Embodiments herein comprise a printing/copying media output device or terminal that includes a single media output tray that can be used as a flat tray or a basket tray. The media output tray has a first portion that connects to a media output device, a second portion at the opposite (distal) end of the first portion from the media output device, and a hinge between the first portion and the second portion connecting the first portion to the second portion. In some embodiments herein, the hinge is positioned at an approximate midpoint of the output tray and the first portion is approximately the same size as the second portion. By folding the tray at the hinge, the tray can be converted from a flat tray to a basket tray.

The present disclosure relates to printer/copier output trays. U.S. Pat. No. 6,830,401 discloses conventional structures for flat printer/copier output trays. U.S. Pat. No. 6,824,129 discloses conventional structures for basket printer/copier output trays. Both patents and the patents (and disclosures to which they refer) are fully incorporated herein by reference.
The structure shown in FIG. 5 is similar to the structure shown in U.S. Pat. No. 6,830,401, mentioned above. In FIG. 5, the printer 100 has an input tray 200 and an output tray 300 connected to the printer 100 body 400 at a connection point 460. The input tray 200 and the output tray 300 can include respective input and output print media support surfaces 210 and 310. The support surfaces 210 and 310 can be configured to support an entire piece of print media having, for example, dimensions 8½ inches by 11 inches, such as a conventional standard size paper and/or A4 paper, etc.
The support surface 310 can include a surface formed by extending the output stop 330. The support surfaces 210 and 310 may only support a portion of a piece of print media. The support surfaces can be flat or curved and can have cavities where a portion of the print media is not supported. By way of example only and not by limitation, the cavity 320 for the output stop 330 of the output tray 300 could result in portions of the output print media not being supported by the other output print media support surfaces 305,310. This could also be the case with the input print media support surface 210.
The input tray 200 and the output tray 300 can be configured to rotate from an open position to a closed position. However, the trays 200 and 300 can be open and closed in a different manner. In this regard, any means that will result in the opening and the closing of the trays of the printer can be used.
The input print media support surface 210 of the input tray 200 is positioned outboard of the output print media support surface 310 of the output tray 300 (i.e., the input print media support surface 210 is positioned a distance further from the center of the printer 100 than the output print media support surface 310) when the input tray and the output tray are in the closed position. This is a result of the rotation of the input tray 200 to the closed position, where the input tray 200 is positioned below the output tray 300 when the trays are in the open position. However, it is noted that the output print media support surface 310 of the output tray 300 could be positioned outboard of the input print media support surface 210 of the input tray 200 when the input tray 200 and the output tray 300 are in a closed position. This could be the case, by way of example, when the input tray 200 is positioned above the output tray 300 when the trays are in the open position.
FIG. 6 is similar to the structure disclosed in U.S. Pat. No. 6,824,129. In FIG. 6, the printer device includes a body or housing 22 in which the various operating components, e.g., paper transport mechanism 32, 34, 36, 38 print heads (P) 40, 42,44, 46, etc., are located and to which a power supply 14 is connected. The printer 20 includes a multi-directional paper or sheet input tray 24. The tray 24 is constructed to hold a stack of plural paper sheets 10 or other printable sheet material (media), and to enable such sheets to feed to the printer from the top of the stack/tray (i.e., a "top feed" tray) or can be constructed to feed from the bottom of the stack/tray (i.e., a "bottom feed" tray). The bottom of the tray is defined as that part of the tray which supports the paper. The input tray can be used with cam-type pick up roller printers.
Irrespective of the type of the input tray 24, the printer 20 itself is configurable to enable it to be disposed in one of two orientations so that when the device 20 is located on the wall 11, or on some other vertically oriented surface, its input tray 24 is in a generally vertical direction and when the device 20 is located on the shelf 13 or on some other horizontally oriented surface its input tray 24 is also in the generally vertical direction. It should be noted that the paper input tray 24 can be oriented so that it is in a precise vertical orientation, or it may be directed in a generally vertical orientation, e.g., at some acute angle with respect to horizontal. Moreover, that acute angle can be relatively large, e.g., 45 degrees or more, to enable each sheet of paper 10 or other printable material to make use of gravity to effect or facilitate the entry of the each sheet of paper or other printable material into the device 20. Thus, the term "generally vertical direction" as used hereinafter should be understood to have a broad meaning. It should be noted that if the tray is in a precisely vertical orientation it would need some modification to keep the paper in it from falling forward. In the printer shown, the input tray is limited to two positions. By widening the space that the paper enters the printer from the rotary device, one can readily provide a printer enabling one to adjust the tray somewhat (e.g., 5 degrees) at those positions.
The printer 20 also includes a dual directional outlet or exit port 26 located at a lower point on the housing and through which paper or other printable sheet material that have been printed with indicia by the print head of the printer exit for collection. In order to collect the printed sheets 10 exiting from the printer's outlet 26, the device includes an outfeed or outlet tray 28. The outlet or outfeed tray 28 is in the form of a basket hingedly mounted adjacent the outlet 26 so that it is oriented in a generally vertical direction, e.g., either precisely vertical or at some acute angle to vertical. The basket may be constructed in accordance with the teachings of U.S. Pat. No. 5,924,808, (the complete disclosure of which in incorporated herein by reference) wherein the basket section is collapsible, or may be of a fixed shape and configuration, e.g., molded, of plastic such as that of U.S. Pat. No. 5,913,628 (the complete disclosure of which in incorporated herein by reference)
Thus, the tray/basket 28 can be a preformed unit that is hingedly connected to the device 20 so that it is suspended from the device and hangs in a generally vertical direction irrespective of whether the device is mounted vertically or horizontally. Moreover, the basket/tray 28 is constructed so that its front wall 28A extends at an acute angle to vertical. Further, the back wall has a first upper section 28D and a second lower section 28B that can be at an angle, or parallel to the front wall 28A so that a basket structure is formed that will hold the sheets of paper 10 and prevent the sheets of paper 10 from falling out of the basket tray 28.


In order to measure the load on a server and perform its allotment with high efficiency, the communication from a client to a server is monitored. The communication data size per connection is measured as the load on the server, the change of the communication data size per connection is detected, the maximum is recorded, and if the communication data size decreases at the time when the maximum is detected, the load on the server is judged to be heavy.

