According to the invention, reliability is calculated in consideration of an uncertain error due to noise in three-dimensional measurement, thereby obtaining correct reliability as compared with a conventional technique. To achieve this, a three-dimensional measuring apparatus includes a projector which projects a striped light pattern onto an object, a camera which captures a reflected light pattern from the object onto which the striped light pattern is projected, and a calculation processing unit which executes various arithmetic operations. The calculation processing unit includes a noise calculating unit and a reliability calculating unit.

Field of the Invention
The present invention relates to a three-dimensional measuring technique of measuring the surface shape of an object.
Description of the Related Art
There is known a pattern projecting method to measure the shape of an object based on deformation of a pattern projected onto the object, using the principle of triangulation, by projecting a plurality of kinds of light patterns onto the object and capturing the object upon projection of each light pattern. By using the Space Coding method as an example, a measuring method and the concept of reliability will be explained below.
The arrangement of a general apparatus for measuring a three-dimensional shape and the concept of three-dimensional measurement will be described with reference to FIG. 11. A three-dimensional measuring apparatus generally includes a projector 102 which projects a light pattern onto an object (an object to be measured) 110, and a camera 103 which captures a reflected pattern from the object 110. The projector 102 projects, onto the object 110, a striped light pattern in which a bright section and a dark section alternate with an arbitrary width. The striped light pattern includes a plurality of predetermined pattern shapes. Every time each of the pattern shapes is projected, the camera 103 captures the pattern shape to acquire image data. Let (X, Y, Z) be the boundary position between a bright section and a dark section of the object 110. (X1, Y1) represents the position of the intersection point of the display element surface of the projector 102 and a straight line which connects the boundary position (X, Y, Z) with the principal point of the projector 102. Similarly, (X2, Y2) represents the position of the intersection point of the sensor surface of the camera 103 and a straight line which connects the boundary position (X, Y, Z) with the principal point of the camera 103. Note that the position (X2, Y2) of the intersection of the sensor surface of the camera 103 is obtained by the horizontal coordinate of the image sensor (CCD, CMOS, or the like) of the camera 103. The horizontal coordinate is determined by the horizontal and vertical widths of the image sensor. For a 640×480 image sensor, the x-coordinate in the horizontal direction ranges from 0 to 640 and the y-coordinate in the vertical direction ranges from 0 to 480. Similarly, the position (X1, Y1) of the intersection point of the display element surface of the projector 102 is obtained by the horizontal coordinate of a projection sensor. A distance L between the projector 102 and the camera 103 is the base line length and is determined based on the arrangement condition of the apparatus. It is possible to obtain the boundary position (X, Y, Z) of the object 110 using those parameters according to the principle of triangulation. It is thus possible to measure the three-dimensional shape of the object 110 by obtaining the boundary position (X, Y, Z) for the entire surface of the object 110.
The shape of the striped light pattern will be explained. A striped light pattern of a binary code called a gray code having a coding error resilience will be described below with reference to FIGS. 12A to 12C. A section which is observed as black on a captured reflected pattern corresponds to "0", and that which is observed as white corresponds to "1". Referring to FIG. 12A, the entire pattern is divided into two regions, which are encoded as "1" and "0". Referring to FIG. 12B, four regions of bright and dark sections are encoded as "1", "0", "0", and "1", and irradiated with a corresponding striped light pattern to be captured. Furthermore, referring to FIG. 12C, eight regions are encoded as "1", "0", "0", "1", "1", "0", "0", and "1", and irradiated with a corresponding striped light pattern to be captured. When the regions are sequentially irradiated with these three kinds of striped patterns, each region can be represented by three bits. That is, the respective regions can be described by (1, 1, 1), (1, 1, 0), (1, 0, 0), (1, 0, 1), (0, 0, 1), (0, 0, 0), (0, 1, 0), and (0, 1, 1). Since a space can be divided into eight regions using the three striped light patterns in this manner, the Space Coding will be referred to as 3-bit Space Coding hereinafter. Then, the respective striped light patterns shown in FIGS. 12A to 12C will be respectively referred to as 1-bit striped light pattern, 2-bit striped light pattern, and 3-bit striped light pattern hereinafter.
To perform three-dimensional measurement in more detail, regions of bright and dark sections are irradiated with n striped light patterns while sequentially reducing the regions in size. Then, by assigning region numbers obtained by dividing an irradiation region of the projector into 2n regions, the respective regions can be determined. In three-dimensional measurement in which a region is divided into 1024 regions, 10-bit Space Coding is performed.
The merit of the gray code lies in that even when a coding error occurs at a region boundary due to a shift or blur of a striped light pattern, such error is merely determined to be a neighboring region, and does not cause any coding error as a largely shifted region. For this reason, the Space Coding method using the gray code is generally used.
To improve the precision in three-dimensional measurement by the Space Coding method, a horizontal coordinate position x (to be referred to as "boundary position" hereinafter) of the boundary between bright and dark sections has to be decided from captured image data. The boundary position between bright and dark sections will be described with reference to FIGS. 13A and 13B. FIG. 13A is a graph when the ordinate plots the luminance values of image data obtained by capturing a 2-bit striped light pattern, and the abscissa plots the horizontal coordinates x. Ideal boundary positions are shown in the lower portion of FIG. 13A. In FIG. 13A, since the bright and dark sections have different luminance values "1" and "0" at the boundaries, the boundary positions between the bright and dark sections are uniquely decided. That is, positions a and b can be decided as boundary positions. However, in actual measurement, a moderate change is observed in the vicinity of each boundary in an image actually captured by the camera 103 due to the influences of, for example, a blur of a striped light pattern, the reflectance of an object, and ambient light, as shown in FIG. 13B, and boundary positions cannot be uniquely decided, thus causing measurement errors.
To avoid such program, a method which assigns reliability indicating measurement precision to each measuring point, and does not use measuring coordinates if the reliability of the coordinates is equal to or lower than a threshold is disclosed (for example, see Japanese Patent No. 3996560 which is to be referred to as reference 1 hereinafter).
In reference 1, an object is irradiated with full-illumination light corresponding to a bright section on the entire pattern and full-extinction light corresponding to a dark section on the entire pattern in addition to a striped light pattern. The upper limit luminance value obtained by the full-illumination light and the lower limit luminance value obtained by the full-extinction light are obtained and used to calculate contrast, thereby setting it as reliability.
In the technique disclosed in reference 1, the contrast of a striped light pattern is set as reliability. In this case, the influence of a luminance exerted by noise in three-dimensional measurement is not considered. Three-dimensional measurement actually includes uncertain noise (to be referred to as noise information in the three-dimensional measurement hereinafter) due to the camera, object, projector, ambient light, and the like. Consequently, the reliability based on the contrast obtained in reference 1 does not include noise information in three-dimensional measurement, and thus has an incorrect value.

Three-dimensional measuring apparatus and control method therefor


A sliding apparatus of a cooling module for a vehicle, constructed so that the cooling module slides in a rearward direction of the vehicle when a front impact force acts on the cooling module mounted to a front end module, may include a slide slot formed in a longitudinal direction of the vehicle, a bushing unit slidably coupled to the slide slot, and a rotary arm supporting at a first end portion thereof a back portion of the bushing unit wherein the rotary arm supports the bushing unit in a forward direction of the vehicle while the bushing unit moves along the slide slot in the rearward direction of the vehicle by the front impact force when the front impact force exceeding a coupling force applied to a second end portion of the rotary arm is transmitted from the bushing unit to the rotary arm.

1. Field of the Invention
The present invention relates to a sliding apparatus of a cooling module for a vehicle, which allows the cooling module to slide rearwards when impact force is transferred to the cooling module (a radiator or a condenser) mounted to the front portion of the vehicle, thus preventing the cooling module from being damaged.
2. Description of Related Art
Recently, module systems which combine several parts into one unit package have gradually been increasing in number so as to reduce the number of assembling processes when a vehicle is manufactured, thus reducing manufacturing costs and a manufacturing defective ratio. Thereby, a front bumper, a radiator and an air-conditioning condenser (a cooling module), and a head lamp are mounted to a front end module (FEM) in the form of a package.
FIG. 1 is a plan view illustrating a conventional cooling module mounted to a front end module, FIG. 2 is an enlarged view illustrating the important parts of a conventional sliding structure of the cooling module, and FIG. 3 is an operation view illustrating the state in which the cooling module slides when impact force acts on the conventional cooling module.
First, as shown in FIGS. 1 and 2, the conventional cooling module 10 for a vehicle, such as a radiator or a condenser, is mounted to the front end module 30 via a mounting bracket 20. A bumper back beam 1 is placed in front of the front end module 30 so that a bumper is installed to the bumper back beam 1.
Here, if the cooling module 10 is completely fixed to the front end module 30, the cooling module 10 may be damaged when impact force acts on the cooling module 10. Thus, when the impact force is transferred, the cooling module 10 slides in the transferred direction of the impact force (generally, the rear portion of the vehicle), so that the damage to the cooling module 10 is prevented.
As shown in FIG. 2, the sliding structure for the cooling module 10 includes a slide slot 21 which is formed in the mounting bracket 20 in the longitudinal direction of the vehicle. A bushing 11 extending from the cooling module 10 is fitted into the slide slot 21.
The bushing 11 is an elastic member which is elastically deformable. In the state where the bushing 11 is fitted into the slide slot 21 as shown in FIG. 2, the lower surface of the bushing 11 is in close contact with the upper surface of the mounting bracket 20. FIG. 2 shows a normal state before impact force is transferred to the cooling module 10.
When impact force is transferred to the cooling module 10 in the normal state of FIG. 2, the bushing 11 extending from the cooling module 10 moves to the rear portion of a vehicle body along the slide slot 21, so that the state of FIG. 3 is obtained. At this time, since the impact force transferred to the cooling module 10 is larger than frictional force between the bushing 11 and the mounting bracket 20, the bushing 11 slides rearwards.
As such, when the cooling module 10 is subjected to the impact force, the cooling module 10 slides rearwards, so that the damage to the cooling module 10 is prevented or minimized.
However, the conventional sliding structure for the cooling module 10 is problematic in that the cooling module 10 is supported only by the frictional force between the bushing 11 and the mounting bracket 20 in the normal state where impact force does not act on the cooling module 10, so that vibration and noise may be generated due to the cooling module 10 being weakly mounted, and the cooling module 10 may undesirably slide rearwards when the vehicle starts suddenly.
The problems become more serious when the bushing 11 hardens because of deterioration of the bushing 11. Actually, owners having older vehicles complain about the vibration and noise which are generated in the bushing 11 of the cooling module 10, so that there is a pressing need for overcoming the problem of the vibration and noise.
The information disclosed in this Background of the Invention section is only for enhancement of understanding of the general background of the invention and should not be taken as an acknowledgement or any form of suggestion that this information forms the prior art already known to a person skilled in the art.

