A radar level gauging system for determining a filling level of a product contained in a tank by transmitting and receiving microwave signals over at least two functionally independent channels. Each channel has an electronics unit with transceiver circuitry arranged on a printed circuit board and processing circuitry connected to the transceiver circuitry for determining the filling level based on a relation between transmitted signals and received signals, and each electronics unit is electronically and galvanically separated from other electronics units. The system further comprises a single antenna for emitting microwave signals into the tank, and a hollow waveguide for guiding microwave signals between each transceiver circuitry and the antenna. Each electronics unit further comprises feeding circuitry arranged on the printed circuit board, the feeding circuitry comprising at least one feeding probe protruding into the waveguide for feeding the microwave signals into the waveguide.

Radar level gauging (RLG) to measure the level of a filling material, such as a liquid or a solid like a granulate is an increasingly important method for level gauging in tanks, containers, etc. Many different types of RLG systems are previously known. An example of such a systems is disclosed in U.S. Pat. No. 7,106,247 by the same applicant.
For many applications, such as for instance in radar level gauging systems for a tanker's load containers, at least one overfill alarm that is functionally independent of the level measuring system is required. Functional independence here means that a fault in one system does not render the other system(s) inoperative. Such independence can be achieved by ensuring that there is no common electrical circuits and cabling, i.e. there must not be any galvanic contact between different measuring systems. However, fixed mechanical constructions for example, which cannot normally go wrong, may be shared. Thus, due to safety restrictions, environmental laws and requirements, etc, there is often a need for several measurements of the surface level of the medium in the container, which measurements are completely separated and independent from each other. The user further may want redundancy in measured values which may require more than one installed measurement system, which may require at least two complete independent level gauges.
Several such radar level gauging system providing two or more functionally independent channels are previously known. For example, U.S. Pat. No. 6,414,625 by the same applicant discloses a device and a method for measuring the level of the surface of a filling material in a container involving more than one radar channel for obtaining a measured value of said level, where the level values measured in said channels are obtained independently of each other. This is accomplished by use of at least two microwave signals distributed in separate channels fed to the same antenna unit, whereby the at least two signals are used to measure the level independently of each other. Said microwave signals are distinguished by means of a detectable characteristic.
A further example of such a system using several channels for feeding one and the same antenna is disclosed in WO 03/025523, also by the same applicant. In this system, the gauging system comprises a feeding mans, which has two or more wave guide members for forwarding the wave guide signals to and from the antenna.
Independent radar level gauges using the same physical antenna but otherwise electrically independent have found use for redundancy at a low cost. The method to connect more than one sensor to one antenna is a very cost effective way to implement e.g. a system with a level sensor and an independent overfill alarm, etc, and has gained wide acceptance among users and authorities. However, previously known systems of this type typically requires complex feedings arrangements, involving complex combiners, couplers and the like, and are therefore relatively complex and costly. Further, these known systems are also impaired by relatively large signal and measurement errors.
For example, the above-discussed system disclosed in WO 03/025523 uses an old turn-style junction as the coupling device to connect the sensors to the antenna, with a coaxial cable to each sensor. The coaxial connectors have due to their design and specifications a rather high VSWR (Voltage Standing Wave Ratio) which introduces an off-set error which is difficult to predict, and in addition the coaxial cables introduce an internal length which will add near-zone errors. Especially for frequencies where standard SMA (SubMiniature version A) connectors cannot be used, typically for frequencies above 18 GHz, the additional cost is also not negligible and the VSWR is bigger.
There is therefore a need for an improved RLG system with two or more independent radar level gauges using the same physical antenna.

Abstract: The present invention enables a very simple, cost-effective and reliable feeding for each channel.


A portable emergency medical monitoring and transmission system capable of sending a message to a personal caretaker and/or an emergency response center. The system includes a wearable monitor/transmitter device including a glucose level detector, a geolocation system, and a communication interface to send and/or receive a message. A processor operable within the device collects information produced by the glucose level detector and the geolocation system to determine whereabouts and existence of a hypoglycemic or hyperglycemic condition of the patient. Upon detecting an unsafe medication condition, the processor assembles a message that includes patient identifier data, whereabouts of said patient, and an emergency alert indication; and activates a transmitter to transmit an emergency message in response to a hypoglycemic or hyperglycemic condition. An optional caretaker receiver receives the message and produces a local alarm indicating that the patient requires assistance. A transmission path of the transmitter conveys, in response to an emergency alert indication, the emergency message to an emergency response center indicating that the patient needs help.

This invention relates to an emergency medical monitoring and response system and method, but more specifically, to a wearable device and related support personnel communication equipment to detect an emergency medical condition of diabetic patient and/or to report such condition to a personal caretaker.
Diabetes afflicts a significant portion of the population. The disease affects persons whose bodily functions are unable to maintain a proper blood glucose level without medication, diet or treatment. An insulin injection is common treatment when glucose levels rise when bodily functions fail to produce sufficient insulin while sugar consumption treats low blood glucose levels. If an unsafe blood glucose condition remains untreated—even for a few moments—the patient may lose consciousness, become comatose, suffer irreparable brain damage, and possibly die. As such, persons suffering from diabetes must constantly be monitored and guarded against hypoglycemia or hypoglycemia, which restricts the person's activity and mobility.
Thus, a goal of the present invention is to enable substantially unrestricted mobility of diabetic individual without an undue risk of a lapse in treatment should an emergency condition arise.
It is another goal of the present invention to provide a wearable device that automatically monitors blood glucose levels and to prompt the patient to take appropriate action and, when the patient is unable to perform self-treatment, to transmit an emergency message as to the patient's condition and whereabouts to a personal caretaker and/or emergency medical response center, such as a hospital or an ambulatory service.
It is another goal of the present invention to provide a wearable device, as aforestated, that includes a location detector such as a GPS receiver, and a transceiver, such as a cellular telephone interface, to provide a transmission of the patient's condition, whereabouts, or other information.
It is another goal of the present invention to provide a wearable device that automatically treats a diabetic upon detection of an unsafe blood glucose level should the diabetic fails to implement self-treatment within a predetermined period of time after detection of an unsafe diabetic condition.

Personalized emergency medical monitoring and transmission system


A fluid dispensing closure includes a closure base having a deck, a skirt for securement to a container finish and a recess in the deck. The recess includes a first annular wall extending from the deck within the skirt, a second annular wall extending radially inwardly from the first annular wall at a position spaced from the deck, and a third annular wall extending toward the deck from an inner periphery of the second annular wall. A dispensing valve of flexible resilient elastomeric construction has a peripheral portion captured in compression between a collar and the third annular wall, and a concave central portion with at least one dispensing slit. In the preferred embodiment, the collar includes a flat annular deck, and a first annular wall extending from an outer periphery of the flat annular deck and engaging the third annular wall on the base to secure the collar and the valve to the base such that the outer surface of the annular deck of the collar is flush with the outer surface of the deck of the closure base.

U.S. Pat. No. 6,672,487 discloses a dispensing package for fluid products that includes a container having a body for holding a product to be dispensed and a finish with an open mouth. A closure base includes a skirt externally secured to the container finish and a wall coaxial with the container mouth. A collar has a deck with a central opening aligned with the mouth and a wall secured to the wall on the closure base. A dispensing valve of flexible resilient elastomeric construction has a peripheral portion captured between the collar deck and the base wall for securing the valve in position and simultaneously functioning as a seal between the base and the collar. A lid is integrally hinged to the collar or to the base.
Although the dispensing closure and package disclosed in the noted patent address problems theretofore extant in the art, further improvements remain desirable. In particular, it is desirable to provide a fluid dispensing closure of the subject type in which the dispensing valve and the valve retention collar are disposed within the closure base so as to provide a low profile appearance, inhibit removal of the collar and the valve and/or facilitate cleaning of the closure deck. A general object of the present invention is to provide a fluid dispensing closure, a dispensing package and a method of making a fluid dispensing closure that address one or more of these objectives.
A fluid dispensing closure in accordance with one aspect of the present invention includes a closure base having a deck, a skirt for securement to a container finish and a recess in the deck. The recess includes a first annular wall extending from the deck within the skirt, a second annular wall extending radially inwardly from the first annular wall at a position spaced from the deck, and a third annular wall extending toward the deck from an inner periphery of the second annular wall. A dispensing valve of flexible resilient elastomeric construction has a peripheral portion captured in compression between a collar and the third annular wall, and a central portion with at least one dispensing slit. In the preferred embodiment of the invention, the collar includes a flat annular deck, and a first annular wall extending from an outer periphery of the flat annular wall and engaging the third annular wall on the base to secure the collar and the valve to the base such that the outer surface of the annular deck of the collar is flush with the outer surface of the deck of the closure base. In the most preferred embodiment of the invention, these outer surfaces are in a plane that is at an acute angle to the axis of the closure base skirt so that any moisture that may collect on the outer surfaces tends to drain from the surfaces. Other aspects of the invention contemplate a fluid dispensing package that includes such a closure, and a method of making such a fluid dispensing closure.

Dispensing closure, package and method of manufacture


By increasing accelerator opening APO from time t1, kick-down shift is started at time t2. While the kick-down shift is carried out by changeover from a release element to an engagement element, a motor torque tTm that is increased as Tmo with an increase in accelerator opening APO is restricted as follows. In a shift initial stage from time t2 to inertia phase start time t3, motor torque tTm is restricted to not exceed upper limit value Tlimit obtained by subtracting an inertia phase progressing torque increment Tip from an inertia phase end outputtable maximum motor torque Tmo2 that is outputtable with motor rotation speed Nmo2 at inertia phase end time t4. During an inertia phase (t3-t4), the motor torque tTm is restricted to a value Tlimit+Tip.

