A condenser lens is disposed in a position facing an objective lens via a specimen, a reflection mirror is movably disposed in the vicinity of an outermost part of a transmitted illuminative light path on the side of a transmitted illuminative light source from the condenser lens, and a laser beam output from a laser oscillation unit is reflected by the reflection mirror and is incident upon the condenser lens.

1. Field of the Invention
The present invention relates to a total internal reflection fluorescence microscope for performing fluorescence observation by use of an evanescent light generated by total internal reflection illumination.
2. Description of the Related Art
In recent years, a total internal reflection fluorescence microscopy (hereinafter referred to as TIRFM) has attracted attentions as a microscope for fluorescence observation of a living thing. In this TIRFM, an illuminative light is totally reflected by a boundary surface between a cover glass and a specimen, and a fluorescent substance is excited using a light called an evanescent light which leaks into a small region having a size of several hundreds nm or less on a specimen side. In this TIRFM, only the fluorescence of the small region in the vicinity of the cover glass is observed. An observed image of TIRFM provides a very dark background. Accordingly, it is possible to observe fluorescence having a high contrast and faint fluorescence.
Additionally, in a site of biological research using TIRFM, there are a case where a shallow plane is to be observed with good contrast in the vicinity of the boundary surface between the cover glass and the specimen, and a case where the evanescent light is extended to a certain degree of depth to observe a broad range. Therefore, it is desirable to change a leak-out depth of the evanescent light in accordance with the specimen.
The leak-out depth of the evanescent light from the boundary surface is described, for example, in D. Axelrod's document "Total Internal Reflection Fluorescence at Biological Surfaces". Accordingly, the following equation is established.d=λ/4π√{square root over ((n12·sin θ12−n22))}  (1),where d denotes the leak-out depth of the evanescent light, λ denotes a wavelength of the light, n1 denotes a refractive index on the incidence side, θ1 denotes an incidence angle, and n2 denotes a refractive index on an emission side.
Therefore, when the incidence angle θ1 of the illuminative light with respect to the boundary surface, that is, an inclination angle of the illuminative light with respect to a normal to the boundary surface increases, the leak-out depth d of the evanescent light becomes shallow. In actual TIRFM, a laser beam having a high coherent property is used, and the incidence angle of the illuminative light is adjusted. Accordingly, the incidence angle of the laser beam onto the boundary surface changes, and the leak-out depth of the evanescent light is adjusted.
FIGS. 17A to 17C are diagrams showing a function of TIRFM described in Jpn. Pat. No. 3093145. An objective lens 1 has a numerical aperture with which total internal reflection illumination is possible. A specimen 3 is laid on a cover glass 2. A mirror 4 is movable in a direction crossing an optical axis direction of the objective lens 1 at right angles.
A laser beam 5 for use as the illuminative light is incident upon the mirror 4. In this state, as shown in FIGS. 17A to 17C, the mirror 4 moves in the direction crossing the optical axis direction of the objective lens 1 at right angles. Accordingly, an incidence position of the laser beam incident upon the objective lens 1 moves in a direction distant from an optical axis of the objective lens 1. By the movement of the incidence position of the laser beam, the incidence angle of the laser beam 5 emitted toward the boundary surface between the cover glass 2 and the specimen 3 from the objective lens 1 changes. The laser beam 5 emitted from the objective lens 1 is totally reflected by the boundary surface between the cover glass 2 and specimen 3 via an immersion oil 6 as shown in FIG. 17C.
FIG. 18 is a constitution diagram of TIRFM described in Jpn. Pat. Appln. KOKAI Publication No. 2001-013413. The TIRFM includes a laser illuminating device 7 which outputs the laser beam 5. In the TIRFM, the laser beam 5 is incident upon a side surface 10 of a point ball lens 9 of a condenser lens for transmission illuminating 8 and the total internal reflection illumination is possible. The laser illuminating device 7 is rotatable with respect to a microscope main body 11. The laser illuminating device 7 rotates centering on an intersection of the boundary surface of the cover glass 2 and specimen 3 and the observation optical axis. Accordingly, the laser beam 5 changes its incidence angle with respect to the boundary surface between the cover glass 2 and specimen 3.
Additionally, the incidence angle of the laser beam 5 needs to be inclined by a critical angle or more, at which the total internal reflection occurs. Here, assuming that a refractive index on a cover glass 2 side via the boundary surface between the cover glass 2 and specimen 3 is n1, and a refractive index on a specimen 3 side is n2, a critical angle θc is represented by the following equation (2).sin θc=n2/n1  (2)
Therefore, conditions of the incidence angle θ1 for realizing the total internal reflection illumination is represented by the following equation (3).n1·sin θ1>n2  (3)
On the other hand, to incline an incident light of the laser beam 5 passing through the objective lens 1 as in the Jpn. Pat. No. 3093145 shown in FIGS. 17A to 17C, a maximum incidence angle θmax that can be set depends on the numerical aperture (NA) of the objective lens 1, and is represented by the following equation (4).n1·sin θmax=NA  (4)
Therefore, for the conditions for realizing the total internal reflection illumination, the NA of the objective lens 1 needs to be larger than the refractive index n2.
In general, a refractive index of a living cell is about 1.37 to 1.38. The NA of the objective lens 1 for use needs to be about 1.4 at minimum.
At present, a magnification of the objective lens having an NA of 1.4 or more is limited to a high magnification of 60 times or more. To realize a high NA by the objective lens 1 having a low magnification, an effective diameter of the objective lens 1 needs to be increased. However, it is difficult to increase the effective diameter of the objective lens 1 while keeping a standard diameter of an attaching screw of the objective lens 1. Therefore, in the TIRFM shown in FIGS. 17A to 17C, total internal reflection fluorescence observation at a magnification of about 20 or 40 times is impossible.
In the TIRFM shown in FIG. 18, when the laser beam 5 is incident from a condenser lens for transmission illuminating 8 side, an illuminative range can be set without depending on the objective lens 1. Accordingly, the total internal reflection fluorescence observation using the objective lens 1 having a low magnification is possible.
However, in the TIRFM shown in FIG. 18, the laser illuminating device 7 is disposed right beside the point ball lens 9 of the condenser lens for transmission illuminating 8. Additionally, the laser illuminating device 7 itself needs to be rotated. Therefore, a considerable space is necessary including a holding section of a rotary mechanism and a space of a track of the rotating laser illuminating device 7. Consequently, a space in which the specimen 3 is laid is compressed. It is supposed that operation properties are remarkably impaired.
An irradiation range of the laser beam is set in such a manner that an observation range of the objective lens 1 having the low magnification can be illuminated. Then, in the observation with the objective lens 1 having the high magnification, only a part of the irradiation range of the laser beam is observed. Therefore, the laser beam with which another part is irradiated is useless.
An energy density of the laser beam on the surface of the specimen 3 is in inverse proportion to an irradiation area. In the observation with the objective lens 1 having the high magnification, the irradiation range of the laser beam is condensed so as to illuminate only a range required for the observation, and the energy density of the laser beam is preferably enhanced.
Especially, there is an experiment for the purpose of detection of very weak fluorescence such as a single molecule. In this experiment, the irradiation energy density of the laser beam is required to be as high as possible. On the other hand, in the TIRFM, the leak-out depth of the evanescent light is changeable. In recent years, the TIRFM has been spread in the site of the biological research. Furthermore, there has started to be a demand for the simultaneous illuminating of a plurality of optional wavelengths in optional depths.
This background has the following actual circumstances. Improvement of fluorescent protein such as GFP has been advanced, and it becomes easy to observe a dynamic state or a function of the living cell with multicolored fluorescence. Moreover, as seen also from Axelrod formula (equation (1)), the leak-out depth of the evanescent light depends also on the wavelength of the light. Therefore, there is a principle problem that a range to be observed differs, when the wavelength differs even at the equal laser beam incidence angle. There is also a realistic problem that a depth position of a tissue in a cell corresponding to each wavelength differs.
In the TIRFM, it is possible to switch the incidence angle or the wavelength of the laser beam at a high speed using mechanical means or electric driving means such as a motor. However, in cases where a simultaneous property in a strict meaning is required such as a case where a fast phenomenon is traced, there is a restriction on a high-speed switch. In this case, it is necessary to simultaneously-illuminate introductory portions of the laser beams disposed in a plurality of places.
However, in the TIRFM shown in FIG. 17A, a dichroic mirror is used in order to reflect the laser beam on a objective lens 1 side and to transmit the fluorescence on an observation side.
Additionally, when there are a plurality of wavelengths to be illuminated, the dichroic mirror needs to have wavelength characteristics of the corresponding multi-band. The dichroic mirror of the multi-band has a high difficulty in manufacturing, and is expensive. Furthermore, the dichroic mirror of the multi band has a bad separation level of the wavelength, and brightness and SN ratio of a fluorescent image are deteriorated. When the illuminative wavelengths are to be further increased halfway, the dichroic mirror needs to be newly prepared again.
On the other hand, to prevent the dichroic mirror from being used, as shown in FIG. 19, it is possible to dispose a total internal reflection mirror 12 in a position of an outermost portion of a pupil of the objective lens 1. However, it is necessary to dispose another total internal reflection mirror 13 also in the outermost portion of the pupil of the objective lens 1 on an opposite side in order to prevent the laser beam 5 totally reflected by the boundary surface between the cover glass and the specimen 3 from passing on an observation side.
Therefore, a considerable part of the pupil of the objective lens 1, which should have been originally used 100% for observation, is lost by the respective total internal reflection mirrors 12, 13. Therefore, a capability of the objective lens 1 is deteriorated.
In the TIRFM shown in FIG. 18, as described above, the laser illuminating device 7 is disposed right beside the point ball lens 9 of the condenser lens for transmission illuminating 8, and additionally the laser illuminating device 7 itself needs to be rotated. Therefore, a considerable space is required including the space of the track of the holding section of the rotation mechanism or the rotating laser illuminating device 7. In this constitution, when the laser illuminating device 7 including an emission angle adjustment section of independent laser beams is to be disposed, two laser illuminating devices at maximum can be disposed on opposite sides of the condenser lens for transmission illuminating 8.
Moreover, each TIRFM has a common problem. There is a case where a plurality of wavelengths are observed by the use of the evanescent lights having different depths. For example, when a shallow region is observed with B excitation, and a deep region is observed with G excitation, the B and G excitations can be simultaneously observed only in the shallow region. In this case, the image of the G excitation can only be observed as a defocused background image. Therefore, for example, the whole cell film is dyed by a fluorescent reagent, and the image of the TIRFM in the deep region can be used only in limited applications such as grasping of an approximate size of the cell.
While the objective lens is fixed, the surfaces in the different depths can be simultaneously observed. Then, the application of multi-wavelength TIRFM can further be broadened to simultaneous observation of forms of small organs in the vicinity of the cell film and inside the cell.