Sliding apparatus of cooling module for vehicles


A method and apparatus where a source delivers graphics data to a target, which receives and displays the graphics data. The source of the graphics data controls how the graphics data is to be displayed at the target. The source transmits a display control signal prescribing a manner in which the video signal is to be displayed in relation to the graphics data. A target receives the video signal, the graphics signal, and the display control signal, and combines the video signal and the graphics data in the manner prescribed by the display control signal to form a combined display at the target.

1. Field of the Invention
The present invention relates generally to data exchange and processing thereof; more particularly, the present invention relates to a method and apparatus where a source delivers graphics data to a target, which receives and displays the graphics data, particularly where the source of the graphics data controls how the graphics data is to be displayed at the target.
2. Background of Related Art
Nowadays, a plethora of products exist for receiving and/or displaying video signals, e.g., television broadcasting stations, satellite broadcasting services, video feed services, or the like. These video signal receiver products may range from products that receive and process video signals only in analog form, to products that receive and process video signals in digital form, and to products that are capable of receiving and processing video signals in analog and digital form. Some products are equipped with other integrated features, e.g., recording capabilities, or the like. The available features for displaying (e.g., picture-in-picture (PIP), picture-in-graphics (PIG), double screen, or the like) the video signal also vary widely among the products.
There are equally diverse products or sources for delivering the video signals, e.g., over-the-air broadcasting stations, cable operators, direct satellite services, live video feed services, or the like. Many of these sources send, in addition to the video signals, graphics data to be displayed at a receiver for providing programming guide, advertisement, value added services (e.g., stock quotes, news service, etc.), or the like. Graphics data can be in any visual form, e.g., a text, a still picture, an interactive menu screen, or the graphics data may itself be another video stream.
For example, FIG. 1A shows a conventional video/graphics data transmission and reception arrangement 100, where a source of video signal, an AV source 101 sends graphics data together with the video signal to a receiver product, e.g., an AV target 102. Conventionally, the graphics data and video signal are combined by a mixer 104 in the AV target 102, and the combined signal is sent to a display 103, which provides a display of the graphics data and/or the video to a viewer.
However, in the conventional video/graphics data transmission and reception system thus described, because the A/V source 101 does not send information regarding how the video and graphics data are to be combined, the A/V target 102 must decide how the graphics data is to be displayed, particularly in relation to the video signal, which may be simultaneously displayed with the graphics data. Thus, the mixer 104 combines the received video signal and the graphics data without knowing how the source of the graphics data, e.g., the A/V source 101, intended to display the graphics data. The mixer 104 typically resorts to the most simple method of combining the two signals, e.g., simple overlaying, even if the AV target 102 is capable of more advanced display features, e.g., the PIP, PIG, Double Screen, or the like.
Specifically, in the case of a digital television (DTV), which may be, e.g., connected to a set-top-box (STB) via an IEEE1394 serial interface (as specified by "IEEE 1394, Standard for High Performance Serial Bus", published 1995, which is incorporated herein by reference), the DTV receives the graphics data and the video signal (i.e., an MPEG transport stream) from an STB. The transmission of the video signal and the graphics data is governed by standards, e.g., in the United States, The Electronics Industries Alliance (EIA) Standards, EIA-775-A, "DTV 1394 Interface Specification," published April 2000, and/or EIA-799, "On Screen Display Specification," published June 1999, both of which are incorporated herein by reference. Because these standards do not provide means for the STB to send control information with respect to the manner in which the graphics combined with the video signal or by itself are to be displayed, the task of deciding how the two displays are to be proportioned and combined with respect to each other is nevertheless still left up to the receiver product, i.e., the DTV.
The existing standards at best provide overlaying the graphics data display over the video display by allowing specifications of "pixel definition," which may define the location, size, and gain factors of pixels for the graphics data, and thereby allow simultaneous display and blending of the two displays, i.e., by attenuating the graphics data so as to make the graphics data appear somewhat transparent in the foreground with the video display visible in the background. The pixel definition, however, is part of the graphics data, and does not define the relationship between the video display and the graphics display. Moreover, these conventional systems heretofore do not allow the source of the graphics data to specify how the video display is to be proportioned in relation to the graphics data display. Accordingly, despite the fact that many conventional digital television sets are capable of advanced display features, e.g., the PIP, PIG, Double Screen, chroma keying, color keying, or the like, these features are not utilized to allow the DTV to know how the graphics data is intended to be displayed. Thus, the DTV in a conventional system typically performs a simple overlaying of one display, e.g., the graphics, over the other display, e.g., the video signal, and the graphics data/video signal is displayed as shown in FIGS. 1A and 1B.
Thus, the receiver product may display 105 only the graphics data over the entire screen as shown in FIG. 1B, or at best simultaneously display 106, 107 the graphics data and the video signal in a manner in which the graphics display covers, and thus, obscuring a portion of the video display as shown in FIG. 1C.
The above-described conventional graphics/video transmission and display method and system do not utilize available display features of the receiver/display product, and thus, do not provide the most effective and the most user-friendly display of the graphics/video.
Moreover, the conventional method and system heretofore does not allow the source of the graphics data, which can determine a most desirable way in which the graphics data is to be displayed to specify how the graphics data display is to be proportioned with respect to the video display to be presented to a viewer.
Thus, there is a need for a system and method of transmitting and displaying graphics data that allow a user-friendly display of graphics data with the most efficient utilization of the display capabilities of the receiver/display product.
There is also a need for a system and method of transmitting and displaying graphics data that allow the source of the graphics data to determine, at least in part, how the graphics data is to be proportioned in relation to the video display and ultimately displayed to a viewer.

Remote display control of video/graphics data


A method and apparatus for measuring the strength of a human thumb or finger. Strength can be measured when the thumb or finger moves in at least two substantially opposing directions.