Conventionally, an electric automobile as described in Patent Literature 1 is known as an electric vehicle equipped with an automatic transmission as described above.
The electric automobile includes an electric motor solely as a power source and the automatic transmission disposed between the electric motor and driving wheels, and allows the automatic transmission to convert motor torque from the electric motor and transmit the thus converted motor torque toward the driving wheels.
In the automatic transmission, shift from a gear stage (shift stage) as selected to a target gear stage is performed by changeover of transmission friction elements between engagement and release.
Upon carrying out the changeover of transmission friction elements between engagement and release during the shift operation, a predetermined time (shift time) is necessary from start of the shift operation to finish of the shift operation for such a reason that it is required to carry out changeover between a release-side transmission friction element to be switched from an engagement state to a release state and an engagement-side transmission friction element to be switched from a release state to an engagement state.
On the other hand, since a large torque is required upon depressing an accelerator pedal, the automatic transmission is downshifted (kick-down shifted) to a low-side gear ratio. Also, during a shift time in which the downshift is executed, it is necessary to transmit a large torque responding to depression of the accelerator pedal toward the driving wheels.
Further, generally, upon controlling the electric motor, a target motor torque requested by a vehicle driver is determined from motor rotation speed and an amount of depression of an accelerator pedal, and the electric motor is controlled such that the motor torque reaches the target value.

Kick-down shift control device for electric vehicle


An electron source includes: linear thermionic cathodes for emitting electron beams; an electron beam lead-out electrode which is disposed substantially in a parallel relationship with the linear thermionic cathodes and is formed with apertures for passing the electron beams therethrough; and a plurality of support members for supporting the linear thermionic cathodes each of which has a contact portion held in contact with at least a portion of the linear thermionic cathodes; wherein each of the apertures of the elctron beam lead-out electrodes is disposed so as to confront the contact portion of the support member.

The present invention relates to an electron source of a display unit for use in a television receiver, a terminal display of a computer, etc.
Conventionally, in an electron source employing a linear thermionic cathode, there has been a drawback that the cathode itself is vibrated during drive of the electron source, thereby resulting in a variation of the quantity of emitted electron beams. In order to prevent vibrations of the cathode, Japanese Laid-Open Patent Publication Nos. 63-187538 (1988) and 2-33838 (1990) and U.S. Pat. No. 4,887,000 propose a countermeasure in which a support member having a contact portion held in contact with a portion of the cathode is provided.
One example of a known electron source employing a linear thermionic cathode is described with reference to FIG. 1, hereinbelow. In FIG. 1, a striped back signal electrode 32 is formed on an insulating substrate 31. A plurality of linear thermionic cathodes 33 are provided in a direction perpendicular to the face of the drawing sheet of FIG. 1 so as to intersect with the back signal electrode 32. A grid electrode 34 is provided above and substantially in parallel with the cathodes 33. In order to prevent vibrations of each of the cathodes 33, a cathode support means 36 which is obtained by forming holes on a flat plate is provided such that the holes confront the back signal electrode 32. Hence, in FIG. 1, the cathode support means 36 has a plurality of wall portions 36A. The cathode support means 36 is constituted by a metallic substrate 36a formed with the holes by etching or the like and a heat resistant insulating member 36b coated on the metallic substrate 36a. Meanwhile, the cathode 33 is strained so as to be lightly pressed against the cathode support means 36. Although not specifically shown, all the above mentioned components of the known electron source are enclosed in a vacuum vessel,
The operation of the known electron source of the above described arrangement is described as follows. In FIG. 1, when a voltage which is positive relative to the cathode 33 is applied to the grid electrode 34 so as to heat the cathode 33 to temperatures enabling emission of electrons therefrom and a predetermined potential is imparted to the back signal electrode 32, the area in the vicinity of the cathode 33 corresponding to a portion of the back signal electrode 32 having the predetermined potential imparted thereto partially has an electric field in which electrons can be emitted from the cathode 33. As a result, an electron beam 35 is emitted from the cathode 33. The known electron source employing the linear thermionic cathode 33 described above is used for a picture display device disclosed in, for example, U.S. Pat. No. 31,876.
However, in the known electron source, surface of the insulating member 36b adjacent to its portion held in contact with the cathode 33 is electrically charged in a driving state of the cathode 33. Thus, even if a pair of neighboring sheet portions 32A of the back signal electrode 32, which interpose each of the wall portions 36A of the cathode support means 36, are set at a quite low potential, such a state is brought about in which electron beams are emitted at all times from portions of the cathode 33 held in contact with the cathode support means 36. Electron beams emitted from the portions of the cathode 33 held in contact with the cathode support member 36 pass partially, as leaked electron beams, through apertures of the grid electrode 34 as shown by the broken lines in FIG. 1. Accordingly, a switching voltage required for switching the electron beams on and off becomes extremely high.
In order to completely eliminate the leaked electron beams, a distance between the aperture of the grid electrode 34 and a portion of the insulating member 36b held in contact with the cathode 33, namely, actually a pitch of stripe of the back signal electrode 32 and a pitch of the apertures of the grid electrode 34 is required to be increased.
On the contrary, if electron beams should be finely controlled spatially without changing these pitches, it is impossible due to the leaked electron beams to create a state having no electron beam.

Matsushita Electric Industrial Co., Ltd.


An artificial knee joint comprising a femoral component secured to the distal portion of a femur and a tibial component secured to the proximal portion of a tibia so that both the components are brought into sliding contact with each other via sliding surfaces, wherein the femoral component is provided on a rear central section of the sliding surface with a spherical or elliptical convex sliding surface and the tibial component is provided on the rear central section of the sliding surface with a spherical or elliptical concave sliding surface so that both the sliding surfaces are brought into sliding engagement when the artificial knee joint comprising the femoral and tibial components is bent deeply, whereby a person with this artificial knee joint can take a deep knee bending posture when sitting, which cannot be attained by conventional technology.

1. Field of the Invention
The present invention relates to an artificial knee joint used to properly restore knee joints significantly deformed by chronic rheumatism or osteo-arthritis, or those broken in traffic accidents or during disasters.
2. Prior Art
A conventional artificial knee joint replacement treatment is conducted by cutting the distal portion of the femur and the proximal portion of the tibia of a knee joint damaged or broken by disease or accident, and by inserting and securing a femoral component and a tibial component to the distal portion of the femur and the proximal portion of the tibia respectively so that the femoral component slides on the sliding surface of the tibial component, thereby allowing the knee joint to be bent.
When the femoral component of the artificial knee joint slides on the tibial component as described above to perform a knee bending movement, if the fermoral component 1 of the artificial knee joint rotates on the front upper surface of the tibial component 2 of the knee joint as shown in FIG. 5, the movable range of the femoral component 1 is limited, preventing a person with the artificial knee joint from taking a deep knee bending posture when sitting and thus causing inconvenience during his daily life. To solve this problem, a method has been taken wherein a post provided on the tibial component of an artificial knee joint controls the femoral component to ensure a bending movement between the femur and the tibia (for example, Japanese Laid-open Patent Application No. 63-132651). In the above-mentioned case of the method wherein the post provided on the tibial component controls the femoral component at the time of the bending of the artificial knee joint to securely offer a sufficient movable range to the artificial knee joint, the post receives all loads and undergoes stress concentration. The post is, therefore, deformed or broken and cannot attain desired functions.


A zoom lens has a plurality of lens units including, in order from its object side to image side, a first lens unit having a negative refracting power composed of two lens elements including a biconcave negative lens and a positive lens, and a second lens unit having a positive refracting power composed of four lens elements including a positive lens and a negative lens. During zooming from the wide angle end to the telephoto end, a distance between the lens units changes, and the second lens unit moves toward the object side. The zoom lens has an aperture stop that moves integrally with the second lens during the zooming and satisfies a specific condition.

1. Field of the Invention
The present invention relates to a zoom lens in which the lens unit located closest to the object side has a negative refracting power. The present invention also relates to an image pickup apparatus, such as a digital camera, a video camera, or a camera-equipped cellular phone, equipped with a zoom lens.
2. Description of the Related Art
It has been conventionally known that a type of zoom lens in which the lens unit located closest to the object side has a negative refracting power is more advantageous in achieving a large angle of view and size reduction than a type of zoom lens in which the lens unit located closest to the object side has a positive refracting power. In addition, zoom lenses in which the lens unit located closest to the object side has a negative refracting power is also advantageous in reducing the thickness (i.e. the length along the optical axis) of the zoom lens in the state in which the lens barrel is collapsed, and therefore such zoom lenses are used, for example, as taking zoom lenses of compact digital cameras.
Among this type of zoom lenses in which the frontmost lens unit has a negative refracting power, there have been known zoom lenses in which the number of lenses in the first lens unit having a negative refracting power is as small as two, and the number of lenses in the second lens unit having a positive refracting power is four, whereby good optical performance is achieved (see patent documents 1 to 9 listed below).
The zoom lenses disclosed in patent documents 1 to 9 have the first lens unit (i.e. the frontmost lens unit) composed of two lens elements including a negative lens and a positive lens. This lens configuration is advantageous in reducing chromatic aberration in the first lens unit and in reducing the size of the zoom lens with respect to the diametrical direction. Furthermore, the negative lens in the first lens unit is designed to have a biconcave shape in the paraxial region, whereby the negative refracting power of the negative lens on the optical axis is shared by the object side surface and the image side surface. This is advantageous in reducing spherical aberration. Still further, the second lens unit is composed of four lens elements. This provides a sufficient degree of freedom in the design of the second lens unit and is advantageous in achieving good correction of aberrations in a small size zoom lens.
In recent years, image pickup apparatuses that use a CCD or CMOS sensor have replaced film cameras to become the mainstream. The size of image pickup apparatuses such as digital cameras and video cameras can easily be made small because the image pickup area thereof is relatively small.
In the field of digital cameras and video cameras that use a small image pickup element, there is a demand for image pickup apparatuses that is small in the thickness direction and has a high zoom ratio and a wide angle of view. There are known zoom lenses that are intended to be used in small-size image pickup apparatuses, as disclosed in, for example, patent documents 10 to 13 listed below.    Patent Document 1: Japanese Patent Application Laid-Open. No. 2003-114386    Patent document 2: Japanese Patent Application Laid-Open. No. 2005-258059    Patent Document 3: Japanese Patent Application Laid-Open. No. 2006-003539    Patent Document 4: Japanese Patent Application Laid-Open. No. 2006-195064    Patent Document 5: Japanese Patent Application Laid-Open. No. 2006-201599    Patent Document 6: Japanese Patent Application Laid-Open. No. 2006-227197    Patent Document 7: Japanese Patent Application Laid-Open. No. 2007-114727    Patent Document 8: Japanese Patent Application Laid-Open. No. 2007-140359    Patent Document 9: Japanese Patent Application Laid-Open. No. 2007-272216    Patent Document 10: Japanese Patent Application Laid-Open. No. 2003-241091    Patent Document 11: Japanese Patent Application Laid-Open. No. 11-52246    Patent Document 12: Japanese Patent Application Laid-Open. No. 2006-194957    Patent Document 13: Japanese Patent Application Laid-Open. No. 2008-46529