Total internal reflection fluorescence microscope


Techniques are described for synchronizing internet (“over the top”) video streams for simultaneous playback. In particular, techniques are described to improve the performance and accuracy of stream synchronization among participant media player applications playing a same video content item, for example, as part of a “watch party.” The techniques can be further augmented to allow interaction between the users watching the presentation, e.g., by sending messages to other users or by annotating the video presentation with comments, and can be further used to enable “cross device control,” a feature that enables multiple users, or a single user with multiple devices, to control a shared video playback session on another device. For example, two users watching a streaming video on a set-top box connected to a TV in their living room could each use an app on their respective smart phones to pause/play/seek the playback session, providing a more collaborative experience.

Streaming video over data networks (e.g., the internet) has become increasingly popular as the availability of high-bandwidth internet connections has increased. Video streaming refers to a type of video delivery mechanism where the data for the video is continuously delivered to a client device over a data network (e.g., the internet) as the user is viewing the video. Video streaming allows a user to start viewing portions of the video without having to first download the entire video.
Pre-recorded video content or live video content can be streamed over the internet using streaming protocols such as HTTP Live Streaming (HLS) and MPEG Dynamic Adaptive Streaming over HTTP (DASH). Such streaming protocols typically divide video content into a series of video segments and generate a streaming manifest file (also referred to as an index file) that references these video segments. A client device can interpret the streaming manifest file to fetch the video segments and seamlessly assemble the video segments to play the video content. Users sometimes like to watch video content in groups, that is, to watch the same video content at the same time at multiple separate client media player applications. Synchronizing internet ("over the top") video streams for simultaneous playback to allow multiple users to watch the same video content at the same time presents a number of challenges. Some systems for synching streaming video use the Real-time Transport Protocol (RTP) and the Real Time Streaming Protocol (RTSP), potentially with multicast addressing, to send video content out to multiple clients at the same time. This approach can work but presents several challenges for systems that deliver a modern online video service based on HLS and MPEG-DASH.

Synchronizing internet (“over the top”) video streams for simultaneous feedback


An image forming apparatus and an image forming method capable of preventing image noise caused by separation discharge between a photosensitive member and a recording sheet while suppressing to a minimum limit the reduction in production efficiency, by detecting environmental conditions and changing the transport spacing of the recording sheet in accordance with the detected environmental conditions.

1. Field of the Invention
The present invention relates to an image forming apparatus such as electrophotographic copiers, printers or the like and image forming method, and more specifically relates to an image forming apparatus and image forming method for changing the recording sheet transport spacing according to environmental conditions.
2. Description of the Related Art
In image forming apparatuses of the electrophotographic type such as copiers, printers and the like, an electrostatic latent image of the image to be reproduced is formed on the surface of a photosensitive member, said latent image is developed as a toner image, and said toner image is transferred onto a recording sheet and subjected to a fixing process to form the finished image on said recording sheet.
In the aforesaid processing, for example, the surface of a photosensitive member is uniformly charged to a negative polarity by a charger beforehand, and the image to be reproduced is projected onto the charged surface of the photosensitive member so as to discharge the area in which the image is projected, and this image is developed by toner charged to a negative polarity such that said charged toner only adheres to the image area and forms a toner image. In order to transfer the toner image formed on the surface of the photosensitive member onto a recording sheet, a charge having an opposite polarity (positive) is applied to the recording sheet via a transfer charger disposed on the underside of said recording sheet so as to transfer said toner image to the recording sheet. At this time, the recording sheet is electrostatically adhered to the photosensitive member because the photosensitive member is charged with a negative polarity and the recording sheet is charged with a positive polarity. Therefore, in order to separate the recording sheet from the photosensitive member, the charge of the recording sheet is neutralized by a seperation charger in a process to separate the recording sheet from the photosensitive member.
When the recording sheet separates from the photosensitive member, the charge of the recording sheet is neutralized to a certain degree although not completely neutralized by the separation charger, such that a residual positive charge remains on the recording sheet and the photosensitive member is charged with a negative polarity. Therefore, when the trailing edge of the recording sheet separates from the photosensitive member, a discharge is generated between the sheet and the photosensitive member in a phenomenon called a separation discharge which causes the position corresponding to the trailing edge of the recording sheet on the surface of the photosensitive member to be charged with a positive polarity. In the present specifications, the trailing edge of the recording sheet is defined as the edge of the recording sheet on the downstream side relative to the recording sheet transport direction in the image forming apparatus.
After the toner image formed on the surface of the photosensitive member has been transferred to the recording sheet, the photosensitive member is subjected to an optical erasure process by passing below an eraser lamp to eliminate the remaining residual charge. In the part of the photosensitive member charged with a positive polarity by the aforesaid separation discharge, however, the residual charge cannot be eliminated by the optical erasure process and travels to the charger with the residual positive polarity charge intact. Although a charge of negative polarity is imparted to the photosensitive member by the charger, a potential difference cannot accumulate in aforesaid area of the residual charge of positive polarity such that a shift occurs in the surrounding charge to the positive polarity side at position corresponding to the trailing edge of the recording sheet on the surface of the photosensitive member, and toner adheres in this area by the developing process for a subsequent image so as to cause black lines (noise) in the developed image.
FIG. 5 illustrates the situation in which black lines (noise) appear in a subsequent image when the photosensitive member has a residual charge of positive polarity due to separation discharge. A toner image formed on the surface of photosensitive member "a" having a diameter D is transferred onto a first recording sheet P1', and when a separation discharge is generated at point S when the trailing edge of recording sheet P1' separates from photosensitive member "a", a residual positive charge is imparted at area S on the surface of photosensitive member "a". An image to be transferred to a second recording sheet P2' is subsequently formed on the surface of photosensitive member "a". At this time, a line-like toner image is formed in the area of residual positive charge when said image is developed by toner due to the positive charge remaining at area S on the surface of photosensitive member "a". When the transport spacing M between the first recording sheet P1' and second recording sheet P2' is shorter than the circumferential length L (=.mu.D) of the photosensitive member "a" (M<L), the line-like toner image adhered by the residual charge imparted by the separation discharge is developed as line "t" on the image transferred to the second recording sheet P2'.
Particularly in systems which form color images, a plurality of image formations are repeated for the separate colors, and the transfer process of transferring the toner on the surface of photosensitive member is also repeated a plurality of times. Therefore, there is an increase in the residual charge on the recording sheet and separation discharge readily occurs.
In color image processing, unlike typical monochrome image processing, colored image is also formed in the area of the background of an image. Therefore, an image is frequently formed in the area of the trailing edge of the recording sheet and separation discharge readily occurs.
Heretofore two measures have been proposed as countermeasures to the previously described image noise induced by separation discharge. A first countermeasure is a method wherein a charge is imparted by a charger to the area of abnormal charge induced by separation discharge so as to return said area to its original potential. Specifically, a charger is disposed on the downstream side of the transfer charger and on the upstream side of a cleaner (i.e., a device which cleans the surface of the photosensitive member by removing residual toner remaining on said surface after a toner image formed on the photosensitive member has been transferred to recording sheet) relative to the direction of rotation of the photosensitive member, and this charger imparts a potential of opposite polarity to the area of the photosensitive member charged by separation discharge to return said area to its original potential, and thereafter said charge is erased by an optical erasure process.
This method, however, requires the provision of a charger to correct the potential of the photosensitive member in addition to the essential construction for a normal electrophotographic process, and is disadvantageous insofar as this method increases the number of components and cost. Notably, in tandem-type image forming apparatuses, the aforesaid method produces deeper disadvantages than increased number of components and cost due to the necessity of multiple preparations. Tandem-type image forming apparatuses include image forming apparatuses provided with a plurality (in this example, four) electrophotographic processing units of a plurality of colors corresponding to, e.g., yellow (Y), magenta (M), cyan (C), black (Bk), to form color images, wherein the toner image of each color formed on the surface of a photosensitive member provided with said electrophotographic units are consecutively transferred to and overlaid on a recording sheet to form a color image.
When the aforesaid charger is disposed downstream from the transfer charger and upstream from a cleaner relative to the direction of rotation of the photosensitive member, the spatial arrangement of the charger cannot be assured without enlarging the diameter of the photosensitive member. On the other hand, when the diameter of the photosensitive member increases, the size of the image forming apparatus also increases. Particularly in the case of tandem type image forming apparatuses, enlarging the diameter of the photosensitive member produces a markedly greater effect on size than in the case of typical image forming apparatuses (of the type which form images using a single processing unit) because each of the photosensitive members of a plurality of electrophotographic processing units must be enlarged. In tandem type image forming apparatuses provided with delay memory to adjust the shifting of image data processing timing among the various electrophotographic processing units, increasing the size of the photosensitive member results in increased distance between said electrophotographic processing units and necessitates a delay memory of greater capacity.
A second countermeasure is to increase the transport spacing between recording sheets. Specifically, if the transport spacing of the recording sheets is lengthened so as to be greater than the circumferential length of the photosensitive member, the abnormally charged area of the photosensitive member charged by separation discharge will not enter the region to which an image to be transferred to a subsequent recording sheet is formed, as can be clearly seen in FIG. 5. When the transport spacing of the recording sheets is increased in this way so as to be greater than the circumferential length of the photosensitive member, the photosensitive member must idle rotate (rotation without image formation) at least one rotation to pass under the charger before image formation to neutralize the abnormal charge. Accordingly, when the charger imparts a charge to the surface of the photosensitive member in the image formation stage, the influence of the separation discharge is eliminated and the surface of the photosensitive member can be uniformly charged.
The following disadvantages arise, however, when the transport spacing of the recording sheets is increased. A first disadvantage is a reduction in production efficiency caused by a reduction in the number of image formations that can be accomplished per unit time. A second disadvantage is the increased cost of a single image formation sheet caused by the reduced service life of the photosensitive members and developing devices due to the increased operating time of said photosensitive members and developing devices compared to the same number of image formations when the transport spacing between recording sheets is not increased.
For example, when the diameter of the photosensitive member is 60 mm and the processing speed is 120 mm/sec, the transport spacing of the recording sheets must be a minimum of 60 mm.times.3.14, or about 190 mm to avoid the effects of separation discharge. In typical image forming apparatuses, a transport spacing of about 60 mm is adequate even considering the scanner return time.
In image forming processes for A4 size portrait oriented (i.e., the lengthwise direction of the sheet is parallel to the transport direction) recording sheets, the typical image forming apparatus produces 120.times.60/(210+60)=27 sheets/min, whereas increasing the transport spacing of the recording sheets to avoid the effect of separation discharge produces 120.times.60/(210+190)=18 sheets/min. That is, even at identical processing speeds, the number of image formations that can be processed per unit time is reduced to about 2/3. Furthermore, the service life of consumable components is also reduced by this same ratio.