1. Field of the Invention
The present invention generally relates to a system and method for measuring the motor strength of a human thumb or finger.
2. Background of the Invention
Despite great technological advancements in the field of hand surgery over the past twenty-five years, grip and pinch strength are the only two ways to quantitatively measure motor strength in the hand. A grip meter can be used to assess these parameters to make assessments as to focal areas of strength and weakness in the hand that may be due to primary muscle pathology, nerve and motor end-plate disease, and/or disorders of bone and joint. Variations in pinch such as tip, chuck, or key pinch are commonly used to mimic various activities of daily living. The Medico-Legal Society and workers compensation communities, as part of disability and return to work assessments, extensively use hand surgery research, daily clinical practice and the data obtained from grip and strength measurements.
The limitation of grip and pinch tests I have determined lies in the fact that both of these testing modalities evaluate muscle groups that are innervated jointly by the median and ulnar nerves. Grip strength is a composite function with contributions from all the palmar digits, as well as synergistic firing of intrinsic and extrinsic digital flexors. The extrinsic flexors of the sublimis and profundus groups of the hand are dually innervated in the forearm, whereas the intrinsic flexors are primarily ulnarly innervated, and the radial two lumbricals are median innervated.
With pinch strength, the same issues exist. The abductor policies brevis is served almost entirely by the median nerve. The adductor pollicis and the first dorsal interosseous are nearly completely ulnarly innervated. The remaining muscles, the flexor pollicis brevis and the opponens pollicis, show wide variations in median and ulnar innervations.
A quantitative measure of forces generated in pure palmar thumb adduction and abduction, I have determined, could serve as an adjunct to grip and pinch strength in the following conditions:
osteo-arthritis pre-operation and post-operation;
rheumatoid arthritis pre-operation and post-operation;
thumb reconstruction after trauma;
reconstruction of congenital differences;
following tendon transfer surgery; and/or
following tumor resection and reconstruction.
Instruments that evaluate the function of the human hand can be divided into three general types. First, instruments that measure the motor strength of the thumb and fingers in various positions of pinch and grip. Second, sensory measuring devices that assess fine touch, sharp-dull, two-point discrimination, pressure and temperature sensation. Third, dexterity measuring devices that assess neuromuscular coordination such as pegboard or Moberg instruments.
While existing pinch strength devices assess global functioning of the intrinsic thumb muscles, there is no known instrument that significantly, substantially and/or completely isolates one or more muscles that are enervated by the motor branch of the median nerve. As the motor branch enters the thenar eminence, I have determined that it enervates the abductor pollicis brevis, the opponens pollicis, and the superficial head of the flexor pollicis brevis. Other muscles are powered by the terminal motor branches of the ulnar nerve. These muscles are the deep head of the flexor pollicis brevis, the adductor pollicis, the first dorsal interosseous, and some fibers of the opponens pollicis. The simple act of pinch is actually a complex interplay of all the above muscles, and therefore there is no way to independently assess the function of those muscles that are enervated by the median nerve alone.
Muscles that abduct, or bring the thumb out of the palm in a vector perpendicular to the palm, are innervated by the median nerve. Muscles that adduct, or bring the thumb back toward the palm, are innervated by the ulnar nerve. There is no known device that can measure the force generated by these muscles.
For example, one known apparatus for exercising the human hand is described in PCT Publication WO/018018A2, which is incorporated herein by reference. As shown in the schematic illustration of FIG. 1, the assembly 110 includes two major components, a tension member 112 and a compression member 114. The compression member 114 is formed of a resiliently compressible material, such as open cell polyurethane foam, and in the embodiment that is illustrated, is configured as a generally spherical ball 116.
The tension member 112 is configured as an elongate, unitary tether 118 formed of a suitable elastomeric material, such as flexible PVC or latex rubber, for example. The tether 118 includes a main cord 120 that extends through a bore 122 in the compressible ball 116. A thumb loop 124 is mounted on the lower end of the main cord so as to project from the bottom of the compressible member, and a stabilizing web 126 is formed on the upper end of the cord. The stabilizing web protrudes slightly above the upper end of the ball, and finger loops 130, 132, 134 and 136 are attached to the web by comparatively short, narrow elastic cords 140, 142, 144 and 146. The finger cords 140–146 extend from the stabilizing web at predetermined angles so as to develop the correct force vectors for property exercising the hand.
The thumb loop and the finger loops are sized to fit over the middle phalanges of their respective digits, and are also provided with outwardly projecting tab portions 148 which aid in placing the loops by providing a grip for the fingers of the opposite hand.
Tapered junctions 150, 152 are preferably formed where the web and the thumb loop join the main cord. In addition to providing added strength and resistance to tearing in these areas, the tapered junctions 150, 152 engage corresponding recesses 154a, 154b at the ends of the bore 122 through the compressible ball member, thereby providing a firmer, more stable fit between the two members.
Thus, when the exercise assembly is installed on a user's hand, the fingers and thumb are able to move through their full ranges of motion, with the tension member offering a predetermined degree of resistance in the extension-abduction or adduction direction and the compression member providing a predetermined degree of resistance in the flexion-adduction-opposition direction. Moreover, the resistance is apportioned properly amongst the fingers of the hand, and the confirmation of the assembly ensures that the muscles and tendons are exercised together in a coordinated fashion. In addition, the configuration of the compressible ball and the tether structure enable the assembly 110 to be used with either hand, by simply reversing the assembly and installing the cords on the corresponding fingers of the other hand.
Therefore, the apparatus shown in FIG. 1 in no way quantitatively measures the forces generated by the thumb in abduction and adduction.

System and method for measuring the motor strength of a human thumb or finger


An integrated circuit and an operating method thereof are provided. The integrated circuit includes memory cells, at least one first word line, second word lines, bit lines and write-assist bit lines. The at least one first word line is electrically connected to at least one row of the memory cells. The second word lines are electrically connected to other rows of the memory cells. Two bit lines are located between a column of the memory cells and two write-assist bit lines. The bit lines and the write-assist bit lines are configured to be electrically disconnected with each other when at least one of the memory cells electrically connected with the at least one first word line is configured to be written, and electrically connected with each other when at least one of the memory cells electrically connected to the second word lines is configured to be written.

A memory integrated circuit includes an array of memory cells, which can be implemented as volatile memory cells or non-volatile memory cells. The volatile memory cells, such as random-access memory (RAM) cells, require power to maintain its stored information. On the other hand, non-volatile memory cells, such as read-only memory (ROM) cells, can maintain stored information even when not powered. The electronic data can be read from and/or written into the array of memory cells through various control lines. During writing operations, the voltage written into far-end memory cells is inevitably dropped from the voltage applied at a near side of the array of the memory cells. Therefore, writing ability for the far-end memory cells is generally lower than writing ability for the near-end memory cells, and an appropriate write assist scheme for the far-end memory cells is required.

Integrated circuit and operating method thereof

Taiwan Semiconductor Manufacturing Company, Ltd.


A random number generating unit includes an external containment casing and a measurement cone within the external containment casing, to which liquid detection contacts are attached. One or more terminals on a random number generation integrated circuit, which terminals connect to the liquid detection contacts are included, as is a primary reservoir connected to a secondary reservoir containing a pump and a dropper to provide a bead of liquid from the pump, wherein the bead falls on the measurement cone to be detected by the liquid detection contacts and then fall into the primary reservoir.

1. Technical Field
The present invention relates in general to the field of computers, and in particular to generating random numbers. Still more particularly, the present invention relates to a method and system for generating random numbers with a liquid-and-plate based generator.
2. Description of the Related Art
A random number generator is a computational or physical device designed to generate a sequence of numbers that does not have a pattern, so that the sequence can be treated as being random. Random number generators have existed since ancient times, in the form of dice and coin flipping, the shuffling of playing cards, the use of yarrow stalks and many other methods.
It is universally agreed is that any "random number generator" based solely on deterministic computation cannot be regarded as a "true" random number generator, since its output is inherently predictable. John von Neumann once famously said "Anyone who uses software to produce random numbers is in a state of sin".
Even carefully chosen pseudo-random number generators are an unacceptable replacement for true random numbers for some applications. Rigorous (and expensive) numerical analysis is often needed to have confidence their use is acceptable in those applications in which they are appropriate. Particularly for security applications, the use of pseudo-random numbers instead of true random numbers can completely compromise the application for which they are being used.
There is a general consensus that true random numbers are most likely to be found by looking at physical processes which are, as far as we know, unpredictable. A physical random number generator is based on an essentially random atomic or subatomic physical phenomenon. Examples of such phenomena include radioactive decay, thermal noise, and shot noise. Physical random number generators that rely on quantum mechanical processes have the advantage that the sequences they produce are completely unpredictable, if we assume that current theories of quantum physics are correct.
Applications in scientific, military, and cryptography fields require true random numbers that are not deterministic. Because generating these true random numbers requires a source of entropy that can be used to create an unpredictable sequence, sensitive applications frequently use radioactive source as described above. The points in time that radioactive sources decay are in no way uniform or periodic. However, many entropy sources such as radioactive decay timing are often very expensive.
The above, as well as additional purposes, features, and advantages of the present invention will become apparent in the following detailed written description.

Liquid and plate-based random number generator

International Business Machines Corporation


An array of electronic devices includes at least one throttlable device in the array of devices and a management module connected to the at least one throttlable device for reducing heat effects to an overheating device from neighboring devices in the array of electronic devices device. The management module is configured to detect the overheating of the overheating device, detect at least one throttlable device neighboring the overheating device and in the array of devices, and throttle the at least one throttlable device. The array of devices are an array of blade servers within a blade center, and the management module is separate from the at least one throttlable device.

1. Field of the Invention
The disclosure relates generally to electronic systems and, more specifically, to a system and method for controlling throttlable devices within an array of devices in a computer system.
2. Description of the Related Art
Many types of electronic devices are assembled in arrays. For example, a single blade center may include several blade servers arrayed one next to another. A byproduct of the operation of the electronic devices is heat, and since the array of electronic devices are typically located in a confined area, heat generated by a single electronic device affects neighboring electronic devices and vice-versa. Many electronic devices, however, are sensitive to heat, and as a result, many electronic devices include one or more fans to cool the devices.
An issue associated with these arrays of devices occurs when one of the electronic devices overheats. The overheating may be for many reasons, but a typical reason for a device to overheat is that one or more of the fans cooling that particular device have failed. If the overheating device was alone, the overheating may not be a serious issue. However, since the overheating device is in the midst of an array of other heat-producing devices, the issue of overheating is exacerbated. Once the temperature of the device rises to a certain level, the device may fail or failsafe measures within the device may cause the device to shut down.
Although the shutting down of a particular device among an array of devices may not be a serious issue, in other instances, if the device is performing a critical function, the failure (or shutting down) of the device is an occurrence to be avoided. There is, therefore, a need for system and method for reducing the heat effects to a particular overheating device from neighboring devices in an array of devices.

Device throttling system from neighboring device


A method and apparatus for generating computer configuration rules comprising receiving configuration data regarding a plurality of computers, analyzing the configuration data to determine associations within the configuration data, and generating configuration rules from a result of the analysis.

