is not always feasible due to energy and processing power constraints in robots and non-availability of memory for complex tasks such as map merging, map storage etc. Further, a model is needed for offloading decision in the current setup where the results demonstrates the efficacy of the proposed dynamic offloading framework over static offloading strategies.

System and method for offloading robotic functions to network edge augmented clouds


A device and method for the establishment of quality parameters of a digital map. A currently determined position of the vehicle and a measured value of an attribute of this position is used to calculate a quality parameter which serves as additional information for the data of the digital map. A driver assistance system constitutes an improved aid for a driver of a vehicle, since, in addition to the data of the digital map, the driver assistance system uses the feedback information of the quality parameter.

Driver assistance systems are electronic accessories in motor vehicles for assisting the driver in certain driving situations. The emphasis here is often on safety aspects, but also on increasing the driving comfort. These systems intervene semi-autonomously or autonomously in the drive, control (for example fuel system, brake system), steering or signaling devices of the vehicle, or warn the driver just before or during critical situations by means of suitable man-machine interfaces. Most driver assistance systems are at present conceived in such a way that the responsibility remains with the driver and the driver ultimately continues to be in control. In this context, digital maps are to a certain extent made available to the driver assistance systems.
The accuracy of use of digital maps in driver assistance systems depends substantially on the accuracy and reliability of the map material which is used as a basis. The method which is generally used to attempt to ensure the highest possible degree of accuracy and reliability is that the map manufacturer produces new maps as often as possible. However, in this process both relative and absolute geometric errors occur during the data collection process. Furthermore, errors are possible due to changes in the road sections as a result, for example, of new building measures between two data collection intervals. The same applies to the attributes of a specific position such as a speed limit or the permitted maximum weight of a vehicle, because incorrect data collection may also have occurred here.

Establishing quality parameters of a digital map


Provided herein are nicotine polymer-stabilized nanoparticles, formulations thereof, and vaccines. Also provided herein are methods of treating and/or preventing nicotine addiction in a subject in need thereof.

The U.S. Surgeon General has commented that stopping smoking represents the single most important step that smokers can take to enhance the length and quality of their lives. Despite the well evidenced improvement to health and quality of life, smokers can have severe difficulty smoking due the physical addiction to nicotine contained in cigarettes and other smoking products, including e-cigarettes. While many modalities ranging from mental health therapies to nicotine replacement therapy, the failure rate in overcoming nicotine addiction is still high. As such, there exists a need for improved therapies that can assist with stopping and/or preventing nicotine addiction.

Virginia Tech Intellectual Properties, Inc.


A system and method for permitting bi-directional failover in two node clusters utilizing quorum-based data replication. In response to detecting an error in its partner the surviving node establishes itself as the primary of the cluster and sets a first persistent state in its local unit. A temporary epsilon value for quorum voting purposes is then assigned to the surviving node, which causes it to be in quorum. A second persistent state is stored in the local unit and the surviving node comes online as a result of being in quorum.

A storage system is a computer that provides storage service relating to the organization of information on storage devices, such as disks. The storage system may be deployed within a network attached storage (NAS) environment and, as such, may be embodied as a file server. The file server or filer includes a storage operating system that implements a file system to logically organize the information as a hierarchical structure of directories and files on the disks. Each "on-disk" file may be implemented as a set of data structures, e.g., disk blocks, configured to store information. A directory, on the other hand, may be implemented as a specially formatted file in which information about other files and directories are stored.
A filer may be further configured to operate according to a client/server model of information delivery to thereby allow many clients to access files stored on a server, e.g., the filer. In this model, the client may comprise an application, such as a database application, executing on a computer that "connects" to the filer over a computer network, such as a point-to-point link, shared local area network (LAN), wide area network (WAN), or virtual private network (VPN) implemented over a public network such as the Internet. Each client may request the services of the file system on the filer by issuing file system protocol messages (in the form of packets) to the filer over the network.
A common type of file system is a "write in-place" file system, an example of which is the conventional Berkeley fast file system. In a write in-place file system, the locations of the data structures, such as inodes and data blocks, on disk are typically fixed. An inode is a data structure used to store information, such as meta-data, about a file, whereas the data blocks are structures used to store the actual data for the file. The information contained in an inode may include, e.g., ownership of the file, access permission for the file, size of the file, file type and references to locations on disk of the data blocks for the file. The references to the locations of the file data are provided by pointers, which may further reference indirect blocks that, in turn, reference the data blocks, depending upon the quantity of data in the file. Changes to the inodes and data blocks are made "in-place" in accordance with the write in-place file system. If an update to a file extends the quantity of data for the file, an additional data block is allocated and the appropriate inode is updated to reference that data block.
Another type of file system is a write-anywhere file system that does not overwrite data on disks. If a data block on disk is retrieved (read) from disk into memory and "dirtied" with new data, the data is stored (written) to a new location on disk to thereby optimize write performance. A write-anywhere file system may initially assume an optimal layout such that the data is substantially contiguously arranged on disks. The optimal disk layout results in efficient access operations, particularly for sequential read operations, directed to the disks. A particular example of a hybrid write-anywhere file system that is configured to operate on a filer is the SpinFS file system available from Network Appliance, Inc. of Sunnyvale, Calif. The exemplary SpinFS file system utilizes a write anywhere technique for user and directory data but writes metadata using a write in place technique. The SpinFS file system is implemented within a storage operating system of the filer as part of the overall protocol stack and associated disk storage.
Disk storage is typically implemented as one or more storage "volumes" that comprise physical storage disks, defining an overall logical arrangement of storage space. Currently available filer implementations can serve a large number of discrete volumes (150 or more, for example). Each volume is associated with its own file system and, for purposes hereof, volume and file system shall generally be used synonymously. The disks within a volume are typically organized as one or more groups of Redundant Array of Independent (or Inexpensive) Disks (RAID). RAID implementations enhance the reliability/integrity of data storage through the redundant writing of data "stripes" across a given number of physical disks in the RAID group, and the appropriate caching of parity information with respect to the striped data. As described herein, a volume typically comprises at least one data disk and one associated parity disk (or possibly data/parity partitions in a single disk) arranged according to a RAID 4, or equivalent high-reliability, implementation.
It is advantageous for the services and data provided by a filer or storage system to be available for access to the greatest degree possible. Accordingly, some storage system environments provide a plurality of storage systems (i.e. nodes) in a cluster where data access request processing may be distributed among the various nodes of the cluster. Executing on each node is a collection of management processes that provides management of configuration information (management data) "services" for the nodes. Each of these processes has an interface to a replicated database (RDB) that provides a persistent object store for the management data. In addition, the RDB replicates and synchronizes changes (updates) made to the management data by the management processes across all nodes to thereby provide services based on replicated data throughout the cluster. This data replication is the key to providing management from any node in the cluster (a single system image). To be clear, these are not "replicated services" in the normal use of the term (independent services without data sharing); rather, these are independent services which utilize replicated data as a means to enhance availability and autonomous capabilities within a cluster-wide single system image.
In cluster environments the concept of a quorum exists to ensure the correctness of the data replication algorithm, even in the event of a failure of one or more nodes of the cluster. By "quorum" it is meant generally a majority of the "healthy" (i.e. operational) nodes of the cluster. That is, a cluster is in quorum when a majority of the nodes are operational and have connectivity to other nodes; in addition, all nodes in the quorum have read/write (RW) access to the replicated management data (i.e. can participate in incremental updates to that data). By requiring that each update be synchronously propagated to a majority of the nodes (a quorum), the replication algorithm is guaranteed to retain all updates despite failures.
Broadly stated, a quorum of nodes is established by (1) ensuring connectivity among a majority of operational nodes; (2) synchronizing a baseline of management data among the nodes and (3) allowing a majority of operational nodes to participate in incremental changes to that baseline data. In clusters containing an even number of nodes, e.g., four nodes, one of the nodes is typically assigned an epsilon value to its quorum weight, thereby enabling quorum formation without a strict majority, e.g., (2+e)/4 is sufficient. In a two-node cluster, (1+e)/2 is sufficient (the single epsilon node). The epsilon assignment is an aspect of cluster configuration; all the nodes must agree on the epsilon assignment.
The value of requiring quorum for update in a cluster lies in the correctness and completeness of replication. This is illustrated by the "partition" problem. A partition occurs when connectivity is lost to one set of nodes as a result of a power failure or other failures to the cluster. The cluster may continue to operate with the remaining set of nodes; all nodes can read their management data, and if that set is sufficient to meet quorum requirements, all the member nodes can update the data. If connectivity is then lost within this set, and is subsequently restored to the other set of nodes, it is possible that the second set will have access only to the management data present before the first connectivity failure. In this case, it will not be able to form quorum, and will not be able to perform updates. If there were a sufficient number of nodes to establish quorum, then at least one of them would have seen the latest updates (as a participant in the prior quorum), and all the nodes in the second set would have the update capability. The quorum requirement guarantees that updates can only be made when the latest data is available.
A noted disadvantage of such quorum-based data replication systems is the inability to meet quorum requirements, thereby preventing any update (write) operations from occurring. This can occur as a result of communication failures, problems with health of individual node(s), or a combination of these problems. In clusters that utilize these services, the inability to form quorum may prevent an administrator from modifying the management data so as to reconfigure the cluster into an operational state.
This is particularly problematic in the case of a two node cluster, wherein the failure of either node forces the cluster out of quorum (1/2), as a single node is not a majority of the number of nodes in the cluster. A solution that enables the two node cluster to achieve a measure of failover is the use of the epsilon value. Here, one of the nodes in the cluster is assigned the epsilon value in addition to its own voting value. If the non-epsilon node fails, the surviving node may continue to operate in quorum as it has a (1+e)/2 quorum voting value (weight). However, a noted disadvantage of the use of an epsilon value is that failover may only occur in one direction, i.e. to the node with epsilon. That is, if the node with epsilon fails, the cluster will not failover to the node without epsilon as it would not be in quorum (1/2). Thus, the use of an epsilon factor in assigning quorum voting weights only partially alleviates the problem of two node clusters; i.e., only a unidirectional failover is possible when using an epsilon-assigned quorum voting system.