Image forming apparatus and image forming method for changing sheet transport spacing according to environmental conditions


This invention is concerned with a transmission control method and apparatus in a collision interval for a collision of multidimensional hopping patterns. In the present invention, each orthogonal wireless resource in the coordinate of the multidimensional orthogonal resource can hop according to the hopping pattern negotiated between a transmitter and a receiver, and each corresponding channel is distinguished by the hopping pattern. A specific multidimensional hopping pattern is allocated to each secondary station. The hopping pattern is either permanently allocated to the secondary stations or temporarily allocated from the primary station during a call set-up. The permanent allocation of the hopping pattern to the secondary stations is achieved when the hopping pattern is identified based on a unique identifier, such as ESN of the secondary station. The hopping patterns of the secondary stations are mutually independent so that the coordinates of the same orthogonal resource is allocated to different secondary stations in a simultaneous manner in a specific moment. Through this invention, in order to improve the performance of the multidimensional resource hopping multiplexing system, refining transmission and perforation mechanisms for the collisions of multidimensional resource hopping patterns can reduce the overall perforation probability.

(a) Field of the Invention
The present invention relates to a digital communication method and a system thereof, and specifically to an apparatus and method for a statistical multiplexing of channels based on a multidimensional orthogonal resource hopping method in case where each channel has a variable transmission rate less than a basic transmission rate R in wire/wireless communication systems using a plurality of low-activity communication channels mutually synchronized through a single medium.
More specifically, the present invention relates to a multiplexing apparatus and method in a system composed of a primary station and a plurality of secondary stations mutually synchronized, the primary station identifying a channel to each secondary station using a multidimensional orthogonal resource hopping pattern, the multidimensional orthogonal resource hopping pattern corresponding to the secondary station including an intentional(non-random) hopping pattern allocated by the primary station during a call set up or a pseudo-random hopping pattern unique to the secondary station. The coordinates of the multidimensional orthogonal resources in hopping patterns of a different channel can be identical(matched) (this phenomenon will be referred to as a "multidimensional hopping pattern collision"). In this case, whether or not the channels are matched is determined from the transmit data symbols for all transmit channels of the primary station related to the multidimensional hopping pattern collision. If a data symbol having at least one unmatched channel is transmitted, the corresponding data symbol interval is turned off and the transmission power of all channels off in data symbol transmission may be increased as much as a predetermined amount for a predetermined time as defined by the protocols so as to compensate for a loss of the average bit energy of missing data of all the related channels.
In this description, the primary and secondary stations correspond to a base station and mobile stations, respectively, in the existing systems. The primary station is in communication with multiple secondary stations. The present invention relates to a statistical multiplexing method applicable in a synchronized channel group maintaining orthogonality in the direction from the primary station to the secondary stations.
(b) Description of the Related Art
The present invention can be embodied independently in each channel group for a system maintaining orthogonality only in each channel group, e.g., a quasi-orthogonal code (QOC) used in the cdma2000 system that is a candidate technology of the next generation mobile communication system under standardization, i.e., IMT-2000, or a multi-scrambling code (MSC) to be used in the WCDMA system. With the channels of a primary station classified into channel groups having a same transmitter antenna beam as in a sectorizing or smart antenna system, the present invention can also be embodied independently in each channel
For expediency in explaining which part of the prior art is modified in the embodiment of the multiplexing system of the present invention, the following description will be given on the basis of the IS-95 (cdmaOne) system that is a conventional mobile communication system now in commercial use.
In the digital/analog FDM (Frequency Division Multiplexing) communication system according to prior art, a primary station allocates available FA (Frequency Allocation) to a secondary station irrespective of the channel activity during a call set up, and the secondary station returns the FA to the primary station for another secondary station after termination of the call.
In the TDM (Time Division Multiplexing) communication system according to prior art, a primary station allocates one of available time slots in one FA to a secondary station irrespective of the channel activity during a call set up, and the secondary station returns the time slot to the primary station for another secondary station after termination of the call.
In the FHM (Frequency Hopping Multiplexing) communication system according to prior art, a primary station is in communication with a secondary station using a negotiated frequency hopping pattern irrespective of the channel activity during a call set up, and determines whether to allocate a new channel according to the number of allocated channels. But the FHM system has no control function of the present invention for not sending symbols of the related channel in order to reduce possible errors at the channel decoder of the receiver in the case of a hopping pattern collision.
In the OCDM (Orthogonal Code Division Multiplexing) communication system according to prior art, a primary station allocates an available orthogonal code symbol in an orthogonal code to a secondary station irrespective of the channel activity during a call set up, and the secondary station returns the orthogonal code symbol to the primary station for another secondary station after termination of the call.
In the description of the prior art, the same reference number will be assigned to the parts having the same function as in the description of the present invention.
FIG. 1 is a schematic of a system according to an example of the prior art and an embodiment of the present invention, in which channels 121, 122 and 123 formed from a primary station 101 to secondary stations 111, 112 and 113 are in synchronization with one another and have mutual orthogonality.
FIG. 2a is a schematic of a transmitter of the primary station for a part corresponding to the common component between the prior art and the present invention, and FIG. 2b is a schematic of a transmitter of the primary station for a traffic channel in the example of the prior art. A pilot channel 200 must be present by the respective subcarriers SCs, because it is used as a channel estimation signal for initial synchronization acquisition and search and synchronous demodulation at the secondary stations of FIG. 1. The pilot channel 200 is a channel shared among all secondary stations in an area that is under the control of the primary station. As illustrated in FIG. 2a, the pilot channel 200 is used to provide a phase reference for synchronous demodulation by transmitting a symbol of a known pattern without channel coding or channel interleaving. Like the pilot channel 200, a synchronous channel 210 is a broadcasting channel uni-directionally transferred to all the secondary stations in an area that is under the control of the primary station. The synchronous channel 210 is used for the primary station to transfer information (e.g., visual information, the identifier of the primary station, etc.) required in common to all the secondary stations. The data through the synchronous channel are sent to a spreader and modulator, which will be described later in FIG. 3, via a convolutional encoder 214, a repeater 216 for symbol rate control, a block interleaver 218 to overcome burst errors, and a repeater 219 to control a transmit data symbol rate. A paging channel 220 is a common channel used in the presence of an incoming message to the secondary station or for the purpose of responding to the request of the secondary station. Plural paging channels can be used.
The data transmitted through the paging channel are sent to an exclusive OR operator 236 via a convolutional encoder 224, a symbol repeater 226 and a block interleaver 228. The output of a long code generator 232 is sent to a decimator 234, which decimates the output of the long code generator 232 using a long code mask for paging channel 230. The exclusive OR operator 236 exclusive-OR operates the data from the block interleaver 248 with the decimated output of the long code generator 232 and then sent to the spreader and modulator of FIG. 3. A traffic channel 240 of FIG. 2b is a channel allocated to each secondary station during a call set up and exclusively used by the secondary station until a call termination. The traffic channel is used to transfer data from the primary station to each secondary station. The traffic channel is sent to a CRC (Cyclic Redundancy Check) encoder 241 to check errors in the unit of a predetermined time called a frame (e.g., 20 ms in the IS-95 (cdmaOne) system), a tail bit inserter 252 to insert tail bits that are all "0" for independent channel coding in the unit of frames, a convolutional encoder 244 and then a symbol repeater 246 to correct the transmit data symbol rate according to the transmit data rate.
Subsequent to symbol repetition, the traffic channel is sent to a block interleaver 248 to convert burst errors to uniformly distributed errors, and then to a scrambler 256. The output of the long code generator 232 is decimated into a PN (Pseudo-Noise) sequence by the decimator 234 using the long code mask 250 generated from an ESN (Electronic Serial Number) allocated by the respective secondary stations. The scrambler 256 scrambles the traffic channel from the block interleaver 248 using the PN sequence.
The scrambled traffic channel is sent to a PCB (Power Control Bit) position extractor 258 to extract a PCB position from the PN sequence to insert a PCB for controlling the transmission power from the secondary station. A PCB puncture and insert section 260 punctures a data symbol corresponding to the PCB position among the scrambled data symbols from the scrambler 256, and inserts a PCB. The PCB-inserted traffic channel is sent to the spreader and modulator of FIG. 3.
The position of the transmit data symbol for transmission time hopping multiplexing according to the present invention can also be detected using the decimated PN sequence as described above.
FIGS. 3a, 3b and 3c illustrate an example of the spreader and modulator using the conventional code division multiplexing technology.
The spreader and modulator of FIG. 3a uses the existing IS-95 (cdmaOne) system based on a BPSK (Binary Phase Shift Keying) data modulation system.
The spreader and modulator of FIG. 3b spreads I/Q channel transmit data with a different orthogonal code symbol in the structure of FIG. 3a. The spreader and modulator of FIG. 3c employs a QPSK (Quadrature Phase Shift Keying) data modulation system so as to transmit double the data of FIG. 3a with the same bandwidth. The QPSK data modulation system is adapted to cdma2000, one of the candidate technologies of the IMT-2000 system.
The spreader and modulator of FIG. 3d use the QPSK data modulation system in order to transmit double the data of FIG. 3b with the same bandwidth. FIG. 3e shows a spreader and modulator using a QOC (Quasi-Orthogonal Code) modulation system usually adapted in cdma2000, one of the candidate technologies of the IMT-2000 system.
FIG. 3f shows that I/Q channel transmit data are spread with a different orthogonal code symbol in the structure of FIG. 3e.
Referring to FIG. 3a, signal converters 310, 330, 326, 346 and 364 convert logic signals of "0" and "1" to actual transmit physical signals of "+1" and "−1", respectively. The individual channels of FIG. 2 are sent to spreaders 312 and 332 via the signal converters and spread with the output of a corresponding Walsh code generator 362. The spread channels are then sent to amplifiers 314 and 334 to control their relative transmission power.
After passing through the spreaders 312 and 332 using an orthogonal Walsh function 362 fixedly allocated to each channel and the amplifiers 314 and 334, the channels of the primary station are all sent to orthogonal code division multiplexers 316 and 336.
The multiplexed signals are then sent to QPSK spreader and modulators 318 and 338 using short PN sequences generated from short PN sequence generators 324 and 344 for discrimination of the primary station. The spread and modulated signals are sent to low-pass filters 320 and 340 and modulators 322 and 342 for transition to a transmit band. The signals modulated with carriers are sent to a wireless section (not shown) such as a high power amplifier and then transferred via an antenna.
Referring to FIG. 3b, signal converters 310, 330, 326, 346 and 364 convert logic signals of "0" and "1" to actual transmit physical signals of "+1" and "−1", respectively. The individual channels of FIG. 2 are sent to spreaders 312 and 332 via the signal converters and spread with the output of a corresponding Walsh code generator 362 by the I/Q channels. The spread channels are then sent to amplifiers 314 and 334 to control their relative transmission power. After passing through the spreaders 312 and 332 using an orthogonal Walsh function 362 fixedly allocated to each channel and the amplifiers 314 and 334, all the channels of the primary station are sent to orthogonal code division multiplexers 316 and 336. The multiplexed signals are then sent to QPSK spreader and modulators 318 and 338 using short PN sequences generated from short PN sequence generators 324 and 344 for discrimination of the primary station. The spread and modulated signals are sent to low-pass filters 320 and 340 and modulators 322 and 342 using carriers for transition to a transmit band. The signals modulated with carriers are sent to a wireless section (not shown) such as a high power amplifier and then transferred via an antenna.
FIG. 3c is the same as FIG. 3a, excepting that the signals generated in FIG. 2 are sent to a demultiplexer 390 for QPSK, rather than BPSK, using an in-phase (I) channel and a quadrature phase (Q) channel in sending different information data. The demultiplexer 390 and the signal converters 310 and 330 are used to realize QAM (Quadrature Amplitude Modulation) instead of QPSK.
FIG. 3d is the same as FIG. 3b, excepting that the signals generated in FIG. 2 are sent to a demultiplexer 390 for QPSK, rather than BPSK, using an in-phase (I) channel and a quadrature phase (Q) channel in sending different information data.
FIG. 3e shows that the transmit data are spread with a spreading code generated using the quasi-orthogonal code mask for discrimination of a channel from the primary station to the secondary station in FIG. 3c. Orthogonality is not maintained in the code symbol group using a different quasi-orthogonal code but in the code symbol group using a same orthogonal code mask.
Accordingly, the system proposed in the present invention is applied only to the orthogonal code symbol group using a same quasi-orthogonal code mask and maintaining orthogonality.