With a rapid spread of the Internet and Intranet over the recent years, an efficient utilization and service stability of a network service server have been requested. Optimum sharing of the services to the servers is indispensable for the efficient utilization and stable service supply of the servers, and, for attaining this optimum sharing, it is required that a load of the server be accurately recognized.
The followings are known methods of recognizing the load of the server in the prior art.
(1) Agent Method
This is a method in which a program for counting an activity ratio of resources such a CPU, a memory etc is installed into the server. When an agent itself increases the server load and communicates with the outside, there occurs an interference with a load measuring accuracy by the agent such as consuming a band therefor. Further, the agent program must be installed into the server, and hence there arises a problem of being lack of a general-purposed characteristic and large in instruction cost.
(2) Load Measurement Communication Method
This is a method of issuing a ping command to the server and performing a pseudo service communication therewith, and obtaining a server load from a response time. The communication for the measurement, however, consumes a band on the route, and the server is also burdened with a load for the response, resulting in an interference with the load measurement. Further, the server is required to support a protocol etc used for the measurement, and there is still the problem of being lack of the general-purposed characteristic.
(3) Counting Method of VC count, Connection Time, Connection Frequency, Connection Error Rate and Response Time
This is a method of obtaining the server load from a VC count, a connection time, a connection frequency, a connection error rate and a response time with respect to the server, which are counted during a routing process in a router for routing a packet from a client to the server. This method is, however, based on a behavior of the server when establishing the connection, and therefore an error is large. A large quantity of connections are needed for enhancing the accuracy, so that this method is not suited to the services where a large amount of communications are performed with a small number of connections. Further, the routing is indispensable, and hence a problem is that a throughput of the server is restricted by a throughput of the counting method.
(4) Hit Count/Hit Rate Calculation Method
This is a method in which an access count (hit count) and an access frequency (hit rate) are counted per content such as an access target file by checking the packets to a WWW server, and the server load is obtained from a result of this counting. This method needs a packet analyzing process per protocol for specifying the access target file and is incapable of corresponding to a new service. Moreover, a performance of the server must be already known. There is no alternative but to obtain the server performance from catalog values or empirically in order to give the server performance beforehand. The server performance is, however, largely influenced by a system architecture and an operation mode. Therefore, a problem is that the catalog performance value based on the standard architecture and mode is not precise, and at least one trouble is inevitable when obtained empirically.
As explained above, any method is not capable of detecting the server load efficiently at a high speed without putting a burden on the server.
Further, the server load can not be thus accurately recognized, and it is therefore difficult to allocate the services provided by the server.
The following methods are proposed only in terms of sharing the services.
(5) Round Robin DNS Method
This is a method wherein, in DNS (Domain Name System) services, a mapping of one domain name to a plurality of IP addresses of the server is set in an entry table, in response to a client's request for an inquiry about the server IP address, the respective servers are allocated cyclically (Round Robin) according to the entry table, and the IP address of the allocated server is selected to respond to the client, thus sharing the services to the plurality of servers.
According to this Round Robin DNS method, however, the services can be shared only at an equal or simple service sharing rate, and each server must perform the service in accordance with the sharing rate allocated irrespective of its capability and dynamic load state. Therefore, there is a difference in the load sate between the servers, and the method is inefficient on the whole. Further, pieces of DNS inquiry information are normally cached on the client side, and hence a problem is that, even if the rate changes, this change can not be immediately reflected.
(6) Sharing Method Using Hash Table
This is a method of allocating entries in a Hash table for managing the connections to the servers, and the services are shared to the servers at a rate corresponding to the number of entries to be allocated.
In this method, to begin with, when the client makes a request for the service, the entry is determined from the client address and the service as well. This request is sent to the server to which that entry is allocated. Then, the services of which the number corresponds to a ratio of the number of entries allocated, are shared to the servers. Thus, the efficient utilization of the servers is actualized by allocating the many entries to the high-performance server or by re-allocating the entries to the server with the high load to servers having a comparatively low load.
According to this sharing method using the Hash table, however, a Hash function for generating a Hash value with no bias is necessary for properly reflecting a ratio of the number of Hash entries in the service sharing rate. In general, however, it is impossible to find out the Hash function for generating the Hash value with no bias with respect to all sorts of distributions of Hash keys (client addresses, port numbers etc). Further, the accuracy of the sharing rate is proportional to the number of Hash entries, and hence a multiplicity of entries are needed for enhancing the accuracy, resulting in more of consumption of storage resources (buffers) usable for managing the connections. There arises a problem that a large quantity of accesses can not be handled.
(7) Sharing Method Based on State and Performance of Server
This is a method of sharing the services of which a quantity corresponds to the load and a performance ratio by predicting a magnitude of the server load or predicting a performance ratio between the servers by counting a response time by issuing the ping command to the server and counting a connection time and a connection error rate during a routing process by routing the packet from the client.
According to this method, however, the services for whichever client are equally shared to the servers regardless of a throughput of the client, a length of the route to the client and a bandwidth, so that the utilization efficiency of the server can not be maximized.
A difference in the performance (especially, a speed) and the load of the server do not appear in QoS (Quality of Service) to the client with its route becoming a bottleneck due to a short or long bandwidth of the route and to the client having a low throughput.
Reversely, the difference in the performance and the load of the server exerts a great influence on QoS to the client connected to a near and high-speed line or to the client exhibiting a high throughput. Such being the case, there is a problem in which when trying sharing equally all the services for the clients, it follows that more server resources than needed to the clients are shared, or there is nothing but to share the deficient server resources.
As described above, the problems are inherent in both of the server load recognizing method and the server sharing method in the prior art.
The present invention, which was devised to obviate the above problems, aims at recognizing the server load efficiently at the high speed without putting any burden on the server, sharing the services in accordance with the dynamic load state in the server, accurately reflecting the service sharing rate obtained by setting and the adjustment in the service sharing, and maximizing the utilization efficiency of the server by sharing the services in a way of estimating the necessary server resources for every client.

Network server load detection system, sharing system and method


A standby database system or another replica data system replicates changes, made to data blocks at a source database system or another primary data copy, to replicas of the data blocks at the standby database system or other replica. While replicating the changes to the data blocks thereof, the standby database system (or other replica) receives queries (or reads) issued thereto and computes the queries based on data read from the data blocks thereof.

Information can be important and valuable and procedures are undertaken to protect it. In a procedure referred to as data replication, modern enterprises replicate data that is primarily updated and or accessed at a storage system, referred to herein as a "primary data system" (sometimes called a source data system), is replicated or duplicated at another storage system or location, referred to herein as "replica data system." The data stored at the primary system is referred to herein as primary data or a primary copy and the data stored at the replica system is referred to as replica data or a replica copy.
Database systems (DBMSs) are often protected using replication. Typically, one DBMS maintains the primary copy of a database and another database system, referred to herein as a standby database, maintains a replica of the primary copy. The standby database system is used to back up (or mirror) information stored in the primary database system or other primary copy.
For a DBMS protected using replication, data files, redo log files and control files are stored in separate, logically or physically identical images on separate physical media. In the event of a failure of the primary database system, the information is preserved, in duplicate, on the standby database system, which can be used in place of the primary database system.
The standby database system is kept up to date to accurately and timely reproduce the information in the primary database system. Typically, archived redo log records ("redo records") are transmitted automatically from the primary database system to the standby database system. Information from the redo logs is used to replicate changes on the primary database system to the standby database system.
There are two types of standby database systems, a physical standby database system and logical standby database systems, which differ in the way they archive information. In a physical standby database system, changes are made using physical replication. Under physical replication, updates made to a data unit of contiguous storage (herein "data unit") at the primary data system are made to corresponding data unit replicas stored at the replica system. In the context of database systems, changes made to data blocks on the primary database system are replicated in replicas of those data blocks on the physical standby database system.
A data block is an atomic unit of persistent contiguous storage used by a DBMS to store database records (e.g. rows of a table). Thus information stored on the primary database system is thus replicated at the lowest atomic level of database storage space and a physical standby database system is essentially a physical replica of the primary database system. When records are read from persistent storage, a data block containing the record is copied into a buffer of DBMS's buffering system. The buffer usually contains many other rows and control and formatting information (e.g., offsets to sequences of bytes representing rows or other data structures, lists of transactions affecting rows).
To replicate changes from the primary database system, the standby database system scans the redo records generated for the primary database system. Redo records record changes to data blocks between a previous version of a data block and a subsequent version of the data block. A redo record contains enough information to reproduce the change to a copy of the previous version. Using information in a redo record to reproduce a change recorded by the record to a copy of the previous version of the data block to produce the subsequent version of the data block, is an operation referred to herein as applying the redo record.
Another approach to replicating data is that of the logical standby database system. With the logical standby database system approach, DBMS commands that modify data on the primary system are in effect re-executed on a logical standby database system to essentially duplicate the changes made to the primary database. While executing the same DBMS commands guarantees that changes are replicated at the transactional level, the changes are not replicated at the data block level.
For various reasons, this change in replication strategy allows a logical standby database system to be available for reporting applications while replication is being performed. The ability to support reporting with data known to be fresh and without having to lag in updates is beneficial because it allows use to be made of the redundant hardware instead of just having it serve singly as a backup system.
Physical standby database systems typically have comparatively high performance, relative to logical standby database systems. However, a physical standby database system is unavailable for read operations unless application of redo records from the primary database system is stopped. However, delays in updating the physical standby database system, such as are caused by stopping application of redo while the standby database is open for reads, may allow it to lag to a greater degree from the primary database system. This concomitantly exposes fresh data in a primary database system to the risk of corruption or loss without adequate archived backup information available. Delays in updating the physical DBMS also introduce the possibility of read operation on data that may increasingly be at variance from the primary database system.
Thus, there is a need to allow read operations to physical standby databases in a way that eliminates or minimizes delays to updating the physical standby database system.
Physical replication in other contexts has similar limitations and needs. For example, in remote mirroring, data on a primary disk volume or file system is replicated on replicas of the primary disk volume or file system. The data units physically replicated are sectors, which are the atomic units of contiguous store read and written to disk. The data units of a primary disk volume or file system are replicated on the replicas of the disk volume and file systems. The changes to data units are recorded by change descriptions. Information about changes in a change description is used to reproduce the changes to copies of the sectors.
Therefore, there is a need for any system using physical replication to allow read operations to replicas to be performed in a way that eliminates or minimizes delays to updating the replica with changes to primary data.
The approaches described in this section are approaches that could be pursued, but not necessarily approaches that have been previously conceived or pursued. Therefore, unless otherwise indicated, it should not be assumed that any of the approaches described in this section qualify as prior art merely by virtue of their inclusion in this section.

Readable physical storage replica and standby database system


A microscope control unit which is composed of a bracket-shaped support frame having a support area, a pillar standing vertically erect on the support area, and a support arm, which emanates from the upper end of the pillar and is aligned parallel to the support area.