System and method for establishing bi-directional failover in a two node cluster


A bipolar junction transistor includes a dielectric layer formed on a predetermined region of a substrate, an opening formed in the dielectric layer and a portion of the substrate being exposed, a semiconductor layer formed on a sidewall and a bottom of the opening and on a portion of the dielectric layer outside the opening, a spacer formed on the semiconductor layer to define a self-aligned emitter region in the opening, an emitter conductivity layer being filled with the self-aligned emitter region and a PN junction being formed between the emitter conductivity layer and the semiconductor layer, and a salicide layer formed on the emitter conductivity layer and on the portion of the semiconductor layer extending outside the opening.

1. Field of the Invention
The present invention relates to a bipolar junction transistor (BJT) and its fabricating method, and more particularly, to a self-aligned BJT and a self-aligned method for producing the same.
2. Description of the Prior Art
A bipolar junction transistor utilizes two type of carriers, "electrons" and "hot holes", to transmit current. The BJT continues to be a basic circuit element in integrated circuits due to its high switching capability and current carrying capacity. However, the electrons/holes mobility of a silicon BJT, which has a silicon substrate, is lower and not suitable for being applied in high frequency devices. Therefore, the silicon BJT has been replaced with a GaAs BJT, which has a GaAs substrate, or a SiGe hetero-junction bipolar transistor (HBT) in recently semiconductor processes.
Please refer to FIG. 1 to FIG. 5, which are schematic diagrams illustrating a conventional method for forming a silicon BJT. As shown in FIG. 1, the silicon BJT is formed on a P-type single crystal silicon substrate 10 including a heavily doped N type (N+) region 12 and heavily doped P type (P+) regions 14 formed on the substrate 10. First, an N-epitaxial layer 16 is thermally grown on the substrate 10, which has a thickness of about 1.2 micrometers (μm). During formation of the epitaxial layer 16, dopants of the N+ region 12 and the P+ region 14 diffuse upward into the epitaxial layer 16. Then, a silicon dioxide layer 18 and a silicon nitride layer 20 are formed on the epitaxial layer 16, respectively. A photolithographic and etching process is performed to remove a portion of the silicon nitride layer 20, the silicon dioxide layer 18 and the epitaxial layer 16 to expose a portion of the epitaxial layer 16, thus forming a plurality of openings 22 in the silicon nitride layer 20, the silicon dioxide layer 18, and the epitaxial layer 16.
As shown in FIG. 2, a thermal growth process is performed to oxidize the exposed epitaxial layer 16 to an oxide layer 24, which fills in the opening 22, with a top surface of the oxide layer 24 being approximately equal to a top surface of silicon dioxide layer 18. After that, the remained silicon nitride layer 20 is removed. During thermal growth of the oxide layer 24, the dopants of the N+ region 12 and the P+ region 14 are diffused further upward to broaden the N+ region 12 and P+ region 14. Afterwards, a photoresist layer 26 is deposited on the oxide layer 24, and the photoresist layer 26 is exposed and developed to form an opening 27 in the photoresist layer 26. Then, suitable N-type dopants, such as phosphorus (P), are ion implanted through the opening 27 to form an N+ collector region 28 within the epitaxial layer 16 and beneath the oxide layer 24.
As shown in FIG. 3, the remnant photoresist layer 26 is removed and another patterned photoresist layer (not shown in FIG. 3) is formed on the oxide layer 24. A wet etching process or a reactive ion etching (RIE) process is performed to remove a portion of the oxide layer 24 above the epitaxial layer 16, thus forming an opening 30 in the oxide layer 24. Then, a P-polysilicon layer 32 and a silicon dioxide layer 34 are formed on the substrate 10, respectively. Typically, the polysilicon layer 32 has a thickness of about 8000 angstroms (Å), and the silicon dioxide layer 34 has a thickness of about 5000 to 6000 Å. A patterned photoresist layer (not shown in FIG. 3) is formed on the silicon oxide layer 34, and a photolithographic and etching process is performed to remove a portion of the silicon dioxide layer 34 and the polysilicon layer 32 to form an opening 36 in the silicon dioxide layer 34 and the polysilicon layer 32, and a portion of the epitaxial layer 16 is exposed.
As shown in FIG. 4, a silicon dioxide layer 38 is thermally grown on the substrate 10 that covers a bottom and a sidewall of the opening 36 uniformly. Typically, the silicon dioxide layer 38 has a thickness of between 0.2 to 0.4 μm. During formation of the silicon dioxide layer 38, P-type dopants of the polysilicon layer 32 diffuse downwards into the N-epitaxial layer 16 to form P-extrinsic base regions 40 within the epitaxial layer 16. Then, a directional RIE process is performed to remove a portion of the silicon dioxide layer 38 in the bottom of the opening 36 and on the oxide layer 24. Further, a relatively low-energy, high-dose ion implantation is performed to form an N shallow emitter region 42 within the epitaxial layer 16, which has a thickness of about 0.2 μm, by implanting the arsenic (As) ions through the opening 36 into the epitaxial layer 16. Similarly, a relatively high-energy, high-dose ion implantation is performed to form an N+ raised subcollector 44, which has a thickness of about 0.2 micrometers, by implanting phosphorus (P) ions through the opening 36 into the epitaxial layer 16. The energy and heat cycling conditions for the phosphorus implantation are selected such that the bottom of the raised subcollector 44 nominally submerges into the N+ region 12. And a relatively middle-energy, low-dose boron ion implantation is performed to form an intrinsic base region 46 beneath the shallow emitter region 42 and above the raised subcollector 44, by implanting the As ions through the opening 36 into the epitaxial layer 16.
Finally, as shown in FIG. 5, a photolithographic and etching process is performed to form two contact vias (not shown in FIG. 5) on the polysilicon layer 32 and the collector region 28. Then, a metal layer is filled in the contact vias and the opening 36 to form three metal contacts 50, 52, and 48, and the conventional BJT is completed.
As stated above, the conventional method for forming the BJT is very complicated. Although the intrinsic base region 46 and the emitter region 42 of the BJT are formed by the self-aligned method, the extrinsic base regions 40 are formed by the thermal diffusion process. So that the contact area between the intrinsic base region, the extrinsic base region and the collector region cannot be controlled precisely. Thus causing higher capacitance between the base region and the collector region and the conventional BJT is not suitable for being applied in high frequency devices. In addition, the interference of the PN junction of the BJT is clearer, the performance of the device is better. However while the SiGe HBT can function in high temperatures, the interference between the SiGe epitaxial layer and silicon of the SiGe HBT will generate a plurality of intersectional arrangements and thus destroy the its high speed characteristic. For this reason, the temperature for forming the SiGe epitaxial layer has to be controlled to be below 700° C. But the conventional BJT has to utilize the thermal diffusion process many times, and therefore the conventional method is not suitable for forming the HBT.

This patent is subject to a terminal disclaimer.

Bipolar junction transistor and fabricating method


A program synthesis system comprises a function decomposition unit for decomposing a function according to a predetermined specification so as to obtain detailed functions of the specification, a similarity decision unit for retrieving intermediates similar to the detailed specification detailed by the function decomposition unit, a design process fusion unit for fusing a plurality of design processes, the design process fusion unit including a matching decision unit for deciding matching between design processes having high similarities with respect to the intermediate decided by the similarity decision unit, an object synthesis unit for synthesizing an object on the basis of a new design process synthesized by the design process fusion unit, a design process intermediate knowledge base for storing intermediates from which intermediates similar to the specification detailed by the function decomposition unit are retrieved, and a design process conversion on knowledge base for storing a conversion knowledge for detailing the specification, a conversion knowledge for the intermediate, and a knowledge in a minimum unit for performing processing.