Zoom lens and image pickup apparatus equipped with same


A plant pot is capable of preventing roots from winding and lengthening excessively therein. The pot includes a container which has an open top, a base, and a surrounding wall. The surrounding wall has a bottom end connected to the base. The base has a central portion, a plurality of spaced apart connecting portions which extend radially from the central portion to the bottom end, and a plurality of holes which are confined by the connecting portions and the surrounding wall. The holes are elongated along the direction of the surrounding wall and are closely adjacent to the surrounding wall. Parts of the base close to the surrounding wall are mostly opened and are substantially free of corner spaces which would assist root winding and excessive lengthening.

1. Field of the Invention
This invention relates to a plant pot, more particularly to a plant pot having a base, a surrounding wall, and a plurality of holes formed in the base and close to the surrounding wall.
2. Description of the Related Art
Plant growth relies on roots for absorbing nutrients, water, and oxygen. In a plant cultivating pot, roots tend to extend to the spaces between the wall of the pot and the soil where they can get more oxygen. Since the roots are geotropic, they tend to extend toward the bottom of the plant pot after extending along the space adjacent to the pot wall. FIGS. 1 and 2 show two conventional plant pots 10 and 10' which include respectively a base 12 and a surrounding wall 11. The base 12 of FIG. 1 has a circular central hole 121 therein, while the base 12 of FIG. 2 has a plurality of circular holes 122, whereby excess water can flow out of the plant pots 10 and 10' through the holes 121, 122. When the root ends 201 of the plant 200 in the pot 10 or 10' reach the base 12, they wind along a corner space formed between the base 12 and the wall 11, thereby resulting in longer roots without increasing the number of root branches. Because the plant 200 must absorb nutrients via the root ends 201, the winding roots which have fewer root ends 201 can not effectively absorb the nutrients for the growth of the plant 200. Moreover, when the plant 200 is uprooted for transplanting to soil or another pot, the longer root ends 201 are liable to break. Since the plant 200 has few and remote roots, breakage of the roots may significantly affect plant growth and may even cause the plant to wither. On the other hand, when the roots are long, a deeper hole is needed in soil or in a new pot for transplanting, thus resulting in added inconvenience.


The present disclosure relates to an anode electrode active material for a secondary battery containing nickel cobalt molybdenum oxide, an anode electrode for a secondary battery including the same, a secondary battery including the anode electrode for a secondary battery, and a method for manufacturing the same. The novel anode electrode material for a sodium secondary battery containing nickel cobalt molybdenum oxide according to the present disclosure allows intercalation/deintercalation reaction of sodium ion during charge/discharge and does not undergo significant volume change during the intercalation reaction because structure is maintained stably during repeated charge/discharge. As a result, electrode damage and electric short circuit are decreased and, thus, improved electrochemical characteristics can be achieved in long-life and high-rate capability.

The application of a lithium secondary battery is extending as the markets of energy storage system (ESS) and electric vehicles are extending. However, lithium metal used in the lithium secondary battery is rare and can be obtained only in restricted regions and its price is rising gradually due to rapidly increasing demand for lithium secondary batteries. In addition, there is a limitation in using a lithium-ion battery as an environment-friendly energy storage device due to environmental pollution, etc. occurring during lithium mining. For these reasons, a sodium secondary battery is being developed in order to replace the lithium secondary battery. The sodium secondary battery can be produced at a lower cost than the lithium secondary battery and is advantageous in terms of price because sodium is abundant and distributed uniformly throughout this planet. In addition, since the physical and chemical properties of sodium are similar to those of lithium, the problems occurring during the development of the sodium secondary battery are being overcome quickly using the existing technologies known for the lithium secondary battery. But, sodium ion is 1.3 times larger than lithium ion with an ionic radius of 1.2 Å, and is 3.3 times heavier. In addition, it is disadvantageous over lithium ion because of a potential higher than lithium by 0.33 V. In addition, development of an anode electrode material capable of replacing graphite is necessary because the intercalation/deintercalation reaction of graphite, which has greatly contributed to the commercialization of the lithium secondary battery, hardly occurs in the sodium secondary battery. Accordingly, researches for finding out a new anode electrode material which is low-priced like graphite and exhibits superior life characteristics and high-rate capability are being carried out actively.
Researches on the anode electrode of the sodium secondary battery are focused on carbon-based materials, alloy materials, transition metal oxides, etc. Carbon-based anode electrode materials may be classified into graphite-based materials and non-graphite-based materials. For the graphite-based materials, the reversible intercalation/deintercalation reaction of sodium ion hardly occurs in commonly used carbonate-based electrolytes. The non-graphite-based materials have unsatisfactory life characteristics and high-rate capability. The representative candidates of the alloy anode electrode materials include silicon and tin. Silicon is known to be able to store a large quantity of lithium by reacting with lithium ion and creating a Li15Si14 phase. Meanwhile, although it is theoretically known that sodium ion can form a NaSi phase, researches are not being conducted actually because it lacks electrochemical reactivity. Tin has electrochemical reactivity but has the problem of decreased performance caused by volume expansion. The transition metal oxide-based anode electrode materials which store ions through conversion reactions exhibit high theoretical capacity because one or more sodium ion can react with one atom. However, the conversion reaction-based materials exhibit unsatisfactory life characteristics and high-rate capability because existing chemical bonds are broken and new chemical bonds are formed when they react with sodium. At present, various researches are ongoing in order to solve these problems and develop an anode electrode material that can be applied to a sodium secondary battery.

Anode electrode active material for sodium secondary battery comprising nickel cobalt molybdenum oxide, anode electrode for sodium secondary battery comprising same, sodium secondary battery including anode electrode for sodium secondary battery, and method for manufacturing same

Korea Institute of Science and Technology

Dongguk University Industry-Academic Cooperation Foundation


A display apparatus, wherein a display controller configured to perform a first display processing in which display informations from a starting point display number to a second target display number which is between the starting point display number and a first target display number corresponding to an approach-touch area are displayed on a display portion as to-be-displayed informations such that a difference between the display number of the to-be-displayed informations displayed at a start and an end of a unit time is a first value, and then perform a second display processing in which display informations from the second target display number to the first target display number are displayed as the to-be-displayed informations such that a difference between the display number of the to-be-displayed informations displayed at a start of an end of the unit time is a second value which is smaller than the first value.

1. Field of the Invention
The present invention relates to a display apparatus and an input apparatus.
2. Description of the Related Art
There is known an apparatus configured to change a display position of a slider on a slide bar displayed on a display surface on the basis that a user has touched the slider and slides or drags his or her finger on the display surface, and configured to perform display for causing the user to visually recognize that informations from information corresponding to a position before the change of the display position of the slider to information corresponding to a position after the change are moved on a display screen in order. As the apparatus of this type, there is a slide-bar operating apparatus in which a total amount of informations to be displayed corresponds to a movable range of a slider, and an amount of informations in which the apparatus can display at a time corresponds to a width of the slider.


A system and method determines members of a team in a contact center to handle a request. The method is performed by a formation device by receiving a user request from a user device, the user request associated with a type of user request. The method includes determining a plurality of member types required in handling the request based upon the type of request. The method includes determining a plurality of agents of the contact center, the agents collectively having the member types. The method includes transmitting a request to a plurality of member devices of the contact center respectively associated with each of the agents to participate in a real-time communication with the user device in handling the user request.