The invention relates to a microscope control unit comprising manually operable, cylindrical operating elements for x/y-adjustment of a mechanical stage and alternatively for the z-adjustment of the focus setting of a microscope.
It is well-known to attach, to the underside of mechanical stages, manually operable operating elements that separately transmit, e.g., by means of cable controls or gearwheels, the rotation of cylindrical barrels to the stage surfaces to be displaced. The frictional forces to be overcome in this case give the operator a feeling for the stage movement. At least one of the moved stage surfaces usually carries the operating elements along. The operator's hand must follow on the working surface. The operating elements must be attached to different sides of the microscope stage for left-handers or right-handers. The possibility of retrofitting is associated with a higher design effort. Sufficient clearance for the positioning of the hand rest and arm rest for the operator must be kept free in the area of the microscope stage surface.
For motor-driven stage adjustments, the rotation of the operating elements attached to the mechanical stage can be converted to electrical counter and control pulses. The operating elements can be provided with adjustable friction torques to simulate the feel of a mechanical coupling between operating element and stage movement for the operator.
For motor-driven stage adjustments, it is also known to accommodate the manually operable operating elements in separate housings and to transmit the control signals for the stage adjustment through electrical lines and plug connections attached to the mechanical stage. To this end, trackball and joystick control units are well-known in particular. Both right-handers and left-handers can operate these control units since they can be freely positioned on the work stage. The disadvantage is that the mechanical stage cannot be reliably set to a precise position because of the ease of movement of the operating elements. In the joystick controller, the operating lever automatically jumps back to the zero position after the operator lets go of a setting that was achieved. To make a correction or choose a new setting, the operator must again make out the zero position by touch with his/her finger. An undesired stage adjustment can be triggered by accidently nudging the operating lever.
For manual, mechanically-operated stage adjustments when using control units with interconnected coarse and fine adjustments of the operating elements, a rapid stage adjustment over large adjustment paths and a precise positioning in a small observation area are usually accomplished through different gear ratios. The respective operating elements are usually arranged coaxially aligned with one another with different roll diameters so that the operator can comfortably change his/her grip from coarse to fine adjustment or vice versa.
For electronic transmission of the motion of the operating elements to servomotors, it is possible to adjust different translations of the counter and control pulses to the engine speeds by means of electrical switches and software programming.
In addition to operating elements for the x/y mechanical-stage adjustment, microscopes also have operating elements for the z-adjustment of the mechanical stage or of the body tubes for the focus setting of the lens. These are usually attached to the microscope stand and therefore require a laborious change of grip from the microscope stage to the microscope stand.
The housings of the already described trackball and joystick controllers therefore also have additional control wheels for the z-drive in handy proximity to the x/y operating elements. The operator must therefore prepare himself/herself for different reactions to the different movements for adjusting a control level or for the rolling of a ball and the rotating of a wheel. The operator is therefore required to exercise additional concentration when changing grip from one operating element to another.


An alignment system for a mezzanine-type printed circuit board is provided. The alignment system includes tab portions formed from the insulating material of the printed circuit board, in which the tab portions engage receptacles and limit movement of the printed circuit board.

This section is intended to introduce the reader to various aspects of art, which may be related to various aspects of the present invention that are described or claimed below. This discussion is believed to be helpful in providing the reader with background information to facilitate a better understanding of the various aspects of the present invention. Accordingly, it should be understood that these statements are to be read in this light, and not as admissions of prior art.
Computer servers are used by a wide array of users in various configurations. Server systems often comprise multiple server blades housed in a chassis and/or in standard rack mount. As processing needs and computing performance have increased, server blades have become more powerful while being reduced in size. Thus, chassis and rack mount systems are capable of enclosing an increasing number of these small form factor server blades that deliver an increasing amount of performance. While the server blades are intended to be fully functional computer servers, sometimes it is desirable to add functionality or interfaces to a server blade through the use of expansion cards, such as peripheral circuit interconnect (PCI) cards. Conventional expansion cards, in which the card inserts perpendicular to the system board of the server, are usually not feasible in a server blade in which the chassis height is much smaller than a standard rack server. Such expansion cards for blade servers typically have a mezzanine-type design, in which the expansion card is inserted or installed parallel to the system board of the server. The installation and alignment of such mezzanine-type expansion cards introduces a number of design challenges and considerations.

Apparatus for inexpensive mezzanine-type card board-to-board connector blind mate alignment system using printed circuit board material

Hewlett-Packard Development Company, L.P.


A device for successively transporting sheets in a platen press includes gripper bars with respective ends fixedly attached to two flexible of endless loop elements. Each loop element is engaged respectively with an intermittent drive wheel and at least one free wheel. A rectangular working chase and a movable platen arranged on both sides of the path of the grippers of the said bar. Nozzles are connected to a compressed air supply, for directing air jets towards the movable platen during a stopping phase of the gripper bars, in order to successively stop the sheets between the working chase and the movable platen. The nozzles are located below the transverse rear edge of the working chase.

The present invention refers to a device for successively transporting sheets in a platen press. It comprises gripper bars, having respective ends which are fixedly attached to two flexible elements in the shape of endless loops. Each loop is engaged respectively with an intermittent drive wheel and at least one free wheel. A rectangular working chase and a movable platen are arranged on both sides of the path of the grippers of the bar. Nozzles connected to a compressed air supply direct air jets towards the movable platen during the stopping phase of the gripper bar, in order to successively stop the sheets between the working chase and the movable platen.
To transport a sheet, the gripper bar seizes it at the front edge and brings it between the working chase and the cutting plate fixed on the movable platen of the platen press. At the end of the path, the gripper bar strongly decelerates before stopping and is raised as soon as it comes out from the transverse rear edge of the working chase.
During this abrupt deceleration of the gripper bar, it is important to prevent deformation of the sheet and to force the sheet to remain practically flat. When a flexible sheet thus transported undergoes a strong deceleration, it primarily deforms downwards due to the force of gravity exerted on it. That is the reason why the grippers of the gripper bar are preferably located at the level of the lower face of the profile forming the gripper bar, so that the sheet travels as near as possible to the movable platen.
To avoid upward deformation of the decelerated sheet, it has already been proposed to form a flow of compressed air between the sheet and the board fixed inside the working chase of the platen press. However, in solutions suggested up to now, the nozzles that blow compressed air are arranged behind the transverse rear edge of the working chase, so that the air flow is interrupted before the grippers fully stop. Consequently a relatively large space still separates the platen from the working chase. Therefore, the air blower stops before the sheet and the space which remains at this moment between the working chase and the movable platen does not exclude further deformation of the sheet under the effect of the strong deceleration.

Device for successively transporting sheets in a platen press


Provided is a data processing system and a method for generating states of a model defined within a modelling application. The modelling application generates a state of the model based on the values of a number of input variables. A modification means alters the values of the input variables, and provides those altered values to the modelling application to cause a new state of the model to be generated. The modification means repeats the production of altered values such that a set of states of the model is generated. A display means produces a graphical representation of each state of the model in the set and displays the graphical representations on a display device. The system includes control means, responsive to signals received from an input device, to enable a user to select graphical representations from those displayed and to place the selected graphical representations in a predetermined area of the display device; and weighting means for automatically assigning a weighting to each graphical representation within the predetermined area, this weighting being dependant on the position of the graphical representation within the predetermined area. The modification means is responsive to the weighting of each state of the model to produce altered input variables for a subsequent set of states of the model. The generation of the set of states of the model and display of their graphical representations is then repeated.