1. Field of the Invention
The present invention relates to a program synthesis system for generating a program by synthesizing an object described in an object-oriented language on the basis of a predetermined specification, e.g., a formal specification described in an algebraic specification description language.
2. Description of the Related Art
When an object described in an object-oriented language is generated on the basis of a given formal specification, the following methods are employed.
In one method, a given formal specification is detailed stepwise according to a predetermined procedure by positive intervention of man, and thereafter, an object is synthesized. In this method, however, since the program is generated by intervention of man, it is difficult to guarantee quality of the generated program. Furthermore, different programs may be generated depending on the degree or method of intervention of man. Therefore, it is difficult to generate a high-quality program unless the above-mentioned method is executed by a considerably skilled person.
A method of synthesizing an object by an automatic certification scheme has also been studied. However, the size of a program which can be generated is very small yet. Therefore, it is difficult to generate a program having a practical level size. As described above, it is difficult to synthesize a high-quality program having a practical level size. For the purpose of improving productivity of software, component conversion or re-utilization techniques of software have been proposed. However, the component conversion or re-utilization techniques of software suffer from the following problems, and requirements for high productivity cannot always be satisfied.
The conventional component conversion or re-utilization techniques of software suffer from the following problems. That is,
1) Since these techniques have no conversion knowledge for functionally decomposing given predetermined specifications, the specifications cannot be effectively functionally decomposed. PA1 2) No efficient retrieval means for retrieving components having similar functions has been established.
3) No procedure for partially correcting a retrieved component has been established.
As described above, it is very difficult to synthesize a program on the basis of a given predetermined specification while assuring both high productivity and high quality.
As the reference associated with the present invention, Zohar Manna and Richard Waldinger, "The Logical Basis for Computer Programming; Vol. 2 Deductive Systems", ADDISON-WESLEY PUBLISHING COMPANY (1990) is known.

Apparatus and methods for generating a program by synthesizing an object described in an object-oriented language


This method includes a step for the extraction of robot control program creation data from an animation program displaying an assembly sequence for the manufacturing of an assembled product with a plurality of parts, a step for the addition of predetermined robot control data to the robot control program creation data, and a step for the creation of a robot control program relating to the assembly operations of the assembled product using the robot control program creation data and the predetermined robot control data. A robot control program for manufacturing an assembled product with a plurality of parts can be easily generated.

Manual labor by operators is being increasingly replaced by the automated labor of robots for assembling a plurality of parts so as to manufacture an assembled product (product). In recent years, the automation of assembly operations by use of robots has increased with the goal of minimizing personnel expenses.
Incidentally, in order to assign a robot the task of assembling a plurality of parts so as to manufacture an assembled product, the robot must be taught the assembly operations in advance through the use of a teaching pendant or through offline teaching using a robot simulator, etc. (Patent Literature 1).

Robot control program generation method and apparatus


A method measures the positions of centers of curvature of optical surfaces of a multi-lens optical system. The spacings between the surfaces are measured along a reference axis using an interferometer. Subsequently the centers of curvature of the surfaces are measured using an optical angle-measuring device. In the course of the measurement of the position of the center of curvature of a surface situated within the optical system, the measured positions of the centers of curvature of the surfaces situated between this surface and the angle-measuring device and the previously measured spacings between the surfaces are taken into consideration computationally. In this way, a particularly high accuracy of measurement is achieved, because desired spacings do not have to be fallen back upon.

1. Field of the Invention
The invention relates to a process and to an apparatus for measuring the positions of centres of curvature of optical surfaces of a multi-lens optical system.
2. Description of the State of the Art
In the course of the manufacture of high-quality multi-lens optical systems the lenses have to be oriented with respect to one another with high accuracy. In order to be able to carry out such an orientation it is necessary to determine the positions of the optical surfaces metrologically. Even if during the adjustment of the lenses a check of the positioning accuracy is dispensed with, such measurements are regularly carried out at least within the scope of quality control.
A crucial geometrical quantity in connection with the surveying of multi-lens optical systems is constituted by the positions of the centres of curvature of the optical surfaces. Ideally the centres of curvature lie exactly on a common reference axis which, as a rule, should coincide with the axes of symmetry of the lens mounts receiving the lenses. In real optical systems, however, in consequence of tolerances of manufacturing and assembly the centres of curvature are randomly distributed around this reference axis. If the spacings of the centres of curvature from the reference axis are too great, the imaging properties of the optical system deteriorate in intolerable manner.
A process for measuring centres of curvature of optical surfaces of a multi-lens optical system is known from DE 10 2004 029 735 A1. In this process the positions of the centres of curvature of the individual optical surfaces are measured successively with the aid of an autocollimator. The first surface for which the position of the centre of curvature is surveyed is that surface which is situated nearest to the autocollimator. As soon as the position of the centre of curvature of this first surface has been determined, the following, second surface is surveyed. However, the first surface influences the surveying of the second surface. For this reason, the optical effect of the first surface has to be taken into consideration computationally in the determination of the position of the centre of curvature of the second surface. In the consideration of the optical effect of the first surface the design data of the first surface are fallen back upon, and in particular the desired radius of curvature and the desired spacing with respect to the second surface (i.e. the centre thickness of the first lens). In addition, the previously measured position of the centre of curvature of the first surface is taken into consideration computationally.
The manner of proceeding is the same for all further surfaces. In the course of the computational evaluation the measured positions of the centres of curvature of all optical surfaces situated ahead, and otherwise the design data, are consequently always taken into consideration.

Measurement of the positions of centres of curvature of optical surfaces of a multi-lens optical system


A DMOST driver circuit responds to the current flowing in the DMOST and the voltage appearing across it. The current and voltage are multiplied together in a g.sub.m amplifier which is coupled to drive a first input of a diff-amp. The diff-amp has its second input coupled to a source of reference potential. The diff-amp output is coupled to the DMOST gate to create a stabilizing negative feedback loop. The first diff-amp input is also coupled to a reference potential related threshold voltage so that the drive to the DMOST will be controlled by the DMOST power dissipation multiplied by a predetermined constant which is chosen to provide a safe dissipation level.

The invention relates to so-called diffused metal oxide semiconductor transistor (DMOST) drivers. Such drivers are disclosed in U.S. Pat. No. 4,888,505, Ser. No. 189,442, which was filed by Timothy J. Skovmand on Mar. 2, 1988. It is titled VOLTAGE MULTIPLIER COMPATIBLE WITH A SELF-ISOLATED C/DMOS PROCESS. A DMOST can drive a load so that the load voltage closely approaches the supply. In order to do this the gate must be overdriven to a significant extent and this necessitates a source of potential that is higher than the operating supply. In this application the boosted potential is achieved by means of a voltage multiplying rectifier driven by the circuit clock. A number of other versions of such "boost" circuits are well known in the art. The above patent issued on Dec. 19, 1989, as U.S. Pat. No. 4,888,505, is assigned to the assignee of the present application and its teaching is incorporated herein by reference.
Such DMOST devices can be constructed to be junction isolated using a complementary semiconductor metal oxide semiconductor (CMOS) process that can also include more conventional bipolar elements normally found in the well-known monolithic silicon planar epitaxial PN junction isolated IC devices. A power DMOST can be created from a large number of small parallel-connected elements. The operating voltage can be kept reasonably high and the current conducting capability can be made substantial. For example, the on resistance of a power DMOST can be made as low as a fraction of an ohm.
Typically, the prior art DMOST IC devices were shut down when the chip temperature exceeds some predetermined threshold. It would be desirable to electronically limit the power dissipation without having to wait for the chip to heat.


The invention pertains to certain genetic variants on Chr5p12 and Chr10q26 as susceptibility variants of breast cancer. Methods of disease management, including diagnosing increased and/or decreased susceptibility to breast cancer, methods of predicting response to therapy and methods of predicting prognosis using such variants are described. The invention further relates to kits useful in the methods of the invention.