A contact center may be used by a provider to enable a user to submit a query or request for an issue or a service handled by the provider. Specifically, one or more agents may be employed at the contact center who receives a ticket associated with the query/request such as via email or a voice communication or who receives a request to handle the query/request of the ticket. The ticket may include all relevant information for the agents to be selected to properly generate a response for the user. The agents may utilize any available resource to determine the correct response for the ticket. For example, the agent may rely upon proprietary tools, publicly available information, privacy information corresponding to the user, etc.
The query/request may require more than one agent employed by the contact center. For example, the request may require a first specialist for a first component of the request, a second specialist for a second component, etc. Accordingly, the user may be connected to a first agent who has the qualifications of the first specialist to subsequently be handed off to a second agent who has the qualifications of the second specialist, etc. In this manner, the user may be forwarded continuously until each component of the request is handled. However, this may lead to the user being inadvertently forwarded to an agent who is not equipped to handle a particular component. Furthermore, a single component may require one more or more specialists which may result in the user being forwarded back to a previous agent. That is, the process of resolving the request may become increasingly inefficient as the user is forwarded to more and more agents.
In another example, the user may be limited in an amount of time available to resolve the request. The contact center may be configured to allow multiple agents qualified in handling the request to be selected concurrently in handling the request. However, when people become involved, there may be scenarios where the roles taken by the agents are incompatible or redundant and the process of resolving the request becomes inefficient as the agents may not fully cooperate with each other or a particular role is missing. When this occurs, the limited available time may be insufficient to resolve the request.
Outside a contact center environment when an amount of time becomes more available, a team may be formed to handle a request. However, conventional systems often only determine the team based upon qualifications and skills who can best address the components of the request. This way of selecting a team does not consider how the team members interact with each other such as the roles that each member may assume which may be detrimental in handling the request. Therefore, the efficiency in completing a request may be increased through consideration of behavioral information of team members and compatibility among them during team formation. For example, a Belbin model may be used in which team compatibility forms a basis in team formation. However, this type of team formation has the luxury of time that the contact center cannot afford particularly if the request is performed in real-time such as with voice communications.
Thus, there is a need for a system to form teams including a plurality of agents to handle a request in a contact center that incorporates team compatibility among the agents.

System and method for compatibility-based team formation


A model of arterial restenosis in domestic pigs using deep injury to the coronary arterial media resulting in extensive proliferative response. Metal wire coils are delivered percutaneously to the coronary arteries of pigs with an oversized, high pressure (14 atm) balloon and left in place for 5-6 weeks. During placement, the balloon expands the coils and delivers them securely within the arterial lumen causing fracture of the internal elastic lamina by the coil. An extensive proliferative response occurs and is associated with a lumenal area narrowing of at least 50% Immunohistochemical studies confirms the prominence of smooth muscle cells in the tissue. The histopathologic features of the proliferative response are identical to those observed in cases of restenosis post-angioplasty.. This model closely mimics the proliferative portion of human restenosis both grossly and microscopically. It may thus be useful for understanding human restenosis and for testing therapies aimed at preventing restenosis after balloon angioplasty or other coronary interventional procedures.

1. Field of the Invention
This invention relates to a method for inducing arterial restenosis in an animal model in order to study potential therapies for application to restenosis occurring in human patients after balloon angioplasty or other coronary interventional procedures.
2. Description of the Prior Art
Blood vessels narrowed or occluded by disease have been surgically repaired or replaced in bypass procedures for many years. More recently, percutaneous transluminal coronary angioplasty (PTCA) and intraluminal endovascular grafting procedures employing PCTA balloons and expandable stents have been developed and widely employed to avoid the expense and trauma of vascular surgery.
Despite the high initial success rate and widespread use of percutaneous transluminal coronary angioplasty (PTCA), restenosis appreciably limits the effectiveness of this valuable revascularization method. (See K. M. Kent, "Restenosis After Percutaneous Transluminal Coronary Angioplasty," Am. J. Cardiol. 61:67G-70G, 1988, and A. J. R. Black, et al, "Repeat Coronary Angioplasty: Correlates of a Second Restenosis," JACC 11:714-718, 1988.) Restenosis occurs in 25-45% of all patients within 6 months, and attempts to pharmacologically prevent or reduce it using anti-platelet agents, anticoagulants, corticosteroids, and calcium channel blockers have been unsuccessful. Mixed results have been reported with oral fish oil therapy and aggressive lipid reduction. See references cited in "Restenosis After Balloon Angioplasty - A Practical Proliferative Model in Porcine Coronary Arteries," by Robert S. Schwartz, et al, Circulation 82(6):2190-2200, December 1990, and "Restenosis and the Proportional Neointimal Response to Coronary Artery Injury: Results in a Porcine Model" by Robert S. Schwartz et al, J Am Coll Cardiol; 19;267-74 February 1992, incorporated herein by reference.
Restenosis develops as a consequence of the injury to the arterial wall by the dilation of the balloon in the PTCA procedure. In this procedure, the angioplasty balloon is inflated within the stenosed vessel, or body passageway, in order to shear and disrupt the wall components of the stenosed vessel to obtain an enlarged lumen. With respect to arterial atherosclerotic lesions, the relatively incompressible plaque remains unaltered while the more elastic medial and adventitial layers of the body passageway stretch around the plaque. This process produces dissection, or a splitting and tearing, of the body passageway wall layers, wherein the intima, or internal surface of the artery or body passageway, suffers fissuring. This dissection forms a "flap" of underlying tissue which may reduce the blood flow through the lumen, or block the lumen. Typically, the distending intraluminal pressure within the body passageway can hold the disrupted layer or flap, in place. If the intimal flap created by the balloon dilation procedure is not maintained in place against the expanded intima, the intimal flap can fold down into the lumen and close off the lumen, or may even become detached and enter the body passageway. When the intimal flap closes off the body passageway, often immediate surgery is necessary to correct this problem.
Although the balloon dilation procedure is typically conducted in the catheterization lab of a hospital, because of the foregoing problem, it is always necessary to have a surgeon on call should the intimal flap block the blood vessel or body passageway. Further, because of the possibility of the intimal flap tearing away from the blood vessel and blocking the lumen, balloon dilations cannot be performed upon certain critical body passageways, such as left main coronary artery, which leads into the heart. If an intimal lap formed by a balloon dilation procedure abruptly comes down and closes off a critical body passageway, such as the left main coronary artery, the patient could die before any surgical procedures could be performed.
Additional disadvantages associated with balloon dilation of elastic vascular stenoses is that many fail because of elastic recoil of the stenotic lesion. This usually occurs due to a high fibrocollagenous content in the lesion and is sometimes due to certain mechanical characteristics of the area to be dilated. Thus, although the body passageway may initially be successfully expanded by a balloon dilation procedure, subsequent, early restenosis can occur due to the recoil of the body passageway wall which decreases the size of the previously expanded lumen of the body passageway. For example, stenoses of the renal artery at the ostium are known to be refractory to balloon dilation because the dilating forces are applied to the aortic wall rather than to the renal artery itself. Vascular stenoses caused by neointimal fibrosis, such as those seen in dialysis-access fistulas, have proved to be difficult to dilate, requiring high dilating pressures and larger balloon diameters. Similar difficulties have been observed in angioplasties of graft-artery anastomotic strictures and postendarterectomy recurrent stenoses. Percutaneous angioplasty of Takayasu arteritis and neurofibromatosis arterial stenoses may show poor initial response and recurrence which is believed due to the fibrotic nature of these lesions.
Accordingly, many attempts have been made to develop expandable intraluminal vascular grafts, and methods for expanding the lumen of a body passageway, which prevents recurrence of stenoses in the body passageway, can be utilized for critical body passageways such as the left main coronary artery of a patient's heart, prevents recoil of the body passageway wall, and allows the intraluminal graft to be expanded to a variable size to prevent migration of the graft away from the desired location, and to prevent rupturing and/or erosion of the body passageway by the expanded graft. See, for example, U.S. Pat. Nos. 4,739,762, 4,922,905, and 4,800,882.
Despite the improvement in PTCA and stent technology and procedures, efforts to reduce or eliminate restenosis after PTCA have largely been unsuccessful. In part, these efforts have been hindered by the lack of knowledge of the pathophysiologic mechanisms of human restenosis, and the lack of an accurate animal restenosis model with substantial proliferation. Histologic observation of restenotic tissue from living patients has become readily available with the advent of directional atherectomy. Given this information, there is considerable interest in identification of an animal model similar to human restenosis.
Previous angioplasty animal models have not addressed the proliferative aspects of restenosis directly, instead concentrating on the atheromatous nature of the lesions. The model described by Sanborn has been frequently utilized. (See T. A. Sanborn, et al, "The Mechanism if Transluminal Angioplasty: Evidence for Formation of Aneurysms in Experimental Atherosclerosis," Circulation 1983; 78: 654-660.) In this model rabbits fed atherogenic diets have serum cholesterol levels frequently exceeding 1000 mg %. The resulting atheromatous lesions of the aorta, iliac and femoral vessels contain many foam cells in addition to intimal thickening. Although balloon denudation of endothelium increases proliferation, many foam cells are present in contrast to human restenosis. Another model of restenosis in pig carotid arteries involves endothelial denudation with neointimal proliferation. In this model, however, significant proliferative stenosis are not produced unless caused by occluding, organized thrombus. The carotid or iliac arteries of these models contain proportionally more elastin and are elastic vessels, while the coronary arteries contain proportionally more smooth muscle. These non-coronary vessels may thus be less suitable for a coronary artery restenosis model since smooth muscle proliferation is likely a major factor in the genesis of restenosis.
Lack of a practical animal restenosis model has limited the ability to investigate such potential therapies. If such a model were available, it might have the additional benefit of yielding insight into the mechanisms of the restenosis process itself. In "A Practical Proliferative Model in Porcine Coronary Arteries," by Robert S. Schwartz, et al, Circulation 82(6):2190-2200, December 1990 and "Restenosis and the Proportional Neointimal Response to Coronary Artery Injury: Results in a Porcine Model" by Robert S. Schwartz et al, J Am Coll Cardiol; 19;267-74 February 1992, we describe an experimental animal model of human coronary restenosis developed in domestic swine which accurately mimics the proliferative component of human restenosis, and is practical as well as inexpensive.

Method for providing a restenosis model in porcine coronary arteries


The present invention implements an apparatus for calibrating a phase locked loop (PLL) circuit. The apparatus includes a detector for detecting frequencies of a reference signal and a controlled oscillator contained in the PLL circuit. The detector outputs the frequency difference to a control circuit. The control circuit is programmed to adjust one or more control signals to the controlled oscillator based upon the frequency difference in an orderly fashion to complete the calibration process.