1. Field of the Invention
The present invention relates to a data processing system and method of operation, and in particular to a data processing system for generating states of a model defined within a modeling application.
2. Description of the Related Art
Typically such a data processing system will run a software application in which a model can be defined by a number of equations, variables and constants. For example a spreadsheet application could be used to model the financial state of a company over a number of years. The state of the model might depend on a large number of variables, and typically the model will be responsive to information used to alter those variables, and hence to alter the state of the model.
Likewise, running the modeling application might result in a number of financial and other predictions indicating the success or otherwise of the modeling process. The user will generally wish to change a number of the input variables to produce a good set of predictions. However this is not always a straightforward task for the user.
The user's difficulty generally arises from the need to remember how the model variables changed and the result of those changes, before the next set of changes can be made. Typically, graphs may be used to help in this visualization process, e.g. giving financial and market share results over a number of years. Even so, after a number of variable changes, the user's memory of the actual shape of the graphs will quickly fade, making it very difficult to choose the optimum direction to change the values of the input variables.
Existing prior art techniques, such as "What-if" programming, allow the user to adjust the input variables, or alternatively to instruct the modeling application how to do so, and the user then judges the various outputs produced. Even if these techniques are useful in many cases, it is almost impossible to use them when there are more than four or five input variables to be set up. It is difficult to keep track of past experiments, and the user gets distracted by the mechanism of setting up the variables or the instructions for the experiments.
Other techniques, such as those used in "solver" and "optimizer" tools of existing modeling applications, are not useful in situations where the user cannot readily define the result that he/she is trying to achieve; moreover they only produce a single value as a result and can only be defined by a mathematical equation.
European Patent Application EP 0,628,918 describes a "Mutator" technique for controlling the input variables of a standard or special purpose modeling application. The basic Mutator concept is to let the system randomly alter the input variables of the modeling application within predetermined limits, and to then provide the new input variables to the modeling application to generate a new state of the model. This process can be repeated a number of times to produce a series of mutated states of the model, the user then being presented with a visual representation of this series of "mutated" states of the model. Based on this, the user can then select the best of the representations for a subsequent iteration of the mutation process. The decision as to which representations are "best" is a subjective decision made by the user, and will be dependent on the overall state of the model that the user is aiming to achieve. The states corresponding to the representations selected by the user are referred to as "parents", whereas the states produced in a subsequent iteration of the mutation process are referred to as "children".
Various features are described in the above referenced European patent application to be employed by the user when selecting parent states for a subsequent iteration. One feature allows the user to flag some of the states of the model as "good" or "bad", and this judgement is then used to steer or bias the mutation. Another feature allows the user to select and `marry` parent states to produce children that share characteristics of their parents. Typically, the user interacts with the mutation system by means of a selection device, such as a mouse, firstly selecting from a menu a characteristic, such as "good" or "bad", to be associated with subsequently selected representations, and then selecting the representations that the user considers to exhibit that characteristic, thereby associating that characteristic with the selected state(s). The user can then select another characteristic from the menu, and then make some further selections or modify one or more old selections. In this way the states selected as bad are discarded and disappear from the screen while the states selected as good are kept for use as parents in a subsequent iteration of the mutation process. Moreover, the user can apply weighting values to selected states, such as those state(s) selected as good. This would typically be done by selecting a weighting function from the menu and then clicking a number of times on such state(s), where the number of clicks on a particular representation equates to the weighting given to that state. According to the above prior art approach, the states selected as "good" would generally have an icon associated with them to indicate their selection, but would remain in their original position. Additionally numbers would be provided with the icons to indicate the weighting value given.
It is advantageous for the user to make use of the above features, since experience has indicated that the Mutator system operates most effectively when a user chooses several potential parents at each mutation step.
However, in spite of the above features facilitating a quicker generation of satisfactory mutated scenarios, they are not very easy or intuitive to use, and can be rather cumbersome. When the user is not only selecting parent states but also weighting (or "ranking") them, the above technique becomes particularly cumbersome, since the user has to select a weighting function and then revisit the selected states in order to apply the desired weighting to them. Indeed experience has shown that users often avoid using these separate features because of the user effort required.

Data processing system and method for generating states of a model defined within a modelling application


Enrichment for human Keratinocyte Stem Cells KSCs to a high degree of purity can be successfully achieved on the basis of a cell surface component whose expression is proliferation-related in conjunction with an integrin such as the xcex16xcex24 integrin. Transferrin receptor may be used as the cell surface component that is proliferation related. Enrichment of Transit amplifying cells can also be achieved by use of a variation of this method. The enrichment follows on from harvesting of cells from an epithelium, preferably rich in stem cells.