Breast cancer is by far the most common cancer in women worldwide. Current global incidence is in excess of 1,151,000 new cases diagnosed each year [Parkin, et al., (2005), CA Cancer) Clin, 55, 74-108]. Breast cancer incidence is highest in developed countries, particularly amongst populations of Northern European ethnic origin, and is increasing. In the United States the annual age-standardized incidence rate is approximately 125 cases per 100,000 population, more than three times the world average. Rates in Northern European countries are similarly high. In the year 2008 it is estimated that 184,450 new cases of invasive breast cancer will be diagnosed in the U.S.A. and 40,930 people will die from the disease [Jemal, et al., (2008), CA Cancer J Clin, 58, 71-96]. To this figure must be added a further 67,770 ductal and lobular carcinoma in-situ diagnoses expected in 2008. From an individual perspective, the lifetime probability of developing breast cancer is 12.3% in U.S. women (i.e., 1 in 8 women will develop breast cancer during their lives). As with most cancers, early detection and appropriate treatment are important factors. Overall, the 5-year survival rate for breast cancer is 89%. However, in individuals presenting with regionally invasive or metastatic disease, the rate declines to 84% and 27%, respectively [Jemal, et al., (2008), CA Cancer J Clin, 58, 71-96].
Increasingly, emphasis is falling on the identification individuals who are at high risk for primary or recurrent breast cancer. Such individuals can be managed by more intensive screening, preventative chemotherapies, hormonal therapies and, in cases of individuals at extremely high risk, prophylactic surgery. Mass screening programs constitute a huge economic burden on health services, while preventative therapies have associated risks and quality of life consequences.
Genetic Predisposition to Breast Cancer
The two primary classes of known risk factors for breast cancer are endocrine factors and genetics. Regarding the latter, approximately 12% of breast cancer patients have one or more first degree relatives with breast cancer [(2001), Lancet, 358, 1389-99]. The well known, dominant breast cancer predisposition genes BRCA1 and BRCA2 confer greatly increased breast cancer risk to carriers, with lifetime penetrance estimates ranging from 40-80%. The presence of BRCA1 and BRCA2 mutations can account for the majority of families with 6 or more cases of breast cancer and for a large proportion of families comprising breast and ovarian or male breast cancer. However such families are very rare indeed. BRCA1 and BRCA2 mutations are found much less frequently in families with fewer cases or in families characterized by breast cancer cases only. Together, mutations in BRCA1 and BRCA2 can account for 15-20% of the risk for familial breast cancer. In non-founder populations, if all common BRCA mutations could be detected, between 2-3% of incident breast cancer patients would be expected to harbor a mutation [Gorski, et al., (2005), Breast Cancer Res Treat, 92, 19-24; (2000), Br J Cancer, 83, 1301-8]. This low "chance to find" statistic precludes the responsible use of BRCA mutation testing outside families with an obvious hereditary predisposition (Anon[(2003), J Clin Oncol, 21, 2397-406]). Rare, high penetrance mutations are known to occur in the TP53 and PTEN genes, however, these together account for no more than 5% of the total genetic risk for breast cancer [Easton, (1999), Breast Cancer Res, 1, 14-7]. Linkage studies have been largely unsuccessful in identifying any more, widespread mutations conferring high risk for breast cancer [Smith, et al., (2006), Genes Chromosomes Cancer, 45, 646-55].
Recent epidemiological studies have indicated that the majority of breast cancer cases arise in a predisposed, susceptible minority of the population [Antoniou, et al., (2002), Br Cancer, 86, 76-83; Pharoah, et al., (2002), Nat Genet, 31, 33-6]. Data from twin studies and observations of the constant, high incidence of cancer in the contralateral breast of patients surviving primary breast cancer indicate that a substantial portion of the uncharacterized risk for breast cancer is related to endogenous factors, most probably genetic [Lichtenstein, et al., (2000), N Engl J Med, 343, 78-85; Peto and Mack, (2000), Nat Genet, 26, 411-4]. Knowledge of the genetic factors that underpin this widespread risk is very limited. Segregation analyses predict that the uncharacterized genetic risk for breast cancer is most likely to be polygenic in nature, with risk alleles that confer low to moderate risk and which may interact with each other and with hormonal risk factors. Nevertheless, these studies predict as much as 40-fold differences in relative risk between the highest and lowest quintiles of a distribution that could be defined by genetic profiling that captures these low to moderate risk alleles [Antoniou, et al., (2002), Br Cancer, 86, 76-83; Pharoah, et al., (2002), Nat Genet, 31, 33-6]. 88% of all breast cancer cases are expected to arise amongst a predisposed 50% of the population and the 12% of the population at highest risk accounts for 50% of all breast cancer cases [Pharoah, et al., (2002), Nat Genet, 31, 33-6; Pharoah, (2003), Recent Results Cancer Res, 163, 7-18; discussion 264-6]. Much focus is therefore directed towards the identification of such genetically predisposed individuals and developing personalized medical management strategies for them.
We and others have shown that there is a significant familial risk of breast cancer in Iceland which extends to at least 5th degree relatives [Amundadottir, et al., (2004), PLoS Med, 1, e65; Tulinius, et al., (2002), J Med Genet, 39, 457-62]. The contribution of BRCA1 mutations to familial risk in Iceland is thought to be minimal [Arason, et al., (1998), J Med Genet, 35, 446-9; Bergthorsson, et al., (1998), Hum Mutat, Suppl 1, S195-7]. A single founder mutation in the BRCA2 gene (999-del5) is present at a carrier frequency of 0.6-0.8% in the general Icelandic population and 7.7-8.6% in female breast cancer patients [Thorlacius, et al., (1997), Am J Hum Genet, 60, 1079-84; Gudmundsson, et al., (1996), Am J Hum Genet, 58, 749-56]. This single mutation is estimated to account for approximately 40% of the inherited breast cancer risk to first through third degree relatives [Tulinius, et al., (2002), J Med Genet, 39, 457-62]. Although this estimate is higher than the 15-25% of familial risk attributed to all BRCA 1 and 2 mutations combined in non-founder populations, there is still some 60% of Icelandic familial breast cancer risk to be explained. First degree relatives of patients who test negative for BRCA2 999del5 remain at a 1.72 fold the population risk for breast cancer (95% CI 1.49-1.96) [Tulinius, et al., (2002), J Med Genet, 39, 457-62].
Genetic risk is conferred by subtle differences in the genome among individuals within a population. Genes differ between individuals most frequently due to single nucleotide polymorphisms (SNP), although other variations are also important. SNP are located on average every 1000 base pairs in the human genome. Accordingly, a typical human gene containing 250,000 base pairs may contain 250 different SNP. Only a minor number of SNPs are located in exons and alter the amino acid sequence of the protein encoded by the gene. Most SNPs may have little or no effect on gene function, while others may alter transcription, splicing, translation, or stability of the mRNA encoded by the gene. Additional genetic polymorphism in the human genome is caused by insertion, deletion, translocation, or inversion of either short or long stretches of DNA. Genetic polymorphisms conferring disease risk may therefore directly alter the amino acid sequence of proteins, may increase the amount of protein produced from the gene, or may decrease the amount of protein produced by the gene.
As genetic polymorphisms conferring risk of common disease are uncovered, genetic testing for such risk factors becomes important for clinical medicine. Recent examples are apolipoprotein E testing to identify genetic carriers of the apoE4 polymorphism in dementia patients for the differential diagnosis of Alzheimer's disease, and of Factor V Leiden testing for predisposition to deep venous thrombosis. More importantly, in the treatment of cancer, diagnosis of genetic variants in tumor cells is used for the selection of the most appropriate treatment regime for the individual patient. In breast cancer, genetic variation in estrogen receptor expression or heregulin type 2 (Her2) receptor tyrosine kinase expression determine if anti-estrogenic drugs (tamoxifen) or anti-Her2 antibody (Herceptin) will be incorporated into the treatment plan. In chronic myeloid leukemia (CML) diagnosis of the Philadelphia chromosome genetic translocation fusing the genes encoding the Bcr and Abl receptor tyrosine kinases indicates that Gleevec (STI571), a specific inhibitor of the Bcr-Abl kinase should be used for treatment of the cancer. For CML patients with such a genetic alteration, inhibition of the Bcr-Abl kinase leads to rapid elimination of the tumor cells and remission from leukemia.
Understanding of the genetic factors contributing to the residual genetic risk for breast cancer is limited. Variants in two genes have been rigorously confirmed as low penetrance breast cancer risk genes; CHEK2 and ATM [Renwick, et al., (2006), Nat Genet, 38, 873-5; (2004), Am J Hum Genet, 74, 1175-82]. Furthermore, a recent report establishes a link between variants on chromosomes 2q35 and 16q12 and increased risk of estrogen receptor positive breast cancer (Simon, S N. et al. Nat Genet. 39:865-9 (2007)). Many other genes have been implicated however their contribution to breast cancer risk has not been confirmed in analyses employing very large sample sets [Breast Cancer Association, (2006), J Natl Cancer Inst, 98, 1382-96].
No universally successful method for the prevention or treatment of breast cancer is currently available. Management of breast cancer currently relies on a combination of primary prevention, early diagnosis, appropriate treatments and secondary prevention. There are clear clinical imperatives for integrating genetic testing into all aspects of these management areas. Identification of cancer susceptibility genes may also reveal key molecular pathways that may be manipulated (e.g., using small or large molecular weight drugs) and may lead to more effective treatments.

Genetic variants on chr 5p12 and 10q26 as markers for use in breast cancer risk assessment, diagnosis, prognosis and treatment


A system and method are provided for forming expansion joints within artificial ground cover. An elongated expansion joint support is coupled with a length of expansion joint material. A lower end portion of the expansion joint support is shaped to engage a ground surface. The two structures may be coupled with one another in different positions to vary the resulting expansion joint height. The lower end portion of the expansion joint support may be shaped to have a ground engagement wall and to receive ground engagement spikes. No component parts need be removed from the system after the application of artificial ground cover adjacent thereto, thus permitting simultaneous application of ground cover on both sides of the expansion joint.

Expansion joints are commonly found in various forms of artificial ground cover, including concrete forms such as sidewalks, driveways and other slab structures. Expansion joints may also be used in other forms of ground cover that may be comprised of masonry, various metals, and other such materials that are prone to expansion and contraction throughout seasonal temperature changes. The expansion joints help to cushion the effect of expansion and contraction, thus preventing cracking, heaving and other such ill effects.
Expansion joints are typically formed from durable, resiliently deformable materials. Fiber-board is an example of one common expansion joint material which is formed from natural and man-made fibers that are bonded together using asphalt or other known bonding agents. Other expansion joint materials include closed-cell polyfoam, rubber, cork, cross-linked ethylene vinyl acetate and closed-cell neoprene. The expansion joint material selected may depend upon various factors presented in each particular application. Some factors may include cost, climate and type of material used in the formation of the artificial ground cover. Regardless of their construction, expansion joint materials are typically formed to have a thickness that ranges between ¼ of an inch to 1 inch. Common widths range from 3 inches to 12 inches and their lengths are commonly found in four to ten foot sheets.
Commonly, expansion joint material is positioned adjacent an existing section of ground cover, such as concrete, prior to applying new ground cover immediately adjacent thereto. In instances where expansion joint material is to be positioned in an area where no existing ground cover exists, contractors typically position ½″×4″ or 1″×4″ backboard behind the expansion joint material and stake the backboard in place. The new ground cover is then applied over the ground surface adjacent the expansion joint material. Once the ground cover has sufficiently cured, the backboard and stakes are removed and the next section of ground cover may be applied to the ground surface, adjacent the opposite side of the expansion material. This method of forming an expansion joint has several shortcomings. First, the ground cover is applied to the ground surface in multiple stages over a period of two or more days. The increased number of trips to and from a job-site become time consuming and expensive over time. Secondly, as depicted in FIG. 2, expansion joint material is frequently provided in widths that are insufficient to span the full thickness of the ground cover being applied. Accordingly, as the ground cover is applied to the ground surface adjacent the expansion joint material, the ground cover will not be segregated from adjacent, existing ground cover. This results in the two sections of ground cover being abutted immediately adjacent one another and defeats the purpose of installing an expansion joint at this location. In other instances, also depicted in FIG. 2, the ground surface is improperly prepared, leaving depressions or other recesses at the location where an expansion joint is required. In these instances, expansion joint material that would otherwise be of sufficient width for the thickness of ground cover being applied will be insufficient to span the distance from the bottom of the depression to the surface of the ground cover being applied. The result will produce a single section of ground cover without the appropriate expansion joint structure.
Accordingly, what is needed is a novel system and method for forming expansion joints that enables a user to prepare an entire site for a single pour or application of artificial ground cover. Such a novel system and method should also enable a user to vary the vertical positioning of expansion joint material in a given location while effectively segregating adjacent sections of ground cover.