1. Field of the Invention
The present invention generally relates to computer network management. More particularly, the present invention pertains to a method and apparatus for generating configuration rules for computing entities within a computing environment using association rule mining.
2. Description of the Related Art
Typically, a data center is a facility within a computing environment that is used to house mission critical computer systems and associated components. A data center includes environmental controls, such as air conditioning, fire suppression, and the like, redundant/backup power supplies, redundant data communications connections and high security among others. A bank, for example, may have a data center, where all its customers' account information is maintained and transactions involving these data are performed. Likewise, in another example, practically every company either mid-sized or larger has some kind of data center with larger companies often having dozens of data centers. Besides, most large cities have many purpose-built data center buildings in secure locations near telecommunications services. Most collocation centers and Internet peering points are located in these kinds of facilities.
Conventional enterprise data centers frequently accommodate thousands of servers, running hundreds of applications. For instance, in such circumstances, it is difficult to administer these servers so that all the servers are appropriately configured, patched, and the like, in accordance with the applications they host.
In order to handle the aforementioned circumstances, the current practice is to utilize discovery tools to gather configuration data from the data center. Test the configuration data gathered against a set of predefined rules, such as templates, reference configurations, gold standards, and the like, usually derived from 'best practices' or IT policies. Eventually, flag the violations or anomalies for administrator attention.
Although, anomalies or violations amid the servers, other data elements (i.e. storage, network, and the like), and the applications they host are detected by utilizing the aforementioned practice, this practice merely facilitates testing of the gathered configuration data against the predefined rules (or hard coded set of rules.) This is owing to the fact that not all applications, in conventional data centers, have their corresponding reference template specified. In certain scenarios, even if the templates for some applications are specified, not all configuration parameters (or rules) may be codified as some of the rules will be inevitably overlooked owing to human error. Besides, the templates may be incomplete and incompletely instantiated. Also, as data centers evolve over time, these rules have to be updated accordingly. Inevitably, templates will lag behind the state of the data center, because configuration sanity-checking takes lower priority than keeping the applications available, updated and secure.
Data centers are usually managed in 'silos.' Within a given data center, storage administrators independently manage storage devices and specify their templates. More specifically, server templates are independently specified by server administrators, and so on. In such scenarios, configuration settings that span across these silos cannot therefore be easily captured in templates. Thus, configuration errors that occur due to lack of coordination among these administrators often remain undetected until they actually result in a potential problem.
As stated above, existing tools require a hard-coded set of rules against which the configuration data is checked. However, such tools fail to discover unanticipated types of configuration errors. Moreover, domain expertise is needed to create these set of rules.
Accordingly, there is a need in the art for methods and apparatuses to facilitate automated configuration rule definition.

Method and apparatus for generating configuration rules for computing entities within a computing environment using association rule mining


In a data transmission system in which a cyclic redundancy checksum value is derived in respect of each block of data bit values to be transmitted over the system, the checksum value in respect of blocks of data bit values intended for preselected ones only of the stations of the system is preloaded with a predetermined or netkey value to be used by the preselected stations such that only those stations can correctly decode the signals intended for them.

The present invention relates to data transmission systems including a plurality of transmitter/receiver stations, and in particular although not exclusively to such systems in which data signals from any one station are transmitted over a medium common to all stations, the medium being either wired or wireless.
In such systems it is important that the data signals are received at the correct destination and without corruption. At the same time it is often desirable that the data signals are receivable only at selected stations of a system, either to enable the operation of groups of stations within the system as separate networks or, by restricting reception to selected stations within a group, to reduce unnecessary workload on receiver processors which are not required to receive particular data signals. For example, respective groups of stations in adjacent factories may be required to operate as separate networks while utilising a common radio frequency channel, where the area coverages of radio signals being transmitted within the groups may overlap.
One method of checking whether data signals have been received correctly is to use a cyclic redundancy checksum (CRC), where the data to be transmitted is divided into convenient packets or groups of packets, each packet or group being subjected to a mathematical operation known to both the transmitter and the intended receiver of the data so as to arrive at a convenient digital checksum value that is transmitted with the packet or group. A receiver performs the identical mathematical operation on the received data and compares the resultant digital value with that transmitted with the packet or group. If the two checksum values are identical, the receiver knows to a high degree of probability that the data packet or group has been received correctly. If there is any difference, that data packet or group may be arranged to be retransmitted, for example by the absence on the transmission medium of any acknowledgment of correct reception by the intended receiver station.


A terminal device includes: a housing; a screen arranged on the housing; a first lens arranged in the housing and disposed on a back of the screen; and a turnover module arranged on the hack of the screen in the housing and configured to change an orientation of the first lens, so that the first lens faces towards a first direction or a second direction of the screen, the second direction being different from the first direction.

Along with the development of a terminal technology and popularization of an intelligent terminal device, users are increasingly seeking for a full screen having a high screen-to-body ratio. A front camera of the terminal device occupies a certain space of the screen and reduces the screen-to-body ratio of the terminal device. Presently, setting the front camera as a pop-up type camera or an under-display hole type camera is an important manner for the terminal device to implement the full screen. However, the existing manners for implementing the full screen need to provide a hole on the terminal device, thus exposing the camera to collect environmental light to generate an image. For example, holes are set on sides of adjacent screens of the terminal device to expose the pop-up type camera, and a hole is set on the screen of the terminal device to expose the under-display hole type camera. As a result, user experience is affected.

Terminal device, lens adjustment method and computer-readable storage medium

Beijing Xiaomi Mobile Software Co., Ltd.


Sheet-like polyurethane moldings are produced by impregnation of porous sheets with a prepolymer containing free isocyanate groups and reversibly blocked isocyanate-reactive groups or containing free isocyanate-reactive groups and reversibly blocked isocyanate groups, and subsequent reaction of the prepolymers in a heated mold.

Sheet-like polyurethane moldings are used, in particular, for interior trim of vehicles. They can be produced by impregnation of porous, sheet-like materials with polyurethane systems and the subsequent reaction of these systems to give polyurethanes. Polyurethane systems which can be used are isocyanates, for example in the form of dispersions, or prepolymers containing isocyanate groups, the isocyanate groups then reacting with water. Atmospheric moisture and/or the moisture present in the porous, sheet-like materials may be sufficient for this reaction. The porous, sheet-like materials are customarily first introduced into the mold and there impregnated with the premixed polyurethane system.
Porous, sheet-like materials which can be used here are synthetic foams such as flexible or semirigid polyurethane foams, or fabrics such as glass wool or fabrics of natural fibers such as felts or plant fibers.
For molding and for accelerating the reaction, the sheets are usually placed in a heated mold after impregnation. During this process step the moldings can also ba provided with laminating materials such as films or mats. This gives moldings having a sandwich structure.
The known processes for producing sheet-like polyurethane moldings have disadvantages. When dissolved isocyanates are used, solvents are given off. To overcome this deficiency it is proposed in EP-A-276 465 that aqueous isocyanate suspensions be used for impregnating the porous materials. However, this process results in relatively long demolding times since evaporation of the water takes a long time.
When using polyurethane systems for producing sheet-like moldings, it is necessary for the systems to have a sufficiently long pot life in order to avoid the foaming prior to complete impregnation of the porous material. The viscosity of such polyurethane systems is usually very high. As a result, particularly when using sheet-like materials based on plant fibers, impregnation with the polyurethane systems can be incomplete. Flow problems occur when impregnating the materials in the mold.
It is an object of the present invention to develop a simple and inexpensive process for producing sheet-like polyurethane moldings which avoids the disadvantages of the prior art.

Production of sheet-like polyurethane moldings


An optical device has the structure to perform switching and attenuation of an optical beam with reduced polarization dependent loss (PDL). The optical device includes a birefringent displacer and two liquid crystal (LC) structures. The first LC structure is used to condition s-polarized components of the optical beam and the second LC structure is used to condition p-polarized components of the optical beam. Each LC structure has a separate control electrode so that the s-polarized components of the optical beam and the p-polarized components of the optical beam can be conditioned differently and in such a manner that reduces PDL. The optical device may be configured for processing multiple input light beams, such as the multiple wavelength channels de-multiplexed from a wavelength division multiplexed (WDM) optical signal.

1. Field of the Invention
Embodiments of the present invention relate generally to optical communication systems and components and, more particularly, to a liquid crystal-based optical switch and attenuator.
2. Description of the Related Art
In optical communication systems, it is sometimes necessary to perform 1×2 switching of an optical signal, where an input light beam enters an optical switching device through an input port and is directed to one of two output ports. There are also more complicated optical switching schemes, such as 2×2, 1×N, and N×N optical switches, which may be realized by combining multiple 1×2 optical switches.
In addition to routing of signals by optical switches, attenuation of signals in optical communication systems is needed, for example in an optical communication system that employs wavelength division multiplexing (WDM). In such an optical system, information is carried by multiple channels, each channel having a unique wavelength. WDM allows transmission of data from different sources over the same fiber optic link simultaneously, since each data source is assigned a dedicated channel. The result is an optical communication link with an aggregate bandwidth that increases with the number of wavelengths, or channels, incorporated into the WDM signal. In this way, WDM technology maximizes the use of an available fiber optic infrastructure, such that what would normally require multiple optic links or fibers instead requires only one. In practice, different wavelength channels of a WDM signal typically undergo asymmetrical losses as they travel through an optical communication system, resulting in unequal intensities for each channel. Because these unequal intensities can compromise the integrity of the information carried by the WDM signal, an optical device or array of optical devices is used in WDM systems to perform wavelength-independent attenuation to equalize the respective intensities of the channels contained in a WDM signal.
Liquid crystal (LC) based optical switches are known in the art for switching and attenuation of the channels contained in a WDM signal, and in some applications offer significant advantages over other optical switch designs, but there is one drawback related to the polarization state of an input light beam. Because LC-based optical switches rely on rotating the polarization state of linearly polarized input light to perform switching functions, the input light beam must have a single known polarization state for such an optical switch to vary the optical path of the light beam as desired. However, optical signals transmitted over optical fibers are usually randomly polarized, i.e., the optical signals have a random superposition of the s- and p-components, and each polarization component must be treated separately by an optical switch.
One approach known in the art for managing s- and p-polarized components of a light beam for LC switching of the light beam involves performing a polarization "walk-off" with a birefringent optical element to spatially divide the light beam into s- and p-polarized light beams or components. Polarization walk-off can be performed when an optical signal is first introduced into an LC-based optical switch, for example, as the optical signal exits an optical input fiber and becomes a free-space beam. After a birefringent optical element separates the optical signal into two physically displaced s- and p-polarized components, the polarization of one of the components can be rotated 90° to match the polarization of the other. In this way, the optical signal is converted into a pair of closely spaced, parallel beams having the same polarization state, and this pair of beams can be treated together by the optical switch as a single light beam having a known polarization state. However, such an approach requires the optical signal to be in the form of two parallel beams, sometimes over a long path length, which increases the likelihood of large polarization dependent losses (PDL) that degrade signal quality. In addition, because a relatively large optical assembly is needed to perform the polarization walk-off as the optical signal exits the fiber, an undesirably large spacing between the input and output ports of the optical switch, e.g., greater than 1 mm, results.
Alternatively, an LC-based optical switch can divide an input beam into s- and p-polarized components, then manage the attenuation and switching of each component separately. Such an approach can result in significant PDL, however, due to the different attenuation performance of an LC material toward s- and p-polarized light. FIG. 1 illustrates the electro-optic behavior of an LC optical attenuator with respect to incident s- and p-polarized light and includes attenuation curves 191 and 192. The abscissa of graph 100 represents voltage applied to the LC optical attenuator and the ordinate of graph 100 represents resultant attenuation of a light beam normally incident on and passing through the optical attenuator. Attenuation curve 191 illustrates the attenuation of the light beam that is s-polarized and attenuation curve 192 illustrates the attenuation of the light beam that is p-polarized. As shown, the attenuation curve of p-polarized light differs substantially from the attenuation of s-polarized light. Thus, when the s- and p-polarized components of a light beam are both conditioned by the LC optical attenuator, each component is attenuated by a different amount, resulting in PDL 193. For example, at applied voltage Vo, the LC optical attenuator attenuates s-polarized light 10 dB and p-polarized light 12 dB, producing a PDL 193 of 2 dB.
While switching and attenuation of optical signals are known in the art, each of these operations is typically performed by a different optical device. The use of one optical device to perform switching and another device to perform attenuation in an optical communication system increases the size and complexity of the system, makes erosion of signal quality more likely due to misalignment of the optical devices, and requires a first independent control signal to complete the switching function and a second independent control signal to complete the attenuation function.
Accordingly, there is a need in the art for an optical switch for use in an optical network that has a minimal number of components and closely spaced input and output ports and can perform switching and low-PDL attenuation of an optical signal having an arbitrary combination of s-polarized and p-polarized light.