FIG. 3f is the same as FIG. 3e, excepting that a separate Walsh code generator is used for I- and Q-channels so as to spread I/Q channel transmit data with a different orthogonal code symbol.
FIGS. 4b and 4c show a signal diagram explaining a multiplexing method in which orthogonal resources are allocated to the signals generated in FIGS. 2 and 3 by the respective channels to transmit the signals.
With a primary station in communication with secondary stations, the data rate by the respective secondary stations may be variable over time. Let the channel-based maximum transmission rate allocated to the secondary stations by the primary station be a basic transmission rate R, the frame-based average transmission rate may be R, R/2, R/4, . . . , or 0 according to the frame-based amount of data transferred from the primary station to the secondary stations.
FIG. 4b is a signal diagram showing that the frame-based instantaneous transmission rate is adjusted to the average transmission rate, which method is applied on the forward link in the IS-95 (cdmaOne) orthogonal code division multiplexing communication systems.
In FIG. 4b, when the frame-base transmit data have a transmission rate below the basic transmission rate, dummy information is used to compensate for the deficient part and thereby match the frame-based instantaneous transmission rate to the average transmission rate.
FIG. 4c shows that the instantaneous transmission rate is classified into a basic transmission rate R and 0 (no transmission) and that an average transmission rate for a given frame is adjusted according to the percentage of an interval having a transmission rate of R or 0.
In FIG. 4c, instead of the ON/OFF switching of transmit symbol units that are spreading units used in the present invention, the ON/OFF switching of time slot units that are power control units is used in adjusting the frame-based average transmission rate, while maintaining the amplitude of the reference signal for a closed loop power control of the reverse link in the IS-95 (cdmaOne) system.
Contrary to the present invention, there is no orthogonality between channels on the IS-95 (cdmaOne) reverse link.
In FIGS. 4b and 4c, the common pilot channel is used in parallel with a channel to the secondary stations. But the pilot channel, which is used at the receiver as a reference for synchronization, channel estimation and power control, can be transmitted by time division multiplexing as in the conventional GSM (Global System for Mobile) or WCDMA (Wideband CDMA) system. The pilot channel in this case is called "pilot symbol" or another various names such as preamble, midamble or post-amble according to the multiplexed position.
FIG. 4d illustrates the conventional frequency division multiplexing system, in which communication channels from a primary station to plural secondary stations use a different frequency allocation (FA). The frequency division multiplexing system of the present invention includes the OFDM (Orthogonal Frequency Division Multiplexing) system actively studied for satellite broadcasting.
For OFDM, the FA of the individual subcarrier channels is not completely independent but overlapped, but may be included in the orthogonal resource of the present invention, because orthogonality between the subcarrier channels is secured.
FIG. 4e illustrates the conventional time division multiplexing system such GSM, in which communication channels from a primary station to plural secondary stations use a same frequency allocation (FA) but the time slots in the frame are exclusively allocated by the respective secondary stations.
FIGS. 4f, 4g and 4h apply a frequency hopping system to the conventional frequency division multiplexing system of FIG. 4d for the purpose of strengthening frequency diversity and security. FIG. 4f shows frequency hopping in the unit of time slots. FIG. 4g shows regular frequency hopping in the unit of transmit data symbols. FIG. 4h shows irregular frequency hopping in the unit of transmit data symbols. The system of FIG. 4g brings focus into frequency diversity, and that of FIG. 4h has importance on frequency diversity and security for preventing a monitoring by an unauthorized receiver.
Frequency hopping multiplexing includes fast frequency hopping multiplexing in the unit of symbols or partial symbols and slow frequency hopping multiplexing in the unit of several symbols. The systems of FIGS. 4f, 4g and 4h applied to the time division multiplexing system of FIG. 4e provide frequency diversity.
In fact, the use of frequency hopping in the unit of time slots or frames is optionally given in the next-generation mobile communication system, i.e., GSM for the purpose of strengthening frequency diversity rather than security.
FIG. 4i illustrates the conventional orthogonal code division multiplexing system such as cdma2000 or WCDMA systems. In FIG. 4i, the communication channels from a primary station to the respective secondary stations are established using the same frequency allocation (FA) and all time slots in the frame. The primary station allocates a fixed orthogonal code symbol to each channel during a call set up, and each secondary station returns the orthogonal code symbol to the primary station for another secondary station involving another call set up. Accordingly, all the data symbols in the frame are spread with the same orthogonal code symbol. The transmitters of the primary station corresponding to FIG. 4i are presented in FIGS. 3a to 3f.
FIG. 4j is a signal diagram of a transmit signal from the primary station in the conventional ORDM (Orthogonal Resource Division Multiplexing) system, in which channel-based fixed allocation of orthogonal resources is illustrated. ORDM is applied to most of the conventional digital communication systems.
The receiver of the secondary station corresponding to the transmitter of the primary station according to the example of the prior art as shown in FIG. 4i is similar to the transmitters of FIGS. 3a to 3f except for the despreading part. Thus, FIG. 5 shows a schematic view of a receiver corresponding to the transmitter of FIG. 3a. The received signal through an antenna is demodulated with carriers at demodulators 510 and 530 and low-pass filtered at low-pass filters 512 and 533 into a baseband signal. The sequences, which are generated from PN-I/Q short code generators 520 and 540 and the same with PN sequences used at the transmitter, are synchronized and multiplied by the received baseband signal at multipliers 514 and 534. The multiplied sequences are cumulated for a transmit data symbol interval and sent to despreaders 516 and 536. A channel estimator 550 extracts a pilot channel component from the baseband signal with an orthogonal code symbol allocated to the pilot channel to estimate a transmit channel, and a phase recovery section 560 compensates for the phase distortion of the baseband signal using the estimated phase distortion value. If the pilot channel is subject to time division multiplexing rather than code division multiplexing, a demultiplexer is used to extract the pilot signal part and the intermittent phase change between the extracted pilot signals is then estimated by interpolation.
FIG. 6 shows the structure of a receiver for a channel without a PCB insertion from the primary station like the above-stated paging channel, where the PCB is a command for controlling the transmission power from the secondary stations to the primary station. After the phase compensation in FIG. 5, the signals are fed into maximum ratio combiners 610 and 620. With a QPSK data modulation at the transmitter as illustrated in FIG. 3b, the combined signal is sent to a multiplexer 614 for multiplexing; alternatively, with a BPSK data modulation, the two signals are added. The resulting signal is then sent to a soft decision section 616 for soft decision. The output of a long code generator 622 formed by a long code mask 620 is sent to a decimator 624. The signal from the soft decision section 616 is multiplied by the decimated output of the long code generator 622 by a multiplier 618 for descrambling. The receiver of the secondary station for a channel subject to orthogonal code hopping multiplexing according to the embodiment of the present invention is similar in structure to the receiver of FIG. 6. For the synchronous channels, the components related to the long code descrambling process are omitted.
FIG. 7 shows the structure of a receiver for a channel with a PCB insertion from the primary station like the above-stated traffic channel, where the PCB is a command for controlling the transmission power from the secondary stations to the primary station. After the phase compensation in FIG. 5, the signals are fed into maximum ratio combiners 710 and 720. With a QPSK data modulation at the transmitter as illustrated in FIG. 3c, the in-phase (I) component and the quadrature (Q) phase component are sent to a multiplexer 714 for multiplexing; alternatively, with a BPSK data modulation as illustrated in FIG. 3a, the in-phase (I) component and the quadrature phase (Q) component are added. The resulting signal is sent to an extractor 740 for extraction of a signal component corresponding to the PCB from the primary station and then to a hard decision section 744 for hard decision. The signal from the hard decision section 744 is transferred to the transmission power controller of the secondary station. The data symbol generated by removing the PCB from the received signal of the multiplexer 714 is sent to a soft decision section 742 for soft decision. The output of a long code generator 722 formed by a long code mask 720 generated from the identifier of the secondary station is sent to a decimator 724. The signal from the soft decision section 742 is multiplied by the decimated output of the long code generator 722 by a multiplier 718 for descrambling.
FIG. 8 illustrates that the received signal processed in FIG. 7 is subject to channel deinterleaving at block deinterleavers 818, 828 and 838 and channel decoding at convolutional decoders 814, 824 and 834 to reconstitute data transferred from the primary station. For a synchronous channel 810, the signal from the soft decision section is sent to a sampler 819 for symbol compression that is a reversed process of the symbol repeater 219 by accumulation of the received signals, thereby reducing a symbol rate. The signal from the sampler 819 is sent to the block deinterleaver 818 for channel deinterleaving. Before a channel decoding at the convolutional decoder 814, the channel-deinterleaved signal is sent to a sampler 816 for another symbol compression that is a reversed process of the symbol repeater 216. The signal from the sampler 816 is sent to the convolutional decoder 814 for channel decoding, thereby reconstituting the synchronous channel received from the primary station. For a paging channel 820, the signal from the soft decision section is sent to the block deinterleaver 828 for channel deinterleaving. The channel-deinterleaved signal is sent to a sampler 826 for symbol compression according to the transmit data rate that is a reversed process of the symbol repeater 226. The signal from the sampler 826 is sent to the convolutional decoder 824 for channel decoding, thereby reconstituting the paging channel received from the primary station. For a traffic channel 830, the signal from the soft decision section is sent to the block deinterleaver 838 for channel deinterleaving irrespective of the transmit data rate. The channel-deinterleaved signal is sent to a sampler 836 for symbol compression according to the transmit data rate that is a reversed process of the symbol repeater 246. The signal from the sampler 836 is sent to the convolutional decoder 834 for channel decoding and removed of a tail bit for frame-based independent transmit signal generation by a tail bit remover 832. As in the transmitter for the transmit data part, a CRC bit is generated and compared with a CRC bit reconstituted by channel decoding to determine whether or not there is an error. When the two CRC bits are matched, it is determined that there is no error, thereby reconstituting traffic channel data. If information about the transmit data rate in the unit of 20-ms frames is not stored at the transmitter, the channel deinterleaved signals are channel-decoded independently for all possible transmit data rates and then the CRC bits are compared to determined the transmit data rate from the primary station. For a system in which the transmit data rate is separately transferred, only the channel decoding process for a corresponding data rate is needed.
There are four conventional methods for maintaining orthogonality between channels from the primary station to the secondary stations as shown in FIG. 1. The first method is to use the frequency division multiplexing so that the primary station fixedly allocates FA to the secondary stations during a call set up as illustrated in FIG. 4d. The second method is to use the time division multiplexing so that the primary station fixedly allocates time slots to the secondary stations during a call set up as illustrated in FIG. 4e. The third method is to allocate a hopping pattern controlled to avoid a collision of the primary station during a call set up as illustrated in FIGS. 4f, 4g and 4h to the secondary stations, or to use the total bandwidth composed of multiple subcarriers for a single secondary station at a given time in a given area, as in the military use. The fourth method is to allocate unoccupied orthogonal code symbols by the primary station during a call set up and spreading channels as illustrated in FIG. 4i.
Apart from the frequency hopping multiplexing method, the other three methods have a common feature that the primary station allocates fixedly orthogonal resources (e.g., frequency, time, or orthogonal code) to the secondary stations. The frequency hopping multiplexing method is primarily used for the security purpose in many applications supporting a sufficient quantity of resources, as in the military use. Hence, the frequency hopping multiplexing is not aimed at an efficient use of resources.
It is therefore difficult in the above methods to efficiently use the resources when the limited orthogonal resource is allocated to the channels having a low activity or a variable transmit data rate less than or equal to a basic transmission rate.
A rapid channel allocation and release is required in order to fixedly allocate the resources as in the prior methods and increase the utilization of the resources. But, a considerable part of the confined resources are not used for actual data transmission but allocated to the control information for data transmission because the control signal information for frequent channel allocation and release is transferred.
Even with a rapid procedure of channel allocation and release, the data to be transmitted must be buffered during a period from its arrival at the primary station to transmission via the steps of channel allocation (or release) message transmission and confirmation. The required buffer capacity in this case increases with an increase in the processing time of the procedures.
In the method of fixedly allocating resources during a handoff to an adjacent cell, the handoff is hardly acquired even when the channels in the adjacent cell have a low activity, because there is no available resource to be allocated.
Furthermore, important information such as control information that necessarily requires a confirmation step after a transmission must be buffered for retransmission. But the required buffer capacity can be reduced only by transmitting the resources with a shortest delay in the transmission such as datagram transmission that does not require a confirmation step.