System and method of forming expansion joints


A rotary tray having a plurality of disk mounting sections is pivotally supported by a central shaft arranged on a tray support face of a casing, a rim protruding from a lower face of the rotary tray is movably set on a sliding face block arranged in an outer circumferential section of the tray support face, and disk mounted on a desired disk mounting section is opposed to an optical pickup when the rotary tray is intermittently rotated by a predetermined angle, and the sliding face block is engaged in a space formed between a recess step circumferential face, which is formed along an inner edge of an outer circumferential section of the tray support face, and a support frame integrally formed in the outer circumferential section and being opposed to the recess step circumferential face.

1. Field of the Invention
The present invention relates to a disk changer type disk player such as DVD (Digital Versatile Disc) changer set which is compact and capable of rotating smoothly and quietly.
2. Description of the Related Art
An example of a disk changer type disk player is disclosed in Japanese Unexamined Utility Model Publication No. 4-58842. The conventional disk changer type disk player is explained as follows referring to FIGS. 7 and 8. There is provided a rotary tray 1 having a plurality of disk mounting sections 1a. This rotary tray 1 is pivotally supported by a central shaft 4 arranged on a tray support face 3 of a casing 2. A rim 1b protruding from a lower face of the rotary tray 1 is movably set on a plurality of guide rollers 5 that are arranged in the outer circumferential section 3a of the tray support face 3 at the angular interval of 120xc2x0.
As shown in FIG. 8, each guide roller 5 is inserted into a recess 6 formed in the outer circumferential section 3a of the tray support face 3. The support shafts 5a protruding from both end faces of the guide roller 5 are respectively pivotally inserted into a shaft hole 7 and a long groove 8 formed on an inner face of the recess 6. An outer circumferential face of the guide roller 5 is covered with a rubber layer, the frictional coefficient of which is high. When the rotary tray 1 is rotated in the direction of arrow xe2x80x9caxe2x80x9d, each guide roller 5 is rotated via the rim 1b, so that the rotary tray 1 can be smoothly rotated.
As shown in FIG. 8, there is provided a drive mechanism 11 including: an swing arm 11a, one end of which is pivotally supported by a support shaft 9, the other end of which is provided with a cam follower 10; and a rotary cam 11b, a cam groove 12 on the outer circumferential face of which is engaged with the cam follower 10. A spindle motor 13 is fixed to the swing arm 11a, and a turn table 14 is attached to a drive shaft 13a of the spindle motor 13. An optical pickup 15 is movably arranged on the swing arm 11a. A chuck arm 17 supports a damper 16 being opposed to the turn table 14 so that the damper 16 can be moved upward and downward in a predetermined range. A forward end of the chuck arm 17 is connected with a central portion of the casing 2 via the central shaft 4, and a rear end of the chuck arm 17 is connected with a side wall of the casing 2.
As shown in FIG. 8, in the above structure, when the rotary cam 11b is rotated so that the swing arm 11a is moved upward via the cam groove 12 and the cam follower 10, disk D is chucked by the turn table 14 and the damper 16, and moved to the rotary tray 1 side. When the spindle motor 13 is driven, the turn table 14 is rotated, and the optical pickup 15 is moved in the radial direction of disk D. Due to the foregoing, information recorded on disk D can be read out and played back by the optical pickup 15.
In the above structure, the diameter of the guide roller 5 for supporting the rotary tray 1 is, for example, about 8 mm. That is, the diameter of the guide roller 5 is relatively large so that the guide roller 5 is voluminous. Therefore, it is difficult to make the casing 2 compact, and further the position at which the guide roller 5 is arranged is restricted and the number of the guide rollers 5 is also restricted. (In this example, three guide rollers are provided.) As a result, the rotary tray 1 tends to be supported unstably.
In some cases, the rotary tray 1 is deformed by residual strain generated in the process of forming, and errors tend to be caused in levelness of the lower edge of the rim 1b. Due to the foregoing, contact pressure of the rim 1b with each guide roller 5 can not be kept uniform, so that it becomes difficult to rotate the rotary tray 1 at a constant speed. Accordingly, there is a possibility that the optical pickup 15 can not correctly read out information from the disk.
Further, when the guide roller 5 is rotated, irregular slippage is caused at the contact point of the guide roller 5 with the rim 1b and also at the contact point of the support shaft 5a of the guide roller 5 with the shaft hole 7 and also at the contact point of the guide roller 5 with the long groove 8, that is, irregular slippage is caused at the three contact points. When slippage is caused as described above, a relatively high intensity of noise is generated, which makes a user uncomfortable.
It is an object of the present invention to provide a disk changer type disk player which is compact and capable of rotating smoothly and quietly.
In order to accomplish the above object, the present invention according to a first aspect provides a disk changer type disk player including: a casing having a tray support face; a recess step circumferential face formed along an inner edge of an outer circumferential section of the tray support face; a plurality of support frames arranged in the outer circumferential section at regular intervals in the circumferential direction, each support frame having a substantially C-shaped frame body integrally formed in the outer circumferential section and being opposed to the recess step circumferential face and a pair of substantially L-shaped engaging pieces integrally protruding from both ends of the frame body; a central shaft disposed on the tray support face; a rotary tray having a plurality of disk mounting sections, the rotary tray being rotatably supported by the central shaft; a rim protruding from a lower face of the rotary tray; a plurality of sliding face blocks, each sliding face block is engaged in a space formed between the recess step circumferential face and the support frame; and an optical pickup, wherein a disk mounted on the disk mounting section is opposed to the optical pickup when the rotary tray is intermittently rotated by a predetermined angle, wherein the sliding face blocks are made of fluororesin, the frictional coefficient of which is low, and wherein the rim is in slidably contact with the sliding face blocks.
According to the above structure, each sliding face block is supported by the C-shaped frame body of the support frame and the recess step circumferential face so that the sliding face block can not be moved in the horizontal direction, and at the same time each sliding face block is supported by a pair of L-shaped engaging pieces integrally protruded from both end portions of the frame body so that the each sliding face block can not rise up. Therefore, each sliding face block can be positively fixed at a predetermined position on the outer circumferential section on the tray support face.
Height of the sliding face block to support the rotary tray is very small, that is, the sliding face block is not voluminous. Therefore, the sliding face block can not be a cause to hinder the reduction in the size of the casing. Therefore, it is possible to arbitrarily determine the positions at which the sliding face blocks are arranged and it is also possible to arbitrarily determine the number of the sliding face blocks, so that the rotary tray can be stably supported.
Further, even when the rotary tray is deformed by residual strain generated in the process of forming and errors are caused in the levelness of the lower edge of the rim, since the weight of the rotary tray is supported by a large number of sliding face blocks, it is possible to keep the contact pressure of each sliding face block with the rim to be substantially constant so that the rotary tray can be stably rotated. Due to the foregoing, the optical pickup can accurately readout information from the disk.
Further, when the rotary tray is rotated, slippage is caused only at one contact point of the rim with the sliding face block. Furthermore, the sliding face block is made of material, the slipping sound of which is very small. Therefore, compared with the conventional rotary tray, an intensity of the sound is very low, and the rotary tray supported by each sliding face block can be stably, quietly rotated over a long period of time.
The present invention according to a second aspect provides a disk changer type disk player including: a casing having a tray support face; a central shaft disposed on the tray support face; a rotary tray having a plurality of disk mounting sections, the rotary tray being rotatably supported by the central shaft; a rim protruding from a lower face of the rotary tray; a plurality of sliding face blocks arranged in an outer circumferential section of the tray support face at regular intervals in the circumferential direction; and an optical pickup, wherein the sliding face blocks are made of fluororesin, the frictional coefficient of which is low, and wherein the rim is in slidably contact with the sliding face blocks.
According to the above structure, height of the sliding face block to support the rotary tray is very small, that is, the sliding face block is not voluminous. Therefore, the sliding face block can not be a cause to hinder the reduction in the size of the casing. Therefore, it is possible to arbitrarily determine the positions at which the sliding face blocks are arranged and it is also possible to arbitrarily determine the number of the sliding face blocks, so that the rotary tray can be stably supported.
Further, even when the rotary tray is deformed by residual strain generated in the process of forming and errors are caused in the levelness of the lower edge of the rim, since the weight of the rotary tray is supported by a large number of sliding face blocks, it is possible to keep the contact pressure of each sliding face block with the rim to be substantially constant so that the rotary tray can be stably rotated. Due to the foregoing, the optical pickup can accurately read out information from a disk.
Further, when the rotary tray is rotated, slippage is caused only at one contact point of the rim with the sliding face block. Furthermore, the sliding face block is made of material, the slipping sound of which is very small. Therefore, compared with the conventional rotary tray, an intensity of the sound is very low.
According to a third aspect of the invention, each sliding face block is engaged in a space formed between a recess step circumferential face, which is formed along an inner edge of an outer circumferential section of the tray support face, and a support frame integrally formed in the outer circumferential section and being opposed to the recess step circumferential face.
According to the above structure, only when each sliding face block is engaged in a space formed between the recess step circumferential face on the tray support face and the support frame opposed to it, the sliding face block can be fixed at a predetermined position.
According to a fourth aspect of the invention, the support frame includes a substantially C-shaped frame body, which is integrally formed in the outer circumferential section of the tray support face, and also includes a pair of substantially L-shaped engaging pieces integrally protruding from both end portions of the frame body, and each sliding face block is engaged in a space formed among the frame body, both the engaging pieces and the recess step section circumferential face.
According to the above structure, each sliding face block is supported by the C-shaped frame body of the support frame and the recess step circumferential face so that the sliding face block can not be moved in the horizontal direction, and at the same time each sliding face block is supported by a pair of L-shaped engaging pieces integrally protruded from both end portions of the frame body so that the each sliding face block can not rise up. Therefore, each sliding face block can be positively fixed at a predetermined position on the outer circumferential face on the tray support face.
According to the fifth aspect of the invention, each sliding face block is made of fluororesin.
According to the above structure, each sliding face block is made of fluororesin, the frictional coefficient of which is low. Therefore, the rotary tray supported by each sliding face block can be stably, quietly rotated over a long period of time.