Liquid crystal optical switch configured to reduce polarization dependent loss


Invention provides a cheaper and practical protocol for the construction of a wide variety of 1-Amino-2-naphthalene-carboxylic acid derivatives and their structural analogues that proceeds with high yields in a single step via intramolecular cascade cyano ene reaction.

1-Amino-2-naphthalenecarboxylic Acid Derivatives are the intermediates of Dyes and Pigments useful in Peptide Synthesis. There is less literature available on preparation of 1-Amino-2-naphthalenecarboxylic Acid Derivatives. An article titled "Efficient Synthesis of 1-Amino-2-naphthalenecarboxylic Acid Derivatives via a Sequential Michael Addition/Enolate-Nitrile Coupling Route and Its Application to Facile Preparation of 9-Amino Analogues of Arylnaphthofuranone Lignans" by Kazuhiro Kobayashi et al, published in J. Org. Chem 1997, 62, 664-668, wherein, a method for the general preparation of 1-amino-2-naphthalenecarboxylates and nitrites, which is based on the tandem Michael addition/enotate-nitrite coupling reaction between alpha-lithio derivatives of 2-atkylbenzonitriles and alpha-beta unsaturated carboxylic acid derivatives is described.
The reaction of 2-(alpha-lithioalkyl)benzonitriles, generated in situ by treatment of 2-alkylbenzonitriles with LDA in diglyme, with alpha-beta unsaturated carboxylates and nitrites produced 1-amino-3,4-dihydro-2-naphthalenecarboxylates and carbonitriles in 54-98% yields through Michael addition of the lithio nitrites to alpha-beta unsaturated carboxylic acid derivatives, followed by zinc iodide-promoted intra molecular enolate-nitrile coupling of the resulting enolate intermediates. The dihydronaphthalenecarboxylic acid derivatives were converted to the corresponding 1-amino-2-naphthalenecarboxylic acid derivatives in 43-99% yields on dehydrogenation with palladium on activated carbon in refluxing p-cymene. The synthesis is depicted in scheme 1 below.

The process disclosed in the above prior art involves multiple steps and hence not feasible on industrial scale. Also, the process requires consumption of large quantities of hazardous chemicals with longer reaction time with less efficiency and narrow substrate scope.

Cu-mediated annulation for the production of 1-amino-2-naphthalenecarboxylic acid derivatives

Council of Scientific & Industrial Research


An analog electronic timepiece, including: a stepping motor; a first indicating unit which makes a step rotation by a predetermined first rotation angle according to the step drive; a second indicating unit which makes a step rotation by a second rotation angle which is smaller than the first rotation angle in conjunction with the step rotation of the first indicating unit; an independent rotation control unit; an interlocking rotation control unit; and a rotation selection unit which activates the independent rotation control unit when current processing is in an operation mode where the rotation position of the first indicating unit is changed or in an operation state where the rotation position of the first indicating unit is temporarily changed and which activates the interlocking rotation control unit when a setting relating to a final rotation position of the first indicating unit is fixed.

1. Field of the Invention
The present invention relates to an analog electronic timepiece.
2. Description of Related Art
Conventionally, there have been analog electronic timepieces which can perform display relating to various functions in addition to the time display function. Some of the analog electronic timepieces include function hands and rotating plates used for display relating to other functions and used for indicating the function types of the displayed contents in addition to time hands such as hour hands and minute hands which are used when displaying time and a date wheel displaying an indicator indicating a date.
In such multifunctional electronic timepiece, each of the hands and the rotating plates is required to have its own operation which is different from the time display and is able to be rotated independently by an individual stepping motor and a gear train mechanism in some cases. However, when the number of the hands and the rotating plates increases, more electric power is required to drive the stepping motors and more space is required to provide the stepping motors and the gear train mechanisms, leading to enlargement of timepieces. Thus, in some of such electronic timepieces, a function hand and a rotating plate which do not need to operate independently are combined so as to be rotated in conjunction with each other by a single stepping motor and the configuration and location of the gear train mechanisms are contrived to save the space, which is described in Japanese Patent Laid-Open Publication No. 2010-223689, for example.
However, since there is a limit to the number of stepping motors which can be located inside a timepiece having a predetermined size, stepping motors cannot be effectively utilized if they are provided for independently driving the hand and the rotating plate which operate less frequently. On the other hand, if a plurality of hands and rotating plates which perform display independently are operated by a single stepping motor, the number of operations of the stepping motor increases to maintain a plurality of display contents accurately and more operation time is required for maintaining the accurate display condition, leading to inferior usability for a user.
The present invention relates to an analog electronic timepiece which can operate a plurality of hands effectively without deteriorating usability for a user.


A jetting device and a method of jetting droplets of viscous medium onto a substrate. The jetting device includes a jetting outlet through which the droplets are jetted. The jetting device further includes a wall located at the jetting outlet, downstream of the jetting outlet seen in the jetting direction. The wall is provided with an orifice through which jetted droplets are permitted to pass through. A gaseous flow is provided within the space past the jetting outlet such that an adverse effect on the performance of the jetting device is prevented, the adverse effect resulting from the accumulation of viscous medium residue at the jetting outlet.

Devices of the above mentioned kind are known and are primarily intended to be used for jetting droplets of viscous medium, e.g. solder paste or glue, onto a substrate, e.g. an electronic circuit board, prior to mounting of components thereon. An example of such a jetting device is disclosed in WO 99/64167. The jetting device comprises an eject chamber for containing a small volume of said medium prior to the jetting thereof, an eject nozzle communicating with the eject chamber, eject means for jetting said medium from the eject chamber through the eject nozzle, and supply means for feeding said medium into the eject chamber. In WO 00/62587 there is disclosed an assembly comprising such a jetting device.
The production speed is an essential factor in the manufacturing of electronic circuit boards. This has lead to a desire of increasing the speed at which a substrate is provided with viscous medium, a way of effecting this is to perform the actual jetting "on the fly", i.e. without stopping for each location on the substrate where viscous medium is to be deposited. A further way to improve the manufacturing speed of electronic circuit boards is to eliminate or reduce the need for operator interventions.
Both of these measures require good and reliable performance of the device used in the process, as well as a high degree of accuracy and a maintained high level of reproducibility during an extended period of time. The high quality requirements of the electronic industry and the detrimental consequences of errors appearing in circuit boards even further emphasise these requirements.

Jetting device and a method of jetting device


The invention relates to composition and methods of use thereof for controlling insects. The compositions comprise aminopeptidase inhibitors or metallopeptidase inhibitors and further comprise a non-strongly-chelating peptidase inhibitor. The compositions are preferably applied topically, and preferably cause inhibition of hatching of insect eggs and/or inhibition of the development and/or mortality of insect larvae.

