This disclosure describes, generally, tools for navigation of tree structures. For example, a software application comprising a user interface for allowing a user to navigate a tree structure is described. The user interface comprises a graphical element including the tree structure. The tree structure comprises multiple nodes which represent a hierarchical view of data within the structure. One of the nodes is set as the active node. The computer software application also includes a storage element to store a list of previous active nodes. The graphical element is in conjunction with a first navigational element configured to step backward through the list of previous active nodes, and to set the stepped to node as the active node. The graphical element is further in conjunction with a second navigational element configured to step forward through the list of previous active nodes, and to set the stepped to node as the active node.

Tree data structures are a common way to represent hierarchical information in software application such as, file folders, database relations, software code class trees, system registries, etc. Such tree structures facilitate access to information by organizing the information in a logical manner. However, as the information being represented becomes larger and more complex, the tree structures grow to include more nodes and a greater number of levels in the hierarchy. Consequently, these larger tree structures become increasingly difficult for users to navigate, and very few innovations in managing these tree data structures have been made.
Specifically, larger trees include more information for a user to search through. In addition, the information that the user is looking for may be deep within the hierarchy of the tree. As such, if a user is not already aware of where to find the information they are searching for, the user may be required to follow potentially long branches. Even if the user does happen to know where the information they are looking for is located, the user may still be required to browse through several nodes in order to get to their desired location.
Furthermore, navigation in large trees becomes even more difficult when a tree includes many levels of sub-nodes. This is due to the fact that exploring those levels requires the user to scroll both horizontally and vertically in order to fit a new level within a window's viewing area. As the user scrolls down more and more levels, the user must remember their position within the tree. Remembering tree positions in large trees becomes increasingly difficult. This problem is compounded when a user employs a find or search option. Following a search the user has virtually no way to orient themselves within the tree structure.
Consequently, as a user searches through a tree structure, the user may easily become disoriented, and have difficulty returning to their starting location. Further, as a user navigates through the tree structure they may lose track of previously selected nodes. For these reasons, among others, there is a need for improvements to navigational tools in a hierarchical tree data structure.


A compact tension testing apparatus for determining the peel strength of a circuit line or film bonded to a substrate. A force gauge is mounted on an apparatus using low friction air bearings to allow the force gauge to self-align with the peeling location of the circuit line or film, thereby providing essentially orthogonal positioning relative to the substrate.

Tensile testing machines are commonplace. Typically, a material test sample is clamped to a horizontal platform, and a clamping device attached to a force gauge is lowered in a vertical direction and attached to the test sample. Means are provided to move the clamping device and force gauge in an upward direction, thereby causing a tensile force to be applied to the test sample.
Commonly, samples are destructively tested in a large tensile testing machine, wherein a sample to be tested must be sacrificially extracted from a larger specimen for the sake of the test. Once the test has been completed, the sample is usually discarded, which can be prove to be very costly.
Typical tensile testing machines used for laminate bond testing only provide peeling movement in one direction, so that the electrical circuit line or other sample on a substrate being tested must be lined up along the one direction of movement. Unfortunately, this requires the substrate to be repositioned and clamped whenever a circuit line has a directional orientation different from the previous test direction. Further, when peeling a circuit line from a substrate, the force gauge must be constantly moved in order to keep the force gauge directly over the peeling location. This is necessary in order to ensure that a true force reading of the force perpendicular to the substrate is being measured.

International Business Machines Corporation


A FIFO queue is utilized to provide control information to the appropriate time slot in a time multiplexed serial link between an interface chip and a CODEC. The FIFO queue allows rewriting or replacement of any control registers present in the queue without requiring that a new entry be placed in the queue. A particular control register which is placed in the queue then maintains its place as the queue is emptied, even though the control register may be written one or more times while the control register entry is in the queue waiting for transmission to the CODEC. The loss of the prior command information is not a problem as the data rate of the serial link is still sufficiently high so that any minor transitory change which may have been desired would be of minimal effect in any regard and would have been inaudible to the human.

1. Field of the Invention
The invention relates to FIFO queues used to pass information between two devices, and more particularly to a FIFO queue where entries in the queue can be replaced without reordering the queue.
2. Description of the Related Art
As current computer systems become more and more complicated, one trend is that more and more functions are being placed onto a single chip. However, one resulting problem limiting this integration is the number of pins needed on the chips. An increase in the pin count increases the costs of the chip and beyond certain pin count levels manufacturing both the chip and the circuit board becomes very complicated and thus expensive. Therefore it is desirable to reduce the number of pins on the chip. This leads to a trade off between function integration and cost.
Part of the pin count problem derives from the fact that the most common interfaces in computer systems are done in a parallel manner because of speed considerations. Addresses and data are provided in a parallel manner so that higher bandwidths can be obtained for a given clock rate. While serial links have been considered in some cases, one of the problems in general with a serial link is that it is often significantly slower than an equivalent parallel interface. For a given clock speed the serial link is at least N times slower, where N is the number of bits which must be transferred across the serial link to provide the same information which would be provided at one time is a parallel interface. This reduced data rate has limited the number of applications of serial links inside computer systems, so that even though they may have certain pin count advantages, the performance disadvantages limit their uses.
A further problem arises when interfacing between two devices, one that is higher speed and one that is lower speed. In this case it is very common to use a first in/first out (FIFO) queue to compensate for the differences between the data rates. FIFO queue logic is relatively conventional and will handle most situations where the higher speed device provides data in a burst fashion and can be held off when the FIFO queue is full, but conventional FIFO logic cannot handle the situation where the higher speed device cannot readily be held off, do that the FIFO queue would be readily overrun in those cases.
Another ongoing development in computer systems is the increasing use of audio, particularly high quality audio. This requires the use of a CODEC chip in the computer to perform the necessary digital and analog conversions. One characteristic of the CODEC chips is that quite often they have a number of control registers used to control their operation, which control registers it is desirable to read and write at a very high rate, as compared to the relatively slow data rates of audio data. It may take a relatively large number of control register operations to provide mode changes and these changes are often performed at a very high rate by the controlling processor. While this high rate of control versus the low data rate for the actual audio data is not a problem when a parallel interface is used, if a time multiplexed serial link is used, which is commonly utilized in digital signal processors (DSP) which are used to perform significant audio filtering and other operations, then a problem develops because the available effective transfer rate for the control registers is greatly reduced. In such a serial link control register information is often passed only in a single or very limited number of time slots in a serial fashion. This effectively slows down the maximum actual data transfer rate of the control information to that of the frame rate of the serial link.
When the device having the time multiplexed serial link is also connected to a bus of a much higher speed, such as one of the parallel busses present in the computer system to receive control information from the system microprocessor, it is quite possible to overrun the operations to the control registers in relation to the effective speed of the serial link. This is contrasted with the requirements of the audio where a relatively slow data transfer rate can be used to help reduce costs of the various components.
Therefore, it would be desirable to develop a structure which could balance the use of a time multiplexed serial channel to a CODEC with the need to rapidly provide the control information which is necessary for operation of the CODEC without greatly increasing costs of the components.


A method for manufacturing an organic light emitting device including a photo diode and a transistor includes forming a first semiconductor layer and a second semiconductor layer on separate portions of a buffer layer formed on the substrate; forming a gate metal layer on the first semiconductor layer, the gate metal layer covering a central region of the first semiconductor layer; forming a high-concentration P doping region and a high-concentration N doping region in the first semiconductor layer by injecting impurities into regions of the first semiconductor layer not covered by the gate metal layer to form the photodiode; forming a source and drain region and a channel region in the second semiconductor layer; and removing the gate metal layer from the central region of the first semiconductor layer by etching and simultaneously forming a gate electrode by etching, the gate electrode being insulated from the channel region of the second semiconductor layer, to form the transistor.

1. Field of the Invention
Aspects of the present invention relate to a method for manufacturing an organic light emitting device, and more particularly to a method for manufacturing an organic light emitting device having a photo diode whose intrinsic region is prevented being doped with impurities by covering and doping an upper portion of the intrinsic region with a gate metal.
2. Description of the Related Art
Organic light emitting diodes are the next-generation display devices having self-light emission properties. Organic light emitting diodes have excellent physical properties in terms of viewing angle, contrast, response time, power consumption and the like, compared to the liquid crystal display devices (LCDs).
The organic light emitting device includes organic light emitting diodes comprising an anode electrode, an organic thin film layer and a cathode electrode. Types of organic light emitting devices include passive matrix type in which organic light emitting diodes are coupled between scan lines and signal lines in a matrix mode to constitute pixels; and an active matrix type in which the operation of respective pixels is controlled by a thin film transistor (TFT) that functions as a switch.
However, the general organic light emitting devices have problems that, because an organic thin film layer that emits the light is composed of organic materials, the film quality and light emission properties deteriorate with time, which leads to reduction in luminance of the light. Also, the contrast of the organic light emitting device may be worsened by the reflection of light incident from the outside.

Method of manufacturing organic light emitting device having photo diode


A mechanical rotary vane vacuum pump has high and low vacuum stages for a pumped gas. Each stage includes a rotor for vanes cyclically driven about a common axis that is eccentric to a cylinder of a stator; the stator of each stage includes an inlet and outlet for the pumped gas. An oil seal between inlets and outlets for each stage is in a narrow gap between the stator and rotor. An interstage structure includes a flow path between the stages for the pumped gases and a shaft drivingly connected the rotors of the stages. An oil flow path comprises a first passage through the interstage structure leading radially to the shaft. The shaft includes diametrically opposed oil metering flats or cavities longitudinally aligned with an outlet of the first passage. A second passage through the interstage structure is longitudinally aligned with the cavities and leads tangentially from the peripheries of the shaft and a bore for the shaft. The second passage is in fluid flow relation with the cylinder of the low vacuum stage so oil metered by the cavities bursts into the second passage and flows to the cylinder of the low vacuum stage to form the oil seal and lubricate surfaces between the rotor and stator.