This invention relates to a method of enriching for and isolating subpopulations of epithelia cells, isolation of keratinocyte stem cells, to keratinocyte stem cells and uses for keratinocyte stem cells.
In common with other rapidly renewing tissues such as the haemopoietic system and the intestinal epithelia, the human epidermis is in a process of constant regeneration. Terminally differentiated cells lost continuously from the skin surface, are replaced by an intricate and highly regulated proliferative process within the basal layer of the epidermis. Stem cells in these rapidly renewing tissues are the earliest progenitors of a hierarchy of proliferative cells which are ultimately responsible for the generation of all mature cells for the lifetime of an individual (Lajtha, 1979). In murine epidermis, this process is achieved by two kinetically distinct subpopulations: (a) keratinocyte stem cells (KSC) which represent a minor subpopulation of relatively quiescent cells, defined by their great proliferative potential and an unlimited capacity for self renewal, identified as slow-cycling, 3H-Tdr label-retaining cells; and (b) transit amplifying (TA) cellsxe2x80x94the progeny of the stem cells, with a limited proliferative capacity identified as a pool of rapidly proliferating cells that are lest from the basal layer to terminal differentiation within 4-5 days (Potten, 1983: Morris et al, 1985; MacKenzie and Bickenbach, 1985; Potten, 1986; Bickenbach et al, 1986). In addition, a third Subpopulation of basal keratinocytes representing post-mitotic differentiating cells in the early stages of keralinisation can also be identified (Potten, 1983; Morris et al, 1985; MacKenzie and Bickenbach, 1985; Potten, 1986; Bickenbach et al, 1986; Christophers, 1971; Allen and Potten, 1974). Human epidermis has similar populations.
Given that all proliferative activity in the human epidermis is restricted to the basal layer, this is presumably where the stem cells and TA cells reside. It has also been established that the hair follicle can act as an important reservoir of epidermal stem cells, and that cells within the bulge region have extensive proliferative potential. Physiological cell renewal in interfollicular epidermis however, is most likely to be achieved by stem cells and TA cells within the basal layer. However there are no molecular markers that distinguish between basal keratinocytes that have made a commitment to differentiate (TA cells) and immature stem cells.
In the haemopoietic system, multilineage reconstituting stem cells can be physically separated from committed progenitor cells (analogous to the TA cells of the epidermis). based upon differences in their expression of cell surface markers (Civin et at, 1984; Spangrude et al, 1988; Berenson et al, 1991; Terstappen et al, 1991; Baum et al, 1992). Clearly the availability of appropriate cell surface markers on basal epidermal cells would greatly facilitate the isolation and characterisation of human KSCs. However, the cell surface antigenic phenotype of these cells remains relatively poorly defined.
One of the best studied classes of cell surface molecules expressed by keratinocytes are the integrin superfamily of cell adhesion receptors. Integrins are heterodimeric cell surface glycoproteins that primarily mediate the attachment of basal keratinocytes to extracellular matrix proteins found in the basement membrane, but can also mediate intercellular adhesion. In vivo, basal keratinocytes express the xcex21 integrins xcex13xcex21 and as well as the integrin xcex16xcex24 (Peltonen et at, 1989; Carter et al, 1990a Carter et al, 1990b). Important evidence for proliferative heterogeneity in human basal keratinocytes has been provided by recent work using a fluorescence activated cell sorting (FACS) approach, demonstrating that both cultured and primary human foreskin keratinocytes could be separated into cells with high levels of xcex21 integrin (xcex21 bright) which had a high plating efficiency assayed after two weeks in culture, compared to those keratinocytes with low levels of this integrin (Jones and Watt, 1993; Jones et al, 1995). Furthermore, bright keratinocytes were shown to be capable of generating an epithelial sheet when grafted onto mice, suggesting that this fraction of the basal layer contain KSCs (Jones et al, 1995).
In vivo studies suggest that epidermal stem cells constitute between 1%-10% of the basal layer depending on the methodology used (Morris et al, 1985; MacKenzie and Bickenbach, 1985; Bickenbach et al, 1986; Potten and Hendry, 1973; Morris and Potten, 1994). Since approximately 40% of the basal layer in human foreskin exhibits high levels of xcex21 integrin in vim (Jones et at, 1995) it is highly likely that basal keratinocytes with this phenotype contain both the KSC population and a significant number of TA cells and therefore there are drawbacks in the use of cells enriched for high level expression of xcex21.
An object of one aspect of the invention is to generate a more purified population of keratinocyte stem cells than has been achieved by prior art methods. An object of a further aspect of the present invention is to provide methods for purifying subpopulations of epithelial cells.
A strategy for distinguishing between the TA cells and the KSCs of the epidermis based on the use of two cell surface antigens has been shown to be effective. In view of functional data demonstrating the role of integrin xcex16xcex24 in mediating adhesion of basal keratinocytes to the basement membrane via hemi-desmosomes (Sonnenberg et al, 1991; Dowling et at, 1996; Georges-Labouessee et al, 1996; Van-der-Neut et al, 1996) it was hoped that this integrin may provide a suitable marker for epidermal stem cells since these cells are permanently anchored to the basement membrane.
It is now shown that while basal keratinocytes expressing low levels of xcex16xcex24 represent a subpopulation of post-mitotic, differentiating keratinocytes, this integrin is expressed at high levels on both the KSC and TA cells. Thus this cell surface marker alone, cannot be used to separate KSCs from TA cells to a high degree of purity but can do so to a degree of purity higher than where xcex21 integrin is used.
It is the finding of the inventors that enrichment for human KSCs to a high degree of purity can be successfully achieved on the basis of a second cell surface component whose expression is proliferation-related in conjunction with xcex16xcex24 integrin. The experiments conducted to date have used transferrin receptor as the cell surface component that is proliferation related. It is also suggested that sufficient purification should be achievable where another marker capable of identifying KSC and TA cells (and perhaps also cells that have been differentiated further) is used in place of xcex16xcex24 in the above two step process and that other marker might be another integrin such as xcex12xcex21 or xcex13xcex21 .
In a first aspect the invention could be said to reside in a method of enriching a viable population of KSCs from a population of epidermal cells comprising,
a) a first enriching step of enriching for cells carrying a high level of cell surface integrin from the population of epidermal cells to form a partially enriched pool, and
b) a second enriching step of removing cells that carry high level expression of a marker associated with proliferation from the partially enriched pool.
Conversely TA cells might be purified from KSCs whereby a proportion of cells with low expression of a marker associated with proliferation are removed from the partially enriched pool.
The epidermal cell population might be derived (torn a tissue sample of the skin. This method normally involves the separation of epidermis from the skin sample, before the enrichment. One particularly good source of KSC cells is from the basal layer of the epidermis. The proportion of these cells that are KSCs will depend upon the type of skin, and the age of the individual concerned. It is estimated for example that about 10% of neonatal foreskins are KSC cells but a lesser proportion will be present in the basal layer of the epithelium of adults. Hair follicles are also known to be a reservoir of stem cells and might be used as a source rich in KSCs.
It has been shown that significant enrichment can be achieved in the first step by the use of xcex21 in the first enrichment step, and it is thus thought that integrins xcex12xcex21 or xcex13xcex21 could be used in this enrichment. xcex21 is however less effective in the two step enrichment process than xcex16xcex24 integrin because it recognises epidermal cells that have developed past the TA stage and therefore the first enrichment step leads to a lesser enrichment than by use of xcex16xcex24 integrin which recognises only KSC cells and TA cells.
The marker associated with proliferation that has been used by the inventors is one that is recognised by monoclonal antibody 1007 and has now been identified as being the transferrin receptor. There are a number of commercially available monoclonal antibody preparations that also recognise transferrin receptor. Alternative markets that are associated with proliferation can also be used examples of these include but are not limited to the EGF (Epidermal Growth Factor) receptor, and perhaps also the IGF (Insulin Growth Factor) receptor and the KGF (Keratinocyte Growth Factor) receptor.
It will be understood recognition of cells carrying the cell surface markers that form the basis of the separation can be effected by a number of different methods, however, all of these methods rely upon binding of a binding agent to the integrin molecule, followed by a separation of chose that have high levels of binding from those that have low levels of binding. The most convenient binding agents are antibodies or antibody based molecules, preferably being monoclonal antibodies or based on monoclonal antibodies because of the specificity of these latter agents. Antibodies can be used for both steps. However other agents might also be used, thus ligands for these integrins such as extracellular matrix proteins including laminin-5 or collagen I or IV may also be employed to enrich for cells carrying xcex16xcex24. Likewise transferrin itself could be used as a means for detecting the levels of transferrin receptor, in place of 10G7 or other antibody directed against transferrin receptor.
The antibodies may be attached to a solid support to allow for crude separation. The separation techniques employed should maximise the retention of viability of the fraction to be collected. Various techniques of different efficacy may be employed to obtain relatively crude separations. The particular technique employed will depend upon efficiency of separation, associated cytoxicity, ease and speed of performance, and necessity for sophisticated equipment and/or technical skill. Procedures for separation may include, but are not limited to, magnetic separation, using antibody-coated magnetic beads, affinity chromatography and xe2x80x9cpanningxe2x80x9d with antibody attached to a solid matrix. Techniques providing accurate separation include but are not limited to, FACS.
In the experiments conducted thus far the xcex16xcex24 has been selected on the basis of the portion being identified, i.e. xcex16, however the xcex24 portion could equally well be used. Commercially available monoclonal antibody preparations that recognise xcex16 are available for these for example those known as GOH3 and 4F10.
It is found that by using an accurate separation method a purified KSC cell population can be achieved, which is believed to have less than 1% non KSC cells, however using cruder enrichment techniques a variety of levels of purified KSC cells can be produced, and may be useful at lower levels of purity. It is believed that purity levels of greater than 50% or at least greater than 70% may be useful for an improved formation of an epidermal layer which can be used as a graft for a skin lesion. A substantially purified KSC cell population of greater than about 90% is thought to be useful for not only the formation of an epidermal layer but also for use as a starting cell population for genetic modification whereby exogenous nucleic acid is introduced to express a desired product, which may be used in gene therapy.
In this regards it is considered that enriching for KSCs on the basis of the presence of xcex21 alone integrin will result in a population with only a limited capacity to provide a differentiated skin graft, it is suggested that selection of the xcex16xcex24 on its own may result in a sufficiently pure population of KSC cells to achieve an enhanced capacity to produce a differentiated epidermal layer. With a higher purity of KSCs it is expected that a graft should repopulate faster and should persist longer.
The capacity to isolate substantially purified KSCs opens up significant useful potential in some quite major areas.
Firstly autologous repair of skin lesions, by the formation of a layer of skin generated from cells isolated from the same individual. Methods of generating epidermis from epidermal cells are found for example in U.S. Pat. No. 5,712,163 by Parenteau et al which also refers to other references therein, particularly in column one which are incorporated herein by reference. It is suggested that these methods will be applicable where KSCs and TA cells of the present invention are used.
Secondly the accessibility of skin makes KSCs an ideal candidate for generic manipulation and gene therapy for the treatment of both skin disorders and systemic deficiencies. Thus exogenous nucleic acid would be introduced into autologous KSCs, to produce a therapeutically useful substance. The cells can be formed into an epidermal layer which could be grafted onto the skin of the individual concerned and act as a means for long term release of the therapeutic compound. The compound is thus introduced systemically. The compound might be one that is not produced by the individual as a result of a congenic defect, or a disorder that has developed, for example diabetes. Purification of KSCs according to the present invention are suggested to give rise to a skin graft of greater persistence and accordingly the gene therapy should last longer than would otherwise be possible. Suggestions for gene therapy using KSCs for gene therapy have been made with one of the acknowledged deficiencies being recognised as the lack of purified KSCs.
A third useful result of this invention relates to the enhanced capacity to find markers associated with proliferation of various cell sub populations of the skin involved in the early proliferative events and to enhance the understanding of these early proliferative events, with the greater potential to discover the reason for defects in the proliferative process which lead to cancers.
The invention could therefore also be said to reside in a composition including an enriched cell population of KSC cells capable of being enriched by firstly enriching a cell population for cells that carry an integrin marker and secondly reducing the number of cells that carry a marker associated with proliferation. Such compositions might include a tissue layer suitable for autologous skin graft application and a genetically modified population of KSC cells.
In a further form the invention could be said to reside in a composition formed from an enriched cell population of KSC of this invention. The composition could be the result of an epidermal layer that is used as a skin graft that has been derived from KSCs.


A voltage-controlled capacitor circuit and related circuitry. The voltage-controlled capacitor circuit includes a metal-oxide semiconductor (MOS) varactor, a diode varactor, and/or a capacitor with fixed capacitance. The MOS varactor, the diode varactor and the capacitor are electrically connected in parallel or in series to form a capacitor with a preferred characteristic of voltage-controlled capacitance.