Insects cause significant pest problems in a wide variety of animals and plants worldwide, with estimates of 13% of crop production lost each year despite current control measures. Insect species of the orders Lepidoptera, Hemiptera, Orthoptera, Coleoptera, Psocoptera, Isoptera, Thysanoptera and Homoptera cause massive losses to many horticultural and broadacre crops and stored and manufactured grain products. Diptera, Anaplura, Malophaga and Siphonaptera cause parasitic infections in animals and man. Other orders (Hymenoptera, Dictyoptera, Isoptera) include important domestic and industrial pests.
Many of the known control measures for insects depend on the use of chemical insecticides, for example chlorinated hydrocarbons (DDT, endosulfan etc), organophosphates (chlorpyrifos, diazinon, malathion, parathion), organocarbamates (carbaryl, methomyl, proxypur) and synthetic pyrethroids (cypermethrin, deltamethrin).
Problems associated with the use of chemical insecticides include the development of resistance by target insects (organophosphates, synthetic pyrethroids), the persistence of the chemicals in the environment and in plant and animal tissues, and the harmful effects on non-target organisms (organochlorines, insect growth regulators).
Boron compounds (borax, polybor) have also been used for insecticidal purposes. Boron compounds are stable, kill insects relatively slowly at practical doses (Mullens and Rodriguez, 1992), and ingestion of large doses by humans can be lethal (Anon, 1991)
Other categories of insecticide include insect growth regulators (IGRs) and insecticidal bacterial toxins (eg. Bacillus thuringiensis (Bt) toxins). IGRs are compounds that interfere in some way with chitin synthesis. They include juvenile hormone analogues (methoprene), chitin synthesis inhibitors (fenoxycarb, diflubenzuron, flurazuron) and triazine derivatives (cyromazine). Resistance has been noted to many classes of IGR. Resistance is also developing in certain lepidoterans to Bt toxins. It is technically difficult with both IGRs and Bt toxins to ensure adequate insect kill at an appropriate stage in its life cycle. Some IGRs are stable and may pose environmental hazards.
The most useful groups of insecticides are those having high insecticidal activity and low environmental persistance (organophosphates, synthetic pyrethroids). The greatest problem associated with these, however, is the development of resistance by target insects. It is believed that 90% of insecticide use is still based on classical neurotoxic insecticides. The search for alternative low-residual insecticides which are effective on insects resistant to existing insecticides is thus particularly urgent.
Agents referred to as synergists may be used to maximise effectiveness of particular insecticides. Synergists may or may not be insecticidal in their own right. Blood and Studdert (1988) define a synergist as an agent that acts with or enhances the action of another. As an example, it may be noted that piperonyl butoxide is a synergist for synthetic pyrethroids. Synergists which are effective in combination with a particular insecticide may not be effective in combination with other insecticides. Synergists can be used to overcome problems of insect resistance, although insect resistance to synergists can also occur. The role of synergists in insecticidal formulations can be vital for achieving a commercially viable result, and for insecticide resistance management. The search for effective synergising combinations is as urgent as the search for effective insecticides per se (Forrester et al, 1993).
Recently attention has focused on insect peptidases, inhibition of which may provide a possible means of insect control. Peptidases are ubiquitous enzymes which break down proteins and peptides, and thus assist with digestion both in the gut and in cells. They are involved in tissue reorganisation during embryo development, moulting and pupation in insects. They are also involved with defence against invading organisms and with protein regulation.
Peptidases are a widely variable group of enzymes. Currently they are classified according to:
(1) the reaction catalysed PA1 (2) the chemical nature of the catalytic site, and PA1 (3) the evolutionary relationship as revealed by structure (Barrett, 1994) PA1 N-acetyl-L-phenylalanine ester (APNE) PA1 N-acetyl-L-tyrosine ethyl ester (ATEE) PA1 N-benzoyl-L-tyrosine ethyl ester (BTEE) PA1 N-benzoyl-L-tyrosine-p-nitroanilide (BTPNA) PA1 L-glytaryl-L-phenylalanine-p-nitroanilide (GPPNA) PA1 N-succinyl-L-phenylalanine-p-nitroanilide (SPAPNA) PA1 L-glutaryl-L-phenylalanine naphthylanide (GPNA). PA1 (a) effective inhibitors of the above category suitable for the genetic transformation of plants have not been identified, PA1 (b) the apparent role of these enzymes is minor relative to the dominant cysteine and/or serine peptidase activities in the gut of insects. PA1 (a) control of insect infestation by direct application to a plant or animal vulnerable to such infestation; PA1 (b) reduction of insect numbers by application of the agents of the invention to insect habitat or breeding sites; PA1 (c) control, either by way of prophylaxis or reduction in severity, of infections in plants or animals which are transmitted by insects; and PA1 (d) control, by way of prophylaxis or reduction in severity, of infections in plants or animals which are consequential upon insect infestation. PA1 1. Select representative active peptidases, which may be purified or in compositions comprising the active enzyme. PA1 2. Select an enzyme activity assay for each of the representative peptidases by selecting an appropriate substrate for the enzyme and conditions for the reaction so as to yield an appropriate quantifiable endpoint in a convenient time. PA1 3. The test compound is considered to be a peptidase inhibitor if a reaction inhibition of 50% or greater is found in any of the above enzyme activity assays. PA1 trypsin and chymotrypsin inhibitors, such as PA1 4-(2-aminoethyl)-benzenesulfonylfluoride hydrochloride (PEFABLOC) PA1 serine or cysteine peptidase inhibitors derived from legumes, vegetables, fruits or cereals; PA1 cystatins and E-64; PA1 carboxypeptidase inhibitors from potato or other sources; PA1 Eglin C; PA1 L-leucinethiol. PA1 (a) The animals treated by the methods of the invention are selected from the group consisting of humans, sheep, cattle, horses, pigs, poultry, dogs and cats. PA1 (b) The plants treated by the methods of the invention are selected from the group consisting of cotton, oil seed crops, ornamental plants, flowers, fruit trees, cereal crops, vine crops, root crops, pasture plants and vegetables. PA1 (c) The insects to be controlled in the case of horticultural and broadacre applications of the invention are Lepidoptera, Hemiptera, Orthoptera, Coleoptera, Isoptera, Thysanoptera or Homoptera, in the case of insect infections in animals are Diptera, Anaplura, Malophaga or Siphonaptera, or in the case of domestic or industrial pests are Isoptera, Dictyoptera and Hymenoptera. PA1 (d) The transgenic plants are selected from the group consisting of cotton, oil seed crops, ornamental plants, flowers, fruit trees, cereal crops, vine crops, root crops, pasture plants, and vegetables, and PA1 (e) The transgenic organisms to be resident in or on an animal or plant are Bacillus sp or Pseudomonas sp or Mycobacteria sp. PA1 Preparing a suitable vector comprising a nucleotide sequence that codes for a peptide agent that inhibits an aminopeptidase or "non-strongly-chelating" peptidase and a promotor wherein the nucleotide sequence is capable of being expressed by a host contained the vector. PA1 Incorporating the vector into the host; and PA1 Maintaining the host containing the vector under conditions suitable for transcription and translation of the nucleotide sequence into said peptide agent.
The International Union of Biochemistry and Molecular Biology (IUBMC), In:Enzyme Nomenclature (1992), classifies peptidases by enzyme class (EC) categories. These categories are EC 3.4.11 to 3.4.19 for exopeptidases (those enzymes that only act near the ends of peptide chains) and EC 3.4.21 to 3.4.99 for enzymes that preferentially act on the inner regions of peptides. Group EC 3.4.99 is a group of peptidases for which the catalytic mechanism is unrecognised or uncharacterised.
An overview of the peptidase classes and their relationship to insect biochemistry is outlined below.
1. Serine Peptidases
This group includes serine-type carboxypeptidases EC 3.4.16, and serine endopeptidases EC 3.4.21.
Serine peptidases are typically recognised by a catalytically active serine amino acid at their active site, and by their sensitivity to an enzyme inhibitor, 3,4-dichloroisocoumarin (3,4-DCI). The preferred pH range for activity of mammalian serine peptidases is 2-8; however insect serine peptidases are commonly adapted to alkaline conditions (pH 9 to over 11 in some lepidopteran larvae).
The activity of serine peptidases in insects is also commonly defined by reaction of the enzymes with synthetic substrates. The three common categories of insect serine peptidases (trypsin-like, chymotrypsin-like and elastin-like) can be identified in this way. Trypsin-like serine peptidases react with synthetic substrates P-tosyl-L-arginine methyl ester (TAME), .alpha.-N-benzoyl-L-arginine ethyl ester (BAEE), .alpha.-N-benzoyl-DL-arginine-p-nitroanilide (BAPNA) and benzoyl-DL-arginine naphthylamine (BANA).
Chymotrypsin-like peptidases may be identified by their reaction with:
Elastase-like serine peptidase inhibitors may be identified by their reaction with synthetic substrates such as N-succinyl-ala-ala-pro-leu p-nitroanilide (SAAPLpNA) (SEQ ID NO:1)
The activity of serine peptidases may also be described in terms of their reaction with enzyme inhibitors. Serine-group peptidases are generally inhibited by Di-isopropyl-fluro-phosphate (DipF/DFP), and paraphenyl methyl sulphonyl fluoride (PMSF). Trypsin-like peptidases are inhibited by tosyl-L-lysine chloromethyl ketone (TLCK). Chymotrypsin-like peptidases are inhibited by tosyl-L-phenylalanine chloromethyl ketone (TPCK). Elastase-like peptidases are inhibited by Eglin-C.
A number of naturally occurring proteins have been found to be able to inhibit serine peptidases. These include the crystalline soybean trypsin inhibitor of Kunitz (SBTI) and the soybean trypsin inhibitor of Bowman-Birk (BBTI). Various other legume seeds contain peptidase inhibitor at 1-4% of total protein, for example chickpea trypsin/chymotrypsin inhibitor (CI), Lima Bean trypsin inhibitor (LBTI) and cowpea trypsin inhibitor (CPTI) (MacIntosh et al, 1990). Animal-derived serine peptidase inhibitors include bovine pancreatic trypsin inhibitor (BPTI, Aprotinin), egg-derived ovomucoid and alpha-1-antitrypsin from blood.