Oil sealed, mechanical rotary vacuum vane pumps have been extensively utilized in the past, both as primary pumps for vacuum loads of 10.sup.-4 -10.sup.-1 mm. of mercury, or as fore pumps in combination with diffusion pumps for vacuum loads of greater than 10.sup.-4 mm. of mercury. Such pumps usually include several stages, referred to as high and low vacuum stages. Each stage includes a plurality of vanes that cyclically rotate about the axis of a rotor eccentrically mounted in a cylindrical bore of a stator. As the vanes turn, they pump gas between inlet and outlet ports that are physically close to each other in the stator, but which are as far as possible from each other in the pumped gas flow path. To this end, the rotor and stator are designed so there is a very narrow gap between them in a region bridging the inlet and outlet ports. An oil seal is formed in this region by a dam for the pumped gas. The dam is formed by oil supplied to the pump for sealing and lubrication purposes. In a two stage pump, the rotors of the high and low vacuum stages are drivingly connected by a shaft that extends through an interstage structure between the high and low vacuum stages.
As disclosed in the textbook High Vacuum Pumping Equipment by B. D. Power, 1966, Reinhold Publishing Corporation, New York, page 18, it is known to intermittently feed oil to a vacuum pump by way of metering flats on a shaft for the rotor of one of the stages. The flats are diametrically opposite from each other and aligned with radially extending passages. One passage leads from a source of oil, on one side of the shaft, while the other passage leads to one of the stages on the other side of the shaft. This prior art device has several advantages because the amount of oil supplied to the stages is a direct function of the sealing requirements of the stage, due to the coupling of a metering mechanism directly to the rotor.
However, the radial disposition of both passages for feeding oil to the shaft and for feeding oil from the shaft to the vacuum stages has a substantial disadvantage. In particular, oil droplets supplied by a metering flat to the conduit leading to the vacuum stage encounter a relatively high flow impedance. The high flow impedance occurs because the droplets have a tendency to impinge on a wall of the conduit leading from the flat. Because the oil droplets impinge on the wall, a dam has a tendency to be formed immediately downstream of the flat, frequently preventing the flow of oil to the vacuum stage until the conduit has been filled.

Oil flow metering structure for oil sealed mechanical vacuum vane pump


Disclosed is a switch having first and second mated substrates defining therebetween a number of cavities. A plurality of wettable surfaces is deposited in one or more of the cavities. A switching fluid, held within one or more of the cavities, serves to connect and disconnect at least a pair of the wettable surfaces in response to forces that are applied to the switching fluid. The wettable surfaces are formed at least in part of a material that does not form alloys with the switching fluid.

Fluid-based switches such as liquid metal micro switches (LIMMS) comprise first and second mated substrates that define therebetween a number of cavities. Deposited within one or more of the cavities are a plurality of wettable surfaces that may be connected and disconnected by applying forces to a switching fluid. In some cases, the wettable surfaces may comprise electrodes, and the switching fluid may electrically connect and disconnect the electrodes to thereby control the propagation of electrical signals through the switch. In other cases, the switching fluid may connect and disconnect the wettable surfaces to block and unblock a plurality of windows in the cavities, thereby controlling the propagation of optical signals through the switch.

Switches having wettable surfaces comprising a material that does not form alloys with a switching fluid, and method of making same


A safety fuze for use in military and commercial applications, includes a fuze body that is attached to a trigger mechanism, an energetic train contained within the fuze body, and a non-energetic fuze delay mixture that is formed in a rod form so that it can dropped inside the fuze body, without modification to the other components of the safety fuze. Preferably, the non-energetic fuze delay mixture is made of foamed celluloid.

Safety is a very important design aspect of a hand grenade (or an explosive) fuze in military and commercial applications. Conventional fuze designs account for a time delay period from initiation, for the detonation to occur, in order to ensure that the grenade is cast outside the explosion hazard area.
To this end, numerous conventional hand grenade fuzes have been proposed, some of which are described in the following publications: U.S. Pat. Nos. 3,823,669; 3,926,122; 4,063,514; 4,167,905; 4,730,559; 5,196,649; 6,082,267; 6,965,542; 7,197,983; and 7,712,419, and Statutory Invention Registration H251, issued Apr. 7, 1987 to Field.
These and other fuze designs propose the use of delay elements that are either mechanically, chemically, electrically, or electro-magnetically operated. However, these conventional designs could present various inherent problems, particularly when used in the field, under adverse and stressful conditions.
More specifically, the grenade delay mixtures constitute major concerns in the armed forces. These concerns arise from the dwell time requirement between the activation of the grenade to the detonation. This time cycle is critical to the function of the grenade as well as to the safety of the soldier.
The issue of delay composition mixtures is a continuous issue in the fabrication of grenades, such as the M67. Numerous conventional hand grenade fuze designs include delay mixtures that use an energetic pyrotechnic mixture, which require complex manufacturing and production capabilities. Additionally, due to the characteristics of the delay mixture, end items can sometimes exhibit inconsistent burn times.
What is therefore needed is a fuze design that addresses the foregoing and other concerns, and that provides a solution thereto. Particularly, the fuze design should address the robustness of the delay mixture via a non-energetic mixture approach. Prior to the advent of the present invention, the need for such a fuze design has heretofore remained unsatisfied.

The United States of America as Represented by the Secretary of the Army


A combined oil quality and fuel contamination sensing system includes a capacitive dielectric sensor and pressure sensing arrangements for measuring the dielectric constant of the oil and the pressure of the oil, respectively, with the oil pressure being indicative of oil viscosity and contamination. The sensors take measurements as oil flows through an internal combustion engine and provide an indication of the cause of a problem with oil in an engine. The system may also include a microcomputer and circuitry for generating an indication of dielectric constant and circuitry for generating an indication of the presence of contaminants within the engine. The system may also include an additional sensor measuring the temperature of oil within the system to adjust oil dielectric constant and viscosity indications. The capacitive dielectric sensor constitute the principal restriction in the flow path between an input high pressure sensing port and an outlet low pressure port.

1. Field of the Invention
The present invention relates to an oil quality and viscosity sensing system, and more particularly, pertains to an oil quality evaluation system employing arrangements for detecting fuel leakage into the oil.
2. Description of the Related Art
One of the most important factors that contributes to the efficiency and durability of internal combustion engines is lubrication. As engine oil xe2x80x9cbreaks downxe2x80x9d it is less effective in protecting an engine from damage caused by friction between engine parts. More specifically, the normal life span of motor oils is limited by thermal breakdown, additive depletion and carbon particulates that result from the combustion process.
The deterioration of engine oil is marked by a decrease in the viscosity of the oil. The dielectric constant of engine oil provides an indication of the deterioration of the oil or lack thereof. It is known that the dielectric constant of the lubricating oil, in internal combustion engines for example, increases with oil deterioration during operation of the invention. The dielectric constant of motor oil is typically between 1.6 and 3.2 depending upon its brand and age. For example, the dielectric constant of a particular brand of motor oil may increase from 2.19 to 2.35 after 400 hours of use in a particular internal combustion engine under certain operating conditions. Thus, it is desirable to have an indication of when engine oil has deteriorated to the point where it should be changed. By measuring the dielectric constant of the motor oil, it may be determined when such a change should occur.
Premature lubrication failure can also result from the presence of contaminants in the engine oil such as coolant (glycol ethylene), fuel or water. The presence of these contaminants in motor oil is often indicative of a mechanical failure such as a damaged head gasket or a broken piston ring. Thus, it is also desirable to have arrangements for detecting the presence of these substances in engine oil.
Water and engine coolant have dielectric constants of approximately 87.5 and 37.9, respectively, and fuel has a dielectric constant of about 2.0. Therefore the introduction of such contaminants can significantly change the dielectric constant of the fluid which circulates through the engine for the purpose of lubrication. As a result, a condition of engine oil contamination could be mistaken for severe engine oil deterioration or vice versa.
The dielectric constant of oil is also influenced by the temperature of the oil and by the specific formulation of a given brand of oil.
Accordingly, an object of the present invention is to provide a combined oil quality and viscosity sensing system which distinguishes between the conditions of engine oil deterioration and contamination and provides separate indications of these conditions.
Another object is to provide a combined oil quality and viscosity sensing system which utilizes a combination of capacitive sensors to provide an indication of engine oil breakdown for a wide variety of engine oil conditions.
Another object is to provide a combined oil quality and viscosity sensing system which adjusts the engine oil measurements to compensate for the effects of engine oil temperature changes.
The related art in the field discusses the use of a capacitive sensors to determine oil deterioration and contamination. U.S. Pat. No. 5,824,889, issued to Dr. Kyong Park and assigned to Kavlico Corporation, discloses the use of a capacitive oil sensor to detect oil deterioration and contamination. U.S. Pat. No. 5,540,086, also issued to Dr. Park and assigned to Kavlico, discloses an oil deterioration sensor. U.S. Pat. No. 4,227,419, also issued to Dr. Park and assigned to Kavlico, discloses a capacitive pressure transducer. The foregoing patents of Dr. Park, one of the co-inventors in the present case, are hereby incorporated by reference into this specification.
In a specific illustrative preferred embodiment of the present invention, oil enters an internal combustion engine through a path and passes through a first pressurized port. The oil pressure is measured at the first pressurized port, and then flows through the combined system through a network of conduit. In the combined system, the oil is exposed to a capacitive sensor for determining the dielectric constant of the oil. After exposure to the capacitive sensor, the oil continues to flow through the combined system, passing through a second pressurized port. The oil pressure is again measured at this pressurized port. The oil then flows out of the system through a second path and on to the rest of the internal combustion engine. In an alternative embodiment, the oil is also exposed to a temperature sensor while in the system for measuring the temperature of the oil. In yet another embodiment, oil pressure may be measured at only one point in the system for a measurement of viscosity of the oil.
The presence of gasoline or other fuel which may leak into the lubricating oil of an internal combustion engine may adversely affect the validity of dielectric measurements of oil quality. Thus, with gasoline having a dielectric constant of about 2.0, the addition of gasoline to the lubricating oil mentioned above would reduce the dielectric constant and would make the oil appear not to have deteriorated as much as has actually occurred. Conversely, the addition of a substance with a very high dielectric constant would increase the dielectric constant of the oil and would make the oil appear to have deteriorated much more than has actually occurred.
Accordingly, a system illustrating the principles of the invention includes a capacitive sensor for determining the dielectric constant of lubricating oil, and a viscosity measuring arrangement, which would indicate whether gasoline or other low viscosity substance is present in the lubricating oil. In a preferred system, a temperature sensor would also be included, as viscosity and dielectric constant measurements are affected by temperature.
In accordance with a specific illustrative embodiment of a combined oil quality and viscosity sensing system, the present invention includes a housing, a first capacitive plate mounted within the housing, a second capacitive plate, and an insulating material between the housing and first capacitive plate. The capacitive plates are mounted such that fluid including oil circulates within a gap between the first and second capacitive plates thereby defining a capacitive dielectric sensor. The respective capacitances provide an indication of the dielectric constant of the oil within the gap. It is further noted that one of the capacitive plates may be a part of the housing.
In one specific illustrative embodiment, the oil viscosity is determined by the difference in oil pressure being applied to the engine, for example by the oil pump, and the oil pressure following passage through a restricted path, with the capacitive dielectric sensor constituting a major restriction in the flow path. This difference in pressure may be determined by a differential pressure transducer, such as a capacitive pressure transducer; or alternatively the pressure at each point may be measured separately, and the pressure difference may be determined by electrically combining the signals, or by mathematical subtraction in an associated computer or microprocessor.
A system according to one illustrative embodiment of the invention may include a high pressure oil input port, a capacitive sensor coupled to receive the oil, and a low pressure output port, with oil from said high pressure port and from said low pressure port being applied to pressure sensing arrangements for determining the differential pressure. Electrical circuitry is provided for (1) determining the dielectric constant of the oil from the capacitance of said capacitive sensor; (2) determining viscosity from said pressure sensing arrangements; and (3) to indicate both the oil quality and whether there is fuel contamination.
In another aspect of the present invention, the oil quality and viscosity sensing system further includes a temperature sensitive resistive element thermally coupled to the circulating oil for providing a temperature adjustment to the indication of dielectric constant and viscosity, and circuitry utilizing the temperature to adjust both the dielectric constant and viscosity indications.
Consequently, in a preferred embodiment of the combined system described above, a user of the present invention may introduce new oil to an internal combustion engine and receive an initial indication of oil quality and fuel contamination. Thereafter, subsequent readings over time would provide the user with information concerning the progression of any changes in oil quality as well as fuel contamination. The change in dielectric constant and pressure over time allows the user to detect a cause for oil deterioration and proceed accordingly. The addition of a temperature sensor allows a user of this embodiment to add further detail to the analysis of the condition of the lubricant within an engine.