As semiconductor line widths decrease, designers and programmers are configuring the devices to run at faster speeds. In addition to the demand for higher speed devices, demands also exist for device performance with higher levels of signal accuracy. One example of electronic devices where signal accuracy is of great importance is devices that communicate wirelessly.
One tool used by designers to improve the accuracy of a signal is a phase locked loop (PLL). A PLL is an electronic control system that generates a signal that is locked to the phase (and frequency) of an input or "reference" signal. PLLs are widely used in radio, telecommunications and computers to generate stable frequency signals, or to recover a signal from a noisy communication channel. A PLL includes specific circuit components to adjust the control voltage of a voltage controllable oscillator until its output phase is identical to that of the reference signal.
FIG. 1 illustrates a sample PLL 100. Here, the reference signal 102 is input to the reference divider 104. The reference divider 104 reduces the clock rate of the reference signal to a rate that the other components can process. After dividing the frequency of the reference signal (if needed), the reference divider 104, passes the signal to the phase detector 106.
The phase detector 106 is the control element of the PLL 100. The phase detector 106 compares the phases of its two input clocks (in this example, the reference signal supplied by the reference divider 104 and the output of the voltage controllable oscillator feedback divider 112) and provides a corrective signal that is filtered which controls the oscillator to force the phase between the two compared clock signals to zero. In this example, the phase detector 106 provides a control signal to the loop filter 108.
The optional loop filter 108 receives the control signal from the phase detector 106 and creates a low pass filtered version of the phase detector output (VLF). For a voltage controlled oscillator (VCO) with a positive transfer function slope, the loop filter output voltage increases if the oscillator should produce a higher frequency signal, and conversely, is lowered if the oscillator should produce a lower frequency signal to match the two clock phases. The voltage controlled oscillator output is provided to an optional feedback divider 112. In FIG. 100, the feedback divider splits the output of the controlled oscillator 110 into two signals; one output provides the feedback input to the phase detector 106 for further comparison; the second output signal is an output signal 114.
The PLL described in FIG. 1 is a typical approach to producing phase locked signals. When implemented in an integrated circuit, PLL circuit performance can vary greatly over different silicon processes, voltage and temperature. A slight temperature change can change the value of the circuit components (e.g., the loop filter) or functionality of other PLL elements. Under some combinations of silicon process, supply voltage and temperature, there are occasions when the loop filter cannot produce a voltage signal that will result in the controlled oscillator producing a signal with the same phase as the reference signal. To avoid this undesirable condition, a PLL trimming method that calibrates components of the PLL, in particular the controlled oscillator, is often employed.

Programmable linear trimming method and system for phase locked loop circuit calibration


A swab roller formed from an elongated stem having a first end terminating with a covering and a second end terminating with a covering. A casing tube placed over a portion of the elongated stem is sized to allow the rotation of the elongated stem within the casing tube. The covering is formed from an absorbent material such as cotton or foam. The swab roller can be constructed of inexpensive components, such as paper for general use or from medical grade materials or sterile packaging for specialty use.

Swabs are well known in the industry for use in cleaning. A conventional swab employs an absorbent covering located on either end of an elongated stem. The absorbent material can be made from a variety of materials, with cotton likely the most well-known. The elongated stem may be made of paper, plastic or similar material having stiff or bendable properties. The absorbent material may be attached by an adhesive or with frictional engagement. A problem with the conventional swab is that the absorbent material is held in a fixed position, wherein the swab can be abrasive when drawn across a sensitive member.
For instance, in cosmetics, the drawing of a swab across the skin may operate to remove matter from the skin. In many instances, the use of the swab would be beneficial in applying various types of cosmetics, in essence avoiding removal of applied cosmetics. This may be accomplished by dabbing the swab across the skin, or causing the absorbent material to roll across the skin by spinning the elongated stem between the applicant's fingers. This can be a difficult task to master, especially if the applicant does not have good dexterity.
A more pointed example may be found in the medical field, wherein the drawing of a swab across the skin may cause irritation. In many instances, the usefulness of the swab would greatly increase if the swab was rotated across the skin, wherein the absorbent material would operate as an applicator. Surgical incisions, skin burns, and other tissue wounds must be carefully treated to prevent infection. Surgical incisions must also be dressed periodically to facilitate healing. Tissue wounds may be dressed using sterile saline, iodine, peroxide or the like disinfectant. The use of a swab applicator facilitates the process by providing a single use applicator that can be dipped into a disinfectant before use. Medical use is not limited to surgical incisions; most every type of skin issue would benefit from a single use applicator that applies ointments without the fear of dragging or otherwise irritating the skin. For instance, skin issues such as dermatitis, eczema, impetigo, psoriasis, rosacea and so forth would benefit from a single use applicator of ointment that does not require the applicator to have special skills. When the applicator is wiped or dragged directly over the wound to apply the disinfectant or ointment, not only can the applicator cause skin irritation, it can spread infection from one area to another. If the applicator is rolled over the wound, the motion avoids the transfer of the infection from one portion of the wound to the other. This requires the applicator to match the surface speed of the absorbent material to that of the swab movement. However, conventional swab heads are typically small in circumference and fixed to the handle of the device. A person can manually rotate the elongated stem and cause the swab to rotate as well, but the dexterity required to match the surface speed of the head to that of the handle is difficult and can be cumbersome.
While the above-mentioned use of applicators can be accomplished by rotating the elongated stem between the fingers during use, the rotation requires a certain amount of dexterity. In many instances, the individual may not have the dexterity or patience, or may be wearing gloves, making rotation of the elongated stem between the fingers difficult, if not impossible, to perform.
Prior art attempts to make a rotating applicator are complicated and expensive. U.S. Patent Publication 2012/0260931 discloses a cosmetic handheld applicator assembly. The applicator assembly system employs a handle, a motor, and a coupling assembly for releasably receiving a set of detachable and interchangeable makeup brushes selected for applying a cosmetic to a surface area of the body zones.
WO2017059198A1 discloses a makeup brush which has a generally cylindrical body having a first end adapted to be rotatably coupled to a motorized makeup brush support, a second end defining a recess therein that is adapted to receive a plurality of bristles, and a central axis that extends between the first end and the second end.
CN2928060Y discloses an electric therapeutic otitis curer, which comprises a shell and a cotton bar. A direct current supply and a direct current motor are arranged on a shell. A cotton bar is arranged on the front of the shell and is connected to the motor through a drive shaft.
CN202740621U discloses a partial sterilizer having a handle, storage battery and a motor. The partial sterilizer is characterized in that a rotating head is arranged at the front end of the handle, and a cotton ball clamp is arranged on the rotating head.
CN203989448U discloses a rolling applicator having a universal joint arranged at the top end of a handle and matched with a ball socket and a ball.
CN205434676U discloses a medical care cotton swab auxiliary device. The device includes a cylinder branch. A right hand member of the cylinder branch is provided with a handle, and the left side of the cylinder branch is provided with a dwang; the near-end of the dwang and cylinder branch is connected through a damping pivot. The left end of the dwang is provided with a connection socket, and the left end surface middle part is provided with the blind hole. The blind hole inner circle is provided with the elastic gum ring. The elastic gum with intra-annular pegged graft holds a cotton swab.
CN105362062A discloses a nasal cleaner using a water spray type cotton swap as a cleaning head, and an infusion tube with an infusion bottle connected with each other to form the water spray washing and scrubbing linkage type nasal cleaner.
CN204594716U discloses a swab that can prevent rotary droing. It comprises a locking cap, swab, and external packing union coupling, with three recesses in a rigid plastic locking cap. The anti-removal swab connection package has a center shaft that is set with the cap and groove, such that swab end is set with a rib by a clamping connection.
CN206366094U discloses a portable medical cotton stick, including a cavity handle with a cotton stick on one end and a source of iodophor at the other end. The iodophor passes through a threaded connection between the cavity handle.
CN206372389U discloses a disinfection cotton swab having a main part forming a cavity plastic tubing, a middle part of cavity plastic tubing being an air chamber with both upper and lower ends having an iodophor cavity and an alcohol cavity.
JP2014128447A discloses a cosmetic tool for applying an adhering cosmetic onto a skin uniformly. The applicator includes a rotating application part having an implanted brush.
What is needed in the industry is a disposable rolling swab applicator that is inexpensive to manufacture and is not dependent upon an individual's dexterity for operation.


There is disclosed a unique water treatment system which incorporates a unique primary valve. The primary valve comprises an interconnected first part and second part. The first part attaches to a water source and provides untreated water to water treatment units which are controlled by the second part of the primary valve. Untreated water flows to a first water treatment unit and subsequently through a valve to the second part of the primary valve and to use or to a second water treatment unit. From the second water treatment unit the water flows to the second part of the primary valve and to use. The second part of the primary valve has a unique bore and slideable shaft valve structure. The water treatment units can purify the water and/or add substances to the water.