The invention provides compounds of the formula (I) having ROCK kinase and/or protein kinase p70S6K inhibiting activity: wherein A is a saturated hydrocarbon linker group containing from 1 to 7 carbon atoms, the linker group having a maximum chain length of 5 atoms extending between R1 and NR2R3 and a maximum chain length of 4 atoms extending between E and NR2R3, wherein one of the carbon atoms in the linker group may optionally be replaced by an oxygen or nitrogen atom; and wherein the carbon atoms of the linker group A may optionally bear one or more substituents selected from oxo, fluorine and hydroxy, provided that the hydroxy group when present is not located at a carbon atom α with respect to the NR2R3 group and provided that the oxo group when present is located at a carbon atom α with respect to the NR2R3 group; E is a monocyclic or bicyclic carbocyclic or heterocyclic group; R1 is an aryl or heteroaryl group; and R2, R3, R4 and R5 are as defined in the claims.

Protein Kinases
Protein kinases constitute a large family of structurally related enzymes that are responsible for the control of a wide variety of signal transduction processes within the cell (Hardie, G. and Hanks, S. (1995) The Protein Kinase Facts Book, I and II, Academic Press, San Diego, Calif.). The kinases may be categorized into families by the substrates they phosphorylate (e.g., protein-tyrosine, protein-serine/threonine, lipids, etc.). Sequence motifs have been identified that generally correspond to each of these kinase families (e.g., Hanks, S. K., Hunter, T., FASEB J., 9:576-596 (1995); Knighton, et al., Science, 253:407-414 (1991); Hiles, et al., Cell, 70:419-429 (1992); Kunz, et al., Cell, 73:585-596 (1993); Garcia-Bustos, et al., EMBO J., 13:2352-2361 (1994)).
Protein kinases may be characterized by their regulation mechanisms. These mechanisms include, for example, autophosphorylation, transphosphorylation by other kinases, protein-protein interactions, protein-lipid interactions, and protein-polynucleotide interactions. An individual protein kinase may be regulated by more than one mechanism.
Kinases regulate many different cell processes including, but not limited to, proliferation, differentiation, apoptosis, motility, transcription, translation and other signalling processes, by adding phosphate groups to target proteins. These phosphorylation events act as molecular on/off switches that can modulate or regulate the target protein biological function. Phosphorylation of target proteins occurs in response to a variety of extracellular signals (hormones, neurotransmitters, growth and differentiation factors, etc.), cell cycle events, environmental or nutritional stresses, etc. The appropriate protein kinase functions in signalling pathways to activate or inactivate (either directly or indirectly), for example, a metabolic enzyme, regulatory protein, receptor, cytoskeletal protein, ion channel or pump, or transcription factor. Uncontrolled signalling due to defective control of protein phosphorylation has been implicated in a number of diseases, including, for example, inflammation, cancer, allergy/asthma, diseases and conditions of the immune system, diseases and conditions of the central nervous system, and angiogenesis.
Apoptosis or programmed cell death is an important physiological process which removes cells no longer required by an organism. The process is important in early embryonic growth and development allowing the non-necrotic controlled breakdown, removal and recovery of cellular components. The removal of cells by apoptosis is also important in the maintenance of chromosomal and genomic integrity of growing cell populations. There are several known checkpoints in the cell growth cycle at which DNA damage and genomic integrity are carefully monitored. The response to the detection of anomalies at such checkpoints is to arrest the growth of such cells and initiate repair processes. If the damage or anomalies cannot be repaired then apoptosis is initiated by the damaged cell in order to prevent the propagation of faults and errors. Cancerous cells consistently contain numerous mutations, errors or rearrangements in their chromosomal DNA. It is widely believed that this occurs in part because the majority of tumours have a defect in one or more of the processes responsible for initiation of the apoptotic process. Normal control mechanisms cannot kill the cancerous cells and the chromosomal or DNA coding errors continue to be propagated. As a consequence restoring these pro-apoptotic signals or suppressing unregulated survival signals is an attractive means of treating cancer.
The signal transduction pathway containing the enzymes phosphatidylinositol 3-kinase (PI3K), PDK1 and PKB amongst others, has long been known to mediate increased resistance to apoptosis or survival responses in many cells. There is a substantial amount of data to indicate that this pathway is an important survival pathway used by many growth factors to suppress apoptosis. The enzyme PI3K is activated by a range of growth and survival factors e.g. EGF, PDGF and through the generation of polyphosphatidylinositols, initiates the activation of the downstream signalling events including the activity of the kinases PDK1 and protein kinase B (PKB) also known as Akt. This is also true in host tissues, e.g. vascular endothelial cells as well as neoplasias.
Protein Kinase p70S6K
The 70 kDa ribosomal protein kinase p70S6K (also known as SK6, p70/p85 S6 kinase, p70/p85 ribosomal S6 kinase and pp70s6k) is a member of the AGC subfamily of protein kinases. p70S6K is a serine-threonine kinase that is a component of the phosphatidylinositol 3 kinase (PI3K)/AKT pathway. p70S6K is downstream of PI3K, and activation occurs through phosphorylation at a number of sites in response to numerous mitogens, hormones and growth factors. This response may be under the control of mTOR since rapamycin acts to inhibit p70S6K activity and blocks protein synthesis, specifically as a result of a down-regulation of translation of these mRNA's encoding ribosomal proteins. p70S6K is also regulated by PI3K and its downstream target AKT. Wortmannin and rapamycin cause a decrease in p70S6K phosphorylation at sites dependent of the PI3K pathway. Mutant p70S6K is inhibited by wortmannin but not by rapamycin suggesting that the PI3K pathway can exhibit effects on p70S6K independent of the regulation of mTOR activity.
The enzyme p70S6K modulates protein synthesis by phosphorylation of the S6 ribosomal protein. S6 phosphorylation correlates with increased translation of mRNAs encoding components of the translational apparatus, including ribosomal proteins and translational elongation factors whose increased expression is essential for cell growth and proliferation. These mRNAs contain an oligopyrimidime tract at their 5′ transcriptional start (termed 5′TOP), which has been shown to be essential for their regulation at the translational level.
In addition to its involvement in translation, p70S6K activation has also been implicated in cell cycle control, neuronal cell differentiation, regulation of cell motility and a cellular response that is important in tumor metastases, the immune response and tissue repair. Antibodies to p70S6K abolish the mitogenic response driven entry of rat fibroblasts into S phase, indication that p70S6K function is essential for the progression from G1 to S phase in the cell cycle. Furthermore inhibition of cell cycle proliferation at the G1 to S phase of the cell cycle by rapamycin has been identified as a consequence of inhibition of the production of the hyperphosphorylated, activated form of p70S6K.
The tumor suppressor LKB1 activates AMPK which phosphorylates the TSC1/2 complex in the mTOR/p70S6K pathway, therefore feeds into p70S6K through a PKB independent pathway. Mutations in LKB1 cause Peutz-Jeghers syndrome (PJS), where patients with PJS are 15 times more likely to develop cancer than the general population. In addition, ⅓ of lung adenocarcinomas harbor inactivating LKB1 mutations.
A role for p70S6K in tumor cell proliferation and protection of cells from apoptosis is supported based on its participation in growth factor receptor signal transduction, overexpression and activation in tumor tissues. For example, Northern and Western analyses revealed that amplification of the PS6K gene was accompanied by corresponding increases in mRNA and protein expression, respectively (Cancer Res. (1999) 59: 1408-11—Localization of PS6K to Chromosomal Region 17q23 and Determination of Its Amplification in Breast Cancer).
Chromosome 17q23 is amplified in up to 20% of primary breast tumors, in 87% of breast tumors containing BRCA2 mutations and in 50% of tumors containing BRCA1 mutations, as well as other cancer types such as pancreatic, bladder and neuroblastoma (see M Barlund, O Monni, J Kononen, R Cornelison, J Torhorst, G Sauter, O-P Kallioniemi and Kallioniemi A, Cancer Res., 2000, 60:5340-5346). It has been shown that 17q23 amplifications in breast cancer involve the PAT1, RAD51C, PS6K, and SIGMA1B genes (Cancer Res. (2000): 60, pp. 5371-5375).
The p70S6K gene has been identified as a target of amplification and overexpression in this region, and statistically significant association between amplification and poor prognosis has been observed.
Clinical inhibition of p70S6K activation was observed in renal carcinoma patients treated with CCI-779 (rapamycin ester), an inhibitor of the upstream kinase mTOR. A significant linear association between disease progression and inhibition of p70S6K activity was reported.
p70S6K has been implicated in metabolic diseases and disorders. It was reported that the absence of p70S6 protects against age- and diet-induced obesity while enhancing insulin sensitivity. A role for p70S6K in metabolic diseases and disorders such as obesity, diabetes, metabolic syndrome, insulin resistance, hyperglycemia, hyperaminoacidemia, and hyperlipidemia is supported based upon the findings.
ROCK Kinases
The ROCK kinase family comprises two known members: ROCK1 and ROCK2:                ROCK1. Synonyms: Rho-associated protein kinase 1; p160 ROCK; P160 ROK; p160 ROCK-1, Rho-associated, coiled-coil containing protein kinase 1; Rho kinase 1; ROK beta.        ROCK2. Synonyms: Rho-associated protein kinase 2; p164 ROCK; p164 ROK; p164 ROCK-2; Rho-associated, coiled-coil containing protein kinase 2, Rho kinase 2; ROK alpha.
The process of metastasis involves a restructuring of the cytoskeleton as well as cell-cell and cell-matrix adhesions allowing cells to break away from the tumor mass, invade local tissue, and ultimately spread throughout the body. These effects on cell morphology and adhesion are regulated by members of the Rho GTPase family.
Activated RhoA is capable of interacting with several effector proteins including the ROCK kinases ROCK1 and ROCK2. ROCK1 and ROCK2 can be activated by the RhoA-GTP complex via physical association. Activated ROCKs phosphorylate a number of substrates and play important roles in pivotal cellular functions. The substrates for ROCKs include myosin binding subunit of myosin light chain phosphatase (MBS, also named MYPT1), adducin, moesin, myosin light chain (MLC), LIM kinase, and the transcription factor FHL. The phosphorylation of theses substrates modulate the biological activity of the proteins and provide a means to alter a cell's response to external stimuli.
Elevated expression of RhoA and RhoC, as well as the Rho effector proteins ROCK1 and ROCK2, are commonly observed in human cancers, including in the progression of testicular germ cell tumours, small breast carcinomas with metastatic ability, invasion and metastasis of bladder cancer, tumor progression in ovarian carcinoma.