Combined oil quality and viscosity sensing system


A bow string drawing and releasing device including a rigid frame within which a pair of jaws are pivotally arranged. An operating rod is rearwardly positioned and is adapted to be rearwardly pulled to pivot the jaws from a normally closed, bow string retaining position to an open, bow string releasing position. A handle grip portion extends rearwardly from the frame and the operating rod extends through the handle grip portion. In one embodiment, the handle grip portion is adapted to rotate relative to the frame. In another embodiment, the handle grip portion is adapted to pivot relative to the frame for triggering purposes.

The present invention relates generally to the field of archery equipment and more particularly is directed to a pivoting type of bow string drawing and releasing device.
As set forth in my previous patent, U.S. Pat. No. 3,948,243, persons who enjoy the sport of archery have found that the speed, accuracy and distance to which arrows can be propelled is a direct function of the spring constant of the bow and the strength of the archer necessary to pull the bow string through a distance against the natural spring bias of the bow itself. As bows become sturdier, they offer a greater resistance to bending and so require greater strength on the part of the archer to produce the desired results.
It is the usual practice to employ two fingers to pull the bow string rearwardly. Of course, definite limitations are presented because all of the strength of the archer cannot be readily applied to the bow string by employing only the two fingers for bow string drawing and releasing purposes. By employing a mechanical bow string drawing device, the pressure limitations created by the interaction of the bow string itself upon the fingers of the archer when drawing bow string can be overcome to a considerable degree. In addition to U.S. Pat. No. 3,948,243, previously mentioned, U.S. Pat. Nos. 1,542,159, 2,488,597, 2,977,952, 3,343,839, 3,604,407 and 3,800,774 all show exemplary types of prior art bow trigger mechanisms.
The prior art bow trigger mechanisms with which I am familiar are generally satisfactory in performance, but some are somewhat limited in their application due to the complexity of the systems and in the difficulty in operation presented by the various prior art mechanisms. The present invention represents an improved trigger mechanism of the pivoting type which some archers will find easier or more comfortable to operate than the devices heretofore developed.


In a wavelength division multiplexed optical communication network which includes a transmitter including a multiplexing arrangement (15-17) for wavelength division multiplexing signal beams of a plurality of channels into the multiplexed signal beam for reception by at least one receiver (12) capable of producing a data carrying intermediate frequency signal by using a local optical beam in receiving the signal beam of a selected channel, the transmitter comprises a modulating arrangement (15) for frequency modulating optical beams of the channels into frequency modulated beams by channel discrimination signals (18) having different frequencies in correspondence to the channels before (19) the signal beams are multiplexed. Besides a receiving arrangement (21-25, 31-32, 35-38) for producing the data carrying intermediate frequency signal and prior to production thereof an information carrying intermediate frequency signal by using the local optical beam in receiving a multiplexed optical beam into which the frequency modulated beams are wavelength division multiplexed, the receiver comprises a detecting arrangement (26, 33-34) for detecting one of the channel discrimination signals in the information carrying intermediate frequency signal in correspondence to one of the channels that should be received as the selected channel. Besides a receiver circuit (21-25) and a level detector (31), the receiving arrangement comprises a scrambling (32, 35, 36) and a sweeping (35, 37, 38) arrangements.

This invention relates to wavelength division multiplexed (WDM) coherent optical communication, which is alternatively referred to either as frequency division multiplexed (FDM) coherent optical communication or briefly as wavelength division multiplexed optical communication.
The wavelength division multiplexed optical communication can deal with a great number of channels and is effective for use in a large-capacity trunk-line optical communication system. In a transmitter of a wavelength division multiplexed optical communication network, signal beams of a plurality of channels of different wavelengths are wavelength division multiplexed into a multiplexed signal beam for transmission through an optical fiber. In a receiver which is typically an optical heterodyne receiver, the multiplexed signal beam is received through the optical fiber by using a local optical beam of a controllable wavelength which is adjusted so as to produce a data carrying intermediate frequency signal in response to one of the signal beams of one of the channels that should be received as a selected channel.
In the transmitter, laser diodes are used in general as optical beam sources for generating optical beams of the respective channels. It is known that each laser diode emits the optical beam of a source wavelength which varies in a wide wavelength range dependent on a bias current supplied to the laser diode and its ambient temperature. The controllable wavelength is therefore swept as a swept wavelength in a sweep range during start of reception of the multiplexed signal beam and subsequently stabilized by automatic frequency control (AFC) at an optimum wavelength after the data carrying intermediate frequency signal is obtained in response to one of the signal beams that is of the selected channel.
The sweep range must be sufficiently wide to cover the wavelength range. It may therefore happen that the controllable wavelength is stabilized at a wrong wavelength rather than at a correct wavelength of providing the data carrying intermediate frequency signal in response to the signal beam of the selected channel, particularly when the channels are spaced apart by a narrow wavelength or frequency separation. As a consequence, it is indispensable to use a channel discrimination method of discriminating between the channels, namely, the correct wavelength from wrong wavelengths, in order to insure stabilization of the controllable wavelength at the correct wavelength. In a conventional channel discrimination method, channel discrimination bits of a set are time division multiplexed on the signal beam of each channel.
It should be noted in connection with such an optical communication network that the multiplexed signal beam has a polarization state which is unavoidably subjected to fluctuations while the multiplexed signal beam is transmitted from the transmitter to the receiver through the optical fiber. It is known in the art that polarization control is effective in removing adverse effects which would otherwise result from the fluctuations. On carrying out the polarization control, a polarization control unit is used in the receiver to control the polarization state of a predetermined one of the multiplexed signal beam and the local optical beam so that the polarization state of one of the multiplexed signal and the local optical beams becomes coincident with that of the other of the multiplexed signal and the local optical beams. Thereafter, the multiplexed signal and the local optical beams are combined together into a combined beam for detection of the data carrying intermediate frequency signal.
More particularly, the polarization control unit is controlled so that the data carrying intermediate frequency signal may always have a maximum power level. Consequently, the polarization control is not carried out while the receiver is not supplied with the multiplexed signal beam. This may result in a disadvantage such that the data carrying intermediate frequency signal can not be obtained either when the multiplexed signal beam is first supplied to the receiver or when supply of the multiplexed signal beam is once suspended and then restarted.
In order to get rid of the disadvantage, an optical heterodyne homodyne detection apparatus is revealed in U.S. Pat. No. 4,903,342 which is issued to Yamazaki, the present inventor. According to the Yamazaki patent, the polarization control unit is subjected to scramble control, namely, is scramble controlled during start of sweep of the controllable wavelength to vary the polarization state of the predetermined one of the multiplexed signal and the local optical beams in a scrambled fashion so as to insure production of the data carrying intermediate frequency signal irrespective of the polarization state of the multiplexed signal beam.
The scramble control, however, results in an inconvenience when used in combination with the conventional channel discrimination method. The inconvenience is as follows. Inasmuch as it is impossible to demodulate the data carrying intermediate frequency signal into a reproduction of the channel discrimination bits during progress of the scramble control, the scramble control must temporarily be suspended when an intermediate frequency signal is obtained as a temporary intermediate frequency signal. This is in order to judge whether or not the selected channel is really indicated by temporary channel discrimination bits which are demodulated from the temporary intermediate frequency signal as a reproduction of the channel discrimination bits of a certain set. If the selected channel is not indicated by the temporary channel discrimination bits, the scramble control must be repeated until the selected channel is really indicated by such temporary channel discrimination bits. As a result, a long searching time interval is necessary to search for the selected channel before start of reception of the signal beam of the selected channel.