1. Field of the Invention
The invention relates to a voltage-controlled capacitor circuit and related circuitry, and more particularly, to a metal-oxide semiconductor (MOS) varactor and a diode varactor to form a capacitor with preferred a characteristic of voltage-controlled capacitance and other circuits with related applications.
2. Description of the Prior Art
In modern information business, all kinds of data, information, video, and so on are all transmitted electronically; therefore, a processing circuit for dealing with electronic signals becomes the most important foundation of modern information business. For example, in common information systems (such as a personal computer), a global clock is required to coordinate all digital circuits in the system, so an oscillator for generating clock is an indispensable circuit block for modern digital circuits. In addition, to synchronize circuits with different clocks, phase loop lock (PLL) circuits are needed, and a precise voltage-controlled oscillator (VCO) is essential for the PLL to generate different frequencies of signals. Furthermore, in some precise filters, resister-capacitor (RC) filters, in which filter frequency can be adjusted, are utilized frequently.
With filter characteristics of an RC filter and the oscillation characteristic of an LC oscillator, it is possible to adjust each of them by modifying the capacitance value. Please refer to FIG. 1. FIG. 1 is a schematic diagram of a prior art VCO10. The VCO10 has a pair of coupled MOS transistors T1, T2 to form an oscillation circuit, and voltage Vd biases the VCO10. The gate electrodes of T1 and T2 are input ends of the VCO, and are connected electrically with nodes NP2 and NP1 separately. The drain electrodes of T1, T2 are output ends of the VCO, and are electrically connected to Np1 and Np2 separately. A current source Ip0 that is electrically connected to the source electrodes of transistor T1 and T2 provides current for the circuit. And a pair of coupled diodes Dp1 and Dp2 serve as varactors, and their cathodes are electrically connected to nodes Np1 and Np2. Their anodes being controlled by the voltage Vc0 makes these two diodes Dp1 and Dp2 reversed-biased, and results in a depletion region in the PN-junctions of each of them. This will make Dp1 and Dp2 form an equivalent capacitor between each of their anodes and cathodes. The capacitors provided by the diode Dp1 and Dp2 can form an LC tank with a pair of coupled inductors Lp1 and Lp2. The capacitor provided by the diode Dp1 and the inductor Lp1 can be regarded as the load of the transistor T1. If the transistor T1 receives an input oscillation signal from its gate electrode and outputs the signal through Np1 to the load, it is equivalent to modifying the phase of the input oscillation signal. The input oscillation signal enters the gate electrode of the transistor T2 through node Np1 after being phase-modified by the transistor T2 again, and from node Np2 it will feedback to the transistor T1 once again. According to the feedback mechanism mentioned above, it will produce a periodical oscillation signal at nodes Np1 and Np2.
Since the VCO10 deploys the LC circuit to generate a resonant signal, the frequency of the resonant frequency is proportional to 1/√{square root over ((L0·C0))}; where L0 is the inductance value of the inductors of Lp1 and Lp2, and C0 is the equivalent capacitance value of the diodes Dp1 and Dp2. In VCO10, the diodes Dp1 and Dp2 serve as voltage-controlled varactors. The capacitance of the varactors can be simply modified by changing the voltage across the anode and the cathode. Furthermore, changing the voltage means changing the resonant frequency of the VCO, and this will achieve the goal of voltage-controlled frequency. Please refer to FIG. 2A and FIG. 2B. FIG. 2A and FIG. 2B are schematic diagrams of the relationship between the voltage and the equivalent capacitor across the anode and the cathode when a diode is used as a varactor. When a diode D0 acts as an equivalent varactor, with a capacitance of Ca0 between Na1 (cathode) and Na2 (anode), a relationship between Va12 (the voltage across cathode and anode) and Ca0 is shown in FIG. 2A; where the X-axis is the voltage of Va12, and the Y-axis is the capacitance of Ca0. On the other hand, FIG. 2B shows a relationship between the reciprocal and square root of the capacitance of Ca0 and the voltage of the Va12. When the diode D0 is applied into LC-VCO, it is better for the circuit designer to linearly voltage-control the resonant frequency of the VCO. Since the resonant frequency is proportional to 1/√{square root over (Ca0)}, it represents that a linear relationship between the controlled-voltage and 1/√{square root over (Ca0)} would be better. But as FIG. 2B shows, the voltage Va12 across the diode D0 does not show a reasonable linearity with 1/√{square root over (Ca0)}, and would be a problem when designing the circuit. Moreover, that the characteristic of a voltage-controlled-capacitor diode varactor is mostly decided by a semiconductor manufacturing process, which cannot be adjusted by the method of circuit design, makes it inflexible to be applied into circuit design.
In the prior art mentioned above, a diode is used as a varactor. Now that MOS processes have developed, MOS can now be used as a voltage-controlled varactor too. Please refer to FIG. 3, which is a schematic diagram of the voltage-controlled characteristic of a MOS when used as a varactor. The gate electrode of the MOS M0 form an end at node Nb1, the source and the drain electrodes of the transistor MO are both connected at node Nb2 to form another end. Then an equivalent capacitor Cb0 is formed between Nb1, Nb2, and M0. FIG. 3 is a relationship schematic diagram between the capacitance of Cb0 and the voltage of Vb12. Where the X-axis is the voltage of Vb12 and the Y-axis is the capacitance of the equivalent capacitor Cb0. As FIG. 3 shows, when the transistor M0 is a voltage-controlled varactor, the voltage-controlled characteristic of it becomes more sophisticated, and more non-linear. Though a small segment of the characteristic curve appears to be linear, it is too narrow to be flexibly used in circuit design.

Voltage-controlled capacitor circuit and related circuitry with diode and MOS varactors


A method for generating a block-based image histogram from data compressed by JPEG, MPEG-1, and MPEG-2, or uncompressed image data employing block-based linear quantization to generate histograms that include color, brightness, and edge components. The edge histogram, in particular, includes the global edge features, semi-global edge features, and local edge features. The global edge histogram is based on image blocks of the entire image space. The local edge histogram is based on a group of edge blocks. The semi-global edge histogram is based on the horizontally and the vertically grouped image blocks. A method for generating block-based image histogram with color information and brightness information of image data in accordance with an embodiment of the present invention extracts feature information of an image in terms of the block and updates global histogram bins on the basis of the feature information. The method for generating block-based image histogram with color information and brightness information of image data minimizes quantization error by employing linear weight and updates values of histogram bins. The error that occurs at a boundary between bins of the histograms and the linear weight depends on the distance between the histogram bins.

1. Field of the Invention
The present invention relates to a method for generating a block-based image histogram from data compressed by JPEG, MPEG-1, and MPEG-2, or uncompressed image data. In particular, the method employs block-based linear quantization to generate histograms that include color, brightness, and edge components.
2. Description of the Related Art
JPEG is the international standard for still images and MPEG-1, 2 are for moving pictures. Regarding the compressed image information, feature information is necessary for applications such as extracting key frames, searching images, and browsing.
To extract such feature information, a brightness and color histogram that express relative frequency of brightness and color (red, green, blue) in an image is widely used. Methods comparing histograms have been proposed for searching digital video applications. As histograms are used for searching images and detecting motion change, it is proposed that conventional histograms be improved. That is, conventional single component histograms with discrete quantization and color have been developed, and therefore composite histograms that employ linear update and soft decision are adopted for effective and efficient image description.
U.S. Pat. No. 5,805,733 "Method and system for detecting scenes and summarizing video sequence" disclosed a method that employs color histograms and edge maps for detecting motion change. Though the method is effective in that it extracts color information in consideration of the human eye, it doesn't use brightness information. A method disclosed by a technical paper "Color Indexing" published by International Journal of Computer Vision receives color information and measures similarity of images by histogram intersection method. However, this method doesn't use brightness information and therefore accuracy is not good enough. Also, since the conventional methods generate histograms using a discrete quantization method, a relatively large number of histogram bins are needed to achieve good performance. Consequentially, these methods are not efficient in terms of storage and similarity measurement.
In addition, because the conventional methods perform feature extraction in terms of pixel in generating histograms, feature information is very restrictively generated.

Method for generating a block-based image histogram

Electronics and Telecommunications Research Institute


Compounds of the formula I:

Neurodegenerative diseases such as Parkinson's disease, Lewy body dementia and Huntington's disease affect millions of individuals. Parkinson's disease is a chronic, progressive motor system disorder that afflicts approximately one out of every 1000 people, with hereditary Parkinson's disease accounting for 5-10% of all of patients. Parkinson's disease is caused by progressive loss of mid-brain dopamine neurons, leaving patients with impaired ability to direct and control their movements. The primary Parkinson's disease symptoms are trembling, rigidity, slowness of movement, and impaired balance. Many Parkinson's disease patients also experience other symptoms such as emotional changes, memory loss, speech problems, and sleeping disorders.
The gene encoding the leucine-rich repeat kinase 2 protein (LRRK2) has been identified in association with hereditary Parkinson's disease (Paisan-Ruiz et al., Neuron, Vol. 44(4), 2004, pp 595-600; Zimprich et al., Neuron, Vol. 44(4), 2004, 601-607). In-vitro studies show that Parkinson's disease-associated mutation leads to increased LRRK2 kinase activity and decreased rate of GTP hydrolysis compared to wild-type (Guo et al., Experimental Cell Research, Vol. 313(16), 2007, pp. 3658-3670. Anti-LRRK2 antibodies have been used to label brainstem Lewy bodies associated with Parkinson's disease and cortical antibodies associated with Lewis body dementia suggesting that LRRK2 may play an important role in Lewie body formation and pathogenesis associated with these diseases (Zhou et al., Molecular Degeneration, 2006, 1:17 doi:10.1186/1750-1326-1-17). LRRK2 has also been identified as a gene potentially associated with increased susceptibility to Crohn's disease and susceptibility to leprosy (Zhang et al., New England J. Med. Vol. 361 (2009) pp. 2609-2618.
LRRK2 has also been associated with the transition of mild cognitive impairment to Alzheimer's disease (WO2007/149789); L-Dopa induced dyskinesia (Hurley et al., Eur. J. Neurosci., Vol. 26, 2007, pp. 171-177; CNS disorders associated with neuronal progenitor differentiation (Milosevic et al., Neurodegen., Vol. 4, 2009, p. 25); cancers such as kidney, breast, prostate, blood and lung cancers and acute myelogenous leukemia (WO2011/038572); papillary renal and thyroid carcinomas (Looyenga et al., www.pnas.org/cgi/doi/10.1073/pnas.1012500108); multiple myeloma (Chapman et al., Nature Vol. 471, 2011, pp. 467-472); amyotrophic lateral sclerosis (Shtilbans et al., Amyotrophic Lateral Sclerosis "Early Online 2011, pp. 1-7); rheumatoid arthritis (Nakamura et al., DNA Res. Vol. 13(4), 2006, pp. 169-183); and ankylosing spondylytis (Danoy et al., PLoS Genetics, Vol. 6(12), 2010, e1001195, pp. 1-5).
Accordingly, compounds and compositions effective at modulating LRRK2 activity may provide a treatment for neurodegenerative diseases such as Parkinson's disease and Lewie body dementia, for CNS disorders such as Alzheimer's disease and L-Dopa induced dyskinesia, for cancers such as kidney, breast, prostate, blood, papillary and lung cancers, acute myelogenous leukemia and multiple myeloma, and for inflammatory diseases such as leprosy, Crohn's disease, amyotrophic lateral sclerosis, rheumatoid arthritis, and ankylosing spondylytis. Particularly, there is a need for compounds with LRRK2 affinity that are selective for LRRK2 over other kinases, such as JAK2, and which can provide effective drugs for treatment of neurodegenerative disorders such as Parkinson's disease.