Serine peptidases having alkaline pH optima are recognised to be of primary importance as soluble enzymes in the digestive fluids of insects. Examples include sphingidae (Miller et al, 1974), noctuidae (Ahmed et al. 1976, 1980; Ishaaya et al, 1971; Prichet et al, 1981; Teo et al, 1990; Broadway and Duffy, 1986), bombycidae (Sasaki and Suzuki, 1982; Euguchi and Iwanito, 1976; Euguchi and Kuriyama, 1985), pieridae (Lecadet and Dedonder, 1966; Broadway et al, 1989) pyralidae (Larocque and Houseman, 1990; Houseman et al, 1989; Mohammed and Altias, 1987) and diptera (Bowles et al, 1990). Cristeller et al (1992) showed that serine peptidases were implicated in the (casein) digestive activity of twelve phytophagous lepidopterans. In this article Christeller found that no other type of peptidase showed significant evidence of digestive activity. Serine peptidases have also been found to exhibit a dominant role in keratin-digesting lepidopterans (Christeller et al, 1994; Prowning and Irzykiewicz 1962; Ward, 1975 a, b). Furthermore, they have an important role in the digestive activity of some coleopterans (McGhie et al, 1995, Dymock et al, 1992), some orthopterans (Sakal et al, 1989; Christeller et al, 1990), some heteropterans (Cohen 1993) and in some dipterans (Bowles et al, 1990).
The digestive serine peptidases vary considerably both in number and in catalytic properties within and between species (Applebaum, 1985). In some instances inhibitors of serine peptidases in insect diets have been recognised to cause feeding deterrence as well as digestive inhibition (Dymock et al, 1992).
Trypsin-like serine peptidases have been recognised to be involved in the key growth regulatory area of molting. They exhibit several roles including process control, exposure of chitin fibrils to chitinase enzymes and in recycling of cuticular material (Samuels and Paterson, 1991).
Because of their dominant metabolic roles, their common natural occurrence, and the occurrence of many natural inhibitors in plants and animals, serine peptidases have received the most attention as agents for insect control. It is important to note that the context for use of serine peptidases in insect control has almost entirely been in the area of transgenic plants.
2. Cysteine (Thiol) Peptidases
This group includes cysteine-type carboxypeptidases (EC 3.4.18) and cysteine endopeptidases (EC 3.4.22).
These enzymes are characterised by possession of a catalytically active cysteine residue at their active site and by their sensitivity to certain inhibitors. Cysteine peptidases are characteristically activated under reducing conditions (added cysteine, dithiothreitol or other reducing agents). Cysteine peptidases are soluble enzymes generally found in midgut contents of insects. Mammalian cysteine peptidases commonly function in low pH conditions, although in insects, near neutral or mildly acidic pH values are favoured (Wolfson and Murdock, 1987).
The activity of cysteine peptidases is exemplified by their reaction with synthetic substrates n-.alpha.-benzoyl-L-arginine-p-nitroanilide (BAPNA) or benzoyloxy carbonyl-phe-arg-7-(4 methyl) coumaryl amide (Z-Phe-Arg-MCA). The activity of cysteine peptidases may also be described in terms of their reaction with enzyme inhibitors such as iodoacetamide, iodoacetate, heavy metals, p-chloromercuribenzoate, cystine cyanide, N-ethyl maleimide and characteristically, E-64. E-64 is a small peptide (L-trans-epoxy-succinyl-leucylamido-(4-guanidino-butane) obtained from a strain of Aspergillus japonicus. Naturally occurring cysteine peptidase inhibitors have been identified in microbes (E-64), plants (oryzacystatins I and II from rice grains and potato multicystatin (PMC) from potato tubers), and animals (hen-egg cystatin, HEC). Antipain is another well-known cysteine peptidase inhibitor.
Cysteine peptidases play a major role as soluble digestive enzymes of the gut of some insects, notably coleopterans (Orr et al, 1994; Thie and Houseman, 1990; Liang et al, 1991). The use of cysteine peptidase inhibitors for the control of insects has been largely explored in the context of transgenic plants (Orr et al, 1994; Wolfson and Murdock, 1987).
3. Aspartic Peptidases (EC 3.4.23)
These enzymes are typically recognized as possessing two aspartyl residues at the active site. Many aspartic peptidases are most active at low-pH values. Synthetic substrates for these enzymes include N-carbobenzoxy glutamyl-L-tyrosine and N-acetyl-L-phenanyl diiodotyrosin. Characteristic inhibitors for aspartic peptidases include pepstatin and diphenyl diazomethane (McDonald, 1985). Pepstatin is a naturally occurring inhibitor from a microbial source.
Applebaum (1985) has suggested some significance of aspartic peptidases to dipterans. Wolfson and Murdock (1987) have demonstrated some growth inhibition of a coleopteran (Colorado potato beetle larvae) by pepstatin; however, greater inhibition of growth was obtained by targeting cysteine peptidases.
An extensive search of the literature on peptidases has shown that only a limited amount of research has been conducted on insect aspartyl peptidases for insect control, either by transgenic modification of plants or by topical application. Christeller et al (1992) found that aspartic peptidase activity is apparently not evident in phytophagous lepidopteran gut material.
4. Metallopeptidases
These enzymes are typically recognised as possessing a catalytically active metal ion (commonly zinc) at the active site, and by their sensitivity to chelating agents. The metallopeptidase category includes some endopeptidases (enzymes that cleave within the peptide chain) and exopeptidases (enzymes that cleave amino acid(s) from the termini of peptides). Exopeptidases can further be categorised as carboxypeptidases (which cleave amino acid(s) from the C terminus) or aminopeptidases (which cleave amino acids from the N terminus).
Metallo endopeptidases (EC 3.4.22)
These enzymes have not been implicated in insect biochemistry, except for a possible role in wool digestion by keratinophagous lepidopterans (Prowning and Irykiewicz, 1962; Ward, 1975 a and b; Christeller et al, 1990, 1994).
Metallo carboxypeptidases (EC 3.4.17)
Metallo carboxypeptidases require a bivalent cation (usually Zn.sup.2+) for activity. They exist in both free and membrane-bound forms and favour activity at high (8-10) pH. Synthetic substrates for carboxypeptidases include hippuryl-DL-phenyl-lactic acid and hippuryl-L-arginine, for carboxypeptidase type A and B, respectively. Carboxypeptidase A-like enzymes appear to be more common in insects, and have been found in orthopterans, coleopterans, dipterans and lepidopterans.
Synthetic inhibitors for metallo carboxypeptidases include 1,10-phenanthroline, ethylene diamine tetraacetic acid (EDTA), .beta.-hydroxyquinoline and phosphoramidon. A naturally occurring inhibitor for metallo carboxypeptidase is potato-derived carboxypeptidase inhibitor (PCPI).
Carboxypeptidase enzymes in both free and membrane-bound forms have been recognised in mid-gut material from lepidopteran larvae (Ferreira et al, 1994; Christeller, 1990). Christeller et al (1992) described these enzymes as expected components of the protein digestion system. Prior to the priority date of this application these enzymes were not apparently recognised as targets for transgenic modification of plants, let alone as components of topical control agents.
Aminopeptidases (EC 3.4.11-3.4.13)
Aminopeptidases hydrolyse amino acids from the N-terminus of peptide chains, and are generally classified according to their dependence on metal ions (Zn.sup.2+ or Mg.sup.2+). The best studied aminopeptidases are found in the digestive tracts of mammals in both membrane bound and soluble forms. Aminopeptidases are commonly named with a suffix letter designating their pH optima, acidic (A) basic (B) or neutral (N), or by their membrane bound (M) state or by the number and type of amino acids cleaved from peptide substrates. These names are not exclusive; thus a leucine aminopeptidase M or N is an enzyme that preferentially but not exclusively removes leucine from a peptide, is membrane bound and whose activity is optimal at neutral pH. Aminopeptidases show preferential hydrolysis of leucyl, arginyl, methionyl, aspartyl, alanyl, glutamyl, prolyl, valyl and cysteinyl residues; however, substrate specificity is usually broad, and also depends on the other residues in the peptide chain (Taylor, 1993 a and b). Most aminopeptidases are metallopeptidases, although a few bacterial enzymes are known not to require metal ions for activity (Taylor, 1993 a and b). There are apparently few natural inhibitors of aminopeptidase.
Insect aminopeptidases usually have alkaline pH optima and are generally inhibited by bestatin (Taylor, 1993) and phenanthroline (Barrett, 1994).
Substrate specificities are broad, as stated above, but typical substrates include leu-pNA, arg-pNA, met-pNA and pro-pNA.
Metallo aminopeptidases are inhibited by chelating agents (such as EDTA), which can either remove the metal ion from the peptidase or form an inactive complex with the enzyme (Terra & Ferriera, 1994). The action of a particular chelator will vary with the type of aminopeptidase as well as with the chelator's own structure.
Aminopeptidases have been also recognised as part of the insect complement of digestive peptides, and are thought to be involved in the terminal stages of protein digestion (Terra & Ferriera, 1994). Christeller et al (1990, 1992) has asserted that exopeptidases (including aminopeptidases) will be of little use for insect control because of the minor role of these enzymes in the digestion of dietary protein relative to serine and cysteine peptidases.
Insect larval growth retardation following exposure to specific leucine aminopeptidase (LAP) inhibitors has not been reported. Christeller et al (1990) have shown with crude field cricket gut extracts that although exopeptidase levels, particularly LAP, are significant in this insect, exopeptidases contributed only 16-20% of protein digestion. In Christeller's study, it was further found that in the presence of two effective serine peptidase inhibitors, the contribution of exopeptidases to protein digestion was greatly reduced. This was attributed to lack of oligopeptide chain ends to act as substrates for exopeptidases. This further indicated a minor role for aminopeptidases in insect control.
The above findings teach strongly away from the use of exopeptidase inhibitors (principally aminopeptidase inhibitors) as insect control agents, and teach particularly strongly away from the combined use of serine peptidase inhibitors and aminopeptidase inhibitors as insect control agents.