WDM optical communication wherein optical beams are modulated by channel discrimination signals of different frequencies by data signals


A system for collecting and evaluating data records comprises a configuration device associated a data collection device associated, and a data monitoring device. The devices are registered with a server. The data collection device transmits a task to the server over a network. The data collection device receives the task from the server and records a data record in response to the task. The data collecting device groups the data record with metadata to produce a verified data record and transmits the verified data record to the server. The data monitoring device receives the verified data record from the server and facilitates the evaluation of the verified data record. The evaluation of the verified data record is used to generate an updated verified data record comprising evaluation results and updated metadata and is transmitted to the server and added to a portfolio.

Currently the licensing of professionals such as doctors, surgeons, engineers and others, occurs across several years of course curriculum, technique practice and perhaps simulations. In particular, hand-on, practical exams are difficult to assess. These sessions are observed by an examiner or teacher and rated qualitatively by that person. After several years of training and education a paper based record with the cumulative comments of all teachers is submitted to a licensing or certification authority. The decision to grant a license is measured against a set of standards based on the qualitative description of an applicant's training as well as on the quantitative grading system used.
There are several drawbacks of this traditional approach. One drawback is that the authority granting the license or certification may never have actually observed this professional's techniques nor expertise and is basing the decision mostly on the qualitative assessments of the student's teachers and examiners.
Another drawback is that for a class of many students there are likely several different examiners. Each examiner will have slightly different standards and experience and will grade students differently using their own set of different subjective standards.
To ensure consistency and fairness, practical examinations may be recorded or videotaped by various methods. However, this approach has the limitation that it is difficult to ensure the content veracity of the recording. Digital and analog files may be altered and edited and this tampering can be very difficult to detect. Tests, questionnaires, and surveys may be accessed surreptitiously in advance. As well, evaluation results may also be tampered with. To ensure a fair evaluation, a licensing or certification authority must be sure that recordings and results have not been tampered with and that it shows the performance of the actual student performing the procedure or exam on the date indicated.

Evidence based digital training portfolio


An electrolytic cell comprising a walled enclosure including a cathode sidewall has busbar structure external to the cell. The busbar structure can include a gird bar releasably secured at the sidewall. It also may include a foraminous interface member between the gird bar and the sidewall, as well as have a small cathode busbar member on the sidewall. The small busbar member is typically located above and adjacent to the gird bar. Particularly when the gird bar and foraminous interface member are present, there can be internal support members for the cathodes directly secured to the inside face of the cathode sidewall. Furthermore, intercell connection may be handled directly to the outside face of the cathode sidewall. The overall structure can provide reduced potential for sidewall stress corrosion cracking, reduced cathode manufacturing cost, and accommodation of stress relief for the cathode weldment.

1. Field of Invention
The invention relates to electrolytic cells, particularly high amperage diaphragm electrolytic cells. The cells, typically chlor-alkali diaphragm cells, may operate at current capacities of upwards of about 200,000 amperes.
2. Description of the Related Art
It has been known to construct such cells where cathode outer sidewalls, made of electrically conductive material, are encircled with buss structure. For example, there has been shown in U.S. Pat. No. 3,390,072, a high amperage electrolytic cell wherein the sidewall is connected to a source of electrical current through an encircling bar-type bus member, sometimes referred to as a gird bar.
There has thereafter been developed busbar assemblies for diaphragm-type electrolytic cells wherein busbars are connected only to the cathode sidewall and have angled edges. For example, in U.S. Pat. No. 3,783,122, there are shown busbars of triangular shape, which busbars are shorter than the sidewall. Further in the development of angled busbars, several busbar strips, some of which can have triangular-shaped faces, may be utilized. This has been shown in U.S. Pat. No. 3,904,504, wherein it is disclosed to have a cathode busbar structure comprising several busbar strips. The numerous busbar strips, having different relative dimension, are welded to the sidewall.
With regard to fastening busbars to the sidewall, a combination of fastening means may be utilized. Generally, welding can provide for desirable electrical contact between the sidewall and a busbar. However, it is known to bolt a busbar to the sidewall, then weld the busbar at its edges to the sidewall. Bolting can assist in positioning of the busbar on the sidewall, then welding can assure desirable electrical contact as well as assisting in maintaining busbar positioning.
A more recent innovation for providing electrical current to electrolytic cells has improved the gird bar structure for distributing electrical current to the cathode sidewall. Thus as shown in U.S. Pat. No. 4,834,859, a gird bar is provided on a sidewall. In the structure of the innovation of this patent, distributor bars are placed on the inside of the sidewall at the upper and lower regions of the gird bar. These distributor bars conduct electrical current from the sidewall to an exterior face of an inner tube sheet. Cathode tubes are then positioned at the interior face of the tube sheet.
More recently, it has been proposed to provide a wall-sized busbar for the cathode sidewall. Such a structure is shown in U.S. Pat. No. 5,137,612. This patent discloses such a wall-sized busbar and the busbar is interface bonded to the cathode sidewall. The wall-sized busbar can have an extension section for attaching jumper switches.
It would nevertheless be desirable to provide a busbar structure for a cathode sidewall having not only efficient current distribution, but also reduced potential for sidewall stress corrosion cracking. It would also be desirable if such structure could provide reduced cathode manufacturing cost as well as accommodate stress relief characteristic.
It has now been found possible to provide an efficient cathode sidewall busbar structure having reduced potential for sidewall stress corrosion cracking. The structure of the innovation can further include a cathode sidewall assembly having reduced cathode electrical resistance, i.e., reduced structure drop during electrolytic cell operation. Other features of the present invention pertain to reduced cathode manufacturing cost as well as accommodation of stress relief for the cathode weldment.
In one aspect, the invention relates to an electrolytic cell wherein the cell comprises a walled enclosure providing at least one cathode sidewall for the enclosure and with there being cathode busbar structure external to the cell for conducting electrical current from the cathode sidewall to outside the cell through an outer gird bar extending along an outside face of the cathode sidewall. Within this framework, the invention of this aspect provides the improvement in busbar structure comprising:
a solid and elongated outer gird bar member releasably secured at the sidewall outside face; and
a small, solid cathode busbar member situated on the sidewall at least substantially adjacent to said gird bar member, which small busbar member is releasably secured to the sidewall outside face and is directly in contact with the sidewall.
In another aspect, the invention relates to an electrolytic cell wherein the cell comprises a walled enclosure providing at least one cathode sidewall for the enclosure and with there being cathode busbar means external to the cell, including an outer gird bar extending along an outside face of the cathode sidewall, and interior cell structure at an inside face of the cathode sidewall and including cell cathodes incorporating internal support members. Within this framework, the invention of this aspect provides the improvement in such structure comprising:
a solid and elongated outer gird bar member releasably secured at the sidewall outside face; and
internal support members supporting the cathodes situated within the electrolytic cell, with the internal support members being directly secured to the sidewall inside face.
A still further aspect of the invention pertains to interconnected electrolytic cells wherein each cell comprises a walled enclosure providing at least one cathode sidewall for said enclosure and electrical intercell connector means are present between adjacent cells, with interior cell structure including cell cathodes incorporating internal cathode support members. In this still further aspect, the improvement in such structure comprises:
an intercell connector means which is connected directly to an outside face of the cathode sidewall; and
interior cell structure directly secured to an inside face of the cathode sidewall.
Still other benefits and advantages of the invention will become apparent to those skilled in the art to which it pertains upon a reading and understanding of the following detailed specification.


Stroma-free hemoglobin cross-linked with reagents that mimic 2,3-diphosphoglycerate and transform stroma-free hemoglobin into a physiologically competent oxygen carrier which is retained in vivo for adequate periods of time, and thus can be used in fluids for transporting oxygen is described.