Aminopyrimidine derivatives as LRRK2 modulators

Abstract: Compounds of the formula I:

Abstract: or pharmaceutically acceptable salts thereof,wherein m, n. X, R1, R2, R3, R4 and R5 are as defined herein. Also disclosed are methods of making the compounds and using the compounds for treatment of diseases associated with LRRK2 receptor, such as Parkinson's disease.


A photonic synthesizer includes a multifrequency optical source to produce a signal of interest from a pair of lasers, which may be self-injection locked chip lasers. The signal is referenced to a high frequency clock using a photonic mixer/divider based on an electro-optical modulator and a relatively slow photodiode. The electro-optical modulator produces optical harmonics from the beams from the pair of lasers, where one harmonic from the first laser beam and one harmonic from the second laser beam beat on the photodiode. A phase locked control signal is generated for controlling the output frequency of one or both of the two lasers. The output signal of the photonic synthesizer is generated using a relatively fast photodiode based on a difference in frequencies of the pair of lasers. The output signal may be a millimeter wave-band signal. The photonic synthesizer can be formed as a photonic integrated circuit (PIC).

A photonic frequency synthesizer is an opto-electronic device that generates or synthesizes a radio frequency (RF) signal, such as a microwave-band or millimeter wave-band RF signal, on demand. Such signals may be used in various applications including communications receivers and Radar devices. Existing RF frequency synthesizers (whether electronic or photonic) often have technical limitations in generating broadly tunable spectrally pure microwave or millimeter wave signals. These limitations may include i) narrow frequency range, which is usually less than an octave, ii) slow tuning speed, iii) large physical dimensions, iv) limited accuracy, and v) limited spectral purity. Aspects of the systems, devices, apparatus, and methods described herein are directed to addressing these limitations or other issues on existing devices.

Wideband photonic synthesizer stabilized to a reference clock using photonic components


A climbing wall assembly for educational and recreational purposes. The climbing wall assembly has a plurality of adjacently positioned wall panels, each having an exterior paint/aggregate textured surface adapted for educational purposes. A plurality of wall apertures are provided for mounting hand hold structures so that a plurality of climbing paths may be provided. Markable paint/aggregate climbing wall surfaces are also provided. Removable magnetic and metallic educational elements may also be utilized by the climbers. A paint/aggregate layer having metallic or magnetic particles mixed therein may be utilized to provide the magnetic climbing wall surface and to provide magnetic qualities to climbing wall components.

The present invention relates generally to climbing wall assemblies and particularly to climbing wall assemblies that are utilized for educational and recreational purposes. More particularly, this invention relates to climbing wall assemblies comprised of wall panels having exterior surface structures adapted for use with associated removable educational element structures. This invention further relates to climbing wall surfaces formed of paint/aggregate mixtures.
The rock climbing and bouldering sports have become increasingly popular activities. As a result, artificial climbing and bouldering walls are increasingly being used for training purposes by climbers. The climbing wall assemblies of the present invention are provided to introduce children into the climbing sports in a safe and educational manner.
The climbing wall assemblies of the invention are constructed and arranged for educational climbing wall activities. The climbing wall assemblies are comprised of versatile, cooperating elements which provide the ability to create a plurality of climbing routes to be used by climbers. The elements may be easily changed and adjusted to provide a variety of educational climbing activities. The climbing wall assemblies of the invention are economical to manufacture, easy to install and are versatile in use.
The climbing wall assemblies of the invention may be comprised of wall panels to create climbing walls. The invention further provides a wall climbing surface which is textured to provide a natural rock look and feel. Wall plates and hand holds are mounted to the wall panels or climbing wall structures. The wall panels are constructed and arranged to be mounted to a load bearing structure such as a wall of a building or a free standing structure, for example. The climbing wall assemblies may include adjoining writing board wall panels having smooth surfaces, i.e., a "chalkboard" or a "white board" surfaces, including those having metallic and magnetic properties for receiving erasable markings. The climbing wall assemblies may include adjoining molded wall panels having metallic or magnetic surface properties for use with magnetic or metallic educational elements. Alternatively, a paint or coating layer having metallic or magnetic particles may be applied to a climbing wall or other climbing wall component, i.e., a hand hold, wall plate or educational element structure. The paint or coating layer may also include an aggregate so as to provide a textured surface for the climbing wall and to climbing components used in connection with the climbing wall.
The climbing wall assembly may also incorporate the use of wall plates and hand holds which preferably are molded of a plastic composition and which may incorporate metallic particles for use with magnetic educational elements. The wall panels, wall plates and hand holds are all constructed and arranged to provide a versatile and adjustable climbing wall assembly that permits a plurality of climbing routes to be created and which allows markings to be made on the wall panel surfaces and magnetic or metallic elements to be easily placed and moved by climbers for recreational and educational use.
Although the prior art teaches the use of wall structures and hand holds that are used for climbing purposes and other prior art discloses the use of magnetic elements with respect to hand holds, these prior art devices are restricted and limited in use and do not disclose or suggest the climbing wall assembly and components of the present invention. The combination of the molded wall panels, hold or wall plates and hand and foot hold structures having markable and erasable surfaces and/or surfaces with metallic or magnetic properties for use with magnetic or metallic elements are not provided in the prior art. A need exists in the wall climbing art for such climbing wall assemblies. There is a further need to provide a magnetic surface on a climbing wall in an inexpensive, effective and easy manner and to provide a climbing wall with a textured exterior surface having the look and feel of a natural climbing environment.
The present invention provides a climbing wall assembly that is versatile and permits numerous climbing routes to be created and utilized for educational purposes. Further, the present invention provides inexpensive and easy to apply magnetic and metallic surfaces to climbing wall surfaces and associated components.

This patent is subject to a terminal disclaimer.


A fiber optic transceiver incorporating a lens array with an integrated mirror and method of creating the same is disclosed. The transceiver includes the lens array and transceiver housing used to convert optical signals to electrical signals. The lens array includes a fiber side that can be connected to a fiber optic connector. The lens array also has a device side that can be connected to a photodetector. The lens array also includes a mirror that is positioned to transmit an optical signal received from the fiber side to the device side. Both the fiber side and the device include lenses used to provide focused transmission of optical signals. Accordingly, optical signals can be transmitted from a fiber optic connector to a photodetector in a compact and efficient manner at high bandwidths.