Apart from a digestive role, aminopeptidase activity has been demonstrated in the moulting fluid of the lepidopteran Manduca sexta (Jungries, 1979). However, again the role of aminopeptidases appears to be secondary to the role of serine (trypsin-like) peptidases. No naturally occurring inhibitors of aminopeptidases or metallopeptidases important in insect development have been reported as effective in retardation of moulting. None have been used to provide insect-resistant transgenic plants.
Theoretically there appears to be a high potential for using peptidase inhibitors to control insects which are resistant to chemical insecticides. Firstly, the mechanism of action of peptidase inhibition is different from the mechanism of action of organophosphates and synthetic pyrethroids. Secondly, the amino acid sequence of the active sites of peptidase enzymes appears to be highly conserved (Taylor, 1993), thus indicating a low potential for mutation without consequent loss of activity. Finally, in the event that insect resistance to a particular peptidase inhibitor occurs, this resistance should not carry over to other peptidase mediated metabolic events.
However, there are significant problems associated with the use of peptidase inhibitors for the control of insects. High use rates may be required, leading to a product which is not cost-effective. Furthermore, whilst the peptidase inhibitor may limit larval growth, it is possible that a plateau is reached in the dose-response curve, even at elevated use rates. Peptide-based or protein-based peptidase inhibitors, while presumably non-residual in the environment, may be difficult to store over extended periods, and may lose efficacy when delivered in hard water. Subtle issues involving the source of a particular enzyme inhibitor may need to be addressed. For example, anomalous responses involving growth inhibition of Costelytra zealandica by soybean, potato and cowpea trypsin inhibitor and growth stimulation by lima bean trypsin inhibitor have been noted (Dymock et al, 1992).
Considerable research has centred on biochemical investigations of insect protein metabolism, principally digestive metabolism, using insect tissues, gut extracts, semi-purified or purified enzymes in vitro.
Much of this work has been directed toward the selection of enzyme inhibitors for the transgenic modification of plants by investigating the relationship of digestive enzymes with protein or peptide based inhibitors (Applebaum, 1985; Christeller et al, 1989, 1990, 1992; Lenz et al, 1991; Teo et al, 1990; Pritchett et al, 1981, Santos and Terra, 1984; Dow, 1986; Sakal et al, 1984, 1989).
Relatively fewer studies demonstrate a direct adverse influence of peptidase inhibitors on insect growth and/or reproduction. Serine and cysteine peptidase inhibitors have been shown to reduce the larval growth and/or survival of various insects, including Callosobruchus macalatus, Leptinotarsa decemlineata, Heliothis spp, Spodoptera exiqua, Costelytra zealandica, Teleogryllus commodus, Diabrotica sp, Manduca sexta, red four beetle and bean weevil (Gatehouse and Boulter, 1983; Shuckle and Murdock, 1983; Shade et al, 1986; Wolfson and Murdock, 1987; Broadway and Duffey, 1986; Hilder et al, 1987; Dymock et al, 1992; Orr et al, 1994; Burgess et al, 1994; Hines et al, 1990).
Generally insect growth inhibition has been achieved with inhibitors of principal digestive enzymes of the gut, and a method for selection of appropriate insecticidal inhibitors based on these enzymes has been described by Christeller et al (1992).
None of the above studies appears to be directly aimed at the production of topical insect control agents through interference with protein metabolism. In International Patent Application No. W094/16565 by Czapla, however, a minor claim cites the topical use of aprotinin or another serine peptidase inhibitor with 90% homology to aprotinin for control of the European corn borer (ECB) and Southern corn rootworm (SCR). It was claimed that aprotinin could be used alone or in combination with an insecticidal lectin. Czapla found that incorporation of aprotinin at 20 mg/ml of diet killed 100% of neonatal ECB larvae in a laboratory assay, and killed 60% of neonatal SCR. Ingestion rates as high as these would be difficult to achieve by topical application, and treatment costs would be unlikely to be competitive with chemical insecticides. Czapla found that the serine peptidase inhibitor SBTI (Kunitz and Bowman-Birk) and the cysteine peptidase inhibitor cystatin were less effective than aprotinin.
Direct feeding of SBTI to blood sucking insects has been investigated by Deloach and Spates (1980). They found raised mortality and suppressed egg hatch when SBTI was encapsulated in bovine erythrocytes and used as a bait for horn-fly. Various natural peptidase inhibitors (principally of serine peptidases) are known in blood. However, they have limited efficacy in protecting the animal from insect attack (Sandeman et al, 1990).
Wolfson and Murdock (1987) observed that whilst there is extensive documentation on the presence and distribution of peptidase inhibitors in plants, and these inhibitors are presumed to be targeted at insect digestive peptidases, there is little direct evidence to support their efficient action in inhibiting insect growth and development. These authors demonstrated that larval growth reduction in Colorado potato beetle could be obtained by feeding E-64 (a cysteine peptidase inhibitor) at threshold levels of 50 .mu.g/ml on potato leaves. However at a much higher application level (1000 .mu.g/ml) a plateau in mortality of 74-85% was found, which is insufficient for practical use. SBTIs (Kunitz and Bowman-Birk) were ineffective as growth retardants, and there was only a small response to pepstatin.
A research paper by Dymock et al (1992) has discussed the inhibition of growth of a larval coleopteran (New Zealand native grass grub) by peptidase inhibitors. The research was focussed on the genetic transformation of important pasture species, as the grubs feed on roots. Bioassays showed growth inhibition using serine peptidase inhibitors. Some anomalous responses to particular inhibitors were noted (inhibition by SBTI, POT I, POT II, CpTI, stimulation by LBTI). Cristeller et al (1989) had previously identified trypsin as the principal gut peptidase in the above grub, despite the fact that normally coleopteran gut peptidases are predominantly of the cysteine category. Generally the use rate of peptidase inhibitors required to achieve mortality was too high to be cost effective in topical use.
Compositions that function by inhibition of metallopeptidases (including aminopeptidase or LAP) have not been commercially developed for the control of insects. In fact, the prior art teaches away from the use of peptide-based aminopeptidase inhibitors or metallopeptidase inhibitors for insect control, because:
Shenvi (1993) has discussed the use of .alpha.-amino boronic acid derivatives as effective inhibitors of mammalian aminopeptidases. Shenvi notes that certain intermediates in the synthesis of .alpha.-amino boronic acid derivatives have insecticidal properties; however these intermediates did not have an amino group, and are not suggested to act either as aminopeptidase inhibitors or peptidase inhibitors of any sort.
The hexadentate metal chelating agent EDTA has been recognised by Samuels and Paterson (1995) and Ferreira and Terra (1986) to be an inhibitor of an aminopeptidase derived from the moulting fluid and digestive membranes. There is no recognition of any insecticidal effect of EDTA; however general claims for the insecticidal action of metal chelating agents have been made by Tomalia and Wilson (1985, 1986). No supporting evidence was presented. The use of metal chelating agents for insect control would be expected to be adversely influenced by the use of hard water for spray application, or if there was mineral or soil contamination of the materials to be treated.
We have now surprisingly found that compositions comprising an aminopeptidase inhibitor or metallopeptidase inhibitor and further comprising a non-strongly-chelating peptidase inhibitor are able to prevent the hatching of insect eggs and/or the development of insect larvae. The person skilled in the art will recognise that the vast majority of aminopeptidase inhibitors are in fact non-strongly-chelating, as this term is defined herein.
It will be clearly understood that the invention is applicable to the control of insects via a variety of mechanisms. The methods of the invention may, for example, result in the actual killing of insects, or in the interruption of insect growth and development so that maturation is slowed or prevented. Prevention of hatching of insect eggs is particularly desirable, since many economically important insects cause damage as a result of the feeding activities of their larvae.
It will be also understood that because of the wide variation of individual biochemical capacities within members of the class Insecta, responses to particular inhibitors and/or combinations of inhibitors will vary between species. Thus it is possible that some compositions within the scope of this invention will be poorly effective or even ineffective against some insects, while being highly effective against others. Variations in responses may also be seen at subspecies level or at different stages in the life cycle for particular insects, or even with the diet of the insects. Those skilled in the art will be able to match relevant inhibitors to insect targets by application of normal trial and error laboratory and field experimentation.
It will also be apparent to the person skilled in the art that the invention may be utilised in variety of ways, including but not limited to:
For the purpose of this specification, the term "peptidase inhibitor" is to be understood to be any compound able to inhibit any peptidase.
In practical terms a peptidase inhibitor can be identified by the following process.
Specifically, a metallopeptidase inhibitor or an aminopeptidase inhibitor may be identified in this way.
The term "non-strongly-chelating peptidase inhibitor" is to be understood to mean a peptidase inhibitor that chelates Zn.sup.2+ ions less strongly than EDTA in a competitive binding assessment. Both EDTA and the inhibitor should be at the same concentration in the reaction mixture, which may conveniently be 0.1 mM. The person skilled in the art will be able to choose appropriate reaction conditions and methods for determining Zn.sup.2+ distribution (eg. using multinuclear nuclear magnetic resonance (NMR), UV spectroscopy, voltametric techniques and soft ionization mass spectroscopy).