1. Stroma-Free Hemoglobin
Intravenously injected (infused) crude hemolysates and extensive hemolytic processes produced in vivo by immunological reactions involving intravascular lysis of red blood cells, are known to produce a clinical syndrome characterized by disseminate intravascular coagulation. This syndrome is often fatal and is produced by the residual red blood cell walls (stroma) and their fragments, so infused into circulating blood. Stroma-free hemolysates do not show this toxicity (See Rabiner et al, J. Exp. Med., .126:1127 (1967). As a result, it has been desired to use stroma-free hemoglobin as an oxygen carrier in cell-free transfusional fluids.
However, the use of stroma-free hemoglobin has the following two disadvantages: In vivo, the retention time of the stroma-free human hemoglobin is very short, i.e., it has a half-life on the order of 1-4 hours (see Rabiner et al, supra; and De Venuto et al, Transfusion, 17:555 (1977)). "Half-life" is defined as the time necessary to eliminate 50% of the infused hemoglobin from circulating blood. Further, outside of the red blood cells, hemoglobin has a high affinity for oxygen which, in vivo, would prevent the release, i.e., the transport, of oxygen from hemoglobin to the tissues. These disadvantages are directly the result of the molecular structure of hemoglobin.
Hemoglobin is a tetrameric molecule having a molecular weight of 64,500 Daltons. The tetrameric molecule is formed of two pairs of alpha and beta subunits. The subunits are held together as a result of ionic and Van der Waals forces, and not as a result of covalent bonds. When hemoglobin is oxygenated, i.e., combined with oxygen, it readily forms alpha-beta dimers having a molecular weight of 32,250 Daltons. These dimers are not retained in vivo by the kidneys and are eliminated through the urine.
The tetrameric structure of hemoglobin also provides a binding site for 2,3-diphosphoglycerate. Inside red blood cells, 2,3-diphosphoglycerate combines with hemoglobin in order to decrease its oxygen affinity to a level compatible with oxygen transport. The binding of 2,3-diphosphoglycerate and hemoglobin is purely electrostatic and no stable covalent bonds are formed. Thus, when red blood cells are ruptured and 2,3-diphosphoglycerate is not retained inside the cells by the cell wall, it is released from hemoglobin. As a result, hemoglobin acquires a higher oxygen affinity. This prevents the transport of oxygen from hemoglobin to the tissues. The level of this higher affinity is sufficient such that the oxygen affinity can be considered "non-physiological".
Because of the many appealing qualities of hemoglobin, i.e., its ability to reversibly bind oxygen, the low viscosity of a hemoglobin solution and its easy preparation and storage for long periods of time, various attempts have been made in order to overcome the above described disadvantageous characteristics of stroma-free hemoglobin. These various attempts are discussed in more detail below.
2. Chemical Treatments for Preventing the Formation of Dimers
The formation of alpha-beta dimers, which are not retained in vivo, can be prevented by coupling the tetrameric molecules of hemoglobin with large molecular weight matrices, ranging from 20,000 to 275,000 Daltons. For example, matrices such as dextran (see Tam et al, Can. J. Biochem., 56:981 (1978); and Bonneaux et al, Experientia, 37:884 (1981)) and hydroxyethyl starch (see Baldwin et al, Tetrahedron, 37:1723 (1981); and U.S. Pat. Nos. 4,412,989, 4,900,816, 4,650,786 and 4,710,488) have been employed. This coupling prevents the elimination of hemoglobin in vivo from the kidneys by way of the urine. Other types of polymeric coupling employing collagen, collagen degradation products, and gelatin as a supporting matrix have also been employed (see U.S. Pat. No. 2,591,133; U.S. Pat. No. 3,057,782; and Bowes et al, Biochem. Biophys. Acta., 168:341 (1968)). However, the oxygen affinity of the resulting coupled hemoglobin is even higher than that of stroma-free hemoglobin, and thus hemoglobin coupled in this manner cannot be advantageously employed as an oxygen transport medium.
Other known treatments for preventing the formation of alpha-beta dimers are based on reactions which polymerize the tetrameric molecules of hemoglobin to form so-called "polyhemoglobins". Polyhemoglobins can be obtained using bifunctional reagents, such as glutaraldehyde (see Hopwood et al, Histochem. J., 2:137 (1970)) or diimidate esters (see Mock et al, Fed. Proc., 34:1458 (1975); and U.S. Pat. No. 3,925,344). These bifunctional reagents form covalent bonds between the amino groups present on the surface of different hemoglobin molecules producing intermolecular cross-links. There are 40 or more of such amino groups belonging to lysyl residues on the surface of mammalian hemoglobins (44 in human hemoglobin). Thus, a large number of possible combinations of hemoglobin molecules occur. As a result, the polyhemoglobin reaction products are a heterogeneous mixture of various molecular species which differ in size and shape. The molecular weights thereof range from 64,500 to 600,000 Daltons. The separation of individual molecular species from the heterogeneous mixture is virtually impossible. In addition, although longer retention times in vivo are obtained using polyhemoglobins, the oxygen affinity thereof is higher than that of stroma-free hemoglobin.
Besides the various treatments discussed above which result in formation of heterogeneous mixtures of polyhemoglobin, reagents have been developed which are capable of producing an internal cross-link of the hemoglobin subunits with little or no formation of polyhemoglobins. More specifically, the formation of cross-links between the beta subunits of hemoglobin using 2-N-2-formylpyridoxal-5'-phosphate and borohydride and bis-pyridoxal polyphosphates have been carried out (see Benesch et al, Biochem. Biophys. Res. Comm., 62:1123 (1975); and Benesch et al, Biochem. Biophys. Res. Comm., 156:9 (1988)). The oxygen affinity of the thus treated hemoglobin is decreased to levels similar to that of normal blood. However, the reagents employed therein are very difficult and costly to synthesize, and thus these methods are disadvantageous.
Other reagents have been employed in order to effect internal cross-linking of the hemoglobin subunits. These reagents are commonly known as "diaspirins". Diaspirins are diesters of bis-3,5-dibromosalicyl containing succinyl, fumaryl or other dicarboxylic acid residues. These reagents produce covalent cross-links between two beta or two alpha subunits of an individual hemoglobin molecule. While better results are obtained using liganded (oxy- or carboxy-) hemoglobin, such a treatment does not sufficiently affect the oxygen affinity characteristics of stroma-free hemoglobin, and thus can not be advantageously employed (see Walder et al, J. Mol. Biol., 141:195 (1980); and U.S. Pat. Nos. 4,061,736, 4,001,200;, 4,001,401, and 4,053,590).
It should be stressed that according to pertinent literature, i.e., Walder, Biochemistry, 18:4265-4270 (1779); Walder et al, J. Mol. Biol., 141:195 (1980); and Zaugg, J. Biol. Chem., 255:2816-2821 (1980), activated dicarboxylic acid of increasing length, above that of the 4-carbon chain of succininc and fumaric acid, show a progressively lower reactivity with both liganded and unliganded hemoglobin so that activated sebacic acid (10-carbons long) produces no reactions with human hemoglobin.
In U.S. Pat. Nos. 4,473,496 and 4,857,636, linear alpha-omega or heterocyclic polyaldehydes containing negatively charged groups are described as suitable for both decreasing the oxygen affinity of hemoglobin and for producing inter- and intramolecular cross-linking of hemoglobin. These reagents include carbohydrate-containing molecules, such as raffinose, and mono- and polyphosphorylated nucleotides partially oxidized with periodate, so as to obtain aldehydic groups. The coupling reaction is based on the formation of Shiff bases of the aldehydic groups with the amino groups of the hemoglobin molecule. The Shiff bases are then transformed into covalent bonds by reduction with sodium or potassium borohydride, or another strong reducing agent.
In U.S. Pat. No. 4,584,130, cross-linking of hemoglobin with bifunctional reagents is disclosed. The reagents disclosed therein are based on an electron withdrawing group which modulates the reactivity of two peripheral active groups. However, the electron withdrawing group remains within the cross-linking bridge after the reaction. In the reagent of the present application, when an electron withdrawing group is employed, it is present in the leaving group only (e.g., 3,5-dibromosalicyl), and therefore it does not remain in the cross-linking bridge after the chemical reaction of the activated carboxyls with the amino groups of the protein.
3. Chemical Treatments for Decreasing the Oxygen Affinity of Stroma-Free Hemoglobin
The most widely used chemical modification of stroma-free hemoglobin so as to decrease the oxygen affinity thereof employs the use of pyridoxal-5'-phosphate and sodium or potassium borohydride (see Bensch et al, Biochem., 11:3576 (1972)). The resulting product is commonly referred to as "PLP-hemoglobin" and has satisfactory oxygen affinity, i.e., oxygen affinity very near that of the red cells present in normal blood.
Other known chemical modifications of hemoglobin have been carried out using phosphoric acid derivatives of carbohydrates (e.g., glucose-6-phosphate) (see McDonald et al, J. Biol. Chem., 254:702 (1979)); carbamylation (see Manning, Meth. Enz., 76:159 (1981)) and carboxymethylation (see DiDonato et al, J. Biol. Chem., 258:11890 (1983)). In each of these treatments, the amino-terminal end of the beta subunit of hemoglobin is permanently substituted with the above described reagents.
In addition, none of these chemical treatments discussed in this section stabilize the tetrameric structure of hemoglobin so as to prevent the formation of alpha-beta dimers. Thus, the resulting hemoglobins do not have prolonged retention times in vivo.
4. Combined Chemical Treatments for Preventing the Formation of Alpha-Beta Dimers and Decreasing the Oxygen Affinity of Stroma-Free Hemoglobin
As discussed above, the production of physiologically competent stroma-free hemoglobin-based oxygen carriers necessitates two separate treatments. That is, one treatment is necessary for preventing the formation of alpha-beta dimers in vivo and a second treatment is required for decreasing its oxygen affinity. The most widely employed combination of treatments is that of reacting glutaraldehyde with PLP-hemoglobin to form pyridoxylated polyhemoglobins (see Seghal et al, J. Surg. Res., 30:14 (1981). Intramolecular cross-linking of PLP-hemoglobin has also been obtained using diaspirins (see Tye et al, Prog. Clin. Biol. Res., 22:41 (1983)).
It should be noted that only stroma-free hemolysates or washed red blood cells are utilized in the above-cited articles. That is, purification procedures for isolating the hemoglobin component of the stroma-free hemolysates are not described therein. Thus, what is defined as stroma-free hemoglobins therein is in actuality stroma-free hemolysates.
More specifically, about 95% of the hemolysate components is hemoglobin. The remainder consists of proteins and polypeptides whose pharmacological and immunological toxicity is not known. When used for infusion in animals, several grams of hemolysate-containing hemoglobin are injected. Thus, undesirably, hundreds of milligrams of substances of unknown biological activity are also infused into animals when employing a hemolysate.
It should also be noted that in the above-cited references, purification procedures for isolating the desired hemoglobin products from the reaction mixture are not described therein. It is impossible to avoid the presence of overreacted and underreacted hemoglobins in the reaction mixtures. These products do not have the desired functional and molecular characteristics.
For the above reasons, it is advantageous to perform chemical treatments on purified hemoglobins, and then to purify the product of the reaction.
The reagents of the present invention present clear advantage over previously employed divalent reagents for producing intramolecular cross-linked hemoglobin. Specifically, using the present cross-linking reagents, the resulting cross-linked hemoglobin of the present invention has a lower oxygen affinity, and can be obtained in a much higher yield. While the cross-link is still intramolecular, the hemoglobin of the present invention has been found to be stable, not only against dissociation, but also against physical agents like heat, pH and aging. Thus, the formation of ferric hemoglobin is greatly retarded with the cross-linked hemoglobin of the present invention. This allows the use of high temperature heat treatments for eliminating pathogens, the use of lyophilization procedures and to effect storage in liquid form in the cold and at room temperature.