The present invention relates to a fiber optic transceiver having efficient connection structure. More specifically, the present invention relates to a fiber optic transceiver assembly that receives and transmits at faster data rates while reducing signal loss by incorporating a compact lens array having an integrated folding mirror.
Modern fiber telecommunication and data communication systems use transmitter/receiver components, commonly known as transceivers. As is well known, fiber optic transceivers facilitate bi-directional signal transmissions between electronic devices and fiber optic system components. The transceivers include photodetectors, which convert received optical signals to electric signals which can then be used by many electronic devices. Photodetectors are typically positioned at the receiving end of the fiber optic data, video, or audio link. The most common photodetector is the semiconductor photodiode, which produces current in response to incident light. In addition, the transceivers also include transmitter components which produce optical signals. The transmitter portion may include light emitting diodes, laser diodes, or similar components to produce optical signals in response to provided electrical signals. Coupling optical signals into and out of an optical fiber often requires the use of precise optical components to ensure efficient signal transfer. Unfortunately, these optical components are potential sources of signal loss due to contamination or imperfections.
Demand for bandwidth in fiber communication systems is limitless. From economic and practical perspectives, it is desirable to minimize the size of all fiber optic components in the system. In fact, certain systems, such as those used for data transmission networks, equipment used for national defense, and the like, require compact yet efficient fiber optic components. As such, it is beneficial to reduce the size of components, provide the most efficient system layout, and eliminate unnecessary parts. Simply stated, there exists a need for a compact fiber optic transceiver assembly that reliably performs at high data rates.
The efficient connection of fiber optic cables is important in maintaining efficient operation. To maintain this efficient operation, it is desirable to avoid unnecessary bending or twisting of optical fibers. Thus, the geometry of the fiber connections is also important. Because connections are made directly to the transceiver, this geometry also affects the length of electrical connections mentioned above.
It is commonly known that, both optical and electrical signal losses increase as the number of components and connections in a fiber optic system are increased. These signal losses are very critical given the high frequency at which these systems operate. Light sources, such as lasers, and/or optical detectors are often connected to an electric amplifier which has electrical leads. These connections can be a source of signal loss, and often result in reductions in performance because of the electrical lead lengths. Accordingly, it would be very beneficial to provide fiber optic transceiver assembly that does not require long electrical leads between the optoelectric components and related electronic amplifiers.
Despite efforts by fiber optic transceiver manufacturers to standardize and minimize fiber optic transceivers, there still exists a need for a compact fiber optic transceiver assembly that performs at high data rates. In addition, there exists a need for a fiber optic transceiver assembly that efficiently and compactly couples optical signals from a standard fiber array connector to a transceiver without bending fiber optic cables. There also exists a need for a fiber optic transceiver assembly that allows for reduced length of electrical leads between the laser or detector photodiode, and the related amplifiers.

Lens array with integrated folding mirror


A system and method is provided for artificially lifting fluids from a formation. The system utilizes a production control unit having a jet pump assembly and valving to both lift the desired fluids and to provide well control.

In the production of hydrocarbon based fluids, artificial lift equipment can be used to produce a fluid to a surface location or other desired location. For example, a jet pump may be utilized to provide the artificial left. However, operation of a jet pump typically requires the use of two flow passages. A power fluid is pumped down through a flow passage to the jet pump, and commingled production is returned through another flow passage to the surface or other collection point. Due to the dual flow passage configuration, the use of jet pumps in some environments, e.g. offshore production, is rendered difficult as a result of regulations requiring that well control be maintained in a catastrophic situation. Specifically, such well control can be difficult and/or expensive because both fluid passages used in operation of the jet pump must be closed in a catastrophic event.

System and method for offshore production with well control


An object is to, for physical properties, holding force, contact area, and insertion force in a trade-off relationship, set the holding force to 37 N or more, the contact area to 0.72 mm2 or more, and the insertion force to 90 N or less. A press-fit terminal is to be press-fitted into a through hole formed in a circuit board. A press-fit part includes a beam and an eye hole that is surrounded by the beam. The beam includes two parallel parts that are parallel to each other. In the press-fit part, G1/G2 is 0.20 or more and 1.05 or less where a front-side spring strength is G1 [mm3] and a rear-side spring strength is G2 [mm3] calculated under the following conditions, and G is 0.007 mm3 or more and 0.012 mm3 or less where a spring strength G [mm3] is G1+G2.

Japanese Unexamined Patent Application Publication No. 2008-165987 discloses a press-fit terminal that includes: an introduction portion formed at a tip of the press-fit terminal and to be introduced into a through hole in a circuit board; a pressure holding portion that is connected to the introduction portion and is press-fitted and held in the through hole; and a main body portion connected to the pressure holding portion, and has an opening extending in a longitudinal direction from a center of the pressure holding portion toward the main body portion and the introduction portion.

Press-fit terminal, connector for board, and board-equipped connector


An exercise device is provided for exercise of the limbs by a seated person. The device is a flat seat that can have a back attached. Typically, the seat and back can be cushions or similar articles that can be used in conjunction with existing seats in a vehicle. One or more resilient straps are provided with grips and attached around the perimeter of the seat and back so that the seated individual can perform exercise.

The present invention is directed to an exercise device for use for attachment to a seat or chair, and particularly for use in a vehicle by either the passengers or operator of the vehicle. More particularly, the present invention is directed to a seat cushion and connected exercise equipment that is attachable, for example, to the seat of a vehicle to provide a facility for allowing the occupant of the seat to perform a variety of exercises while seated in the vehicle.
Increasingly, both at work and leisure, individuals find themselves in seated positions for extended periods with little or no opportunity for physical activity and with a resultant diminution of their faculties. In particular, for example, driver fatigue and tension brought about by lack of physical activity on long trips in cars, trucks, airplanes, and other motor vehicles or crafts is a leading cause of accidents. While it has long been recommended that drivers and others operating vehicles over long distances routinely and periodically stop and get out of the vehicles to exercise themselves, such interruptions are not always practical, for example, in situations where stopping and resting facilities are not available or where traffic makes such stops inadvisable or impossible. In such situations, lengthy periods of remaining seated with minimal movement of the body and limbs can induce a form of fatigue as well as a hypnotic fixation on the road ahead that ultimately can result in the driver becoming dangerously drowsy and inattentive.
Accordingly, there is a need for a system for providing stimulating activity in the form of exercise to individuals required to be seated over extended periods, particularly to both the passengers and operator of vehicles, especially when involved in long, uninterrupted trips or when driving in heavy traffic or over extended periods of time. Such a system should be portable, relatively inexpensive and adaptable to standard seating arrangements. The system should also provide an effective and varied form of exercise for the individual without interfering with the individual""s activity such as operating a vehicle or requiring that the vehicle stop during the exercise regimen.
Additional objects and advantageous of the invention will be set forth in part in the description which follows and in part will be obvious from the description or may be learned by the practice of the invention. The device can also accommodate leg exercises.
To achieve the above and other objects of the invention and in accordance with the purpose of the invention as embodied and broadly described herein, an exercise device is provided which comprises a seat cushion having a bottom and back, and a provision for the attachment of elastic straps with hand grips at various locations on the cushion to provide a device to enable the user to engage in an exercise regimen involving the arms and hands while seated on the cushion. By including a provision for attachment of the exercise straps at a variety of locations around the perimeter of the seat cushion, a large number of exercises can be performed by the individual including stretching and lifting using both the arms and wrists. Further, the degree of elasticity of the exercise straps can be varied to suit the needs of the particular individual using the device and the length of the straps can also be varied to better accommodate individuals of different size and to accommodate different exercise activities. It is to be understood that this general description and the detailed description which follows, while exemplary and explanatory, are not restrictive of the invention.
The accompanying drawings, which are incorporated in and constitute part of this specification, illustrate the embodiments of the invention and, together with the description, serve to explain the principles of the invention.
The back portion and bottom portion are hinged relative to each other at 22 to permit folding.


Provided is a self-calibrating time code generator and method for generating an accurate time code (e.g., an accurate IRIG waveform). The self-calibrating time code generator includes a phase-locked loop configured to provide a generated output signal based on a phase difference between an absolute time reference signal and a compensated generated input signal, an IRIG encoder configured to couple a present time value with the generated output signal to form an IRIG waveform, a delay difference indicator configured to provide a time interval value based on a comparison of corresponding pulse edges of the generated output signal and the IRIG waveform, and a numerical delay component configured to delay the generated output signal by the time interval value to form the compensated generated input signal used to time-align the IRIG waveform with the absolute time reference signal to form the accurate IRIG waveform.

The present invention generally relates to self-calibrating time sources, and more specifically, to a self-calibrating time code generator that dynamically compensates for time delays to generate an accurate time code waveform.
A self-calibrating time source may be used to provide calendar and time-of-year information to a variety of devices for a variety of reasons. For example, sequential events recorders record occurrences of events, and then store a record of each occurrence in a report. The time of the occurrence of each event is also included with the event in the report. The time of the occurrence stored for each event is often derived from a time code generator. Thus, the more accurate the self-calibrating time source, the more accurate the recorded time of each event occurrence in the report.
Self-calibrating time sources may also be used to provide synchronization for various devices. For example, some devices are configured to take a number of measurements of an ongoing process at precisely predefined instants of time. Such a device may be required to measure a process parameter such as a voltage, a current, a temperature, a strain measurement, etc., once per second exactly on the second, (e.g., the measurements must be taken exactly at midnight, exactly one second after midnight, exactly two seconds after midnight, etc.). For example, digital fault recorders used in the power system industry require sampling of data from a power line, referenced to time. As a result, such devices often synchronize their measurement activities to a time code generator. Thus, the more accurate the self-calibrating time source, the more accurate the measurement timing.
Implementation of a time source often introduces inherent time delays. That is, the design of, and the components used to implement the time source are often responsible for inherent time delays during operation. Noise coupling into the time source, and loading or line-induced delays may also contribute to time delays. In addition, the time delays may dynamically vary over time, due to temperature variations or component aging. Such delays directly reduce the time accuracy and therefore the performance of the devices requiring the time information.

Schweitzer Engineering Laboratories, Inc.