The present invention is directed to a valve for use in water treatment systems where an input water can be diverted to optionally be treated more than one time. More particularly the input water can be subject to at least two purification steps or optionally to at least one purification step and at least one substance additive step, or two substance addition steps.
In most of the home water purification systems the water will undergo a single treatment step. This usually will be a water purification step. In such systems there is a valve with a set flow of water from a water source, such as a spout at a sink. At the spout water source there usually is a diverter valve where the water can be diverted and passed to the purification step or it can be flowed directly into the sink. The water would be flowed into the sink in the instances where the water would be used for cleaning purposes such as countertop, dish or pan or pot cleaning. Also the water would be flowed directly into the sink when the water would be used for watering plants. When for personal use, the water diverted to purification usually would be flowed to a single purification step and then to use. That is, the water is flowed directly from a purification step to use. These purification steps will remove particulates and various dissolved substances. These systems use a simple one part diverter valve. Such a one part diverter valve is used on the present water purification products available from Western Water International, Inc. of Forestville, Md. and available under the AQUASPACE trademark.
The present invention is directed to a water treatment system that besides having a water purification step, also optionally has an additional water treatment step. After the water flows through the water purification step it can be flowed directly to use or it can be flowed to an optional second treatment step. This optional second treatment step usually is in a series arrangement with the first purification step. Between the first step purification step and the second treatment step there is a T-junction valve. This T-junction valve is operated in conjunction with a unique primary diverter valve that is attached to a water source, such as a spout. This primary diverter valve besides having in a first part for flowing the source water directly to use or to a purification step, can in a second part receive diverted the water either from the water purification step or the water purification step and an additional water treatment step. The present system provides the versatility to flow water directly to use, flow the water to a purification step, or flow the water from the purification step to an additional water treatment step such as a substance addition step. In the second part of the diverter valve there is an input channel from the water purification step and separate input channel from the water treatment step such as a substance addition step. This second stage has a valve, such as a slider valve, with a plurality of inlet channels and an outlet channel. The outlet channel flows the water to ultimate use. The inlet channels are arranged to be in alignment either with the inlet from the water purification step or the inlet from the water treatment step such as a substance addition step. When in an alignment with the water purification step, water from the water purification step will flow through the second part of the diverter section and to the outlet channel for use. When in an alignment with a substance addition step, water from the substance addition step will flow through the second part of the primary valve and to the outlet channel for use. This two part primary valve provides for the versatility of having the water undergo a single or multiple treatment steps.

Valve for use in a water treatment system


An air-fuel ratio control system for an internal combustion engine, which is capable of accurately estimating an exhaust gas state parameter according to the properties of fuel, thereby making it possible to properly control the air-fuel ratio of a mixture. The air-fuel ratio control system 1 estimates an exhaust gas state parameter indicative of a state of exhaust gases, as an estimated exhaust gas state parameter (AF13 NN) by inputting a detected combustion state parameter (DCADLYIG) indicative of a combustion state of the mixture in the engine 3, and detected operating state parameters (NE, TW, PBA, IGLOG, TOUT) indicative of operating states of the engine 3, to a neural network (NN) configured as a network to which are input the combustion state parameter (DCADLYIG) and the operating state parameters (NE, TW, PBA, IGLOG, TOUT), and in which the exhaust gas state parameter is used as a teacher signal (step 1), and controls the air-fuel ratio based on the estimated exhaust gas state parameter (AF_NN) (steps 3, 4, and 24 to 28).

1. Field of the Invention
This invention relates to an air-fuel ratio control system and method for an internal combustion engine and an engine control unit, for controlling an air-fuel ratio of a mixture supplied to the engine.
2. Description of the Related Art
Conventionally, there has been disclosed an air-fuel ratio control system e.g. in Japanese Laid-Open Patent Publication (Kokai) No. 2004-360628. In this air-fuel ratio control system, when an O2 sensor is active, the amount of fuel to be supplied to the engine is controlled based on an exhaust air-fuel ratio detected by the O2 sensor, whereby air-fuel ratio feedback control is carried out. On the other hand, when the O2 sensor is not active during the start of the engine, the air-fuel ratio feedback control is not carried out, but the amount of supply fuel is controlled without being based on the exhaust air-fuel ratio to control the air-fuel ratio by open control.
As described above, according to the conventional air-fuel ratio control system, the amount of supply fuel is controlled without being based on the exhaust air-fuel ratio during the start of the engine, so that e.g. when fuel difficult to burn is used, the output power from the engine is lowered, which causes degradation of a combustion state and drivability. To avoid such inconveniences, it is considered that a target value of the air-fuel ratio is set to the rich side. In this case, however, the output power from the engine becomes too large when fuel is easy to burn, whereby exhaust emissions are increased and drivability is degraded. Further, when the exhaust emissions are increased, a catalyst containing a large amount of a noble metal has to be used for reducing the exhaust emissions, which results in the increased manufacturing costs of the catalyst.

Air-fuel ratio control system and method for internal combustion engine, and engine control unit


Human kininogen domain 3 (HK-D3) polypeptides and biologically active variants and derivatives of HK-D3 are anti-angiogenic. These molecules are used to inhibit angiogenesis or treat a disease or condition in which angiogenesis is pathogenic. Because of their anti-angiogenic potential, these molecules compounds are useful in the treatment of cancer by inhibiting or reversing the growth of primary or metastatic tumors.