Hemoglobin intramolecularly cross-linked withlong chain divalent reagents


A method for separating a mixture of 5'-phosphorothioate mononucleotides, a mixture of 5'-phosphorothioate oligonucleotides, or a mixture of both 5'-phosphorothioate mononucleotides and 5'-phosphorothioate oligonucleotides comprising electro- phoresis through a gel of at least 12% polymerized linear acrylamide containing at least 50% formamide or other denaturing organic solvent. This method can resolve phosphorothioate oligonucleotides differing by only a single base. Samples of less than 1 nanogram in microliter volumes can be conveniently handled.

Oligonucleotides that are complementary or "antisense" to specific genes or RNA sequences are relatively small, synthetic molecules having an average molecular weight of about 10 kilodaltons (kD). These antisense molecules have had widespread use in the field of selective gene regulation with consequent therapeutic implications. Phosphate backbone modification of such oligonucleotides provides nuclease resistance and greatly enhances the usefulness of these analogs. Such modifications include the substitution of phosphodiester internucleotide linkages with linkages such as methylphosphonates (Murakami et al. (1986) Biochem. 24:4041-4046; Agrawal et al. (1987) Tetrahedron Lett. 28:3539-3542; Sarin et al. (1988) Proc. Nat. Acad. Sci. (U.S.A.) 85:7448-7451), phosphorothioates (Burgers et al. 1979 Biochemistry 18:592-596; Agrawal et al. (1988) Proc. Natl. Acad. Sci. (U.S.A.) 85:7079-7083; Agrawal et al. (1989) Nucleosides and Nucleotides 8:819-823; Agrawal et al. (1989) Proc. Natl. Acad. Sci. (U.S.A.) 86:7790-7794), and phosphoramidates (Agrawal et al. (1988) Proc. Natl. Acad. Sci. U.S.A. 85:7079-7083; Agrawal et al. (1989) Nucleosides and Nucleotides 8:819-823).
Of special interest are phosphorothioate analogs in which one non-bridging oxygen atom has been substituted for a sulfur atom on the phosphate group in each internucleotide phosphate linkage. This modification is a conservative substitution which increases nuclease resistance without significantly impairing the hybridization of the antisense molecule with target mRNA. As synthesized, these analogs are usually found as diastereomeric mixtures due to chirality at their phosphorous group. In a context of new drug research, development and manufacturing of such analogs requires that the issues of oligomer length, base composition, base sequence, chemical purity, and stereochemical purity be successfully addressed.
Synthetic oligonucleotides are presently a standard reagent in most laboratories using molecular biology techniques. As synthesized, these oligomers generally exist as mixtures of truncated oligomers in addition to the desired oligomer. Since the purity and chemical identity of a particular oligonucleotide is crucial to many applications, the ability to characterize synthetic oligonucleotides analogs on a routine basis is important.
The absolute length and the degree of length heterogeneity of prepared oligonucleotides have been assessed by electrophoresis in high resolution denaturing polyacrylamide slab gels (PAGE) (see, e.g., Current Protocols in Molecular Biology, Green Publishing and Wiley Interscience, N.Y., 1988) and by capillary gel electrophoresis through polyacrylamide cross-linked gels (6% T, 5% C) (Hjerten (1967) Chromatographic Rev. 9:122-213) modified with from 10% to less than 30% (volume:volume) formamide (Rocheleau et al. (1992) Electrophoresis 13:484-486). Detection of oligonucleotides separated on such gels has been accomplished by autoradiography and laser-induced fluorescence. Ultrathin slab gels (less than 100 .mu.m in thickness) have also been used for high speed DNA sequencing (Brumley et al. (1991) Nucleic Acids Res. 19:4121-4126; Ansorge et al. (1990) Nucleic Acids Res. 18:3419-3420). Alternative separation methods include ion exchange chromatography, reversed phase high pressure liquid chromatography (HPLC), and gel high performance capillary electrophoresis (HPCE) (see, e.g., Edge et al. (1981) Nature 292:756-762; U.S. Pat. No. 4,865,707).
Oligonucleotides with phosphorothioate linkages are more difficult to resolve than phosphodiester-linked DNA due to the existence of diastereomer isomers (2n, where n=the number of chiral centers, which is equivalent to the number of phosphate groups). In addition, difficulty in resolution may be due to increased hydrophobicity of the former. These molecules, while separated, interact hydrophobically with ion exchange column supports and in many cases co-elute. Thus, they cannot be separated by the above methods in their existing formats.
The separation of phosphorothioate oligonucleotide analogs is problematic for other reasons as well. When phosphorothioate oligonucleotides are assembled using either methoxyphosphoramidite or H-phosphate chemistry, they are in the form of diastereomeric mixtures due to chirality at their phosphorous groups. As a result, although they migrate through polyacrylamide gels and HPLC columns like their corresponding phosphodiester counterparts, phosphorothioate oligonucleotides give broader peaks and run more slowly than phosphodiesters because of their increased hydrophobicity. They are also known to interact with the HPLC column support. In addition, phosphorothioates run into stereochemical problems when separated by reversed phase HPLC. General analytical methods have not been devised for establishing the ratio of the optical isomers at each unsymmetrical substitution phosphorous linkage in an analog having many such sites of local chirality.
HPLC of oligodeoxyribonucleotides containing one or two phosphorothioate internucleotide linkages using a reversed-phase column (RP-HPLC) has been reported (Stec et al. (1985) J. Chromatogr. 326:263-280; Agrawal et al. (1990) Nucleic Acids Res. 8:5419-5423). However, this method is of limited use because of the small differences in the hydrophobicity of these analogs with increasing chain length (Agrawal et al. (1990) J. Chromatogr. 509:396-399).
Oligodeoxyribonucleotide phosphorothioates containing 10 or fewer nucleotides has also been achieved by HPLC on strong anion-exchange (SAX) columns (Agrawal et al. (1990) J. Chromatogr. 509:396-399). In this method, oligonucleotide phosphorothioates were converted to their phosphodiester counterparts in one step, and then were analyzed by HPLC. Unfortunately, oligonucleotides phosphorothioates containing more than 10 nucleotides can not be analyzed by this method because of their strong interaction with the SAX medium. Thus the separation of oligonucleotide phosphorothioates by this method is limited by its oligonucleotide length dependency.
Length-dependent separation of phosphorothioate analogs by HPLC using a weak anion-exchange (WAX) column has also been accomplished (Meletev et al. (1992) Analyt. Biochem. 200:342-346). However, the peaks obtained were broader than those obtained for their phosphodiester counterparts, possibly because of their diastereomeric backbone. Ion-pair HPLC has also been used to analyze oligonucleotide phosphorothioates (Bigelow et al. (1990) J. Chromatogr. 533:131-140), but length-dependent separation was not achieved.
Thus, what is needed are better analytical methods of separating oligonucleotide analogs cleanly, rapidly, efficiently, and which are not limited by the size range of the molecules being analyzed.

Separation of phosphorothioate oligonucleotides by capillary gel electrophoresis


A method for efficiently filling a QIT which isolates an ion range by employing a sequential part of supplemental broadband waveforms where the first such supplemental broadband waveform is applied during the period that the e-beam ionization bombardment takes place and the second such broadband waveform is applied after the e-beam bombardment ends.