This patent is subject to a terminal disclaimer.

Electronics and Telecommunications Research Institute

Korea Advanced Institute of Science and Technology


In an optical transmission tube comprising a tubular cladding and a core within the cladding having a higher index of refraction than the cladding, a strip-shaped reflecting layer is longitudinally extended between the cladding and the core. Light passing through the core is reflected and scattered by the reflecting layer to emerge from the tube through an area of the outer surface of the cladding opposed to the reflecting layer. The optical transmission tube is prepared by dispersing scattering particles in a monomer solution; filling a tubular cladding with the monomer solution; resting the cladding horizontally for allowing the scattering particles to settle on a lower inner surface of the cladding; and thereafter, causing the monomer solution to polymerize and solidify within the cladding.

1. Field of the Invention
This invention relates to an optical transmission tube comprising a tubular transparent cladding and a transparent core having a higher index of refraction than the cladding and a method for preparing the same. More particularly, it relates to an optical transmission tube allowing directional light emergence from one side or outer surface area of the cladding. It also relates to a linear illuminant system having improved water resistance, improved environmental resistance and a low power consumption for driving.
2. Prior Art
Since optical transmission tubes comprising a tubular cladding and a core in the cladding having a higher index of refraction than the cladding are generally designed so as to transmit as much light as possible from one end to the other end thereof, only a low luminance is generally available near the side surface of the tube. One possible measure for increasing the luminance at the side surface of an optical transmission tube is by corrugating the cladding inner surface for scattering light. This measure is difficult to apply to the method for producing an optical transmission tube by filling a tubular cladding with a core-forming polymerizable monomer liquid and pressurizing the liquid for causing the monomer to polymerize because the cladding becomes likely to rupture.
It may also be envisaged to disperse scattering particles in the core for increasing the luminance at the side surface of an optical transmission tube. It may occur to those skilled in the art to disperse scattering particles in a monomer liquid and then polymerize and solidify the monomer. However, there has never been available a method of adding scattering particles to a monomeric liquid and polymerizing the liquid in a controlled manner such that the scattering particles are distributed in a limited area, that is, to form a reflecting layer, at the end of polymerization.
Known illuminant devices capable of providing linear light emission over a length of several meters include neon tubes and fluorescent tubes. The neon tubes and fluorescent tubes require high voltages, with the risk of electric shocks and leakage. They cannot be used in water and at places where rain or snow reaches. Since the tubes are formed of glass, they cannot be used at places where failure of glass tubes by physical collision of people or vehicles is expectable.
Where the neon tubes and fluorescent tubes are used in a bent form, the glass tubes must be worked to the desired curvature, which requires skilled workers and hence, leads to an increased cost. The power consumption of neon tubes and fluorescent tubes is as high as several tens of watts per meter. For a long term of operation, they must be installed where a commercial power supply is available.
To solve these problems, optical transmission tubes in the form of a flexible tube filled with a transparent core liquid or flexible transparent polymer and strands of plastic optical fibers have been proposed. The system includes a light source and an optical transmission tube which receives light from the light source at one end thereof. The optical transmission tube is designed such that light may emerge from a side surface area of the tube over a length of several tens of meters. Since the light source can be separated from the light emerging area, this system can be used in water, outdoor or even in an environment with the risk of explosion. The system is free of the risk of breakage, eliminates complex cumbersome working such as glass working, and is readily applied at a necessary site.
These optical transmission tubes provide light emergence over a length of several tens of meters. Since the light emergent efficacy at the side surface is low, a high power light source of about 50 to 250 W is required in order to provide an increased luminance. When such an optical transmission tube is used in water, outdoor or in an environment with the risk of explosion for the purpose of providing side surface light emergence, a means for protecting the light source is necessary. As a consequence, the light source is increased in size and its accommodation is significantly limited.