1. Field of the Invention
The present invention in the field of biochemistry and medicine is directed to angiogenesis-inhibitory polypeptides comprising a part of human kininogen, particularly, the D3 domain (HK-D3) and variants thereof, and their use in diagnosis and therapy of diseases associated with endothelial cell migration and proliferation. In particular these polypeptides are useful in treating subjects with cancer.
2. Description of the Background Art
Angiogenesis, the formation of new capillaries form pre-existing ones (Folkman, J., N. Engl. J. Med., 1971, 285:1182–1186; Hanahan D. et al., Cell, 1996, 86:353–364), is a normal part of embryonic development, wound healing and female reproductive function. However, angiogenesis also plays a pathogenic role in the establishment and progression of certain diseases. Cancer, rheumatoid arthritis and diabetic retinopathy are examples of such diseases (Carmeliet P. et al., Nature, 2000, 407:249–257). Anti-angiogenic therapy holds promise in inhibiting the progression of these diseases.
Angiogenesis can be triggered by several pro-angiogenic cytokines. In the setting of cancer, tumor cells under hypoxic conditions secrete vascular endothelial growth factor (VEGF) and/or fibroblast growth factor (bFGF). These proteins diffuse and bind to specific receptors on endothelial cells (ECs) in the local vasculature, perturbing the balance of pro- and anti-angiogenic forces in favor of angiogenesis. As a consequence of binding these proteins, ECs are activated to (a) secrete enzymes that induce remodeling of the associated tissue matrix, and (b) change the patterns and levels of expression of adhesion molecules such as integrins. Following matrix degradation, ECs proliferate and migrate toward the hypoxic tumor, resulting in the generation and maturation of new blood vessels.
Interestingly, many anti-angiogenic factors result from the degradation of matrix proteins—i.e., are a result of the action of pro-angiogenic enzymes. Examples include endostatin, a fragment of collagen XIII (O'Reilly, M. S. et al., Cell 1997, 88:277–285); kringle 5 of plasminogen (O'Reilly, M. S. et al., Cell, 994, 79:315–328) and PEX, the C-terminus non-catalytic subunit of MMP-2 (Brooks PC et al., Cell, 1998, 92:391–400).
The concept has emerged that, due to the abundance of pro-angiogenic factors, these anti-angiogenic molecules are unable to overcome the pro-angiogenic balance in a primary tumor. However, since they are secreted into circulation, these anti-angiogenic molecules are capable of inhibiting angiogenesis at other locations where tumor cells may have begun to invade. Consequently, micro-metastases comprising these tumor cells at these new locations remain dormant. This hypothesis explains the puzzling observation made by surgeons many years ago: at various times after surgical removal of a primary tumor in a patient with no obvious metastatic disease, the patient returns with advanced metastatic disease.
Thus, clinical intervention by treatment with one or more of the anti-angiogenic factors could inhibit the angiogenic process and halt tumor growth as well as metastasis. Significant evidence in the literature (cited above) supports this notion.
Biochemistry of High Molecular Weight Kininogen
Two forms of kininogen, high molecular weight kininogen (HK, Mr=120 kDa), and low molecular weight kininogen (LK, Mr=68 kDa), have been identified in human plasma (Jacobsen S. et al., Br J Pharm 29:25–36, 1967). HK is an α-globulin with a plasma concentration of 90 μg/ml (Proud D et al., J Lab Clin Med 95:563–5574, 1980) (FIG. 1), and LK is a α-globulin with a plasma concentration of 220 μg/ml (Muller-Esterl W et al., Biochim Biophys Acta 106:145–152, 1982). These proteins are derived from the alternative splicing of a single gene (Kitamura N et al., J Biol Chem 260:8610–8617, 1985), and share a common heavy (H) chain, which contains domains 1, 2 and 3, termed D1, D2 and D3 (Colman R W et al., Blood 90:3819–3843, 1997). However, while LK contains only a 4 kDa light (L) chain (D4L), the ˜46 kDa L chain of HK contains domains 5 and 6 (D5 and D6, respectively).
Each domain of HK has a unique function. For example, D1 binds calcium, and D2 inhibits calpain (Colman et al., supra). The cell binding regions of HK are contained within D3 and D5, while D6 binds plasma prekallikrein and coagulation Factor XI. In intact HK, D4 links the H and L chains; D4 also includes the nonapeptide, bradykinin (BK) which is released from HK by kallikrein via cleavage between Lys362-Arg363 and Arg371-Ser372, leaving behind a cleaved molecule consisting of a 62 kDa H chain and 56–62 kDa L chain, which are bonded by an intrachain disulfide between Cys10 and Cys596. A subsequent cleavage at a site near the N-terminus of D5, results in reduction of the Mr of the L chain to ˜45 kDa (Kaplan A P et al., Blood 70:1–15, 1987).
Released BK is a potent vasodilator and an agonist for ECs. Kallikrein-mediated cleavage of HK occurs on the EC surface, and may be mediated (a) directly by plasma kallikrein or (b) after binding of prekallikrein to cell-bound HK, followed by its activation to kallikrein by an EC cysteine protease. Thus the EC is an important site for HKa generation. Phorbol myristoyl acetate (PMA)-stimulated ECs bind increased amounts of HK (Colman et al., supra) suggesting acceleration of this process on "activated" ECs. The observation that ECs produce HK mRNA and protein further supports the physiological importance of this process (Schmaier A H et al., J Biol Chem 263:16327–16333, 1988).
The release of BK from HK is accompanied by a structural rearrangement in the remaining two-chain kininogen molecule, HKa and the acquisition of several novel properties. For example, cleavage of HK to HKa allows the latter to bind to artificial anionic surfaces (Colman et al., supra); interactions that are mediated by residues of the His-Gly-rich region within D5 of HKa (amino acids 420–458) (DeLacadena R A et al., Protein Sci 1:151–160, 1992; Kunapuli S P et al., J Biol Chem 268:2486–2492, 1993).
Furthermore, HKa, but not HK, is anti-adhesive, inhibiting the spreading of osteosarcoma and melanoma cells on vitronectin, and of ECs, platelets and mononuclear cells on vitronectin and fibrinogen (Asakura S et al., J Cell Biol 116:465–476, 1992). The structural rearrangement of HKa involves a change in the orientation of HKa domains relative to each other.
HK exists as a linear array of three linked globular regions, with the two peripheral regions connected by a thin strand (Colman R W et al., J Clin Invest 100:1481–1487, 1997). The strand may represent the disulfide bridge between D1 and D6, as it is no longer apparent following reduction. Studies with epitope-specific monoclonal antibodies (mAbs) determined that the globular domains on the ends of HK represent the prekallikrein-binding region (within D6 of the L chain) and the cysteine protease inhibitor region (D2 and D3 of the H chain), while the central nodule represents the anionic surface binding region within D5.
After kallikrein-mediated cleavage, the two-chain molecule, HKa, retains the trinodular structure, though the three globular regions rearrange in a pattern resembling vertices of a triangle. In this structure, the anionic surface binding and prekallikrein binding regions are more closely apposed. Because the EC binding regions within HK have been mapped to sites within D3 of the H chain and D5 of the L chain ((Reddigari S R et al., Blood 81:1306–1311, 1993; Herwald H et al., J Biol Chem 270:14634–14642, 1995; Hasan A et al., J Biol Chem 269:31822–31830, 1994; Hasan A et al., J Mol Biol 219:717–725, 1995) and since the latter regions in the linear sequence overlap extensively with the anionic surface binding regions of HKa, the orientation of the cellular binding regions within HK and HKa must differ. This conclusion implies that HK and HKa are likely to interact differently with ECs, a hypothesis supported by functional studies demonstrating that HKa, but not HK, is a potent inhibitor of proliferation and inducer of apoptosis in ECs.
Interactions of HK with ECs
A. Identification of Cell Binding Regions within HK
HK was reported to bind with high affinity to human umbilical vein ECs (HUVEC) (Reddigari et al., supra; van Iwaarden F et al., J Biol Chem 263:4698–4703, 1988; Zini J M et al., Blood 81:2936–2946, 1993; Hasan A et al., Blood 85:3134–3143, 1995). The presence of Zn2+ is an absolute requirement for binding, whereas Ca2+ either inhibited or had no effect on binding. Internalization of HK has also been reported (van Iwaarden F et al., Blood 71:1268–1276, 1988).
The binding of HK to ECs is mediated through interactions involving both its H and L chains, and several studies have led to the identification of specific regions that mediate binding within D3 (Herwald H et al., supra) and D5 (Hasan et al., J. Mol. Biol., supra) (one of which overlaps with the BK sequence within D4). These regions were identified by the ability of synthetic peptides with corresponding sequences to compete with intact, labeled HK for binding to HUVEC.
In contrast to HK, little information is available concerning the binding of HKa to ECs. In one study, cleavage of biotinylated HK by increasing amounts of kallikrein led to a progressive diminution in binding of the cleaved ligand. In contrast, others reported that HKa was more potent than unlabeled HK in inhibiting the binding of radiolabeled HK to ECs (IC50=73 nM for HKa vs 335 nM for HK) (Reddigari et al., supra). Although these IC50 values are difficult to reconcile with a reported Kd (30–40 nM) for the binding of HK to ECs, they nevertheless suggest differences between HK and HKa in their interactions with cells.
B. Endothelial Cell HK/HKa Receptors
HKa inhibition of EC proliferation in vitro is a unique property of HKa as HK, which binds to ECs, nevertheless lacks this antiproliferative effect. Moreover, the observed difference in binding to ECs exhibited by HK and HKa suggests potential differences in function. HKa could inhibit EC proliferation by several mechanisms. First, it might induce detachment of ECs from their matrix through direct interactions with integrins, thereby leading to interruption of integrin-mediated signaling and MAP kinase phosphorylation, leading to apoptosis. However, other than one report that single-chain HK binds to Mac-1 (αMβ2 or CD11b/CD18) on monocytes, there is no evidence for interactions of kininogen with integrins.
The binding of HKa to ECs was also not inhibited by a blocking antibody against the β3 integrin chain, suggesting that HKa does not interact with αvβ3, an integrin which plays an important role in angiogenesis (Colman R W et al, J Clin Invest 100:1481–1487, 1997). HKa might interact in either a specific or non-specific manner with an ECM protein(s), thereby preventing its interaction with an EC integrin receptor. However, there is no data to support this hypothesis. The fact that HKa inhibited the proliferation of HUVEC plated on fibronectin, gelatin, and Matrigel, suggested effects independent of matrix identity. HKa might inhibit the binding of growth factors to cellular glycosaminoglycans, such as heparan sulfate, or to specific growth factor receptors. However, this explanation is unlikely, since withdrawal of growth factors does not lead to EC apoptosis within 6 hours—a time frame in which HKa induced apoptotic changes.
McCrae's group recently observed that the cleaved form of HKa inhibited bFGF-stimulated angiogenesis in vivo. (Zhang J-C et al., FASEB J. 14:2589–600, 2000). In vitro, HKa potently inhibited the proliferation of HUVEC and human dermal microvascular ECs (HDMVEC), inducing EC apoptosis. Several peptides were identified with sequences corresponding to the binding regions within D3 and D5 of HKa that inhibited EC proliferation at low μM to nM concentrations. Comparison of the sequences of overlapping peptides used in these studies led to the identification peptides of 4–8 amino acids that mediated this activity. Compared to the antiproliferative effects, the anti-adhesive effects of HKa appear to be of less importance since EC adhesion was only modestly inhibited at HKa concentrations >100 nM, whereas anti-proliferative effects were observed at concentrations as low as ˜1 nM. McCrae (WO 00/35407; PCT/US99/28465) has described variants of the 8-mer peptide X1-Asn-Asn-Ala-Thr-Phe-Tyr-Phe-Lys-X2, which are discussed in the context of EXAMPLE I.

Human kininogen D3 domain polypeptide as an anti-angiogenic and anti-tumor agent


The present invention is based on the discovery of genetic polymorphisms that are associated with psoriasis and related pathologies. In particular, the present invention relates to nucleic acid molecules containing the polymorphisms, including groups of nucleic acid molecules that may be used as a signature marker set, such as a haplotype, a diplotype, variant proteins encoded by such nucleic acid molecules, reagents for detecting the polymorphic nucleic acid molecules and proteins, and methods of using the nucleic acid and proteins as well as methods of using reagents for their detection.