In recent years the quadrupole ion trap (QIT) has been becoming of great importance in analytical instrumentation. The QIT was first disclosed in 1952. The history of its development and details of its construction and operation have been set forth in various papers, including the book entitled "Quadrupole Storage Mass Spectrometry" by March and Hughes, published by John Wiley & Sons 1989. Briefly, the QIT is a mass spectrometer which employs radio frequency fields and does not require the use of a magnet for separating ions and providing a mass spectrum of an unknown sample. The sample to be analyzed is first dissociated/fragmented into ions inside the QIT, which ions are charged atoms or molecularly bound groups of atoms. The QIT is capable of providing motion restoring forces on selected ions in the three orthogonal directions and can therefore retain the selected ion inside the QIT.
There are several common techniques in use for determining the spectrum of ions in the QIT. By manipulating the electric fields within the trap, it has been possible to scan, i.e. cause consecutive values of m/e of the stored atoms to become unstable, so that the separated ions pass into a detector and the detected ion current signal intensity, as a function of the scan parameter is the mass spectrum of the ions being analyzed.
An alternative scan method employs a single supplemental dipole frequency applied to the quadrupole trapping field combined with changing the quadrupole RF field voltage so as to bring the secular motions of the trapped ions of consecutive m/e sequentially into resonance with the supplemental field causing their amplitudes to increase until the ion leave the trapping region. This method of scanning is referred to as resonance scanning. Other non-scanning spectrum determining techniques are described in another application (Varian Case No. 93-22) entitled "A Method of Space Charge Control for Improved Ion Isolation in a QIT", filed Jan. 10, 1994. These other methods include measuring image current and integrating it to determine amount of charge in the trap in a manner similar to the Ion Cyclotron Resonance Spectrometer detection (ICR) and FT-ICR or by simultaneously ejection of ions in the trap by a DC voltage applied to one end cap or setting the RF trapping voltage to zero. The simultaneously ejected ions could then be separated by the technique of ion selection employed in time-of-flight spectrometers.
There are several important experiments where it is very important to first isolate within the QIT an ion of a particular m/e or a range of such ions. One such particular experiment is called MS/MS. This is the experiment where a particular ion is isolated, as a parent ion, then the parent is dissociated by gentle collisions, generally called collision induced dissociation (CID) to obtain daughter ions. The commonly assigned U.S. Pat. No. 5,198,665 described earlier as a related patent describes one such isolation method for CID.
There are three types of sample ionization methods in common use. These are E-beam or Electron Ionization (EI), Collision Induced Dissociation (CID) and Chemical Ionization (CI). The e-beam is an adjustable energy electron beam which is caused to impact the ions at high velocity and causes violent fragmentation of a particle. CID is where the ions formed by other processes, such as EI or CI are caused to oscillate in the trap which results in collisions with a background gas resulting in the fragmentation of the ion to form an ion of smaller m/e and a neutral fragment. CI relates to a technique for inducing a chemical reaction between two different materials to form an ionic product.
To carry off a chemical ionization experiment, a neutral reagent gas is introduced into the trap and is ionized by use of an e-beam. The resulting ions of the reagent gas then react with a neutral sample to form an ion of the sample; usually by a proton transfer reaction from the reagention to the neutral sample. One problem with this approach is that the spectrum is too complex and creates several reagent ions which have different chemical properties as well as sample ions form by both EI and CI and the desired ion needs to be isolated.
It is known that species of the reagent ion have quite different properties. The different species transfer different amounts of energy to a sample molecule. Electron bombardment methods produces CH.sub.2.sup.+, CH.sub.3.sup.+, CH+.sub.4.sup.+, CH+.sub.5.sup.+, C.sub.2 H.sub.3.sup.+, C.sub.2 H.sub.4.sup.+, C.sub.2 H.sub.5.sup.+, C.sub.3 H.sub.5.sup.+. These ions are formed by direct bombardment as well as by ion molecule reactions between precursor ions of the reagent gas (formed by EI) and the remaining neutral reagent gas. Each type of ion will produce a different series of product ions when chemically ionizing a sample. Accordingly, the spectra can be very complex. There is a need to provide a single mass isolated reagent ion.
New QIT techniques for isolation of ions have been developing rapidly. However, the available techniques have drawbacks. Marshall, et al. U.S. Pat. No. 4,761,545 taught the use of an inverse Fourier transform with non-linear phasing to produce a supplemental broadband waveform which was applied to the QIT end caps. The Marshall waveform has a notch in the frequency spectrum to eject those ions from the trap whose secular resonance frequencies are outside the notch and to isolate those ions whose secular frequencies are within the notch. Franzen, et al., European patent 362432A1 teaches use of a notched broadband supplemental waveform to selectively store ions and increase their population during e-beam ionization. Kelly, U.S. Pat. No. 5,134,286 created the broadband waveform by employing uniform noise and filtering to obtain a notch. In my earlier '665 patent, a method for isolating a single narrow range of ions is disclosed employing a two step process for CID which employs the scan of the RF field in combination with a supplemental dipole field scanned resonant ejection for the lower m/e ions and a broadband waveform with no notches for ejecting the larger m/e ions. The Marshall, Franzen and Kelly approaches employ low values of RF field during ionization. This results in poor mass resolution for high mass values. My earlier method has improved high mass resolution but has a problem in that after ejection of lower m/e ions, it has no means for ejecting newly formed lower m/e ions which are created by CID during the final step of ejecting the higher mass ions. These lower m/e ions are called "shadow ions".
Louris, U.S. Pat. No. 4,686,367 discloses the method for producing CI reagent species in a trap by electron bombardment. Rejection of the ions above a selective cut-off by mass instability scanning is disclosed. Kelly, in U.S. Pat. No. 4,196,699, uses filtered noise on the end caps during ionization to eject unwanted ions of the reagent and sample gas during ionization. Weber, et al., U.S. Pat. No. 4,818,869 and Barberich, Intern. J. Mass. Spec. and Ion Proc. V 94, P. 115-147 (1989) teaches ion isolation by a method to mass select the CI reagent ion after the end of the initial ion formation period, i.e. the ionization time plus a precursor reaction period. In this method, the precursor ions, which themselves may be reagent ions must be in the trap to form other species of reagent ions. After the end of the reagent formation period, a DC pulse is applied. This does not prevent the formation of additional low mass reagent ions by charge exchange or ion forming processor after the DC pulse mass isolation step. Also, the filtered noise method of the Kelley patent must allow the trapping of all the precursor ions since it is on only during the e-beam ionization step, period A of FIG. 4 of '689 patent, and is off during the reaction step, period B in FIG. 4 of '689 patent. Accordingly, Kelly also has no provision for isolation of a single mass isolated reagent species, without also isolating all precursor ions that lead to the formation of the desired reagent ions.


A safety element is disclosed for influencing or inspecting fluid media in a duct, in particular a double-walled safety duct whose walls are separated by a hollow space. The safety element has a housing formed by walls and flanges for sealingly connecting it to the duct. The housing is surrounded on all sides by a second wall (6) separated from the first wall (5) by a hollow space (7) which is closed in a gas-tight manner and can be connected with measurement equipment for inspecting its contents. The hollow space (7) communicates through one or several bores (13) with a groove (15) shaped around the duct into the sealing surface (14) of the flange (1) or its seal (18).

1. Technical Field of the Invention
The invention concerns a safety function element to influence or control fluid mediums in a line, in particular a double-walled safety line whose walls are spaced at a distance to each other through a hollow space, the element being provided with a housing formed by walls and having as well flanges by means of which it can be connected tightly to the line.
2. Description of the Prior Art
In piping systems in many cases easily inflammable or explosive liquids as well as gases and products that endanger the water and are injurious to health and the environment are transported. Because an uncontrolled release of the transported medium would result in significant damage and risks, for preventive purposes, the use of double-walled safety lines is known, whose walls are spaced at a distance to each other through a hollow space. In this way not only is protection against an escape of the medium directly improved, it is also possible to connect the hollow space to a measuring device to check its contents, for example, a detection device for specific gases or a pressure gauge. Therefore a leak report and subsequent cut-off of transport through the line is effected as soon as the medium enters the hollow space so that the risk of a spillage affecting the environment is completely ruled out.
As a rule, lines are provided with a multitude of function elements. Examples are non-return or shutoff valves, slide valves, pumps or flow meters, which are connected respectively, via flanges, to the line pipes which may comprise rigid or flexible material. In the region of the function elements no suitable measures are known to provide protection against the medium leaking. On the one hand, this has the consequence that operationally the function elements represent a considerable source of danger with leakages occurring with above average frequency compared with the line. On the other hand, during the construction of a line it means significantly higher expenditure because permanent access must be guaranteed, also by statute, even if the line is laid underground, to the function elements. Therefore, in the state-of-the-art, the function element is fitted either in a shaft or an underground loop so that significant extra costs are the disadvantageous consequence. In addition to the function elements themselves, the flanges, to which they are connected, for example, by means of bolts to fit tightly with the adjacent line, represent further regions in which leaks occur especially frequently.


The present invention relates to a luminous keyboard, including a key, a support plate, a switch circuit board, a light guide plate, and a direct-type light emitting element capable of generating a beam. The support plate is located below the key, and the switch circuit board is disposed on the support plate. The light guide plate is located below the support plate and includes a concave structure, and the concave structure forms a reflective surface inside the light guide plate. The direct-type light emitting element is located below the concave structure. When the beam enters the light guide plate, the beam is reflected by the reflective surface to be fully reflected in the light guide plate, and the light guide plate guides the beam to be projected to a peripheral area of a key.