Optical transmission tube, making method, and linear illuminant system


Technologies are generally described for manufacturing an optical device by attaching a light-emitting element to an optical element through a resin. In various examples, a method is described, where a substrate is provided to have a through-hole at a position in the substrate where an optical element is to be mounted. A resin in liquid state may be injected into the through-hole in the substrate. Further, an optical element having a light-emitting portion may be mounted on the substrate such that a center of the tight-emitting portion is self-aligned with a center of the through-hole due to a surface tension of the resin in liquid state. The resin may be cured such that the optical element is fixed to the substrate.

Unless otherwise indicated herein, the approaches described in this section are not prior art to the claims in this application and are not admitted to be prior art by inclusion in this section.
In implementing an optical communication system, alignment of an optical element such as a light-emitting element with another optical element such as an optical waveguide may be required. In such system, the light-emitting element such as a semiconductor laser or an LED (light-emitting diode) may serve as a source for generating optical communication signals while the optical waveguide serves as a channel for optical signal propagation. Accordingly, precise alignment of the light-emitting element with the optical waveguide may be important for providing a high speed and quality communication performance with minimal light propagation loss.
Some methods for alignment of a light-emitting element with an optical waveguide have been developed for practical use. In this example method, individual optical elements can be mounted by a machine manipulator at predetermined positions on a substrate which has been machined with high-precision machining process or MEMS (micro-electro-mechanical systems) process. Due to the limitation of machining precision and mechanical manipulation precision (which is typically on the order of about a few micrometers), precision of alignment may also be limited to a micron order. Thus, this example method may not be applicable to high-precision alignment at a submicron level.
In another example method, alignment of a light-emitting element with an optical waveguide can be controlled based on a result of performing optical detection, e.g., checking whether the optical performance satisfies desired characteristics, Since the precision of alignment in this method depends on optical detection accuracy, alignment for a submicron level precision may be achieved by fine-tuning a control system for optical detection. However, each alignment operation may require an optical detection operation, resulting in increase of the entire manufacturing costs.
As described above, with the conventional optical element alignment methods, it may be difficult to perform alignment operations in such a way that both high quality and low cost requirements are met. However, in some cases, there may be demands for aligning and mounting optical elements with high precision and at low cost.


A URL and a categorization associated with the URL are received. A key associated with the received URL is determined. An operation is performed on a database using the determined key. Examples of such operations include inserting the categorization into the database, changing a value associated with the key in the database, removing a key-value pair from the database, and querying the database.

Firewalls and other security devices/programs typically enforce policies against network traffic based on a set of rules. In some cases, the rules may be based on uniform resource locator (URL) information, such as by preventing a user from accessing a site reachable at specific URL (e.g., denying access to http://www.example.com), or by preventing a user from accessing a site based on a categorization of the URL (e.g., denying access to sites classified as "social networking" sites or "pornographic" sites). Unfortunately, due to a variety of factors, such as the sheer volume of URLs in existence, as well as the dynamic nature of content, it can be difficult to efficiently enforce rules that make use of URL information.

Key-value storage for URL categorization


A method of detecting a stealth virus is provided by culturing a sample under conditions in which any stealth virus in the sample is able to induce a cytopathic effect. A method for culturing a virus is also provided by (a) cocentrifuging a sample of said virus with a permissive cell line of indicator cells; (b) inoculating the cell mixture into culture vessels; (c) adding viral enhancing medium to the culture; and (d) detecting in vitro a cytopathic effect in the permissive cell line.

A. Chronic Fatigue Syndrome
Palca, Science, 249:1240-1241 (1990) and Palca, Science, 254:1726-1728 (1991) describe attempts to identify a causative agent for chronic fatigue syndrome.
DeFreitas et al., Chemical Abstracts, 114: Abstract No. 205331c (1991) describes retroviral sequences related to human T lymphotropic virus type 2 in patients with chronic fatigue immune dysfunction syndrome.
Gupta et al., Scandinavian Journal of Immunology, 33:319-327 (1991) describes a comprehensive immunological analysis of chronic fatigue syndrome. The analysis of cell mediated and antibody mediated immunity was performed in 20 patients with chronic fatigue syndrome and 20 age and sex matched healthy controls.
B. Culture Techniques
Werner, Lancet, II:258-259 (1979) describes the isolation of foamy viruses from patients with de Quervain Thyroiditis and the detection of a cytopathic effect.
Freshney, Culture of Animal Cells: A Manual of Basic Technique, pp. 127-136 (Alan R. Liss Inc., 1987) describes the maintenance of cell cultures and states that four factors indicate the need for replacement of culture medium: (1) a drop in pH; (2) high cell concentration; (3) cell types such as transformed cells, continuous cell lines and some embryonic cells that deteriorate rapidly at high cell densities; and (4) morphological deterioration of the cell such as granularity around the nucleus, cytoplasmic vacuolation, and rounding up of the cells with detachment from the substrate.
DiLuca et al., Virology, 175:199-210 (1990) describes the replication of viral and cellular DNA in human herpesvirus 6-infected cells and the use of medium RPMI 1640 containing 10% fetal calf serum.
Ablashi et al., International Journal of Cancer, 42:787-791 (1988) describes the use of human hematopoietic cell lines for the propagation of HBLV (human herpesvirus 6) in RPMI 1640 supplemented with 10% FBS and antibiotics.
Rethwilm et al., Nucleic Acids Research, 18:733-738 (1990) describes an infectious molecular clone (pHSRV) of the human spumaretrovirus (HSRV). pHSRV derived virus produced foamy virus typical cytopathie effects in susceptible cultures.

Stealth virus detection in the chronic fatigue syndrome


An apparatus for producing images of the invention improves the driving accuracy of an intermediate transfer belt and a photoreceptor drum and synchronizes variations in revolving speed of the intermediate transfer belt and the photoreceptor drum, thereby effectively holding down generation of jitter.

1. Technical Field of the Invention
The present invention relates to a technique for producing images used for electrophotographic digital copying machines or color printers and, more specifically, to an apparatus for producing images in which a driving accuracy of a photoreceptor drum and an intermediate transfer belt is improved and variations in revolving speed of these two parties are synchronized to improve a color matching accuracy.
2. Related Art
A technique of producing images applied to an MFP (Multi-Function Peripherals) apparatus of an intermediate transfer system is disclosed in Japanese Unexamined Patent Application Publication No. 9-222826 as an apparatus for producing images in the related art.
In this apparatus for producing images, resonance frequency oscillations of a drive system of a revolving body drive unit such as a photoreceptor drum are attenuated by a flywheel provided on a drive shaft of the photoreceptor drum.
The apparatus for producing images in the related art is generally provided with a revolving body drive unit 1 having a common drive motor as shown in FIG. 6. The revolving body drive unit 1 interlocks a motor output shaft 2a of a drive motor 2 with a belt drive shaft 4a of an intermediate transfer belt 4 via two-stage reduction gear train 3, and interlocks the motor output shaft 2a of the drive motor 2 with a drum drive shaft 5a of a photoreceptor drum 5 via a three-stage reduction gear train 6, so that the intermediate transfer belt 4 and the photoreceptor drum 5 are driven by the common drive motor 2. In other words, the revolving body drive unit 1 in the related art drives the intermediate transfer belt 4 and the photoreceptor drum 5 separately and independently.
In FIG. 6, reference numeral 7 designates a primary transfer unit and reference numeral 8 designates a secondary transfer unit. In FIG. 6, chain lines designate pitch circles of respective gears which constitute two-system multi-speed reduction gear trains 3, 6, respectively.
Therefore, variations in revolving speed of the intermediate transfer belt 4 and the photoreceptor drum 5 are not synchronized due to their individual driving, whereby there is a risk of generating jitter at a primary transfer position.
Although a motor drive force from the drive motor 2 is transmitted to a drive roller 4a of the intermediate transfer belt 4 via independent two-stage reduction gear train, since the belt drive system of the photoreceptor drum 5 and the drum drive system of the intermediate transfer belt 4 are independent from each other, the belt drive system is not affected by inertia of the flywheel, and hence the inertia moment is small. Therefore, the intermediate transfer belt 4 has a weakness for (has a tendency to follow) variations in load from the outside, is likely to cause unevenness of revolution, and is likely to generate the jitter. The term "jitter" means such phenomenon as drifting or unevenness (shading) of color due to fine variations in speed or unevenness of revolution of the intermediate transfer belt.

Abstract: In the apparatus for producing images, the intermediate transfer belt of the intermediate transfer unit and the photoreceptor drum are driven by a drive motor via single system reduction gear mechanism, and a belt drive gear for driving the intermediate transfer belt and a drum drive gear for driving the photoreceptor drum are meshed with each other. A drum drive shaft for driving the photoreceptor drum preferably includes the drum drive gear and a flywheel. The photoreceptor drum is set to the downstream side of a multi-speed reduction gear train which constitutes the single system reduction gear mechanism with respect to the intermediate transfer belt.