Psoriasis is a common, chronic, T-cell-mediated inflammatory disease of the skin affecting ˜2-3% of whites of European descent. Although this disease is found in all populations, its prevalence is lower in Asians and African-Americans and also declines at lower latitudes. The most common form, psoriasis vulgaris, is characterized by varying numbers of red, raised, scaly skin patches that can be present on any body surface, but most often appear on the elbows, knees and scalp. The onset of disease usually occurs early in life (15-30 years) and affects males and females equally. Up to 30% of individuals with psoriasis will develop an inflammatory arthritis, which can affect the peripheral joints of the hands and feet, large joints, or the central axial-skeleton. Pathologically, psoriasis is characterized by vascular changes, hyperproliferation of keratinocytes, altered epidermal differentiation and inflammation. In particular, the reaction of cells in the epidermis to type 1 effector molecules produced by T-cells results in the characteristic pathology of the plaques.
The genetics of psoriasis are complex and highly heritable as evidenced by an increased rate of concordance in monozygotic twins over dizygotic twins (35%-72% vs. 12-23%) and a substantially increased incidence in family members of affected individuals (first-degree relatives 6%); however, it is clear that environmental effects are also responsible for disease susceptibility. Ten genome-wide linkage scans have resulted in strong evidence for a susceptibility locus in the MHC region on 6p21 (PSORS1 [MIM 177900]), but have not yielded consistent evidence for other regions.
Linkage and association in the MHC (6p21) are thought to be due to HLA-C, in particular psoriasis susceptibility effects are thought to be caused by the *0602 allele, although other candidate genes in the area may also contribute to disease predisposition. Association studies have identified three genes under linkage peaks, with considerable evidence for linkage disequilibrium with psoriasis, namely SLC9A3R1/NAT9 and RAPTOR (KIAA1303) in 17q25, and SLC12A8 in 3q21. Several other genes including VDR, MMP2, IL10, IL1RN, IL12B, and IRF2 (Genetic Association Database, OMIM) have been associated with psoriasis in sample sets of varying sizes and of different ethnicities; however, without more data from additional independent studies, it is difficult to draw statistically sound conclusions about whether these markers are truly associated with disease. Thus, there remains a need for the discovery of reliable markers that can associate themselves with psoriasis, and in turn, would facilitate the diagnosis and treatment of the disease.
The discovery of genetic markers which are useful in identifying psoriasis individuals who are at increased risk for developing psoriasis may lead to, for example, better therapeutic strategies, economic models, and health care policy decisions.
SNPs
The genomes of all organisms undergo spontaneous mutation in the course of their continuing evolution, generating variant forms of progenitor genetic sequences (Gusella, Ann. Rev. Biochem. 55, 831-854 (1986)). A variant form may confer an evolutionary advantage or disadvantage relative to a progenitor form or may be neutral. In some instances, a variant form confers an evolutionary advantage to the species and is eventually incorporated into the DNA of many or most members of the species and effectively becomes the progenitor form. Additionally, the effects of a variant form may be both beneficial and detrimental, depending on the circumstances. For example, a heterozygous sickle cell mutation confers resistance to malaria, but a homozygous sickle cell mutation is usually lethal. In many cases, both progenitor and variant forms survive and co-exist in a species population. The coexistence of multiple forms of a genetic sequence gives rise to genetic polymorphisms, including SNPs.
Approximately 90% of all polymorphisms in the human genome are SNPs. SNPs are single base positions in DNA at which different alleles, or alternative nucleotides, exist in a population. The SNP position (interchangeably referred to herein as SNP, SNP site, SNP locus, SNP marker, or marker) is usually preceded by and followed by highly conserved sequences of the allele (e.g., sequences that vary in less than 1/100 or 1/1000 members of the populations). An individual may be homozygous or heterozygous for an allele at each SNP position. A SNP can, in some instances, be referred to as a "cSNP" to denote that the nucleotide sequence containing the SNP is an amino acid coding sequence.
A SNP may arise from a substitution of one nucleotide for another at the polymorphic site. Substitutions can be transitions or transversions. A transition is the replacement of one purine nucleotide by another purine nucleotide, or one pyrimidine by another pyrimidine. A transversion is the replacement of a purine by a pyrimidine, or vice versa. A SNP may also be a single base insertion or deletion variant referred to as an "indel" (Weber et al., "Human diallelic insertion/deletion polymorphisms", Am J Hum Genet 2002 October; 71(4):855-82).
A synonymous codon change, or silent mutation/SNP (terms such as "SNP", "polymorphism", "mutation", "mutant", "variation", and "variant" are used herein interchangeably), is one that does not result in a change of amino acid due to the degeneracy of the genetic code. A substitution that changes a codon coding for one amino acid to a codon coding for a different amino acid (i.e., a non-synonymous codon change) is referred to as a missense mutation. A nonsense mutation results in a type of non-synonymous codon change in which a stop codon is formed, thereby leading to premature termination of a polypeptide chain and a truncated protein. A read-through mutation is another type of non-synonymous codon change that causes the destruction of a stop codon, thereby resulting in an extended polypeptide product. While SNPs can be bi-, tri-, or tetra-allelic, the vast majority of the SNPs are bi-allelic, and are thus often referred to as "bi-allelic markers", or "di-allelic markers".
As used herein, references to SNPs and SNP genotypes include individual SNPs and/or haplotypes, which are groups of SNPs that are generally inherited together. Haplotypes can have stronger correlations with diseases or other phenotypic effects compared with individual SNPs, and therefore may provide increased diagnostic accuracy in some cases (Stephens et al. Science 293, 489-493, 20 Jul. 2001). As used herein, the term "haplotype" refers to a set of two or more alleles on a single chromosome. The term "diplotype" refers to a combination of two haplotypes that a diploid individual carries. The term "double diplotype", also called "two-locus diplotype", refers to a combination of diplotypes at two distinct loci for an individual.
Causative SNPs are those SNPs that produce alterations in gene expression or in the expression, structure, and/or function of a gene product, and therefore are most predictive of a possible clinical phenotype. One such class includes SNPs falling within regions of genes encoding a polypeptide product, i.e. cSNPs. These SNPs may result in an alteration of the amino acid sequence of the polypeptide product (i.e., non-synonymous codon changes) and give rise to the expression of a defective or other variant protein. Furthermore, in the case of nonsense mutations, a SNP may lead to premature termination of a polypeptide product. Such variant products can result in a pathological condition, e.g., genetic disease. Examples of genes in which a SNP within a coding sequence causes a genetic disease include sickle cell anemia and cystic fibrosis.
Causative SNPs do not necessarily have to occur in coding regions; causative SNPs can occur in, for example, any genetic region that can ultimately affect the expression, structure, and/or activity of the protein encoded by a nucleic acid. Such genetic regions include, for example, those involved in transcription, such as SNPs in transcription factor binding domains, SNPs in promoter regions, in areas involved in transcript processing, such as SNPs at intron-exon boundaries that may cause defective splicing, or SNPs in mRNA processing signal sequences such as polyadenylation signal regions. Some SNPs that are not causative SNPs nevertheless are in close association with, and therefore segregate with, a disease-causing sequence. In this situation, the presence of a SNP correlates with the presence of, or predisposition to, or an increased risk in developing the disease. These SNPs, although not causative, are nonetheless also useful for diagnostics, disease predisposition screening, and other uses.
An association study of a SNP and a specific disorder involves determining the presence or frequency of the SNP allele in biological samples from individuals with the disorder of interest, such as psoriasis and related pathologies and comparing the information to that of controls (i.e., individuals who do not have the disorder; controls may be also referred to as "healthy" or "normal" individuals) who are preferably of similar age and race. The appropriate selection of patients and controls is important to the success of SNP association studies. Therefore, a pool of individuals with well-characterized phenotypes is extremely desirable.
A SNP may be screened in diseased tissue samples or any biological sample obtained from a diseased individual, and compared to control samples, and selected for its increased (or decreased) occurrence in a specific pathological condition, such as pathologies related to psoriasis, increased or decreased risk of developing psoriasis. Once a statistically significant association is established between one or more SNP(s) and a pathological condition (or other phenotype) of interest, then the region around the SNP can optionally be thoroughly screened to identify the causative genetic locus/sequence(s) (e.g., causative SNP/mutation, gene, regulatory region, etc.) that influences the pathological condition or phenotype. Association studies may be conducted within the general population and are not limited to studies performed on related individuals in affected families (linkage studies).
Clinical trials have shown that patient response to treatment with pharmaceuticals is often heterogeneous. There is a continuing need to improve pharmaceutical agent design and therapy. In that regard, SNPs can be used to identify patients most suited to therapy with particular pharmaceutical agents (this is often termed "pharmacogenomics"). Similarly, SNPs can be used to exclude patients from certain treatment due to the patient's increased likelihood of developing toxic side effects or their likelihood of not responding to the treatment. Pharmacogenomics can also be used in pharmaceutical research to assist the drug development and selection process. (Linder et al. (1997), Clinical Chemistry, 43, 254; Marshall (1997), Nature Biotechnology, 15, 1249; International Patent Application WO 97/40462, Spectra Biomedical; and Schafer et al. (1998), Nature Biotechnology, 16: 3).

This patent is subject to a terminal disclaimer.

Genetic polymorphisms associated with psoriasis, methods of detection and uses thereof


A display apparatus removably attachable to a fuel pump filler gun. A display carrying body configured, when fitted onto the filler gun, to cover an upper part of a gun head of the filler gun, a pair of side panels extending down from the carrying body on either side thereof to lie along either side of the gun head, respectively, when the carrying body is fitted onto the filler gun, a display card support provided on an upper face of the display carrying body, and the side panels having gripping structure for use when attaching the display apparatus to the filler gun.

1. Field of the Invention
The present invention relates to a display apparatus removably attachable to a fuel pump filler gun, the filler gun including in sequence a gun barrel, a gun head, and a gun handle, the barrel joining the gun head at a first junction, and the gun handle joining the gun head at a second junction.
2. Description of the Related Art
Such a display apparatus is e.g. described in the co-pending U.S. patent applications Ser. No. 08/284427, 08/590407, 08/610961 and continuation-in-part application of the latter, filed 3rd Jul. 1996.


A method, an apparatus, and a computer program product for generating and processing random numbers are provided. An apparatus comprises a processing system that includes a processor, a random number generator and a pair of buffers. A first buffer receives low-entropy random numbers generated by the random number generator and a second buffer provides high-entropy random numbers directly to a processing system. The processing system may directly access the second buffer in response to an instruction executed by the processing system. The processing system responds to an interrupt based on occupancy levels of the buffers by conditioning low-entropy random numbers read from the first buffer to obtain high-entropy random numbers that are then stored in the second.

1. Field
The present disclosure relates generally to digital communication systems, and more particularly, to apparatus and methods for supplying random numbers to a processing system.
2. Background
Random numbers are used extensively in communications systems, security and encryption, simulation and gaming, and in other applications. Random numbers are commonly obtained using a hardware random number generator (RNG), which generates a sequence of numbers that appear to be uncorrelated or to have no apparent pattern. RNGs are implemented in hardware to improve throughput, particularly in applications such as simulation and gaming which make frequent use of random numbers. RNGs are also used in order to reduce the processing overhead required to generate random numbers and to minimize latency, which may be measured as the time between requesting and receiving a random number.
RNGs typically generate pseudorandom numbers that are correlated to some degree, and are therefore not completely unpredictable. Entropy measurements may be used to quantify quality of randomness of a random number. Modern RNGs may yield 8 bits of real entropy for 10 bits generated (an entropy rate of 0.8), which is generally less than entropy rates required by computing systems.
Some systems condition low-entropy numbers generated by an RNG using a cryptographic function to obtain random numbers with significantly higher entropy. Conventional systems include cryptographic functions logic circuits in the RNG to permit random numbers to be generated quickly, asynchronously and with low response latency. The addition of cryptographic functions can significantly increase the complexity of the RNG hardware, causing increased usage of integrated circuit area and increased power consumption.
Consequently, there is a need for a high throughput, low-latency RNG that occupies less die area and consumes less system power.

Interrupt driven hardware random number generator