Common computer-peripheral input devices include mice, keyboards, trackballs, and the like, where keyboards can be used to directly enter words and characters into a computer, and therefore, draw great attention from users and input device manufacturers.
Referring to FIG. 1, FIG. 1 is a schematic structural diagram of the appearance of a conventional keyboard. A plurality of keys 10 is exposed on a surface of a keyboard 1, and the keys 10 are classified as generic keys 101, number keys 102, function keys 103, and the like. The keys are provided for a user to touch and press with fingers, to generate a corresponding signal input to the computer, to enable the computer to implement a function of the touched and pressed key. For example, the generic keys 101 are used for inputting symbols such as English letters, the number keys 102 are used for inputting numbers, and the function keys 103 are used for providing various functions such as F1 to F12. The conventional keyboard 1 is a keyboard for a notebook computer.
With the evolution of technologies, keyboard manufacturers are devoted to researching and developing various keyboards having particular functions, such as a luminous keyboard, to meet various requirements of different users. An internal structure of a conventional luminous keyboard is described below. Referring to FIG. 2, FIG. 2 is a structural sectional view of a conventional luminous keyboard. A conventional luminous keyboard 2 includes a plurality of keys 20, a membrane switch circuit 21, a light guide plate 22, a light emitting module 23, a support plate 24, and a reflector plate 25. The key 20 includes a key cap 201, a scissors-type connecting element 202, and an elastic element 203. In the conventional luminous keyboard 2, an arrangement sequence of the foregoing components from top to bottom are the key cap 201, the scissors-type connecting element 202, the elastic element 203, the membrane switch circuit 21, the support plate 24, the light guide plate 22, and the reflector plate 25, and the support plate 24 located between the membrane switch circuit 21 and the light guide plate 22 can bear the key cap 201, the scissors-type connecting element 202, the elastic element 203, and the membrane switch circuit 21 thereon.
In the key 20, the key cap 201 is exposed out of the conventional keyboard 2 and can be touched and pressed by a user, the scissors-type connecting element 202 is used for connecting the key cap 201 and the support plate 24, and the elastic element 203 penetrates through the scissors-type connecting element 202 and is in contact with the key cap 201 and the membrane switch circuit 21 separately. The membrane switch circuit 21 includes an upper circuit board 211, an isolation layer 212, and a lower circuit board 213. The upper circuit board 211 has a plurality of upper conductive parts 2111. The isolation layer 212 is located below the upper circuit board 211 and has a plurality of isolation layer holes 2121 corresponding to the plurality of upper conductive parts 2111. The lower circuit board 213 is located below the isolation layer 212 and has a plurality of lower conductive parts 2131 corresponding to the plurality of upper conductive parts 2111, so that the plurality of lower conductive parts 2131 and the plurality of upper conductive parts 2111 form a plurality of key switches 214. The upper circuit board 211, the isolation layer 212, and the lower circuit board 213 are all made of a transparent material, and the transparent material is made from polycarbonate (PC) or polyethylene (PE), to have a light transmission effect.
The light emitting module 23 includes a power supply circuit board 231 and a plurality of light emitting elements 232 (only two are shown). The power supply circuit board 231 is located below the membrane switch circuit 21 and is used for supplying power to the plurality of light emitting elements 232. The plurality of light emitting elements 232 are disposed on the power supply circuit board 231 and extend into a plurality of reflector holes 251 of the reflector plate 25 and a plurality of light guide plate holes 221 of the light guide plate 22. When the plurality of light emitting elements 232 is powered on, the plurality of light emitting elements 232 generates a plurality of beams B, and the plurality of beams B is projected to the light guide plate 22. The light emitting elements 232 are edge-type light-emitting diodes (LEDs). A function of the light guide plate 22 is guiding a plurality of beams B to be projected to the key cap 201. The reflector plate 25 is disposed below the light guide plate 22 and can reflect the plurality of beams B to project the plurality of beams B upward, so as to avoid waste of the beams B. Two side edges 252 of the reflector plate 25 are bent upward and wrap a plurality of side edges 222 of the light guide plate 22, to avoid a light leakage phenomenon on the side edges 222 of the light guide plate 22.
In the conventional luminous keyboard 2, each key cap 201 has an out-light area 2011, and the out-light area 2011 is a position where a letter or a symbol is located. The position of the out-light area 2011 corresponds to the position where a light guide dot 223 is located on the light guide plate 22, so that the beam penetrates through the light guide dot 223 and is guided upward to the out-light area 2011. When the beam B transmitted and guided in the light guide plate 22 is projected to the light guide dot 223, the light guide dot 223 can guide the beam B to be projected upward. The beam B projected upward can sequentially penetrate through support plate holes 241 of the support plate 24 and the membrane switch circuit 21, and further penetrate through the out-light area 2011 of the key cap 201, so that a letter or a symbol on the key cap 201 can transmit light and have a light emitting effect.
Recently, users expect that a light emitting effect of each key in a luminous keyboard can be controlled. For example, a key A is controlled to emit light, but a key B is controlled not to emit light. However, the foregoing conventional luminous keyboard 2 cannot meet the foregoing requirement. To satisfy requirements of users, a direct-type luminous keyboard needs to be used. In the direct-type luminous keyboard, a single direct-type LED is disposed below a key cap of each key, so that a light emitting situation of each direct-type LED can be controlled separately to satisfy the requirements of the users. A beam generated by the direct-type LED is directly projected upward to the corresponding key cap. Therefore, a light projection effect of the direct-type luminous keyboard is excessively concentrated, and a light evenness effect cannot be achieved.
Therefore, a luminous keyboard having a function of separately controlling a light emitting situation of a key and having an even light-emitting effect is needed.


An accessory for fluoroscopy equipment is provided to support the x-ray tube and detector on a pedestal with respect to a patient limb for quantitative bone densitometry measurement. Software loaded into the associated digital imaging fluoroscopy equipment provides necessary correction of the images for the quantitative accuracy needed for bone densitometry. Alternatively, a specialized detector or extremely low form factor image intensifier may be inserted in the pedestal to be used in lieu of the fluoroscopy equipment detector. A similar software correction is performed on an associated computer when a separate detector must be used.

Portable x-ray fluoroscopy machines provide an x-ray source held in opposition to an electronic image detector, typically on a C-arm, so that x-rays from the x-ray source are received by the image detector. The C-arm may slide through a collar so as to allow it to be rotated to different angles about the patient. Further, the collar may be supported by a pivoting arm providing additional freedom in the positioning of the C-arm.
When the C-arm is correctly positioned, the x-ray source is activated and x-rays pass through the patient to be received by the image detector which provides electronic signals to a video monitor. For larger mobile C-arm systems, the video monitor is typically held on a separate cart or may be suspended from the ceiling on a fixed bracket to be connected to the mobile unit when the mobile unit is in place.
With improvements in electronic hardware and in particular the development of compact image intensifiers and CCD video cameras, it has become possible to build extremely compact mobile C-arm systems. Such systems may make use of increasingly powerful desktop computer technology for image processing and other tasks and may use compact digital printers for producing images.

Densitometry adapter for compact x-ray fluoroscopy machine


A composition comprising okadaic acid for use as a positive control in assays for the detection of ciguatoxins and methods for making such compositions. In a preferred embodiment, the okadaic acid composition further comprises a carrier selected from the group consisting of fish extract, oils, oil/organic solvent mixtures, fatty-acid solutions, and non-ionic detergent solutions. A kit for detecting the presence of ciguatoxin or related polyether marine toxins in fish, comprising positive control supports impregnated with a composition comprising okadaic acid.

Ciguatera poisoning is a particular type of fish poisoning which results from the ingestion of contaminated fish. Intoxication is associated with the consumption of toxins produced by the tropical dinoflagellates, including Gambierdiscus toxicus, which are subsequently passed along the marine food chain to man. Ciguatoxins are polyether marine toxins, and approximately 27 different ciguatoxins are known, approximately 23 of which are toxic to man. Ciguatera toxins are odorless, tasteless, heat-stable, and generally undetectable by simple chemical tests.
Humans are susceptible to ciguatera poisoning, both from eating toxic herbivores which ingest the dinoflagellates while feeding on red or brown algae, and from eating carnivores which have eaten the toxic herbivores. An accurate assessment of the incidence of ciguatera poisoning is not available; however, it is estimated that, each year, from 10,000 to 50,000 people who live in or visit tropical and subtropical areas suffer from ciguatera poisoning. Additionally, the threat of this contamination results in enormous economic losses in the recreational and commercial exploitation of fishery resources in the affected areas. With increased utilization of tropical reef fish in the continental United States, through interstate commercial trade and tourist travel, incidents of ciguatera poisoning are on the increase.
The onset of the clinical symptoms of ciguatera poisoning occurs within 10 minutes to 24 hours following the consumption of contaminated fish. Ciguatera poisoning affects the digestive system (resulting in abdominal pain, diarrhea, vomiting, nausea); the cardiovascular system (resulting in bradycardia, hypotension, tachycardia); and the neurological system (resulting primarily in paraesthesia and dysesthesia).
Immunological methods have been developed for the identification of ciguatoxin in fish, such as those described in U.S. Pat. No. 4,816,392. These methods offer a relatively simple method of assaying for ciguatoxin. However, such assays incorporate the requirement for "controls." Positive and negative controls are necessary in such assay reactions so that the user of the assay can determine if the reagents are functioning correctly. Also, positive and negative controls provide standard reactions with which the user can compare test assay results to determine if a positive or negative reaction has been obtained. The term "positive control" as used herein means a composition which reacts with antibodies or other assay reagents in a manner similar to ciguatoxin-containing fish extracts to give a positive reaction when assayed. The term "negative control" refers to a sample which contains all the components of a test assay sample, except for a ciguatoxin-containing fish extract or such toxins, and which does not react with antibodies against ciguatoxin, therefore giving a negative reaction when assayed.
Previously, fish extracts have been used as a positive control for ciguatoxin assays. However, such extracts vary in their composition, with respect to the ciguatoxins they contain and the concentration of the ciguatoxin(s) present, and, therefore, also vary in their reactivity. As a result, fish extracts exhibit variable reactivity and give results that are not reproducible. Also, to determine the toxicity of ciguatoxin in fish extracts, toxicity assays, such as assaying the toxicity of the ciguatoxin in mice, have to be performed. Such assays are time-consuming and expensive.
An additional drawback of the use of fish ciguatoxin extracts is that, for mass production of kits for the assaying of fish which may contain ciguatoxin or other "screening" assay methods, enormous numbers of toxic fish would be required for the production of ciguatoxin extract for the positive controls. The requirement for such large amounts of ciguatoxin extracts could make the routine testing of fish impractical or too expensive to be feasible, and results would vary with different fish ciguatoxin extract preparations.
There exists a need, therefore, for a composition which will reliably and reproducibly react in a ciguatoxin assay to mimic the results that would be obtained with a ciguatoxin-contaminated fish and which is readily available and relatively inexpensive.