Progression of tumors to invasive and metastatic forms requires that tumor cells undergo dramatic morphologic changes, a process regulated by Rho GTPases. Actomyosin contractility is a mechanism by which cells exert locomotory force against their environment. Signalling downstream of the small GTPase Rho increases contractility through ROCK-mediated regulation of myosin-II light chain (MLC2) phosphorylation.
The ROCK kinases are thought to participate in the induction of focal adhesions and stress fibers and to mediate calcium sensitization of smooth muscle contraction by enhancing phosphorylation of the regulatory light chain of myosin.
In vivo studies have also shown that ROCK inhibition reduced the invasiveness of several tumor cell lines. ROCK inhibitors, such as Y-27632 or WF-536, have been used in some studies to demonstrate these properties.
Inhibitors of ROCKs have been suggested for use in the treatments of a variety of diseases. These include cardiovascular diseases such as hypertension, chronic and congestive heart failure, cardiac hypertrophy, restenosis, chronic renal failure and atherosclerosis. Also, because of its muscle relaxing properties, inhibitors may also be suitable for asthma, male erectile dysfunction, female sexual dysfunction and over-active bladder I syndrome.
ROCK inhibitors have been shown to possess anti-inflammatory properties. Thus they can be used as treatment for neuroinflammatory diseases such as stroke, multiple sclerosis, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and inflammatory pain, as well as other inflammatory diseases such as rheumatoid arthritis, irritable bowel syndrome, and inflammatory bowel disease. Based on their neurite outgrowth inducing effects, ROCK inhibitors could be useful drugs for neuronal regeneration, inducing new axonal growth and axonal rewiring across lesions within the CNS. ROCK inhibitors are therefore likely to be useful for regenerative treatment of CNS disorders such as spinal cord injury, acute neuronal injury (stroke, traumatic brain injury), Parkinsons disease, Alzheimers disease and other neurodegenerative disorders. Since ROCK inhibitors reduce cell proliferation and cell migration, they could be useful in treating cancer and tumor metastasis. Finally, there is evidence to suggest that ROCK inhibitors suppress cytoskeletal rearrangement upon virus invasion, thus they also have potential therapeutic value in anti-viral and anti-bacterial applications. ROCK inhibitors are also useful for the treatment of insulin resistance and diabetes.
ROCK Inhibitor Y-27632
Adhesion of tumour cells to host cell layers and subsequent transcellular migration are pivotal steps in cancer invasion and metastasis. The small GTPase Rho controls cell adhesion and motility through reorganization of the actin cytoskeleton and regulation of actomyosin contractility. Cultured rat MM1 hepatoma cells migrate in a serum-dependent, Rho-mediated manner, through a mesothelial cell monolayer in vitro. Among several proteins isolated as putative target molecules of Rho, the ROCK kinases are thought to participate in the induction of focal adhesions and stress fibres in cultured cells, and to mediate calcium sensitization of smooth muscle contraction by enhancing phosphorylation of the regulatory light chain of myosin. Transfection of MM1 cells with cDNA encoding a dominant active mutant of ROCK conferred invasive activity independently of serum and Rho. In contrast, expression of a dominant negative, kinase-defective ROCK mutant substantially attenuated the invasive phenotype.
A specific ROCK inhibitor (Y-27632) blocked both Rho-mediated activation of actomyosin and invasive activity of these cells. Furthermore, continuous delivery of this inhibitor using osmotic pumps considerably reduced the dissemination of MM1 cells implanted into the peritoneal cavity of syngeneic rats. These results indicate that ROCK plays an essential part in tumor cell invasion, and demonstrate its potential as a therapeutic target for the prevention of cancer invasion and metastasis.
VEGF induced the activation of RhoA and recruited RhoA to the cell membrane of human ECs. This increase in RhoA activity is necessary for the VEGF-induced reorganization of the F-actin cytoskeleton, as demonstrated by adenoviral transfection of dominant-negative RhoA. Rho kinase mediated this effect of RhoA, as was demonstrated by the use of Y-27632, a specific inhibitor of Rho kinase. Inhibition of Rho kinase prevented the VEGF-enhanced EC migration in response to mechanical wounding but had no effect on basal EC migration. Furthermore, in an in vitro model for angiogenesis, inhibition of either RhoA or Rho kinase attenuated the VEGF-mediated ingrowth of ECs in a 3-dimensional fibrin matrix. CONCLUSIONS: VEGF-induced cytoskeletal changes in ECs require RhoA and Rho kinase, and activation of RhoA/Rho kinase signaling is involved in the VEGF-induced in vitro EC migration and angiogenesis.
Y-27632 can relax smooth muscle and increase vascular blood flow. Y-27632 is a small molecule that can enter cells and is not toxic in rats after oral administration of 30 mg/kg for 10 days. Effective doses for the use of this compound are approximately 30 μM. It reduces blood pressure in hypertensive rats, but does not affect blood pressure in normal rats. This has led to the identification of Rho signalling antagonists in treatment of hypertension (Somlyo, 1997 Nature 389:908; Uehata et al., 1997 Nature 389:990).
The use of a specific inhibitor of ROCK, Y-27632 (Uehata, et al., Nature, 389, 990 994, 1997, Davies, et al., Biochemical Journal., 351, 95-105, 2000, and Ishizaki, et al., Molecular Pharmacology., 57, 976-983, 2000), has demonstrated a role for this enzyme in Ca2+ independent regulation of contraction in a number of tissues, including vascular (Uehata, et al., Nature., 389, 990-994, 1997), airway (Ilikuka et al., European Journal of 30 Pharmacology., 406, 273-279, 2000) and genital (Chitaley at al., Nature Medicine., 7(1), 119-122, 2001) smooth muscles. In addition, Jezior et al. British Journal of Pharmacology., 134, 78-87, 2001 have shown that Y-27632 attenuates bethanechol-evoked contractions in isolated rabbit urinary 35 bladder smooth muscle.
The Rho kinase inhibitor Y-27632 has been tested for the following disease applications:                Hypertension (Uehata et al., 1997 IBID; Chitaley at al., 2001a IBID; Chrissobolis and 15 Sobey, 2001 C. Circ. Res 88:774)        Asthma (Iizuka et al., 2000 Eur. J. Pharmacol 406:273; Nakahara et al. Eur. J. Pharmacol 389:103, 2000)        Pulmonary vasoconstriction (Takamura et al., 2001 Hepatology 33:577)        Vascular disease (Miyata et al., 2000 Thromb Vasc Biol 20:2351; Robertson et al., 2000 Br. J. Pharmacol 131:5)        Penile erectile dysfunction (Chitaley et al., 2001b Nature Medicine 7:119; Mills et al., 2001 J. Appl. Physiol. 91: 1269; Rees et al., Br. J. Pharmacol 133:455 2001)        Glaucoma (Honjo et al., 2001 Methods Enzymol 42:137; Rao et al., 2001 Invest. Opthalmol. Urs. Sci. 42:1029)        Cell transformation (Sahai et al., 1999 Curr. Biol. 9:136-5)        Prostate cancer metastasis (Somlyo et al., 2000 BBRC 269:652)        Hepatocellular carcinoma and metastasis (Imamura et al., 2000; Takamura et al., 2001)        Liver fibrosis (Tada et al., 2001 J. Hepatol 34:529; Wang et al., 2001 Am. J. Respir. Cell Mol Biol. 25:628)        Kidney fibrosis (Ohlci et al., J. Heart Lung Transplant 20:956 2001)        Cardioprotection and allograft survival (Ohlci et al., 2001 IBID)        Cerebral vasospasm (Sato et al., 2000 Circ. Res 87: 195).ROCK Kinase and Cardiovascular Disease
There is growing evidence that ROCKs, the immediate downstream targets of the small guanosine triphosphate-binding protein Rho, may contribute to cardiovascular disease. ROCKs play a central role in diverse cellular functions such as smooth muscle contraction, stress fiber formation and cell migration and proliferation. Overactivity of ROCKs is observed in cerebral ischemia, coronary vasospasm, hypertension, vascular inflammation, arteriosclerosis and atherosclerosis. ROCKs, therefore, may be an important and still relatively unexplored therapeutic target in cardiovascular disease. Recent experimental and clinical studies using ROCK inhibitors such as Y-27632 and fasudil have revealed a critical role of ROCKs in embryonic development, inflammation and oncogenesis. This review will focus on the potential role of ROCKs in cellular functions and discuss the prospects of ROCK inhibitors as emerging therapy for cardiovascular diseases.
Abnormal smooth-muscle contractility may be a major cause of disease states such as hypertension, and a smooth-muscle relaxant that modulates this process would be useful therapeutically. Smooth-muscle contraction is regulated by the cytosolic Ca2+ concentration and by the Ca2+ sensitivity of myofilaments: the former activates myosin light-chain kinase and the latter is achieved partly by inhibition of myosin phosphatase. Rho signaling pathways in vascular smooth muscle cells are highly activated in hypertension, a condition associated with a variety of vascular diseases, including restenosis injury and atherosclerosis.
Hypertension is a cardiovascular disorder characterized by increased peripheral vascular resistance and/or vascular structural remodeling. Recently, rapidly growing evidence from hypertensive animal models suggests that small GTPase Rho and its downstream effector, Rho-kinase, play an important role in the pathogenesis of hypertension. Activation of the Rho/Rho-kinase pathway is essential for smooth muscle contractility in hypertension. A greater RhoA expression and an enhanced RhoA activity have been observed in aortas of hypertensive rats, such as genetic spontaneously hypertensive rats and N(omega)-nitro-L-arginine methyl ester-induced hypertension.
ROCK Kinase and Neurological Diseases
Abnormal activation of the Rho/ROCK pathway has been observed in various disorders of the central nervous system. Injury to the adult vertebrate brain and spinal cord activates ROCKs, thereby inhibiting neurite growth and sprouting. Inhibition of ROCKs results in accelerated regeneration and enhanced functional recovery after spinal-cord injury in mammals, and inhibition of the Rho/ROCK pathway has also proved to be efficacious in animal models of stroke, inflammatory and demyelinating diseases, Alzheimer's disease and neuropathic pain. ROCK inhibitors therefore have potential for preventing neurodegeneration and stimulating neuroregeneration in various neurological disorders.
The development of a neuron requires a series of steps that begins with migration from its birth place and initiation of process outgrowth, and ultimately leads to differentiation and the formation of connections that allow it to communicate with appropriate targets. Over the past several years, it has become clear that the Rho family of GTPases and related molecules play an important role in various aspects of neuronal development, including neurite outgrowth and differentiation, axon pathfinding, and dendritic spine formation and maintenance.
One common denominator for both neurite outgrowth inhibition and neurite repulsion is actin rearrangements within the growth cone. Central to the regulation of the actin cytoskeleton in both neuronal and non-neuronal cells is the Rho family of small GTPases. Rho family members cycle between an inactive GDP-bound form and an active GTP-bound form. Several lines of evidence suggest that manipulating the activity state of Rho GTPases may modulate growth cone collapse and neurite outgrowth inhibition.
More recently, behaviorally, inactivation of Rho pathway can induce rapid recovery of locomotion and progressive recuperation of forelimb-hindlimb coordination. These findings provide evidence that the Rho signaling pathway is a potential target for therapeutic interventions after spinal cord injury.