An operational amplifier that decreases idling current, widens a voltage output range, and increases load driving capacity. The operational amplifier includes a first output transistor connected to a high potential power supply. A second output transistor is connected between the first output transistor and a low potential power supply. The first and second output transistors generate an output signal at a node between the first output transistor and the second output transistor. An idling current control circuit controls the collector current of the first output transistor in accordance with the base voltage of the second output transistor to control the idling current of the first and second output transistors.

The present invention relates to an operational amplifier, and more particularly, to an operational amplifier having an output circuit that uses a bipolar transistor.
There is a demand for decreasing the power supply voltage and power consumption of semiconductor devices used in electronic equipment. Accordingly, it is required that such semiconductor device employ an operational amplifier (op amp) that efficiently amplifies signals.
FIG. 1 is a schematic circuit diagram of a prior art op amp 100. A first input signal IN1 is provided to the base of a PNP transistor Tr1, and a second input signal IN2 is provided to the base of a PNP transistor Tr2. The collectors of the transistors Tr1, Tr2 are connected to the collectors of NPN transistors Tr3, Tr4, respectively. The NPN transistors Tr3, Tr4 configure a current mirror circuit.
When the voltage of the second input voltage IN2 is greater than that of the first input signal IN1, the collector current of the transistor Tr2 decreases. This decreases the base current and the collector current of an NPN transistor Tr5.
When the voltage of the second input voltage IN2 is less than that of the first input signal IN1, the collector current of the transistor Tr2 increases. This increases the base current and the collector current of the transistor Tr5.
When the collector current of the transistor Tr5 decreases, the base current and collector current of a first output transistor Tr6, which is an NPN transistor, increases. Further, the base current and collector current of a PNP transistor Tr7 decreases.
When the collector current of the transistor Tr5 increases, the base current and collector current of the first output transistor Tr6 decreases. Further, the base current and collector current of the PNP transistor Tr7 increases.
When the collector current of the transistor Tr7 increases, the base current and collector current of a second output transistor Tr8, which is an NPN transistor, increases. Further, when the collector current of the transistor Tr7 decreases, the base current and collector current of the second output transistor Tr8 decreases. Since the first and second output transistors Tr6, Tr8 are both NPN transistors, a quasi-complementary circuit configures an output circuit of the op amp 100.
The collector current of the transistor Tr7 is the collector current of an NPN transistor Tr9. An idling current setting circuit, which includes transistors Tr10–Tr12 and a resistor R, controls the base current of the transistor Tr9.
The idling current setting circuit receives the output voltage Vo. When the output voltage Vo increases, the idling current setting circuit functions to increase the base current and collector current of the transistor Tr9. When the output voltage Vo decreases, the idling current setting circuit functions to decrease the base current and the collector current of the transistor tr9.
The base voltage of the transistor Tr9 is the sum of the output voltage Vo and the base-emitter voltages VBE6, VBE7, VB9 of the transistors Tr6, Tr7, Tr9. The base voltage of the transistor Tr9 is also the sum of the output voltage Vo and the base-emitter voltages VBE10, VBE11, VBE12 of the transistors Tr10–Tr12. Accordingly, the base-emitter voltage VBE10 of the transistor Tr10 is substantially the same as the base-emitter voltage VBE6 of the transistor Tr6.
When the input signals IN1, IN2 increase the collector current of the transistor Tr5, the collector current of the first output transistor Tr6 decreases, the collector current of the second output transistor Tr8 increase, and the output voltage Vo decreases.
When the input signals IN1, IN2 decrease the collector current of the transistor Tr5, the collector current of the first output transistor Tr6 increases, the collector current of the second output transistor Tr8 decrease, and the output voltage Vo increases.
The base-emitter voltage VBE10 of the transistor Tr10 sets the idling current (bias current) Id, which flows through the output transistor Tr6. The collector current of the transistor TR10 sets the idling current of the transistor Tr8.
When allowable supply currents I1, I2 of current sources 1a, 1b are the same, the idling current Id that flows from the power supply Vcc to the ground GND via the output transistors Tr6, Tr8 is represented by the following equation. In the equation, Q6, Q7, Q9, Q10, Q11, and Q12 respectively represent the size of the transistors Tr6, Tr7, Tr9, Tr10, Tr11, and Tr12.Id=I2×Q9/Q12×Q7/Q11×Q6/Q10
The second output transistor Tr8 is an NPN transistor. Thus, the minimum output voltage VoL may be decreased to substantially the level of the ground GND. However, the voltage difference between the output voltage Vo and the power supply voltage (Vcc) must be greater than the sum of the base-emitter voltages VBE10, VBE11, VBE12 to have the idling current setting circuit function normally. Thus, the maximum output voltage VoH cannot be increased to the power supply voltage.
The idling current Id must be decreased to decrease power consumption. To decrease the idling current Id, the supply current I2 of the current source 1b may be decreased. However, a decrease in the supply current I2 would decrease the maximum output current of the second output transistor Tr8 and reduce load driving capacity.
To increase the load driving capacity by increasing the output current of the first output transistor Tr6, the first output transistor Tr6 may be Darlington-connected. However, a diode-connected transistor must be arranged between the bases of the first output transistor Tr6 and the transistor Tr7 to equalize the base-emitter voltage of a Darlington-connected first output transistor with the base-emitter voltage VBE10. In such case, the supply current I1 of the current source 1a would affect the value of the base-emitter voltage of the first output transistor Tr6. Further, differences between Darlington-connected first output transistors would increase fluctuations of the idling current Id.
When a complementary circuit is employed as the output circuit (i.e., the second output transistor Tr8 being a PNP transistor), a base-emitter voltage VBE of the first output transistor (NPN transistor) Tr6 would exist between the power supply Vcc and the maximum output voltage VoH. Further, a base-emitter voltage VBE of the second output transistor (PNP transistor) Tr8 would exist between the minimum output voltage VoL and the ground GND. Accordingly, the range of the output voltage Vo may not be sufficient.


There is provided a recording apparatus including a colorimeter unit. The colorimeter unit includes a colorimeter including a color-measuring device that acquires colorimetric data from a recording surface of a recording medium; a first member that is a frame that supports the colorimeter; and a second member that is a frame fastened to the first member using a fastening device. The fastening device has an elastic member and fastens the first member and the second member together relatively movably against the elastic force of the elastic member.

1. Technical Field
The present invention relates to a recording apparatus equipped with a colorimeter unit that measures the colors of a colorimetric pattern recorded on a recording medium using a color-measuring device.
2. Related Art
In printed-matter production sites, color proofing has been performed in which proofing is performed before final printing, and it is determined, with reference to an image displayed on the printed sample proof and a color patch for indication that is displayed together with the image, whether the color of image data is reproduced with high fidelity.
On the other hand, digital matching is widely used in which the color of an image on a CRT monitor and the color of an image displayed on the print sample output from an output unit, such as a printer or an image sensor, are electrically matched on the basis of a color management file called a profile. The digital matching is executed in print-data production sites and printed-matter production sites (see JP-A-11-326056).
In recent years, color proofing, called offpress proofing, is widely used in which a proof sheet is directly output from print data for making a printing plate to reduce the time required for proofing, and an ink-jet recording apparatus equipped with a color-measuring device is used to output such a proof sheet.
A colorimeter that includes the color-measuring device is accommodated in a housing frame together with a drier and is incorporated in an ink-jet recording apparatus, as an integrated colorimeter unit. The colorimeter is supported by a main frame, and the drier is supported by a drier frame. The fastening of the main frame and the drier frame and the fastening of these frames and the housing frame are performed using screws to achieve high-rigidity frame structure as a whole.
The main body of the ink-jet recording apparatus is slightly distorted, for example, in the surface of the main body facing the color-measuring device and holding a recording medium, due to variations in component accuracy, assembly accuracy, etc. In such a case, the high-rigidity frame structure causes the problems below.
The high-rigidity frame structure of the colorimeter unit causes variations in the distance between the color-measuring device and the holding surface (surface to be measured, hereinafter referred to as a colorimetric surface) in a region to be measured (hereinafter referred to as a colorimetric region) if the holding surface has the distortion, with the colorimeter unit mounted in the recording-apparatus main body. That is, the colorimeter unit cannot be deformed so as to absorb the distortion of the holding surface to thereby shape the overall form along the distortion by itself because of the high rigidity of the frame structure. This precludes the distance between the color-measuring device and the holding surface from being held constant in the entire colorimetric region due to the influence of the distortion of the holding surface. The inconstant distance in the entire colorimetric region will decrease the colorimetric accuracy of the color-measuring device.
In particular, a large-sized recording apparatus has the problem of generating the distortion to decrease the colorimetric accuracy because the holding surface that holds the recording medium is long in the crosswise direction of the recording apparatus.


Peptide analogues are provided with amino acid sequences of the corticotropin-releasing factor superfamily, but having at least one amino acid residue that has been replaced with a D-amino acid residue or a D-amino acid analog. The peptide analogues have anti-inflammatory activity while having a receptor selectivity and thus a disassociated ACTH response.

The vascular tree is a complex network of blood vessels designed to maintain, at its outermost subdivisions, a surface area between blood and tissues for the exchange of gases and nutrients and for the drainage of waste products. During the early stages of inflammation, the sensitive mechanisms relating to microvascular perfusion are altered so that vascular integrity is compromised, blood contents leak into tissues, and hemostasis may develop. In the whole organism, severe and abrupt injury to the microcirculation distorts tissue architecture, impedes delivery of oxygen to cells, and causes extensive fluid loss from the vascular compartment, leading to edema, electrolyte imbalance, shock, and other circulatory disorders. The search for and identification of agents that modulate the immediate responses of inflammation may generate drugs with clinical benefit.
Studies have shown that certain peptides can act as agonists to inhibit inflammation, defined by Cotran et al. (Robbins: Pathologic Basis of Disease, (4th ed., 1989), Ed. Robbins, 2:39-86, Philadelphia: Saunders) as the reaction of vascularized living tissue to local injury. Specific antagonists, by design, work one-on-one against substances that promote inflammation, and the efficacy of a single antagonist may be limited if more than one mediator is released during tissue injury. An agonist, a term introduced by Reuse (Br. J. Pharmacol., 3, pp. 129-62 (1948)) to describe a chemical that activates biological events, would be more efficacious than an antagonist if it could suppress convergent processes initiated by more than one inflammatory mediator. The concept of drugs as anti-inflammatory agonists was discussed by Svensjo and Persson in 1985 (Handbook of Inflammation, Ed. Bonta, 5:51-82, Amsterdam: Elsevier) and by Wei and Thomas ("Anti-Inflammatory Peptide Agonists," Annual Review of Pharmacology and Toxicology, 33, pp. 91-108, 1993).
One or two of us have previously described several different types of peptides useful for anti-inflammatory methods. Thus, U.S. Pat. No. 4,682,930 issued Jan. 9, 1996, titled "Anti-Inflammatory Composition and Method with Des-Tyr Dynorphin and Analogues," inventors Wei and Thomas, describe compounds of the dynorphin family as anti-inflammatory agents.
U.S. Pat. No. 5,480,869, issued Jan. 2, 1996, titled "Anti-Inflammatory Peptide Analogues and Treatment to Inhibit Vascular Leakage in Injured Tissues," inventors Wei and Thomas, describe small peptides having a six amino acid core where one of the amino acid moieties is in the D-configuration.
U.S. Pat. No. 5,374,621, issued Dec. 20, 1994, titled "Neurotensin and Method for Inhibiting Vascular Leakage," inventor Wei, describes neurotensin and analogs useful for anti-inflammatory purposes. Neurotensin is a 13-amino acid residue peptide and is related to an 8-residue peptide, named xenopsin. These peptides affect various physiological functions, such as blood flow, digestion and temperature regulation.
Corticotropin-releasing factor (CRF, also called CRH or corticoliberin) was first characterized as a 41-residue peptide isolated from ovine hypothalami by Vale et al. (1981). Subsequently, the sequence of human-CRF was deduced from cDNA studies and shown to be identical to rat-CRF, and then caprine, bovine, porcine, and white sucker fish CRF were characterized. The CRF of hoofed animals show considerable differences from man, but the pig and fish sequences differ from the human/rat sequence by only 2 out of 41 residues.
Peptides with homologous structures to mammalian CRF are found in cells of certain frog skins and in the urophysis of fish. In fact, the structure of sauvagine, the 40 amino acid peptide isolated from the skins of Phyllomedusa frogs, was reported several years before Vale's description of ovine-CRF in 1981. The structure of sucker fish urotensin I was reported just months after the description of ovine-CRF and resulted from an independent line of inquiry by Lederis's group in Canada. Although sauvagine and urotensin I release adrenocorticotropin (ACTH) from the pituitary, the natural physiological functions of these peptides in the tree-frog (Phyllomedusa species that live in arid regions of South America) and in the sucker fish remain unknown. The mystery deepened when Lederis' group (Okawara et al., "Cloning and Sequence Analysis of cDNA for Corticotropin-Releasing Factor Precursor from the Teleost Fish Catostomus commersoni, " Proc. Natl. Acad. Sci., 85:22, pp. 8439-43 (1988)) showed that the sucker fish not only had urotensin I in its tail-organ but also had CRF in its brain. The co-existence of CRF and urotensin I in the sucker fish suggested that there were other CRF-like peptides in mammals. Vaughan et al., "Urocortin, a Mammalian Neuropeptide Related to Fish Urotensin I and to Corticotropin-Releasing Factor," Nature, 378:6554, pp. 287-92 (Nov. 1995), using antibodies to urotensin I as an investigative tool, recently discovered a CRF-like peptide in rat brain which was called urocortin. The functional inter-relationships and amino acid sequences of CRF superfamily peptides which include CRF, urotensin I-like peptides, and sauvagine are known to the art.
Receptor proteins for CRF were first cloned in 1993 and shown to belong to the second family of 7-transmembrane domain G.sub.s -protein coupled receptors. Two different genes were described encoding the receptors, CRF-R1 and CRF-R2, there being two different splice variants, .alpha. and .beta., for CRF-R2. The distribution of messenger RNA (mRNA) that codes for the synthesis of CRF-R1 is predominantly located in the pituitary, cerebellum, cerebral cortex and olfactory bulb and corresponds well with the location of immunoreactive CRF materials in the brain, as well as CRF binding sites as measured by radio-iodinated ligands. These results indicated that CRF-R1 was the receptor for endogenous CRF and moreover, this relationship was coupled to ACTH release. CRF-R2, however, was found to have a distribution that had little correspondence to the known sites of CRF synthesis. For example, CRF-R2 is found the heart muscle, lung and arterioles of peripheral tissues, but mRNA for CRF synthesis is not found in such tissues.
The pharmacological profile (or pattern of responsiveness) of CRF-R2 receptors to activation by peptides of the CRF superfamily was also clearly different from CRF-R1. Cells transfected with CRF-R1 and CRF-R2 are both sensitive to the cAMP stimulatory effects of human/rat CRF, frog sauvagine, sucker fish urotensin I and rat urocortin. However, the rank order of potency for cAMP stimulation in cells expressing the CRF-R2 receptor was sauvagine>urotensin I=urocortin >h/rCRF whereas sauvagine, urotensin I, urocortin and h/rCRF were about equipotent in cells transfected with CRF-R1 receptor. In assays for ACTH-release, sauvagine and urotensin I are about equipotent to h/rCRF, so again, based on pharmacological profile, it is clear that CRF-R1 is coupled to ACTH-release in physiological systems. The functional activities coupled to CRF-R2 activation are less clear, although it would appear that the natural hormone for activating this system is an urocortin or an urotensin I-like peptide, instead of a CRF-like peptide. In an earlier study (Wei and Kiang, "Peptides of the Corticoliberin Superfamily Inhibit Thermal and Neurogenic Inflammation," European Journal of Pharmacology, 168, pp. 81-86, 1989), it was shown that the intravenous potencies (measured as the median effective dose or ED50) of sauvagine, urotensin I and h/r CRF for suppression of heat-induced edema in the rat were 0.44, 1.5, and 5.9 nmol/kg, respectively. This pharmacological profile, when linked with the fact that CRF-R2 are located in peripheral tissues, indicated that selective activity of agonists at the CRF-R2 receptor paralleled anti-edema potency.
In summary, CRF regulates ACTH secretion via CRF-R1 receptors located on the anterior pituitary. CRF also has several direct actions on central and peripheral tissues, for example CRF has anti-inflammatory inflammatory properties and may have beneficial effects in Alzheimer's disease because it enhances learning and memory in animal models. In these actions on inflammation and memory, CRF is acting mainly on CRF-R2. The natural ligand for CRF-R2 may be peptides such as urocortin, which resemble more closely urotensin I, the peptide that was first identified in fish.
Some therapeutic methods and uses for CRF are described by U.S. Pat. No. 4,801,612, inventors Wei and Kiang, issued Jan. 31, 1989, titled "Method of Inhibiting Inflammatory Response," and U.S. Pat. No. 5,306,710, issued Apr. 26, 1994, titled "Method for Treating Endotoxin Shock with CRF," inventor Wei, which describes use of a CRF to decrease the leakage of blood components into brain tissue produced by various adverse medical conditions, and thus to treat a patient for injury to or disease of the brain, central nervous system or musculature in which edema is a factor.
However, the anti-edema activity of CRF is also associated with its ACTH-releasing activity. This is disadvantageous therapeutically because excessive steroid release can lead to adverse effects, a constellation of symptoms and signs called "Cushing's Syndrome," exhibiting effects such as a loss of muscle mass, thinning of bone, redistribution of fat, etc. Accordingly, a compound for therapeutic use with a more selective anti-edema property but having a reduced, or disassociated, ACTH release would be therapeutically beneficial.
Another limiting factor in the actions of CRF is its binding to CRF binding protein. This protein present in the body, especially in the brain, complexes to CRF with high affinity and reduces the available amount of "free" CRF for pharmacological actions. One approach to reduce CRF's ability to bind to the binding protein has been to modify the human/rat CRF to more closely resemble the ovine variant of CRF. A group of researchers has described some ligand requirements for CRF binding protein in Endocrinology, 136:3, pp. 1097-1102 (Sutton et al., 1995). They showed that in the regions where human/rat CRF differ from ovine CRF, namely, residues 22, 23, and 24 in the 41-amino acid peptide, conversion of the human residues, Ala, Arg and Glu to Thr, Lys, and Asp removes affinity of the variant for the binding protein. Thus, in the synthesis of new analogs, the changes in these three residues will increase the amount of "free" CRSF for pharmacological activities.
Another approach taken in attempts to modify the CRF peptide has been to shorten its overall length. Thus, elimination of resides 1-4 at the N-terminus of ovine CRF has been shown to not alter biological activities or ACTH-release potency. (See Kornreich, J. Med. Chem., 35, pp. 1870-1876 (1992).) Although chemical manipulation of the CRF molecule has modest success in modifying the affinity of CRF for binding protein, and a modest shortening of its length whilst retaining activity, as well as increasing its potency for ACTH-release, so far the features of the CRF that determine receptor selectivity have not been identified. However, a CRF-like compound would be therapeutically useful if it had an anti-edema property but also had reduced, or disassociated, ACTH release.

Anti-inflammatory compositions and method with corticotropin-releasing factor analogs

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