The Institute of Cancer Research: Royal Cancer Hospital


A method and apparatus for inspecting pattern defects emitting a laser beam, adjusting a light-amount of the laser beam, converting the light-amount adjusted laser beam into a slit-like laser light flux, lowering coherency of the slit-like laser light flux, and irradiating a sample with the coherence reduced slit-like laser light flux. An image of reflection light from the sample is obtained, and a detector is provided which includes the image sensor for receiving the image of the reflection light and for converting it into a detected image signal. An image processor is provided for detecting defects on patterns formed on the sample in accordance with the detected image signal.

The present invention relates to inspection of patterns and/or foreign matters, for detecting or examining defects, such as short-circuit and/or open-circuit or the like, on the patterns as a target of inspection, and relates, in particular, to a method and an apparatus, for inspecting the defects and/or foreign matters of the patterns formed on, such as, a semiconductor wafer, a liquid crystal display, and a photo-mask, etc., for example. Hereinafter, it is assumed that the defects include the foreign matters, in the meaning thereof.
Conventionally, in such kind of an inspection apparatus, as is described in Japanese Patent Laying-Open No. Hei 7-318326 (1995) <hereinafter, conventional art 1>, an image is detected on the patterns to be examined or inspected by means of an image pick-up element, such as a line sensor, etc., while moving the patterns to be inspected, so as to compare an image signal detected with one which is delayed by a predetermined time in gradation thereof, thereby acknowledging inconsistency or anti-coincident to be a defect.
Also, other conventional art, relating to the defect inspection of patterns to be inspected, is known from Japanese Patent Laying-Open No. Hei 8-320294 (1996) <hereinafter, conventional art 2>. In this conventional art 2 is described a technology, for examining the patterns to be inspected, for example, a semiconductor wafer, in which areas high pattern density, such as the memory mat portions, etc., and low pattern density, such as peripheral circuit portions, etc., are mixed with each other, wherein gradation conversion is conducted on digital image or video signal, which is obtained through A/D conversion of the image signal detected, so that a predetermined relationship can be established between the high density areas and the low density areas on the patterns to be inspected, in particular in the brightness or the contrast thereof, rather than the frequency distribution thereof, and this image signal converted in gradation is compared with other gradation conversion image signal for comparison, under the condition of being fitted to each other in position, thereby inspecting minute or microscopic defects thereon with high accuracy.
Furthermore, the conventional art for inspecting the patterns on a photomask is already known, for example, Japanese Patent Laying-Open No. Hei 10-78668 (1998) <hereinafter, conventional art 3>. In this conventional art, it is described that the UV light rays are irradiated upon the mask, equally, in which coherence is lowered by rotating a diffuser panel inserted within an optical path, with using a UV laser beam as a light source, such as, an excimer laser or the like, so as to calculate out a characteristic amount or quantity from the obtained image data of the mask, thereby deciding or examining good or bad, i.e., the quality thereof. And, a projection exposure apparatus with using an excimer laser therein is already known, for example, in Japanese Patent Laying-Open No. Sho 59-226317 (1964) or Japanese Patent Laying-Open No. Sho 62-231924 (1987), etc.
For LSI manufacturing in recent years, the circuit patterns formed on a wafer come to be minimized, such as, 0.25 μm or less than that in the pattern width thereof, responding to the needs of high integration; thus it nearly reaches up to the limit on the resolving power of an image-forming optical system. For this reason, development is advanced on application of high NA technology or an optical super resolving power technology.
However, the NA technology also reaches up to the limit thereof, physically. Accordingly, a substantial or intrinsic approach is trying to shift the light wavelengths to be applied for the detection into the regions of the UV light and DUV light, i.e., shortening the light wavelength.
Further, due to the necessity of conducting the inspection with high speed, it is impossible to adopt the method of scanning the laser beam focused or converged thinly on a sample. On the contrary, when trying to illuminate with irradiating the laser beam spreading out all over a visual field, however the illumination of the laser beam generates speckles, or an overshoot or an undershoot, being called by a "wringing", at an edge portion of the circuit pattern, thereby bringing about a problem that the image cannot be obtained of good quality.

Method and apparatus for inspecting pattern defects

Hitachi High-Technologies Corporation, Ltd.